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Pentec Health, Inc, Boothwyn, PA, 483 Issued 4/1/2013 (PDF - 924KB) The Compounding Shop St. Petersburg, FL, Amended 483 Issued 3/25/2013 (PDF - 10MB) The Compounding Shop St. Petersburg, FL, 483 Issued 3/22/2013 (PDF - 1.3MB) Medaus, Inc., Birmingham, AL, 483 Issued 3/22/2013 (PDF - 712KB) PharMEDium Services LLC, Memphis, TN, 483 Issued 3/22/2013 (PDF - 10.4MB) Specialty Compounding Pharmacy, Cedar Park, TX, 483 Issued 3/22/2013 (PDF - 744KB) Drugs are Us, Inc. (dba Hopewell Pharmacy), Hopewell, NJ, 483 Issued 3/21/2013 (PDF - 1.5MB) Lowlite Investments, Inc. (dba Olympia Pharmacy), Orlando, FL, 483 Issued 3/21/2013 (PDF - 717KB) Nora Apothecary and Alternative Therapies, Inc., Indianapolis, IN, 483 Issued 3/21/2013 (PDF - 309KB) IV Solutions of Lubbock, Lubbock, TX, 483 Issued 3/20/2013 (PDF - 3.7MB) Foundation Care LLC, Earth City, MO, 483 Issued 3/19/2013 (PDF - 867KB) Axium Healthcare Pharmacy (dba Balanced Solutions Compounding), Lake Mary, FL, 483 Issued 3/15/2013 (PDF - 638KB) College Pharmacy Incorporated, Colorado Springs, CO, 483 Issued 3/15/2013 (PDF - 1.3MB) Lowlyn Pharmacies, Inc., Blanchard, OK, 483 Issued 3/8/2013 (PDF - 732KB) Central Admixture Pharmacy Services, Inc. (CAPS),
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The ORA Electronic Reading Room displays copies of ORA records. We are making these records publicly available either (1) proactively at our discretion or (2) because they are "frequently requested" per the Electronic Freedom of Information Act Amendments of 1996. Some records may be redacted to remove non-public information (see 21 CFR Part 20). For other ORA documents, please visit the ORA home page and the FDA Warning Letter page ; for other FDA documents, please visit the FDA Freedom of Information (FOI) page. RSS Feed for ORA FOIA Electronic Reading Room [what's this?]
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Title Alexion Pharmaceuticals, Inc., Smithfield, RI, 483 Issued 8/6/2012 St. Jude Medical 2013 Pharmacy Inspections Impax Laboratories, Inc. Hospira Inc. ORA Workplans Kasel Associates Industries, Inc., Denver, CO, 483 Issued 9/28/2012 Hill-Rom, Inc., Batesville, IN, 483 Issued 1/11/2013 RTI Biologics, Inc. Celltex Therapeutics Corporation, Sugarland, TX, 483 Issued 4/27/2012 Alaunus Pharmaceutical LLC, Framingham, MA, 483 Issued 11/16/2012 Ameridose New England Compounding Center (NECC) Shelhigh, Inc., Union, NJ, May 2, 2007, FDA Requested Recall MedImmune, UK, Ltd., 483 Inspectional Observations, Liverpool, UK, dated 03/26/2007 United States v. American National Red Cross, Civil Action No. 93-0949 (JGP), 02/06/2008 (JGP) Posted Date April 09, 2013 April 05, 2013 April 05, 2013 March 29, 2013 March 20, 2013 March 15, 2013 February 13, 2013 February 08, 2013 December 26, 2012 December 06, 2012 November 19, 2012 October 31, 2012 October 25, 2012 October 22, 2012 October 22, 2012 October 22, 2012
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Changzhou SPL Company, Ltd., Changzhou City, Jiangsu, China, 483 Inspectional Observations, 02/26/2008 Johnson and Johnson Sunland, Inc. McNeil Healthcare Chamberlain Farms Inc., Owensville, IN, 483 Issued 8/31/12 Cryolife, Connie J. Jones, Kennesaw, GA, 30144, FDA Inspectional Observations, dated 2/14/2003 Pet Jerky Consumer Complaints Received by ORA District Consumer Complaint Coordinators (January 1, 2007 - July 2, 2012) San Francisco Herb and Natural Food Company, Fremont, CA 483 Issued 7/16/2012 Alkis Togias, M.D./Johns Hopkins Asthma & Allergy Clinic, Baltimore, MD.: FDA 483 Inspectional Observations; (Baltimore) 06/28/2001 Jerky Pet Food Lab Samples Analyzed - 1/1/2007 - 7/2/2012 Egg Rule Assignment 483s Guidant Corporation, 483 Inspectional Observations, St Paul, Minnesota, dated 12/15/2005 02/09/2006 Diamond Pet Food Processors, Gaston, SC, FDA 483 Inspectional Observations, dated 12/21/2005 - 01/19/2006 Able Laboratories, Inc., Cranberry, NJ, FDA 483 Inspectional Observations, dated 05/0207/01/2005 CryoLife, Inc., Kennesaw, GA, FDA Inspectional Observations, dated 10/9, 10, & 14/2003 Exemplar Pharmaceuticals LLC, Fall River, MA 483 issued 3/21/2012 Egg Rule Assignment Establishment Inspection Reports Infupharma, LLC Diamond Pet Food Processors of SC LLC, Gaston, SC, 483 Issued 4/20/2012 Genentech Inc., South San Francisco, CA 483 issued 9/27/2011 American National Red Cross / Biomedical Services Snokist Growers IntelliCell Biosciences, Inc., New York, NY 483 issued 12/12/2011 APP Pharmaceuticals, Grand Island, NY 483 issued 7/8/2011 Regeneron Pharmaceuticals, Inc., Rensselaer, NY 483 issued 3/31/2010 Jensen Farms Novartis Consumer Health H & P Industries, Inc. (Triad Group) Integra LifeSciences CooperVision, Inc. Akorn, Inc. Jazz Pharmaceuticals, Inc., Palo Alto, CA 483 issued 5/6/2011 Sandoz, Inc. (Novartis) Ben Venue Laboratories Zimmer Inc., Warsaw, IN 483 issued 7/22/2011 Invacare Corporation Thermo Pac LLC (Simply Thick) Delta Airlines Inc., Atlanta, GA 483 issued 2/2/2011 Professional Disposables International and Nice Pak Products
October 22, 2012
October 19, 2012 October 11, 2012 October 05, 2012 October 01, 2012 September 13, 2012
September 06, 2012
August 20, 2012 July 17, 2012
July 17, 2012 July 12, 2012 July 11, 2012
July 11, 2012
July 11, 2012
July 11, 2012 July 10, 2012 June 27, 2012 May 15, 2012 May 15, 2012 May 09, 2012 April 25, 2012 April 13, 2012 April 04, 2012 March 15, 2012 March 02, 2012 February 09, 2012 January 27, 2012 January 25, 2012 January 13, 2012 December 22, 2011 December 21, 2011 December 16, 2011 December 12, 2011 December 06, 2011 November 21, 2011 November 18, 2011 November 11, 2011 October 28, 2011 September 29, 2011
Sprouters Northwest Inc., Kent, WA 483 issued 1/21/2011 Cetero Research Depuy Orthopaedics Terumo Cardiovascular Systems Corporation Bravo Farms Cheese, LLC Tiny Greens. Urbana, IL 483 issued 1/28/2011 Duran and Sons LLC Derry, NM 87933 483 issued 11/22/2010 Sally Jackson Cheeses Oroville, WA 98844 483 issued 12/17/2010 Evans Vaccine, Ltd., affiliate of Chiron Corp., Liverpool, UK, November 17, 2004: Utah Medical Products, Inc. (UTMD), Salt Lake City, Utah - 483 Inspectional Observations (483) and Establishment Inspection Reports (EIR) for inspections in 2001-2004*. NBTY, Inc. Boca Raton, FL 8/25-9/5/08, 483 Inspectional Observations, Establishment Inspection Report (EIR): Wyeth Pharmaceutical, Pearl River, NY 8/27-10/8/08, 483 Inspectional Observations, Establishment Inspection Report (EIR): Peanut Corporation of America (PCA), Blakely, GA: Peregrina Cheese Company, Brooklyn, NY 483s issued 3/19/03, 2/5/04, 4/5/06, 12/21/07, 2/17/09, 3/17/09 Caraco Pharmaceutical Laboratories Stryker Corporation Plainview Milk Products Cooperative Bravo Farms Cheese, LLC, Traver, CA 483 issued 12/1/2010 Gilead Sciences Inc., San Dimas, CA 483 issued 2/12/2010 Sanger Fresh Cut Produce Co. LLC, San Antonio, TX 483 issued 10/26/2010 Scenic View Dairy LLC Estrella Family Creamery, LLC, Montesano, WA 483 issued 9/10/2010 Abbott Labs, Inc. (Similac) Scientific Protein Laboratories, LLC Hillandale Farms of Iowa, Inc., New Hampton, IA 483 issued 8/26/2010 Quality Egg LLC, Galt, IA 483 issued 8/30/2010 Unico Holdings Documents L. Perrigo Co. Setton International Foods Genzyme Corporation. Allston, MA. Form 483 (Inspectional Observations). 09/15/08 10/10/08 Care-Tech Labs, Inc., St. Louis, MS 483 issued 5/22/2008 Amylin Pharmaceuticals Inc., West Chester, OH 483 issued 12/23/2009 Ohm Laboratories, Inc., Gloversville, NY 483 issued 8/12/2009 Thumb Oilseed Producers' Cooperative, Ubly, MI 483 issued 2/23/2010 Basic Food Flavors, Inc., North Las Vegas, NV 483 issued 3/4/2010 Matrixx Initiatives Inc. Baxter Healthcare Corporation, Cleveland, MS, Form 483 signed 2/5/2010 Mid-States Closeouts, Inc., Ellsworth, WI 483 signed 12/21/2009 U.F. Union International Food Co., Inc., Union City, CA, EIR signed 7/24/2009 Quesos Mi Pueblito, LLC, Passaic, NJ FDA Form 483 signed 9/3/09
September 20, 2011 July 22, 2011 April 14, 2011 April 12, 2011 April 04, 2011 February 04, 2011 December 23, 2010 December 22, 2010 December 21, 2010 December 21, 2010
December 21, 2010
December 21, 2010
December 21, 2010 December 21, 2010
December 21, 2010 December 21, 2010 December 21, 2010 December 08, 2010 November 24, 2010 November 03, 2010 November 02, 2010 October 26, 2010 October 26, 2010 October 19, 2010 August 30, 2010 August 30, 2010 July 07, 2010 July 07, 2010 May 14, 2010 March 29, 2010
March 16, 2010 March 11, 2010 March 11, 2010 March 09, 2010 March 09, 2010 March 01, 2010 February 17, 2010 February 17, 2010 January 25, 2010 January 20, 2010
Won Feng Trading Inc, Nashville, TN FDA Form 483 issued 11/12/2009 Willamette Shelling, Inc. Unilever Covington, Covington, TN FDA Form 483 12/11/2009 (1 page) Pepsi Bottling Group, LLC Genzyme Corporation, Allston, MA, FDA Form 483 11/13/2009 American Red Cross 2009 Adverse Determination Letters Haifa Smoked Fish, Inc. Care-Tech Labs Inc., Signed Consent Decree issued 9/8/2009 Aunt Mid's Produce Company Bi-County Farm Bureau Coop Association Teva Parenteral Medicines, Inc. Irvine, CA. Form 483 (Inspectional Observations). 7/13/09 7/24/09 Tasty Baking Co Inc. Philadelphia, PA. Form 483 (Inspectional Observations). 07/09/09 07/13/09 Quality Formulation Laboratories, Inc. Paterson, NJ. Form 483 (Inspectional Observations) 12/10/08 1/13/09 Trans-Packers Services Corporation. Brooklyn, NY. Form 483 (Inspectional Observations). 06/01/2009 - 07/06/2009 Forest/Inwood Laboratories, Inc., Farmingdale, NY, FDA 483 dated 10/23/1998; (6 pages) Time Cap Labs, Inc., Farmingdale, NY, FDA 483, inspection 03/26 - 05/05/1998; (11 pages) New York Blood Center, Inc., New York, NY, Establishment Inspection Report (EIR), 10/29/1996 to 12/20/1996; (35 pages) Bioport Corporation, Lansing, MI, FDA 483, dated 10/10-26/2000; (18 pages) Chi Van Dang, M.D., Ph.D./John Hopkins School of Medicine, IRB, FDA 483 Insp. Observations (Baltimore) 09/07/2001 Chi Van Dang, M.D., Ph.D./John Hopkins, Bayview Medical Center, Human Subjects Committee, FDA 483, Insp. Observations (Baltimore) 09/07/2001 Gary J. Oulette, Executive Director, American Red Cross, Greater Chesapeake & Potomac Blood Service Region, FDA 483, Insp. Observations (Baltimore) 06/21/2002 posted 07/15/2002 Nestle USA, Inc. Danville, VA. Form 483 (Inspectional Observations). 06/18/2009 07/09/2009 University of Illinois @ Urbana - Champaign (Sponsor), Champaign, Illinois, 01/29, 30 & 31/2003, FDA Inspectional Observations Nestle USA, Inc., Danville, VA EIRs for inspections completed 3/12/2009, 11/02/2007, and 2/21/2007 Guidant Corporation, Saint Paul, MN, September 22, 2005, FDA 483 Inspectional Observations, dated 08/22/2005 - 09/01/2005 Andrx Pharmaceutical, Inc., 483 Inspectional Observations, Fort Lauderdale, FL, dated 03/06/2006 - 04/18/2006 Bausch & Lomb, Inc., 483 Inspectional Observations, Greenville, SC, dated 03/22/2006 05/15/2006, Manufacturer and Repackager/Relabeler establishment types Sanofi Pasteur, Inc., 483 Inspectional Observations, Swiftwater, PA, dated 04/18/2006 04/28/2006 and Warning Letter dated 06/30/2006 FDA issued an notice of default letter, dated June 20, 2008 to Dr. Amile A. Korangy, M.D. and the Korangy Radiology Associates FDA issued an adverse determination letter, dated June 3, 2008 to the American National Red Cross. The letter was sent via FAX and Certified Mail. Peanut Corporation of America (PCA), Blakely, GA: Consumer Complaints
January 07, 2010 December 30, 2009 December 28, 2009 December 24, 2009 November 25, 2009 November 12, 2009 November 10, 2009 October 15, 2009 October 15, 2009 August 11, 2009 July 31, 2009
July 24, 2009
July 20, 2009
July 15, 2009
July 13, 2009 July 13, 2009 July 13, 2009
July 13, 2009 July 13, 2009
July 13, 2009
July 13, 2009
July 10, 2009
July 10, 2009
June 30, 2009
June 30, 2009
June 29, 2009
June 29, 2009
June 29, 2009
June 26, 2009
June 26, 2009
June 25, 2009
Nestle USA, Inc., Danville, VA EIRs for inspection completed 9/12/2006, 9/14/2005, and 7/14/2004 General Mills, Minneapolis, Minnesota. Warning Letter response. 05/14/09 Clarcon Biological Chemistry Laboratory, Roy, UT. 483 (Inspectional Observations). 04/28/09 05/04/09 American Blanching Company, Fitzgerald, GA 4/8/08: Establishment Inspection Report (EIR), (5 pages) KV Pharmaceutical, Saint Louis, MO, 12/15 2/2/09, FDA Form 483 (Inspectional Observations), (37 pages) Advanced Medical Optics, Inc., 483 Inspectional Observations, Santa Ana, CA, dated 05/29/2007 - 06/25/2007, (12 pages) Apotheca, Inc., Woodbine, IA, Inspectional Observations (483), 8/19 8/28/2008 , (5 pages) Neways, Inc., Salem, UT, Establishment Inspection Report (EIR), 8/18/2008, (7 pages) Novartis Consumer Health, Lincoln, NE, Establishment Inspection Report (EIR) 9/9 9/11/2008, (13 pages) Marietta Corporation, Cortland, NY, 8/18 19/08, Establishment Inspection Report (EIR); (9 pages) Peanut Corporation of America (PCA), Plainview TX, FDA Form 483 (Inspectional Observations) 2/4/09 2/26/09; (7 pages) Del Rey Tortilleria, Inc., Chicago, IL: FDA Form 483 (Inspectional Observations), 12/04/08 01/08/09 (3 pages) TEVA Animal Health, St. Joseph, MO 483 issued April 21, 2009 (20 pages) Zimmer Durom Cup Recall Packet, 2007-2008 (162 pages) Eli Lilly and Company, Indianapolis, IN. Inspection January 29 to February 23, 2001, Warning Letter, FDA 483 and responses from firm: Schering-Plough, Manati, Puerto Rico: Boston Scientific, 483 Inspectional Observations, six locations:
June 25, 2009
June 17, 2009 June 17, 2009
June 04, 2009
June 04, 2009
June 02, 2009
June 02, 2009 June 02, 2009 June 02, 2009
June 02, 2009
June 01, 2009
May 29, 2009
May 28, 2009 May 27, 2009 January 21, 2009
January 21, 2009 January 13, 2009
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This document lists observations IIUl.. Ic by the FDA representatlvefs) during the inspection of your facility . TIl<;Yare Inspectional observations, and do not represent It final Agency detcnmnetiou regarding your compliance. If you have an objection regarding IlIl observation, Of have implemented, or plan 1 0 implemen t, correc tive action in response to an observation, you may discuss the objection or action with the FDArepresenwivc(s) during the inspection or submit this Inrorrnauon to fDA at the address above. Tfyou have any questions, please contact FDA at the phone number and address above.
DURING AN INSPECTION OF YOUR FIRM W E OBSERVEO;
The following d efi ciencies a IJV for all 'irriectable drusr croducts that are processed at vour acut an In en e ora nus a Ion v ia In a eco an .1ll ravenous In ee on:
OBSERVATION 1
Procedures designed to prevent microbiological contam ination ofdrug produ cts purporting to be sterile do not includ e adequate validation ofthe sterilization prccese-.
Specifically, A) SOPs for aseptic processing were not followed and aseptic techniques used during the processingof drug products arc deficient as demonstrated by the following observations made on 3/l 8~ 19/13 : 1) Personnel with exposed. skin (face and neck) were observed leaning their head and torso inside and resting forearms on surfaces while processing injectablcs inside the ISO 5 Laminar Air Flow (LAP) hoods. 2) Personnel working inside an ISO 5 tAF hood Specialty Infusion (Sf) #3 LAF hood was observ ed leaning into the hood, with her face positioned over an open container while drawing solution into a syringe. 3) An employee processing injectable drug products in an ISO 5 LAP hood was observed to have facial hair exposed. 4) During filling of an SI morphine syringe prescription, a plastic cup containing reconstituted morphine powder was taken out of the hood and reintroduced without first disinfecting it.
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5) A technician preparing to work in 81 #2 did not disinfect equipment including packaged syringes , cap s, vial s, and mi xing containers before placing them in the ISO 5 LAF hood. 6) The following observations were made about the surfaces inside the ISO 5 LAF hoods where injectable dru g products were being processed : a) Whitish re sidues were apparent on the~ grating covering thellEPA filters in the back of the horizontal Dow hoods and on the light covers inside the ISO 5 LAF hoods. b) Dark, amber-colored stains were apparent on the HEPA filter of the horizontal flow ISO 5 LAF hood and in the crevice along the sewn of the filter grate. c) Dark splatters were apparent on the light fixtures above the critical work space inside a ISO 5 LAF hood. 7) Equipment and production supplies were placed in front of the IIEPA filters in the horizontal flow ISO 5 LAF hoods in a manner that appeared to obstruct airflow to th e critical workspace. 8) Dispensing of non- sterile morphine and bupivicaine powders was not confined within an ISO 5 LAP hood. 9) IV bags stored in an uncontrolled manner for examples, port facing ncar floor , bags on rack near floor, bags hanging halfway out of the ISO 5 area wita ports exposed, and bags not spayed as required with H) Your firm ascpticall~ the injectable Morphine IT, Morphine /Bupivacainc, FentanyIlBupivacaine, FcntanyIlBupivacaine/Clonidine and stock solutions utilizing a . The followin g observations listed below were obs erved: 1) There were no validation records available for th~ sterilization step. 2) According to testing procedures is to be performed to assure the integrity of~ used. There were no records describing how th~ will be wetted, how much pressure will be applied and what the specifications for t h e _ value arc.
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INSPECrIONAL OBSERVAll0m
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3) There were no instructions on how the _ value will be calculated and thc specifications. unit were incomplete and did not describe how to 4) Procedures on how to use the sterile . :fill the syringes, how to aseptically remove th~ cover from package, how to attach the . and deliver the solution. S) For 15 Morphine IT syringes orders. 8 Fentany l 1 Bupivacaine orders and 15 Morphine /Bupivacaine orders ~ was documented to assure the integrity of th~ sterilization step .
e) The media fills conducted 09/1 712012 through 03/1912013 do not simulate the production of injectable drug product s produced in your facility. The pos itive contro ls were performed for the media ~ used in the media fill studies. The media used in the media fill have not been verified to support microbial growth. Additionally. the procedure 4.16 PrOCCS1; Verification was incomplete in that the SOP does not describe the steps for adding contents of the ampoule. sanitizing the work area and aseptically attaching the needle.
OBSERVAT ION 2
Clothing of personnel engaged in the of drug products is not appropriate for the duties they perform. Specifically, A) Gowning apparel is not sterile and does not provide coverage of the eyes, exposed skin, and hair on the face 3IId neck: of
the personnel who process injectable drug products insidethe ISO 5 LAP hoods.
B) Gowning practices are deficient in that disposable lab coats are Inmgup in the (sO 8 anteroom andreused by personnel who are returning from lunchbreaks to processing inside the ISO5 LAF hoods.
OBSERVATION 3
Buildings used in the manufacture, processing, packing, or holding of a drug product do not have the suitable construction to facilitate cleaning,maintenance, and proper operations. Specifically,
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A) On 3/18/13. the following deficiencies were observed in the design and maintenance of the cleanroom and ISO 5 LAF hoods that are used for the processing of injectable drug products: 1) Pre-filters installed on ISO 5 [ ,AF hoods were not fitted inside the filter frames and were covered in dust 2) Light covers above the work space inside an ISO 5 LAF hood were bowed so that openings were visible between the light bulbs and the cover.
3~inspection and cleaJj}8:hroutine preventative maintenance, and IX:.iodic ft,'fclaccment o - llters on the ISO 5 I oods was not performed as required per the SOP or Laminar Flow Hood Maintenance.
4) LarOe~ps were present between the doors separating the ISO 8 and ISO 7 areas that support
the IS
oods.
B) The _ I S O 5 LAP hood certifications performed by a third party vendor in June 2012 and Jan. 201 3 were not adequate to demonstrate adequate control of air flow, performance of equipment
respon sible for assuring air quality, and the absence ofmicroorganisms. in that : ISO 5 I AF hoods and samples were 1) Surface sampling was performed in only _ taken from the samllhoods in June 2012 and January 2013. 2) Smoke studies were not performed under dynamic conditions with in the ISO 5 LAF hoods. 3) No criteria was established to measure acceptability and uniformity of air velocity across the HEPA filters inside the ISO 5 LAF hoods (aka clean air benches).
OBSERVATION 4
Equipment and utensils are not cleaned, maintained, and sanitized at appropriate intervals to prevent malfunctions and contamination that would alter the safety, identity, strength, quality or purity of the drug product. Specifically,
Eiii PLOYI:E($) $IClNA~
100...."
SEE REV ERSE OF TH IS PAGE

l(}RM Jll)A .!CJ 1' ~1tl81
Anita R. Miohael, I nve s t i gat o r

J u l i a n n e C.
~cCullouqh ,
t7":~
OAT ~
I nvest igator
Ii'OSPECTJONAL OBSRRVA-rro-e
04 / 0 1 / 2 0 13
M (fij 4 OF i plIlJES
fl'E\IJOC'S l'Jlr.'lON OAilO:llTIl
D EPARTI\-flo:NT OF II F.!\I.111 AND H UMAN SI:RVln: s

Dr.nRICT~ANDPHOI1" ..AA.U.R R
-,F ' OOD AND DRUG ADMINIl,1:RAIION
US Cus toK~ou se , Rm 900 2n d & Ch estn u t St Ph i l a d e l phia, PA 19106 ( 2 15) 597 -439:) ~'ax : (2I5) 597- 087 5 I ndus t ry I n f o r n ati on : www. fda .gov/oc/in dustry
TO:
FIRM
03 / 18/ 2 013 - 0 4/ 01/20 13*

30064892 93
NN.'"
Joseph C . Cosgrove , Ch airma n a r.d Chief
E:x e cut ~l ~ ' v ~c,,-,O~f~f~,~ ' c~e~r "--'
-l
Products
sTRlE ....OOOESS
Pe n t e c Health, Tn c.
CITY, S ....I F, l'I' CllDI:, COl)'fT'l"f
Bo oth wyn , PA
19 0 61 - 3 1 3 2
Producer o f I n je c table Oru
!f!I!!!I!IIlI!!
sur aces InSI e c
OBSERVATION 5
Cleaning validation studies were not conducted for the ISO 5 LAF hoods to establis h clean, dirty, and sterile hold time ~ and determine the effectiveness of cleanin methods to remove roduct resid ues and microorganisms. Only
0 5
are used.
s.
to clean and sanitize
Sampling and testing plans for drug products are not described in written procedures which include the method of sampling and number of'units per batch to be testod.
Specifically,
1. For Proplete IV (containing Pro sol, De xtrose and Water for Injection) the testing plan described in the procedure End Product T esting 4.22 does not inc1ude sample size (number ofTY bags to be pulled) or data to support th e sample is rep resentative. For exam ple. the procedure read s products will be submitted on ba sis but does not indicate how many samples will he pulled for testing. Additionally, the procedure End Product Tes ting 4.22 indicates the sample will he tes ted for st erility for a period o~ from date of production. Testing records provided documen_ _ sterility. Also, no endotoxin studies are performed on the final product.
a _
mglml 2. For the Stock Solutions Bupivacaine 30mglml, Morphine SOmg/ml, or Hydromorphone I (lO th e procedure is inc omplete in that, it doe s not include the sample size o r a description of the sampling plan. Procedure 6.4 Quality Assurance of'Batched Compounds indicates to ~lect representative samples of the drug bat ch but do es not explain the numbers o f samples that will be pul1ed or how the sam ples will be selected.
3. The SOPs concerning sterility and en dotoxin testing for injectab le drugs were not signed or approved by a qualified person.
C per the test 4. Finished products were not in cubated method. The end prod uct test log for March 20 13 indicated that IDlIN an d IPN injectable products were inc ubated at temperatures above 39 "C .
31_
t----~-_, -E"'~) SIG .....T1Jll.E -
Anita R . J u l ianne C . M c Cul l ough. I nvest i ga to

f.'jSI'F crl(}~AI.
- - - -- - - - -- -- - - -- - - - - - -'_.M"""el$slu:l",__- - I Mi c h a e l, I nve s t. Lq a't.or- tlIl Ar ......

0 4 /0 1 / 20 13
ORSER" ATlO~S
lJU'ART"lEJ\T 01. HEAl:IU AND IIU~IAN S.:RVICES
f---o;m~~~oi;jeNJ""""
soonA."ID DRL'G ~TRATI(l.N
15 . :fE(S) CF"iWECTICN
U S Cus t omhou se , Rm 90 0 2n d Ph i.La dc Lp h i a , PA 191 06

N""" A!"&l rIlLE OF I ~ C/V """"" lU \\iH '..,M
~ Fr lMl
&
Che stnut St
03/18 /2 013
FE ~UM9i:1l
04/01/2013*
(21 5 ) 597-43 90 Fax : (215 ) ~ 9 7 -08 7 5 Indus try I n forna tion : www . fda . gov / oc / inuus try
LSW...,
30064892 93
ro.
!-iR/.,lNO'ilF
J os e ph C. Cosgrove , Chair ma n and Chi e f Executive Off i cer

~'tll ~ AOD RSSS
Pontec Heal th, I n c .

"TV, STATE,L IP CODE, OO'J!<TRY
4 Cre e~ Pkwv Ste A

1YP~
... 'TA IlIt"'F ~ r NtiFt:.CTI:O
Boo t hwyn, PA
1 90 61-3132
Produ ce r of In j e ctabl e Dr u g Pr o du c t s
OBSERVATION 6
There is no wriucn testing program designed to assess the stability characteristics (If drug products. Specifically,
1. There is no w tritten s tability program in place or stability data available for prescrvative free Proplete (containing Prosol, Dextrose and Water for Injection) to support a 21 before use date. The final product is not sterilized by filtration Of any other means . 2. There is no written stability program in place or stability data available for the preservative free Stock Solutions Bupivacaine 30mglml, Morphine 50mg1ml, or Hydromorphone ] OOmglml 10 support a 14 before usc date. These Stock solutions arc further processed with non-sterile powders such as Bupivacaine, Morphine, Hydromorphone or Fentanyl. The final preservative free injectable drug is steril~ but not tested to assure sterility. The final drug is assigned a 3 before use date.
OBSERVATION 7
There is a failureto thoroughlyreview any unexplained discrepancy and the failure of a batch or any of its components to meet any of its specifications whether or not the batch has been already distributed.
Specifically, A) On 12/06/2012 Bupivacainc 30mg/mL was OOS with a result of 111.52% concentration of33.46 No investigation into the root cause was mg/mL. 'Ih e specification forpotency/purity 1S performed. Additionally, there was no laboratory investigation conducted to determine if the sample was prepared correctly, expiration dates for materials, and if the method was validated. B) Recurring organisms found in the ISO 7 and ]808 classified support areas were not thoroughly investigated and trended, includingPasfeurella SlJD., and no nroduct impact assessment was made.
OB SERVATION 8
The control systems necessary tu prevent contamination or mix-ups are deficient Specifically,
F MP!.OYEE(I",) S'G NilT\.O<E
llA i1i I""'1I'tl
SEE REVERSE OFTHISPAGE

F'OR),I FPA #3 (Omt)
Ani ta R. Mic h ae l, I n ve s ti ga t or t?;,(~/~ J ul i a nne C. M cCu l l ough, I n ve s t i gat o r~ L

I'll!> W)IJS l;I'>fI'Tm ODOOI F I1'
04/ 01/2Q13
PACE 60F 8 PAGES
I~SI'I:Cl'JONAL OBS
Mf"VATTONS
.
oiSi'RiCr AD~ """ "HOlENlJl,iiiLR
DEl'ARTl\t:E1'''TOFHEALm A.'\ 'D m.-"fA,N SERVICES

FOOD M"D !?!tUG Amffi'U_ST.RA 'gQ!'!...
W;TUlll Oi' ~~CT IONl
US Cua t.cmhou s e ,
R'T. 900 2n d & Ch e stnut St Philadelphia, PA 1 91 0 6 Fax : ( ? 1 5 ) 597-0 875 (?IS) 597 - 4390
03 /18/2013 - 0 4 / 01 / 20 13 *
...
3 00648 97.93
I ndus try Inforna t ion : www . fda .aov/oc/ industry

_,0,"10 TrTlECflN~I\IIOlJJ\I.. TIl........oM RLPO RTISnu
TO:
' mtAtl"ME
Jos e p h C. Cosq r o ve,
Ch ai rm a n a n d Chie f Execut ive Of f Lc e r

sli~~i:OS
Pcntec Health , I n c .
COTY. ST~1E. ~ ~ C O ~ F. 00\.0<
4 Creek Pkwy Ste A

TYPE f ST/IIlU 9H..... 'ff INSl' Ee TFll
Boothwyn, PA
1 90 6 1 - 3 132
Producer o f I n je c t abl o Drug Products
1) Personnel and environmental monitoring of surfaces and active air sampling is not performed
on each day that injectable drugproductsareprocessed inside the ISO 5 LAF hoods
2) Personnel monitoring does not include sampling of employees' foreheads, labcoats, or
sleeve cuffs.
3) ISO 5 LAF hood environmental and personnel monitoring samples are not incubated according to the prescribed test procedure. 4) Testing of ISO 5 I,AF hood environmental and personnel monitoring samples is not adequate to detect all objectionable organisms that may be present, including yeast and mold
5) paddles that arc used for environmental and personnel monitoring are not qualified or challenged before use to assure they are capable of microbial growth.
6) The incubato rs arc not qualified or subjected to a periodic preventative maintenance program.
OBSE RVATi ON 9
Written procedures arc lacking which describe in sufficient detail the receipt, identification. storage. handling, sampling, testing, approval, and rejection of components, drugproduct comainers, and closures. Specifically,
Component vendors have not been qualified and verification of the identity and potency of drug components, and verification of the sterility and dcpyrogenicity of drug components, processing equipment, and packagin g components is not performed.
""'f'\.DYE4:l) ~ 1",""TUlIE
l>'\TE ISS\:ED

lUltM FDA ~~ IOW!l
An ita R . Michael , I n v est i ga t o r Juliann e C . McCu l l ough , I n v e st igatDr(p OJ1~

l'Il.I'VI<lU ~E'DmON OIlSCtElli
tNt{
0 4/ 01 /20 1 3
PAGE10l'3 PAGl'S
[NSrECnONAL OR,SERVAn ONS
DEPARTMENT OF HEA.LTDA."ID HUMAN Sf.R:VlCES

FOODAND DRUn ADMlNlSTRA TION
m .....Rlc:r AOORE'BSMo r HO NE I<I.JMtlER
rlAlEI"J
QF'1NSPi..CY ioN
US Cus t omhous e , Rill 900 2nd & Chest nut S t Philadelphi a, PA 1 9106 (215 ) 5 97-43 90 Fa x : (215) 5 97 - 0875 I ndus try I n f ormat i on : www . fda . gov / oc/i n dust ry
0IM1E"'.Nll nllE I;F lorl~I DUIo.L TO w-Kl MREFORT ISsuOO
0 3 /1 8 / 2 0 13
>EJ !'f.MIEI<
0 4 / 01 / 20 13*
3006 48 92 93
TO :
FIM\l
J o s eoh C. Cos o r ove, Cha i rman and Chi e f F.xec u tive Of.fic e r
5TRFF.T""'REOO
"""'F
...-iiff
Pe n t ec He al l h , I r:..c .
CITY, s-r""i;"lF. O' CUOE ,=
4 Cr eek Pkwy Ste A

TYl'f' Fli;"iJL_ONT IN ~?FC TF ll
Boot hwyn , PA
1 9 061-3132
Pr odUCl::!r of I n j ec tabl e Dr-uq Products
--
--
* DAT ES OF INSPEC TION:: 03/1812013(Mon)" 03/1912013(Tue)"0312012013(Wed)" 0312112013(fhu), 0312612013(iiJe), 03127f2013(Wed), 041OW:013(Mon)
_
l'OR .... l'J} A 4113 (11I11)II)
....ru~
Ln v e s t i. q a t or-
An ita R _ Mi c hae l ,
Julian nG C . McCul lough ,

~;U;VKl1 J8 JD)IT\OH
:~t:'"l ~~ I nve s t i gat r . ' / . . . i 0 4/ 01/2 013

PAUl! 3
O~ " PA(;f; ~
_~ #
r ED
00 SOJm'Jl
ViSPECfiONA1 O}( SERYAll0NS
The observations of objectionable conditions and practices listed on the front of this form are reported:
1. Pursuant to Section 704(b) of the Federal Food, Drug and Cosmetic Act, or
2. To assist firms inspected in complying with the Acts and regulations enforced by the Food and Drug Administration
Section 704(b) of the Federal Food, Drug, and Cosmetic Act (21 USC 374(b)) provides:
"Upon completion of any such inspection of a factory, warehouse, consulting laboratory, or other establishment, and prior to leaving the premises, the officer or employee making the inspection shall give to the owner, operator, or agent in charge a report in writing setting forth any conditions or practices observed by him which, in his judgement, indicate that any food, drug, device, or cosmetic in such establishment (1) consists in whole or in part of any filthy, putrid, or decomposed substance, or (2) has been prepared, packed, or held under insanitary conditions whereby it may have become contaminated with filth, or whereby it may have been rendered injurious to health. A copy of such report shall be sent promptly to the Secretary."
DEPAH.TMt;NT m ' IIt: ALT H !\ ~ D HUl\.lAN SI:RVI(t;S

rOOD AND DR UG ADMINISTRAT ION
OIS TPICT ' DOIlESS >.NO_ Nl.lMBER OATlhS1Of INSOECTJON
555 Winderley Pla c e , Suite 200 M;\ it la nd, FL 3275 1 (407 ) 47 5- 47 0 0 Fax : ( 407 ) 475 -4768 I n d u s t r y I n f o r n a t i o n : www.fda .gov/oc/industr v
""ME ANti f m::rOF INorYlOI!.Ol.TO WHOMREPORT lSSVEC
0311 8 / 20 1 3
~ ,-
03/22/2013
30 046 68624
TO:
"~M _
Shi rle y M. Spelich ,
Pha rm a c y Depa r t me nt
Man age r
e TRUT"'''''''~
THE COMPOUNDING SHOP,

CIT\'. STATE, Z"" CODE, COUNTRY
INC.
4000 Pa rk St N
PE ESTABlI SHIoIENT
I~CTED
St Petersburg , FL
33709 -4034
Producer of ste ri le druCJs
This document lists observations made by the FDA representativets) during the inspection of your facility. They are inspcctionaJ observations, and do not represent a final Agency determination regarding your compliance. If you have an objection regarding an observation. or have implemented, or plan to implemcot, corrective action in response to an observation. you may discuss the obj ection or action with the FIJA representativets] during the inspection or submit this information to FDA at the address above. If you have any questions. please contact FDA at the phone number and addressabove,
DURING AN INSPECTION OF YOUR FIRM WE OBSERVED;
OBSERVATI ON 1
Procedures designed to prevent microbiological conta mination of drug products purporting to be steri le are not establi shed, written, and follo .....ed. Spec ifically,
a)
Owing the aseptic preparatio n of De xam ethaso ne PF, lot # 031520 13@20, performed o n 3120/ 13 by a pharmacy tec hnician in ISO 5 hood in c1ean room # I, we observed the following deficienc ies in aseptic technique: I ) After touc hing an unsa nitized pen to document info nn ation in the Logged Formula Work shee t located in the pass -thru t unnel bet ween the pharmacy (uncontrolled area) and the ISO 7 c1eanroom, the techn ician quickly proceeded to grab and tra nsfer wrapp ed suppl ies and instruments store d in a cart in the ISO 7 cleanroo m into the ISO 5 hood without proper sanitizat ion of hand, and supplies. closely line d- up ope n 10cc vials whe n manual ly filling 2) The technician worke d directly ove r the m with a product-filled syri nge fitted with a 3) Once open vials were filled the technician o pened the wrapper containing rubber stoppers. and grabbed and pressed a stopper on each vial directly with her gloved hands. Gloved hands we re sanitized too ls were used to hand le only once at the beginn ing of the fill ing operation and no sanitized 0 1 ste rile contai ners and closu res. No further sterilizatio n is conducted for this prese rvative-free d rug prod uct and no sterility and endotoxin testing is performed. During th e repac kaging operat ions of Bevacizumab 1.25mglO.05ml injectable, lo t # 03 1520 13@19, prepared on 3/ 18/ 13 by a pharmacy technician in the ISO 5 safety hood in C hemo Roo m # 1, we observed the follow ing defic iencies in aseptic tec hnique: I) A non-sterile mat stored in an open plastic bin in (he ISO 7 cleanroom was placed directly onto the working surface of the ISO 5 hood witho ut any sanitization. These single-use mats are previously stored uncovered and unwrapped o n an o~n shelf in the pharmacy ( uncontrolled area with a sink.) unt il sup ply is depleted in the ISO 7 clean room, a t which time they are tra nsfe rred to the open bin in the ISO 7 cleanro om. 2) The tcchnician placed the decrimping tool , alcoho l pads, and the sealed via l ofbevacizumab (Avastin) directly onto the mat without proper san itization ofthe supp lies and g loved hands.
b)
AMENDMENT1
fIAf'l CYEEISl SCNATURE
coe esosc
. I nves t i ga t o r~~ ~
SEE REVERSE OFTH ISPAG E

FORM FDA .f8J (OWS)
CDR Ileana Barre t o- Pett i t ,

Ni c h ol as P . Diorio ,
nEVI OU $ H>JTI(IN OBSOU:TI!
Irive s t. Lqa t or-
,...-
."'
03/2 5 / 2 0 13
' ''0 I Of I Ql'''GES
INSPECfIONAL OBSE RVATIONS
DEPART1\-IEl"rliOF II[ ALT H AND

D<s TR'cT ADDR ESS At<[) PHONE NUMBER
H U~I A'"
SERVICES
OA TE1 Sl OF I'IsPE CTll,>N
FOOD AND DRUGADMlNISTRATI ON
555 Winderley Pl a ce , Suite 200 Ma itla nd , FL 32751 (407 ) 475-4700 Fax: (407) 475 -4768
03/1 8/2013
Fa NuMBE"
- 03/22/2013
3004 66862 4
Industry Information : www .fda .qov!oc/industry

NA ME.....D TInE OF I.DMJIJAl TO \'>HOM"EF>OI<' ISSUED
Shirley M. Spelich, Pharmacy .THE ". COMPOUNDING SHOP, INC.

TO:
"""' ~
e"",, SU
Department Manager
5n=' -"""""S5
4000 Par k St
TI', 2 ""COOE,
C<JlMqy
T'1<>E FSTA aJSJoHF >IT SOI'C'l'D
St Potersburg , FL
3)
33709 -4034
Producer o f s terile drugs
After sanitization of hands, she decrimped the Avastin vial, removed the rubber stopper with gloved hands, and placed the oren vial on a plas tic holder placed onto the non-ste rile mat. She then proceeded to work directly over the ope n vial to w ithdraw O .05cc of bevacizu mab to fill a total of syringes. Each syri nge was recapped with Its original cap. This operation lasted about 30-45 minutes and sanit ization of hands was cond ucted once at the beginning of the operation.
The same deficiencies were observed in the repackaging of Bevacizumab I .25mglO.05ml injectab le, lot # 03I l 20 13@l ;10 ) conducted immediately after the co mplet ion of the above named lot. Both lots were distributed the next day, 3/ 19/ 13 without completion of'thr sterility test performed by a contra ct laboratory . A 90-day expiration date of 6/ 13/ 13 was assigne d to these preservative-free batches. c) During the syringe filling operation of Morphine/Clonidine 25mg/500mcg/ml, lot 03 1920 13@45 and Morphine Sulfate PF l OOmg/ml injectable, lot 03 192013@42, we observed the technician forcefully 'banging' the plunger end of the capped syringe against the surface of the ISO 5 hood in order to remove an air bubble from the large syringe. This practice obse rved for both fills can potentially increase particulates in the ISO .5 environment. Media fills conducted by the flrm within the ISO 7 (ISO 5) env ironments were found to be deficient in that: I. They do nut accurately si mulate product ion processt:s and conditions that would best represe nt worst case conditions and opt imize detection of any micr obiological contam ination. For example, the firm's media fill procedure uses . . . . vials and does not represent the worst possible case for 50 and 100 m l vials filled at the firm. Similarly , media fi lls do not demonstrate lengthy processes of30-45 m inutes as observed during repackaging operati ons of bevac izumab syringes on 3/18 /13 . 2. No growth promotion test is performed on the media prepared in-house to demonstrate that it promotes growth of gram-negative and gram positive bacteria, yeast and mold . 3. The med ia fill reco rds do nor include sufficie nt detail such as which ISO 5 env ironment Dr room was used to conduct each med ia fill. There is no antimicrobia l effectiveness data for injectable and opthalmic drug products co nta ining preservatives such . Some ofthese drug products include Progesterone in Sesame Oil as or 100mglmi injectable, hydroxy progesterone caproate, and randrolo oe decanoate (o live oi l) 200mgfml injectab le. In addition, they have not evaluated whether the sesame oil or olive oil inhibit or promote growth of m icroorganisms.
d)
e)
OBSERVATION 2
Aseptic processing areas are defic ient regard ing the syste m for monitoring environmental conditions. Specifically, your firm has not established adequate written proced ures for environmental monitoring (EM) that describe
AMENDMENT 1
Et.FI.OYEEIS)SIGNA TlJI<E
SEE REVERSE OF THIS PAG E

tVII JI1 flM ""'(...""')
CDR Ileana Barreto - Petti t Inve sti gator Nicholas P. Diorio , Investigator
""'VKliJS tJ"fIO'<OO \Ol J.:l ~
Qrff
o.o. T'EISSlIEO
03/25/2013
r~lih l
INSP E<"'T IO NAL OBSER' ATIONS
ot 10 M lihS
DEPARTME NT Of HEALTH A ND HUMAN SERVl ns

o'S .... H;T Al)l)RF$S A"O _ _BER
soou ANi) lJIHXl
AlJM INISTRAT ION

D/lTEiSlOF"sPE ~
555 Winder ley Place, Suit e 200 M aitland , FL 32751 (407 ) 475- 4700 Fa x : (407) 475- 4768 Industry Information : www. f d a . q ov / o c / i n d u s t r v
N.'ME mol OF INDlVfJU"'- TO'MiClM I!6'ORlISSUEo
03/18/2013
FE! NJ """R
- 03/22/2013
3004668624
TO:
FIRM........
Shi r ley M. Spelich , Pharmacy Departmer.t Manager

.;T~ ~~1 .....-~""
THE COMPOUNDING SHOP , INC .

CITV. STATE. ZiPCOOE. Coutro!V
4000 Park St
TvPE ESTAB u _NT INSPE CTED
St pot.oz-cbuzq, FL
33709 -4034
Producer of sterile drugs
t iming of samp les (during or at the conclus ion ofoperations), specific samp ling eq uipme nt and techniques. alert and act ion levels , and appropr iate response to deviations from alert or actio n levels. Pharmac y tec hnicia ns only follo w the "Touch plate general locations for air samp ling(settle plate) and _ locations for s urface sam pling testing" form wh ich list_ (touch plates) w ithout any instructi ons. Upon re view of 20 12-20 13 EM records and interv iew of the pharmacy technician respo nsi ble for sampling, the following practices were found:
a)
b)
c)
d)
0)
Surface samples are only ta ken aft er cleaning and san itization of the ISO 5 hood and ISO 7 c1eanroom and not during or immediate ly afte r production . Samp ling locations are not acc urately specified when taken. For example, the touch sample location reported on the plate as "s tainless steel tab le" was identified by the technician who took the samp le as the ISO 5 hood surface and not the stainless steel tab le in the ISO 7 roo m; whereas the pharmacist who read the plate iden tified this location to us as the sta inless stee l table in the ISO 7 cleanroom. The location "stainless stee l table" is actually the ISO 5 hood. Resu lts of plate readings performed by the pharmacists are not consistent ly reco rded and do not sho w date of readi ng. It was reported that prior to the inspection plates were rea d afte r 14 days, and not after about 3-5 days of incu bation. It was also reported that plates were often dry upon read ing at 14 days. There are no established alert limits. The phann acist repon ed only an "action" leve l o ~ for both the ISO 5 and ISO 7 areas, without any j ustification for these limits. No env iron me nta l mo nitoring was co nducted bet ween 12/3- 19/ 12 and In - 2/6/ 13 due to reported unavailabi lity of plates. During the period of In -2/6/13, the finn produ ced a tota l o. injectable and opthalmic drug prod ucts. Enviro nmenta l exc ursions are not investigated, organisms are not identified, and corrective act ion is no t ta ken when action levels arc exceeded. For exa m lc, these arc some of the exc ursions that were recorded: Date Readm e Documented action 13 cfu in cart w/ supplics " will start wiping every day andre-test"; no 7/25/12 in Chern room (ISO 7) investigatio n was conducted and no 10 was eerformed. No action. This location is referred by the 7/26/12 3 cfu in stain less steel table in che m room technician as the ISO 5 hood. 7f26112 3 cfu in stainless stee l N o action. Th is location is referred by the table in steri le roo m technician as the ISO 5 hood. 7/30/ 12 5 cfu on stoo l in chern No act ion room 12 cfu "finger touch" No action. No investigation was conduc ted 8/1 0/1 2 and no lD was performe d. 8/21/12 "Growth multiple No act ion. No investigation was cond ucted colonies" on stool in and no ID was performe d. aseptic room. 9/10fl 2 4 cfu in stai nless steel No act ion. This location is referred by the & table in chern ro om te chn ician as the ISO 5 hood.
10/12/ 12
AM ENDMENT 1
E.......OYEElS ) SIG.....T\J RE
D/l fE ISSUED
SeE REVERSE OF THIS PAG E

!'UK'" ~ DA . " lll'Mlll)
CDR I leana Barreto-Pett it,
I n ve s t i ga t or Nicholas P . Diorio , Inves tigator

"""VKJIJS tarrK....QtbOU' 'E
{k7f
03/25/2D13
PAGE ) Of 10 PAGE S
INSPECTIO'lAL OBS ERVATI O'lS
"' 555
_.
COMPOUNDI NG SHOP, INC.
pc't e r ab uz-q , FL
g)
l>EP.o\RTi\lENT O F HEAtHI A!li l> II U).l.o\:~ SERVIO:S

HllJl) ANU UKOO A1JM1N ISTIlA IJON
W inder l e y Place , Sui t e 200 Ma itland , FL 32'751 (401 ) 41 5- 4100 Fax : (401) 415 - 4768 Indust rv I n f ormati on : www . f da . uov/ oc /industrv
TO:
03/181201 3 3004668624
- 03/2 2/20 13
,-THE: ,
St
~.
Sh i rl ey M. Sp e lict. Pha rmacy D e pa r t ment Manaqer
4000 Pa r k St
3370 9-4034
Producer of sterile d rugs
-_.
On 3120/ 13, upon inspec tion of EM samp le plates held next to the incubator awaiting reading by a pharmacist we observed a plate thai showed a glossy white, large microbial colon y that covered about 75% of the media . The plate was labeled as "3 15 sta inless stee l table sterile roo m"; this is the ISO 5 hood where all injectables are prepared . On 3/2 1/ 13, we verified that the plate was read : it was doc umented as +2 cfu and no action was taken. Upon interview of the pharmacist who read the plate, we found 01.11 that she d id not know that tile "stainless stee l table" wall the sample for the ISO 5 hood.
Fingertip samp ling of pharmacy technicians performing aseptic operat ions in the ISO 5 hood is not conducted at least daily after prod uction of steri le injectab le, intrathecal and optha lmic drug products. Viable monitoring of air (settle plate) is not conducted in the ISO 5 hood at least daily during product ion of injectable , intrathecal and opthalmic drug products.
h)
;)
.
OBSERVATION 3 Equipment and utensils are not maintained at appropriate interv als to preve nt contamination that would alter the sa fety, identity, strength, qua lity or purity of the drug product. Specifically, a) On 3/ 18/13 upon inspection of t he ISO 5 horizontallaminar flow hood used to prepare sterile injectable and optha lmic products in vials, the follow ing defici encies were observed:
I. 2.
3.
4.
At least te n ( 10) ex posed rust areas around the top light panel. A white patch about 2 "'1:2" on the the HEPA filter about 12" inches from the bottom surface and the right side panel. This patch was reported by a pharmacy technician as a "repa ir patch" that has been there for a long time. Numerous splattered brownish stains across the lower half o f the HEPA filter and cover gr ill. Dark area s of di fferent sizes on several places on the HEPA filter.
b) On 3120/ 1~ 3. upon inspect ion of the vertical laminar flow bicse fety ISO 5 hood where repackagi ng operations of bevec izumab are conducted. browni sh areas appeari ng to be rust were observed below the bottom air vent across the front side of the hood . c) On 3/ 18113, while observing re-pa ckaging ope rations of Bevacizumab, lot # 03 1520 13@19 and 031520 13@20, we observed brown ish stains resembling rust on the surface and legs of the sta inless stee l table in the ISO 7 cleanroom. We observed the technician place a tray of eighty (80) empty syringes on top of this tab le and then placing the tray directly on the ISO 5 surface ofthe hood without sanitizing the bottom of th e tray.
AMENDMENT 1
E~_noRE
coe eecee

I'O K."I filA . 114 1.... ""'>
CD R I l eana Barr eto -Pe tti t , I n vesti g ator Ni ch o l a s P. Di ori o , I nv es t i ga t o r

PRl!VlUU5 h"IllTIU!"
~ ,,('
0 3/ 25 /2 013
1' ~Vl:.. Ot
lJIJWI.>..,...
INSI'ECfIOSA L OBS ERVATIO NS
IVtJIUi-S
OlPARTM l NTm II EALTH A ND H U MA~ SERVIn s

HJO l) ANO UKUG ADMINISIRAT ION
555 Win de r ley Place , Suit e 2 00 Maitland , FL 32 7 51 (407) 4 7 5 -4 7 00 Fa x : (407) 4 75 - 47 68 Indu s t ry Information ; www .fda . ov/oc/in d us t r
WME
~NO
03 / 18/ 20 13 - 03/2 2/2013
300 4 66 86 2 4
mL..E OF
INDlVl DUI'J. TO 'M<I&l FtEPOFlT ISSUED
TO:
Shirley M. Spelich, Pha rmacy D e partment Mana er

40 0 0 Pa r k S t N Producer of sterile dru s
THE COMPOUNDING SHOP, I NC . St Pete rsburg , FL 33709-4034
OBSERVATION 4
Each batch of drug product required to be free ofobjectionable microorganisms is not tested through appropriate laboratory testing. Specifically.
a) None of the finished sterile drug products produced at the firm have undergone microbiological method suitability testing.
The method suitability testing is required to demonstrate the drug product test samples do not inhibit growth in sterility test media. For example; I . The firm performs in-house sterility testing on all intratheca l sterile drug products that include such finished products as: morphine sulfate injection, morphinelbaclofen injection, hydromorphone!bupivacaine injection, an iid. !I.I1II!!I morphineffentanyVclonidine injection. Sterility testing is performed by ofup to drug products with different formulations into one sterility growth vial contammg The firm has not performed method suitability testing for the pooling of these drug products into one test. Also, there is no reconcilability of the sterility of each individual lot. 2. The firm uses a comracr resung laboratory 10 conduct sterility testing on finished sterile drug products such as Avastln (Bevacizumab). The contract testing laboratory has not conducted method suitability test ing on the Avastin
( Bevacizumab) ste rility tes t.
b) The firm prcpares lll!lll!ll"'II!II!II!!1I11!II!I!IIIII!III!II!~ sterility testing on all intrathecal sterile drug products. A review of the finn 's .
0 , .
for use in perfonning microbiological preparation found:
I . The finn routinely sterilizes the prepared medium b) . The manufacturer's preparation instructions stare to the prepared medium a The finn has not perfonne d any stud ies to show the is equivalent to the manufacturer's validated . Additionally, the finn's have not undergon and the gauges nave not been calibrated 2. The manufacturer's preparation instructions state to verify the final pH of the sterilized media i~ . units. The firm does not check the pH ofthe sterilized media. 3. The firm does not use suitable strains o f indicator microorganisms when performing growth promotion testing on the . sterility test media. Instead, a technician 'spits' saliva into a specimen cup. dilutes with water and uses ~ aliquot for the growth promotion. 4. The firm docs not document the in-house steri lity testing on raw data worksheets. There is no documentation of
AMENDMENT 1
CDR I leana B a r r e t o - ~e c t i t, I n ve stigat o r Ni cho l as P . Di o r io , I n v e s t i ga t o r

INSI' ECrIO'lA L O BSERVATlO~S
03/25( 2013
Dl:PART!'II I': NTm II l:ALTIl AND IIU~IAS S. :R\/ICES soon A}lLJ lJKtJ(j AllMINlS1 II.ATlO N
M
~ ~~
-, ,-TO :
CJTY . fIT..
555 W i n d e r l ey Pl a ce , Sui te 2 0 0 Maitland , rt, 32751 (407 ) 4 7 5 -4 7 0 0 Fa x : ( 40 7) 4 7 5 -4 76 8 I ndu s t rv In f orma t i o n : www .fda . aov /oc /i ndu s t r v Shi rl e y M. Sp eLi.ch , Pharm acy De pa rtme nt Manaqer
u
0 3/18 /2 0 13 3004668624
0 3/ 2212013
THE COMPOUND ING SHOP, I NC.

St Petier ebuz-c, FL
40 0 0 Park St N
"""-_"" - ' : " '0
33709- 403 4
Pr o duc er o f sterile dr uqs
test samp le preparations. materials and instruments used, and consistent documentation of final test result readings of the sample and controls.
OBSERVATION 5
Procedures designed to prevent microbiological contamination of drug products purporting to be sterile do not include adequate validat ion ofthe sterilization process. Specifically.
aj Your finn failed to validate the used to sterilize all intrathecal. injectable and opthalm ic drug products produced by your firm from non-sterile components. In add ition, your finn has not e1>tablis ; r bioburden limits in order to determine ifit exceeds the maximum capability o f th bj
sterilizatio n process parameters for s t erilization of inj ectable drug products prepared from nonsterile components have not been validated . lJrug products such as Glycerin injectable are prepared from non-steri le prior to sterilization. These products are not tested for sterility prior to liquid glycerin and not _ release. of all injectable, intrathecal The results of the bubble point lest performed after conducting sterilization b) and opthalm ic drug products were nOI doc umented by the finn prior [0 3/ 14/20 13.
c)
OBSERVATION 6
Aseptic processing areas are deficient regarding air supply that is filtered through high-efficiency particulate air filters under positive pressure. Specifica lly, a) T he inital qualification o f the ISO 7 cleanrooms and the ISO 5 hoods completed on 411 4/12 by a contractor after the construction of the new c1ea nroom was performed under static "as built" conditions only. Tht re-q ualitication performed on 10/3112 reported that "up to two pharmacy personnel" were prese nt in the cleanroom dur ing qualification; however. these individuals were not identified and no one at the finn remembers being inside the c1eanroom during its latest qualification . Smoke studies of laminar air flow were reponed as acceptab le, but were not recorded and the report did not clearly specify if taken under dynam ic conditions. magnehelic gauges as identified on the gauge) for air press ure between the pharmacy, b) Monitoring of _ anteroom. and two \2) c1eanrooms is deficient in that:
I .
AMENDMENT 1
Er.oPLO'IU"($) _lURE
~~~
SEe REVERSE OF THIS PAGE

1'0 "-'" I'l'" 0""("''''')
CDR Il e a n a Barr e to- Pe t t i t , Inve st iga t or Ni c h o l a s P. Diorio , Inves ti g a t o r

......VIOO5~DIT lU " """""'-"11<
~
03125/20 13
PA(,iE OQf lO P.... vU
INSPECTJONAI, O BSI:R"ATIONS
DEPART MENT OF IU:AI.T H AND HWolA'i SERVICES

FOOD AND URUU ADMINISTRATION
llJoTE(Sl 01' NSf>ECnotl
555 W i n d e r l e y Place , Suite 200 M a i t l a nd, FL 32751 (407) 4 7 5- 4 7 0 0 Fa x : (407) 4 7 5 -4 76 8 I n d u s t r y Inf o r mati on : www . fda . g o v / o c/ i n d u s t ry TO: Shirley M. S el ich , Pharma c y
I NC.
z ,~
03 / 18 / 201 3 - 03/22 /20 13

F Ei NUMllE~
3004 6 686 2 4 Man ager
D e part~ e nt
THE COMPOUND ING SHOP,

C ,TV, sr .. rs,
4000 Par k St N Pr o d uc e r of steri le dru g s
com , COU Nn ",
St Petersburg , FL
33709-4034
demonstrate that the steril_
in spray bottles remains sterile until consumed. ISO 5 hoods.
c) Non-sterile wipes are used to wipe the interior surfaces of the_
d) Documentation of cleaning for the months of January and February 2013 is incomplete in that cleaning of the sterile room and anteroom was not documented for the month of January 20 13; similarly. cleaning of the chemo rooms I & 2 and certain areas of the sterile room were not documented forthe month of February 20 13. Therefore, it is not known if the third-party contractor conducted the required cleaning activities during these months. e) A sma ll broom was observed in the ISO 7 anteroom immediately below the air hand dryer. This broom cannot be properly cleaned and sanitized and would potentially generate excessive particulates.
OBSERVATION 8
There are no written standards or specifications, methods of testing, methods of cleaning, and methods of sterilization to remove pyrogenic properties. Specifically,
in-house are not identif j" .diW .;.th . , c) Wrapped glass vials, rubber stoppers and beakers sterilized and sterilization date, cyle, expiration date or a unique number that would allow traceback to the or
load'batch.
AM ENDMENT 1
DATE ISSU ED
seE REVERSE OF THIS P AGE
CDR Il e a n a Barreto-Pettit , Invest igator Nichola s P , Di o rio , Inve stigator

INSP I:CfIO "'lAL OBSEKVAT10:'oiS
03 /25/ 2013
Pl\tiE 8 UI" 10 PI\ GES
DEPART\I t:NTOf IIEALTII AND H UMA~ SERVICJ.:5

FOOl) ANl) lJ1WG ALl M lN1S1 RAT ION
O IST~'cT
AOORESSAtfO _
....... a ~ ~
o.o.TE(S! Of _
~eINUllBER
CT1<)N
i n d e r l e y Place , Suite 200 555 W Maitland , FL 32751 (407\ 475 -4700 fa x: (407j 475 -4768 Industry In formation : www .fda.gov/oc/industry
mo
Of "ID"":llJAl TO \f>ttO/Il RE"O'lT lSS'JEO
03/18/2013 3004668624
03/22/2013
TO:
Shirley M. Spelich , Pharmacy Department Manager

S TF<UlAOO R~ SS
THe COMPOUNDING SHOP, INC .

CITY, "'-Ai'lL 2'" COl>i', CCt)N'tllv
4 00 0 Park St N
_P;TA...."""'E.... INsPE cTED
St
Petersburg , FL
33709-4034
Producer of sterile drugs
OBSERVATION 9
Clothing of personnel engaged in the manufacturing and processing ofdrug products is not appropriate for the duties they
perfo rm.
Specifica lly. a) Operators performing aseptic operations in ISO 5 hoods re-use sterile gowns throughout a production day. As sampling of sleeves is not performed. your fum has no assurance that the ste rility ofthe sleeves is maintained. During the preparation of Dexeamethasone PF, lot 031520 13, on 3120/13, we observed the technician sitting in front of tile ISO 5 hood and the bottom of the sleeves frequently touching the ISO 5 working surface of tile hood. b) Facility-ded icated scrubs and shoes for all employees (including those working in the c1eanrooms) are stored on an open shelf rack in the firm's bathroom where employees change their clothes before going into the controlled cleanrooms to don ster ile ga rments. The firm's bathroom is not a suitable area for changing into facility-ded icated clothing.
OBSERVATION 10
Testing and release ofdrug product for distribution do not include appropriate laboratory determination of'satlsfactory conformance to the final specifications and identity and strength of each active ingredient prior to release. Speci fically, a) Injectable drug products prepared from non-sterile components an~sterilizcd are not routinely tested for potency, ster ility and endotoxin prior to release. Some of the injectable drug prod ucts include: methotrexate, testosterone, mitomycin, polidocanol, and dexamethasone. b) Intrathecal drug products such as morphine sulfate, morphine/clonidine, and hydromorphone are not tested for potency and endotox in prior to release.
OBSERVATION 11
There is no written testing program des igned to assess the stability characteristics of drug products. Specifically,
AMENDMENT 1
E...,..OYEE(S) S K7<ATURE
o.o.n; ,ssoro

~()RM
CDR Ileana Barreto-Pettit,
Inves ti ga tor Nicho las P. Diorio , Invest igator

""VouuS e,,, ' IV'<Of!>OI'> W
.Jr.WJ
03/25/2013
H"~ 9 0 ' )0
t IlA 4IU (1l'MI>I)
INSPt:CTIONAI, ORS I:R\' ATIONS
''''''+:$
DEPARH ILT\rjT OFH EAlTH A1'ID HUMAN SERVICES

FOOD A1'.D DRUG ADMlNISfRAHON
O,S....,CT AOC>RFSS A"O """"'" N'-"'BER OAtE($)OF W;PECTION
5 5 5 Winde r ley Pl a c e , Suite 200 Ma i t la nd, FL 327 51
03/18/2 013
FE'NUI.'B ER
- 03 / 22/ 2013
(4 07 ) 475-470 0
TO,
FlA M"''''''
Fax : (407) 47 5-4768
3004668624
Indu stry In forma tion: www ,fda ,qov /oc/industry

NAAIE,o,'lO TTTlE Of' INOI IIIW Al TO """""" REPORT ISScEO
Sh irley M. Spel ich, Ph a r mac y Department Manager

''' "~~T AOD'<~'"
THE COMPOUNDING SHOP, INC ,

CITY, STATE ZIPCOO.,COJIffi!V
4 00 0 Park S t
TYOEEm"ABl ,_>(IINSPl'CTl'O
St
Pete rsbu r g ,
.L
33709 -40 34
Producer of s ter i le druGs
a) Your finn lacked valid analytical and sterility data to support the 90-day expiration date assigned to repackaged syringes of preservative-free Bevacizu mab drawn from singl e-use vials According to your finn 's personnel, the expiration date was based on an article publis hed in the U.S. Opthalmic Review 2007 which stated that the potency of Bevacizu mab in syringes degraded 8.8% at three (3) months. However, this inform ation is not specific to your finn 's operat ions and does not address potential sterility issues. b) Your finn lacked analyt ical and sterility data to support the expiration date of 90 days for preservative -free inj ectable drug products such as Dexamethasone P.F. 4mg/ml inj ectable prepared from non-sterile components.
OBSERVATI ON 12
Routine ca librat ion of mechanical and electronic equipment is not performed according to a written program designe d to assure proper performance. Specifica lly. the firm docs not have a written program for and does not ca librate the following equipment: a) The refiigerator thermometers have not been calibrated. The firm's refrigerators are used to store such bulk products such as Avast in, Ascorbic Acid Inj ection, Amphotericin B, and retention samp les of sterilized Finished drug products. b) The: autoclave thermometers and pressure gauges have not been cal ibrated. c) The depyroge nation oven thermometer has not been caljbrared. d) The thermomete r in the firm's incubator has not been calibrated. The incubator is used to conduct in-house finished product sterility testing, media fills, and incubation of microbiology p lates used in environmental mon itoring .
AMENDMENT 1
~loF'I.O\'f;E( SJ
s .......TuR
DAtE ISSUEO

rul Ol
~ IM
CDR I l eana Bar ret o-Pett it , I nv e st i g ~~ , ~~ Nicholas P. Dio~io, Investigator ~I1l>-VlOllS l:1li1 '"'' ""'''(..ETE
'...l
03/25 /2013
PAOf'. 10 OF 10 ' AOES
"-'I "'_l
INSI' ECfIO!'lAL OBSERYATIO NS
3/ 2212013
13 : 4'3
7272El'3281 4
THE COMPOUNDING SH OP
PAGE
er/re
-,
~ .
DEY"RIMENT OF HtJ\Ull ,,:W IIl,;MAN SERVl CES

eee
FOOO AND CRUel A o."'lNl~AnON
~
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,~
555 W .1nd e rl e y Pl ace . Su i t.e 2 00 M,.. i ':: l l1nd . FL 32151 (4 0 7 ) 47 5- 4 7 0 0 F ax : ( 407 ) 47 5-4] ;;8
0 311 812 013

, ~-
- 03/1 212013
! l\d u9 t r y Info::ma tion :
"" ~ TO""""" '"
TO ,
- ~.
Sh i rle y M. S ~e li Ch .
,-
www.fda . cov / oc / ~ ndu s t r v

~ba rU\acy
30 0 H 6B62 4
D~ pd .r tme nt Ma naq 8 ~
5T" <~T _
TH E CO MPOUN DI NG S HOP , TN:: .

"" .O .N '1.l"o;OQlL
40 0 0 Pa r k St N
s< Pe t e : s b u,ro , fL
33 70 9 -4 034
Pr o duce r ot
~ t e r il e
d =uas
Thle docv mutl lists obJCtV:IrioM made by the FDA rep~Ulfl v(4) duri ng Ihe insptJottof yo ur facilit)'. They Me inspoctl.ol:a1 Omen.lltiMaS, llDd ee not ~c~11 final Ageno;y detaminarion reg.vdil'lg: your comrlillll<:e. Iryo u have fIfI objcdon rc:~:n8 lI'\ obscratinn. (II" MV<l mplcmcmed, or plGD to jmplcrrotnt, correcti ve oaioll in re..~ t(I an ob servation. you m lY discuss ~ objection. 01' aWorl with [he FilA. rcp~ IMi"'c(S ) during the inspection Of" JU bmit this in(onn tlion to FDA It the Md rcss ~r:. Jf you heve lilly qlJCstim " pleese contllct FDA " tile phorIe numba- lind addn;::;:s _boYl;.
DURING Nl INSPEcnON OF YOUR FIRM WE OBSERVED:
OBSERVATION 1
Proccdt1re3 designed 10 prevent miaobiologica1 contaminatitln of dru& prodlKtS pwporting to hi: sterile arc DC< esta blished.
written, and followed-_
Specifically.
a)
During the :n eptle preparation of DcxamethA..~o PF, lot # 03 1~20 I3@2 0, performed on 312 0/13 by a phannac)' technici an in ISO S hood in c1ean room Itl , we observed the ronowing deficienci es i n Meptic techniq ue: I) Afkr touching an un..~niti7..ed perl to docv mem infonnlnion In the t ogged Formula Worksheet located fn the pe ss-thru tunn el between the pharmacy (uncontrolled area) and the ISO 7 cteanroom , the tech nician quickly prDCCedod to grab and transfer wrapped supplies end insrruments stored in II. cart in the ISO 7 cleanrocm toto the ISO S hoed without proper san itization ofhand8 and supplies. closely Ilncd-up open lOcc vials whcn manually filling The technician worked directly OVCT 2) them with a productfUled syringe 1jtted with rubber stoppers, and 3) Once o pen via ls were filled, the technician opened the wrapper contolnlng gra bbe d and pressed a stopper on each vial directly with her gloved hands . Gloved hands were sanitized only enee At the beginning ofthe filling operation and no sanitized ~ too1s were used to handle eterile eontainers an d closures. No f'ardJer sterilixatioll is conducted r preservative-free drug product and no sterility and exJdotoxin testi ng ill performed.
th,'
b)
During the repackaging operations ofBevacizumeb 1,25mg1O,O$ml injectable, lor # 031520 13@19, prepared on 3/18113 by a pharmacy techn ician in the JSO 5 safety hood in Chemo Room #1. we observed the following deficie ncies in aseptic technique: I) A non _stn-ito mat stored in 1I1i open pla,mc bin in tho ISO 7 c1eanroom Wall pla ced directly onto the workin g surface ofthe ISO j hood without ~y sarlitlzation, these slng le-us<: mats arc previously stor ed uncovered and llnWfllPped on an open shelf in the pharmacy (uncon tro lled area with ll11ink) until supply Is depleted in the ISO , eleanrccm, at which time they are trnnsferred to the Opc'D bin in the ISO 7 cleanroom. 2) The tee hnid an pla ced the clecrimping tool. lllcoho l pads, and the sealed vial of bcvtlcizumilb (Avastin) direct ly onto the mat without proper f>31IiliDition of the mpplles and glo ved hands. 3) After ~ itizarion of hands.,. she deerimpcd the A va.rtirI vial, r~d the rubber :stopper with gloved haods. an d placed the open vial (H). a pla stic holder placed onto l1.lc: non- sterile mat . S he then proceeded to work
t ~-.r",":
se~REVERSE
CDR Ilea ~a Ba rreto Pe t t it , Invest ig~t ~~ ~

Nicholas P. Diorio .
~ mcnooo""""""'l'
"'''' '::o>.EI
OF THIS PAGE
_"lftM ~ -,
Inve ~t i ga toyi ~a_ ",.e.:r
P {JO
0312212~13
essescnc....AL oR s Rv"nOflo'S
.. "Go;" I 01' to .. _ 5
83/ 22 /26 13
13 : 49
72720 928 1 4
THE COM POU NDI NG SHOP
PAGE
82!1El
DEV"RTMENT OF HI:i\LTH AND HlTMANSERVICES

Ilocr IWlIR .SS ANI) "H~ . Nl.""ll'"
FOOD ANDDRUG ADMThumA'rIO~
....""'m'Of 1~"1 1ON

Sl~ i te
5 5 .li W.i. nderle:y E'lace ,
200
M ai tli.md , FL 3 2 7 51 ( ~ 07 ) 475-4 100 Ftl x: { ~O 7 l ~ 75 -4 766 I n dus t r v In forma tion: www .fQa.Qov!oc/i ndu stry
-~,
0311 8/ 2 01 3 - 0 3/2 2/ 20 13
~,
3 0 0 466E6 :?; 4
., . .. ..
rc r
.~
~
sru eaev
~
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","
M.
S p g l i ch, Fharma cv D epart men t Ma n a n er

>;'met . """"""'"
T HE COM1;>OUNDING SHOP ,
A
.Z1 P Cll llE. C:O U 'lT ~"
I NC .
400 0 l?ar k s r
~Ge.'rAaiilME"""' ~
N
ED
St
Pet e r :;bur l":T . FL
3370 9 4 0 ';.(
Pro ducQr of s t e ri le dr u o~
directly over me open vial to withdraw O.O.'ke orbevaelannab to fill a total of syringes. Each ayrlnge was recapped with its original cap. This operation tasted abcer 3()..4S minutes and sanitization of hands was conducted once at the beginn ing ofthe operation. The same deficiencies were observed in the repeekagin g of Bevacizum ab I 2 5mglO.OSml injectable, lot # 031 S2013@20 )~ conducted inunediately after the completion oflhe above named lor. Both lots were distributed the next day, 3 19/13 without completion ofth; sterility rest performed by a contract laboratory. A 90-<lay expiration date of 6/ 13/13 was assigned (0 these preservative-free batches.
c)
During the syringe filling operation of MorphinelClonidine 25mglSOOmcgiml. lot 03192013@45andMorphine Sulfate PF IOOmglml injectable, lot 03 J 920l 3@42, we observed the technician foreefully 'banging' the plUnger end of the capped syrin ge again st tho surf'lU:e of the ISO 5 hood in order eo remove an air bubble from the large syringe. This practice observed for both fil1.s can potentially increase paniculates in the rso 5 envrrcemeat,
Med ia fills Conducted by the firm within the TSO 7 (ISO 5) environments were found to be deficient in that: 1. They do not aCQffiltelysimu late production processes nnd conditions that would best represert worst cas e conditions and optimiu detection ofany microbiological centamination. For examp le, the firm's medi a fill procedure uses . vials and does DOt represent [he worst possible case for 50 and 100 ml vials fHled at the finn. Similarly, media fills do not dem onstrate lengthy processes of3(}.-45 minutes as observed during repackaging QperatiQns ofbevacizumab syrin ga em 3/ 18/ 13 . 2. No growth promotion test is performed on Ule media prepared in-house to demonstrate that. it promotes growth of gram -ne gative and gram pqsit ive bacteria. yeast and mold. 3. The media Fill records do not include suffick:n( detail such as which ISO 5 envir onment or room was used to conduct eac h media filL There is 'IW antimicrobial effectiveness data injectable and opthalmic drug products containing preservatives such a 01 SOme of the lie dru g products include Pecgesrerone in Sesame Oil IOOmgiml injectable, bydroxyprogestcrone caproate, and nandeolone decanoate (olive oil) 200mglml iDjeclable. III addition, they have not evaluated wbethcr the sesame oil or olive oil inhibit or promote grewth ofmicroorgani!J'nS.
d)
e)
rot
OaSERVATION 2 Aseptic processing areas are defic ient regarding the sy stem for monirerlng environmental con ditions.
S pc ci fiu lly> yo ur I1rm hll~ rIO! dbiblixhcd adequate wr inen procedures for environmental mcnitcnng (.EM) that describe timin~ of samples (duri~ or at tb~ conclusion of operations). SPe>mlC sampling equipmcllIllIld techniques, alen and action levels. and appropriatt response to deviations from alert or action level3. Pharmacy technicians only follow the "Touch plate testing" form which list generat Iecetlone for air aaml'Ting (seale plate) 8n< I OClltlnn.~ for surface sampling (touch plates) without aoy ;nstnlcrlnn.~ . Upon review o(2l)122013 EM records end lnreevtew ofmc pharma cy recbniejtJJ1
E>olPLDTEEl'"l lII'>I'OhTlM:ii.

IIUIlM
C DR I leana Bar reto- I?et t it , j nveatr i qa n orNi c holas P. Diori o, I n Y'e3t igato r
.f/$W>
fJr~
OIl>El:lal.IC~
0 3 / 2 21 20 1 3
t AG EZ OF , .
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lt~srECl10NA1, o"~~v i\ 'ness
fl3/ 22 / 201 3
13: 49
72720928 1 4
THE COMPOUNDING SH OP
PAGE
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DErARTMtNT OF HEALTH Al\b HUMAN SERVICKS FOOD AND ORU() ~rsTRA TION
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555 wind~rJ.ey Place, Suite 200 Mai t la nd, FL 32751 (" 07 ) 475-4700 f'a x:: (40 7 ) 0 5 -1\76B Indu.stry Information: www .fda . aov/oc/industrv
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4 0 0 0 Park S t
St Pe t er s b u r a , FL
33709-4034
Producer of
st~rilc
ciruc 5
respcnsible for sampling, the fo llowine pracrices were found:
,) Surface samp les are onl y tak en after cleaning and san itizati on or thc ISO .5 l100d and [SO 7 cleanroom and no!
during or immediately aftl:r production, Sampling locations arc not acc urately specified when take n. For example, the touch samp le location reported on the plate as "stainless steel tabl e" was identifaedby the technician wM took. the snrnplO!l lIS the ISO 5 hood surface and not the staIn less steel table ill the ISO 7 room : Wher'CM the ph&inaCist who read the plate jdenttfled tbie location to us as the stainless steel table in the ISO 7 c1eanrl;)om. 111e location "stainless steel table " is actually the ISO 5 hood. ej Results of plate readings performed by the pharmacists arc: not cons istently recorded and 00 not show date of reading. It W8$ TCJ:IOI1ed that prior 10 the inspection plates were read after 14 days. end not after about 3~ 5 days of incubation. It was abo reponed that plates were often dry upon reading at 14 day s. d) There are no established alert limits. The pharmacist reported only an "ection" leve l fur both the ISO 5 a nd ISO 7 are as, without an y j ustific at ion for these limi ts. e) No environmental monitoring was conducted between 1 2J3~ 19/12 and I n - 216/ 13 due to reported unavailability of plates. Outin g the period of In 216113. the finn produ ood a lotal injectable and opthalmic drug products. Q Environmental excursions arc not investigated, organisms are not identified, and corrective actio n Is not taken when action levels are exceeded, Fer exemcte. these are some of the exeurslone that were reco rded: Dat e Readin Documented action 7/2511 2 13 cfu in cart wz scpplies "will sum Wiping every iJqy and re.-teY f'; no investigation was conducted and no 10 was in Chc m room (rso 7) b)
o .
otl.
rerformed.
7/2611 2
71.26/12
7/30112
lit/l01l2 3 cfu in stainless steel tabl e in cbem room 3 cflr in st3inle$$ stee l table in sterile room No action. Thi s location is referred by lhe technician as the ISO 5 hood. No act ion. Thi s location is referred by the technician as the ISO 5 hood. No action No action. No investigation was conducted and no ID was performed, No action . No in~ig;rtjon was conducted and no TO was performed, No acti on. This location is referred by the technlctan as the [SO S hood.
.5 cfu on
room
90001
in chem
12 efu "finger touch"
812111 2
91 tOlt 2 & 10 /12/12

g)
"Growth multiple colonies" on stool in asepti c room. 4 cfu in stainless steel table in chem room
On 3/20 11 3, upon lnspe ctton of EM samp le plates held next to the incubator awaiting reading by a phwmaei~t we observed ill plJde that showed a 81() ~y wh~. IArg:a l'nierohial colony that ulYere(\ abom 1.:i% of the media. The plate W<Lo; labeled B3 "3w 15 stainles.9 srecttable sterile room " ; this is the ISO 5 hood where all Inj0ct3blos are prepared. On 3121/ 13, we verified thstthe plate was read; it was documcntcd ee +2 clU and no action was. taken. Upon interview of the phanweist who read the ptarc, we found oue tha t she did not kncw tber the "seamless steel table" was the sample for the ISO 5 hood .
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llEPARTMEl'ITOF HEALtH AND IIlT MANSERVlClS

FOOD ANDDRUG 1JJMfNlSTRAnoN
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03 /1El /2 0 13
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. ..... ... DO QOUI".
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40 00 Park .. St N
Pe te r .sburQ. FL
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3 3 7:) 9 -4 0 3 4
Pr oducer o f steri l e drc.n s
l~
Fingertip $1mpli(lg ofpharmacy technicians perfOflTling aseptic opet'<l1ions in the. ISO' hood is not cOildUCk'd at daily after production of sterile injectable, irrrramecal and opthalmic dJ"u: produe:ts.
Q Viable monitoring of air (settle plate) is not conducted in the ISO 5 hood at 1U!t dai ly during production of
injectable, intrat:he:c.al and opthalmic drug produces.
OBSERVAnON 3
I?.qufpmcnr and utensils arc not maintained lOt appropriate immral s to prevent (:ontaminnion that would site:'the safety.
iden tity. strength, qulllityor purity ofthe drug prodect,
Spedfiealfy,
B) On ) /1811) upon inspection o(the ISO
5 horizonbll3minar f1l)W hood used tc J.lft:pare sterile injecbble aod oplhalmic products In vlets, !he follo" i ng deficiencies were observed:
'.
1. At leeSltcn (lO) exposed rust areas N"OlID'J the top light panel. 2. A while pateh about 2"x2" on th~ the HEPA filter about 12" iDcbe-~ from the bonom surface and the right side panel. Thls patel! was reponed by a pharmacy technician as a "repair p3ICh" lhat has been there for a long time. filter ar)d cover grilL 3. Numerous splattered brownish stains across the lower half of the HEPA" Dark areas of differl'Jllt 1.i2;es on several places on the ImPA filter.
b) On 312011 2. upon inspec:r:ion of the verticallaminnr flow biosafe1y ISO ' bood where repackaging operations of bevacizumab arc conducted. browtsh areas appe:.Tlng to be rust were observed below the bottom air vent across the front side of the hood. e) On 3/18/ 13, while observing re-paekaging operations of Bcvacl7-tlmOlb, lot # 0] 1S2Q13@19 and 03 1$20 13@20, we observed brownish :;tairu re!'iembling rust on the surface and legs of the m inJesssteel table in the ISO 7 deanroom. We observed the technician place a tray of eighty (80) empty syringes on top ofthis table and then ptaelng the tray diroeT.ly on the ISO S surface ofthe hood without sanitizine:the boaom of the lny,
OBSERVATION 4
Each batch of drug product required ' 0 be froe of objec;tiooable mJcroorganisms &$. not tested through appropriate labcretory tesl:;ing..
Specifi~ ny.
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DEPARTMENT OF HEi\LTII AND Hl)M,\N SER.VJCr.S

fOOD AND OP.UO fU)MINISTRA TION
555 W inderl ey ~la c er Suite 200 Ma i.l:.hnd , FL 32751

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a) NOlIe (1fthe firli ~hod sterile drug produc~ produced at the firm have undergone microbiological method suitability testing. The method suftabtliry resting is required to demonstrate the drug product test samples do not inhibit growth in sfcriJity test media, For example;
I. The fitm performs in-house sterility testing on all lntratbecalsterile drug produeu thll.1 inclUde such finished products as: morphine sulfate injection, morpbinelbJlclofun injection, hydromo honelb ivacaine injection, ilrJd, morphinclfcn1anyVclonidim: injection. Sterility resting j$ performed by of rc drug products with different formulations into one sterility growth vial containi The fin:n has not performed method suitability testing for the pooling of these drug products ioto one test. Also, there is no reconcilability of the sterility of each individual lot.
2, The fJm1 uses a contract tcsting labcratcry to conduct sterility testin g on finished sterile drug products such as Avastin [Bevecizumab). The coetrace testing laboratory has not conducted method suitab ility testing on the Ava.~tin (Bevi\Cizumab) sterility test.
The mll.('u6Icturer's . The finn has not performedany t Additionally, the finn 's gauges have not been calibrated.
2. The manufacturer's preparation instructions state to verify the (inal pH of the sterilized media Is The firm does net check the pH ofthe st~li7.eQ medla,
"!I'_.
units.
3. The firm does not use suitable s trains of'tndicatcr microorganisms when performing growth promotion testing on 'spits' saliva into a specimen cup, dilutes with water and uses aliquot for the growth promotion.
th~ sterility test media. Instead, a technician
a..
4. The firm does not document the ln-bouse sterility tc!lting all raw dma worksheets. There is no documentation of test samp le preparations, materials and instruments used, and consistent docamenratlcn final test result readings of the samp le and controls.
or
oesrn,VA1l0N 5
Proceduresdesigned to prevent microbiological contamination of drug prodw;;ts purporting to be sterile do not lnclude adequate "alldation ofthe sterilization process.
Specifically,
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4000 Park. St
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3 3 7 09-4034
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You, finn failed to vali date th used 1 0 sterilizlIlntrnthcc.', injectable . nd,i produ ced by yo ur firm &(111 1 non-steril e components. In additiOll. you r firm has not esta blish btoburden limits in order to determine if it exc eeds the maximum capability ofrh
mie drug r"'''~

.
bJ ! ! ! ! !teriliZiltion process parameters for
steril ization of injectable drug products prepared from non-
men e components have not been validated. Drug: prodUcts such as G lycerin injectable art prepared from non-sterile liquid glycerin and prior sterilizat ion. These products are not tested for sterility prior to
n ot_
c)
release. The resc jts of tbe bubble point test performed after conducting stailization b) and opthalmic dru g products were not docu mented by tho finn prior to 3/ 1412013 .
of all inj ectable. intrathecal
OBSERVATION 6
Asepti o proce ssing are as are de ficien t regarding air suppl)' that is filtered throl,l,r.m high-efflc iency particulate alI filters under positive pr~sure .
Spec lflcally,
a) The 'initaJ qualifi cation ofthe ISO 7 cteanro oms and the ISO 5 hoods completed on 4/14J1 2 by a contractor after the construct ion ofth e new cleareocm was performed under static "a s b uilt" coed jnona only. Th e!!!!l!:-qualifiCalion performed on 10/3/12 reported that "up to two pharmacy pers onnel" were pr esmt in tho c:Ieanroom ing qualification; however, these individuals were not identi fied and no one at the fiTUI remembers being inside the cleenrocm during.Its latest qualification. Smoke studies of)aminar air flow were reported as accepta ble, but were not recorded lind the report did not clearly spe cify if taken under dynamic conditio ns. a" identified on the gauge ) fur air pressure between tho pharmacy, magnehelic gauges _ b) Mon itoring ot anteroom. and two (2) cleanroom s is deficient in that:
1. From 4/1 7/1 2 thru 3120J13, the di fferential pressure read ings for magnehelic gaUges !ft!ll!l!!l! were reported as "0.003"; gauge ~ reported as reading "0~ ; and gau~ reading was not recorded. C cg stat es t e followin g: "0.02 or below- See Phm-macist," When we read the gauges on 3120JI3 , we found tbe followi.llg: gauge . read "0~ (anteroom); gauge . read "0.04" (cleeorocm # 1); gauge. read "0.03" {chem o room # 2); and gauge. (themo room #1) read '"-0.03". The pharma cy technician was no t read ing die gauges correcrly aad therefore the dceumeneencn did not reflect actual readings. Furthermore, the excursion of "0" reading ill gauge . showing no differential air pre ssure between thc anteroom and lhe pharmacy wa shing area had been recorded by the seme pharmacy tecbntcien since 4/17/12 but no notifi cation was made to 3. pharm acist. and no investigation or corrective action had been. taken as ofJ120n 3_ These record s are rot reviewed by a pharm acist.
s have been implemented. 2. No wrmcn preccdurca descr ibing monitoring of differential air pressu re in thc cieenroom
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I leana Bar l:eto-1?et t i t, I nve s-: iQ at:o r mcnc.ras P . 010.r:1 0, Invest i gato r
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FI'VII ..... ~
Shirley M. SpeLd c h , Pharmacy Department M a n a ge r

SHOP,
TH~ COY.POUN~ING
ct "'. '"IIlE.lIF' OODE.O OU''' 'r
I NC.
4000 Pa r k. St
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337 .19- 40 34
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"
OBSERVATION 8
There arc no written standards or spec ificati ons, metho ds of testing, methods of cleaning. and methods of sterilization to remove pyrogenic properties.
Specifically,
a) The ~ cycle has not been validated. The firm use fOT glass vials and beakers m e . Ing ofnl injectable and intr.tthecal dna.vets. The finn has nOl verified the effectiveness oftbc . ~ cycle Using! ! ). The bacterial endotoxin test should be pcrfonncd on ~ ) to oven 'Ie cycle is eapable achieving a 3-log redu ction in endotoxins. Endotoxin testing is not routinely pe ormed on all inj ecrable and intrathecal dru g products. b) Th~ sterllizatiol cyc les ha ve not been validated . The f i t m ! ! ! l i i l i i i i i i i l e used in the filling of injectable and rntrath ocal drug products in vials . The finn does net document or rime f OT any
an
of the stopper
runs.
c) Wmpped glass vials. rubber steppe rs and beak ers sterilized and d in-house are not klentificd with a steri lization date . cyle, expiration date or a unique number that would allow traceback to th. loadlbatch .
0'
OBSERVATION 9
Clothing ofpersonncl enga ged in the manufaeturing and pro cessing ofdrug products is not appropriate for the duties they
perform.
Specificall y,
a) Operators petfonning aseptic ope ratio ns in ISO 5 hood s re-use sterile gowns throughout a production day. As sampling of
sleeves is not 'Performed, your ftnn has no assurance that thc sterility of the sleeves is maintained. During the preparationof
Dexamethasone PF. lot 03 1520 13, on 3120/13. we ob served the technician sitting in from of the ISO S hood and the bottom of the sleeves frequently touchin g me l SO 5 working surface of the hood. b) Facility-dedicated scrubs and shoes fur' all employees (mcillding these working in tht: cleanrcoms) are stcre d on an open
ehelr raek in the flrm'a bathroom when: employees. change their clOttlos before goin g into th e conD'ollad cleenrooms. The firm ':q twhrnom ill not a suitable area for chan~ng into fil.cility-ded iCMOd eIothing,
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THE COMPOUNDING SHCP
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DKI' ARTIltNT OF HEALTIl AND tIUMA'N SERVICES

~.
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FOOD A. ' ID DRTJG ADMINI$Ill.ATION

l1'IT'E(3) OF~TIDH
555 [~indeJ;'J.e.y Place , Sui te 20 0 Mai t l and, FL 32 751 (~0 7 J 4" 15-4700 t a x : ( 4 07 ) 475 -47613 IndU$trv Informati on : www .fda.gov/ oc/ induBtrx
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03/18/20 13 - 03 /22 /20 13

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.sh i r ley M. SpeL i. c h , Ph armacy Denartreent Mana ger
THE COMPO:JNDING SBO P, I NC . <;In.3TIIT

St Pe t e r .: > bu ro, Fe
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OBSERVATION 10
Testing and release of drug product for distribution do not include appropriate laboratory determination of satisfactory conformance to the final specifications and identity and strength of each active ingredient prior to release.
Spccifican y,
a) Injectable drug products prepared (Tom nco-sterile components am sterifized are not routinely tested for potency, sterility and endotoxin prior to release. Some of the injectable drug products include: mefhotr'Cxalc. testosterone. mitomycm, pclidccenol, and dexamethasone. b) lrrtratheca! drug products such as morphinc s ulfate, morphineJclonidine, and hydromorphone au: nor tested for potency and endotoxin prior to release.
OBSERVATION 11
There is no written testing program designed to assess the stability characteristics of drug products.
Specifical(y,
a) Your finn lacked valid analytical and sterility data to support the 9()..day expiration date assigned to repackaged syringes of the expiration dn.te was based em an article published irl the U.S. Opthalmic Review 2007 which stated lhal the potency cf Bevacizumab in syringes degraded 8.80/ 0 at three (3) months. However, this lnformarion is not specific to your finn' s operations and does not address
prcscrvanvc-tree Bevaclzurueb drawn from single-use vials. According to your rmn', personnel
potential lllerility Issues.

b) Your- finn tacked analytical and sterility data 10 suppon thc expiration date of90 days fer preservative-free injectable drug products' such as Dexamethasone P.F. 4melml injectable prepared from ncn-stcrilo components.
OBSERVATION 12
a~.lmre proper
Routine calibration of rne<:banica.t and electronic equipment Is not performed according to a written 'Program designedto performance.
~
Specifically. the firm docs not have a wrinen program for lind
~)
l\9
not calibrate tho following equipment:
The refiiger310r thermometers have not been calibrated. Thc finn's rcfiigeraw rs are used to store such bulk products such Avesun, Ascorbic Acid Injection, Amphotericin B, and retention samples or sterilized finished drug produclS.
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b) The autoclave thetmometcra and pressure ga uges have nat bee n calibrated . c) The depyrcgcnetion oven thermometer has not been ca librated. d) The thermometer in the firm's incubator has not been calibrated. The incubator is; used to conducein-house finished produc t sterility resrlng, media fiUs. and ie ccbarion of microb iology plates used in envirorrrnental monitorinz.
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FOOOAND DR.UG ADMINI$TR.ATION
404 BNA Dr ., Bl dg. 200, Ste . 500 Nashville . TN 3 7217- 25 97 (6IS) 366-1601 Fa x :(615) 366-7 80 2
03 /1 8 /2 0 13 - 03 / 2 2/ 20 13
30 012ge 0 34
~~~~~;:;[Z~t;!~.ii~ii::""foda""."g "o <v ~/Co "c "l,i,n,d" U,,s"t"rSl:.

TO: Medau s, Jne.
C1IY. &TAn:. Ztl' COOl: ,
-L----- - --- - - - - - - - -I
Larr y D. Stephe ns, Chi e f
erating Of f icer
Birmin ham, AL
3 52 42- 9609
Prod ucer o f st e ri l e drug
roduct s
This doc~mCll t lists observations made by the FDA rcprcscntalivo(s) during the irwped ion of your faclllty. TIley are inspcctional observat ~ons. Il!ld do .not ttprt.st1It a fil1fll Agency detenninatioo regarding yout cornpli8TJC<!. lf you have en objection regardi.n& an observanon, or have Implemented, Of plan to impk mcnl, corrective action in response to an observation. you maydiscuss the obja :tionor action with the FDA represenLlJlivc{s) during th~ inspection or submit this information 10 fDA 1Il 1 he address above. If you have any questions, please co ntac t FDA aJ the phone nllmbel' and addressabove.
CURING AN INSPECTJOH OF YOUR FIRM WEOBSERVED:
OBSERVATION 1
Procedures designed to prevent micr obiological contamination of drug products purporting to be sterile do no! include adequate validation of the sterilization process. Specifically, (a.) The firm "as not conducted equipmentqualification for til used to _ sterilize the following finished products Bcrhamcmasone AcetlNAP04; Dexamethasone LA 8 mglmL, Tnamcmolooe Acet 60 mglmL Inj Susp, all of which are made from non-sterile drug components.
(b.) The firm has not performed. integrity testing of the products made from non-sterile drug components.
used
t Q .
all inje<tahle solution drug
OBSERVATION 2
Protective apparel is not
WOOl
as necessary to protect drug products from contamination.
We observed that the appRreJ......ern by perscenet who were producing injectable drug products In the IS0-7 cfeanroomdid not cover all skin areas on the forehead, around the eyes, and on the necks ofthe workers. Hoods and goggles were not used. The baimets, beard covers, face masks, and disposable lab coats that were worn were non-sterile items. The woreers were gowned. as described in the firm's written procedure P&P No. 7.040, "Gowning."
OBSERVATION 3
Procedures designed to prevent miceobiologicel contamination of dnJg prOOl.LClS purporting to be sterile are not established.
pr~ctabl e drug
The firm's media-fill process does not adequately simulate the aseptic processing steps which arc used by the operators to products. SpecifK:a1ly, the firm's media fill we, "Media-Pill Test Procedure for CSP Sterilized
by _
" in""""the operntort' -
Mei s ha R.
:::~:~~M:C:C ~U~1~1~O~U:g~h~.__I~n~v:e:s:t:i:g:a~t:o:r0~:~:;~~~~~;1r-T"""""",-- 1
Wa ~ e r s , I nve s ti g~ to r
03/2212013
lNSPF ..enONAL OBSERVIt,n ONS
OUARTMENT OF HEALTH AI ' iD H"'JM~~ SERVICtS

FOOD I\ND DRUG A!'>M1Nl51RA1lOl'I
404 BNA Dr . , Bldg. 200 , Ste. 50 0 Nas hvi lle , TN 372 17 -2597 ( 615 ) 3 66 - 7BOl ~'il)l: (6 15 ) 36 6 - 7 80 2
03/18 {2 01 3 - 03/2 2/ 20 13
FlS iHiMiiJj
_~~ s~~J:!2rfu.ti1~~~ _= ;;ccf~d ~"-:. !l20 ~V /"o~ c~ /2i"n ~d ~u "$'-t':.rO:Y L

TO;
"""'"
- CIll' o~ ...fti, lIP COOE COl.H1'IlV
3 00 12 9803 4
.-l
- - -- - - - - -
Ld r r y D. Steph ~n s. Chie f oper atin g Officee:, r"'.

iimit ;;ooP.\!!&
l
,
roduc ts
M e daus , Inc.
680 1 CAhaba Va lley Rd S t e 1 16
8 irmin ham, AL
35242 - 9609
Pr od uc er of steri le dru
. H o~ever, the proce ss which is actually used to prod uce all or the firm's inject able druWrodOCls
IS: I
non-sren e
solution,
into sterile
bottles,
to then open the bo ttles multiple rimes, rna en g rnu t1pJe entries into the bulk dru g solutions usiog sterile tubin g, and to then steps after the fill pre-sterilized vial s using a commercia l pumpJfilling machine. (Th ere are no addit ional stcril_ mulliple entries into the bulk drug solur o n.)
OBSERVATiON 4
ASep tic proc essing areas are defk; ie rd regarding the sys tem for lIionitoring environmental conditions. Specifically: (8.) The firm's environmental IOOnitoring program does not assess the routine processing en viro nme nt. In the 150-5 needs, environmental monitoring for viable andno n-viable airbo rne partic ulates and for surface bio burden, is performed at s ixmonths intervals under static cc ed uio ns: however, s ix months is no l an adequate freq uency ofenv iron me ntal moni torin g for the production of injectable dtug produ cts via aseptic pro cessing.
(b.) The finn's environmental monitoring program does not asse ss the rout ine processing en vironme nt. In the ISO-7
cleanroom, environmental monitoring for viable and non-viable eirtcme perticuleres and for surface bioburden, is performed at six-months Intervals IUlder s tatic conditions; however, six months i!i not an adequate frequ ency of enviro nme ntal monitoring for th e production of injectable drug products via ase ptic processing. (c.) Th e firm's glove fingert ip bicburden mnnitoring of opera tors who perform work in rhe IS0-5 hoods does nOI asses s the momh glove bioburd en levels und er routine processing conditions. The glove fin gerti p mon itoring is performed at SD:M intervals; ho wev er. six months is D ot an adequate frequency of glove fingertip monitoring for the productio n of Inj ectable drug produce via asepne processing.
OBSERVATION 5
Aseptic processing areas a re deficient regardin g air suppl y that is filtered through high-efficiency partic ulate air filte rs under positiv e pressure. Specifically : (a.) No moni toring is performed of the air pressure differential between the (S0-7 cieanroom and the adjacent 150 8
anteroom/gowning room. No gauges for measuring room air pressure s are present in the facility. The re are no alarms for
alerting pe rsormel o r poeennal air-pressure differential deviations .
Bruce K. M cCul lough,
I nve.st.Lqa'to r
Me i s h a R_ Haters , Inve s t i g a t or ~
1NSJ'};CTtON,,"LOWi!'.RVATJONS
0 312 2 /2013
P~ 1 Of 6PMIH
DEPARTMENT OF Ht..ALIH AND Ift.!MA,"'l SERVICES

!H>_ ...~iji
FOClD AND DRUG ADMJl<;IS1AATlON
( 6 15 ) 3 6 6 -780 1 Fax : (615) 366-7B02 Indus try I n fo rmation : www. f d a . gov / o c / i ndus t r v _ .oHtITn'\.E Cf'iNlll _ '0_ TO: La r r y D. s t e phens , Chief Ope r at.d nq Off ice r
'0' BNA Dr. , Bl dg . 20 0 , Ste . Nashvi lle , TN 3 72 1 7- 25 9 7

,
500
03/181201 3 - 03/22/2013
m NUM""~
30 0129 8034
, A<O'I:Ss
~",. liI> ;::oo;. (;.dO ....
a e d eue , I nc.
6801 Ca ha b a Va ll e y Rd s e e 116
rrPOiUT--.otf
Birmingham. AL
352 42-960 9
Produ c er o f .sterile drug p r oducts
(b.) No smoke studies have been performed to verity that laminar airflow condi tions cltist inside th e ISO~" hoods, which are used for the production o f injec tahle drug products,
')
alPL OYU: l'll s .....
~
. .....TEIS$<,o;O

I'OJUtI,FDA 013(0",'111";
Bru ce H. McCul lough , I nvestigator ~ Mc i sha R. W a t e r s , Investigator (;;f. ' ...... "'QU$0'D<TIl'l>0_~
0 3/22/2013
PMl E :; Ol'(; j> A(;S
INSI'I:cnONAI.QBSERVAnONS
Dl!:PARTMI.NT OF 'fF..AlTU Al'ID HUMAN SERVlC F ,S fOOD fJ>ID J.:rn.l)G "IlMINJSTRATION

AM> ~ N WIO ""
(li'il"io... ~
BNA Dr. , Bldg . 200, St e . 500 Nas hvil l e , TN 312 1"1-25 9 7 ( 61 5) 36 6- 7801 fa x : (61 5 ) 3 6 6-7 802
NlilEJ>tOTTTu;. oi' ~WS \MiOiI01ibciil'I'
'0'
03 /1 8 / 20 13
ru .
- 0, / 22 / 2013
3001 298 034
Ind us t r y Info rma t i on : www . f da . gov! a c/i ndus t r y

arotb
TO:
;;jj;Iii""NMii!
La rr v O. St e v h e ns, Ch ie f On era ti n o Office r

680 1 Ca h aba Va ll e y Rd Ste 1 16
~
M e daus, I n c.
c l'ff:lfl'.il'l!:" D'~ -; - -
Bi r mi ngham, AL
35242- 960 9
Produce r of steri le d c ua nrodu ct s
OBSERVATION 8
Drug products arc not stored under appropriate conditions of temperature and light so that their identity, strength, quality. and purity are not affected. Specifically. on 0311812013, the Jots ofbulk in-process injectable drug produ ct identified be low stored in _ drug containers, containing drug components, were observed to be store d on the coun ter top Inside the ISO 7 room a t ambient room temperature audlor wirbout Hght resistant protection. Management exp lained if IS a normal practice for these !!l!!l containers to be placed on the counter dai ly between 8:00 am and 5:00 pm Monday through Friday 10 fill unit dose ers. Products labeled "Refrigerate" and "Protect from Light" stored in _ containers includes: I. Meth yl B 12 10 mglmL Lot IJ02 1 22~35 BUD Sf1U13 2. Lipo- Injection wi Lidocaine LoI130JIS.()8 BUD 09/11113 3. Lipo #4 w/ Cyano Bil I mgfml Lot 130 11S7-67 BUD 07114/13 4. B-<:omplex tOO (PE) Lot 130228-40 BUD 5129/2013 5. Magnesium ChI 200 mglmL Lot 130307-60 BUD 09/0J /J 3 6. 2~N A Ascorbate 500mglmL Lot 13031 3-34 BUD 09109/13 7. DMSO Lot 12 1205-56 BUD 06/03/13 8. Ca lcium Sodium EDTA 300mglmL Lot 130306-50 BUD 09102113 9. CalciUIIIChi 10% (PE) Lot 13030834 BUD 09/04113 10. Me-myl B12 1000 MCG Lot 130312 ~21 11. Hydroxy U 12 1000 MC G Lot 130228-26 BUD 8/27/13 12. M IC!B Complex Lot 130123-67 BUD 07/28/13 13. Methyl B 12200 MeG/rot Lot 130129-35 BUD 07128113 14. (3 -100 ml. vials) 'restosrerone Cyp 200 mgtml. 1.0t 130315-8 BUD 911U13 15. Sweet-MCDFlT AlIe- nLot 121213-5 1 BUD6J1lf13 16. Hydrogen Peroxide 3% Lot 130307 70 B UD 9103/ 13 17. Express IV Nutrients Lo113030554 BUD9/O J/1J 18. Me-lb,,' 8 121000 MCG Lot 12114-80 BUD 5/13113 19. (2-3olnL vials) Lipo-lejecrion 'III Methyl B I2 500 MCG L01130301~32 BUD 0&/281 13 Product labeled "Refrigemle" stored in an " " " " container includes: 1. Allen IV Nutrient Lol 13020533 BUD ' 3 Products labeled "Protect from Light " stored in. containers include s: 1. Meth yl B I225mg Lot 130227- 17 BUD 08 ' 13 2. Pyridoxal 100 mp/mL Lot 130301-19 BUD 9/28 f13
UlI'W'I'B' . I") 6lC
SEE REVERSE QFTHISPAGE

J'ORMIINoW
Br uc e H. McCul l ou gh , l nves t iga~~ M ei sha R. W a t e r s, I nve s t i g a t or . .
w '_
03/22 /2013
~AOll~Of H'ACU
""""'OIlS mn1Ol<
QlIS<llFf'E
.lNSPE<.'TIQNAI.OS. s'1!:RVATIONS
DEPARTMEI\"]' Of. HEAL1l1 AJIIl) IIlJMA."ll SERVICES

O< S'T!UCT-"'ANPPHONC "'JMfIEil
FOOD AND DRUG ADMIN ISTRATION

,~~
40. BNA. Dr. , Bldg . 2 0 0 . St e . 500 Nashvi lle , TN 37217-2597 (6 1 5) 3 6 6- 7 80 1 Fa x: ( 61 5 ) 366-7802 I n d u s t r y Info rmation; www. f d a . go v / o c / i n d u s t r v
""'lE ANDTIlU
'NllI _ TOw>IOM RPOllT ISSIM
0311 8 / 2 013
Aitl Nu.wlER
03/22/2013
3 00 1 298 034
,-
TO:
Larry D. Steohe ns , Chief Operat ing Officer

~ fREET ADDRESS
Ne d a u s ,
CIn'. 8T A'IE, ZIP
Inc .
~
68 0 1 Caha b a Va1 1 e v Rd S t e 116

TYF'EES'T.lIllJSIHEHT"SPE<:TED
Birmingham, AL
352 42 -9 609
Produce r o f steri le druc products
OBSERVATION 7
Time limits are not establis hed when appropriate for the completion of each production phase to assure the quality of thc drug product. Speci fically, the firm doc s not have any hold time data to support the completion of each produ ction phase for any of yo ur inj ectable drug products (when not being held under refrigerated or light res istant conditions) including but not Jimited to preparation of the original batch of product , and multiple transfers ofthe produ ct into unit does vials from ~ containers, to as sure the quality of all injectable drug products at your firm.
OBSERVATION 8
Each batch of drug produc t purporting to be sterile is not laborato ry tested to determine conformance to such requ irements. Specifically, sterility testing is performed on each origina l large batch of all inj ectable drug solutions made from non-sterile components after being transferred into . containers. Howev er, sterility testing is not performed on an y batches of drug product filled from th~ contain ers after it has been reopened and exposed to the ISO S environment for ftllm g of unit dose vials.
OBSERVATION 9
Testing and release of drug produ ct for distribution do not include appropriate laboratory determin ation of satisfactory conformance to the final specifications and identity and stre ngth ofeach active ingred ient prior to release. Specifi cally, Dexamethas one 8mglmL Lot 130 118w 11 (Beyond Use Date: July 17, 201 3) was released for dis pens ing on 0 1118 12013 , but sterility test ing results were not rece ived until 02106/20 13. Dexamethasone 8mglmL Lot 120927~ 7 (Beyond Usc Date: March 26, 20 13) was released for diEns!n, on 0912712012, but sterility testing results were not rece ived until sterilization) biological indicator testi ng failed prior to the date 10/15120 12. Both lots were reca lled after receipt of sterility results .
OBSERVATION 10
An adequate num ber of batches of each drug product are not rested to determine an appropriate expiration date . Spec ifically, the firm bas not conducted stability testing nor has data to supp ort any expiration dates (be yond use date s) for any injectable drug products produced. For example, there is no da ta to support the u;se of 6 month beyond use da tes for Llpo Injecti on, Cyano B12, or L ipo wI M ethyl B 12 wI Preservative.
f-.oYEEl'! )'......'TUI'l:
DU E ISSUED

FORM I'DA dJ. 10Ml8)
Bruce H. M ccull oug h ,
Inve 't i ga~

.
INSPt:cnONAL OBSERVA. - noss
M e i s ha R. W a t e r s , Inves tigator
"""' ~ I!DJTI()t> 0Il';(llIl!
03/22/ 20 1 3
~,,(;I;
S 01' 6
~ A Ci 6.. ~
um_NuIIllEII
3721'7~2591
Pf.PARTIlF. !IrI"OF HE!\LTII ANn HUMAN SERVICf:S I'OOD "NO DRUG AD.'.{lNlSTIUl'flON
I Qll;l1i(l ) Di"~
0 4 BNA Dr . , Bldg . 20 0. Ste . 500
Nashvi l l e . 'N
(615) 36 6- 7801
F 4 ><; : ( 615 ) 3 6 6-78 02

ww~.fda. q o v / o c / i ndu s t r v
1l:f,POfIl'......,.,
.~,
03/ 18/ 20 13
3 00 1298 0 3 4
- 03/ 22/2 013
~~ Of' -~l
Industry Informat ion: TO :
r.arr v D . Ste phens , Ch i ef Oce r-e t Lnq Of f Lc e r

Wf.
~.
r "" y ,<; J,
e teoeue , I nc .
.........
35 242 -9 609
680 1 Cahab a valle
Rd Btl;! 116
Bi rminq ham, AL
Produc e r o f st eri le drug product s
OBSERVATION 11
Labo rat ory contro ls do not include determi nation ofconformance (0 ap propriate written spectflcenons for the acceptance of ea ch lot with in each shipment ofcomponents, drug product containers, closures, and drug products used in the manufacture, processin g, packing, or holding ofdru g products. Specifically, the firm does not have any wnnen spec ificatio ns for the acceptance ofeac h lot within each shipmen t of components, drug prod uct containers, closures, dru g products used ill the manu facture, proce ssing, packing, or holding o f dmg products. The firm does not perform supplier qual ification to verify certificates of analysis for any dn.!!' , co mponents, dru g product containers, clos ures, dru g prod uct! used in the prod uction, processing, packing. or hokf m,@. all drug products at yo ur finn .
OBSERVATION 12
Aseptic processing areas are deficient regarding the system for cleaning and disinfecting the room and equipment to produce . aseptic cond itio ns. Spec ifica lly, M 3/18/ ) 3, An operator pro duc ing injectable drug products b1 an !SO~5 hood was observed to IOOve materia ls from the IS07 cle ecroom zone into tbe 150-5 zone without disinfect ing the extertcr se rfeces a fthe materials before movin g e re: a container of bulk drug them into the (SO~5 zone. The materials moved into the 1805 area wi<'.hout disinfec tion w sol ution, a package holding steri le tuhing, end empty , pre-sterili zed, stoppered vials.
\'
.-'
~
fOll..M 'l!_~ a l f""""
~~
Ne i a n a R. Water s . I nvesti gat or a ~~

l'RFVIOUS>:DfnP<~ re
Br uc e H. M CCulloug h.
' ~ lnv.sti 9'to~ ~

INSf'ECnONAL OBSERVA-noss
!)lR:!OO ~E (l
03 /22/2013
I'AGE ~ Ol'6PAGS
.
Dl:P ART MiNf or Il EALTIi AAD II UMAN S UI.V I(: .~" rcoc AHDDRUGADMINISTRATDN
. 0. BNA Dr . , Bldq. 200, St e . ' 00

Na shville . TN
( 6 1~)
03/ 18/20 13 - 03/22/201 3

JOO70 4!>5 42
37217 -2597
P'a x : ( 6 l!
3 6 6 - 7 60 1
3 6 6 - 1 60 2
Indust rv I nfo r1lla t i on : www . f d a . a o v / o c / ind U9 t rv

TO:
Timothv P. Rinlt:J, Gener al Manaqer
PharMDi um Se r vices , LLe.

~.
M e mp h i s . TN
38 1 41 -8 385
6100 Global Dr i ve ~ -Producer o f I n 1e c ta ble Dru a Pr odu ct s
lllis doaImmllists ~ions IIUIdc by lbc FDA reprcsenUll.ivc( s) during the inspccti<m of your lKility. They _ Wpcaional ~ Inc! do noI: ~. final AfJ:nI:y Odaminalion rrptding )'OW" compIianc:c. l fyou ha"'C .. objc:ajoa rqlWding ~ observatioft. or have ilnpkmcntcd. Of plan co imp lcmeat, corrective lCtioa in response10an obscrYation. you ilia)' ~ Ibc objcdion or actioo widJ. the FDA IqIRSmlWve(S) during Ihe inspfion Of sutuUl lhis information 10 FDA .. the 8ddrcss abo .-c. (f you ha\c ...y questiolu. plc:r;c mn ma FDA It tbc pbobc: -..bc:r Ind ~ ....ee,
DURING AH IffSPECT10N OF TOUR F_
WE OBSERVED:
OBSERVA TION 1
"""'.....
Written production and process control procedures m not followed in the execution of production Irld process eoeeot
For example. on ) / 11113 durin& the processing of injcQable dn.Ig produm,.
-= obKrved.;
CONTROLS~.
a) failure 10 follow proced ure CPS-30~. PERSONNEL GOWNING AND ASEPTIC TECItN IQUE AND effective 3113113, in regard5 to:
1) mull iple personnel wiLh exposed facial area:s leanin g inside of tilefront edg e of the LAFH during the processing of injectable drug products, 2) personne l e umining un<:apped syringes . fta filling less than the requ ired _ inside the hood.
3) at least 8 LAFib in which processing was oocurrin g noted trash conlai nen and/or diarps contai nen direct ly aga inst the air intake for the l.AFH 4) multiple personnel cont inually resting their hands on worksurfaces of the LAFH withou t rc-sanitizin g their hands,
$) personn el processing ampul e product movin g the ir hand in front of and over the previous ly opened ampul es,
b) failure to follo w proced ure CPS-606, ~SERVICE CODE CONTROLl. ED SUBSTANC E COMPOUNDING PROCES S", issued 3/ 13/ 13 , in regards 10 prope rly sanitizing the _ _ unk before moving this unit inlo the LAFII. This employee lightly sprayed only the front of the unit with alcohol and did not wipe down all acce ssible IlJ"CllS of the unit as required by this proced ure.
0> '"
-R'\J
,........., tI.'Y
SEE REVERSE
OF THIS PA G E
roll ... "'" . . _
M a rv i n D. Jones , Invest iga t or 0.11 S . Mo l l .. r-, Inve sti'Jilt o r
~. ,h4
// ./
031 22120 13
P.w:lE I Of"...as
--~
I"iSnCTI O"'4.I. OIlSF R\'" TIO''''
IJU' AII.UILNT Ot IILALTIi A/lt.l.l IlL MA!\jSI:II. \ " U:. \

FOOOAND DRUG 1\OI.41N1STKATION
BNA Dr . , Bldg . 200 , Ste . SOO Na s hv i lle , TN 3 12 17 - 2 59 7 ( 6 15) 3 66-7 80 1 Fax : ( 6 1 5 ) 366-18 02 I nd u s t r v I n f o rmat i on : www .fda ....o v/oc/ i ndust rv
'"
03/18/20 13 - 0 3122/2 013 300 1 0 45 54 2
TO :
T i mo thv P. Ri n ks , Ge ne r a l Ma na ~er
Ph a r MEDium Ser v ices . LLC .
61 0 0 Global Dr i v e
Produce r o f In1ectable Drun Products
Hemoh i s, T N
38 1 41 - 83 8 5
OBSERVATION 2
The production vca air supply 1al;ls lID appropriate air filtration system.
Speci6ally, I) the airflow srudics (smoke stud ies) pcrfon lled 01\ the (um's . laminar airflo w hoods (LAfl 1) IDd in the cJcan room wbee injectable drug produ:::ls an: processed an: only documenled by Khcmatic: dnwings. b) 1here is DO docwncnbItion of the prooeuin& activ ittes in the LAt-Hs taking ptsce duri ng dynamic smoke studies., c) tha'e is no documcntatiorl or thc raw data ror IlEPA filter integrity ~ing r<r these hoods aDd clean room.
OBSERVATION 3
PToccdur'e1;
designed to prevent microbiological rontaminalioo or drug products purponing to be sterile are DOC estab lished.
Spec;i( lClllly, a) there is no fi ltration Rep performed during the (UIlIl liUillg uperilltiOlU of the: finished product contDinen ror sterile
injectable drug prodUClS.

b) there is no procedure to specifica lly require saninziag packagin g oomponcn ts prior to placing them in the LAFH. 3/1&113, during the process ing o rinjec;table drug products. we observed;
()Q
I) an employee san itizing only lhc front and back o ra stack or appro ximate ly 15-20 plastic IV bags prior to placing in the LAF H, the to p layer o r emp ty PeA s)Tinge packaging components (st ill in the 2) an employee only lightly spraying with _ manufacturer's pack aging), and then turnin g over a small port ion of them and aga in lightly spray ing wi~ before placing them in the LAFH , c) proced ure CPS-30S, ~ PERSONNE L GOWNING AND ASEPTI C TECHNIQUE AND CONTROLS~, effective 311 3/ 13, docs D ot have req uirements for complete co vering of the facial 8I"Ca. During th is inspection, we noted several employees with their head inside LAFHs with exposed facial areas ,

ro-..
n4OU _ _
ar vi ll D. a c n e a , Invc :::ti g at or M o l le r , Invest iga t o r Dell S. M
",.::r
~
ORSFR\ '"1 10 .....
03/22/2013
PAGE2 01 . PAGE5
,,"S"[OlO~A L
" .......-..rn
Df;PARTM ENT OF HEALTII A "i D Il L'MAN Si:N\'ln;s

fOOD AND ORUQ ADMINIS1lI:A,TION
4 04 BNA Dr . , Bl dg . 200 , sce . 500 Nas h vi ll e , TN 372 17 -25 97 ( 615) 3 66-7801 F'in : : ( 615) 36 6-7802 I ndus t r Inf ormat i o n : www . f d a . ov/oc/in d us t r
TO:
03/ 1B/2013 - 03/22/20 13

300'104 ~5 42
Timoth
P . Ri nk s , Gen e r al M ana e r
Pha r MDium Se rvi ces , LLC .
61 00 Globa l Drive Produ c e r o f I n "e c t ab l e Dru Products
He m h i s , TN
38 1 41-B 3B5
OBSERVATION 4
Laboraiory COIltrob do 001 include the establi.sluncllt of scientifically sound and appropriaIe speciflCalioos and tnt procedures designed to ass ure lhal drug products conform to appropriate staodards of idefltily, strnIgth, qual ily and purity. Specifically, . ) the Ilppef' and lower polt:rq limit$,established by the finn. for the in 'ectab le dm including I combinalion of; mono ~I IUtIoo or example: -..11"'- if applk:able, to give I wider spec ifJCatioo range lhaD the 1lCtive ingredient $pf1C8tion established by the drug prucItJa manufacturer. For example, Fentanyl Citnlle
2mcglmL, the firm speci flCllioo
These
2.2mcgImL)of1abe1claim; and lIy morpbone IOmcglmL, thefum specification is: mcgImLand U.S .P. specification is 9S.o.. IOS.0% (9.SmcglmL-I0.5mcg1mL) of label claim. The fum has various limits established for each finished injectable drug product.
b) failure to utilize pos itive and DegKive coaarob 01" oouduct growth promolioo teUina for the microbi o logical growth media used for daily, weekly, or monthly monitoring of LAFHs, personnel monitoring. environmmtaJ mooiloring. and media fills.,
is: !
meg/mL and the U.S.P. sprcifteation b 90 .(1..110 ~ ( 1.&mcglmL .
monitoring.
c) !he proced ure CPS-707, -MICRO BIOLOG ICAL AND ENVIRONMENTAl. TESTING". effective dale 3114113, does 1101 include specifK' sampling locations, includinR establishmenl of the W~ case samplinr:sites. for routine environmental
OBSERVATION 5
Each balch of drug product purpoetmg 10 be sterite and pyrogen-free is nollaboralory tested to dclermine conformance 10 such requirements. Specifically, the fum does not conduct endotoxin testing on any finished injectable drug products.
OBSERVATION 6
Procedures designed 10 prevenl microbiological contamination of drug products purporting 10 be slerile do nol include adequate validation af thc sterilization process. Specifically. media fills performed by the firm for e<ju ippment/~ss validation ~d employee: q ~1i ficalio nlm o~ ilori ~g do not represent the continuous process of pooling, subassembly, fi~J shed product,mlmg. ~ packagIng. Each media m! IS performed only on one processing stage at a time and does not simulate the enure processmg from the start of ptccessmg to
M~ rvi n D. Jones, I nvesti9~tor ~ Dell S. M o l l e r , Inve st i g~to r

t"i S"[CTlO~A I. ORSI:N\ ATtO 'lriS
03/2212013
.
D I'A RTM U ..,.
orne x r.r u A.'I;I> Il UMA'
FOOO AND DROO ADMlNl STllA
no,..
S .: R ~' ln~"
Na s h v i l l e , TN 3 7 2 1 7 - 2591 ( 6 15) 3 6 6-7 80 1 F'a KI ( 6 1 51 3 6 6 - 78 02
' 04
BN A Or . , Bl dg. 20 0, St e . 500
03/ 1812013 - 03122/2013

30010 455 42
I nd ust r v Inforlrlat i o n: www . fda . oo v/ oc / i nd us t r v

TO :
Timothv P . Ri n ks , Gene r a l M anaaer
PharMEDl um Services , LLe.
ri ve 6100 Gl obal D
Pr odu c er o f
M emchi s , TN
38141 - 8 385
'0ect able
D<u
Produc ts
fmished pal:laging.. Each process Slagc is rested separately for microbial growth..
OBSERVA TtON 7
Testing and release of drug product for dimibuooo do not include appropriaIe bbomOfy detenDinalion of satisfactory conformance 10 the i<km:ity and sumgtb of eacb lICtive ingredient Jrior to release. SpecifICally, faillll'e to perfonn fmished product potenCY/sterility testio g on each kJc. offuUshcd injectable drug product ~distributed. Testing is only performed annually on I nmdom ~ pel" drug prodUCI family.
OBSERVAnON 8
The written stability prognun for drug products does 001 include meaningful and specifIC test methods.
Spe<:iflC&lly. the stabil ity test methods used to ass ign Clq)iratioa dating off misbed injectable dru g prod~ are 001 stabi lity indicating. The firm's $lability testin g peccedures do not include sterility, impurity. or degredant product teuing. For-
example. I ) 1 review of the Final Report for Fentanyl Citntte, dated 1214107, noted the stability samples were not produced at this location and were only rested for visual inspection, assay, pH, andparticle counls through. )'$. Also, only I drug prodllt:t lot was tested. This prndllt:t has 90 day expinttion dating. assigned by the fum. b) a review of thc: Final Report for Propofol in the 20 mL syringe, dated 11/l S/IO , noted the stability samplcs were IKJt prod ~t this IoatM.xJ and were tested for visual inspeQion, pH, avenage globular SV.l:. 1551)', related rompou nds A and B throu days. Also, only I drug produce lot was tested. This product has 30 day expiration daring. assigned by the fum. Furthermore. no nitrogen overlay blanket was used in this testing and no comparison testing with and without nitrogen was conducted. Per record review. this a highly oxidative product and should be processed andpackaged under a nitrogen blanket,
OBSERVATION 9
Cenificates of testing of container! and closures are accepted in lieu of testing without establishing the reliability of the supplier's test results through appropriate validation of lhe test results at appropriate intervals. Specifically, the finn does not conduct any samplingltesting upon receipt of finished injectable drug product containers or clo,",", ,,,, tbe)' '''''' "Pf""O~ I" ..vd wilk.. "t llIIy testing. During II review of complaints for 2012 and 2013. we noted numerous complainls for leaking IV bags and cassettes.
SEE REVERSE OF TH IS PAGE
M a rvi n D. J one s , I nves t i ga t or o l l e r. I nve s t iga t or DelI S. M

~-~
~~
03122/2013
.o.GIE ' Of'PWES
__,,""'ou_
l....srf CllU...'1
"""""'
oll"nr."-"T1O' '''
.
DU'A KHU:I\r o r IlEA L TII A/li D IIU MA N S UI.V l n~ <o; FOOD ANI) DRUGADMINlS11lATlON
Na sh v il le .
. 04 8NA Dr Bldg . 200 , Ste . 500 TN 372 17-25 97 (6 15) 366- 78 01 Fa x : ( 61 5) 36 6-1802
TO:
03/ 18/2013 - 0 3/22/20 13
30070 455 42
I ndus trv In f ormation : www .fda .aov / oc / i ndustr v

TillOt h " P . Rin ks , Gene r a l Hana"er
Pha rHEOium Se rvices , LLC.
6 1 0 0 Glob al. OIl
"'0:
HelllDh i :s. TN
38 1 41-8385
Produ c e r o f I n1eetable Drun Produc ts
OBSERVATION 10 The quality coetrol unit bl;k:s authority to fully iDvestigate crron that ba... e occurred.
SpecifKally, for incubalor temperature monitoring cham, there is
dC'teeced,
DO
evidence to sbow tempe:ralun: UCl1l'!oM:lm have beea
a) between May I and May 15, 2012 incubatorII 2. used to ~Ie media fills, bad IIrecorded tcmpenture: aI degrees F. This temperature exceeded the tempc:mun: limits set for this incubator of. degrees F.
Of
above 100
b) between August 9 and August 16. 2{l12 incubator # 2.used to incubale media liJl s. had. recorded kmperature below 85 degrees F. This temperature exceeded the temperatun: limits set for th is incubator o ~ degrees f.
c)
tereeen May I and May II, 2012 mcubatoc II 3, used UI tDcublue cnvinxu..ClIl.lollI......;Wf;nC rncdioo plateo., did _ - . l
any temperatw'e$.
These records were signedofT15 being reivewed and the quality unit failed to detect and perform corrective aclions required
in pnx:edureCPS-7J2. '7EMPERA llJRE MONITORING~. issue date 1131113.
OBSERVATION 11
There was a failure to handle and store components at 811 times in 8 manna to prevent contamination .
Spec ifically, on 3/ 13113. we o bserved IV d iluent bags containing 0.9% Sodi um Ch loride solution improperly stored, uncovered and unp rotected in 8 gray tole in the unclass ified warehouse area.
OBSERVA TIO N 1 2
Reserve dru g product sam ples an: not reta ined and stored under cond itions con sisten t with producl label ing. Speci fically, the firm docs nol main tain eescrv e samples o f finished inj ectable dru g prod ucts.
SEE REVERS E
Ma,v!n O. Jo ne"
000 1 1 S. Mo l l er ,
,n,.,".o'o<
In ve s t.i q ,.,t o r
~G;) ~ ./. ,__~ ' A,<;
03 /22/2 0 13
, "'" I 01' " {iU
QFTHIS PAGE
pna........
ou_
- ... _.-,,,..
1.. .. rl:......... o '\'''I. O"""f:R' ' 1I0",S
1. Pursuant to Section 704(b) of the Federal Food, " Drug and
Cosmetic Act, or 2. To 'assist firms inspected in complying with the Acts and
I regulations enforced by the Food and Drug Administration
I .,
Section 70i f(b) of the Federal Food, Drug, and Cosmetic Act (21 USC 374{b)) provides:
"Upon completion of any such inspection of a factory warehouse, consulting laboratory, or other establishment, and prior to leaving the premises, the officer or employee making the inspection shall give to the owner, operator, or agent in charge
.report in
or practices observed by him which, in his judgement, indicate that any food,
setting
~ w r i tj n g
forth . any conditions
drug, device, .or cosmetic in such establishment (1) consists in whole or in part of aQY filthy, .putrld.vor decomposed substance, or (2) has been prepared, packed, or held under insanitary conditions whereby it mayhave become co"ntaminated with filth, or whereby it may have been -ren dered )nJuriou~ to .health. A co of such re art shall be sent rom tI to the Secreta "
I; "
JlOFJIUl&
pp;rAIlTMNT OF HEALTH AND flUMAN SERVICES
rocoAND DRUG ADM!Nlm.A11llN
4040 North Cent ral Expressway , Sui t e 300

ual l as ,
~x 7~20 4
D3/ 18/2013 - 03/22 /2 013

300 98 ::'5000
(214 ) 253-5200 Fa x:(214) 253-53 14 Indus t r " I nforma tion: www . fda. no v / oc / i ndust r y
--,
TO:
Raymond L. Sol ano , I I I, Partne r and Pha rma c i st-in-cnar ge undi ng, I.LC 18613
S......c i a l ty C
otIIlIO.
21 1 So uth Bell tRion' 183 N)

'nO"E: ~
CedaI Park , TX
~~
Pr oducer of Sterile Dr u g Produ cts

~ina: an
This document lists observationsmade by the FDAn::plll:iiel1tative(!I) during the iospec:tion of your lil.cility. They lK'C inspectional
IIDd do not ~ a fiaaI Agency dctcnoUnarion ~youroompl;_ If you have an objection
observation, or have implemmted, or plm to implemertt. corrective action in response to an obser'v!'inn, you ma.y dJswssthe objection or action withthe FDArepresenl8tiw(s) during dJe ~on or submit this information to FDA 111 the address Jlbove. If yeu havelOy questions, p lesse cont8(:t FDA lit the phone numberandlIddreslI aboe.
DURING ANINSPECTION OFYOUR ARMWE OBSERVED:
OBSERVATION 1
Procedures desigBed ec prevmt microbiological contamination of drug productspurporting to be sterile are not established
Specifically,
wipe her bare forehead with her glovedhand while facing the ISO 7 clean room area, aod then resume fil.ling operations UDder !he ISO 5 LaminarFlow Hood (I.FA). She _ f1J1mg _ 113M I Magr'le:'Ilum Sulfate 2gm/100mL Sodium Chloride 0.9% 2em!lOOmLJnjectable. I also observedemploYe41 wipe her bere forehead with her gloved band while facing the ISO1 cleanroom area, spray the glcve a1ld ~ resume filling ander the ISO 5 LflI. She was filling lot #O)lS2013MI4 ofAcerylc}'1lleine 20% Inhal~utIon. Neither operator cbaogcd their gloves aftertouebing their bare skin.
8) On 3/1 8113 I observed empl
spray her glove
with_
b) On 3/1S/l3, a pblmOacist from. yow fmn. ) was observed kneelin g witil hands IIlId knees on the ISO 1 clean room 800r retrieving vials that bad fanen under a cart mKITo retrievea plastic containerthat had ftlllen behind the laminar air-flow hood. The eml"lny"., fiid not rt'I-glTWTl or chan ge gloves a.fta' each instance and continued working in tile clean room. The phllI1IlllCist was responsible for handling compOIletIts (i.e. opening the overwraps for the IV bags. plastic trays with solunces and vials. and syringes) and transfeniog items ~ Pbannacy Tedmicians ISO S laminar air-tlow hoods. The ph8l'Jllllcist was also in charge ofoverseeingthe ueptic processing for technicians working simultaneously while the
foUowing products were; prodUced.
aD. under.
BupivK;ane Hydrochloride PF G.75% Injcctable,lot 1# G3182013M12

DMPS (D~&ulfunic Acid) PF 5%
Inje<:table,.I.ot # 03 182013S11l
Magnesium Sulfate2GMllOOmL SodiumChIoride-O.9'A. for Injection, lot # 03162013Ml Cefuzolin2gm la JOOmL Sodium Cblorido 0.9% injectable. lot il 03 152013M I7 Amykysteine 2QO A! (uring powder) 200MGIML lnbalation Solution, lot # 0 3152013M14
SEE REVERSE
OF THIS PAGE
DO'AJrI'MENT 0)1 HEALTH ANOII\I'MAN SEaVJCES

FQODA!'IODAUG~TIJN
4040 N orth Central Expres sway, Suite 300

Dalla s , TX
03/18/2 013 - 03/22/2 013 30098 15000

Pbarmae i st- in -~ha r
7 52 04
t2 14} 253-5200
~~
Pa x: (21 4) 253-53 14
I n d u s tr y I nformati on : www. fda. ov/oc / industr
TO:
Raymond L. Sol an o. III, Partner and

Com oundin , LLC
e
183 NJ
S ecialt
2 1 1 Sout h Bel l
jH
Cedar Park, TX
18 613
Producer of Sterile Drug Products
room. ISO & ante room (gowning area) aDd the prep room where mixingoperations occur.
c) Your firm is not monit.oring the gloves ofeach operator working in dre ISO 5 LFH and ISO 1 clean roomeach day that sterile drugproducts are prepared. SOP 3.030 Environemota1 . . oflbe C5ean Room F a c venice3.0cffeaive !!i!ii.' 6/1111. statcs~el touch plates shall be _ . _ " and.~t sampling is of emp sw w m areasare somettmes sampling their &loves one time per week. For exampk, areVJCW ofthe CIeamoom FacilityPersonnel TouchPlate Log from 911!l2-prcscnt. shows there were no samples takm 1iun any empIO'}'CCl oo.1bc following dates: 9f4-5,
1~12,
17
M20,
24-2j& 27/12, tOO, 9-11, 1d--13, 2223 &. 25/12,
un, 13-14, 19-21, ~27 &29/12, 1213-7,10-13, 17-19,240
28 .t 31/12, 112-3, 7-3, 1().11. 14-17,2125.t 28M3ln3.211, 4-6, 8, 1114. 18--20,22& 2$-28113 and 314-7 & lIMIS/13. Injectable drugproducts were prepll'ed (II eachof these days. On dte dates listedfur January 2013 lot3 of tnjectable~ for office stock or hospital use were prepared OD those dates. 011 the data listed Cot February2013. BpprOXimakly jots of injectable ~product:s for office stock: or bospital use were prepared UI. those dates. On the dates listed for 13, ~ lots ofinjectable dmg products for offi:e stock or hospital use were ptepmed011 those dates. In addition, entries fn (be log an: not doct.llDeD1ed as lhcy 000Jr so if is not possible to veritY the exact date that samples were 1>lren. d) fa' SOP3.030 Enviromnetllal Monitoring of the Clean Room Facility,version3.0 effective611111, statesthat"if an excursion oct:UrS above an action level,lhe Pharlnacist~e or Quality ControlOffieermusa.: be notified and investigation and conectlve aetionshould occur, This may include, buI: is not limitedto, the foI.lowing actions:
Identification ofmferob1allsoIates to determine orlgtn .... review of pressure ~ lnIbnnatian Review ofHEPA
approximate.
and cleanroom certification Review of Logsof Use, Maintenance and Cleaning(LUMACS)
A review of the Clean RoomFacility Surface Samplin& Loa: ftom7l19112 -3/ISJI3. shows chat there were numerous environmental monitoring(llI.IJfiIce sampling)excursions(above alert and/or action levels) during thistime with no documentati.oo ofinwstigations or COJ'Rlctive actiollS taken. Forexample,
i) OIl 813UI2!be samples ttomdle ISO 7 cJeao I'OOD'l tIoot (Site G) were repceee es TMTC (toO many to COUIIt) and 10CfiL ii) On 9nJ12!he samples from the ISO 7 clean room floor (Site 0) werereported as 17cfu and 2O+cfu. The samples from the ISO 8 prep floor (Site B) were reported as 24 and TMTC. iii) On 9114/12 the SllInI'Ie from the Ante mom where gowning 0C0Il'S (Site F) was reponed as 24+. Iv} On9fll1l2 the samples from the ISO 7 clean roMl floor (Site G) and the ante R)(IOl (Site F) were bothreporred as IG-t-cfu. The- sample frmn the c:hemo room (room where ebem.o drugs are prepared) was 12efu . v) OD I ]12112 the sample results Corthe preproom floor (Site B) was 12+cliJ and TMTC. vi) on 12I1112lhe samples tI:om die pRlp floor (Site B) wen: rtlpOfUld as ..)at.., viI) On Ullll3 the samples from the ante t'OOfIl (Site F) were reported as lOcfu and 1O+cfu. viii) On '2112113 the samples from the ante room floor (Site F) were reported as "Jot" aod TMTC.
Alert: levels for these mm ~ for surfaocs
for floor, Action levels fotthcse eees are . for surfaces and for floors.. There is no ~oo of any mvestJgatioo or corrective actionstB1ren in response10 lhese sample
Margaret M. Annes, c so '1YlaAJ)~ "7Y1
Luca s B, Lea ke, cso
arutII.
.-
t'1._ . . .
t
SEE REVERSE
OF ntIS PAGE
/,JIt.,..
loA.A'~
03/2212013
DEI' AKI'MENT 01' lUWU;nl AND HUMAN SERVl CT.S

RX.ll.J ANDDROOADMJNISTRAT10N
4040 Nor t h Cent r a l Expressway , Suite 300 Dallas . TX - ' ~ ;':0 4 (214 ) 253-5200 Fax: (2 14 ) 253-5314 Industry I nforma tion: www . fda. qo v ! oc ! i ndust r
03 / 18 / 2013 - 03 / 22 / 2013 300 98 15000
-TO:
Tlll.I 01' MIIYDJH..
""""'" RE Pa"
Raymond ~ .
So l a no, I II . Pa r t ne r and Pha rma c i st-in-Charge 211 So ut h Rell (Hwy 163 N)

-~
S ecialty Compounding, LLC Cedar Park, TX 7861 3
Produc e r of St eri le Dru
Product s
...wIS.
OBSERVATION 4
Procedures designed to prevent microbiological contamiMtianof drug prodom purporting to be sterile do not include
adequate validation of tbe sterilization process.
Media fins ptrfunned by your firm with eao;b of the operators that won- in tiwllSO ~ l.FH do nnt clMely llimu!ale -=tual
productioD conditions 01 cover worst case or most challenging conditions.
SOP 9.110 SterileCcmpounding Process Validation(Media Fills). version4.0 effective 3f2UI 2, statesthat for mediafilh: for noo-steriJc to sterile prepanItimls., viab are iD the ISO ~ laminar airf1ow hood. and each via) is aseptically filled by iqj . through using a steri le eeedle. aMitionaJ positivecootrol vials are prepared by inj tbrougb. an
. . I>tfrilo needle into simita. viah.
In routine production, your firm fills various size vials as well as syringes. andbatch sizes can be in excess O .
units. for
."""",Ie.
10mLvials oflot 1#03152013M22 of Furosemide 10000mLInjectable were fif1ed 00 3/21/13

2mL vialsof Marphine 5u1fi1te (Prcserw1ive Free) O.5mg1mL Iqjectablewerefilled 011 3119113 JOOmL ,,_ ufCal",iuJII Ol....::uwe 10% ( IO OuQ;lmL) IujlMia.blll were filted OB 3!.W113
OBSERVATION 5
There is no written testingprogramdesigned to assess the stabilitycharacteristics of drug products.

Speeitit:aUy. YO\Il' tir:m does 001: haw: ~ Cllda to justitY tbe Beyon4 Use lJatc (!:SUD) placed on injectable drug injectable drug products prepared by yoW' firm have been tested by a con1ral:ttesting lab in a ''time point study~. There is 110 written protocol to show how the time point study was to be conducted Le. time poina tested, what reses sre to be performed Rleach time pMnt and !'rt.onIge nfsamples. Steri lity tMting _ notnmtinely ped'ormedat the end of shelf life (BUD). YOl1a!so staW that other BUDs were detcnnined by Iikr8tm'ereview.
products.
For example.
a) HydromorJ:Ihone (Pr~ve Free) Sto ck Injection SOmWmLhas a BUD of ISO <kys. Your finn statesthat this BUD is based on samples sent to YOllr contract testing lab. Stenlity was only tested at II days.
SEEREVERSE OF nils PAGE
Margaret
'_A " dl _ eso ~n .~ LI ~ Luca s B. Lelllk~, eso

M.
Ann~ s.
---
tlfC-
0 312 212 013
lNSft:C'TIONAL OIlSERVA110NS
DU'AoRTMNT ()llIIEALTU AND avllU:N u::RVIC'I':S POOD ANDDRoo J\DMlNIrnL\11ON ~- ~
404 0 N~ rth Ce nt ral F.xp re ~ s w8 Y , Suite 300 Dal l a s . TX 75 2 04 ( 2 14 ) 25 3-5200 Fa K: (2 14 ) 253 -5314
0 3/16 12013 - 03 /2 2 /2 01 3
3 00 981 5000
f'ha.rm!l- c i~
Indus trv Information : www.fda . gov / oc /industr y

0
ro
TO,
aavmcn d L . SOldIlO, - I l l,
~dr t.ne.r
and
Special c y Compo undinq , L L e

Sf"lE, ~ ~ OCUfT In
L-ln-Cl"2.I:go::
211 South Be l l
~
Ce da r Park, TX
18 613
Pr o d uce r o f S t e ril e nr uc .l'r oau cts
(HWV 1 8 3 N)
b) Ephedrine Sll1i'ltte (f'miln'lItiy(; Free:;) SOlllgr'mL IDjeetabl~ btu Il BUD of9O days . You date dud this:is based on Infunnatioo from a book by Lawrence TrisseL The book cnly discusses potoocy under spedfic packaging and stmage conditions and does not address sterility orthe ~
c) ~\~~::~ve Free) SOmcglmL has a BU~~~ days alroom tempendme. Your firm steres that this BUD Is basedon II sent to voor oontnK:t testim!: lab. S . . v test:i:Iw: was oulv Mformed 31106 davs.
OBSERVAT1ON I
Each batch of drug product nquired to befree of object:iooable microorganisms is. nottested tbrou&h appropriate 1aboratoJy
testing.
Specifically. your finn does not condutt routine stmilily or endotoxin testing for an iIljecmble drug producu currently prod1tt.ed. You. stanldthat the !ltock 8OlutionB are routine. tested fur and endo$oxins but that finished product is not
routinely msted tmtess. produ"For~le.
units or more IIJ"e filled or
stell'.
, Stock soIlIl.iuu:o lIIl:I UMld to fill finished
lot #02262013M8 ofFenumyl (NICU Syringe) IOmcglmL Injectable was not tested for stcn1ity
lot #03182013818 ofDMPS (Dimercapropropanesulfonic Add) (l'reservariveFree) 5% IDjl:'Ctable was not tested for sterility or endotnxins lot #031UOI3S23 of Sodiwn Phenylbutyrate200 rnghnL lujectablewasnot tested fur sterility or eOOotoJlim Iol: #03132013832 ofGlutathiooefAdenQsine Triphosphate lOOmgllmgfmL Injectablewas not tested fur sterility or
- ..,
endoroxlns lot #0315201358 of HydrogenPeroxide (PreservativeFree) 3.75% lnjectable was Dotesed for sterility or eIldotoxins lot #031SW13S24 ofMettJyloobatamin (Presen'fIliw Free) 12..5mgImL InjectableW8lI not tested for sterilityor
lot 1103182013513 ofMethyloobaJaminfFolic Acid (Preservative Free ) Img!IOtngImL Injectaille was not tested for
"""Iitv " ' _

OBSERVATION 7
Testing and reteeseof drug fKOduct for distribution do not include approprilte laboratof}' detennination ofSlltisfilctcxy COIlfotm:An" to the fmaJ. :'IpOCtfications aIld identity and lltrength of each acriWt in~prior to release. Specifically, your firm does not coodua rool:ine potency kstiDg for all injectable drug products eurtmdy produced. You stated that: the stock oolutioos are routineq;oo for potency buI that finished product is not routinely tested unless. units or more are filled Stock sciucons are used to fill finished. product.
or_
Forexample,
SEEREVERSE OF THfS PAGE
_Ml'U4",, ' _
Ma rgar: - ; Annes ,
Lucas B. Lea ke ,
eso
eso '-1Y\..~
~L-
1Yl. , ~
--
03/22/20 13
' _)OI'UN3H
_mrTnl.........
INSnCJ10NAL OIl5EItVADONS
DIWARTMENT OF IIMLTIl AND IIlJMAN sr;&V.Cl'.$
tUOO AND DllOO AJ:l!..olINISlRTlON
4040 Nor th Cent ral Expre s sway, Su i ts 300 Dall a s, TX 7520 4 (2 14) 253-5200 Fax: (214 ) 2 53-5314 J ndus t r Info rma tion : www.fda.gov/oc/ ind~s try TO:
Ra
03/1 9/ 2013 - 03 /22/2013 30 0 9915000
onct L. Solano, I I I . Partner a nd Pharmacist-in-Charge

Co o un dinq. LLC
S ecialt
211 South Bell (H
1 93 N)
Cedar Park, TX
78613
Pr oduc e r of St e r i l e Drug Products
lot 11I03182013518 ufDMPS ~ewIfonJc Acid) (Preservarlve Free) 5% Injectable was not tested for
poten<y
lot 103112013513 ofSodiumPhenyRnllynne200mgltnL Injectable was I1Ol: reseed forpottllcy
tnt #O:l11,nl1~" 2 ofGh.bthioneIAdenodne Trip.bophate lOOmQllmgImL lnjectab.. wall nottNted to.-poteney Jot fI03l~2013S8 ofHydrogcD. Pt.mxide(Preservative Free) 3.75% Injectable WtI$ not tested fur potency
lot #031520)3524 ofMedtylcobalamin (Preservadvc Free) 12.5mgfmL lrljectabJe W!tS not tested bpoteney lot #03182013813 ofMettrylcobaJaminlFolic Acid (Preservative Free) ImgJlOmgImL Injectable was not tested for
""",",y
OBSERVATtoN 8
Asepti<: lJI"DCdSing areas are deficient regarding Ihe systemfor cleaningand disinfecting the room and equipment to produce
aseptic oooditions.
iiiiE
ly. your fum did not document the use ofa used as cleaningagentsin the lSO 5, ISO 7 and 8 erees. esc were m storage in tho 3c . ed Ante roum aDd the Sterile Prep room. SOP 3.020 Cleaning and MaiDtenance of tile Clean Komn facility, Version 2.0 effective 611111 , states to "Document the disiDfectmt in use on the Cleaning and Maintenance oftbe Clean Room
Facl1ity form" .
---
SEE REVERSE OFTHIS PAGE
03 /22 /20 13
PAGE6 OF 6' AoQI!S
DE:PARTM Jo:ST O F HE ALTH A:\1) H UI\fA,,\; SE RVIC ES FOOD AND DRUG ADMlNTSTRATION
o.o.Tf IS)OF tNSPECHOH
10 W a t e r vi e w Blvd. , 3 r d Fl oo r Pa r sip p a n y , NJ 070 54 ( 973 ) 3 3 1-4 900 Fa x: (97 3 ) 33 1-496 9 Ind u st r y I nfo r ma t i o n : www.fd a .qov/ oc/ i ndustrv
TO :
"'~ .. H~ .. E
03/ 18 /2 013 - 03/21/2 0 13 * 30015 4 56 40
Ge n e
nece aao , RPh"
Co-Owne r
STOEEl OllOIlU S
Drugs Are Us , Inc . d b a Hoce wc Ll, Ph armacv

GOry. STU ," . ZIP GOtII': . C DIJN' IlV
1 W Br oad St
TYf'E S TAB"Sl IIEHT IHS ....CT O
Hop e we ll , NJ
0852 5- 1901
Prod u c e r of Ste r i l e Hu ma n Dr u o Products
This document lists observations made by the FDA representative(s) during the inspection of your facility. They are mspectional observations, and do not represent a final Agency determination regarding your compliance. If you have an obj ectio n regarding an observation. or have implemented. or plan to implement, corrective action in response to an observation. you may discuss the objection or action with the FDA representativet s) during the inspection or submit this information to FDA at the address above. !f you have any questions, please contact FDA at the phone numbe r and address above.
DURING AN INSPECTION OF YOU R FIRM WE OBSE RVED:
OBSERVAn ON 1
Aseptic proces sing areas a re deficient regarding thc system for mon itoring environmental cond itions . Specifically,
a.
On 31l 912 0 1~s for viable air monitor ing were not o bserv ed in the incub ator, although firm documentation sho wed that _ s urface, glo ve fingertip, and viable air environmental mon itori ng plates had been coll ected on 3/14120 13 and were to be read on 3120r.W I 3. In addit ion, there is no assurance the media and incubation conditions can supp ort growt h .
and the uncontrolled office .
b. Differential pressure is not mo nitored betwe en the ISO 6 and ISO 7 areas: ISO 7 and ISO 8 areas; and ISO 8
<. There is no assuran ce that the test to visualize unidirectional air flow and the collection of non-viable particle coun ts were perfonned und er dynamic co nditions, as stated in the most recent repo rt dated 10/1212012. This
study was perfonned d. in the study.
There is no scientific rationale for the frequency of non-viable particle count col lections in the ISO-5, 150 -6, and 150 -7 areas . Data is collected once ever-
Injectable products produced in the asep tic processing area include: Methylcobalamjn 2Smglml Inj ectable, Glyceri n 72% (w/v) Inje ctable, Pyridoxine He l IOOmglml Injectable, and Trimi x Injectable (Papaverine, Phentolamine , Prostaglandin EI
30m;0.5mg/Sm"c pimlt
OBSERVATION 2
Clo thing of personnel engaged in the processing of drug products is not appropriate for the dut ies they perform. Specifically,
Er.oPlO VE E(S) SIG..... JU<E
Karen E . D ' or~z i o, Investiga to r '.. . Nicho las A. vLo La nd , I n ve s t a q e t or ~7-e.---;l--Z--:;>

I]'I; SI' ~:CTlONA L
.I iA "
~ I()<.
03 /2 1 / 2 013
PAGE 1 OF 2 PAG ES
O RSER\, AnONS
DEPARTM I:NT Of' m :ALTH AND HUMAN SF.RVICr,s

FOOD AND DRUG ADMII'ISTRA nON
DlSm""
AOO~ E SS
ANO_
><t.Io'llOR
l""TE(S~ OF _CT lC
a t e r vi ew arvc. , 3 r d !fl oo r 10 W Pa rs i ppa ny , NJ 07054 ( 97 3) 331- 4 900 Fa x : ( 973) 33 1-4 969 Industr
TO :
FI"''' NMoE
03/18/ 2013
FE' _OER
- 03/21/20 13 *
3 0 0 15 4 5 6 4 0
In format ion : www. fda. aov/oc/indus trv

s mEfTMI[)RE M
.......E "" o t m.E OF INOIVlOll.... TO'lM"Ol.! REPOR ISSJ !.D
Gene RaQazzo, RPh , , Co- Owne r
Drugs Ar e
U ,.
a cy I nc . db a Hope well Pha r m

08525-1 90 1
1 W Broa d St
TYI'! !Sa sus..... r;....
IN ~TEO
CJlY , STATE-lIP GOOE, ClXJNTRV
Hooe we ll , NJ
Producer o f St e ri l e Human Dr ug Produc t s
Gowning worn by personnel working in ISO-5 laminar flow hoods does not cover all skin, dothing, and shoes, Gowning consists of a thre e-quarter length sterile disposable coal, bouffant cap, shoe covers, face mask, and sterile gloves, as observed on 3/ 18/2013 .
OBSERVATION 3
An adequate number of batches of each drug prod uct are not tested to determine an appropriate expiration date. Spe cifically, There is insufficient data demonstrating the chemical stability and sterility of injectable drug products thro ughout their beyond use dates, For example:
Pyridoxine 100mgimi Inj ectab le is produced with a 6-month beyond use date Glycerin 72% (w/v) Injectable is produced with II 6-month beyond use date Methylcobalarnin 25mgiml Inj ectable is produced with a a-month beyond use date Trimix Injection (Papaverine, Phentolamine, and Prostaglandi n E l 30mgl0.5mgi5mcglml) is produced with a 2-month beyond use date
DATES OF INSPECT IO f"l :
03/18!'2013(Mon), 03fI912013(Tue), 03121f10 13(Thu)
........oYf. E(S) SlGNATlJRl'

r OR:-l HIli. W (0'111,1 1,
Ka r en E. D'O raz io , I nve s t i ga t or Ni c hol a s A. Vi ola nd , I nve s t iga t or

PREVJOl'5EDITION """"-.l'TI! I~SI'[CTIONAL
I M'~yz..u ~ ~ L-/
I
OBSERVATlO :-i S
DME ISSUED
0 312 1 /20 13
PII. GE 2 0f 2 PII. GJ.:S
The observations of objectionable conditions and practices listed on the front of this form are reported: 1. Pursuant to Section 704(b) of the Federal Food, Drug and Cosmetic Act, or 2. To assist firms inspected in complying with the Acts and regulations enforced by the Food and Drug Administration .
Section 704(b) of the Federal Food, Drug , and Cosmetic Act (21 USC 374(b)) provides: "Upon .completion of any such inspection of a factory, warehouse, consulting laboratory, or other establishment, and prior to leaving the premises, the officer or employee making the inspection shall give to the owner, operator, or agent in charge a report in writing setting forth any conditions or practices observed by him which, in his judgement, indicate that any food, drug, device, or cosmetic in such establishment (1) consists in whole or in part of any filthy, putrid, or decomposed substance, or (2) has been prepared, packed, or held under insanitary conditions whereby it may have become contaminated with filth, or whereby it may have been rendered injurious to health. A copy of such report shall be sent promptly to the Secretary."
FORM FDA 483 (9/08)
I)I;:;PAKT.\tENr O F IU:: A LTH A :-IV H UMAN St: R\ 'I<;I:S

FOOD A};1lDRUG ADMIN I STRATION
5 55 W ind e r l e y Pl a c e, Suite ?OO M a i ~ l an d , FL 3275 1 (40 7 ) 47 5-4 7 0 0 Fax: ( 407 ) 475 - 4 76 8 Indus~ry I n for.nat ion : w~h . t da . g o v / o c/ indust ry TO:
~a rco
03/0 4/20 13 - 03/21/2 013
FE'N"'' ' ,lO R

3 0 09724 0 8 5
(n roi) Lol e i t , CEO I n c . D/ B/ A OlYT.pia
Lowlit e Investment s , Ph ar:ll acy

CITY . STATF, l:l ~ COllE, COUl'<TR V
6700 Con r oy wi ndc r n e r e Rd Su it e 1 40
Cr l a ndo , F:
32835-35D O
Pr oduc e r o f st e r i le d r u g p r oduct s
which
n. The
used for sterilization of drug products, containers, and closures is supplied with is not tested for endotoxin or sterility.
OBSERVATION 2
Procedures designed to prevent microbiological contamination of drug products purporting to be sterile are not established, written, and followed. Specifically, A. Th which was performed for the first time o n 3/1/13 does not simulate all aseptic operations conducted during normal filling of sterile products in the ISO 5 hood. The ~ only simulates This simulated process is not similar to routine filling processes, such as activities observed on 3/4113 in wh ich pre-mixed bulk sterile solution was trans ferred wit h a syringe from a bulk bag into open vials which were then hand stoppered after all of the vials were filled. Th ere is no media fill simulation of lyophilizer loading and syringe filling. B. Aseptic techniques observed on 3/4/13 were inadequate as follows: I. The technician was observe d picking up the stoppers with her gloved hand and placing them onto the filled vials. At this time, the operato r's glove was observed to he tom. In addition, exposed skin was observed at the wrist due to the glove not being pulled up over the sleeve. 2. There was infrequent sanitizing of gloves, especially prior to re-entry into the ISO 5 hood after retrieving items from the lSO 6 buffer room. 3. The technician was observed passing her hands and arms over the top of open vials in the hood that were in the process of being filled.
gO \\> l1S .
C. On 3/20/13, technicians were observed 10 exit the clean room while still wearing their materials off of the shelves and then re-entered the clean room without regownlng. D. Rags of stoppers and vials which have been transferred into the buffer room and the ISO 5 hood.
E.
They retrieved
are not wiped down with sterile disinfectant prior to being
There is no data to support contin ued sterility of previously opene d bags of stoppers stored in the buffer room without being fully re-sealed.
E ~OY;' E(C)
s """"TU,"
Car y n M. M c n ab, I nv e s t i ga t o r J o a n ne E . K ~ n g , I ~ ve sti q a to r
~~IJi.
~
If1Nh
03 /2 1/20 13
-L __
P/I.(,1; 2 OF 6 PAGS
Br o o ke K. Higg i n s , Invcst ~qa t o ~~til1trt~/ ~~

Il\SP ECTI QNAL OnS ERVAn ONS
DEPAKT,'\ll';sr ell? lItALTII A:,\;I) IJLMI\:"l SEKVIU;S

FOOD AND DRCG AD MI!'lISlRATIO N
--- -[l,>, TF (S ) <i'lNsP~<:;r IO ~
-,;,"'- - -- - -- - - - - 1
555 W i nd erl e y Place , Mai t l a nd, FL 3 27 5 1 ( 40 7) 475 - 4 '/00
Su i t e 2 00
47 5 - 1768
-L
0 3/04/ 2013 - 03 / 2 1 /2 01 3*
300 97240 8 ~
Eax r ( 40 7)
www c.c[ cd ~ dc .~ gc oC v " / c O c C c/ cl c , c,d "u ~ sc t= r2Y ~ .....D TITLE a' 1 " .5!V;Ou.oJ:""" TO I'oHOM RF ;;o;.nssDEb
I ndustr y In f o r ma t i o n :
TO ;
xe r co
(nmi )
L o L e i. t ,
CEO
--iii.i~~zF~Ltffiw---------------t-i~ " E ESTAilUSltJE NTIMI'lCII.ll-
Lowli t c I r.v e s t mc n t s , Inc . D/B/A Olynp ia Ph a rmacy
67 00 Conroy W i n d e r me r e Rd Suite 1 40
- --
Or lando , FL
F.
32 835 -3500
Produ ce r of s t c r i Le dr uc p r o du o t;a
Parti ally sto ppered vials co nta ining drug product to be lyop hilized are transferr ed from the hood to the lyophilizer however the pathway is not e ntirely covered by HEPA filters.
OBSERVATION 3
Separate or defined areas to prevent contamination or mix-ups are deficien t regarding operations related to aseptic processing of drug products. Spec ifically, non-sterile Mitomycin API (a cytotoxic) in powder form has bee n used to prepa re Mitomycin Oph thalmic prod ucts in the same ISO 5 ho od wh ere other non-potent drugs are pre pared.
OBSERVATION 4
Aseptic processing areas are deficient regarding the system for monitoring environmental conditions. Specific ally , A . No active micro bial air mo nitor ing is performed in: the ISO 5 hood each day d uring preparation of inj ectable drug prod ucts. TIle most recent passive mo nitoring was performed 011 3/ 1113; prior to that it was performed 10/26/12. B. Microb iologicaJ monitoring of the employee's fingert ips is not performed each day that a balch of sterile product is mixed and/or filled. The most recent operator monitoring was performed on 3/1/13; prior to that it was performed 10/26/12. C. Microbiological monitorin g of the ISO 5 hood surfaces is not performed at the end of each day that a batch of sterile prod uct is mixed and/or filled. The most recent microbial monit oring was performed 3/1113; prior to that it was perfoTITI\..'<l 10/26/12.
D. The current moni tor ing program does not include any no n-viable part icle monitori ng during formulation and filling of injectable pro duc ts.
Ii Th
us ed for air, surfac e a nd fingert ip monitorin g are incubated under amb ient conditions o n a shelf in the buffer room for . days rather than in a 30-35C incubator for 48 - 72 hours as specified by the dlrectlons for usc.
r.V l CVEI',s ) OIG .... ;uRE:
Cary n M. M c n ab , I nv e s t i ga t o r
1-
-'-
Joanne E. Kin g, Invc s t i g<J. t o r ~~L: Brooke K. Hi ggi ns, I nv e s t i ga t o r iI.. ~~ . ~.I f'l
(!MW)'L!i1 . lP1/!-/fa.b
[} "')Jjl"'''J '''A IJ I .;Ii4~G''IH*I~ 1
; "'-"
03 /21/20 13
INSI'J.:CTlO~,'\ L OIISERVi\'I~~)NS
---"
-1
I' AOR "l Of 6 PK d-.S
DEP A RTM LNT or JJEALTII A N') II V:\l A N SKR V l n~'i

FOOD A""D DKUG AI )~!NTSTRA no:>!
'<STIlIe T AIXl'iE-SS...., 'HO"E "..IMBER "" TLI Sl Of ' NSPECT
555 W i nd e rl e y Pl a ce , Sui te 2 00 tca Lt La n d , FL 3275 1 ( 407 ) 4 75 - 47 0 0 Fd X: ( 40 7 ) 4 75 - 47 68 Industr y I nf or m ati o~ : ~~. t d a.gov /o c ! indu st r v
N~~~ A~DTln
03 /04 /20 13
FEIHl"""?
03/ 2 1/ 2 0 13 *
300972 408 5
OI"Ni""",,"""m
.o" R~TT &um
TO:
"IIIM""''''E
Marco (nrru.) Lol c i t, CEO

3TJlEETADOReS
Lowli te Lnves t.me n t s , I nc . O/B!l\. Olympi a Pha rmacy

C:lY . STA~~PCOoE, COl'~mY
6 7 0 0 Con r oy W ind e r :Ttere Rd Su i t e 14 0

TYM:'r6TABU" ''''C:Hr 1 ~".rCT rn
Or lando , FL
321335 - 35 00
Pr o du cer o f steril e drug p r oduc t s
f . No microb iological mon itoring of the air or surfaces is performed in the buffer room which sUlTOUJ1ds the ISO 5 lamina r air tlow hood. The technicians stand in the buffer room while they arc preparing injec table products in the hood and frequently retrieve items from the buffer area for use in the hood.
OBSERVATION 5
Aseptic processing areas are deficient regarding air supply that is filtered through h igh-efficie ncy parti culate air filters under positive pressure. Specifically, A. No static and dynamic airflow pattern studies (smoke studi es) have been performed in the hood or 6 buffer room where injectable drug prod ucts are pr epared. B. There is no continuous monitorin g of air pressure differentials from the classified buffer and ante rooms to the surrounding non-classified lab oratory area.
OBSERVATION 6
Clothing ofpe rsonnel enga ged in the proces sing of drug products is not appro priate for th e duties they perform. Specifically, the gown, booties, hairnet, and faccmask worn in the clean roo m are not sterile. The knee length gown only ties at the neck and waist and does not fully cover street clothes. In addition gown ing does not provide complete coverage of the skin 00 the face and neck
OBSERVATION 7
Asep tic processing areas are defic ient regarding the system for cleaning and disinfecting the room and equipment to produce aseptic conditions. Specifically,
A.
The suitability and efficacy of disinfecting agents and procedures have not been assessed to ensure potential contaminants are adequately removed from the surfaces in the classified areas. Routine cleaning procedures for the ISO 5 hood do not include the use of a qualified sporic idal cleaning agent at an established frequ ency.
EMPLOYEE:(c mr,N.'ru !lE
~
''ll: UF

!'OR'" FD A 4l) (ll~IIl6)
Ca r yn M. Mcr ab, Ln v e s t Lqa t o r- ~JJ1. J o anne 1': . Ki ng , Inv est iga ~or Brooke K. HlgglTIR , Inves tlga t or
l)l'e''' ',;u,,w
t::? . ftU./lah
03 ! 2 1 ! 2 0 13
l'fll:\'IO"'! lIDmo" Ol<SOLl';'IT'
INSrLCflOI\AI , onssn v i\ -norcs
?A (ih 1 OF 6 PAOt;;,;
OEPARnlEj\ ~r
O'ST~ ,CT """"~6
OJ- H EA LTH
A~D
Hl:MA.X SERV ICES

OAT" II\) or lNS"E0116'l
FOOD AND DRUG ADMNISTRATIOK

AND. "0"'" NJto'OCR
5 55 Win derley Pl a ce, Suite 2 00 Mai tl a n d , FL 3/.751

( 40 7 ) 175 - 4 7 00 Fa x : ( 40 7 ) <1 7 5 - 47 68
0 3 / 04 12 013
FE,N uMSJl
03 12 1/2013*
3009 7 24 0 8 5
Ind u s t r y I n f o r n a t i on ; www.fda .gov /oc / indus t r y

.....'E ...-.> trne OF '~OMOJ ," C TOWiioM HPoR T ISSUED
TO:
"~
....
M a rco (Old) L o Le Lt. , CEO

""lIT AlJ()REss
r.ow .t i.t e Inves t n cnts , Ph a r-ma c y

en, STAfL, 1' CODE. WJNTRY
I n c . D/B/ A Ol ymp i a
inder.rere 6700 Co n r oy W Suit. e 14 0 l"'tf'= E ~TARU6 '-NT "".rEe 0
Rd
Or l an d o , FL
32835 -3 5 0 0
Pr od u c er o f ster i l e d rug products
B.
solutions are used to clea n the surfaces of the ISO 5 laminar now hood where in' ectable druz nroducts are mixed and filled.
OBSERVATION 8
Time limits are not established when appropriate for the completion o f each pro ductio n ph ase product.
to
assure the quality of the drug
Speci fically, bulk drug products such as Clprofloxacin 17 mglml Injection and CACO/CO PPER 6.2 mg/rnl INJECTION which are stored for future use may be re-opened or re-entered with a syringe in the ISO 5 hood ~ _ Prod ucts are not consis tently label ed with the initial date of ope ning or entry so as to prevent use after . Furthermo re, ther e is no da ta to SUppOTt continued sterility of bulk drug products due to these practices.
OBSERVATION 9
There is no written testing program designed to asses s the stability characteristics of drug products . There is no stab ility data to support expiration dales applied to injectable drug products and dates are extended beyond those spec ified in the fin n' s form ula wo rkshee ts, for example: A. Glutath ione 200mgl ml i nj ectable lot K5428 was prepared on 11 /28/12 and assigned an exp iration date of 11113 ( I year) althou gh the formula wo rk sheet specifies a . ay expi ry.
D.
C.
Vitami n B Bu ildup Plus Injectabl e lot KOOl4 was prepared on 1111 4/ 12 and assigne d an expiration date of 09113 (10 months) althou gh the torr nula worksheet specifies day expiry. Methylpr ednisolon e Acetate RO rnglml lnj ectable lot K4116 was prepared on 11/ 16/12 and assigned an expiration day expiry. dat e of 11113 ( I year) although the formula worksheet specifies
a .
a .
O. Beta Alanine IGOmg/ml & L-Camosine IOOmglml lnj ec1ion lot K441 9 was prepa red on 1l/19J12 and assigned an
exp iration date of 12/ 13 ( 13 monms although the formula wo rksheet specifies
E. Naproxen 100 mg/ml Inj cctablc lot K4 115
W 3'>
year) although the for mula works heet specifies
a .
a .
day exp iry.
prepared on 11/15/12 and ass igned an ex.pirat ion date of 11/1 3 (I day expiry.
OJr"O VEF .(j; j SIGVTlJf<l
DATE <S$UEO

FO RM FDA 4&] (O 'Mlill
Cary n Mcnab, Invest i g a t o r ~"J'1...-1Ji,. Il1. J!f1Ji h Joan ne E . Ki ng , Inve s t i g a t o r ~~~ Hr oo k e K . Hi g gins , Inv es tigat o r 8~
".
U U? ' . MAr . I -c
AT l fJNS
0 3/2 1/ 2013
.....v'nc ' PrIm"...O,,",,'J!':'Tl
I ~ Sr ~:C11 U N A I ' ore... e nv
PAGl: S OF 6 PAlibS
VEVARTl\IEN f OF HEALTH AND HW"IAN SERVICES
tor~"iRiCf"iii5Di'll.SSAAD 0tt0NE: NUMBER
FOOD A~ DRUG AD"fll'ISTRATIOI'
O~TE :S) OF 1 >ffl " O"tIO N
55 5 Wi ndp.rl c y Pl ace, Su i t e 20 0 M ait land . FL 3 2 7 51 ( 4 07 ) 47 5-4 7 00 Fax : ( 4 07 ) 4 75 - ~ 7 6 8 I n d u s t r y r n t o r rca t i on: ww~.da.gov /oc/ i ndus try
" ""'E,o."D T" ....''''OUAl TO .....10.. OF 1
~l
~j 04 /20 1 3
F E....fIlBOR
0 3 /2 1/2013 *
300 972 40 8 5
ISSU<. O
TO: M a r c o {n mt 1 Loleit , CEO r"...-....r,IE :"owl i t e Tn ve s t rl!'! n ts , I n c . D/ B/ A 01 yrr.p i a
s m ffT ,o.DDft"hS~
Ph arn a c y
C'TI. sr,o.TE. Z,,"COI1F. C<l\J"' HY
6 7C O Co n ro y Wind e rmere Rd Su i t e 1 4 0
TI P, E
AElUSH.... NT ' '' ~ ' '&; TE
Or lando ,
,1
32835 - 3 5 0 0
Pr od'..lc c ::: of s t e ri l e dr ug p r od uc t s
OBSERVATION 10
Dr ug product conta iners and closures were not clean and sterilized and processed to remove pyr oge nic properties to assure that they arc sui table for their intended use . glass vials and rubber stoppers used in Specifically, there is no data to demonstrate that the finn's practice of aseptic filling operations renders them Clean, sterile, and pyrogen free. Load patte rns have not been established, and the is used to assure sterility of the items cycles have not been validate d. A colo r indicator on the exterior of the processed.
OBSERVATION 11
Each batch of drug product purp orting to b e sterile and pyrogen-free is not laboratory tested to determine conform ance 1 0 such requirem ents. Specifi cally endotoxin testing has never been pcrfonned on finished injectab le drug products .
OBSERVATION 12
Labo ratory contr ols do not inclu de the establish m ent of scientific ally sound and appropriate sampling plans designed to ass ure that in-proce ss materials and drug prod ucts conform to appropriate standards of ident ity, streng t h, quality and purity. Specifically, there is no j ustification for th e samp le size (If for sterility testing.
.. DATES OF 11\SP EC'TIO N:
03/04!2013(Mon), 03JOSI2013(Tue), 03J20/2013(Wed), 03i21f20 13(Thu)
E"PlO">"Ef.(S) SlGI<A
ru-e
C<:l ryn H. M::;n a b ,

~Ol{ "
Joa n n e E.
Broo ke K.
In"e<tigato, ~~ ~ _ r d. Hi gg i ns , Lnv e s t Lq a r; r./ i \'4y1j.1J )y0- _0 3 / 21 / 2 013

Ki n g, I n ve s t i ga t or
Th'SPErnONAL OB,, <;f. RVAT10"lS
~AGE 6 OF 6 PA (' ,f;.~
DATE
SS~El:
l'1'" .,.\ {(IOIillfI
""" VI"'" OllITlOI< OBSOiE"TE
1, Pursuant to Sectio n 704(b) of the Federal Food, Drug and Cosmetic Act, or
"Upon completion of any such inspection of a factory, warehouse, consulting laboratory, or other establishment, and prior to leaving the premises, the officer or employee making the inspection shall give to the owner, operator, or agent in charge a report in writing setting forth any conditions or practices observed by him which, in his juoqement, indicate that any food, drug, device, or cosmetic in such establishment (1) consists in whole or in part of any filthy, putrid, or decomposed substance, or (2) has been prepared, packed, or held under insanitary conditions whereby it may have become contaminated with filth, or whereby it may have been rendered injurious to health A copy of such report shall be sent promptly to the Secretary."
O):;l'ARTM :-.T OF HEALTH A1\1) HLMAN SRYICE S

FOODAND DRUG ADMrNISTRATIO,,"
Dl ~ T""'7 A:;>D ~ l," ~"" " ~ ~ .... N ~ " e E.F<
"AIT:S' O" l""pt:::r,O ~
30 0 Riv er P lace, Suite 590 0 De t ::-o i t, MI 4 8 2 0 7

{3 13 ) 393- 8 10 0 F a x : (313) 393 -8::.39
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t 03 /l9/ 2 0 13 "EI" ,,,,meR
03 /2 1/2 0 B
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"-cr
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Ncra Apo t he::a ry and Al t.e r:'.at i v e Thera p ie s, I n c .

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1 101 E. 86th St': :::eet

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4624 0
P:::-odu c e r of St e :::i.l e Dru g Pr-oduc-t s
This document lists obse rvations made by the FDA representativcfs) during the inspection of your facility. They are inspecrional observations, a nd do not represent a final Agency deter mination regarding your compliance. If you have an objection regarding an observation, or have implemented, or plan 10 implement, corrective action in response to an obscrvarirm, you may discuss the objection or action with the FDA representativefs] during the inspection or submit this information to FDA at the address above. If you have any questions, please contact FDA a: the phone number and address above
DURING AN INSPECTION OF YOUR FIRM WE OB SERVED:
O BSERVATION 1
Each batch of drug product required to be free of objection able microorga nis ms is not tested through appropriate laboratory tes ting. Specifically, the fin n fails to ens ure that each hatch of asepti cally proces se d inje ctable drug products, which it distributes, pas ses sterility and endotoxin testing be fore distribution, The last sterility testing was conducted on the pro duct Trimix on d. I ulv 25. ? OO ~ Xo endot oxin te sting has ever been cnndnct..
OBSERVAT ION 2
Te sting and release of drug pro duct for distribution do not inclu de appropriate laborat ory determination of sat isfactory con formance to the identity and strength of each active ingredien t prior to release. Specifically, the finn fails to as sure that each ba lch of aseptically processed injectable drugs it distr ibutes, meet s appropr iate potency limit s before distrihuuon. The last potency testing was conducted on July 25, 200S on Tri mix. For example, Bimix, Trimix and PG E I are rout inclv released with no assay testing crier to dis tribution.
OBSERVATION 3
Pro cedures d:osigned to prevent microb iological contam ination of drug products purporting to be sterile are not established and followed. I} There is no aseptic process validation (media fills) simulating the asepti c pro cesses that take place for producing finished dosage forms. 2) The ISO 5 hood in which aseptic procedures are comple ted was obs erved to ha ve suppli es stored wit hin and above the hood, 'the supplies on top of the hood are used during aseptic p rocessing. 3} The ISO 5 hood is located in an area that is not a class ified area. basis There is no dynamic air 4) The ISO 5 hood has only been cert ified on ll! testing during the certi fication . There was no evidence of sm oke studies eve r being conducted to verify the lam inar air flow , 5) While observing aseptic operations the following deficiencies we re noted:
m . ' CO YE.E jS ) S ' ~~ ~ n.>~ ~

O IIM rn A.
Au s t i n , I nve s ti g a t o r La r ry JV:ari e A. Fadden , Inve s t i ga t o r L~ Q...,-,tJuLJ~.'V'PR V[OI:' :>lTIDI< OBWUT<
".
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03 /2 1 /20 13
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!!'oISPECT I O]';AL onSERVATlOKS
PAGE I OF 3 PAGES
DRPARUfE!\'T O F H.EALTH .ccn H U:\<I A l' SF.RV1CES

fOOD A";D DRUG ADMNISTRATlO~
DIS . R'GT A~D"tt S A~ D
P H O ~ E N L"" ~ r:R
D A Tio:SICf N~~!1.."fiC~
Pl a ce , Suite 5900 De t r o i t , M I 4 820 7 (313 ) 393 -8 100 Fa x : ( 3 l3) 393 -8139 Indus try I nf orma tion : ~~.fda90v /oc/indus try
" "" l ,,~ ~ ~rTl~ OF "'~ ""0lU~' ' 0 ~, HO~ Rep o RT ISsum
3 0 0 Ri v e r
~i / ~ 9 / 2 0 1 3
, EIIM ' SFR
0 3/ 21/ 20 13
hi~'" ~AMf
to:
Charl e s A . Lil".dstrom, O..... r.er
r;!o r a Apothecary and Al ternative
Therapies . I n c .
GIlY, S1A- a . Zf' CODE, C O\J ~ 'R'
I I l l el ,
I
S ~ REh T OOi\i' ss
E.
86th St ree t
~Y"li at1"A.8 l ;t""F!'IT 'NS og=
: :1d :'-a r.a p o l i s , I N
46 24 0
P rod~ c e r
o f St e ri l e Drug Produc ts
a) the op erator had exposed skin on his neck and eye area. h) the operator's movements were no! slow and deliberate within the ISO 5 hood. and using an unglovcd hand 'wiped the from inside c) the operator initially sprayed [he ISO hood surface with working surface of tho: ISO 5 hood. d) the ope rator did not wash hi s hands prior to gowning and donning gloves, which is not ill accord ance with their written pro cedure. 6) th e procedure "Nora Apothecary Pharmacy Policies & Procedures" Effective Febru ary 20 12 is deficient in that: a) th e cleaning procedures do not include the use of spor icidal agents and do not specify to use sterile 70% IPA Currently, no sporicidal cleaning agent is used. The typ e of wipes to use in the hood are not specified, regular household paper towels were ob served to currently be in use . In additio n, the procedur e does not des cribe the gowning of the op erator prior to cleaning the hood area, b) The gowning of operators prior to entering the aseptic processing areas is done u::.ing non-sterile gowning materials including the outer gown, gloves, ha im ct, and shoe covers. the (oil and solvent based 7) There is a failure to ever perform _ pro ducts) and the , Inc. (stock solutions and finished dosage forms). 8) The "paddles" used to do surface samp les, fingerti p samples and air samples are incubated for on a shelf in the pharm acy area. They are placed on top of the comp uter modem, which is on the shelf. The area was observed 10 he dusty and there is no temperature monitoring in room. 9) The pre-filters to the area in which the ISO 5 hood is located has it's ow n HEl'A filter, airflows through a pre- filter prior it bas not been changed since Dec ember to the HEPA filter. according to their procedure. this filter is to be changed 10, 2012.
OBSERVATION 4
Aseptic processing areas are deficient regarding the system for monitoring environmental conditions, Environm ental monitoring of rhe ISO 5 hood docs not occur each time au injectable drug is formulated therein For example, on 3/] 9/20 13, no environmenta l mon itoring was during tho: proce ssing of Bimix Injectable, prescription number _ observed. In addition, personnel monitoring of the operator was also not perform ed on this same day. The last cnvironmental mcm itoring was done Dec ember 10, 20 12 and the last personnel monitoring was done September 17, 20 ]2 ,
OBSERVATION 5
There is no written testing program designed to assess the stabilit y characteristics of drug products. Spec ifical ly there is no stability data for any aseptically processed inj ectable drugs produced by this finn including Binu x (90 day BUD ), Trimix (90 day BUD), PGE-l (90 day BUD) , and the stock solution s P apaverine and Phentolamine haw a 90 day hold time.
!
' MN"Y!~SI ,G.....TVI>E
SEE REVERSE I Lar~y K. Au e t i. n , Inve stigato r OF THIS PAGE I rearae h. Fadden, j nv e a t.Lqa t.ozfO RM F O). 4S3 (eMI8 ,
?' leV"'"" " OF.lON QBSOLETE
!-leA
In;''rf"
ORSER VAT IO!'S
DATI' 'SS U;O
I 0 3/ 2 1/ 20 ::'3
PAG E 1 OF 1 PAGES
L'W LCT I O ~ AL
DEPARTMENT OF HEALTH AND HUMAN SERVICES

FOOD AND DRUG ADMINISTRATION
DISTRICT ADDRESS AND PHONE NUMBER
DATE(S)OF INSPECTION
300 River Place, Suite 5900
Detroit, MI 48207 (313) 393-8100 Fax, (313) 393-8139 Industry Tnformation: www.fda.gov/oc/industry
NAME AND TiTLE OF INDiVIDUAL TO WI-IOM REPORT iSSUED
I
.
I 03/19/2013
FEI NUM""
03/21/2013
TO,
FIR!/. NAME
Charles A. Lindstrom, Owner
Nora Apothecary and Alternative Therapies, Inc.

CITY, STATE:, ZIP CODE, COUNTRY
I 1101
STREET ADDRESS
E.
86th Street
TYPE ESTABLISHMENT INSPECTED
Indianapolis,
IN
46240
I Producer
of Sterile Drug Products
OBSERVATION 6
Written procedures are not established for the cleaning and maintenance of equipment, including utensils, used in the manufacture, processing, packing or holding of a drug product. Specifically, there is no written procedure addressing what steps would be taken to decontaminate the area if there is a broken or spilled vial of beta-lactam products.
I EMPlOYEE(S) SIGNATURE

FORM-FDA 483 (09108)
I Larry I Mane
K. Austin, Investigator A. Fadden, Investigator
~~1N.~icQJ:4u
l.i(Y\.PJA .a
o
,
I
DATE ISSUED
~~
03/21/2013
PAGE30F3PAGES
PREV]OUS EDmON OBSOLETE
INSPECTIONAL OBSERVAnONS
DEPART MEr'\ T OF HEA LH i M D HmtAIlo' Sf. RVICES

OISTRCl ""XlmSS 10M> _ _ _
FOOD AND DRUG ADMlNlS1ll.AT ION

oo.lf(SIOl' "SPEC''"'"
4040 North Ce nt r al Exp ress way , Sui te 300 Dallas . TX 75204

(214 ) 253-5200 Fax : (2 1 4) 253-53 14 Industry I nformation: www .fd a . g o v / o c l ind u s t r y
......., 10M> Tnu: OF N'lIIII<lU<.I. TO......,.. REP<lRT lSSI.JW
03/18/2013
. E'......aEIl
03/20/2013
300 6311680
TO:
IV Solutions of Lubboc k
CIT'I. SlA . .. r::ooE. COUNTRY
Jan Robinson , Vice Pr e sid e n t
of Operations
STllEET _ ss
370 6
1YPI;; ESTA&LI&-..E..... ,_erE)
A 20 th St
Lub boc k , TX
79410
Producer of Steri le Drua Produc ts
This document lists observations made by the FDA rcprescntativc(s) during the inspection of your facility. They are inspectional observations, and do not represent a final Agency determination regardingyour compliance. If you have an objection regarding an observation. or have implemented, or plan to implement. corrective action in response to an observation, you may discuss the objectionor action with the rDA representativets) during the inspection or submit this information to FDA at the address above. If you have any questions, please contact FDA at the phone number and address above.
DURI NG AN INSPECTION OF YOUR FIRM WE OBSERVED:
OBSERVATION 1
Clothing of personnel engaged in the proce ssing of dru g prod ucts is not appropriate for the d uties they perfonn. Spe cifically, yo ur firm uses no n-sterile hair covers, mouth covers, and gowns as cloth ing for personnel who aseptically precess drug products in the clean roo m. On March 18 and 19, 20 13, a techn ician, . was observed ase ptically processing drugs in the ISO 5 Hood, within the ISO 7 clean roo m, with exposed skin on the face and neck and expo sed hair not fully cove red by the techn ician's hair cover. Additiona lly, clothing worn by the personnel outside the clean room in uncl assi fied areas was not com pletely covered by the gowning around the neck area, be low the knee, and aro und the backside ofthe ope rator . The o perator observed was aseptically processing prescript ions for the following aseptically processed dru g produc ts:
I.
2.
Vancomycin- '50mL/ ; total elastomcric pomp'

Vancomyc in . 100mL, total es lastome ric pump s Ceftriaxone - 100roL, total elastomeric pumps
3.
OBSERVATION 2
Build ings used in the manufacture, process ing, packing, or hold ing of a dru g product do not have the su itable construct ion to facilitate cleaning, maintenance, and proper o peratio ns. Specifically , you r ISO 7 Clean Roo m. whe re your . ISO 5 hoods resi de, and where aseptic processing of sterile drugs occurs, has the exhaust air vent _ . rather than be low the ISO 5 wor k bench leve l, potentially putting the ISO 5 hood at greater risk for turbule nt, non -lam inar, air flo w. Yo u have never conducted smo ke studies to verify that you are, in fact, getting non turbulent, lami nar air flow with in your ISO 5 Hoods wher e ase ptic processing of drugs inten ded to be sterile, occurs. Add itionally,I-IEPA filters in yo ur ISO 7 clean room and ISO 8 ante-room are not regularly leak tested durin g _ _ clean room certi ficat ions. Acco rding to clean room test reports , o nly a vis ual chec k and total air flow is measured for the HEPA filte rs supply ing air to the ISO 7 clean room and the ISO 8 ante-room. You have no writte n procedure/proto co l
EW'UI't'Ef{S>6IGNATl..RlO

l O K.'l1 H lA qJ (09"')
Paul C. Mouris , Invest igator p -1 J ~ Scott T. Ballard , Investiga to~~ ~~/ .
DAtE 'SSUSl
"" .
03/20/2013
' AGE 1 OF J PAGl S
""
PRf\llOl!S EDmON (lfIs<JI..E"l1:
I!\SP ECf IO!"iALORSER \ '.4.TIO!\S
Ul:PAKTMEI\. OJ. HEALT H AND HUMA:\, SERV ICES

OlSnlOCT AllORESS...o _ .......aER
FOOD AND DRUG ADMlJ.,lSlRATION

CIO.TE(SI at' ..
cr~
.__
40 40 North Ce nt ral Expre s s way , Suite 300 Dalla s , TX 7520 4 (2 14 ) 253-52 00 Fa x : (2 14) 253-531 4 Industry I n f ormat i on : www.fda . go v/oc/ industry
"'<D1TTl..E
~
0 3/18/2013
f EI _BER
03/20/2013
30 0 63 11 680
"""""""" YO.......,. ..EPOOlT ISSlEII
TO:
J an Robi n son , Vice Pre side nt o f Opera tions
, ,
I V Solutions o f Lubbo ck
COOI!. CO<HTIl'f
370 6 - A 20th St
TI'Pl'-UT_ " " " , S f ' eCTlI
-=
crtv. STATE,
Lub boc k , TX
7 9 410
Prod ucer o f Sterile Drua Products
for how to conduct HEPA filter certifications or the frequency of these certifications.
OBS ERVATION 3
Equipment used in the manufacture, processing. packing or holding of drug products is not of appropriate design to facilitate operations for its intended use and dean ing and maintenance. was observed aseptically processing prescriptions for Specifically, on 3/18r'2013 and 3/19/2013, a technician. Vancomycin and Ceftriaxone within your ISO 5 hood, which has a work bench made of a wood laminate type material with a stainless steel cover that does not completely overlay the wood laminate work bench. A small amount of wood laminate material is exposed around the outer edges o f the work bench. This wood laminate material is harder [Q dis infect than a completely stainless steel work bench.
II"
OBS ERVATION 4
Aseptic processing areas are deficient regarding the system for monitoring environme ntal conditions. Specifically, you do nOI conduct air, or surface, sampling for viable, or non-viable, particles during the aseptic processing of every balch, or at least once per shifts in which drug products, intended to be sterile , are aseptically processed in your ISO 5 hoods. The Pharmacist in Charge stated that the firm aseptically processes of Tobramycin Ampules for Inhalation. _ , and that each batch of this drug product cons ists 0, boxes (each box containing .ampules), depending on the volume needed. Your finn does not cond uct environmental monitoring of any kind on a frequency of at least once per shift when aseptic process ing of any drugs intended to be sterile, occurs. Your firm has no ....-rirten procedure which delineates the frequencies of environmental monitoring in ISO 5 and ISO 7 workstations , and the gowning room. For example, written standard operating procedure (SOP) #8, entitled, Process fo r p"rmnnp! fi ngerlip monitoring with contact plates, does not provide a frequency for con~etine fingertip o;;ampl".s I'I.nd does not call for sampli ng other parts of the personne l cloth ing or gown. Additionally, SOP #10, entitled, Surface cleaning and disinfection sampling assessment pro cedure, does not specify a frequency for collecting samples.
OBSERVATION 5
Procedure s designed 1 0 prevent microbiological contamination of drug products purport ing to be sterile are not established. written, and followed. Specifically, media fills you perform do not represent worst case aseptic processing conditions in terms of batch size and length of aseptic process ing. You aseptically process batches of Tobramycin Ampules for Inhalation which consists 01_ ampules; yet, according to SOP #12, entitled, Aseptic Technique Validation, in your media fills you only
Ew'UU.(S) """""1'\.01
the_
CIO.TE ISSUEO

1'01l. '\oI fDA 4S.)( lI'J"'l
o u r i s , Inv e s t i gat or Paul C. M ..z:r Scot t T. Be Lk a r-d , Inves tigato r

I'RI'VlOOS W m(lI< 08SOlEl'E
r' ~~
--
03/20/2013
PAGE 2
1.~SI'fX rIO!" AL 0 8S f~ R VA T10 ."\ S
on
P,,"GES
4040 Nor th Cent r a l Ex p r e s s way , Su i te 30 0 Dallas , TX 7 52 0 4 (2 14 ) 253 -5200 Fax : (2 14) 253 -53 1 4 I n dus t r y I n f orma t i o n : www. f d a . g o v / o c / i n du st r
DEPARTMENT OFIlEALTIf A."U HUMAN SER\lCES

f OOD AND DRUG ADMINISTRA TION
lE(S) 01' lNsPECTDN
03/18/ 201 3 - 0 3/20/20 1 3 300 6311 680
TO:
J a n Ro binson , Vice President of Ope r a tions 370 6 - A 2 0th St Producer of St e r i le Dr u Prod ucts
IV So l utio n s o f Lubboc k Lu b boc k , TX 7 94 1 0
aseptically process .
ampu les.
OBSERVATION 6
Equipm ent for adequate control over air pressure is not provided when appropri ate for the manufacture, processing, packing or holding of a drug product. Specifically, your firm lacks a system of continuous monitoring of positive pressure differe ntial limits dur ing aseptic processing of drugs intended to be sterile. Your curren t practice is to log the differenti al pre ssure readings from your positive pressure di fferential pressure gauges, representing the differential pressure across your clean room and adjacent gowning room, _ _ Because these gauge s are located outside of the clean roo m itself, if a loss of positive pressure in the clean room occurred during aseptic processing, you may not notice until the clean room differential pressure gauges are read again _ _ Your current clean room differential pressure system has no audible alarm; thus, transi ent excursio ns of ~ pressure would not be observed or recorded.
OBSERVAT ION 7
Reserve samples for drug produ cts are not retained for one year after the expiration date of the drug product. Specifically, you fail to retain and store reserve samples for each batc h of asepticall y processed Tobramycin 150mg/3m l Ampules for Inhalation you produce and distribute.
t" "UI ~ ~ 51 l1lG"iA TlJFIE
SEE REV ERS E O F THIS PAGE

FORM FDA 4J (0!1""'1
Paul C . M ouri s , I n vestigat o r ?~ Scott T . Ba lla rd , Inve5ti g at o ~, .-..: . .,

I~SP ECTIO:'\AL
{(.
~
.
._
./
-/
03/20/201 3
./
O BSERVATI O ~ S
MGE ) OF J PAGES
The observations of objectionable conditions and practices listed on the front of this form are reported: 1. Pursuant to Section 704(b) of the Federal Food, Drug and Cosmetic Act, or 2. To assist firms inspected in complying with the Acts and reoulations enforced by the Food and Drug Administration Section 704(b) of the Federal Food, Drug, and Cosmetic Act (21 USC 374(b)) provides: "Upon completion of any such inspection of a factory, warehouse, consulting laboratory, or other establishment, and prior to leaving the premises, the officer or employee making the inspection shall give to the owner, operator, or agent in charge a report in writing setting forth any conditions or practices observed by him which, in his jUdgement, indicate that any food, drug, device, or cosmetic in such establ ishment (1) consists in whole or in part of any filthy, putrid, or decomposed substance, or (2) has been prepared, packed, or held under insanitary conditions whereby it may have become contaminated with filth, or whereby it may have been rendered injurious to health. A copy of such report shall be sent promptly to the Secretary."
DEPARTM ENTOfi HEALTH AND II UMAN SERVICES

fOOD AND DRUG ADMINISTRA TION
(lj$TlllCl" AIl(lRESS IN:) PHONE
MJMil6\
o,o,TI'(SlOF
80 50 M a r s h a ll Dr i v e . Suit e 205 Le n exa. KS 662 1 4 ( 913) 495 -5 100 Fax : ( 913) 4 95 - 5 11 5 I n d u s t r y In fo rma t ion : www . f d a . g ov / o c / i n d u s t r v
.....::..0 IlEl'OflT <$SUED
0 3 / 11 /2 013 30 0 5364771
-"
03/19/2013 *
TO,
Daniel P . Bl ake l ey, R. Ph CEO, Ph a r maci st - I n-Ch a r g e
...,. .:sr...
Foundat i on Ca re LLe
.~
4 0 ~~ .:;~eway Ct
Ea r t h Ci t y . M O
63 045- 1213
Producer of Steri le Dr u a P r o d uct s
This document lists observations made by the FDA repn:sentative(s) during the inspection ofyour facility. They lite inspecttonal observations, and do not represent a final Agency detenn ination regarding your compliance. If you have an objection regarding an observation, or have: implemented, or preo to implement, corrective: action in response to an observation, you may discuss the: objection or action with the FDA representative(s) during the inspection or submit this information to FDA at the addressabove. (fyou have any questions, please contact FDA at the phone number end address above .
DURING AN INSPECTION Of YOUR FIRM WE OBSERVED:
OBSERVATION 1
Procedures de signed to prevent microbiologi cal contamination of drug products purporting to be sterile are n ot establish ed and followed.
Specifically,
a.
Your media fill procedure and documentation, which are used to validate your sterile processing operations, are inadequate. You failed to a perform media fill simulation, including documenting the following kinds of information: 1) Average and worst case processing times. 2) Document the different kinds of interventions, along with the average and maximum nwnber of interventions. 3) The maximum nwnber(under worst case scenario) or personnel in the c1eanroom (Class 100 i.e. ISO 5 zone) during dynamic processing operations. Your SOP 88.16 "Environmental Testing for Cleanroom" fails to include instructions on daily monitoring under dynamic conditions (when processing occurs) in your Class 100 (ISO 5 zone) c1eanroom as it instructs for _ environmental monitoring only for equipment and air sample (viable and non-viable monitoring). In addition, this SOP does not include all of the equipment contained in your Class 100 cleanroom to be included in your~onitoring program. For example it fails to include and you fail to monitor the following (this is not an inclusive list):
2)
b.
l)~_
Chairs

I'OIIlM 11t14. W (e'NIt)
- --
AMENDMENT 1
Shir ley J . Be r r yma n, Investigat or Mi c hele Pe r r y W illiams . Invest igato r Ant h o n y Bu c ks , Inves t igato r 1!2.~
J/l
0;
~~
,
03 /1 9/ 20 13
"""""'5wmow
f)I ~
L~SP~:crl~O&"F-RV ATIONS
PAGll I OF ' I'4.GES
DErARTMt:NT OF IIEALTH AND HUMAN SER"lCI:S

r OOD AND Oll.UG ADMINIS TRATION
80 5 0 Mar sha ll Dri v e , Su i t e 205 Le nex a , KS 66 214 (913) 4 95 - 5 10 0 Fax: ( 9 13 ) 49 5 -5 115 Industr In forma t i o n: www. f d a . a v/ae / i n dus t r y
_ NlM()U,OI. Q
03/1 1/2013 - 0 3/1 9/2 0 13 * 3 0 0 5 364 7 71
RlOPORT
TO :
Dan iel
A . lP
P.
Bl a kel e y , R. Ph . , CEO, Pha rma cis t -In-Chur 40 1 0 W e d g ewa
Foundat ion Care Lt C

. COUI'(T.....
_ N T 1OI$Pfi<=Tm
Ct Produc ts
Earth Ci t , M O
63 045 - 121 3
Pro ducer o f St erile Dru
3) 4) 5) 6) c.
plastic storage bins located on the lower shelf of one of your long tables; black lastic vial racks used to hold your ampules Speaker located on the bottom shelf of your shan table; Door knobs, walls, and floors.
d.
e.
f.
g.
h.
You failed to perform daily environmental monitoring (or when processing occurs) of your personnel. Your SOP 3CA "Compounding Personnel Training" instructs you to conduet _ personnel monitoring activities only. For example: . was last monitored 10/19/2012 an~ was last monitored 10/1812012. You failed to have a smoke study procedure used to evaluate your cleanroom suite (Class 100) under dynamic conditions and employee . stated you have not conducted a smoke study since the room was installed in 2005. Additionally, you failed to conduct a smoke study after a new air handlin g unit was installed in 2007. You failed to use appropriate aseptic cleaning practices as you do not always use overlapping cleaning strokes, cleaning from the top to the bottom, from the back to the front and from the inside/outside of your cleaning areas and equipment as observed on 3/ 1211013. Your firm has not defmed a frequency or intervals where gloves must be changed out. "8B.4 On 3/11/2013 during Compounding Garb" only states dropped the disinfectant bottle the fill of Hypertonic Saline 4% Lot 4HS4-1 30311. employee once at the end of processing and once during cleaning. He sprayed the bottle with_ , placed it back on the lower shelf, continued to work and did not change his gloves. Neither pharmacist technicians changed their gloves during the process and they only wore one pair of gloves. While observing cleaning operations on 3/11 12013 in the anteroom employee. left the door between the cleanroom (Class 100) and anteroom (Class 10.000) open at least 3 times for over 510 second after cleaning/sanitization of the Clean Room. The door does not automatically close nor is there an airlock between the rooms. You failed to follow your SOP 8B.5 "Hand Wasbing -Sterile Compounding". On 3/11/13 and 3/13/13, your employees . and _ both failed to allow "water to run from fingertips toward elbows" during the rinsing of their hands as required by the procedure.
SEE REVERSE
OF THIS PAGE
FoRMftlAd3~
Sh i r l e y J . Berryman, I n v e s t i g a to r ~ M i c he le Per ry Will iams , Investigator Anth ony Bucks , Inve s t iga t o r
INSPI:CfIQS
"'--
AMENDMENT 1
J-~"-
~-- -
0 3 /19 /2 013
BSt:RVATIONS
P AGI': 1 01' S PAGES
DEPARTMENt or HEALTH AND HUMAN SERVI Cf,S

FOOl> AND DRUG ADMINISTRATION
.....,;g-.0ii51'ii1i Oii' iiOiItliJIi T6\/i& IlEPOi'iT .- .

~:
805 0 M a r s ha ll Dri ve , Suit e 2 0 5 Le n e xa , KS 66 214 ( 913) 4 95 -5 100 Fax: ( 913) 4 95 - 511 5 Ind us try I n f o rma t i o n : www. f d a . g ov/ o c / i ndus try
0 3/ 11/2013 - 03/19/20 13 * 3005364771
Daniel P . Blakeley, R. Ph. , CEO, Pharma c ist- In-Char g e
Foundation Care LLC
4 01 0 Wed e way Ct
Eart h Cit y , M O
6 3 0 45 -1 2 13
Producer of S t e ril e Dr ug Products
OBSERVATION 4
Each batch of drug product required to be free of obj ectionab le microorganisms is not tested through appropriate laboratory testing.
Specifically, you do not perfonn sterility and endotoxin test on a routine basis for Hypertonic Saline which was last tested for sterility in June 2012 .
OBSERVATION 5
The records for components and drug product containers or closures do not include the supplier's lot number.
Specifically.
3.
b.
You did not document the lot number of the TPN bags used in the sterile drug process for the following but not limited to: Tobramycin Lot TAI70-120103B. TA 170-120327B. TAl 70121211A, TAI70-130312B; and Colistimcthate Lot C75- l 20816. Ampule lot numbers used in sterile drug products are not documented. Ampules used in the process arc received from the steri lization company have 3 list of lot number on the shipping carton but do not have lot numbers on the individual bags.
OBSERVATION 6
Equipment and utensils are not ma intained at appropriate intervals to prevent coctaminet lco thai would alter the safety, identity, strength, quality or purity ofthe drug product. ." ,
Specifically, there is no docwnented cleaning of the glassware prior to usc in the cleanroom. You failed to render glassware re-used in yow Cleanroom (Class 100 area) in a sterile condition prior to being introduced into your Cleanroom. This re-used glassware is located on the table s in close proximity to your processing area which includes opened ampules before sealing activities occur. Your SOP 8B.21 "Washing Glassware for usc in the Cleanroom" instructs your employees to . After the washing/drying steps this SOP AMENDMENT 1
. -~
Sh ir l ey J . Ber r yman , Inves tiga t or Mi c he l e Pe rr y W i ll i a ms , Anthony BUCK S , I n vestigat or

INSP[(''110N
Investiga~
.
03/19/2 013
. ~
RVA1l0NS
PAGE 4 Of ! PAGES
F_
80 5 0 M a r s h a l l Dri v e , Su ite 2 05 Lenexa . KS 66 2 14 ( 913 ) 4 9 5- 5 10 0 Fax: ( 913) 4 9 5- 511 5 I n dust ry I n f ormati o n : www . f d a .gov / o c / i ndus t ry
_ TO:
-=-
DEPARTMmr ot'UEALTII AND HUMAN SERVICe;: FOOD ANDDRUGADMINISTRA1lON

(Iot,.~)
<7' HSF'l'
0 3/ 11/20 13 - 03/ 1 9120 13 *
Dan i e l P . Bla keley , R. Ph. , CEO, Pha rma cist -In - Ch a r ae

SlllHT ,\1lCRI;SS
3 00 5 3 6 4 7 71
,~
Fo undat i on Ca re LLe
crrr,"-"'~ . ZIP ~
4 01 0 W e dgeway Cl
~ ~' ~
-,
Eart h Cit y , M O
6304 5- 1213
Produce r o f S t e r ile DruG Pro d uct s
instructs them to This . is located in the anteroom (class 10,000) area which does not have documented cleaning of this storage area. We observed this practice on 311112013 during the cleaning process after the sterile fill of Hypertonic Saline.
OBSERVATION 7
Aseptic processin g areas are deficient regarding the system for cleaning and disinfecting the room and equipment to produce asept ic conditions.
Specifically,
a.
b.
You have not conduced disinfectant effectiveness studies to show the disinfectants used can reduce bioburden on the different surfaces in the cleanroom (Class 100) where you produce sterile products including the following but limited to: Tobramycin, Colistimethate and Hypertonic Saline. The _ used to disinfect the surfaces in the cleanroom (Class 100) (where sterile Tobramycin, Colistimethate, and Hypertonic Saline are filled) is not labeled as sterile .
DATES OF INSPECTION:
03/11f2013(Mon ), 03/12120 13(Tue). 03 /I3no l3{Wed ). 03tI 4l 2013{Thu), 03/ 18!20 13(Mon), 03/1912013{Tue)

l'Oll/lI FDA c J _ I
Shi r l e y J. Be r r yma n , Inves ti gat or M i c h e l e Pe r r y W i l l i a ms , In~~a t or Ant h ony Bu c ks , Inv e st i g a t o r ~
,-
AMENDMENT 1
. )K ~
RSt:RVAnONS
~n
CI
0 3 / 1 9/ 20 13
PRE\fIOIJSWf1lOloI~
lNSPECTI~
l'M;1i ' Of
~ PM;f. S
Section 704(b} of the Federal Food, Drug, and Cosmetic Act (21 USC 374(b provides:
"Upon completion of any such inspection of a factory, warehouse, consulting laboratory, or other establishment, and prior to leaving the premises, the officer or employee making the inspection shall give to the owner, operator, or agent in charge a report in writing setting forth any conditions or practices observed by him which, in his judgement, indicate that any food, drug, device, or cosmetic in such establishment (1) consists in whole or in part of any filthy, putrid, or decomposed substance, or (2) has been prepared, packed, or held under insanitary conditions whereby it may have become contaminated with filth, or whereby it may have been rendered injurious to health. A copy of such report shall be sent promptly to the Secretary."
DEPARTMENT OF IIF" A LUI AND HUMAI\ SERV I CES

FOOrJ AND D){UG A!lMJN 1STRATION
DIST I<lCT APDR' "" Moe ' "..,"" NLMl;:R
l>'.TEf.;) OF '''''''
~
i n d er l e y P l a c ~ , Suite 200 5 55 W M a i t land , FL 32751 {40 7 } 47 5 - 4700 Eax r ( 407 ) 4 75 ~47 6 B I ndus t r v I nfo rma ti on: www. f da. q o v / o c / i n d us t r v
...... EANO .
' ~ OF "" CIYI DlJI'<.
03 /12/2013
rr, U<UM"""
- 03/15/20 13
300325 4930
H> WI1 0 M",,",OIfT I8.3l.fIil:I
TO ;
F'..........E
Mar k C. Mon tgomerv,
Pres ident and CEO

lm<E t:r"""~
Ax ium He al t hcare pha r -nacy dba Ba l a nc ed Solu t ions Comp o u n d i n g

CITY, sr;,TE,lPCOOE.
~N'Tf!Y
55 0 'r ccrcicr.o q y Par k,

lYi>E =,i,iiw5i1MENr ~ EO
suave
1 008
Lak e Mar
;0,
32 7 46-7131
P roducer of Ster ile DruQ Products
This documentlists observations made by tht; FDA rcpreilClilative(S) during u le inspecti on of your facility. They l1TC inspcctional rvations, and do not represent a frnll.1 Agency determination regardingyour compliance. lfyou have lUI objection regarding lUI obse cbservauoc, or have implemeated. or plan to implement, corrective action in response to all observation, you may discuss the objec tio n or action with the FDA represeutativers) during t!Je inspectionor submit this information to FDA at the address above. If you have ~ny questions, please contact rnA at thc phone number and address above.
DURING AN INSPECTION OF YOUR FIRM WE. OBSE.R\IED:
OBSERVATION 1
Dru g products fai ling to meet est ablish ed stan dards, spec ifications, and qual ity control criteria are not reje cted.
Specifically,
l.
2.
On 03/12113, vials of already released and distributed -sterilized triamcinolone acetcnid e inje ctable so lution (6 0mg/ml; 10 m l on each via l) Jot #Ol 1520l3@12wereexamined a nd 7 v ia ls were observed containing black part icles of un-know n origin in the product, One of the vials appeared to contain more than one of these particles. On 03/1211 3, vials of already rel eased and distribute d sterilr chromi um chloride inj ecta ble so lution (4 meg/nil; 10 mJ. on each vial) from lo t #01 182013@9 were examined and I vial was observed to contain a cloth-lfk e filament o f un -known oricin
OBSERVATION 2
Equipmcnt and utensil s are not cleaned , maintained, and sanitized at appropriate interv als to pre vent malfunctions and co ntam ination thai w uul d alter the safety, identity, strength, qua lity or puri ty of the d rug product. Speci fical ly, On March 12, 20 13, during an inspectional wall-through of the pro cessing are a, I observed the fol lowing ins ide of th e "ISO 5" area W IH.. rre all injectable drug products are prepare d including BiMix l.ot N umber 031 120l 3@7, prepared on thls day:
L
2.
3.
Spills and splatters of amb er and clear drop lets and res idue were observed stu ck to the top of the _ heating plate I stirrer on the table on the wall oppostite the entrance to th e suite. Sp latter s of a w hite residu e approxim ately one foot in diameter on the hard transparent air guard behind the table where BiMix Lo t N umber 03112013@7 wasprepared. Segments of the "ISO 5" interior comer ceiling surface where observed to be cracked and/or peeling. These segm ents were observed length .....isc across both sides of th e ceiling ranging in sizes up to 2-4 ind ies. Br i an D . tqi c no Ls on , I nves t ig a t or ~~~ Ge Dman Ri ve r a, ~pve st igator ~ ~ Th o1:".8 S E. F'r i e L, r nv e at t qa r oz - ? ~~ .. ",n"" ~ m,"",,, " f"
,," _ ,,",_ ClJU'L.O"'=!:l) S1G....""""
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0 3 /15 /2 0 13
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D:KP ANTMII.;\,T Of IlEALTIl ANi> H UMAN SKNVIC;F$

FOO D AND DRUG AD MIN ISTRATION
55 5 wi nderley Pl a ce , Sui t e 200 M a i t l a nd , FL 32 75 1 (40 7 ) 475- 470 0 Fax : (4 07 ) 47 5-4768 I ndu s t r y I nf orma ~ i on : www . f de .gov/oc/ i ndu s t ry
E ~OF IND:Wl<,!Il<.l QWHOM RLf'<IRT13S ct.D
03 /12/20)3 - 0 3 / 1 5 / 201 3
3003254930
TO:
Mar k C. Montgoner , Pre s i de nt and CEO
Axium Ee a l t hc a r e Pha rma c y db e Ba l a nc e d o~u~ nCd "i"n"~ So l ut i ons compp~

, 6 AT!:, ZiPCO OE.OOIJiii'iiY
5~C
Te chnolog y Par k , Su ite 1 0 08
~,," l'f!'E ffillfl ClSl1 ""MENi'lNiiPECrEo
-1
Lake Mar y , FL
4.
3274-7 131
Producer of Sterile Drug P r oduct s
The "ISO 5 " room is ~ sq ft room. Only 8 oftne . segments of ce iling w ere covered with l iB PA filters. Fo ur o~ E!TTlents of the ceili ng wer e tilled w ith fluorescent light fixtures wb ile th e six remaini ng segments were ce iling tiles. The area above the processing table (Tab le I) were BiM ix Lot Nu mber 031120 13@7 was madehas 1 light segment and 1 ti le with no HEPA filters const it uting spac e above wher e products arc manual ly filled w itho ut f IEPA filters. For reference this e nvironmental sampling des ignation is IS05 11 for this p rocessing table.
a .
On March 12, 20 13 during an mspectlonal wa lkth rou gh of the process ing area I observed the fo llow ing inside of th e finn's "ISO 7" ante room I gow ning room to ente r th e sterile core wh ere all sterile lnjecteblesare prod uced :
1.
A wash sink with a "U" tube dr ain trap was ob served in the Ante "ISO T" room adjacent to th e "I SO Brow n rust like colorin was observ ed in the base of the sink drai n located in th is area.
5 ~ room.
OBSERVATION 3
Procedu res designed to p revent m icrobiol ugical co nta mination of drug produ cts p urporting to be sterile are not established Spe cifically, 1. As ept ic process validations I media fill procedures do no simulate all production process es. Ail media fills are _ performe d by SOP Number 310 "Sterile Compou n ding Pro cess Validation {Media Fil ls)" which does not simulate the pro cess es and practice s for preparing of inj ectabl e drugs for com merc ial distribution . 2. There is no anti microbial effectivenes s testing data for injectable drug pro ducts contain ing preservatives, such as B etaM cthasone 12 mg/rnl, Inj e ctabl e Solution including lot 01172012@ l S. 3. On 0311 311 3 during the prepar ing of Betamethasone 9 mglml injectable Suspension, lot 03122013@16 t he following defic iencies w ere noted: a) The pre p aring ofBetametbasone injectable suspensions co nsists of
and followed.
b)
c)
Th e technician w as obs erved perform ing variou s tas ks w ithout sanitizing g loves, th en man ipulat ing steri le tran sfer tu bing prior to . Bctamcthasone is not subjected to additional ste rilizations methods bey o nd thi s poin t. beaker stirr ing contents during trans fer of Th e technician w as observed with glove d hand reaching into _ Betamerhasone suspension into 1_ Add itionally, the. beaker was tilte d out o fl ine of air flow and toward the techicians b ody. B eta meth asonc is nol subjected to addi tion al sterilizatio ns methods beyond this point.
FM ~"""""l~ 16,"""TU""
Brian D. Ni c h ol s o n ,
Ge~~n
Inve5t igator~~
03/ 15/ 2013
Ri v e r a , Inves t i gat or ~ Thoma s E. F=i81, I nve s t i g a L O r ~

INSPECTH lNAL OB SER VAn ONS
OlNFllCT ~ "U 1oJtD "HOlE ~IJI,I!lER
DEPAH.TMF'.NT OF II l::Al'fH Af\ O HUMA N SER VICES -oon A"D DRIIGAO)I,ffNISTRATlO"
!>AT """"" ","""
::'55 Win d erle y P l a c e , Sui te 20 0 Mait land , FL 32751 (4 0 7 ) 475 -4700 F ax : (4 07 ) 4 7 5- 47 68 Indust~ y I n f o r ma t i o n : ~~w . f da .qov /oc /indus ~r v
..N.It. ~ mU. O!' : ~I'JI"'lU'<- TO_OM "''l'O ''' l''''!JE-O
03/12/20 13
l'E"llJt; E-~
- 03/ ::'S/2C13
3 003254930
""",,,,,,,,,,
TO:
on t a ome r v, Pr e si d e n t a n d CEO Na r k C. M
stt<U.T ,"",-OM
Ax i um Heal t hcare Pha r ma c y dha aa j an ced ~Oluti O r.S Campour.ding

lTV , STA;a l '~ C OOC , I:QJ riTR'l'
550 'r ec nnc j o q y Pa r k, Suite 10 08

T'!'!'e SFABuS~"E"'T
INsPECTED
:'ak e M a r y, FL
d)
3274 6-7 13 1
Pr o d "Jcer o f S t er:ile Dru g Pro ducts
oj
fj
Technician who w as wearing a non-sterile gown was observed extending his ann ov er vial tray conta in ing open exposed v ials. Th e ~ceh n ician conti nued filling in this manner potentia lly c ontaminating the via ls in the tray. Technician was observed exiting the "ISO S" area into the adjacent "IS O 7~ Ante room on 3 or more occasions during whi ch exposed pro duct was mix ing. Betarn ethason e if; not s ubjected 10 additiona l sterilizatio ns method s beyond th is point. Tech nician was observed throughout the time moving in a manner that did not appear measured, slow, or deliberate. The techn ician freely moves in the entire" sa foot nlSO 5" area without re striction.
a _
OBSERVATION 4
Asept ic processing areas are defi cient r egardi ng the system for monito ring envi ronmental con ditions. Spec ifica lly,
J.
On 311211 3 I observed, Clean Room Surface Sampling Log show ing zero eFU's for results of surface samp les for plates for these surface samp les were in a bin o n th e IS0 5T l , ISOST2 , and ISOSTI taken on 318113. The . tab le. Th ese plates were not d uc for a final reading until 3(15/13. I inspected the . plate for IS05T1 and observed a co lony on the plate which was stored at mom temperature.
2.
The area in which steri le inj ectab le p roducts are compounded is lacking in that the ISO 5 classification ofthis area has not bee n properly qualified in that there has been / 10 airflow st udies (smo ke studi es) performe d and th ere has
been no HEP A filter integrity testing.
J. The firm does not moni lor viab le particulates in the area where inj ectable dru g prod ucts during no rma l operation.
4. There is no monitoring of non-viable and total particulates in the area where ster ile inj ectable drug prod ucts are compounded d uring or immediately afte r producin g each lot of sterile injectable drug products. The Pharmacist In Charge stated they conduct non-v iable air monitoring and surface samples when they are not in op erat ion in the ISO 5 ho od prod ucing ste rile drug prod ucts Perso nne l momtortne is limi ted to the glove s onlv.
5.
OBSERVATION 5
Procedures des igned to preve nt microbiological contam inat ion of drug products purporting to be sterile do not includ e val ida tion ofthe sterilization pro cess . Specifically,
""~'I'I:<;($) "(lW<"'~
.
~~
ccn ssoee
Br l a r. D. Nl c h o l son,
FORM ....A , .. , ,(I' ' '",)
I nVe g t l q a t o ~ ~t(
Gerrr0ll Rive r a, I nv e s ~ i ga t c r 'Ph om a a E. Fr-d e L , Inves t iga to r ~

"""".....'. rom ", (1I'<Ol"""
03/15 / 2 01 3
INS P CnO NAL O llSFRVA TI O NSo
PACEJ OF 'i PAGES
1)t:J'ARTMJ<:N'I 011 IlK...t.rn Af',IlIlUMA.."l Sv.RY ICl> ;S

FOOD AND DRUG APMJNISlRATfOl"
555 Win de r ] e y Place , Su i te 200 Mait l a n d , FL 32 7 51 ( 4 07') 47 5- 470 0 Fax : ( 407) 475-4766
03/ 1 2/2013 raNUM_
03/ 1~/2 0 13
30D 325 4930
I n d us t r y I r.forrra tion : ~~w.t d a .~ov /o c / indus t rv

"""'~N<O TlT U' O F ", MI\~ .......lO""KOlI """"i<T
""'w
TO:
nxiuro
M ar k C. M o n t q ome r y , preside nt and CEO

F. eal t h c a r ~
COO E,CO<JN'TRy
_~ ~ t i o n s
~ TAn;, 1I~
Pharmacy dba Ba lanced Compounding

32746- 7131
55 0 l e c hnol og y Pa r k, Suite 1008

TYPE l:Sl HlUlIH"' I"H'T 'l<S ~""U
Lake M ar y, FL
1.
Producor of Steril e Dr u g
P ~ oduc t s
The. sterilization process for producing hatches of Injectable product has not been validated . The firm has no docu mentati on to qualify the . used wi th regards 1:0 bacter ial retention, extractables, and har dware with challenge compatibility. The finn has no doc umentation to chal lenge the bacterial retention of the. organ isms or bio burden quantity . Dry ingredients used may be non -sterile such as th e Bethamethaso ne P hosphate IISP used to manufacture Bcthamethasone 12 mg/mL Injectable. The bioburden for the se ingred ients is not tested for by the finn.
Th e firm hes not validated the steri lizati on processes such as tho se us ed to process Tri am cinolone Acetonide GO mg/ml, Inj Susp lot 011:>2013@12. such as the bulk sterilizat ion of Methylprednisolone Acetate 60 mglmL lnj Susp (inc1uding lot 020 920 12@3 ) priortofi lling. The product is filled from this bulk withou t further sterilizing methods being applied such as sterile
2.
3. The finn has not val idated bulk sterili zat ion processes by
4.
Jr comp onents such as the stoppers used for sterile inj ectahle The firm has not validated the sterilization pro cess K used in products s uch as Methy lprednisolone Acetat e 60 mg/ml, InjS usp inclu ding lot vials by 020920 12@3 . The firm has not val idated the ster ilizat ion J those used in the manufacrurina ofM ethv l process for any vial s proce ssed at this site such as isolone Acetate 60 marml. Ini SUSD inc luding lot 0209201 2rm.3.
5.
OBSERVATION G
Clothing of personnel engaged in the processing of dru g products is not approp riate for the d uties they perform. Specifically, gowning worn by th e Techni cian inside of the ''ISO 5" area w here all injectable drug pro ducts are prepare d such as the aseptically prepared and filled prod uct Berarnethasone 9 rng/mL inje ctable suspen sion consists of non-sterililizcd gllrb lnchrding only bouffant cap, non-sterile Kendal l Chemo-Satety (open -back tie) gown, face mask, shoe covers and steri le gloves. This face and neck is left uncovered and exp osed.
OBSERVATION 7
Each hatch of drug pro duct purp ortin g 10 b e steri le and pyrogen-free is not labo ratory t ested to determine confor mance to
such requirements.
Specifically, 1. For any Jot o f inj ectable drug product th nt is les s than. 2.
cont ainers no testing is nee ded.
The firm may additi on ally employ a "sk ip lot testing " procedure where Jots of injectabl e and ophtha lmic pr odu ct are

f U ,. ",
m .~ oWI
Br i a n D. K i c~ ols onf I n v e s t i g a t o r _ .~ G 0~an Rive r a , I n v e s t i g a t or r~ ~ Thoma s E . Fri e l, I n ve s ti g ator ~

INSPIOCT I ONAL OHSF.RVATIONS
03/15/ 201 3
",.,...'
D ePART MENT OF HEALTH Af\ l ) Il l M AN SERVICES FOOD AND DRUG AI>MINlSnP,TION

00 1\T ~ .t'T ~l RE OS
"'"0
!'ti~'"' oaJ..
.....
Th\TE(l) Of ""'''''ClION
W i nder ley Pl a c e , Suite 2 0 0 M a itl a nd , FL 3 2 75 1

55b
0 3 112 /20 13
FE' NI,NBER
03 / 1 5 / 2 01 3
( 4 07 ) 475 -4 700 Fa x : ( 4 0"/) 475-4 768 r n ou s t r r nrormat I o n. www .fda .oov/oc /indust ry
_ _ eM a rk TO:
30 032 54930
"
F .oH>
LEOF IOlJIVIDUI\l TOV"HOU F5'O'<TISW EIJ
C. M ont gomer y, Presi de~t an d CEO

W-REl l
AW'lf~
Axi um He a lth ca r e Pha rrr.ac y db a Balanced So l ut i ons Co mpoun dd nq

CIn',"'-"" ( .ZIf'
0Dl11ffllV
55 0 j'och n o.Loq y Pa r-k , Su i t e :l. OO 8

l "1' E tr.1\BI.Ill~ ,", IN""ecnll)
:'ake Mary,
FL
327 4 6- 713 1
Pr oducer of Ster i l e Dr u g Product s
frequently released and distributed witho ut testing. Examp les include Cyclos porin 2% Ophthalm ic; lots 02 1820Ii'al12 021420 13IW13 and Ol O42013rmL
OBSERVATION 8
Separate or defined areas to prevent contamination or mix-ups are deficient regard ing operatio ns related to the rece ipt, ide ntification, storage, and withholding from use of co mponents and drug product containers pending sampling, testing, or examin atio n by the quality co ntrol unit before release for ma nufacturing or packag ing . Specifically, Sto ppers used in the manufacture o f asept ically filled injectable drug products are stored in a bin in the uncovered..
~lSO
5" ar ea
OBSERVATION 9
A n adequate number of batc hes of each drug product are not tested nor are records of such dat a maintained to determine an appropri ate expiration date. Spec ifically, 1. The firm's data that an: sup porting p roduct expirat ion dates for sterile processed prod ucts is not based on site specific, processing conditions at this faci lity. An example iii the BUD date of 180 day s fur such as Methylprednisolo ne Acetate 60 mg/mL Inje ctable Suspension and Betem ethasone 9 mg/ml, Injectable Suspension. 2. None of the formul ations produ ced by your finn ha ve been placed on lo ng term stability to det ermine an appropriate B UD.
-s>:
FOII JIl rnA 4li3 (l1 911l!rl
6..f2k.. j}/Zu/,~E ~PlOY Ef,(S) SION~;l.fIl
5' -t. f) ~
DA l E '''''UW
Br i a n D. Ni cr.ol s on , L n v a s t.L q a t.or a e rmen Ri ve r a , r nvee c r e et c r ~hcma s E . ?rie l , I nv e s t i ga t or I
03 / 1 5/ 2 013
,.,..""..""",.,..,..""""'...,..,,
NS I' f.Cl IO NA'. O HSF:RVAT IO NS
J>A(',E , OF
P,'C .f'!'
The observations of objectionable conditlons and practices iisted on the front of this form are reported:
"Upon completion of any such inspection of a factory, warehouse, consulting laboratory, or other establishment, and prior to leaving the premises, the officer or employee making the inspection shall give to the owner, operator, or agent in charge a report in writing setting forth any condittons or practices observed by him which, in his judgement, indicate that any food, drug, device, or cosmetic in such estabiishment (1) consists in whoie or in part of any filthy, putrid, or decomposed substance, or (2) has been prepared, packed, or held under insanitary conditions whereby it may have become contaminated with filth, or whereby it may have been rendered injurious to health. A copy of such report shall be sent promptly to the Secretary."
Dt:rAR'IMt:NT OF IIEAU" ANDHUMAN SERVICES

FOOD AND DRU G ADMINISTRATION
DISTRIC T
DR$$ /oIl (l
6t h & Ki p li ng St . (P.O . Box 25087) Denver , CO 80225 -0087 (303 ) 23 6-3000 Fax : (303) 2 36-3100 I ndus t ry I n f orma t i on: www .fda. gov/oc /i nd us t ry
E ...... TJ1'LECI" I'lDlYlDWL lO 'MlOM RV'ORl IeeUEO
-~
DATf{S! OF tNSP ECTIOH
03/05/2013
fE l M.lMeEA
03/1512013 *
1 00011 72 34
TO:
F"'Utw.lE
M r . Jerr y S . Gillick , R. Ph . , President/Pha rmacv Manage r

SlREEl ADORfSS
Coll ege Pharmacy I ncorpor at ed

CITY. el A, 'fe. lJ' ecce, COlNIRY
3505 Aus t in Bluffs Par kway Suite 101

l'Il'E eerA, 1lL1 BtJ,lENTINSl'EClEO
Colorado Sprinqs , CO
80918
Producer of Ste r i le Dr-uq Products
This document listsobservations made bythe FDA representative(s) during the inspection ofyour facility. They areinspectional observations, and do not represent a final Agency deterrmnerj on regarding your compliance. If you haveanobiecticn regarding an observ ation, or have implemented. or planto implement, corrective action in response to anobservation, you may discuss theobjection or action with the I'DA representadvets)during theinspection orsubmit this information to FDA at the address above. If you have any questions, please contact FDA at the phone numberand address above.
DURIN G AN INSPECTION OF YOUR FIRM WE OB SERVED:
OBSERVATION 1
Separate or defined areas to prevent contamination or mix-ups are deficient regarding operationsrelated to aseptic processing of drug products. Specifically, the firm does not have documentation supporting the design and maintenance of the facilityto ensure the high quality air required for the productionofthe sterile products.
I)
The area designated as the clean room and identified by the finn as being classified with ISO 5 and ISO 6 areas has been modified structurally and is not supported by continuous monitoring data to be considered a classified for sterile drug production. For example:
area
a.
The clean room HEPA recertification is performe ; however, the recertification does not include leak. testing. The firm also has no documentation supporting that leak testing has ever been performed. In addition, each ofthe classified rooms (includingthe ISO 7 gowning room located immediately outside of the clean room) was recertified at static conditions only. No dynamic evaluations have ever been performedand no active or non-active particulate monitoring is routinely performed outside ofthe review. was located immediately above the ISO 5 workbench where a production employee was observed to be producing sterile product on 3/5/ 13. The production employees stated that the stain was due to drug product which had exploded due to excessive pressure applied when forci ng non-sterile product through a sterilizing . The product which had transferredto the HEPA filter surface was, in-part, non-sterile product. No investigation was performedto assure the continued proper function of'this filter or the effects thai it may have on further sterile processing. Additionally, the exact date of this occurrence could not be determined.
b. The HEPA filter identified as #5 was observed to have been stained on the filter surface. This IIBPA filter
c.
There were a total of_ return vents for HEPA filtcred air each of which were located below the workbench near HEPA #1 and #2. _ vents were covered with!!!!!! which were affixed to the wall leaving only one functioning return vent, The firm could not proVI e any documentation
,.
YORM.JDA 4I3 ("IHI
M a t t h ew R. Dionne , I nves t iga tqs~~ Zache ry L. Mil ler , Investigato~'

PlU<VX"'S w n lON OHSOlHIE
< S) 6IG~l1J R
~t:..-=
DATE Ill.5UO>
03/15 /2013
PMil! I 0 1' 1 PAGl!S
INSrECfIONALO BSERVATIONS
DI': rARTMf;NT OF IlEAL'I'1i ANI) HUMAN St;RVJCES

FOQOANDDRUGADMINlS'JRAn ON
tNSTRlCT AllllfIE SS NIl>PHONE NU"' Bf R
DATE{S)OFI SPECTION
6th & Kipling St . ( P. O. Box 2 5087 ) Den ver , CO 90225- 0 08 7 (3 0 3) 236-3 000 Fa x : (303) 23 6-3 10 0 Indus t r y Inf ormat i on : www . fda . g o v / o c / i ndus t r y
0 3 / 0 5 / 2 01 3 - 03/ 15/2013* 1 00 0 11 72 34 M a n ager
TO:
M r . J erry S . Gi lli c k, R.Ph . , Pr e s ident / Ph a r ma c
Coll e ge Ph a r ma c y I n corporated Co lor a do Spri ngs , CO 9 09 1 8
3 5 0 5 Austin Bl u f f s Pa r kwa y Su it e 1 01
S EtlT.l8U S
~ NT
SPe CTSI>
Prod ucer o f Sterile Drug Pro d u c t s
supporting that they have evaluated what affect this would have on air curre nts within the room or the effects on finished sterile product including the use of smoke study evaluation. 2) Pressu re differentials are not mon itored continuously between areas 01 air quality. For example, the firm's air quality from the IS05 to ISO 6 areas ofthe clean room then to ISO 7 (gowning room) and finally to the ISO 8 (formula preparation area). The only pressure differenti al which is monitored is between tbe ISO 6 area of the clean room and the ISO 7 gowning area an d is not reflective ofthe air quality during routine operations du e to the following; a. The pressure differential is no t monitored continuous ly as the reading is recorded
b. When the door connecting the clean room and ISO 7 room is opened for any reason, the pressure reads 0.0 inches of water. c. The finn doe s not have any mon itoring parameters in place to detennine how long or how often the doors between the classified areas can remain or be opened durin g normal operations prior to investigating the possible effects on finished product quality. d. Altho ugh the pres sure is not mon itored between the ISO 7 and ISO 8 rooms, the finn has pres sure ga uge on the outside ofthe ISO 7 room which read 0.0 inches of water on each day of the inspection. The firm's technic ian stated that the pre ssure between the rooms could not be maintained because there is a wall mounted heater conduit affixed to the wall of the ISO 8 room and extends into the ISO 7 gowning area . This area of the wall, hidden behind an ISO 8 work coun tertop, cou ld not be prop erly sealed shut to maintain room pressures. 3) Environmenta l monitoring performed by the finn is not reflective ofcontinued daily sterile operations. For example: a. Personnel monitoring only occurs durin g employees' gowning re-qua lification/media fill and only includes assess ing the emp loyees' finger tips. This is not reflective ofthe da ily sterile operations or the batches of sterile product prod uced at the facility. Viable and non-viable particulates are not monitored more frequently than durin g the requalification of the clean room and are performe d only at static cond itions. This is 1I0t reflective of the normal dynamic operations which occur during rout ine sterile drug production. bas is which is not The fum performs surface and air microbial monitoring ofthe ISO 5 areas on a _ reflective of the daily sterile operations. In addition, the finn's written procedure for Environmental Monitoring, SOP 8.020.1 does not de lineate speci fic locations where the surface and air sampling should be taken from . The descriptions are recorded by the sampling employee as taken from the ~ ~ bench. Each ofthese benches has approximate ly of work sp~s no
(8)6lGNO.TIJIl
a _
b.
c.
SEE REVERSE
OF THIS PAGE
FO RM 'PA .j8J (09101)
M a t t h ew R. Dionn e , I n v e s t i g a t o r ;.t~ Za c h e ry L. Miller , Investiga to~

""""'OllS EDmOOOJlSOUllll
03/15/2013
IsSrECfIONAL OBSf:RVATIONS
DEPAKTMENT OF IlEALUI ANI} II UMAN SEKVlQ:S

R JOD ANDDRUG ADMINlSTRATION
(llS m,CTA,tnRESS AHl)PIt(lhE _ ElER DATE(S) Of INSPECTr:>N
-,TO:
,,~
(P . O. Box 25087) De nv e r , CO 80 225 - 008 7 (30 3) 236-30 00 Fa x : (30 3) 23 6-31 00 I ndustr y r n r cmra t I on r www . fda . gov / oc / i ndus tr y
OF NlM IllJ.lLW """"' ''''PORTISSUED
6t h & Kipling St .
03/05/2 013 - 03/15/ 20 13*
1 00 011 72 34
Mr .
Jer r y S . Gillic k, R. Ph . , Pre side nt/Pha rmacy M ana ge r
Coll ege Pha r ma c y I nc or p or a t e d

CITY. 8'1.0. TE. ZIP eoee. COUNlR'(
3505 Aust in Bluf f s Pa r kwa y Suite 1 01

TYPE ..-rABllSllM ~NT 'NSf'I':CTED
Co lorado Sp rings , CO
80918
Produce r o f St erile Druq Pr oduct s
way to determine if the employees were selecting from worst case locations.
d.
Rolling carts are used to transport sterile and non-steri le processing materials from the IS07 gownin g area to the clean room Dnring environmental monitoring, the finn obtain s a surface sample from the top surface of the cart, as described by samplin g techn icians, but neglects to test other portions of the cart, including tbe wheels. which make contact with the flooring of both rooms. This environmental monitoring practice is not documented in the Environmental Monitoring procedure, SOP 8.020.1. I reviewed the 2011 , 2012, and 20 13 environmental monitoring results which documented enviro nmental surface testing failures which were never investigated and the isolates were never identified . They included the following:
e.
i, Two clean room cart failures (dated 6/25 / 12 and 7109/ 12) each with one colony forming unit.
ii, Two ISO 5 work surface area failures (dated 5/2/11 and 4/9/1 2) each with one colony forming unit.
4) The areas identified as the ISO 5 sections of the clean room were observed to have various area s with non smooth surfaces for cleaning. For example:
a. Embedded within the wall between the ISO 5 area of the clean room and the ISO 8 room was a pass
through window which is no longer used and was observed to be duct taped shut from the ISO 8 room . Tho track by which the window used to slide open still remai ned exposed within the ISO 5 area.
b. The ISO 5 work bench area had a power outlet track along the wall which extended from the wall
approximately 1 inch and surrounded the circumference of the ISO 5 area s of the room.
c.
d.
Within the ISO 5 areas ofthe clean room along the interior wall there was a piece of duct tape (measuring approximately 2 x 3 inche s) affixed to the wall with no apparent function. Resting on the surface of the ISO 5 area bench top was a radio which is an object which is not easily cleanable.
5) Materials and cleaning supplies for use in the ISO 5 areas of the clean room were not each identified as sterile. In addition, the clean room written pro cedure does not include the specific cleaning agents authorized for use. For example:
a. A production employee was observed to use sterile
and non-sterile during cleaning operations for the surfaces of the area identified as the ISO 5 work bench. Neither ofthese agents were identified as authorize d for use in the finn 's written procedure including the order in which these
..
SEE REVERSE OF T HIS PAGE

FORM PD.\. ~Sl(09,")
M a t t hew R. Di onne, I nvest i ga tor ;"'h;;J Zachery L . M i l ler,

",""'OlPSP.DrIlOH 0l1$Ol1!Tll
DATEISSUEO
I nv e s tig a tor ~
03/1 5/2 013

PAGIl 3 OF ? PAGl!5
INSI'ECTIONAL OBSEKVAnONS
bf:rAkTMENT OF HEALTII AND HUMAN SERVICES

FOOD AND DRUG ADMlNJSlRATlON
STRICTAOOfleSS
AM)
PHO/'E
N U~
OATFCS)Of' INSPECTION
6t h ,. Kipling St. (P. O. Box 2508 7) De nv e r , CO 8022 5 -00 87 (303) 23 6-3 00 0 Fax : (30 3 ) 2 3 6-310 0 Industry I n f o r ma t i on : www. fda.aov/oc/ i ndustry
W.",E ""'" 'I1lU Of' IHOI I'lDUAI.TOWfOM REl'OIIT IS
03/05/2 0 13 - 03 / 15 / 20 13 * 10 0 011 72 3 4
'""_. College
TO:
Mr . Jerry S. Gi ll ick , R. Ph . I
Pres ident/ Pharmacy M anager 3505 Au s t i n Bluffs Par kway Suite 101
T'lP E EST,l8L1S""':NT INSl'EClED
Phar mac y Incorporat e d 80918
CITY , sn.:rn. ZIP CODe , COlNTIlV
Color ado Sprlnas , CO
Pro d u c er of Sterile Drug Products
agents should have been used. b. On 3m 13, during cleaning operations ofthe clean room (as delineated in written procedure 11.100.1) we observed an employee using a tacky roll mop 10remove lint from the ceiling (making direct contact with the surface of the HEPA filters) as part of the . cleaning process. This tool was observed to be stored immediately next to the hand cleansing sink located in the ISO 7 gowning room area.
OBSERVATION 2
Each batch of drug product required to be free of objectionable microorgan isms is not tested through appropriate laboratory testing. Specifically, the firm's current sterility testi ng methods for prepared sterile drug products are not being completed in accordance to their written procedure SOP I 1.050.2 in that their sample size does not match what is required by the procedure and is not sufficient to be representative ofthe batch ofsterile product produced . In addition, their formula worksheets contain spaces for sample documentation, but do not specify how much sample should be tested by the sterile processing employee. There is also no documentation for how much sample was actually selected for testing. For example:
I) The Formula Worksheet for EDTAlMag Sulfate PF 3 gmI1gml20ml injectable involves the production ol. x 100 ml vials ofthe preservative free sterile product. Although not specified on the sampling section ofthe form, 3 x I ml each was tested by the firm for sterility assurance. The sample size according to their procedure should have been .mls from each o' x 100 ml vials.
x 30 ml vials of the 2) The Formula Worksheet for Phosphatidyl Choline I. V. Pres 5% Inj includes the production ster il e injectab le product. Although not specified on the sampling section of the form, 1 x 30 ml vials was sent for testing to a contract lab. llte sample size according to the written procedure should have been a minimum of lml from each ofllvials. x 30 ml vials of 3) The Fonnula Worksheet for Mcthylcobalarnin PF 25 MGI.ML Inj includes the production preservative free sterile product. Although not specified on the sampling section of the form, I x 30 ml vials was tested by the firm for sterility assurance. The sample size according to their written procedure should have been a minimum oflmI from each oflseparate vials. Finally, the finn has failed to perform growth testing for any ofthe media which they purchase for conducting in house sterility testing. In addition, the Eadosefe-P'FS used by the finn to test produced sterile drug products for endotoxin has not been calibrated to assure the quality ofthe data produced by the equipment. The Endosafe-P'I'S was last calibrated in February 2011 despite the User's Guide recommendation calibration.
o .
o .
of_
EMPLOVEEC S/ SIOW\l\,ooe
[)JlTE'S8U~D
SEE REVERSE OF T HIS PAGE

ruR/lt U'I!. .w; (09/01)
M a t t h e w R. Dionne , I n ve s ti g a t o r /WI- ,/, i l l e r, I nve s t i ga t o~ Za c hery L . M ~

I'RF.YIOUS t!DIl1()ll 0/lS0I.HT1l
0 3 /1 5/2 0 13
PAGB 4 OY1PI!. G P. S
INSPECflONAL OBSERVATIONS
DEPARTMENTOI" Ht;ALTII AND IIUMAN SF,RV'Cf;S FOO D AND DRUG AD MINISTRATION

IIATE(Il) OF INS PECTION
6t h & Kipling St . (P .O . BOK 250 87) Denve r . CO 80225-0087 (303 ) 23 6-300 0 Fax : (303 ) 23 6- 310 0 I ndust r I n f o rma t i on : www . f da. gov / oc / i ndus t r y TO:
03/ 05/2013 - 03 / 15 /2 013 * 100011723 4
M r . Jerry S . Gillick , R.Ph. , Pre side nt/ Pharmacy M an a ge r 3505 Aust in Bl uffs Par kway Su ite 101
TYPE ESf - . 1SIlI.<EHfIN9l'EC TED
Col lege Pharmacy I nc o r po r a t ed

CITY, STATE. llP CODE. COI.JlmlV
Colorado Springs, CO
B0 918
Produ c e r of Ste r ile Drug Produ cts
OBSERVATION 3
Each lot of a component liable to objeetionable microbiologieal contamination is deficiently subjected to microbiologieal tests before use. Specifically, the finn's Sterility Supervisor stated that they use approximately 99"iG non-sterile raw materials to produce sterile finished injectable products relying on their sterile methods to ensure product sterility. Proper use of sterile methods depends on their evaluation of the material which they are and they have not routinely challenged certificates ofanalysis provided by raw material suppliers prior to utilization in sterile production of their drug products. Additionally, the finn has never performed bioburden studies or have established limits for bioburden to ensure that the methods used for their finished roducts are ade nate for their sterile rocessin 0 orations.
OBSERVATION 4
Procedures designed to prevent microbiological contamination of drug products purporting to be sterile do not include validation of the sterilization process. Specifically, 1) Personnel qualification for sterile processing is delineated in the firm's written procedure, SOP 11.010.2, which include: media fills. On 3n l 13, during the inspection I observed the media fin process and noted the following:
a.
b.
In accordance with SOP I I.O10.2, and the associated written procedure titled "Media Fill Test for Aseptic Technique 3% Solution Liq", the maximum number ofmanipulations within the clean room environment This is not reflective of the maximum batch size which may during media fill qualification is. potentially be produced by an employee which may total.manipulations.
2) The fum bas not evaluated the container closure systems used to produce sterile product which undergoes further lyophilization to assure that the sterile work in process is properly protected when the partially stoppered vials are transferred from the ISO 5 clean room bench surface to the lyophilization chambers which are maintained in tbe ISO 7 gowning room. 3) 111e . sterilization methods used by the finn have not been properly validated to assure the quality of sterile testing to evaluate . integrity for each product produced at the facility. For example, the firm uses
F.MI'lOve E(tl) ,
lJAT E I&su Eo
M a t t hew R. D i onne , I nve s t i ga t or ~ Za c hery L. M il l er, Inve s ti g a to~ ~
03 / 15/2013
PAGE S on PAOI!:S
I'''',....cos
IIDITIOH 08SOlETB
VrlSPr,cnONAL ODSt;RVA,1l0NS
DEPARTMENT OF In:;ALTHAND II UMAN S.;RVICE.. ~ FOOD ANDDRUG ADMINI STRAnON
6th & Kipl i ng St. (P .O . Box 250 87) Denver , CO 80225 - 0087 (303) 236- 3000 Fa x : (3 03 ) 236-3100 I ndus t r y Infor mat i on : www . f da. gov/ oc / i ndu s t r y
03/05/2013 - 03 /1 5/2 013*

FEI NUMlll'R
10001172 34
TO :
ARM_ E
M r . Je r r
S . Gillick , R.Ph . , President/ Pharmacy M a na e r

6TR~ AIlORI: SS
College Pha r ma c y Incor porat ed

ClTY. STAn. ZIP CODe . COlMlRY
3505 Au s t in Blu f f s Parkway Suite 10 1 Pr oduc e r o f Ste ri l e Dru Products

psi
Colorado S rin s , CO
80918
batch of sterile product produced; however, the ranges for an acceptable . integrity tests range from (po unds per square inch) for each of the ~sed dunng production. In addition: a. The firm has failed to establish a minimum psi required to test the integrity for the
set<;
b. The finn has not properly challenged these. , based on product or raw material bioburden knowledge or other scientific means (including challenge organisms) to assure that their methods are capable of consistently produce sterile product. In addition, the sterility testing conducted by the fum at their facility or contract labs may nor be suffic ient 10 detect microbial contamination potentially due to. failure because they fail to follow their own written procedures for finished product sterility testing sample size which was may nol be reflective of the batch (sec Observation #2). c. The employees document that the minimum has been reached during routine operations for _ integrity testing by signing the batch reeord; however, they do not document what the actual pressure was WhiCh resulted in the passing exam. 4) On 3/5/13, 1 observed the production employee producing Selenium preservative free 40 mcglml injectable products x 2 ml vials and . x 10 ml vials). During th is production, I observed the following pertaining 10 aseptic production practices: a. When the production employee donned her sterile gloves within the clean room area designated as 180 5, she had touched the palm of her ungloved right hand with the sterile glove surface ofher left hand. b. The employee was observed to break the ISO 5 air flow 10 the tops ofthe 2 ml vials with her right gloved hand. This occurred immediately after the tops ofthe vials had already been sterilized using aJ c. After observing the employee sterilizing the 2 m1 vials, she was observed to break the 2 ml vials with her left gloved hand while entering and filling each vial using the ii .
'h .e,.s.oIl5 . ,rr . fl.o.w,. 0the tops of
ll
lI
OBSERVATION 5
There is no written testing program designed to assess the stability characteristics of drug products. Specifically, the finn does not have a stability testing program in place for the more than 5,000 different products produced at their facility, including sterile injectable products. They also do not have a formal change control process 10 assist in delineating when more recent stability tests have to be conducted and their Sterility Supervisor has stated thai product stability testing (including assay) is only performed on product after they have established a beyond use date (BUD). For example:
EMPUI 'I'U:
6IGNA 1 ~
SEE REVERSE
OF THIS PAGE
FO RM I'DA oCU (oMIM)
Mat t hew R. Dionne , I nves t i gator ~~ Za che r y L. M i l l e r , I n v e s ti ga t o r~

PRP.VIOl'$KIJIT\ONOOSOU! rE INsrECfIONAL onS':RVAn ONS
03/15/2013
P A (" d! ~
OPT PAn ES
DEPARTMENT 01<' Il EALlll AND II UMAN St;KVICES

DlSTRICTAIlOIlUS
me_
ff.MIlf.R
fOOD AND IJRUG ADMINISTRATION

DATE(SJOl'
~
6th & Ki p l i n g St. ( P . O. Bo x 2 508 7 ) 03 /05/ 20 13 ,-~ Den v e r . CO 8 022 5-008 7 (303) 236- 3 0 00 Fax : (303) 23 6-31 00 1 0 00 11 723 4 I nd u s t rv In fo rmati on : www. f d a . a o v / o e / i n d u s tr y ~ E "" D TlTl.E Of I/l DM DlJ,O, l 0 ~TO: Mr . Jer r y S . Gi l l i c k, R. Ph Pr e s ident/Pharmacy M anager
~ I A M NMoE
03/1 5/ 20 13 *
6TllEeT AllllAE
College Pharm acy I ncor porat e d

CiTY. ST AlE . :" CODE. coo
3 5 0 5 Austin Bl uffs Parkway Su i t e 101

TI'PE EST.l8UE ....EHT INSPECTED
Col o r a d o Spri n g s, CO
80 91 8
Pro d u c e r o f Steril e Drug Prod u c t s
I)
Their finn had changed the . type for use for EDTAlMag Sulfate on 5/20/20 11 and since this time, they haven't generated any current data supporting a 180 day BUD despite the five stability failures that preceded (including failures in 2005, 2006, 2007, and 2008). Their Sterility Supervisor has stated that the fmn bad dispensed EDTAlMag Sulfate from these failed batches as they do not always perform analyt ical testing for potency prior to distribution.
Addit ionally, the flrm does not perform routin e ongoing stability testing to ens ure that current data continues to support beyond use dates. For example: 2) Methylco b 25 mglml preservative free stability testing in support of a 120 day refrigerated stability has not been reevaluated since April of 201O.
Finally, although sterility testing is performed for each batch of product prod uced, the finn does not have a ongo ing sterility testing program as part of their stability testing to support the current BUD for preservative and preservative free products produced at their facility . Products are selected by the Senior Steri lity Prod uction Personnel for eva luation. This practice is not delineated in a written procedure and the firm could not explain how certain products are selected and others are not. (lor example: 3) Methylcob PF was last placed on extended sterility testing in May of 2010 and has not been re-evaluated since that time.
OBSERVATION 6
Testing and release of drug product for distri bution do not include appropriate laboratory determination of satisfactory co nformance to the final specifications and identity and strength of each active ingred ient prio r to release. Specifica lly, the fmn does not have a written established program and does not conduct routine analytical evaluation of the produ cts produced at their facility for identification or potency of each batch of product produced prior to dispensing to end users.
DATES 0 1" INSPEL'TION:
031092013(Tuc), 03/0712013(Thu), 03/ 14 12013(Thu), 03/ 1512 0I3(1"ri)

fOk llt I'DA O .J(_ l
M a t t h ew R. Dio n n e , Invest igato~_A ~ Za che ry L . M i l l e r, I n vesti g ator, ~~

r JlllVl Ollll ev rnoN QJIllOI.ETI!
{$j SK:><o.TVIlE
DATE IS$ !JEO
0 3 /15/ 2 0 1 3
PAGIl 7 OF 7 PAGll S
I NSPECfIONAL OBSERVATIONS
The observations of objectionable conditions and practices listed on the front of this form are reported: 1. Pursuant to Section 704(b) of the Federal Food, Drug and Cosmetic Act, or 2. To assist firms inspected in complying with the Acts and regulations enforced by the Food and Drug Administration Section 704(b) of the Federal Food, Drug, and Cosmetic Act (21 USC 374(b)) provides: "Upon completion of any such inspection of a factory, warehouse, consulting laboratory, or other establishment, and prior to leaving the premises, the officer or employee making the inspection shall give to the owner, operator, or agent in charge a report in writing setting forth any conditions or practices observed by him which, in his judgement, indicate that any food, drug, device, or cosmetic in such establishment (1) consists in whole or in part of any filthy, putrid, or decomposed substance, or (2) has been prepared, packed, or held under insanitary conditions whereby it may have become contaminated with filth, or whereby it may have been rendered injurious to health. A copy of such report shall be sent promptly to the Secretary."
D PARTME1\'T Of H EALTH
FOOD AND DRL'Q
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Thi s docu ment list$ obsen'ations mad e by the FDA represen lath-etsJ dUri1l2 the inspec tion of \ 'OUf facijiro.. Th c~ are inspectional obseeveuons, and do not represent a final Agtne}' dererm meucn rq:arding your compliance. lf' ycu ha ve an objection regard ir.g an observation, or have ,implemented, or plan to implement. corrective action in response to an c bservazien, you me,.. discuss the objeo;lion or 'actioo ""llh the FDA reprcscnlali"'e(s) duri ng the inspeion or submit this informati on to FDA at the address above. if you r.3H: any se c ontact FDA at the eb cee number and address abo ve. uue:-lions. ctee
I I
I
Procedures designed to prevent micro biological con tam ination of drug products purpo rting ro be s terile are not established .
Scccificallv. a) Your firm does not have any written proced ures desc rib ing how aseptic ope rations are 10 be performed in me ISO 5 and ISO 7 classi fied areas. On 3/4/t3 employe e . was observed performing a sterile _ of Pyrilamine Maleate 2J IIl!;/m L iuj~ ....wic (iu. ffCAaDADAE;37) with bvth steeves of her gown rolled up to he r elbows, exposing bare skin from the wr ist to the elbow. The employee was observed wa lking directly into the c lean room area without proper gown ing, placing the beaker of drug product under the ISO 5 hood. returning to the ISO 8 Ante Room to gown up and then returne d to the JSO 7 Clean RoomllSO 5 l aminar Flow Hood to continue sterili zation and mUng of the drug product. A <;imilar rmce<;<; was observed. with the exception of me rolled up sleeves, on 315113 during the preparation of Ketamine 200mg/mL inj ectabl e lot #C ABDADAF: 13 by employee _ "
erocuct 10 ~ for removal of !'3J11cu lates~ sterilized You use a _ _ ,., perform Ih js~
~, : ou r ~.nn d~ nol ~e~onn . mte~ry testi ng of
VIOU 3/5; 13. uuring un: prepar.u ion uf Amisacln (745} Burferec 5UmJ!/roi. injectab ie, lor ;::.CABu AUAF:lj, tne product was rough a Ij in an unclassified area and then placed into a V1aJ. s toppered an, sterili zed You sta ted thai for some steri le animal pr oducts that ~d. yo ur preparatio n ins truction s allo w for the
Ims
m: s (o
all SIeme oro
th rooueu., numan ana anlOUli re
s~erilizing IonSrnat are
used 10 prepare sterile drug produc ts. c -",," '""e e".C -
--j
OBSERVATION 2
I I
Proc edures desi gned to preven t microbiological con tamination o f drug pro ducts pwpotti ng to be sterile do nor include va lida tion o f the s teriliza tion process. -
Specttle alty,
a) Your firm has
QQt
performed any media fills.
Marga r et M_ Ann es , Torrance J. Sla y t on ,
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DEP.Jt.RT~IE"'T OF
HEALTH i~.' D HlM.~' SER\1CES

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FOODA.'iD DRUGADIolL'liISnv.TION
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11', 1 /(: &17 (1' "
TO :
Lowel l J. Ahl. Pr e s i d e n t
~harma c ie5,
Lowl n
Inc .
30 : NE l Ct n S<:.
Bla nc ha rd, OK
73 0 10
b) There is no assurance that your finn has adequate process co ntrols to pre vent failures of your sterile dru g product. f or esses for suspemions and solutions have not been designed following a scientific rationale. example, the sterilization S reiora ere
OBSERVATION 3
Aseptic processing areas ate deficient regarding the system for monitoring environmentalconditions. Specifically, your firm does not have a written environmental monitoring plan. No environmental monitoring. including
nnet monitorin
is funned under stark or
mamic conditions.
OBSERVATION 4
Employees engaged in the processing of a drug producl lack the uaininA:required to perform their assteoed functions.
Specifically, your firm does not have documentation to show that all employees involved in the preparation of sterile drug products have bun trained. Employee. has no documented training for the preparation ofsterile drug products. Emy!o,J~ =:;;.dcd a _ "Asc . .ric CYmpuw..:1i.ng Tra1,ir.g" course ill]",;) 200:; Uui. iua LlU UU1COf Ulx;wm:ntw aaifling related 10asepti c proccssingordrug products. During this inspection on 3/4/13 It. 315113. we observed EmplQyee .
preparing sterile drug products (Jot #CABDADAE:37 of Pyrilamine Maleate USP 25m!Y'mL injectable, lot #CABDADAF:25 of Amikacin (745) Buffered 50mglmL injectable, and lot #CABDADAF: 13 ofKctamine200m~mL injectable) without properly gowning, including preparing sterile drug products in an ISO 5 laminar flow hood with the sleeves c r hee go....-n rolled u to the elbow ex In bare arms.
SEE REVERSE OF 11115 PAGE

INSPECTIONAL ~BSER~'AnO!llS
DEfARTMEt\-r Of HL-\Lnt A'\l) HDlA.... SR\lCES

fOOD .-\. '\;D DRti G All... t lNl~nu.TIO."
,
j 03 /G4 /2:G13 - 03 )O e: / ~ Q: 3 ~
404 0 Nor th Cent r a l Exores sway . Suite 30e Dal l a s , TX 75 20 4 (214 ) 2 5 3- 5200 Fa x : ( 214 j 253 -53 14 I nd ustry Informa tion : w~d .fda . g ov /oc ;i~d~3t~ -v _ ..... mu. :I TO \O\HCJIl
TO : Lowell J. Ahl , Pr e s i de4t
Lowl yn Pha rmac i e s , Inc .

Blan char d , OK 7 30 1 0
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OBSERVATION 8
Drug product containers and closures were not d ean and ste ril ize d and processed to removeJ*TQgenic properties EO assurethat they are SUItable tor tneu mtenced use.
Specifically, your finn's preparation of glass vials and rubber stoppers for use in sterile animal drug products does nor ensure tfuoy SlrP pyn_~,.J't fT~ ~ l l) "~ . F(>r':"x<,.m~~, a) You r finn receives glass vials and rubber Stoppers that are not depyrogenated and will be filled with non-ste rile drug product and then steri lized or aseptically filled.
.. C) The stoppers are prepared by removing them from the clear plastic shipping bag, wrapping them whb
b) The glass vial preparation includes washing in a bcusebcld-rype dishwasher with household detergent. enclosed in
endthen
and thea
d) Your firm has no ev idence mat these glass vials and rubber stOppers were depyrogenated by your sup plier. In addition.. there are no written procedures or records of vial or stopper prepararicn.
OBSERVATION 9
Each balch of drug product required 10 be free of objectionable microorganisms is not tested through appropriate laboralO!} testing. Speciticatty, your finn does not conduc t routine sterility 01 endotoxin testing for all sterile drug products currently produced. For example, you sratea :..';a: scmc prvd~U arc tested a>:c.:.rdi"g to a ~t~ du.:e . On ::;18: l:i, ..e ccserved '( XXX) different sterile injectable an imal drug products that were approved for shipment to customers. None o f thes e products had been tested for steri lity or endotcxins prior to release. The products observed include: Acetyl-D-Glucosamine 20"10 200mg /mL injectable (lot #CABDADAE:33) DiclazuriI500mg/mL injectable (Iot.#CABDACCB:22) Cyclosporine 2% Ophthalm ic (lot #CABDADAE:34)
I'n edditicn, there is no established written program for conducung sterility and endo toxin resting.
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LfOGPECTlO:"l'AL IlBSERVATI01''iS
DIJ'ARDt!"I'T Of flLUTH Ao"'D HLX"'" SERHCU

FOOD AND DRUG ADMINlSttATION
;
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40 40 North Cent ra ! Exp r~~ s wa y . S ~ i t e 30 0 Dallas. rx 7 520 4 (214 ) 2 53-5200 Fa x ; \21 ~ J 253 -5 31 4 I nd u s t r v I n f o r ma t i o n' w:_ "-< ~ C:O. - ccv / cc zrnocs ..n _"" _ . ... c rv
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P re s ide~t
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t .owt v pr.iH ma c i es, r nc .

73 0 1 C;
, 30: :-!"E 10: t 5,: .
Blanchard, OK
OBSE RVATK)N 10
Testing an d release of drug product for d i~ bution do n ot inc lude appropriaJ.e labor;uOC) determinat ion of saris factory con formance to me final 5plfica..bons and ienrrty an d strength of eac h actt\'e lngredtmt pnor to retease . your fum docs not eondue'! pct eacy resring for all sterile drug producl$ CWTmuy pcodtKed. for examp le, :- Ol.l r ronllC'f'" -1'1" l~fM !t('.c:ording to e ~""' l'It". On ]/'8.113 . w t" ~d ~XX. X ! .ct:, ff~er.t sterile injectable animal dn.tg prod Ud.5 that were appro'led for ~pmrnt to customers, None ofthese products had been teared prior to release. The products obs erved include :
Specjfic~Uy.
~ ..Irrl th<tt Y'1'l'l"
Atttyl-D-GlucOMmine 200/. 200m~'-ml i:::Ijectable (lot :;CABDADAE:3 3) Didazuril 500 mglmL inj ectable (lot #CABDACC B:22) Cyclosporinc 2% Ophthalmic (Jot #CABD ADAE:34)
In addition . there is no cstabl~hed wri tten program fur conducring potency restin8 .
OBSERVA TION 11
Then: is no written tes ting program designed to assess the stab ilil)' characteristics o f drug products . Spec ifica lly, a) Your firm does not ha~e.a written stability program to justify the Beyond Date placed o n sterile clrug products . Your firm does not han any documenwion 10justify bow !he current BUD's were establish ed fo r each ste rile drug product.
use
mum
for example, on the PapaverineIPhenrolaminelProstaglandin 30mg/ l .5mcg'JOmcg;mL product (human ste rile drug) you place a BUD or i6Q r,iays. On me Budesonlde 5mgimL product (animal sterile drug) you place a BUD of 9\} days.
Your firm failed to rm an anti-microbial effectiveness testiD@: to determine whether ingredi ents such as ~ effectively inhibit microbial gro wth in your ste ri le injectable drug products ~
BUD oc:riod.
OBSERVATION 12
Equipment and utensils are not cleaned and sanitized at appropriate inlen-als to pre vent contam ination that would alter liie safety. identiC)', s~ngth, quality or purity cf the drug product.
SpecifICally, your fum's cleaning and disinfection of proces.sing w:ensils and containers does nO Tensure the:--do nOI
contaminate you r steri le injectable drug prcdects. For example
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4 0 40 North Ce n t r al Expr-essway. S u ite 30 0 D a llas . TX 75204 (2 14 ) 253-5200 Fax : (21 4i 253 - 5 314
www . f da _g oY / o c / i ~du st = v
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LowlYn Ph arm a ci e s, I c c .
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a) Your fU1Jl cleans equ ipment and utensils. incl uding glass beakers used 10 process dru products prim to sterilization, by band-washing in a sink with hou sehold dish detergent and tben in a household style dishwash er using ~ousehol d dishw asher deterge nt. The water supplied 10 the sink dishwasher are municipal source and is not further treated, Y our firm has no evidence thai this cl ean ing mezhcd is appropriate for equipment and utensils used 10 produce sterile drug proUUl;;L:o;. .'
and
b) Your firm uses a pair of tw eeze rs to conducted manipulations in the ISO 5 laminar rlow hood of ru bber steppers used ;:0 seal 21835 vials co ntain ing animal drug pro ducts after. steri lization or sterilization. The tweezer s are not . . . prior to use and are disinfected by placing Ute- end of me tweezers in a. beak er with non -sterile . sterilizes bulk non-sterile drug products in from a beaker via an asept ic proce ~ in the 150-5 c) Your firm . laminar ItUW hoed, Tm: nun-swrik: Urug product is mixed in the beaker iocared in an unclassified room and men moved to the laminar flow hood without conducting an y dis infection of the beaker.
DATES OF INSPECTION:
03f04J20iJ(Mon). 03i05120 13(Tue). 03108!20 131fri)
I
I
.
~A04tul~
I I
-..
Margaret An nes, Torranc e J . S l a yt: on ,

PIle''I1IltlS tD!T1O" llIlOOU'fI!
C S O ~'\...."'* 'YY1:fl"""'U/1 eso ~ ~ ./ (". /

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INSPCTIONAL 0& ERVATJO:"iS
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DEPARTI\IENT OF ffEALl H AND HUM AN SE RVICES FOOD AND DRUG ADMINISTRATION

DATE(S) oF ,NS<>ECTION
...""'' ' O T 'n.tOf

TO ;
4 04 BNA Dr- , Bl d g . 2 0 0 , s t e . 50 0 Ne s hv i Ll e , T N 37217 -259 7 ( 61 5) 366 -7801 Fa x : ( 6 1 5 ) 3 6 6 -7 80 2 I nd u s t r I nforma t ion : www . f d a . g ov / o c / i n d u st r

J o dy
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0 3 / 04 / 2 0 1 3 - 03 /0 7 /2 0 13 1 0 00 2 21 951
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Grooms,
Regiona l
Di re c tor , Ph a ma c y
eratio n s
Ce nt ra l Admixtu r e Pharma c y Ser v ices , I nc .

c,,..,., .1 A'1:, l IP t QOl:. "'iv.mn
2 1 1 S ummit Pa r kwa y #1 2 2
Ho me wo od , AL
35 209
Prod u c er of S teri l e Dr u
Pr o d u cts
This document lists observations made by the FDA represeetativers) during the inspectio n of your facility. They are inspectional observations, and do not represent a final Agency determination regarding your compliance. If you have an objection regarding an observation, or have implemented, or plan to implement, corrective action in response 10 an observation, you may diSC USS the objection or action with the FDA representanvefs) during the inspection or submit this information to FDA at the address above. If you have any questions, please contact f DA at the phone number and address above
DURING AN INSPEC TION OF Y OUR FIRM WE OBSERVED:
OBS ERVA TIO N 1

Each ba tch of dru g product req uired to be free o f o bj ectionable m icroorganisms is not te sted thro ugh ap propriate laboratory test ing. Spec if ically , the firm fa ils to e nsure that eac h batch of aseptically p rocessed ster ile d rugs, which it d istrib ute s, passe s ste r ility and endotoxin testing be fore batch d istr ibution . Ac cording to in process In vestiga tio n 1t06-13 0214-005, the firm re cei ve d failing ster ility testing res ult s re pre se nting 18 orders of Ca rd io pleg ia that had a lre ady been rele ase d and d istribu ted , Fo r e x-amp le, two of t hose 18 orders ( numbers 690848 and 690849) of Ca rdiop legia w ith a BUD o n o days we re s hipped to
OB SERVA n ON 2
Test ing and re le ase o f drug pro d uct for d istri butio n do not incl ude app ro priate la boratory d etermination o f satisfac tory confor mance to the ident ity an d stre ngth of each ac ti ve ing redient pr ior to relea se . Specifically, t he firm fa ils to a ss ure th a t eac h batch of asep tica lly pr ocessed st er ile d rug s it di strib utes, meets pred etermined spec ifications (i.e . assay, p H , o smo lalit y, erc.) by way of rele vant che m ical an aly sis , before batch di stributio n, For e xample , Ox ytoci n and C ard iop legia are re leased with no assay test ing prior to d istrib ut ion .
OBSER VATIO N 3
Investiga tio ns of an unexplained d isc repan cy d id not e xtend to o ther dr ug produc ts that may ha ve bee n asso ciated wit h the spec ific failure o r di scr epan c y. The " Invest iga tive/Corr ec tive Ac t ion Reports" identifie d as 06120709005 and 06- 121102-008 were inutiated based on act ion lim its for personne l e nv iro nme ntal monitorin g specificat ions tha t wer e ex ceeded , Th ese samp les are take n on ,however, t he results are not known u ntil the fo llow ing . In the inte rim th e e mp loyee produce s T hese in vesti gatio ns d id no t assess the im pact to product produc ed during the ti meframe betw een
e M'" a ""e($) <lGNA"""
SEE REVERSE OF TH IS PA GE
FORt>t mA oil (OMla,
Mar i e A . Fadden, Co n s ume r Safe ty Pa u l C . M o u r i s , I n v es t i g a t o r

Pll.< "lO llS 0<1"101< OBSOlETE
....f.. Of fice r~ a i1~

, "v( C'
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03/07 /2013
INSl' f.CI"IO NAL OKSERVAl"I OI\S
OEPARTME NT Of HEALTH ANn

I;l<ST."" OOO'tt' . . .
" U ~1 A N
SERVIC ES
o.<tt<. I"" ... .... C' 1ON
-oo _ _"""
FOOD ....ND DRUG AOM INlSTR...T ION
'0' BNA Dr . , Bl d g . 200 , Ste . 500 Na s h v i lle , TN 3 72 17 -2 5 97 ( 61 5 ) 3 6 6 - 78 0 1 Fax : (61 5) 366 - 7 8 02
03 /0 4/2013
'" 10002119 5 1
5,..EfT ilOOR "
- 03/07/2013
Indu s t rv I nformati on : www . fda .aov / o c / indu s t rv

HAUl! AHO'm.t Ol "",,"V"""*'l
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TO:
J ody
K. Gr ooms , Re gional Di r e cto r , Pha rma cy oce r e t rcns

2 11 S ummi
t
Ce n t r a l Admix t ur e Pha r ma c y Se rv ices .
Pe r kwa y 11 2 2
I nc: .
orv. I b'l. ~ COO5
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3 5209
pt; " ._ _ ... " - ' :T1'0
Hom e loood . AL
Prod uce r o f S t e r il e Druq Products
when the sample was ta ke n and the resu lt wa s determined.
OBSERVATION 4
Prorecuve apparel is no! worn as necessa ry 1 0 protect drug products from contamination.
Spec ifically , person nel co nducting aseptic operations within the 1$ 0 5 laminar flow hood were o bserved to have e xpose d face and neck skin as well as e xposed beard hair.
OBSERVATION 5 Equ ipment for adeq uate con tro l e ve r air pressure is not prov ided when app ropria te fo r the manufac ture. processing, pack ing or hold ing ofa dru g prod uct Spectficalty . the firm la cks a syst e m of co ntinuous monitonng of posmve pressure differenual limits dur ing asepti c processing of ster ile d rug prod ucts The: firm's c urrent practice is to log their reading fro m their posinve d iffere ntial press ure gauges re presen ting the ir clea n room s and adja cent roo ms, Becau se these ga uges are located outside of the d ea n roo ms the mse lves, if a loss of pcsiuv e pressure in a clea n room occ urs dur ing ase ptic proce ss ing, t he firm may not not ice unlil the clean room differential press ure gauges are read a~ T he firm's curr ent clean room differential pressure syste m has no aud ible a larm ; thus, trans ient exc ursio ns 0 pressure would not be obs erve d o r recorded.
OBSE RVATIO N 6 Procedures des igne d to preven t microb iological contamination of d rug prod ucts purpo rt ing to be sterile are not estab lis hed A) The firm lacks adequate en vironmen ta l moni tor ing cont rols within the aseptic processing fac ility (i nc lud ing per so nne l gow ning areas ). T he firm does not co nd uct enviro nme nta l monitori ng, ( i.e. vieble/no n-viab !e air sa mpling, su rface to uch plates, microb ia l se ttling pla tes, operator finger s/sleeves) within the laminar flow hood during and afte r the asep tic processi ng op eratio ns of each batc h of finished sterile drug prod uct. S ) No pos iti ve con trols a re incl uded in media fill process va lidatio n batches.
C) No forma l bacterial retentio n testing has bee n co mpleted o n sterile . used in the sterile process ing of Sodi um C hloride, Mag nes ium Sulfate, and Po tassium Phosp hate sterile solutio ns.
th_
of t he no n-sterile to
D) The procedure "Enviro nme nta l Mo nito ring" /iSO P-CA PS4000 172 effe ctive 9/5/12 is inadeq uate in tnar: I ) the spec ified action and ale rt limits fo r mon itori ng of particu late coun ts, a ir bioburd en cou nts. and glo....ed fingertip
l .....OYl _ ........ n.ooo oo.'.EIS.S<JfO
SEE REVE RS E OF THIS PAGE

FOil.... FD... " l ' _ 1
Mar ie A . Fadden , Co ns ume r S a f et y Off ice r o ur i s , In ve s t i g a t o r Pa ul C . M

_VIOUSDI1lCO ~
I'YlI'lP
f<--
03 10 7/ 2013
INSP[CT IO NAl OBStR \ '.o\T 10'll5
, ...a
l Of P.o.GES
DEPARH 1NT OF HEALTH AND HUMAN SERVICES

FOOD AN D DRUG Al)MINlSTRA TION
4 04 BNA Dr., Bl dg . 2 0 0, Ste . 50 0 Nashv i ll e, TN 3 7217 - 2 5 97 (6 1 5 ) 3 6 6- 7 8 0 1 f a x: ( 61 5) 3 66- 1 8 02 I nd u s t r y I n f o r ma t i o n : www , fd a .go v / o c !in du stry
031 0 4 / 20 13 - 03 /0 7 / 2 0 13 10 0 0 2 2 1 9 5 1
TO:
Jo dy K. Gr o oms, Re g iona l Dir ec t or ,
Ph armacy Op e r a t ion s
21 1 Summi t Pa r kwa y # 12 2
Cen t r a l Admi xt ure Pha r mac y Serv ic e s, I nc .

t, r.. STATF. l IP COIlE . c O\JNT ~ .
Ho me wo o d , AL
3 5 20 9
Prod uce r o f Ste r ile Drug PrO d u c ts
-1
bioburden cou nts, are nor based upon the site specific bio burden studie s. T he follo wing environmental mo nitoring action limits are used by the fir m:
,
ii.
Ill.
>V.
OB SERVATION 7
Writte n procedures are lacking for the use of cleaning and sanitizing agen ts des igne d 10 pre ve nt t he contamination of drug produc ts. Specifically , the firm does not use spo ricida l clea ning agents in their ISO .5 la minar flo w hoo ds, wh ere aseptic process ing of steri le drugs occurs,
OB SERVATION 8
Equipment used in the manufact ure, proc essing, packing or ho lding of drug products is not of appro priate des ign to facil itate operat ions for its intended use , Specifically, tape was observed ho lding up clipboards o n the outs ide sash of the ISO 5 T P N hood in the room identifie d by the firm as are.
OBSERVATION 9
T here is no written testing program des ig ned to assess the stab ility characteristics of d rug prod ucts . Specific ally , the firm has no written stabi lily program wh ich requires ongoing sta bility stud ies to show that the aseptica lly proce ssed ste rile d rug pro duc ts whichthey distribut e, cont inue to mee t all re le vant che mical and ste rility spec ifications all the wa y to produc t expiry, or beyond use dates (BUD).
SEE REVERSE OF TH IS PA GE
FORM f DA .. '
(~9fDI )
Mar i e A. Fa dde n , Con s ume r Sa f et y Of f i c e r

Pa u l C . Ho u r i s , Inv e sti gat or
IN srEcn O~ AI .
MI'\f
f~
03 / 07/20 1 3
' AGF. J O"'PA(;fS
0 8 SERV A'J IONS
DEPARTM ENT O f H EA L TH .4.1"0 H UM4.N SE R VICES fOOD AND DRUG ADMINISTRATION

OI S T ~ICT
AOOIlESS A"01'I<ONl' " U"'8.E~
OAT (Sl <Y''''sPECTlO/<
Bldg . 200, Ste. 5 00 ' 0' Nashv ill e, TN 37 2 17 - 2597 ( 615 } 366 - 78 01 f a x : ( 615} 366- 7802 I n d ustr v Info rma tion: www . fd a .gov / o c/industry
BNA Dr . ,
NA " E AND T<lL~ or I/IOI\I1OUAl.
03 /0 4 /2 0 13
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0 3 /0 7 / 2 013
100022 19 51
to
\M'tOM "f "O'l T 'S SUW
TO :
t If!M NA" E
Jod v K. Grooms, Reg i onal
Di r ecto r , Ph armac y Op erat io n s

STREETAOOR E!>S
Cen tra l Admi xt ure Pha rmacy Service s , I nc.

Cii"{&'i7i"E~ ~1tY
2 11 SUfT\111i t Parkway #1 22
TY!'nST ~.s;:;;;i(...TiNSPEci"EC
Homewood, AL
352 09
Pr o d ucer o f S t er ile Druq Prod ucts
O BSE RVATION 10
Procedures describing the handling of all written and oral comp laints regardi ng a drug produc t are not followed. Spec ifically, the procedure "Inquiry/Complaint Handling and Reporting" #SO P-CAPS-40002 17 effec tive 812 512012, section 4.5 7, was nOI followed for a comptainr invol ving a Cardioplegia prod uct in that a sample of the prod uct was returned for assay, but no analysis wa s conducted on the product
O BS ERVATIO N 11
The establishment of laboratory control mechanisms including any changes thereto, are no t drafted by the appropriate organ izational unit. Specifically, on a basis samples of pos itive growth from air bioburden, fingertip touch plates, su rface contact plates or slee ve cover bioburden touch plates are sent to _ There is no wruren proc edure describing the packag ing and shipment o f these samples to ma intain sample integrity.
OBSE RVATION 12
,
Reserve samples for drug products are not retained for one year after the expir ation dale o f the drug product. Specifically, the firm fai ls to retain and store rese rve samples for each lot o f aseptically processed sterile drug product it distributes.
e"'.....O vuISI6..NAT\IIlE
SEE REVERSE OF THI S PAGE

FORM FDA 'I l (0 9101)
Mar ie P .. fadden, Co n s umer Sa f e t y OW Pa u l C. Mo uris, In v e s t igato r
ce'l(Yj ti.W.- 'i-. J J f"'-1 C ,~-
a .
OATt"lSsUEO
03/07 /2013
PAGE . Of .
P .~GES
""",..cu, EDIT'ON0Il""'-Fr!'
I ~ S PE CT I 0";A I.
OBSf:R VA T IONS

FOOD AND DRUG ADMrNlSTRATION
0.0
O F II"S
300 Ri ver P lace , Sui te 59 00
0 3/0 4 /20 13 - 0 3 /0 6/ 201 3

'0
De t roi t , M I
482 07
Fa x ; (3 13) 393-8 1 39
(3 13 ) 39 3- 8 100
30 02 65232 6
I ndus try Information: www . fda .gov/ oc / i ndus t r y

TO : Lawrence D. Curtis , RPh . , Vi ce Presiden t/Co-Owner I nc .
7 9 66 Lovers Lane
P r o d u c er o f Steri le Dr ug Produc t s
Po r t a ge Pharmac
Po r t a g e , MI
4900 2
This document lists observatices made by the FDA repreSl:Il1l:ttive(s) during the inspection of your faeiliLy. They ace inspecticnal observations, and do notrepresent a fInal Agenc)' dotermilllltioo regarding your compliance. !f yau have anobjection regarding an observation, or have implemented, or plan to implement, corrective action in response m an observlltion, you ITIllYW llCUSSthe objectionor ectice with the FDA representatlve(s) during theinspection orsubmit !his infOl1Jllltionto FDA at the address above. If yonhave any questions. please contact FDA at the phone number and address above.
DURING AN WSPECTIOM OF YOUR FtRM WE OBSERVED:
OBSERVATION 1
Proceduresdesigned to prevent microbiological contaminatio n of drug products purporting to be sterile are not established.
written, and followed.
Specifically.
a-Sterilizi~used in~f injectable drugs formulated from non-sterile components (including Chorionic Gonadotro~able. ~hme. and TriMix) were observed to have not been tested quantitatively. in determ ~
tnt
it}' of the
steril izin~ use (qualitative/tactile measure only). On 3/04/2013 we observed the use 0 _ _ uring aseptic processing of injectable products including Chorionic Gonadotropin (HCG) 8000Ul&ml lot 030413.
b-Th~Steril ization cycle for Hydroxyprogesterone Caproate 25Dmg1rnl (formulated from non-sterile components) was ~istent with routine processing instructions on the batch worksheet. For example, as shown on the Hvdro esrerone Caproate1SOmgImllnjectable w orksheet, the _ erilization cycle instruction is! I I I which is less time then that performed in the last qu 1 lea Ion (a verification). The last recor e qualification (a verification) utilizing a Biological Indicator was dated 10/20 1I with the following documente
run parameters:
TIME
Noon
154 pm 2:IS pm 4:08 pm
s pm
The Biological Indicator is a stand alone culture set that is not directly innoculated into product. Hydroxyprogesterone
Caproate 25Omg!ml Injectable lot 02 13131processed in this same ~as recorded with the following cycle
run parameter data:
Reb e c c a E. Dombrows ki, Inve st i ga t or Russ e l l K. Ri ley, I nve sti gato r
V IA.M
!t
1d So b
<
03/0 6/20 13
PAGE I OF 1 PAG1!
INSPECfIONAL OBSERVATIONS
DEPARTMLVf OF H'EALTH AND Hl.JMA}f S~

FOOD AND DRlJO ADMINJ STRArnl
_ . ~
....ElS'l0l"
300 River Pl a ce , sui te 5 900 Det ro it, 482 0 7 ( 3 1 3) 3 9 3 - 8 10 0 r ax : (3 13 ) 3 93 - 8139 I ndus t r v I nforma t i on: www. f da. qov/ oc / i ndus t r y
03 /0 4120 13
~
'"
300 2 6 52326
03/ 0 6/20 13
-'" run.In'.
~
TO:
Lawrence D. Cu r t i s , Rpn . , Vice Pre s i dent/Co-Owner

~
Portage
Pha ~a c y
Inc.
7966 Love r s Lane

~ E.ST"''',,~
art. IT"'~ ~ ~ 0ClUI<Tlt'I'
Porta ge ,
49002
Producer o f St e r i l e Drug Produc t s
Time Ou
~ record supporting the use of the SI with each batch offortrtllated product Aerili zed wi thin ~
noI always indicated. The: resahs oflhe incu bation of the- same after the steriliutkm cycle are so not always recorded. For example, Hydroxyprog esterone Ceproete 250mglml Injmable lot 0213131 was pro cessed in the In 2113/13. No record supporting the use ora BI in this load. and the results of the incubation ofthe same" were provtded.
c- Written procedure SOP 8.020, Biological Indicators, Version 1.0 details the use ofBiologic-a1 Indicat ors (SQ in the
d- The finn',
rso 5 smoke studies are deficie nt as follows:

SO 5 hoods.
i. The firm ha.s no video recording ofsmoke studies ha vi ng been performed on i.
ii. The only evidence ofa smoke study having been performed wa s a notation in a certification repo rt provided by yo ur cleanroom certitkation vendor and this not ation o nly pertained 10 one of ~SO 5 hoods. iii. The smoke studies were performed only in static conditions .
OBSERVAllON 2
Batch productioo and control- records do no! include in-process results fur each batch of drug product produced.
Specifically, The dorom<ntBlion Of th, - ,eru; " ' < ! r oxyprogeueron. Caproate 25!Jmglml Injectable consists only of handwritten stan and stop rimes and the at those tim es. For ecampte.Jce 0213 13L
OBSERVATION 3
Aseptic processing areas an"de ficient regatdiog the system for monitoring environment al conditions. Specifically,

J!1)il.\ f 1'0" <lQ (ftW
Rebecca E. Dombrows ki , Inves t iga t or Russe ll K. Riley , I nvest igator

... ~ Yl<I1!l.mlOIlO!lSCllJl'n
~~-
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1-29
llA~'$iiUED
0 3/0 6/2 0 13
PMiE 201'H".o.QES
INSP ECfIONAL OBSER'VATIONS
DEPARTMENT OF HEALm AND HUMAN SERVICES

FOOD AND DRUGADMINISTRATION
DISTRICT ADDRESSAND PHONENUMBER
OATE(S) OF"INSPECTlON
Detroi t, MI
NAME AND
3 00 Ri ver P l a c e , Suite 59 0 0 48 2 07 ( 3 13) 393 - 8 100 Fax : (3 13) 393- 8 139
0 3 / 0 4/ 2 0 13 - 0 3/06/2013
FE NUMBER
3 00265 2 326
I ndu s t r y Informat ion : www. f da . gov/ oc / i ndu s t r y

r ms OF lNOl\llDUAL TO WHOM REPORT ISSUED
TO :
FlRMNAME
Lawrence D. Curt is , RPh . , Vice Pres i dent / Co -Owner

STREET A{)()FtESS
Portage Pharmacy I nc .
CTY, STAn:. ZIP CODE,CClllHl1iY
79 66 Lovers Lane
TYPEESTA8U&iMENTIMSPECTED
Porta ge , MI
4 90 02
Produce r o f Ste ri le Drug Produc ts
Environmental monitoring ofthe ISO 5 hoods does not occur each time a sterile drug is formulated therein. For example, during processing of Chorionic Gonadotropin (BCG) 2000Ulmi Injectable lot 0304 130 on 3/0412013, no environmental monitoring was observed . In addition, personnel monitoring of aseptic processing employee was also not performed on this same day.
OBSERVATION 4
Clothing of personnel engaged in the processing of drug products is not appropriate for the duties they perfonn. Specifically,
a-Observed gowning on personnel in the ISO 7 space working at the ISO 5 hood was found to include a non-sterile bouffant cap, a non-sterile face mask, and a non-sterile gown. The gloves donned for use in this same space were found labeled as sterile, howeve r the stock supply in the gowning room was found to contain at least one unit that had expired 1/Z013. Chorionic Gonadotropin (BCG) 2000U/mi Injectable lot 0304130 was asepticall y processed on 3/0412013 . b-During cleaning ofthe ISO 7 area on the morning ofJ /05/Z013, an emplo yee was observed wearing the specified clean room garb, however, was noted wearing shorts, exposing a portion of her lower legs. Chorionic Gonadotropin 5000U/Smi Injectable lot 030513F was aseptically processed at the ISO 5 hood within this ISO 7 space later on this same day.
OBSERVATION 5
The operations relating to the processing of penicillin are not performed in facilities separate from those used for other drug products for human use. Specifically,
Cephalosporin drug products are formulated in the same Cleanroom space used for processing other sterile drug products, and written procedures for the separation of operations for cephalosporin drug products from other human drug products were not provided . For example, on 3/01/2013 Cefazolin 50mglml Sterile Ophthalmic, was processed as lot # 030 113E. That same day, Morphine PF 50mWml.Iniectable lot 0301 13J was also processed .
OBSERVATION 6
Each batch of drug product purporting to be sterile is not laboratory tested to determine conformance to such requirements. Specifically,
E~ovet:.fS)
SIGNATlJRE

FORMFDA40(OW08}
Reb e c ca E. Dombrowski , Inves tigator Russell K. Riley , Investigat or

PREVI OUS !DlTIONOIlSOLiTE
fl.-l~
PD
DATE ISSUED
03/06/ 20 1 3
PAGE 3 OF 7 PAGES
INSPE CrIONAL OBSERVATIONS
~ ~,, _
...
_.
DIPAR'I'MEI'\ "T OF HF.ALnt. A."'DHUM4N SERVlCES FOOD!\.\ffl DRUOADMINU 1TRAn ON
300 River Pl ace, Sui te 590 0 Det ro it , HI 4 82 0 7 (31 3 ) 393 -8100 Fa x : (313) 393-8 139 Indus try Informati on : ~~ .fd a .g ov / o c/i nd ost~ y
~~ -
~"'"
1 ~ "P'l'(;T"
03/ 04/2013
TO:
-~~
La wrence D. c ur ti s , RPh . , Vi ce ?resident / Co-Cwner

ST'lfFT A, DllO:S6
'300 ~2 6 52326
- 03 /0 6/ 20 13
Portage Pharmacy I nc .
aTY, srA,,,,, ZPo:JlJII:. O;(;lJN T1Il
7 9 6fi Love r s Lan e

"""" 1!lJf~
""'""EI:TEl>
Portage , HI
49 OC2
Produce r o f Ste rile Drug Produc t s
a, Human Chorionic Gonadotropin Injection 5000U/ 5ml lot 02111 J E. produced 211112013. was released but was DOt tested for endotoxins . b. TriMix (PapaverinelPhentolaminelProstaglandin E l Injection 30mgfO,5mgl201n.c&'ml) lot 02 1J 13B, produced 211112013,
was released but was not: tested for eedotccns.

c . Hydroxyprogesterone' Injection 25OmW5ml101 02 13131, produced 2/13120 13, was released but was not: tested for endctcxins.
OBSERVATION 9
The ~li5hment oftest procedures includin g any changes thereto, are not drafted by the ap propria te organitational unit .
Specifically,
There is no procedure describing bowto perform growth promotion testing o n media. used duri na media fill s For example, during a media fill conducted on 10/412011. growth promotion testing was performed by sterilf!lll!!!!!!l ilrtO a vial and incu~ it no microorganisms were added, When the vial was d ear after inaJbarion. the grow promotion was marked as havi ng passed.
OBSERVATION 10
An adequate number ofbatcltes of each chug product are not tested to determine an appropriate expiration date.
Specifically, The finn has not tested of its products to assess their stab ility in support of 1heir assigned expiration periods. Fo r examp le, MethyloobalamiD Preserved Injection Imw'mJ that the fum has produced has not been stability tested. Instead, the firm reiies o n a document published by a separate organization, however: a. The document does not contain data ; it simply describes ho w to produce the drug and esti mates its expiration period b. The document only addresses potency; it does not add ress sterility o r endvtOJl:imi,
an
c. Th e fonrol. in the docllwerrt is different than Portage Pharmacy's formula

d . The concentration of the produe:t in the document is different than Portage Pharmacy's product ,
~_T.,IiIi

_M)IIlA, .-J _
Reb e cca E. Do!Lb:oowsk i , Inve s tiga t o r Rus s e ll K. Riley, I nv e st i qa ~o r

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0 3/0 6 /2 01 3
I'AO~S 0l' 1 PI\oGU
lNSPECTIONALOBSERVATIONS
iN~ JJb'ri=
300 Ri ve r Place , Su i t e 590 0 Det r o i t , MI 482 07 ( 313 ) 393 -8100 Fa x : (3 131 39 3-8139 I ndu5t r~ In fo ~ t1 on : www . f da. qov / o c / i ndus t r y
"6lIiilU ..... TO ~
_. -
Dt:P.o\R'I'MENT OF HEAl.TH AND HUMAN SI.RVK'l.S FOOD ANDDRUGADMINISTRA TION

~ ~~
03/0 4/ 20 13 - 03 / 06/ 2013

~-
3 00 2652 32 6
-TO:
-.eo
Lawr e nce D. cur t i.s , RPh . , Vi c e

lPeoD!!.
Pr e s id e n~/Co -OWn e r
Po r t a ge Pha rmac y I nc .
.~.
79 66 Le ver s Lane
~Llif""'_
Po r t age, MI
4 90 02
Pr o duc e r o f Ster ile Drug Product s
OBSERVA TION 11
Results of stability testing are not used in determining expiration dates. Specifically, Stability testing ofthe firm's products does not always support assigned expiration periods. For example, a. The stability data for TriMix (PapaverineIPbentolamineiProstaglandin E l Injection J OmglO.5mg/2Omcglml) is deficiem as follows:
i. Stability testing was performa:1 on Prostaglandin 500mg1ml, which is the TriMix product Also, no Papaverine or Phentolamine was present in
hanthal~hjcbisin
e prc u
twas teste
ii. Only potency was tesed. Sterility, ecdctcdn, and preservetive effectiveness wen' not tested.
iii. The stability data only covers 60 days, but the product's expiration period is 90 days.
b. The stability data for Human Cbcrioruc Gonadotropin Injection 5000U/5m1 only coven potency; there is no stability data for sterility or endotoxin.
OBSERVATION 12
Established test procedures are not followed. Specifically, Personnel producing sterile injectable drug produet5from non-sterile components do DOt conduct media fills ~ as required per procedure. For example. only two media fills for the main employee who produces such producta have been conducted, one in the full of2011 and one in the fall of 2012.
OBSERVATION 13 The m;ponsibiliries and procedures applicahle to the quality cont rol unit are not fully followed.
Specifically.
>iii:""'Di:~_

r U in( I"D.\
Rebe c c a E . Dombrows ki , I nves t i ga to r Rus se l l K. Ri l ey , I nve s t i g ato r ,t-jU1...

PUYlO\-'S !IJI'T'IOSO ~l'l'
120
oo.Tl; lti9UEQ
0 3/0 6/20 13
~ M.)f.
oId_'
INSPI; LTIONAL OBSERVAT IONS
6ot' H'A05
DlPAItTMENT OF HEALTH AND HL"M.o\N SDn'lCI:S socc ANDOlU.'G ADNTh1lSTRAnOto:
3 0 0 River Pl ace . Su i t e 590 0 Detroi t , MI 48 2 07 (313 ) 393-B1 00 Fax: (3 13 ) 393 -8139
0 3/ 0 4/20 13 - 03/ CE/ 2013 300 26523 26
I ndu s t r y I nforma t i on : www. f da .gov/ oc / i ndus t r
AND1'l1'l.iOF
"'-
T O:
La wr ence D. Cur t i s , RPh . , Vi ce Pr es ident / Co-Owner

796 6 Lovers Lane
Porta e Pha rmacy Inc . Po r t a ge , MI 49002
Produc e r o f S teri l e Drug Pr o duct s
ion 1.0, is not always followed in that section is not performed (not documented). For vrsue mspecuoe or Hy drexyprcgesterone Caproate 250mg1ml lnjectable
OBSERVATION 14
Records associated with drug product production and control and within the retention period for such records, were not made readily available for authorized inspection. Specifically,
The firm ccutd not provide records of tM most recent media fill, which purportedly OCCUfTed in the fall of 20 12. Retention of such records is required per procedure.
Reb e c c a E. Dombr ows ki , I nvest i gat or Ru s ~ ell K. Riley , Inv es tigato r ~
,
{( ~
0 3/0 612 0 13
I:"riSPE CT IO NAL OBSE RVA110NS
[)[ PAR1-MEr"o' O F II AI.1'1I A ~D

AIlDfOESS,OJC} _
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SF R\ 'ICES
~nm
...-ll
FOOO ,o.ND DRUG ADMINISTRATION
404 0 North Centra l Expres s wa y , S u i te 300 Da lla s , TX 1 520 4 ( 2 14 ) 25 3 -52 0 0 Fax : ( 2 14) 2 5 3- 5 314 I ndust rv Informat i on : www . fda _g o v / o c / i nd u s tr v
02 /2 5/20 1 3 301 00 54 2 6 8
- 03/01/2 0 1 3 --
-TO :
_~ muOf' ~
~_m
Jo h n R. Ca rs o n , Presid ent -CEO
Home Int ens i v e Care Pharma c y , I nc .

Sf...'TE.ZPCOOE.c:cun....
722 0 Lo u is Pasteu r Dr i ve Suite 168

~
Sa n An t o n i o , TX
182 29
Produce r o f S te r ile Dr u a Prod u c t s
This document lists observations made by the FDA representativets) during the inspection of your facility. They are inspectional observations, and do not represent a final Agency determination regarding your compliance. If you have an objection regarding an observation. or have implemented. or plan to implement, corrective action in response to an observation, you may discuss the objection or action with the FDA representetivets) during the inspection or submit this information to FDA at the address above. If you have any questions, please contact FDA at the phone number and address above.
DURING AN INSPE CTION OF YOUR FIRM WE OBS ERVED:
OBSERVATION 1 Procedures designed to preven t microbiological contaminatioo of dru g produ cts purporting to be sterile are not written and followed. Spec ifically, your linn does not have wri tten procedures describing bow aseptic operations are perfonned in ISO 5 and ISO 7 classified areas . 1 1 I pharm acist from yo ur facility wearing a non -sterile lint-free labcoat rested his elbows on the benchtop On 212511 of one-of ISO 5 lam inar air-flow hoods while preparing an order for Morphine'Bupiveca ine, an intrathecal medication used for pain pump steri le administration. On 2125110 13, a phannacist from your facility had an approximate 1 inch -to-z inch gap in coverage from his non-sterile lint free labcoat sleeves and his sterile glo ves while perform ing aseptic filling of the same MorphinefBupivaca ine order. Exposed skin from his forearm was visible while he was work ing inside the ISO 5 lam inar air -flow hood.
OBSERVATION 2 Clothing of perso nnel engage d in the processing of drug produ cts is not appropr iate for the duties they per fo rm. ,ISO 7, and ISO 5 classified areas Spec ifica lly, you r linn's go wning req uireme nts described for operators work ing in ISO X include a single pair o f sterile gloves , a s ingle pair of non -ster ile shoe covers, a single non-ste rile lint-free lab coa t, a single hair net, and a sing le ear-loop face mas k. Your firm doe s not have a written proced ure descri bing the go wning requ irem ents for asept ic operations perfonned in classi fied areas of yo ur facil ity. On 2125/20 13, a pharm acist from yo ur finn was performing ase ptic filling of Mo rph ine/B upivacaine Injecti on inside the ISO 5 lam inar air-flow hood wearing the garments described abo...'e. Exposed skin was observed around the eyes, fore head, and neck for operators processing a sterile drug.
,
t - .OYUlIl_T\.IlE

!'OM'>! YIH 4.J C"IOS1
Ch ris top he r D. Lea ch , Inves t igat or Lu ca s B , Lea ke , I n v est i g ato r

_vn,o; El>IT1Ol'I 0l<Sl:tJm;
I :'Ii SN;Cn O~ AL
('~
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~~
03/0 1/2013
"~Gr,
OBSERVAT IO.'liS
1 Of' "~r,,,~
DE PA RTM E ~ T O~'
H EALTH A:"'D H UM A.... SERV I CES FOOD AND DRUGADMINISTRATION

CATEIS) OF lNSf'ECTroN
40 40 North Centra l Ex p r essway , Su i t e 30 0 Dall a s . TX 75204 (2 14) 2 53- 5200 Fax: (2 1 4 ) 2 53 - 5314 Indust r y Info rma ti o n : www .f d a .gov/oc/ indus t ry TO:
FIRM"""'E
02 /25/ 2013 -
03 /01/ 20 13*
301005 4268
J ohn R . Carson, Pr e s ide n t - CEO

smEEl .o.ooRESS
Home I n t e n s i v e Ca re Pha rmacy , San Ant on i o , TX 78229
I n c.
72 20 Lo u i s Past e ur Dr ive Su ite 1 6 8 Produce r o f St e r i l e Dr u Pr o d u c t s
OBSERVATIO N 3 Separate or defined areas to prevent contamination or mix-ups are deficient regarding operations related to aseptic processing of drug prod ucts. Speci fically, your firm has not evaluated the composition of equipment contact surfaces or the facility layout in order to prevent the contamination of ISO 5, ISO 7, and ISO 8 classified areas used in the production of sterile drug products. You_ ISO 5 laminar airflow hood workbenches are constructed from particle board with a laminated surface on whic~rug prod ucts are aseptically filled. This was confirmed by your firm's Chief of Staff on 2126/20 13. The smoke study conducted by a contracted testing laboratory on December 18th, 20 12 for the IS0-5 laminar air-flow hood was not performed during dynam ic co nditions. The pressure difTerential limits tested by a contracted testing laboratory on December l Sth, 20 12 for the ISO 5 laminar air-flow hood, the ISO 7 area, and the ISO 8 ANTE room were only tested in static conditions. These pressure limits between classified rooms are not actively monitored by your finn during normal operating conditions according to your . Your finn has not set limits for pressure differentials between the ISO 7 and ISO 8 classified areas, firm's Chief of StafT and during aseptic processing on 2125120 13 it was observed that the pressure read ings of the ISO 7 cleanroom and the adjacent ISO 8 ANTE room showed no apparent difference. A spacial gap was observed on 2125120 13 in the doorway between the ISO 7 cleanroom and ISO 8 ANTE room while an operator was processing a sterile drug product.
OBSERVATION 4 Aseptic processing areas are deficient regarding the system for cleaning and disinfecting the room and equipment to produce aseptic conditions.
Doo.TE' SSl.IED

FO il :\! fD A . 01 (lI'O,'\lO)
Chris t opher D. Le ach , I n v e sti g a t o r Luca s B. Le a ke , I n v e s t i g at o r
it-
03/01/ 201 3
I'AOF 10F 41'AGES
PREVIOUS EDmoNOBSOI.,,",
I:\iSr ECT IO :'llAL OBSERVAT IO ro;S
UU'AKT.\It:NT OF IIEAI ,Tlt

DlST ~1CT
A~U
HUMA!'i St:KV ICt:S

OA~) Of' IN~1OI'l
"OOAess ~ N D _
FOO D AND DR UG AD MINISTRATION

"",,,BE,,
40 4 0 No r t h Central Expr-e s swa y , Suite 3 00 Dal l a s . TX 7520 4 (2 1 4 ) 2 5 3 - 5 2 0 0 Fax : (214) 253 -5 3 14 I ndu s t ry I n f o r mati o n : www.fda .gov/ oc/industry
......e.<NO mu; Of' K>I\II DVAi. TO ""101oI R:l:PORlOS WEO
02/2 5 /20 13
FE' tIlJ"'BE R
0 3 /0 1/20 13 *
3010 0 5 42 6 8
TO :
f ,R"' NAAIE
J o h n R. Carson , Pr e sid e n t CEO

S TREeT .lOORESS
Home I n t e n s ive Ca re Ph a r ma c y , I nc .
CITY, STATE, ZIP C<XJE , COUNTRY
72 20 Lo ui s Pasteur Dri ve Su i te 1 68
TY"" lITAllUSHoOENT l""""eTa>
San Anton io , TX
7 82 2 9
Pr odu c e r o f St e ri l e Drug Pro d uct s
OBSERVATION 5
Aseptic processing areas are deficient regarding the system for monitoring env ironmenta l conditions . Specifically, you r finn does not have a wr itten proced ure regard ing the performance of environmental mon itoring of ISO 5 classified areas used to prod uce sterile drug prod ucts. A contrac t testing laboratory performs viable and non-viable monitoring of all ~f thc ISO 5 laminar air-flow hoods during recert ification every ~nly under at rest conditions. The firm has not performed a study in dynamic condit ions. Yo ur finn does not perform environmental mo nitor ing of ISO 5 classified areas outside of the certification evCIJ.
~of sterile
Your finn does not perform any personnel monitoring ofthose operators working in ISO 5 class ified areas during the drug prod ucts . Your firm's pol icy states that personnel monitorin g is only tested during the edia fill qualifications .
OBSERVATION 6
Ther e is no written testing program designed to asse ss the stab ility characteristics o f drug products. Specifi cally , your firm has no written procedure or protocol to de fine how extending the beyon d use date of intrathecal drug products from 24 hours to 30 days is validated and what specifi cations must be met in a sta bility protocol. Additionally, your firm's mana geme nt stated that 80% of all compounded dru g products are labeled w ith extended beyond use dates. Your finn's pharmacy manage r stated that anti-microbial effectiveness testing is not performed by your contract testing laboratory for stability tests of sterile drug products conta ining preservatives to s upport your labeled Beyond Use Dates. Stability testing in supp ort of extended beyo nd use dating for intrathecal drug produ cts was incons istent and does not always include sterility testing. a) Stability results dated 2/ 1120 13 for extended beyond use dates for Bupivac aine ImglmL IN PF NS (lot # 0 11620 13- REG) inclu ded data for potency/p urity, endotoxin, sterility, and particulate matter. b) Stability results dated I127f20 12 for extended beyond use dates for Bup ivacaine 5 mg/m bi n NaCI (lot # 1442363n) included data for potency/pur ity. c) S tab ilitY I:~su lts dated 11/ 17/20 Il for extend ed beyond use dates for Fentany l 50 mcg/m l PF lnj. (lot # Hlc 10121 1\ me included data for ootencwour lrv.
OBSERVATION 7
Procedures design ed to prevent microbiological contamination of drug products purpo rting to be sterile do not include adeq uate validation of the sterilization proce ss. Spec ifically, your firm's media fill val idations conducted for each pharmacist performing ase ptic operations do not include all
E"'PlOYEE(S) s lG.....TvRE

~'ORM .'D ~
Chris t opher D. Leach , I n v e s t i g a t or Lucas B. Le a ke , I n v e s t i g a t o r
C --
I~~D
/.-L
03/ 01/20 13
PAG E J OF 4 P.o.G ES
ollJ (l''J/03)
""""'Ol'" FDIT\Of< OOSOlETE
I:"SPECTI Ol'o:AL ORSER VATIO~S
DEPARTM El'iT OF il EALTi l A~D II mIA~ SERVICE:.'i FOOD AND DRUG AD MINlS TRATlON
O<S Tf'ICT AOOl\:lS AND P>lONE ....... BEI< c,o,Tl'(S) Of' INSPl'C 1lON
40 4 0 Nort h Centra l Expre s sw a y , Su i te 300 Dal la s , TX 7 5204 (2 14) 25 3-5 20 0 Fax : (2 14) 253- 531 4 I nd u s t r y Info rmation : www . fda .gov/ o c /in du s t r y TO: John R. Ca rso n , Preside n t-CEO
02 /25 /20 13 - 03/0 1/ 20 13
301005 4 2 68
Home I n t e n s i v e Car e Ph a r macy , I nc,

CITY , ST ~ TE ,2 IP C(lDI; _ ~
7220 Loui s Pa st eur Dr i v e Su ite 1 68

TYPE EST""'--I SH.IEN ' NSf'ECTEO
San Ant onio , TX
76229
Produ ce r of Steri le Drug Pr o ducts
sources of potential contamination typ ical ofnonnal operating conditions. Your firm's li
our me ra I po ICy ocs not a ress t e use 0 synnges as e mrs e g pr ucr container, and it docs not include all typical manipulations that occur under normal operating conditions--for example the opening and closing of doors between ISO 7 and ISO 8 classified areas during aseptic operations. On 2/22120 13 your finn filled an order for . bags of Magnesium Sulfate Igm in IOOmL Dextrose 5% with a Beyond Use Date of 512312013, lot # HIC022213lDC. Operat ions to include the production of sterile infusion bags are not assessed in your current media fill validations. On 21221201 3 you finn filled an order fo~yringes of Phenylephrine O.4mg/mL-single use ( IOmL) with a Beyond Use Date of 5/23120 13, lot # HIC0222 13-3DC. Operations to include the production of sterile syringes and a production volume of_ individual units are not assessed in your current media fill validations.
* DATES
0 . I NSP ECTION :
02l25fl0 13(Mon), 0212612013(Tue), 02fl 7f2013(Wed), 03/UlflOI3(J'ri)
oos tSSUEO
SEE REVER SE OF THI S PAGE
Chris toph e r D. Leach , Inve stig ator ~ ~ Lu ca s B. Le ake , I n v e s t i g a t o . r .:= ~

I)'Ii SP.Lefl()~AL
03/0 1/2013
PAGE . OF ' PAGES
OBSt:RVAT10JliS
Dt:P.\ . RT\ IL"U ( U U A LT it '\.' D IIl \l",' S[R \ IU:S

FOOD A..'II) DRUG ADM!l'<o1STllAl'lOS
4040 Nor t h Central Expre s s way , Su it e 30 0 Dal l a s , TX 1520 4 (214) 253- 5200 Fa x : (2 14 ) 253 - 5314 Indus try I nfo r mation : www . f da. g ov / oc / i ndustr
TO :
02/2 5/20 1 3 -
03/0 1/20 1 3
300 44 91213
John R. Ca r s on , Pre sident - CEO 122 0 Louis Pa st e ur Dr Ste 176 Produce r o f St e r i l e Dru Pr oducts
Oa Kde ll Pha rma c , I n c San Antoni o , TX 18 22 9- 4535
This document listsobservations made by theIDA represcntativets) during the inspectionof )'OlIr facility. They are inspectional observations. and do not represent a final Agency determination regarding your compliance. If )-oo have an objection regarding an observ ance, IX have implemented, or plan 10 implement. corrective action in response to an ob servance, you may discuss the objection or act ion with the FDA rcpresentativcts) duringthe inspection or submit this information to FDA at the address above. If you have any questions. please contact rDA at the phone number and address above.
DURING AN INSPECTION OF YOUR FIRM WE OBSERVED:
OBSERVATION 1 Procedures designed to prevent microbiological contamination of drug products purporting to be sterile are not written and followed. Specifically. your finn does not have written procedures describing how aseptic operations are performed in ISO S and ISO 7 classified areas. On 2/26120 13. a pharmaci s~ring an order for Vancomycin Ophthalmic drops 2Smg/mL ( IO mL) did not sanitize gloves w itl~ ach time he was observed carrying components from the ISO 8 classified area through the ISO 1 classified area into the ISO S classified laminar air-flow hood. On 2f26!20 13. a phannacist from your facility wearing a non-sterile lint-free labcoat rested his elbows on the benchtop of the ISO S laminar air-flow hood while performing aseptic manipulations of the same Vancomycin Ophthalmic drops 2SmglmL ( IOmL). On 2fl6!20 13. a harmacist from your facilit v shook a vial of in-process dru g componenl sxpirarion Jan. I, 201S), for the purpose of homogenizing the vial e ISO S laminar air-flow hood. OBSERVATION 2 Clothing of personnel engaged in the processing of drug products is nO I appropriate for the duties they perform. Spe cifically, your finn's gown ing requirements described for operators working in ISO 8, ISO 7, and ISO S classified areas include a single pair of sterile gloves, a single pair of non-sterile shoe covers, a single non-sterile lint-free lab coats, a single hair net, and a single ear-loop face mask. Your finn does not have a written procedure describing the gowning requirements for aseptic operations perfonned in classified areas of your facility. On 2fl6120 13. a pharmacist from your finn was performing sterile drug processing of Vancomycin Ophthamlmic drops 2SmglmL ( IOmL)inside the ISO 5 laminar air-flow hood wearing the garm ents described above, Exposed skin was observed around the eyes, forehead, and neck for operators processing a sterile drug.
SEE REV ERSE
OF THIS PAGE
Ch r i s tophe r D. Le a ch, I nves t igat or Luca s B. Le ake , Investi gator

I NSP UTI ()~A I.
0 3/0 1/20 13
O R"'[ R\ 'A T IO ~'"
UU'AK"I .\I l xr O ~ II l ALTII A. ' D m 'M"".; S ~; R\ I Ct:s FOOD AND DRUGADMINISTRATIO!"
404 0 North Central Expressway, Suite 300 Da llas , TX 7 52 0 4 (2 14) 253-5 200 Fa x : (2 14) 2 5 3 - 5 314 I n dustry Inf orma t ion : www . fda . g o v ! o c ! i nd u s tr y TO: John R. Ca r son , Preside n t -CEO
02 /25 /201 3 -
0 3/0 1/ 20 1 3 ~
30 0 4 497213
Oa kd e l l Ph armac , I nc
CITY, ST~ TE , lIP COOl! . COUNTRY
722 0 Lo u i s Pa s t e u r Dr St e 17 6 Pr o du cer o f St e ri l e Dr u Pr o d u cts
San Ant o n i o , TX
78 2 2 9-4 53 5
OBSERVATION 3
Separate or defined areas to prevent co ntam ination or mix-u ps are deficient regard ing operations related 10 aseptic proc essing of drug prod ucts. Specifically, yOUT firm has not eva luated the composition of equipment contact surfaces or the facility layout in orde r to prevent the contam ination ofiSO 5, ISO 7, and ISO 8 class ified areas used in the production of steri le dru g products. Your ISO 5 laminar air-flow hood workbench is construct ed from part icle board with a laminated surface on whic h sterile drug products are aseptically filled. This was co nfirmed by you r firm's Ch ief of Sta ff on 2/26120 13. You r facility has a sink used for hand washing located in the ISO 8 classified area adjacent from the ISO 7 classified area inside which the ISO 5 laminar air-flow hood is used for aseptic operations of sterile drug prod ucts. The ISO 7 and ISO 8 areas are sepa rated by a non -lock ing, swinging door with a visible gap. The smoke study performed by a contracted testing laboratory in Septembe r, 2012 for the ISO-5 laminar air-flow hood was not performed under dynam ic conditions. The pressure ditT erential limits tested by a co ntracted testing laborato ry in September, 20 12 for the ISO 5 lam inar airflow hood. the ISO 7 area, and the ISO 8 ANTE room were only observed durin g at rest cond itions o f operation . These pressure limits between classifi ed rooms are nor actively monitored by yOUT finn during nonnal opera ting condi tions accordin to our firm's Ch ief of StatT. OBSERVATION 4 Aseptic processing areas are deficient regard ing the system for cleaning and d isinfecting the room and equ ipment to produce ase ptic conditions. Speci ficall y, your firm does not have a wr itten procedure describi ng the rotation of cleaning agents and sporacides used to disinfect the ISO 5 laminar air-flow hood , the ISO 7 class ified area, or the ISO 8 ANTE room. Yo ur finn did not document an eva luation ofthe effectiveness 0 used in rotation as the exclusive cleaning agents on the equipment contact surface o f the ISO 5 laminar air-flow hood workbe nch. These prod ucts were obse rved in use on 2/26/20 13, and they were ob served in storage in the ISO 8 classified ANTE roo m. You r _ nOI docurr nt an evaluation ofthe effective ness of ised in rotatio n as clean ing agents on the walls and floors of the ISO 7 classified areas and the ISO 8 classified areas . These roduets were observed in stora e in the ISO 8 classified ANTE room . OBSERVATION 5 Asept ic processing areas are deficient regarding the system for mon itoring environmental conditions. Specifically, your firm does not have a writte n proced ure regarding the perfonnance of environmental monitoring of ISO 5 cla ssified are as during sterile drug processing.
E""'-OYEE(!I) SJa ....
Chr i s t ophe r D. Le a c h , I n ve s t igat or Lu c a s B. Lea ke , I n v e s t i g a t o r ~l--
C5lL03/0 1/20 13
I)t:P AKHI E:H o r IIt ALTII A....O IIl .\IA.... SEK\ ' U :S
f OOD AND DRUG ADMlNISIRATlON
40 40 North Ce nt ral Expre s s wa y , Suite 300 Dall a s , TX 15204 (2 1 4) 253 -5200 Fax : (2 14) 2 53- 5314 Indust ry I nformat i on : www. fda .gov / o c / indus tr
TO :
02/25/20 13 -
03/01/201 3
3004491213
John R . Car s on , Pr esid ent-CEO 1220 Loui s Past eur Dr Ste 116 Produc e r o f Ster i le Dr u
-~
Oa kde1 1 Pharmac Inc

Sa n Anto ni o , TX
1822 9- 453 5
Pr oducts
A contra ct testing la~rfonns viable and no n-viable monitoring of the ISO 5 laminar air-flo w hood during recertification evef)~n ly under at rest conditions. The finn has not performed a study in dynamic conditions. _ doe s not perform environmental mon itoring of ISO 5 classified a reas outs ide of the certification e ve~ Your firm docs not perform any personnel monitori ng ofthose operators working in ISO 5 classified areas during the production of ste rile drug produc ts.. Th e most recent doc ume nted performa nce of "finge rtip" test was performed o n 8/ 15120 12 d urin media flll ualifi cations.
O BSERVATION 6
Th ere is no writte n testing program designed 10 assess the stability characte ristics of drug products. Specifically. although you r firm's ma nagem ent stated on 2fl.6120 13 that approximately 800 A. of com pounded products are given extended beyo nd use dales, your finn has no wri tten procedure to define how extend ing the beyond use date is validated and what spec ifications must be met in a stability protocol. On 212712012 firm management stated that beyond use dates are typic ally ass igned by yo ur linn based on USP recommendations for low risk. medi um risk. and high risk compounded products; however, if exte nded beyond use dates are req uested by customers yo ur firm sends drug product sam ples to a co ntract test ing laboratory for stab ility indicating testing. No wr itten proced ure exists to define sample s ize or what tests are to be perfonned to assess the stabi lity of these dru g produ cts. Yo ur firm's pharmacist stated that anti -microbial effectiveness resting is not perform ed as pan ofyo ur firm's stability rt our labe led B o nd Use Dates. tests on sterile dru roduets co ntainin reservativ es to su
OBS ERVAT ION 7

Procedures designed to prevent microbiological contamination of drug pro ducts purpo rting to be sterile do not include adequate validation of the sterilizatio n process .
Your media fill po licy does nor address the use of syr inges as the fmished dru g prod uct conta iner, and it does nor includ e all typical manipul ations that occur under no-mal operating conditions-fo r example the opening and closing of doors between ISO 7 and ISO 8 classified areas during aseptic ope rations. Media fill validations performed in Au gust, 20 12 were performed according to the , "Em ployee Qualification for Sterile compoU i din l ."i licy. The same po licy states that eac h employee shall be eva luated on his or her designated aseptic process Your firm does not have complete records of all e mployee media fill val idations dating before or after August, .

f OR" fDA UJ/lIMlll )
Ch ristophe r D. Le ach , I nves tig ato r Lucas B. Le ake , I nves tigat or f..,.f....
rx s r t:CT IONA L O RSER\'A T.O~S
03/ 01 / 2013
PAGE l OF . PAGES

DISTRiCT ADDRESS AND PHONE NUMBER DATE(S) OF INSPECTION
4040 North Central Expressway, Suite 300 Dallas, TX 75204 (214) 253-5200 Fax: (214) 253-5314 Industry Information: www.fda.gov/oc/industry
NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT ISSUED
02/25/2013
FEI NUMBER
03/01/2013*
3004497213
TO:
FIRM NAME
John R. Carson, President-CEO

STREET ADDRESS
7220 Louis Pasteur Dr Ste 176

CITY, STATE, ZIP CODE, COUNTRY TYPE ESTABLISHMENT INSPECTED
San Antonio, TX
78229-4535
* DATES OF INSPECTION: 02/25/2013(Mon), 02/26/2013(Tue), 02/27/2013(Wed), 03/01/2013(Fri)
EMPLOYEE(S) SIGNATURE
~.~~~~/
DATE ISSUED

FORM FDA 483 (09/08)
Christopher D. Leach, Investigator Lucas B. Leake, Investigator

PREVIOUS EDITION OBSOLETE
~------~
-~
03/01/2013
PAGE 4 OF 4 PAGES
INSPECTIONAL OBSERVATIONS
DCS11IlCT4lXlRE
.,.......elM REP'ORTISSlJW
DEPARTM ENT OF IlEALTH AlIiD HUMAN SERVICES FOOD AND DRUG ADMIN ISTRATION
OAnm r:1F Il-ISPECTJOH
60 Ei g h th Stree t NE At l ant a , G A 30309 Fa x : ( 4 0 4) 2 53 - 1202 (4 0 4 ) 2 53 -11 61 , I ndu st r v In format io n: www.fda .gov /oc / industry
- . . ANtlTlTI.E O~ IN DMllV......
02/19/2013 - 03/0112 0 13
FEI ~""Ile .
30 0 4969894
",,Ca r
TO :
Da n n y Ba r n e s,
Tr i angl e Coit\poun ding

ClTY, .n"Tl.llP
_.
.
Ph arm D
Pharmac ist I n Ch~ r ae /Owne r

$TIl:!~ T~ .~"
5 5 0 ' Ne w W averl y Pi Ste 11 0

~t .n "" _",,, ,_ C ~
C N
2 7~1l- 7 4 .1 2 .
P r o du c ~ rs
of S.teri le. Dr ).1.q Pr-odu c t;
This document lists observations made by the FDA represcntative(s) during the inspection of your facility. They are inspectional observations, and do not represent a tinal Ag~cy determination regarding your compliance. If you have an objectlcn regarding an observation. or have implemented. or plan to implement, corrective action in response to an observation, you may discuss the objection or action withthe FDA represenlative(s) during the inspection or submit this infonnation to FDA at tne eddress above, If you have any questions. please contact FDA at the phone ~umbet and address above.
DURING AN INSPECTION OF YOUR FIRMWE OBSERVED;
OBSERVATION 1
.
,
There is a failure 10 thoroughly rev iew any une xplained discrepancy and the failure of a balch or any of its component s to meet any of its specifications whether or not the batch has been already d istributed.
Specifically,
Investigations into sterility failures reported by the finn for Sodium Bicarb onate 8.4% PF Inj (4/5/12) and Avastin 2.5 mg Lot# 777 I I-LG4973(10127/ 12) and #80623-LG4973 ( 10120/ 12) are not supported by data in order to substantiate the finn's reported actions o f re-testing samples in order to release the lot from quarantine status and make them available for use. Initial reported sterility failures were not attri buted to laboratory error or to sample handling, but additional samples were retested to determine that the batch was sterile without determination o f root cause for the failure or full documentation of the investigation process. Avastin LOt 777 I I ~LG4973 and Sodium Bicarbonate Lot 11 035-29 were subsequently distributed. , Furthermore, a form al procedure for handling out of specification tests results or non-conforming tests is not available. Policies in place for "Outside Lab Testing, 6.080", and "Skip Lot Random COA Testing, 6.070", include provisions for the evaluati on ~f a compound not meeting expected parameters, but include actions such as re-tests, modification of compounding areas or alteration of storing/shipping condition s to address failure s on tests.: Root cause determination is not required by the policies in place to ensure adequac y of correcti ve/preventive actions or full docume ntation of such ; activities.
,
! i
EIolFUlVE[($) Ill....

FORM fIl" 413 .......,
Bo n it a ' S Ch este r, Investig a tor "~ No r e e n M u n iz , I n v e s t i g at o r

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,U :.!. (fj_
Ll
v~
I" SPEctIOS AL OBsE RVAn O NS
--
lSSueJJ
-,
03 / 0 1 /2 0 13
P" GE 1 OF6 P"GES
DEPARTMENT OF HEALTII
A~ D
HUMA....SERVI CES
0 2/ 1 9/ 20 1 ~
r OOD AND DRUG ADMINlSlRAT1 0N
60 'Ei ght h St reet NE At lant a, GA 3030 9 (40 4) 253 -116 1 Fa x : (4 0 4) 2 5 3- 120 2 Indust r y I nf o rma t i on: www. fda . gov l ocI indus t ry' TO :
- 0 3/Q 1/ 20 l 3
300 49 69894
D a nn y Barnes, Pharm D. , Pha r ma c is t In Cha r e/Owner 550 ' N ew W aver ly Pl - St e 110 Pr oducers of St e ri l e Dr ug Pr od uct
Tr iangle Com po und i ng

C ~ry ,
NC
275 11- 7412
OBSERVATION 2
Procedures designed to prevent microbiological contamination o{drug products purporting to be sterile do not include validation oflhe sterilization process.
Specifically,
a. Sterilization cycles executed on the for products and instruments during routine processing have not been validated to ensure that the cycles are capable of producing sterile products. For example. the following products sterilized in t h e _: Bupivicaine For Compounding 30mglml; Cyclosporine Ophth 0.5% Suspension. Triamcinolone Hexacetonide 3mg/rnJ injectable. Instruments sterilized include small items used during aseptic proce ssing such as spatulas.
are
i
b. Sterilization cycles executed On have not been validated to ensure cycles are capable of produc ing sterile products or instruments and or containers. For example, the following products are st erilized in the : Hydroxyprogesterone Caproate 250mglml injectable, Hydroxyprogesterone Caproate 250mglml PF injectable, and Phenol Oil 5% injectable. Containers sterilized include beakers used during aseptic processing. _
OBSERVATION 3
,
The control systems necessary to prevent contamination or mix,u~s are deficient.
Specifically, your current environonmental program frir monitoring and controlling the ISO 5 clean room areas are inadequate in that : : a. _ Process Simulation Testing conducted'to qualify compounding technicians and aseptic operations are deficient. Simulation tests do not support routine processing operations or evaluate worst case activities that could provide a challenge to manual aseptic operations and present a risk to product sterility (i.e. interventions, representative container/clo sure systems used; maximum personnel, etc) . ' b. ~urface sam pling is not being conducted in areas adjacent to the aseptic processing room, which is also classified as ISO 5.
Boni t a S Che s t e r , Invest iga t o r Nore e n M un iz , I nve s t iga t or

I~SPEcrIO:OO;""L
03/0 1 /20 1 3
OBSERV....TIONS
P,o,GE 2OF ~ PA GES
DEPARTMENT OF ilEALTil A.'D II UMAN SERVICES FOOD ANDDRUG ADMINISTRAT ION

o.oTE(S)OF ..
60 8 ighth St reet N8 At l a n ta , GA 3 0 3 0 9 ( 40 4 ) 253.,.11 61 Fa x: ( 40 4) 2 53 -1 20 2
0 2/ 1 9 / 2 0 1 3 - 03/ 0 1/201 3
Fe l NU..IiEA
3 0 049 6989 4
In dus t r
TO:
I ~form~t iop :
www.fda.gov/ oc /i ndus t r y
Danny Barnes , Pha r m D. , Pbarma ci s t I n CK.a rge/Owner
Tria ng l e Compoundi ng
,.
55 0
Ne~
W a ve r ly Pl Ste 11 0
S te ~i le
Ca r y, N C
2 7 511 -7 41 2
Pr odu cer s o f
Drug Product
c. _ surface sam ples are not incubated at optimal temperatures and duration to detect the growth of fungal organisms. In addition,these samples are only being collected on ~ basis and not during periods of dail y routine sterile processing acti vities. The record s are also deficient in that they do not accurately represent surfaces monit ored. SOP 6.045 .1 "Surf ace Sampling Testing", states that samples are to be collected on ' ", however, results are reponed for for the left and right areas, but they do not definitively define the locations sampled. d. _ viable air sam pling has not been conducted 'in accordance with written procedures. SOP 6.035, " Air Sampling". requires the use of control plates to be exposed in the outside area of the clean room. No controls were used in the months of January-September 20 12, nor on 10/12,19,3112012, nor on 11/2,16,3012012, nor on 12/14/12, or January - Feb. 2013. In addition, ~ plates were not exposed within room s identified:by the finn and as documented in record s provided as: the Ante room, Gowning room , or the Compounding room between January-July 2012,
1111 ,212012, or on 12/1 61l2 llS required.
'
. e. Environmental monitoring of the ISO 5 aseptic processing area including the laminar air flow hood, and personnel monitorin g (i.e. fingertip touch plates) are not being performed du ring daily routine processing. Currently viable air sam ples are co llected _ and personnel monitoring is performed _ . In addition no addition there are ~o monitoring conducted of personnel gowning.
f. The unidirectional flow of air in the aseptic processing room and adjacent ISO 5 classified areas (including the laminar flow hood) has not been confirmed through visual mechanisms (such as smoke , studies) to ensure adequacy for use. I ,
g. The efficacy of disinfectants and cleaning agents u~ed on site for routine operations in the aseptic processing rooms and Laminar Flow Hoods has not been verified to ensure that current cleaning procedures are effective as defined on procedure # 5.161.0. Clean Room Rout ine Maintenance.
. I ,
. i
g. A dark stain W as observed in one of the ceiling HEPA filters inside the ISO 5 aseptic processing during the first day of this inspection. !

fORM FDA 4 ) I.
03 /01/2 0 13
PAG lOf6. PAGS
DEPARTMENT OF HEALTH AND HVMAN SERVICES FOOD ANDDRUG ADMI NISTRATION
Atlanta , GA
60 Ei gh t h St r e et NE 30 309 ( 40 4) 25 3- 11 61 Fa x: ( 40 4) 2 5 3- 12 0 2 I n~u s t~ y _ I nf ormatio n: www. f da . gov /oc / i ndus t ry TO :
0 2/ 19/20 1 3 - 03/0 1 /2 01 3 3004 96 98 94
.11_
Danny
Barne~,
Pha r m D., Pha r mac ist In Cha r e / Owner

snoen ss
Tr i a n I e Com ounding
550 New W aver l y PI Ste 110

Prod~ ~er~ ' ~f ~teri 1 e
Cary , NC
275 11- 7 4 12
Drug Product
OBSERVATION 4
Procedures designed 10' prevent microbiological contamination of drug products purporting to be sterile are not established, written, and followed.
Specifically, Poor aseptic techn iques and practices were observed being ex ecuted during routine operations held on 0211 911 3 inside the sterile compounding room (ISO 5) and associated with repackaging of Avastin (Bevacizumab 25 mgll ml PF CP Syringe) 10 ( 02 192013%777 11 into I ml syringes as follows: 1. Operator's full body suits used for routine operations in the ISO 5 room in order to prevent contamination of material s handled inside and while aseptic fill operations are conducted were reported during the inspection as "non-sterile". : 2. Operator was observed transferring material from . ~) inside the laminar flow hood with abrupt movements and abrupt placement o f filled I ml syringes the working surface . 3. Operator was observed leaning against and pushing " the porta ble laminar flow hood with enough strength to cause it to shake while aseptic filling I ml syringes of Avast in. 4. Exposed skin was observed on the operator's forehead and face while aseptic filling operations were being conducted in the ISO 5 Room . Operator conducting the operation was observed wearin g a face mask which left exposed skin on the sides. Hair was obse rved outside the hair piece (full body suit).
I
OBSERVATION 5
Equipment and utensils are not maintainedat appropriate interva~ to prevent malfunctions and contamination thal would alterthe safety, identity, strength, quality or purity of the drug p~uct.
Specifically, Records are not kept for the maintenance and inspection of equipment. Specifically, a. Record s documenting the qualification of the calibration of Nov 20 12 are not availab le to en sure adequat
EUP~O
lSI SlGW.
. Bo n i t e S Ches t e r , Inve s tig a tor SEE REVERSE Noreen M uniz, I nves t i ga to r ~ OF THIS PAGE
iOihzv.4-- .1 CI'"","-'
,/
03 /0 1 /2 013
INSPECTI OS AI. O BSERVAT10~S
. DEPARTMENT OF HEALTH AND HUMAN SERVICES AND DRUG ADMINISTRATION
rooc
.,
60 Eigh t h Stre et NE
At Lan t.a ; : GA 30309 (40.4 ) 25 3- 1161 Fa x: ( 40 4 ) 253-12 02
AKI E
I~
02 /1 9/20 13 - 0 3/ 0 1/ 20 13
I nd us t r
_
, i nfo r ma t i o n : www. f da.go v/oc /indus t r y
30 0 4969894
TO :
Danny Ba rn e s, Pha r m D"
Pharma c is t In Charg e / Owner 55 0 N ew W a ver l y PI S te 11 0 Produce rs o f St eri l e Drug Pr oduct
Triang le Compoundi n
CIlY.STArt. l lP ~ COI.HTRY
C~ r
, NO 27511 - 74 12
routine cycles executed on site. This _ is used on site for sterilization of products and utensils on site associated to sterile fill operations. ' b. Records documenting the qualification of the are not available to ensure adequate during routine.cycles executed on site. This" is used on site for routine Cycles of containers for aseptic processes and Sterilization of products handled at the ISO 5 Room. c. No calibration has been conducted or documented to ensure that the used in conducting testing of sterilizing ~ is operable for its intended purpose,
OBSERVATION 6
There arc no written procedures for production and process controls designed to assure that the drug products havethe to possess. identity, strength, quality, and purity they PUrport or' are represented ,
Specifically,
Your firm does not have real time stability data to support Beyond Use Dates (BUD) assigned to products filled on site for further use on solutions or sold as finished products, .No stability studies have been conducted on site to support assigned dates up to 6 month s, as described on Procedure 2.600.2, Beyond Use Dating. ' Furthermore, products aseptically filled on site can be-assigned a Beyond Use Date that exceeds the expiration date of active ingredients or drug components used to formulate the product. For example, Hydroxyethylcellulo se (Sterile) 2% Gel Lot# 020l2013%71646@2,madeon02l1113wasassigneda Beyond Use Date of 180 days after the fill date or 7/31113 , However, the Hydroxyethylcellulose NF Powder used as ingredient included an expiration date:of 3/3/13 (the ingredient expires 4 months " before the actual finished product's assigned date). '
, .
l),o.TE ISSUEO
Boni ta S 'Che s t e r , Invest igator" No r een M un i z , In ve stigato r

I:"'SPECTIONAL OBSERVA TJO:"'S
03/ 01/ 2 013

~"GEl OF6 P "GES
DEPARTME/IoTO F IlEALTH AND HUMAN SERVIC ES
fOOD AND DRUGADMIN ISTRATION

llIS1lll<; ' AJOIlt $S MICl DAl'li:(S) 01' INSF'I:TlON
60 Ei ghth Stre e t No At lanta , GA 3 03 09 (40 4 ) 25 3-1161 E"ax: ( 40 4)
02l ~ 9/ 2 013
~ _.
0;3/ 0 1/201 3
253- 12 02
i
3 0 0 4969 8 9 4
Ind us t r y I n f o rma t i on : www . fd a .aov / oc / i nd ust r
-TO:
Danny ' aa r nes , Pharm D. , Pharmac i s t In Cha r ge lOwne r

$Tll ~ ET
'm
Tti ana le Comoound i na
CITY . ST Ale. Zl
,m ,
550 New Waverl y P1 St. 11 0

TYPEeSlI ,IlU_ENTa<SPECTEO
Ca r y, NC
2 75 11 - 74 12
Pr oduce r s of Ste ril e Drug Pr oduct
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80n i ta S Che ste r , Invest i gator No r e e n M un i z , Inve s t igat or ~l..C..-t- '

I'llEViOOS EIlITlOM 0850IEl'E
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A.
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DA.r" ,... ~ Q
0 3 / 0 1 /2013
PAGe 6 Of 6 PAGEs
INSrECTIONAL OBSERVATIONS
............
_...... _.......... _ ..... _-_ ....._ .... _ ...................
The observations of objectionable conditions and practices listed I . on the front of this form are reported: 1. Pursuant to Section 704(b) of the Cosmetic Act, or
Fed~ral
I
Food, Drug and
2. To assist firms inspected in complyind with the Acts and reoutations enforced by the Food and Druo l\dmihistration Section 704(b) of the Federal Food, Drug, and Cosmetic Act (21 USC 374(b)) provides: I "Upon completion of any such inspection of a factory, warehouse, consulting laboratory, or othe~ establishment, and prior to leaving the premises, the officer or employee making the inspection shall give to the owner, operator,l or agent in charge a report in writing setting forth any conditions or practices observed by him which, in his judgement, indicate :thatany food, drug, device, or cosmetic in such establishment (1) consists in whole or in part of any filthy, putrid, or decomposed substance, or (2) has been prepared, packed, or held under insanitary conditions whereby it may have become contaminated with filth, or whereby it may have been rendered injurious to health. A copy of such report shall be sent promptly to the secretarv."..
DePARTMENT OF HEALTH AND HUMAN SERVices

f O OD A ND DRUG AOMINI STRATI ON DISTRICT OFFICE ADDRESS AND PHONE NUt.lBER DATE(S) OF INSPECTION
Kansas City Distr ict Offi ce 8050 Marsha ll Drive Suite 205 Len exa, KS 66214 913495 5100 Industry Infonnation: www.fda.gov/oclindustry
NAME AND TITLE OF INDIVIDUAL TO ......,.OM
2/1927120 13
FE! NUMBER
3003244004
REP~ D~ " f1,r< '" "~ '" UE "D ,------------_--L_-------------- t

STREET ADDRESS
TO: Den is D . Wonningto n, R.Ph . Director of Phann acy

FIR'" NAME
Central Admixture P harma cy Serv ices, Inc.

CITY. STATE AND ZIP CODE
15 12 N. To pping Ave
TYPE OF ESTABLISHMENT INSPECTED
Kan sas Ci ty, Mis souri 64120
THIS DOCUMENT LISTS OBSERVATIONS MADE BY THE FDA REPRESENTATIVE(S) DURING THE INSPECTION OF YOUR FACILITY. THEY ARE INSPECTIONAl OBSERVATIONS: AND DO NOT REPRESENT A FINAL AGENCY DETERMINATION REGARDING YOUR COMPLIANCE. IF YOU HAVE AN OBJECTION REGARDING AN OBSERVATION, OR HAV E II,OPLEMENTEO. OR Pv,N TO IMPLEMEN T CORRECTIVE ACTION IN RESPONSE TO AN OBSERVATION. YOU MAY DISCUSS THE OBJECTION OR ACTION WIT H THE FOA REPRESENTATIVE(Sl DURING THE INSPECTION OR SUBMIT THIS INFORMATION TO FDA AT THE AODRESS ABOVE. IF YOU HAVE A NY OUESTIONS. PLEASE CO NTACT FDA AT THE PHONE NUMBER AND ADORESS ABOII E. DURING AN INSPECTION OF 'l OUR FIRM (@ OSSERVEo
I . Laboratory controls do not include the establishment of scient ifically sound and appropriate sampling plans and test procedures desig ned to assure that drug products conform to appropriate standard s of identit y, strength, quality and purity . Specifically , Your finn has not established testi ng procedures to perform sterility or endotoxin testing on each batch or lot of drug product manu factured at your facility to obtain results prior to releasing and distributing drug products. Testing is performed depending on the drug product. Test samples are sent to an outside laboratory and product is distributed prior to rece iving passing results. 2. Proced ures designed to prevent microbiological contamination of drug products purporting to be steri le are not fully establi shed and/or followed. Specifica lly, Your finn does not have adequate procedures and controls in place to mitigate the ingress of contaminants into the ISO 5 hoods where aseptic compounding of finished drug products take place. The products affected are Oxytocin, Adeno caine (Adenosine, Lidocaine), Lipid Syringes, Total Parenteral Nutrition (TPN) for adults and neonates, Cardiop legic Solution (amino acid enriched solutions of various formulations, which can contain dextrose 5%, KCI, phosphates, NaC I, etc), Continuous Rena l Replacement Therapy, and Diltiazem. Specifically; a) On 2/19 and 2/20 /20 13 personnel were seen with exposed skin around the neck and face entering into the hood breaching the laminar air space. "GOWNING REQUIREM ENTS" SOP-CAPS -4000 171 Effective 20 12-10 05 stet> 9.11. states: Keep head out of the ISO Class 5 work space durin g compounding." Personnel do not don sterile hoods, goggles, hair nets or face masks to protect sensitive pharmaceuticals which are preservative free. b) Your SOP "GOWN ING REQUIRE MENTS" SOP-CAPS -4000 171 Effective 20 12- 10-05 is silent to sterile
REVERSE OF THIS PAGE
SO,
EMPLOYEE(S} NAME AND nTLE jP" ,,1OrTYP"J
DATE ISSUED
Tara L Breckennd ge, Investigator Shirley J Berryman, Investigator
2128/20 13
I
Page 1 o f
DEPAR TM ENT OF HEA LT H A ND HUMAN SERVI CES

FOOD AN D DRUG A DMI NISTRA TION DISTRICT OFFICE ADDRESS AND
~H ONE
NUMBER
DATE(S) OF INSPECTION
Kansas City District Office 8050 Marshall Drive Suite 205 Le nexa, KS 662 14 913-49 5 5100 Industry Information: www.fda.gov/oc/lndustry
NAME AND TITLE OF INDMDUAL TO INHOM REPORT I S ISSUEO
! 211 927/20 13
FEI NUMBER
3003244004
TO; Den is D. Wormin gton , RP h. Director of Pharmacy

FIRM NAME STREET ADDRESS
Centra! Ad mixture Pharmacy Services, Inc.

I l S12N. Topping Ave

I TYPE OF ESTABLISHMENT INSPECTED
Kansas City, M issouri 64120
sleeve and glove practices with regard to specific sanitization practices and consistency . Personnel are not consistent in how they sanitize and _ their hands upon exit and entry back into the hoods. On 2119 and 2/20/2013 some personnel were seen app lying very short burst/quick sprays of _ onto their hands without rubbing and spreading the _ evenly, while other personnel were seen liberally applyi ng _ and thoroughly rubbing, spreadi ng the _ to saturation, You r procedure does not describe in additional deta il intervals where gloves and sterile sleeves must be changed out, except upon . Personnel only change out their sterile gloves and sleeves as they determ ine may be necessary. On 2119-20/2013 personnel were observed workin g up to 2+ hours without determining additiona l sterile glove changes may be necessary after numerous _ sanitization which could degrade the quality of the glove over extended periods of time. During observation employees were seen only of gloves. wearing _ c) P lastic holders are not cleaned and sanitized on a frequent enough basis. Within some of the ISO 5 laminar flow hoods plastic holding conta iners attached w ith suction cups are positioned against one of the side walls. These containers were viewed holding pens, unsterile labels, sterile luer lock caps for syr inges, which were opened, and other sterile or unsterile supp lies or components. The plastic holders are not removed on a daily basis and cleaned, This could compromise asepsis of the ISO 5 zone and pose a risk to product sterility. After marke t _ type hood guards, which are not part of the hood's original design, are affixed to limit personnel breaching the laminar air space. These guards are not removed on a dai ly basis to facilitate cleaning. There are gaps and spray residue visible on these guards which could compromise asepsis of the ISO 5 zone and pose a risk to prod uct sterility. The , used to attach the guard to the hood does not appear to be easily cleanable. It was confirmed, gaps between the surface of the hood and barr ierl guard is only only cleaned approximately d) Electronic computerized scan equipment which cannot be fully cleaned or immersed for sanitization is kept within the ISO 5 hood where compounding occurs. The inability to fully clean the equipme nt could impact asepsis of the ISO 5 hood. e) On 2/ 19 and 2/20/2013 in the room where oxytocin is compounded , the hood s were observed filled with . bags of diluent base solution. The finn has not assessed the impact of the full hood with regard to unidirectional
RE VERSE OF TI-IIS
'EE
, E~ ) SI GNATU R E
EMPLQYEE(S) NAME AND TITLE (Pnnt or Type)
DATE ISSUED
Tara L Breckenridge, Investigator

Shirley J Berryman, Investigator
PREVIOUS EDIllON OBSOLETE
PA GE
2128120 13
FO R M FDA 48 3 (9108)
Page 2 of;
'-l
DEPARTMENT OF HEALTH AND HUMAN SERVICES A NO DRUG A DMINIST RATIO N
rooo
DISTRICT OFFICE ADDRESS AND PHONE NUMBER
DATE(S} OF INSPECTION
Kansas City District Office 8050 Marshall Drive Suite 205 Lenexa, KS 66214
9 13-495-5 100
Industry
2/19-27120 13
FEI NUMBEI'l
Information: www.fda.gov/oc/lndustry
3003244004
NAME AND TiTlE OF INDIVIDUAL TO WHOM REPORT IS ISSUED
TO: Denis D. Wormington. R.Ph. Director of Pharmacy

Central Admixture Pharmacy Services, Inc.

CITY. STATE A ND ZIP CODE
lSI2 N. Topping Ave

TYPE OF ESTABtlSH MENT INSPECTED
KansasCity, Missouri 64 120
Producer of Sterile Drug: Products
airflow. Smoke studies wh ich were performed, are deficient in assuring there is no de grad e in air flow . The smoke did not reach fully to the back of the hood where the bags were stacked to demonstrate airflow integrity was ma intained. 3. Asepti c process ing areas are deficient regardin g the system for mon itoring en vironm ental conditions. Spec ifically, Environmental mo nitoring of personnel via finger tou ch and sleeve tou ch p lates was ob served on 2120/20 13. Personn el sanitized the ir han ds wit h _ , performed one manipul ation pushing a syringe of oxytoc in into a bag of diluent base so lution, a nd the n that tec hnician was immediately sampled as the subject of finger touch and sleeve plates. Th is process negated the potential for bioburden recovery , w hich wou ld be representative of the wo rk env iron ment and personn el practices. 4. Batch production and contro l record s do not incl ude the specific identificat ion of each batc h of comp onent or in-process mater ial used for each batc h of drug produc t produced . Speci fica lly, Your finn docs not track o r document direct product contact comp onent lot numbers in a ny of the batch record documentation. This include s item s such as IV bags, sterile tubing, syringes, etc. Your firm docs not hav e the ability to trace and recall any products whi ch may be a part of a co mpo nent recall or which is otherw ise det ermined to be compro mised. The lot numbers for container bag s are not documen ted . CA PSTMSol ution Report doe s not includ e a lot numbers for the EVA Container bags used in the TPN compounding process . For example: CAPS RX . 19-372367-0-1 only shows the use of "Selected bag x4 J EVA Co ntainer 3000mL" and CAPS RX . 19-3308 19-0-1 shows the use of "Selected bag x42 EVA Co ntainer 4000mL". 5. Written records of inve stigations into unexplained discrepancies do not always incl ude the concl usio ns and follow-up. Spec ifical ly;
a) The investigations for five complaints of leaking bags of TPN rece ived in 20 12 are inadequate. TPN lea king bag co mplaints were reported on the follow ing dates : 1/3/2012, 1/8/20 12,4/1012012, 10/ 11/20 12, and 10/31/2012.
EMPt OYEE($) SIGNATURE
REVERSe
EMPLOYEE(Sj NAME AND TITLE (P"" t or Type)
DATE I SSUED
SEE
OF
PAGE
nes
g!.
Tara L Breckenridge, Investigator Shirley J Berryman, Investigator

2/2812013
FORM FDA 483 (9108)
r age 3 of f~
DEPARTMENT Of HEALTH AND HUMAN SER VIC ES fOOD AND DRUG ADMI NISTRATION OISTfl lCT omce ADDRESS AND PHONE ~ UM BE.fl OATElS} Of
I ~ S PE C T10 N
Kansas City District Office 8050 Mar shall Drive Suite 205 Lenexa, KS 662 14 913-495-5100 Industry Information: www.fda.gov/oc/industry
NA~ E
211 9 27120 13
f EI NUMBER
3003244004
AND TITLE OF INDIVIDUAL TO ......-H OM REPORT IS ISSUED
TO: Denis D. Worm ington, R.Ph. Director of Phann acy

Central Admixture Pharmacy Services, Inc.

CITY, STATE AND ZIP CODE
15 12N. Toppin g Ave

Kansas City , Missouri 64120
Producer of Sterile Dru g Products
The lot number of the bags is not documented in order to conduct an ade quate investigation. It was not docu me nted in the investigation that the manufacturer of the IV bag component was contacted to report the leaking bag(s). In all case s the leaking bag was not returned but destroyed by the hospital and the locat ion of the leak is not ava ilable. The root cause docu mented is "mishandling of the TSP bag by the personnel at the customer site" a nd one was " mishandling of the package by _ ".
b) Despite the return of 16 bags of Oxytocin from a batch of. bags compo unded on 6/20/20 12 for the custome r, you failed to perform any testing of the returned product. The Oxytocin was retu rned by the customer because they reported they did not get the expected resu lt. SOP-CA PS-40002 17, Customer Inquiry/Comp laint Handling and Repo rting , 4.5.7. states "Testing and / or ana lysis to confirm Product Complaint or clarify problem ." And under A. Te sting should include analys is of returned sample prod uct as app ropr iate and includes Lack of Therapeutic Effect. The 16 bags of Oxytocin were returned and des troyed on 7/212012.
6. Aseptic process ing areas are deficient regarding systems for maintaining any equipment used to control the aseptic conditions. Specifically, ISO 5 Lamin ar Flow Hood number 10 was observed to not be maintained in good repai r. There was an approximate 84- inc h crack on the left side wall. Inner side wa lls of hoods were viewed to have spray residue which was dried onto the hoods within the ISO 5 space and not thoro ughly cleaned.
E,/LO'fE E{SlSIGNATURE
SEE REVERSE
OF THIS
PAGE
h.
f L-~~ 'l, ') ;<,

0850_1 E
is:::--
EMPlO'fE E(S) NAME AND TITLE (Prin t"" Type)
DATE ISSUED
Tara L Breckenridge, Investigator Shirley J Berryman, Investigator INSPECTIONAlOBSERVATIONS
2/28/2013
I
Pag e 4 of
FORM FDA 483 (9/ 08)
PREV~~1TI0N
11
IJEP AKTMI:I\T OF Il EALTI l It, !) Il r M,\ N SERVIC ES

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This dccumc r uli>t3 observations made by the FD/\ representativets] during the inspection of your facil:rj _Th0' are inspectioaal observances, unci do 001represent a final Agen~ determination regarding your compliance. If y WJ have an obJcction regan:! i:lg an Obseno'IUion. or have impleme nted, or plan to implement. corrective actioo in response to 1!JI obsc:rvalior.. you lJl.1y diSQI~ the objection or action with rhe FnA ~laI i\'e{;:1 dl.'ling L:" ~ ins pection or submit this in fOTTl'llllion to FDA at the address above. If you have eny quesecns. please cornacr fU A llI. the phone :lU~ber :l.'ld address above.
DURING AN INS PECTION OF YOUR FIRM WE O BS ERVED;
Facilities & E c uinrnent

OBS ERVATION 1 .-_.
A ir -handl ing systems
'
fOf the processing of pecicillio are no t completely separate L '1Jrn those for other drug products for
human U!lOC. Specifically,
The air handling system for the Antibiotic room where penicillin and cephalosporin products are compounded also supplies air to the finn's Ante Room. Gown ing Room. and Product room. The exhaust from the Antibiotic room is into the surrounding non-classified area housing the opcmtions suite. This same non-classified area also provides air 10 the Air Handling Unit supplying air to the TPN room (_ hwnan compounding room ). Additionally review of pressure differential monitoring points on 211 9/2013 revealed the Antibiotic room was at a higher pressure tben the adjacent and connected TPN compounding room. Products compounded in the Antibiotic room include: Ccftriaxone 1gil O mL lot 1 3 - 7 Q 756 0~O on 2Jt S/20t3 Cefazolin 2gm/20mL lot 13-797670-0 on 211 8'2013 Penicillin G potassium lot 13-793827-0 on 2/0512013 Other human products compounded on these same days include: Oxytocin 20 units lot 13-797570-0 a ll 2/ 18120 13 Oxytocin 30 units lot 13 793 650~O on 2/05120 13
'
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A MENDMENT 1
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OBSERVATION 2
The operations relating to theprocessing of penicillin are not performed in faci lities f>eparate from these used for other drug products for human use.
Specifically,
Procedures have not been established for the separation of tasks and segregation of personnel handling penicillin and cephalosporin drug product" from those tor all other human drug products. For example: i-On 2/ L 9:':.0 13, compounding personnel were observed entering and exiting the Antibiotic room during compounding operations. Specifically, we observed an employee entering the Antibiotic room to retrieve a can of bagged dil uents from the Antibiotic room that w ere subsequently used in the compounding of Oxy tocin 1 0 1 13"" .797566-0 within Hood Ii 8 of the TPN roo m. Cettriexone Igi l OmL lot 13-797560-0 was compounded in this Antibiotic room on 2118,'2013. ii- On 211 912013. non-sterile gowning was observed in the gowning room for re-use by operators on this same day. There was no segregation of the re-usable gowning observed hung: on a rack in this space. including the compou nding operator staled to have been operating in the antibiotic room on this day. Au example product compounded on 21!9120 13 is Oxyt ocin lot lJ-797566-0. iii-The 211512013 transfer of _ from bulk containers into spray bottles was stated to have last occurred within Hood # 16 within the Antibiotic room. These filled spray bottles are then placed at each ISO 5 wcrk compounding room. On 2 / 19/20 13, we observed the spraying from one of the 211 5'2 013 station within the refilled bottles of mto components used during compounding of Cardiopleg ia lot # 13-79;90802. Cardioplegia lot # J 3-797625-0-2, and Oxyt ocinlot l 3 ~ 797566-0. as examples.
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AMEND MEN T1

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OBSERVATION 3
There is a lack of wri tten procedures describing in sufficient detail the methods. equipment ami materials to be used for
sanitation.
Specifically,
Writte n procedure SOPCAPS-4000183, Cleaning Procedure, does not clearly establish all minimum exposure
times as supported by validation/eff ectiveness data. Specifically, the "Total Clcandown" that is performed weekly does not specify: _the agent to be used in mopping of the clean room suite floors and the exposure period for the same. _the expos ure time for the dilute bleach rinsed trash barrels within the compounding suite, before replacement of the liner
~
..
The last cleandov..n was performed on 21151 20 13 . Subsequently compounded products include;
-Oxytccin 20 units. lot 13-797566-0 -Cardio plegia lot 13 -i97625..(l -Cardioplegia lot # 13-7979080-2
OBSERVATION 4
Duildings used in the processing of a drug product art' not maintained in a good state of repair.
Specifically,
l'he face of the HEPA grate covering the HEPA filter over ISO 5 workstation as observed with a small amount of a brownish residue, noted during compounding. operations on 2/19:'101 3. Tbis residue was lerer slated to have been easily removed with a cloth .. vipe, but U n: identity of the residue was tlOl confirmed. Products
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Gl e nn J . ?ang ra zz i . R . PI: . , MBA . Dire ctor of Pha rmacy

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co mpounded in this work sta tion o n this day are a ll TI'N prod ucts, incl udi ng lot # 13-79762004 and 1 0t# 1379793 101. O ther produc ts compounded in the TPN roo m at this tim e incl uded O xytoc in lot 13 79i 566-0.
Production
OBS ERVATION 5
Procedures designed to prevent microb iological contamination of drug products purporting to be sterile are not established,
written, and followed.
Specifically, operations at this f'ilcility includethe compou nding ofsrerile- preoncts fr om purchasedsterile finished dosage: forms into sterile diluents or new sterile container closures. Pertaining to these operations; -thc following was noted:
1- Pr o ced ures are not fully e stab lished . for example:

i- Go wn ing used in protection of personn e l wo rking at the ISO 5 workbe nch es was o bserved to incompletely cover a ll expo sed skin su rface s . Spe cifically, no covering over the face and neck beyo nd a mouth/no se mask was observed worn by compound ing per sonnel d uring all compounding operat ions from 2119 2112013. O nly sleeve co ve rs and gloves we re provid ed with certification suppo rting steril ity . Products compounded du ring these sam e days in cl ude : Card iop legia lot 13-778554-0 oll 2!'2 l/20 13 Card iop legia lot lJ-797960-0 on 2/20/2013 Ca rdioplegia lot 13 - 79 7 6 2 5 ~ O on 2/19/20 13 O xyto cin 20 Un its lot 13-797566-0 on 211 91'2013
ii- According to writt en procedure and as shown in supporting records, Environme ntal mon itoring of the ISO 5 :_ workspaces an d personnel monito ring of c ompoundingemployees working. in the sam e occ urs on1
AMENDMENT 1
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Daily Non Viable Particulate r.-J VP) monitoring in the ~u ll d i n g work spaces does not occur during compounding operations. Specifically, this site houses_ ISO 5 work space s used for sterile compounding operations. J\l\:P monitoring was not provided for these same ISO 5 work spaces. during dai ly, compounding operations. Examples of compounded products compounded within these same ISO 5 work: spaces include:
Cardioplegia "High K" lot 13-797960-0 on 2120/2013
Cardioplegia 1 01 13-797625-0-2 on 2/19/2 013

Oxytocin 20 Units lot 13-79/566-0-1 on 2/19/'2013
;i i~i ~pcnsin'g occurs according to written procedure SOP-C:.~ PS.4000 159 Filtration and Filling. and includes direction for the filling ot into non-sterile, re-usable spray bottles (_ isinfectcd spray bottles). This refilli ng activity of_ trom the source containers occurs in an ISO 5 hood, and was last pe rformed on 2115/2013 in Hood # 16. These refilled spray bottles are then stationed at each ISO 5 work station (and elsewhere) and were observed in usc in spraying septa of vials prier 10 compounding (needle puncture). gloved hand sanitization, and ISO 5 bench surface w ipe down during all observed operations. Compounded drug products observed impacted under this observation include:
-Oxytocin Zu units. lot 13-797 566-0 -Cardioplegia lot
13 - 7 9 i 6 ~5 -0
2- Procedures are not followed- Specifically, written procedure SOP-CAPS-4000175. Aseptic Techniqueand/or SOP-CA PS-4000 158. Clean Room Compounding Area - Product Intro-Removal, were not followed on the folio.... ing occasions: i-On 2/ 19:20 13, a compounding employee \\ as obse....-ed stretching sterilized tubing from the ISO 5 workbench space into the ISO 7 surrounding space. This tubing is used as a conduit for components utilized ill compounding
AMENDMENT1 ,-SEE REVERSE OF THIS PAGE
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Cardioplegia lot # 13-79790802. c:!hrought ii-On 2/ 19/2013, a writing utensil (pen), was observed used outside of the ISO 5 hood at work statiOt into the ISO 5 space by pharma cist during revi ew/signing of Magnesium Sulfate lot 1302- 19-MGS " I. iii- Labeling was observed brou ght from outside the ISO 5 hood 1 0 insi de the [SO 5 hood and set atop an opened , sterile T V bag during preparation {or compounding Cardioplegia lot 13-7979 600 on 2i20!2013. iv-Th e upper torso and head of an employee was observed enterin g into the ISO 5 hood of workstation #. '- ' stag ing of Diluent bags for compound ing Oxytocin lot '# 13- jC) 7566-O . uring
v-Over ten large sterile syringes ,in packaging were observed brought into the ISO 5 work space of station . without any sanitization of the outer packaging during compounding preparation of Magnesium Sulfate Syr inges, lot 13-0220 -MAG S04.,Ol on 2/20/13,
\ "j -
~terj.le tubing use~ in connec tion. with the Car~i~rl~gia pu~p at the ISO .~ \Vo~stati~n #.!:'as observed
carried mto (he ISO::: work space without any sanrnza non during compounc mg at Cardioplegia lot # 13-797960-
o.
vii-As observed during compo unding operations during the morning 2119/20 13, "Slow deliberate" motions were not always noted. Specifically, compounding personnel were observed movi ng briskly throueh the 150 "7 surrounding space within the 'TPN ' compounding room, passing beside [SO 5 workbenches_ Products compounded at this time included:
Cardioplegia Jot # Oxytocin lot
13 ~ 79762 50
1 3 ~7975 66-0
La boratory
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AM ENDMENT 1
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OBSERVATION 6
Acceptance criteria for the sampling and resting conducted by the qu ality control unit is not adequate to assure tha: batches of drug prod ucts meet each appropriate specification as a cond ition for their approval and release. Specifically, There is no routin e, batch specific qual ity control analy si s for anticipatory com po unded prod ucts incl uding
Oxyt ocin and Nor-epinephrine req uired accord ing to an y writt en procedure as part of a batch release. For
exa mpl e . no batch spec ific sterility testing was pe rformed (or initi ated). and no QC che mical analys is was performed pr ior to the -releas e o f O xytocin lot 13-797 570 -0 and Cardioplegia lot # 13-797 625-0.
Materials
OBS ERVATION 7 Reports of analysis from component suppliers are accepted in lieu of'testiag each component for conformity witt all app ropri ate written specifications, without establ ish ing the reliability of the supplier's analyses through appropriate validation of !he supplier's lest results at appropriate intervals.
Specifically,
is utilized in com pound ing operations for inj ectab le compounded prod ucts , and is received w ith a C ert ificate of Analy sis from yo ur finn 's supp lier. The reliab il ity of this suppl ier's analyse s was not dem onstrated bv vour firm through appropriate va lidat ion of the supplier's test results at appropriate intervals. For example. USP h')~was received and released for use in yo ur finn on 2/ 112013. 'TIm same ot ot was used in com pound ing Cardioplegia High K lot # 13797 96003 . aHiJ--Ptmicillin G Pete i'iiH ffi le t 13 7c>;.g.214
l
I
AMENDMENT 1
<".... o ..."~ C". ~"',,.i:'i\ili! ~
SEE REV ER S E I Rebec c a E . Domb r owsk1, ::: nve st i gato r! OF THI S PA GE Larry K. nus t i .n . I'nv e o t aqa t or ,
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0 2{ 28 / 2 0 13
DEPART MENT OF HEALT H AND HUMAN SERVIC ES FOOD AND DRUG ADMTNISTRATJO"
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STRt:ET AlJOO\E35
Pha r M EDiu m Servi ces L L e

CITY, STAn; . UP COOf . cou;TflY
4 3 Di s t ri b ution Blvd
r.'F't" ESTA!ll I_"," II<S"Ecn;o
Edison, NJ
08 817 - 60 05
Pr o d u c e r o f St e r i le
D~g
Product s
This doc ument lists observations made by the FDAreprescntativets) during the inspection of your facility. The)' are inspectional observations, and do not represent a fi nal Agency determination regarding your compliance. If you have an objection regarding an observation, or have implemented, or plan to implement, corrective action in response to an observation, you may discuss the objection or action with the FDA representetiveis) during the inspection or submit this information to FDAat the address above, If you have any questions. please contact FDA at the phone number andaddress above.
DURI NG AN INSPECTION OF YOUR FIRMWE OBSERVED:
For the aseptic production of all sterile drug products such as: Propofo ! 1% Injection Emulsion, USP, 10 mg/m l (Lot 13050021E Exp 3(2112013); Nicardipinc HCL 40mg added to 250mL 0.9% Sodium Chloride Injection USP (Lot 130520 IOE, Exp. 5!22/l 0 13); Oxytocin 30 units added to 500mL 0.9% Sodium Chloride Inje ction USP (Lot 13051036 Exp 5n 12013); and Vancomycin HCL 1.25g added to 250mL 0.90 10 Sodium Chloride Injection USP (Lot I3520 18E Exp 3/23/2013): PRODUCTION SYSTEM
OB SERVATION 1
Clothing of personnel engaged in the processing of drug products is not appropriate for the duties they perform. Specifically, sterile drug produc ts arc aseptically manipulated by the c1eanroom operators who weal l l l l l l lgloves, per gowning procedure CPS-305, issue date 11/30120 12. The quality of the sterile gown may be compronnsc y e gowning sequence, which req uires the operators to touch the sterile gown with their bare hands Additionally, the cleanroom exit and re-entry process used by the operators may further compromise the quality of the sterile gown, because the gowns are re-used and re-handled. LABORATORY SYSTEM
OBSERV ATION 2
Each batch of drug product purporting to be sterile and pyrogen-free is not laboratory tested to determine conformance to such requirements. s pccifica. A ) Of th
lots of sterile drug product produced in 2012, only 52 lots were tested for sterility.
B.) There is no endotoxin testing data for any of the lots of sterile drug produced from 112012 to the present date.

~'() I<M
Ru sse l l Gl a p i o n , I n v es ti g a t o r ~~~~ J ames A . Liu bic i c h, I nves tigat o r L~
EUPLOYEE IS ) SIGNATURE
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J.,..-Ld tJ _
02/28 /2013
PAGF I Of J P AGF S
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10 Blv d ., 3rd Floor Parsippany , NJ 0 7 0 5 4 (9 7 3 ) 33 1 - 4 900 Fax : {9 73} 3 3 1- 4 96 9 Industry I n f ormation: www . fda .qov/oc / industrv
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Wal ter T . Kel so , RPh, Ce n t e r Manaqe r

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PharMEDium Services LLC .~ Edison , NJ 08B17 -60 05
"
Di s t r i b u t i o n Blvd
Producer of Ste rile nruc Products
OBSERVATION 3
Test ing and release of drug product for distnbution do not include appropriate laboratory determination of satis factory conformance to the identity and stren gth of each act ive ingredi ent prior to release . Identification and potency testing is not routinely performed on most ofthc firm's 30 or more steri le drug products produced Specifically, on ly 12.7% of the lots produced in 20 12 were tested ; approximate!) . Ofthe test ing that lots tesled) and Oxytocin was done, 99.3% of it was restricted to only two prod ucts; Magnes ium Sulfate Inj ection Iniect ion ( lots tested).
..
OBSERVATION 4
An adequate number ofba tches of each drug product are not tested to determine an appropria te expiration date. Spec ifica lly, the finn's data tha t are supporting produ ct expiratio n dates, suc h as 90 days for Nicar dipine IICL (Pre servative Free) and 30 days for Vanco mycin, is not based on site spec ific, processin g conditions. All expiration dates were estab lished based on dru g prod ucts that were produced and tested at a contract laboratory, Additionally, some of the firm's drug products, such as Vancomycin, have not been re -eva luated since 1999. MATERlALS SYSTEM
OBSERVATION 5
Procedures des igned to prevent micro biological co ntam ination of drug products purporting to be steri le are not established and followed . Spec ifically, there is no antimicro bial effectiveness testing data for steri le drug products cont aining preservat ives, such as Custom Cardioplegia Solutio n and Propo fol.
OBSERVATiON 6
Written proce dures are lacking which describe in sufficie nt detail the rece ipt, ident ificat ion, sampling. testing, and approv al of clos ures, Spec ifica lly, A. The firm doe s not receive or review certi ficates of sterility for the sterile components used 10 process sterile drug products. R . The firm does nOI conduct any samp ling or testing of sterile finished inj ecta ble drug product containers, Th"Y '" approv ed and released for use withou t testing.

PO IL\lm" ... I (.....'
Russel l Gl apion, Investigator ~~~ ~ James A , Liubicict" I nvestigator ~ ~
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02 / 28 /2 0 13
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Se rvices LLC 08 81 7 - 60 05
Edi s on , NJ
4 3 Dis t ribu t i on Bl v d TY"f. f.ST_'''' _C Pr o duc e r o f Sterile Druq Pro d'.Jct s
I OUALITY SYSTEM OBSERVAT ION 7
Written record s of investigation ofa drug complaint do not include the findings of the investigatio n.
Specifically, the firm's complaint investigation # 37 12, initiated on 10105120 12, record ed that two patients experienced fever, chills and flu-like symptoms. after being adminis tered Propofol lnjeclable Emulsion lot 12271033E. The firm's investigation, which was completed on 11107f20 12, was not thorough because the ClI'IIl did not have retains available for visual exam ination and testing. The firm does not collect or store retains for any of their finished sterile drug product lots.
" DAn :S OF L~S P[CT IO~: 02/2012013(Wed). 02I21f20!3(Thu). 0212212013(fri), 02f2& '2013(Thu)
f - . c "U.lIIl1lG....~
SEE REVER SE OF THIS PAGE

m _", 4"' ~
Russel l Glapio~ . I~ve s t igator James A. Liubici ch, I nv e s t i g a t o r

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02 / 28 /2 013
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Il"SP r.cnOSAL O RSER\'An ONS
DEPARTM ENT OF HEALTII AND IIU~lA:-I SERVI CES

FOOD ANDDRUG ADMINISTRATION
asTRICT ADORfSSA/<C F'K;)f. NUMlER
D-' 1 ~:o,
..... Nllt'tiO l""'"
4 04 0 North Central Expre s s wa y , Suite 30 0 Dalla s, TX 75204 ( 214) 253-5200 Fax : (214 ) 253 -53 14 Industry Info r mation : www . f da . go v/oc /in dus t ry
Mt.UE """JTIT1.~ ~ IU WHOU f(kKJKT ISSUED
02 /19/ 2013 - 02 / 27 / 2 0 13 30 0 07177 0 3
TO :
1 r<M ~
Mr. Bruce W. BagbY, General Manager

&TIflfe1~
Pha rMe d i um Services , Llc

QTY,STA
1 2 62 0 W Ai rport Bl v d Ste 13 0
A.fLJSHUENT wseecreu
Sug ar Land , TX
77 478 - 62 00
Producer o f Ste r i le Druq Produc ts
This document lists observations made by the FDA representative{s) during the inspection of your facility. They are inspectional observations. and do 110 t represent a final Agencydetermination regarding yourcomp liance. If you have anobjectionregarding an observation, or have implemented, orplan to implement, corrective action in response to anobservation. you may discuss the objection or action withthe FDA representative(s) during the inspection or submit this information to FDAat the address above. If you have any questions, please contactFDA at the phone numberand address above.
OBSERVATION 1
Equipment and utensils are not cleaned and maintained at appropriate intervals to prevent contaminationthat would alterthe safety, identity, strength, quality or purity of the drug product. Specifically, your finn does not always keep laminar flow hoods visually clean of residue on HEPA filter surfaces and covering grates. Laminar flow hoods are consid ered an ISO 5 environment where mixing and pooling of sterile injectable drug products occurs. On 2119120 13, I obs erved whi te and yellow residue (rough or crys talline in appearance) on the HEPA filte rs and filter manifolds installed on hood (clean bench, model_ numbers 1,2,4, and 5 (four out o. l a m i n a r flow hoods in the clean room). I observed residue in areas up to approximately eight me es square on the filter and manifold surfaces facing the operator work area where sterile injectable drug products were being pooled and mixed . These laminar air flow hoods are designed to move air through the HEPA filter, through the drug handling space, and out of the hood towards the operator who is handling the drug produ ct and other materials. I observed the following examples of drugs mixed or pooled in these hoods at the time I observed the residue described above: Hood # 1 - Oxytocin lot # 13050117S _ 500mL bags; Hoo d #2 .. Heparin lot # I3 050 I3 8S 500mL bags; Hood #4 .. Cefazolin lot # 13050114S~ 100m L bags; Hood #5 .. Heparin lot # I3 050 169S .. 50mL syringes ; Your managem ent stated there is no investigation or corrective action docum ented for these residues .
,-..
0l~~ 1UI'V:

fO RM FDA 4U (Of IN)
Steph en D. Brown. I nv e s t i g a t o r Scott T. Balla r d . Invest igato~~~~~
14/ . J.:L
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IIiSI.EO
02/2 7/ 20 1 3
PAGE I Of. ,AGES
--....PUVIOUS !DITI()H CIIlSClJ!'n
ISSPECTIOSA L OBSERVATIOSS

FOOD AND DRUGADMINISTRATION
DISTRiCTADDRESSAND PHONENUMBER DATE(S)OF INSPECTION
4040 North Central Expressway, Suite 300 Dallas, TX 75204 (214 ) 253-5200 Fax: (214) 253-5314 Industry Information: www.fda.gov/oc/industry
NAME AND TITLEOF INDIVIDUALTO WHOMREPORTISSUED
02/19/2013
FEI NUMBER
02/27/2013
3000717703
TO:
FIRM NAME
Mr. Bruce W. Bagby, General Manager

STREETADDRESS
PharMedium Services, Llc

CITY, STATE,ZIP CODE,COUNTRY
12620 W Airport Blvd Ste 130

Sugar Land, TX
77478-6200
OBSERVATION 2
Clothing of personnel engaged in the manufacturing of drug products is not appropriate for the duties they perform.
Specifically, your firm does not use non-shedding foot covers for employees who work in the clean room where sterile injectable drugs are mixed and pooled. On 2/19/2013, I observed white particles on the floor of the clean room. Particles observed were white and approximately two to three millimeters square. On 2/20/2013, management stated these particles could be shedding from foot covers. I observed foot covers missing an elastic/rubber type of strip from the surface of the cover that contacts the floor of the clean room while employees are wearing the foot covers. On 2/21/2013, I observed white particles on the floor ofthe clean room. I observed particles as follows:
Number of Particles 17 7 18 8 18
Adjacent Hood # 3 5 14 4 2 Drug in Hood
Lot # 130520955 130520605 130520775 130521345 130520825
Norepinephrine Oxytocin Oxytocin Cefazolin 50dium Oxytocin
I observed all particles described above, within a one-foot radius of operators or within one and a half feet of the hood (clean bench) air intake.
EMPLOYEE(S) SIGNATURE

FORM FDA 483 (09/08)
Stephen D. Brown, Investigator Scott T. Ballard, Investigator

PREVIOUS EDITIONOBSOLElE
Q
"fa
DATEISSUED
02/27/2013
PAGE 2 OF 8 PAGES
DEPARTM ENT OF IlEALTIl AND IIU~1AN SERVICES

FOOD ANDDRUGADMINIS'ffiATION
OlSTRlCT ADORESS /lH) PH OI'E N'.Al llf R TE(S) OF INSPECTION
4 040 Nor t h Centra l Exp r e s swa y, Su ite 300

Dallas , TX 75204 ( 2 1 4) 253-520 0 Fax: ( 2 14 ) 253 -5 314 I n d u s t ry Information : www . f da .gov/oc/in d ustry
twA:.um TITLEOF INDIVIDUALTO VM::lMREFOR ISStJ
02/19 /20 1 3 - 02/27/20 13 3000717703
TO :
Mr. Bruce W. Bagby, Gene r a l Manager

12620 W Airpor t Blvd Ste 1 3 0
TYPE ES TASU SI" t.lENT INSPEC Tto
PharMedium Services , Llc

CIT't, srATE,ZlP COO. COUHTtN
Su g a r La n d . TX
77 4 7 8 - 6 2 0 0
Pr oducer of Sterile Drug Products
OBSERVATION 3
Procedures de signed to prevent microb iological contam ination of drug products purpo rting to be sterile are not established. Specifically, A) Yo ur finn does not perform environmental samp lin tip contact plates are only taken from _ employees I obse rved up to six operato rs working in the clean room on .,. was performin g mixin g or pooling operations,
",.v
Other areas of personnel gowns are not sampled as part of environmental monitoring efforts. Betwee n 211921f2013. I observed operators mixing and pool ing drugs within laminar flow ho ods. Gown sleeves and surfaces on the front side of the gown come into contact with hood edges, and drug vials. The opera tor's gloves and sleeves move in the operating space oc cupied by steri le injectable drugs during mixing and pooling operat ions perfonncd by the operator.
Additionally~ ma nagement stated there is no moni torin g of viab le airborne particl es for every lot or shift. Only_ room air an, -hood air samples are collected accordi ng to SOP #CPS-707, dated 9/1 7f20 12. Also, there is n~g of non-viable particles for every lot or shift. Onl~ hood samples (SOP #CPS-303. dated 1/31f2006), and _ room samples (SOP #CPS-307, dated 611 4(20 11) are collected.
B) Your SOP #CPS 719 entitled "Processin documents , in part, that a total of
However, obse rvation of poo ling operations on 2120/13 for the product, Norepinephrine Bitartmte ~ Added to 250ml 0,9% Sodiu m Chloride Inj ection , USP, lot #13051 130S, revealed that your finn was using a total o ~als ofdrug product whic h exceeds th_ ial maximum documented in the equipment validation.
OBSERVATION 4
Each botch ofdrug pro duct required to be free ofobjectionable microorganisms is not tested through appropriate laboratory testing. Specifically, your
finn
h as n ot c o n d ucted ster ility te sting for the majori ty of the lo ts of drug products
SIGMT\.RE
~Pl.on E(S)
Stephen D. Brown, Invest igator Scot t T . Ballard, I nvest igator

PREVlClUSEDITION OBSOLEre
0 F:-8
DATEIS SUEO
02/ 2 7/ 2 01 3
PAGE ] Of. PAGES
INSPECT IONAL O BSERVATIONS
.
OlSTR ICT ADDRESS AHOPHONEtuUBl:R
DEPARTMENT OF HEALTII AND HUMAN SERVICES

FOOD AND DRUG AD MINISTRATION
OA~(S)OF
404 0 No r t h Ce n tral Expre ssway , Su i t e 300 Dallas. TX 7 5 2 0 4 ( 214 ) 25 3 - 5200 Fax: ( 214) 253 -5314 Indu s t ry Info rma t i o n : www.fda.gov/oe / indust ry
NAME ANtI TrTlE OF N:lIVlt:llJl' L TO IM'iOM REPORT ISSUED
02 / 1 9 / 20 1 3 - 02/ 2 7/ 2 0 1 3
,.~o~
3000 71 7703
TO :
,1t<M .............
M r . Bru ce W. Bagby , General M anager

.....eereccse ss
Ph arM e d i um Service s , Lie

CI STATE. ZP COOE, COU N
1 2 62 0 W Airport Blv d S t e 130

T't'PES TA8U SHME.NT INSPECtED
tN
Sugar Land, TX
77478 - 6200
manufactured and distributed. For example, between 1/3/12 and 1/24/13 your firm manufactured and distributed approximately. o t s of drug product (Different formulations/container closures) and conducted sterility testing on ots, For example,
The drug product, Heparin 2,000 Units per 1,000 ml (2 Units/ml) added to 0.9% Sodium Chloride Injection, USP, lot # 13016002S (Expiration date : 3/22113) was manufactured on 1/1511 3 and shipped to a consignee on 1/16/13 without sterility testing. The drug product, Magnesium Sulfate 1 g Added to 50ml 5% Dextrose Injection, USP, lot #13016004S (Expiration date : 3/2113) was manufactured on 1/15113 and shipped to a consignee on 1/ 16113 without sterility testing. The drug product, Calcium Gluconate Ig ( l Omg/ml) in 0.9% Sodium Chloride 100mi Fill in a IntraVia Bag, lot #13016003S (Expiration date: 3/2/13) was manufactured on 1/15/13 and shipped to a consignee on 1/16113 without sterility testing.
OBSERVATION 5
Testing and release of drug product for distribution do not include appropriate laboratory determination of satisfactory conformance to the identity and strength ofeach active ingredient prior to release.
Specifically, your firm has not conducted potency testing for the majority of the lots of drug products manufactured and distributed. For example, between 1/3112and 1/24113 your fum manufactured and distributed approximately _ o t s of drug product (Different form ulations/container closures) and conducted potency testing on 20 lots. For examp le,
The drug product, Heparin 2,000 Units per 1,000 mI (2 Units/m l) added to 0.9% Sodium Chloride Injection, USP, lot # 130 16002S (Expiration date: 3/22/ 13) was manufactured on 1/15/13 and shipped to a cons ignee on 1/16/13 without potency testing. The drug produ ct, Magnesium Sulfate 1 g Added to 50ml 5% Dextrose Injection , USP, lot #13016004S (Expiration date: 3/2/13) was manufactured on 111 511 3 and shipped to a consignee on
EMl't.O'rf:(S) SIGNATUHf
cere ISSUEO

FORM FDA 4U (""'I
Stephen D . Br o wn , Inv estigator@ Scott T. Ba llard . I nv est i gato r

PR.EVlOUS EDITION oosoum:
'i'-
02/2 7/ 2 01 3
PAQE 4 0 F ' PAGeS
L'ISPECTIONAL OBSERVATIONS
DEPARTMENT OF HEALT H AND HUMAN SERVICES

FOOD AND DRUG ADMmISlRATION
[iiSTRJCT ADDRESSANO PHC>IE NUU8R
OATE(S) Of INSPECT ION
4040 North Cent ra l Expressway, Su ite 300 Dalla s , TX 75 2 0 4 ( 214 ) 2 5 3 - 5 2 0 0 Fax : ( 21 4) 253 -5314 Indus trv I n f o rma t i o n : www.fda . g ov /oc/indus try
HAMl" A 0 TITlI!0
I ~ VI OUA.L 1 O WHOlo
02/19/2013
FEI Nl.N8CR
- 02/27 /2013
300 071 770 3
REPOR T ISSUED
TO:
f iiM NAM E
Mr . Bruce W. Bagby , Genera l Manage r 1 2 6 2 0 W Ai rnort Blvd Ste 130 .

fYPEUTA8LI$MUENl' INSA: C EO
PharMe dium Services , Ll c

CITV ~
s uerax Land , TX
774 78 -62 00
Pr oducer of S t e r i le Druq Products
1/16/13 without potency testing.
The drug product, Calcium Gluconate 1g (I Omglml) in 0.9% Sodium Chloride 100mi Fill in an IntraVia Bag, lot #13016003S (Expiration date: 3/2/13) was manufactured on 1/15/ 13 and shipped to a consignee on 1/16/13 without potency testing.
OBSERVATION 6
Drug products do not bear an expiration date determined by appropriate stability data to assure they meet applicable standards of identity, strength, quality and purity at the time ofuse. Specifically, A) Review of "Stability Report" dated 7/16/09 for Norephinepbrine. lot #1330720 and Sodium Chloride . lot #C769000 (Date of compounding: 5/8/09) under test sample designation 2 1 (Expiration date: 58 days) revealed assay results for the following days:
Time 0: Passed
%LC: 107.3, 107.6, and 106.8 (Specification_
Day 15: Passed
%LC: 108.0, 108.0., and 106.0 (Specification:~
Day 30: Passed )
%LC: 95.8. 97.7. and 97.2 (Specification: _ Day 46 : Passed
%LC: 94.5, 92.3, and 92.7 (Specification _ Day 6 1: Failed
1) Three samples %LC: 86.7,92.6, and 92.5 (Specification_ 2) Two samples (re-injection)
EW'I.OYEE(S) SlGHAn..ftE
DATt: ISSUEO

FOU l
Stephen D. Brown , I nVe Stig a t o O Scott T . Ballard, I nvest igator [;IJ

PllEVIOUS EDlT I)Jl OBSOU!'ll!
02 /27 /2 013
PA GE' OF' PAO ES
rnA..au
(09101)
INSPECTIONAL OBSERVATlO:<S
DEPARTMENTOF HEALTH A~" HUMAN SERVICES

f OOD AND DRUG AOMINISTRATION
DIST
S N> PHONE t<f,JI,lBER
O1<TE(S) 01' IN~, ~
4 040 Nor th Ce nt r a l Express way, Suite 30 0 Da l la s, TX 75 2 0 4 (2 14 ) 2 53 -5200 Fax: ( 2 1 4) 2 5 3 - 5 3 14 Industr y Info rmation : www. fda. q o v / o c/ i n dus trv
NAUEAND TTTU: OFH:llVlDUALTOVMOM REPORT lSSUEO
02/ 19/ 2 0 1 3
, ~ ......,.
02 /2 7 / 2 01 3
3000 7177 0 3
TO :
f IRM
NAtIl~
Mr . Bruce W. Bagby, General M a na g er

STR f.E T AOORESS
err- . STA, ~ zp COOE. COUNTKl
PharMedium Servic es, Llc 774 7 8 - 6 200
12 62 0 W Ai rtJort Blvd Ste 13 0

,."" lO S AlllISHMEHT HSPECTED
Su qar Land , TX
Pr odu c er of S t erile Drug Product s
%LC: 85.7 and 87.2
Day 91: Failed
1) Three samples: 90.1, 89.0. and 88.3 (Speci ficalion ~ B) Review of "StabiliIy Report" dated 5/09 for Norephinephrine, lot #1330720 and Dextrose , lot #C764068 (Date of compounding: 5/8/09) under test sample designation 22 (Expiration date: 58 days) revealed assay results for the following days:
Time 0: Passed (Re-Preparation)
%LC: 94.6, 95.1, and 95.6 (Specification:_
Day 15: Passed
Day 30: Passed
%LC: 98.0, 96.8, and 95.3 (Specification:_ Day 46: Passed
Day 61: Failed
1) Three samples %LC: 89.9, 88.6, and 93.8 (Specification: _ 2) Two samples (re-injection) %LC: 89.1 and 85.3
Day 91: Failed
1) Three samples: 87.3, 86.5, and 86.2 (Speeification:_ In each case, the OOS results were confinned as valid by your contract laboratory. However, your firm failed to identify a
EMP\.OVEE(S) SlaNA URE

FORM FDA.13 (otlOl)
Stephen D . Br o wn, Scot t T. Bal l a rd,

I'UVIOUS I!Drt'1ON 0BS0U!Tl!
I nv e s tigatorj::{3
Investigato{~~
o", T'E ISSUED
0 2/ 27/ 2 013
PACE 6 OF 8 PAGES
DEPARTMENT OF HEALTH AND II UMAN SERVICES FOOD AND DR UG ADMINISTRATION

DISTRICT,\QDA:ESS ANJ f>ttONE NUMBER
OA TECS) OFINSPECn::>N
4040 No r th Cent ral Ex pre s s wa y , Su i t e 3 00 Dallas , TX 7 5204 ( 214 ) 25 3 - 52 00 Fa x: ( 214) 2 5 3 -5314 Indus try Informa tion : www .fda . a v/ o e/indu s try
NAMEAND I OF V!OUAL. 0 .. EPOt{TISSUEO
02 /1 9 /20 13 - 02/27/2 01 3
FEI HUY6ER
3 00 07177 03
TO:
fl
~
M r . Bru ce W. Ba g by , General Manag er

A
PharMedium Services . LI e
C , STAT . C
126 20 W Ai
o r t Blvd S te 13 0
ABUSI-f.lE NTINSPECTED
Su a r Land , TX
7 74 78 - 62 00
Producer of Sterile Drug Produc t s
root cause or implement corrective action.

Your finn indicated that statistica l rationale was used to supportthe 58 day expiration date. However, there is no assurance that your finn has generated substantive data to support the 58 day expirati on date.
OBSERVATION 7
There is no written testing program designed to assess the stability characteristics of drug products.
Spec ifically, A) Your firm's stability testin~o include requ irements for anti-microbial elfectiveness testing to determine whether preservatives such as- . l feclively inhibit microbial growth in your sterile injectabY'g products through their Beyond Use Date period. These preservatives are used in the man ufacture ofapproximately. ifferent sterile drug product formulations, Some examples consist of the following: Heparin Sodium 1,000 Un its (2 units/ml) added to 0.9% Sodium Chloride Injection USP 230 Units Oxytocin added to Lacated Ringer's Inj ection USP
B) Your firm has never conducted sterility testing on stab ility samp les for any produ ct formulations.
OBSERVATION 8
The accuracy and sensitivity oftest methods have not been establi shed.
Specifically, your firm does not have data to show that microbial enumeration test methods used for environmental monitoring are capable of recovering and de~e presence of microorganisms on the surfaces of laminar air flow hoods (clean bench, model_ . On 212112013, I reviewed air and surface environmental testing results for January, March and August 2012. During this time, zero colonies w r both surface and air samples collected inside laminar air flow hoods according to th nvironmental Micro Reports (F-707-23). During hoods in Janu and March an~hoods (in August) was sampled this time each 0 up to
EloIPl.OYEE(SI &IO~TVRE
TE ISSUEO

f OR."" FDA 413 (OtlOll)
S tephen D. Br own , I nve s tiga to ( Sc ot t T . Ba l lard, Invest igat o r ~

PlU!VI()US
0 2/ 27/2 013
M OE7 OFI PAQES
~08S0I..m!
INSPECT IONAL OBSERVATION S
DEPARTME/'oT OF HEALTH AND HUMA N SERVICES FOOD ANDDRUG ADMINlSTRAliON

OlSTR AOOReSSANDPHONENlJIN8R DATE(S)
~
INSPfCTIOf\l
NAUE IoHfJ nne
4 040 North Central Expre s s way, Suite 300 Da l las, TX 752 04 (2 14) 2 53 - 5200 Fax: (2 14) 25 3 -5314 I ndu s t I nf o rm a t i on : www.fda . ov/oc/ i ndust
OF INDlIflDl.W.
02 / 19 /2 013 - 02/ 2 7/2 013 3 0007177 03
to VvK:'IM REPOR T ISSUED
TO :
Mr. Bruce W . Bagby , General Manag e r

STRf tT AOOR.f:SS
Pha rMed i um Servi ce s, LI e

CITY . STATE, Z . CO UNTRY
12 620 W Ai
TYPE
o r t Bl vd Ste 13 0 Pr odu c t s
sr"
Sugar Land, TX
7747 8-62 0 0
Producer of Steri l e Dr u
On 2122/2013 , I observed your employees collecting samples for environmental monitorin of hood surfaces and hood air sam les. Hood surfaces were sampled by of the laminar air flow hood. However, prior to using the n each of the samples observed, the 0 erator who mixed or ooled dru roduct in the hood, sanitized the stainless steel surface with There was no work performed in the hood between the time the surface was sanitized and the environmental sample was collected. I observed this practice for five of five samples collected.
OBSERVATION 9
Reserve samples for drug prod ucts are not retained for one year after the expiration date of the drug product. Specifically, your finn does not maintain retent ion samples for any drug prod ucts. For example, Heparin Sodium 25,000 Units (I 00 units/ml) added to 0.45% Sodium Chlorid e Injection USP 2 g Cefazolin Sodium in Sterile Water for Injection USP 40 g Magnesium Sulfate add ed to Lactated Ringer's Injection USP
DA EI 6SUEO

FORM FDA W (0910 ')
S t ephen D . Brown, Inv e stiga t o r Scott T . Ba llard, I nve s t i gato r

02 /27 / 201 3
PAGE' OF' PAGES
J)~; I'ARTJ\J~;N 'I'
OF
t1 ~;AI ; 1H
ANP Hlli\1AN SF.R" ICES

11J\1L(S)0f'1. 6f' L 1
!'OO Il AND DR UG ADMINlSTIt ATION
s u , & Kipling S t.
(1'. 0, Box 25 0fl 7 )
0 2/1 9/ 2 013 -
0 2/ 2 6/20 13 ~
-twJF-mO TlnF OI'lHIi,'v!o"l\ML TOWHOI,i"RI,I'Of>' l OOtlI'Ii
Denv er , CO 80225 - 008" / (30 3) 23 6-3000 Fa x: ( 303) 236-3100 Industry Info r mat ion ; wWI"" "f, dO """ g " o cv "l co ,c ~ /, i ,n,dOu" s" t"r cL Y
3 00 414 6124
"-
-------------------------1
TO : M r ""i1 ii:lNAM C
. Richard
E.
I
Ra s muson ,
IIl C .
o ~lll e r / Pharma c is t smH'T-'O!lfl1'(G
Uni vers it y Pharma c

Sal t Lak e Ci ty, UT
1320 East 2 0 0 South

"TYPE E STAIl Ll~W T INSPE CTED
8 41 04
Producer o f Steri le drug p roducts
Thisdocument lists observations madeby theJIDArepresenllllive(s) during theinspection of your fat:iJity.They aTC inspectlonal observations, anddo not represent a final Agency determination regarding yourcompliance. If you have an o~jection regarding an observation, or haveimplemented, or plan to implement, corrective notion in response to an observation, youmay discuss the objection or action with the PDA representntive(s) duringthe jnspectlon or submit this information to FDA at theaddressabove. If youhave nny questions, please contact n)A at tbe phnne number and address above.
DURING AN INSPECTION OF YOUR FtRM W E OBSERV ED;
OBSERVATION 1
Equipment ami utensils are not sanitized at appropriate intervals to prevent contamination that would alter the safety, identity, strength, q u~lit y or purity or the drug product. Specifically, .O .". F ., .b .,."." .Y . 19 . '.h. .i 2o . 13 . ,.d .".rill an inspcctional luur of the ISO 5 sterile core, J observed the following inside of'Iho firm's Hood wher_lerHe lnjcctablcs arc produced: . e were observed stuck 1) Along the front perforated/poredair guard, spills and splatters of amber and while colored residu to/clogged in these perforations. Approximately Imm of a dusty/fllU.y film was observed suspended/hanging from this residue. Approximately 2 0%of the ~ b)_ metal guard WIlS observed affected with the same; 2) Below the perforated/pored air guard, multiple spills and splatters orambcr, rust, and white colored residue were observed ill It drip-like metal pan. More than OIlC of these splattered spots were observed to be approximately 2 inches in diameter nud approximately 50% of'thc metal pan was observed to be affected wilh the same; 3) Above the work surfaceand directly below the houd's HEPA filter, multiple white residue splatters were observed attached to this suspended perforated/pored ceiling. One of'thesc splatter marks was approximately 6 inches in diameter and the total splattering covered approximately 15% of'thc metal ceiling. According to the pharmacy technician, this had Clever been noticed by him lind possibly occured from a misguidedstream of liquid ejected from n highly-pressurized syringe; 4) 011 both sides of the work surface area, in the crevices between the work surface areaand the side w811s of'thc 180 5 sterile hood, spills a nd.splatterlngs of an umber colored material were observed running along approximately 20% ofhoth of these crevices.
l-Mk o m #i iiiaw..iii'F4:

HH<M
~ I 'i\ ~83
Er~ka
V. Butler,
l nvcst~gut or
"
{rAt, -t,'/ , .-1 f / ~ . " 'U,'.f>'---Jf~

J.<;
~-
.~
Zac her y L. M i lle r , I n v e s t i g a t ~ ~ -- ~

I NSl't:enONA l. (mS~;RVATI O NS
0 2 / 25/2 013
j ll9;OII)
, ,
6th
, Kipling st.
r HONE
DEPARTMENT OF IIEALTIlANI) HUMAN S ERVlCES

FOOD AN n IJRU(J ADlI.J1NJ ~ TRATION
lJAl E((llor ~1SP<:CTlOH
( p . o . Box 2 5087)
0 2/1 9/7.0 13
r-f ' IllAAl8" I"<
0 2 / 26 /2 0 1 3*
Denver , CO 8 02 25 - 00 Wf
( 3 03 ) 2 3 6- 3000 Fa x: (303 ) 236 -3100
w~lW.tda,gov/oc/indust r y f'W.'~ AN~ ili LfOfT'lin~~UAl. TO I".lIOIol rll-'oR TI$livU>
3 0 0 4 14 6124
I n dus try Informa tion :

TO:
Mr . Richa rd E , Rasmus on, Owne r ! Pha r macis l

STll FFT Mll!l" &.~
FIRL " W,Of.
em-Sf'"TE.-;! o POOOI:.'colMf flY
Uni ver s i ty Pharmacy, Inc .

UT
U41 04
TYPE EStOOiil,;; IE , IIT ,r~ Sl'ECTFO
1320 Eu::;l 2 0 0 So u th
S alt La ke Cit y,
Pr odu cer o t Ster i le d rug product s
OBSERVATION 2 Test ing and re lease of drug product for dlsutbutlon do not Include epproprlatc laboratory determination of satisfactory conformance to the final specifications and identity and strength of each active ingredient prior to release. Specifically,
A. Firm released and dispensed Progestcrune/Prcgncnolonc 50rngf2.5mg inj ectio n lot 72 13'72 without test results of
ste rility, cndoioxm s and potency. Progesterone/Pregnenolone 50mgl2.5mg lilt 72 1372 was produced 1/22113 with a hulk y ield amount is 110 dcc umcntat lon in lhe Poneulnrton Workslu..e ' t of/ he number or intlivillual v ~nls filled from thc bulk batch. Director ofCompounding stated they can till approximate ly v ial:" n, Firm released and dispensed bulk hatch of Progesterone/Pregnenolone 5012.5 mg/ml lot 7 16 1~"'Clfomli ng a po tency/assay on both act ive ingredient s. Specifi cation for Progeste rone and Pregnenolone i. lor both activ es. Pirm stated the contrac t lab is having II hard time validating a method for Pregneno lone because it is too clos e chem ical ly to the other active. C. Firm released and dispensed bulk batch OfPro~"e lot 7 11102 without perform ing a 011 Pregnenolone. Pregne nolone specification i. released which can fi ll epproximetel _ vials. . D. After furthe r manipulat ions of the bulk steri le drug product (fi lling of ind ividual prod uct vials), the firm pC rf011l1 Sa sterility test on ly and not endo roxins or potency on the finished drug produc t v ial. For ex_ 01# 720775 bulk batch passed TRIM IX(Papvet'ine/Phe lltolamincJAlprostady l) 17.65/0.588/5.88 injections 1 the spcci flcattons for sterility endotoxlns and potency. After the test results passed speci ficatio n, th e firm Ills the via ls from the bulk batch and tests the finished product vials for sterility only . In addit ion, If nit.. of ster ile drug product are produced from a bulk batch then no testing is performed pe r SOP No . ess t lat 10.009 ti t c "Sterile Prepara tion Release Tests- Steri lity, Bacterial Endotoxin. and Pyrogen Tes t".
!!IIii
.S f
OBSERVATION 3 Procedures designed to prevent micro biological contamin ation of drug products purporting to be sterile do not include adequate validation ofthe sterilizauo np roccsa Specifica lly,
A.
Th~ steriflzatlon process for pro ducing the bulk batc hes of TIU MlX (Papaverine/l'hentola mineiA lprosmdyl) 17.65/0.5 88/5.1111 injeelions, I'rc gcstrone 50mglm l olive oil injeet ioll!), and Progcsteroncrr rcgncnolonc 5012.5mglml sesame oil injections has not been vali dated. The firm has no doc umentat ion to qualify the with rc rarda to bacterial retention, cxtructablcs, an d hard ware compatibility;
UH'I.O\"a($)
~l(JN'.lWE

FO RM PII .\
Erika V. But l er, Inve s t i ga t or zacberyL . Nill e r, I nvestigator~

"'lWIO V ~ PDmONI)Il. "".Rrn
01'3
O"'\ ~ JWJI O
0 2 / 2 6 /7. 01 3 .
PMI!! 2 Of
~ PA(H(,~
411311l'J1IlIl~
INSPECTIONAL OBSlmYATlONS
DF.PARTl'tfENT OF HEALTH AND n Uf\.tAN Sf:RYICFB FOOD AND DRUG AIlM1N1STRh n o

TIOOT FSS NlDPHONH IlJ"' OCfl
6th I< Kipling St. (P .O . Box 25 0 8 7 ) Den ve r, CO 80225 - 0087 (30 3 ) 23 6-3000 Fa x : ( 30 3) 2 3 6-3 1 0 0
l Jl du ~ t ry'. Infor ma t ion : w\~w . fda . Cjov!oc/illdus try w.."EAIl O rmece INlJIVIlIlW.. T01MKW " ,,'OflT IS';\O' D
02 / 19/201 3 - 02 /2 6/2 0 13 * 30041461 2 4
TO:
M r. Richard E . Ra smus on, Owne r-yph a rmao j at
CITy-;-Si"I~i<I> OO[)l,; courJiRY-_U---'"=~--------
Om.vocs Lt.y Pharmacy , Inc.
1 320 East 2 00 So uth f n"irlOSr"al,~m lNS>iCi"wF=~------------
Sa lt Lake City ,
ur
8~ 104
Produce r o f Ster il e drug pr od uct s
such as the case w ith the system used on the Progeserone'Pregnenolone 50f2.5mglrn l sesame oil batches . The um us 110 documentation to chal1enge the bacterial re tention oflh ~ with challenged organisms 01' bioburden quantity . All. ingredients are non-srcrltc for the TlUMIX injections, Progesrrone injections, and Progesterone/pregnenolone and Hydroxyprcgcsterone 250mg/ml sesame oil injeC_ti on~. III addition SOP If 8.012 titled "Compounding of Sterile Solutions", wriuen procedures establis hed for th does not specify the minimum pressure needed for th~ int egrity test to pass. The ten rzauon process for producing the bulk batches of lI drox rogcstcrone 2 50mgfml ses ame oil studies for the volume of batches has not been validated. There is 110 documentation ~ches produced by til .ten izauon pro cess. In ad dition, the _ _ _ _ _ used to sterilize the Ilydrcxyprogestcrone 25 0mglml ses ame oil batches has n~ qualified for usc.
!!I!
B. The finn uses'
nrc the system. The entire unit is or sterilization with no documentation oftime and temp erature. A HI indicat or is placed in Ih rh erc~ studies to demonstrate th o efficacy ef'thc method used to sterilize til 11m!. This_ sys tem is used for tim Progesterone/Pregnenolone 50/2.5mg/m! se same oil hatches.
C. Then: is nu validated sterilization process for s teriliz ing, au eye drop tip package component. J obs erved the firm produce a palie~prcscriWion ophthalmic sterile dru call ed P~ i l1e 1% Ophthalmic gel eye drops lot 722604. The drug w vith a HI and a_ f o.ninutes. T he no n-sterile Ophthalmic eye dro p tip w'U!; Immersed in II beaker 0 lor 110 specifl~Time or a procedure Slating the lim~ th e eye drop tip. After the dru g: was the eye <Imp tip was assembled onto the dru g vial_ _ nud dispensed to the patient.
OBSERVATION 4 Procedures des igned to prevent m icrobiological con1<lm,in~lion of drug produ cts purporting to be sterile are not follo wed . Sp ecifically, On February 19th, 2013, while witnessi ng thc pharmacy technician's sterile aseptic technique, in pro ducing Pilocarpine 1% Opthalmic eye gel lot fi722601 and TR lMIX (Pap aver.ineJPhentolamine/Alprostadyl) 17.65mgfO.588mg/5.88m g. lot II 722609, I observed the following: I } Th e technician's hands and anus were observed inside of the ISO 5 hood without s terile sleev e covers; 2) The techni cian's movements ill 11m 180 5 hood were observed 1 0 be too fast. J) Alone point during sterile compounding. the tcchni cianlofl the ISO 5 hood wlth collected wrappers/trash, passed thro ugh the ISO 7 bu ffer zone, the ISO 7 ante/gowning room, and into the lSO 8- prep room to discard collecte d trash without removing gowni ng mate rials/sterile gloves. He immediatlcy returned to the ISO 7 bu ffer room , through the ISO 7
F"I'lOYFF(SlM'l WlTlJRF
c; L?
02/26 /20 13
P AG~ 30~ $ PAGES
Erika V. Bu l l e r , I n v est i g a t o r {fi':':> zacnery 1" Mille r , I nvesti ga t or~

TNSPECTIONAI , onSERVATIONS
nAl1'(S)Of Il<
ell
6 th Ii< Kipling S t. (P .O. Bo x 2 5 0 87 ) Den ver , CO 80225-00B7 (3D 3) 236 -3000 Fax: (3 0 3 ) 236-31 0 0
02/19/20 1 3 - 02/26/2013 *
r El NU lIlltR
300414 612 4
Indust ry Ln t or mat Lon :

FllWuWE
\-l W\Q .
f da . go v/oclindustry
siii e1TO,i'i(ii> OQ;
NiifCAlII) f!ILh oflHOivloUJiLTi;iv,;;Qi,i llEf'OOi -I$Sl.tD
10:
Mr. Richard ~~ . Ras mu s o n , Owner / Pharmacifl l " , - - - - - - - - - - - - - - - - - -- --1
Clf'l: m-A""'.-Z;p coDf.-colJimly ; '"=CL'-= =---------f-; 1Yl'E E8TAlltf$l-i\tOO I~TEb =='--------------1
Un i v e r 3 i t y Pharmncy , I n c .
132 0 Ba st 200 South
Sa lt La ke
Cit'(~,-,"U~T_O ,,-,'~1~O~ 4
Pr oducer o f Ster ile d rug p roducts

to sanitize his gloves.
ante/gow ning room, and reached inside thc ISO 5 hood for the sterile _
OBSERVAnON 5
The control systems necessary to prevent contamination or mix-up s me deficient.
Specifically, A. There is 110 environmental monitoring or personnel mon itor ing (viable, non-via ble and total peruculatcs) iu the ISO 5 Class 100 Laminar flow hood dur ing or Immediately utter producing storllc Injectable drug produ cts. The pharmacy technician stated they conduct viable air monitoring and surface samples whcn they arc not in operation in the ISO 5 hood producing sterile drug products. Fo r example, "The Environmental Air Sample 1.0gBshows viable air samples were collected in the ISO 5 hood on the following dates: 2rt3/13, 11 12911 2, 10/1211 2, 819/12, 61 5/ 12, 2123112. The frequen cy of the viable air sampling is not cons istent and it is not defined in a procedure. Surface
samples are collected eve mon itoring is only conduct ed durin ) is:)' I .I
, , .
, I M rch n S '
nnbcr of20 12. Personn el to qualify personnel.
H.
is the only disinfectant used to _ d isin fect in the ISO 5 Class is effective again st hactorlal 1no Laminar flow hood. Thcre are no disinfe ction st udies 10 de monstrate thc spores 01' fungi.
C. We observed the inadequat e dis infection of the ISO 5 Laminar flow hood used for aseptic processing of steril e drug 1IIII~~S:,~~~."~1J c Pharmacy technician was observed only wipin g thc table top work surface with a sterile wipe and the ~ isin fccl nnl. He did not remove the stored items ~ bulk batch of Progesterone, eye drop sol ution, . sterile eye drop assemblies] in the hood and did not wipe down the sides or the back of'fh c hood for prcp amtlon or sterile compounding of injectnblcs. In addition , lim SOP titled, "Sterile Co mpounding Room Cleaning an d Disinfecting", No. 5.003 Revision 01 docs not 'describe ill demit how to clean the JSO 5 hondo It reads: I. Remove items from area 2. Clean surface. D. There is 110 rotation ofd isinfecta nts used in the ISO 7 and ISO 8 buffer room, ante room and preparation rooms. hich is used as a sporicide lor the cleaning of'thc uo n-stcrllc pruparatlon area outs t e t IC c can room an ours! C IC ISO 5 homl urca. E. We observed phmmcy tec hnician weigh non-sterile dry act ive ingredients sc ales in between weigh ing the actives for two sc ararc fo rmula tions
011 wei
We observed debris in crev ices of weigh scales and pink dry powd er resid ue which ; had accumu lated in the baek orthc exhaus t intake inside this co ntainment where non-sterile dry ingredients me weighed. F. No smoke stud ies are performed in the ISO 5 Hood in dynamic conditions 10determine unidlrectlonal ntrnow or air turbulence over sterile drug prod uct. In addition, there is 110 mon itoring of the maguehlic pressllre il l the ISO 5
Hood. - -- - - - - n EMPi.a"" QSj $l....lURE' - - - -- - - - - - " cc, , - - - - - - - - - -- - '

FORM !'IM
f~ H(IlI:OSl
tiA'ii1 I6SUUl, -- 02/26/2013
Eri ka V. Butler, I nvestigator Zachery L . Mille r , Invcst igato~

INSI'I-:L TIO N/\ I. (lII%KVI\TIWIS
UEI'ARTMENT or HEALTH ANI>HUMAN SERVIQS

FOOD ANIJ rJRIIO AIJM INISTRA'rlON _
~
AOOflt M ....'"
N "M nei!
M rr
~~
Kipling S L ( P , O. H o x 250B 7 ) Denve r , CO 8 0225 -00 8 '/ (303 ) 2 36- 3000 Fax : (3 03) 236- 3 1 00 6th
&
02 /1 9 /20 13
rn NIJJ.lOR
0 2 / 2 6 / 2 0 13*
300 41 4612 4
Indus t ry I n fo rmation: www. f da . gov /oc/i nd ustry

-w.",~ ANDi iTu. OF '_WI\~00AL 10w.i OM
RU'llIU ls'S\.JED
TO:
Fl AAl/W.',E
Mr ',
Ri chard E . Rasmuson , Owner/ Pharmacis t

SlRe~ TAOORE$Il.
Uni vers it y Pharma c , I nc .

CITY. SfATE. l rJ'OOOE.COUNT>tY
1 32 0 East 2 0 0 South
TYPE EBTlIBllSfWENT mS PEClEO
Salt La ke Ci t y,
UT
8410 4
Produ c Clr of St ClrilG d rug produ c t s
OBSERVATION 6
Result:; of stability testing arc not used in determini ng expiration dates. Specifically, A. There is no stability data to support the sterility or potency of'P rogestcronc rl'rcgncnolonc vials beyond Usc Date (BUD) of 6 months. For exam ple, Pro gestcronc/orcgn cnoton c 50 mgl2.5 mg lot 7 161R4 produced on 9121/12 has a beyond usc date of 31201l 3. H. There is 110 steblftty data to support the potenc y of the TRIM IX (Pupllvcrinc/Phen lu lamillclA l pro.~tlldyl) 17.65mg/0.588mg/5.88 mg injectio ns, Progesterone 50mglml olive 011 injections, refrigerated drug vials Hun of90 days. TriMix IOf 720775 hatch pro duced and refrige rated on 1/8/13 ; BUD of 4/8 / 13. c. There is no sta bility protocol to evaluate cnch of th e drugs for physica l stability, chemical stability, and micrubiotogicnl stubility througho ut the shclfl ife clai med and stora ge co nditions.
..,. -- "'-- -._.- .-"'.-
..,
.-
. '--
-,
~ DATKS OIIINSl' EcnON: 02119/2013(Tue), 02120120 IJ(Wed), 02121f1013( 1110), 02122120l3(Fri), 02I26/2013(Tue)
I.MPI. OYli(S)513t... ,UR.

H lI<'" P"'" 4lQ (0 9/l1!1
Eri ka V. Butl er ,
ze chcr y L . , Mill er, I nvestig ato

PI<""roll~ 1'1l"")~ Oll. <'OU,i,i
InveStigato~
' ~_ ~
~, .
1/,r cJ5tt'.;f:~ .
~ ~L-
OAT t JSSU" O
02/26/2013
PMI!! 5 O F 5 pA(Jr,~
INSI'lWl'l ONAL
{)IJSl;ltVAT Il I~S
DEPARTMENT OF ilEAL111 AND HU~fAN SE RVICE S

- OtSTRlCT A.ODRESSAND PHONE
NUMiie - .-
-- f-1X?P AND DRU G AD M INlS TRA 110N
DA TE \SjOF iNSPECTiON
19,01 E 'ai r c hil d Ir vi ne . CA 92 612 (9 49) 608 -29 00 Fax : (949) 608 - 4417 I nd us t r y I nf o r mat i on : www. f da. gov / oc / i nd us t r y
~E
02119/2 013 - 02/25/2013 *

fEI NUMDER
30 063 453 05
.-.NOTrTLE OF INOIVIOUAL TO \/'M OM RU'OfH ISSUEO
TO:
FIA l,INAAlE
us i l , Pharm . D. , Cheif Exec uti ve Of f icer 1 Founder John D. M

STREET ADOAESS
Ave l l a o f De er Val ley , I nc .

l,;11T. I;jlAlt:. L IP u..lO e ,l,;UVN IHV'
23 620
20th Dr Ste 12
TYPE ESTAlIllSHMENT INSPECTED
Phoe ni x , AZ
8 5085-062 1
Prod uce r of Sterile Drug Pr odu ct s
This document lists observations made by the FDA representativc(s) during the inspectionof your facility. They arcinspectional observations, and do not represent a final Agency determination regarding your compliance. lf you have anobjection regarding an observation. or have implemented, or planto implement, corrective action in responseto anobservation, you may discuss the objectionor action with the FDA representativefs) during the inspection or submit this information to FDA at the address above. If you have any questions, please contact FDA at the phonenumber and addressabove.
[Amendment issued to correct Title of " Report Issued to" and to include clarification to O bservation 2.1 PRODUCTION SYSTEM OBSERVATION 1 Protective apparel is not worn as necessary to protect drug products from contamination. Specifically, a) During sterile drug production, technicians were observed wearing non-sterile gowning with exposed skin within the cleanroom environment. Per the firm's written procedure, SOP 03 S-32, "Personnel Hand Hygiene and Gowning for Cleanroom Entry", Revision I O 1 1~ 1 2 , the finn's uniform components for entry into the cleanroom includes: shoe covers. head and facial hair covers, face mask donned to cover bridge of nose, a non-shedding lab coat or gown, and sterilized gloves. There is no provision for the areas of the face around the eyes and area around the neck. During the walkthrough ofthe facility on 021 19/ 13, operators were observed with exposed skin around the eyes and neck area in the c1eanroom ISO , envirooment in which the ISO 5 Biosafety cabinets are located. h) The finn does employ the use of sterilized gloves in the ISO 5 envirorunents. However, the sterile gloves are donned by the operator in the ante-room area (ISO 7) prior to entry into the clcanroom and subsequent ISO 5 environment. We observed an operator contact the outside of the sterile glove with bare hands white gowning. ~the operator was observed wiping down the interior surfaces of the ISO 5 Biosafety cabinets After cleanr with sterile ipes while wearing the sterilized gloves. Next the operator was observed wiping materials and components with sterile ~ipes and placing them into the ISO 5 Biosafety cabinet. The same operator then proceeded to e~Pt1c processing of drug products within the ISO 5 environment using the same gloves sprayed with sterile and air dried. There were no additional sterile gloves donned within the ISO 5 environment prior to contacting sterile materials for production. Furthermore, the operator's forearms which enter into the ISO 5 environment to perform aseptic operations are covered with non-sterile gowning which is not
AM ENDMENT 2
EW'LOVEEIS) SC NATURE
S EE REVERS E OF THIS PAGE

FORM rnA 40 ( 09/tI.)
Joe y V. Qui ta nia , I nves ti gator Soni a R. Pe terson , I n ve s t i ga t or

PREVIOUS EDmoN OBSOI.El1i
0'11'/.<;(/3
DATE ISSUEO
02/25/20 13
PAGE I OF tI PAGF.S
INSPECrtON" L OIISERYAn ONS
DEPART MENT OF llEALlll AND II UMAN SERVIC ES FOOD A.J';ID. 1)!RP9 .~MlNlSTRAT ION.
DISTRICT ADDRESS ANOP HONE NUMBER
DArEtS)OFiNSPECTION
a-
---j
1970 1 Fa i r ch ild I rv i ne , CA 926 12 ( 94 9 ) 60 8-290 0 Fax: (94 9 ) 608 - 4417 I nd us t ry I nfo r matio n : www. f da . gov / oc / i ndu s t r y
~
02/1 9/20 13 - 02/25/20 13*

FEINUNBER
30063 453 05
OU
'
.... MOM RE
T ISSUED
TO:
FIRM NAAlE
Joh n D. M us i l , Pharm.D . , Chei f Exe c ut ive Office r / Founder

STREET AIJORl;:&S
Avel l a o f Deer Vall e , I nc.

C , STATE,ZI'
e.
23 620 N 2 0t h Dr Ste 12
STABl M llIIsPECtE D
Phoeni x , AZ
8508 5-062 1
Producer of Ste rile Drug Pr odu c t s
adequat e to protect from conta mination.
OBSERVATION 2
Asept ic proce ssing areas are deficient regardi ng the system for monitoring environmental conditions. Specifically, Environmental Monitoring of the firm's ISO 5 Hood environments and ISO 7 Cleanroom Environments used to produce sterile drug products is-io od eq uote- ond does not represent actual production, for example:
a)
b)
Lack of [routine] viable particul ate air monitoring (ISO 7). There is no [r out ine) monitoring of the viable air particulates in the ISO 7 environments during active processing. [There i~v iable particul ate mon itoring co nd ucted by an outside con tractor. I The ISO 5 Biosafe cabinets and Laminar air flow hoods are located within ISO 7 cleanrooms. The firm employs the However, it was ex lained that thi
c)
Lack of active non-viable partic ulate air monitoring (ISO 5). There is no monitorin g of the non-viable air particulates duri ng aseptic processiog of drug products in the ISO 5 environments. Mon itoring is only performed during certification by an outside contractor ever~t static condit ion. Lack of active non-v iable particulate air monitoring (ISO 7). There is no monitoring of the non-viable air particulates during production of drug products in the ISO 7 environments. The ISO 5 Biosafety cabinets and Laminar air flow hoods are located within ISO 7 environments. Monitoring is only performed during certificatio n by an outside contractor every at static condition. Lack of active monitoring of differential pressures. There is no monitoring of the cleanroom pressure differentials during aseptic processin of dru roducts. Differentials ressures of the ISO 7 Ante-room, ISO 7 Chemo room, and ISO 7 IV room are
~nder static condition.
d)
e)
There is no further monitoring of the c1eanroom presswe differential gauges either manually or by eleclronic devices during production.
AM ENDMENT 2
EMPlO'YEE(S) SIGNAru RE DATEI SSUEO

FORl'lI FDA 4U (09101)
Joey V. Quit ani a , In ve s t i ga t o r Son i a R. Pe t e r s on , Invest igator

PIlEVIOU 5liVm ON OOS(ll.ElE
02/25/2013
PAG F- 2 OF 6 PAGES
INS,' I:cnONAL ()8SF.RVATlONS
DEPARTM D.T O F IIEALTI f AND HUMAN SE RVICES

f
U AND DRUG ADMINlSTRAnON
19701 Fa i r child
02/19/20 13 - 02/25/2013'
I r vi ne , CA
NAMEAND rme
926 12
Fax : ( 9 49) 6 08 - 4 4 17 3 0 063 453 05
( 9 49) 608-290 0
I nd us t r
TO :
I nformat i on : www.fda .gov/ oc / indu s t r y

1N00ViOl./Al. TO 'MiOM REPORT ISSU EO
J oh n D. M usi l, Pharm.D. , Che if Exec ut i ve Of fi c er / Founde r 2 3 620 N 20t h Dr Stc 12

STA8U$KIEHT
e e r Valle , I nc. Avel l a o f D

a n'. STATE. I P COOE.coumrt'
crec
Phoen i x , AZ
f)
8 5 08 5 -0621
Produ c e r of Sterile Drug Pr od uc t s
Insufficient frequency of personnel monitoring. Sampling 0 loves post shift of aseptic processing of drug products in the ISO 5 environment is conducted on basis. In addition, personnel monitoring of operator's fingertips is conducted and repeated eve~ _ or each operator. However, sampling of the operator's gloves or arms is not conducted after every lot ~cally processed drug produces in the ISO 5 environment Insufficient freq ue nc~c nta l monitoring of the ISO S Environment, surfaces. Environmental sampling is collected_ However, the locations are rotated and not every ISO 5 surface used for aseptic processing of drug products is sampled. Furthermore, there is no environmental monitoring surface sampling for the aseptic processing of each lot of drug production.
g)
h) Insufficient frequency ofenvironmental monitoring of the ISO 7 cleanrooms (surfaces. Environmental sam lin is collecte and the sam lin locations are rotate
OBSERVATION 3
Procedures designed to prevent microbiological contamination of drug products purporting to be sterile are not.
Specifically, a)
_ I1
Ponents in-house vi~tcrilization utilizing th located in the ISO 7 Ante room. Operators are trained to the use of the equipment verbally through on-the-jo training. However, there is no written SOP outlining the use and maintenance of the equipment. The finn sterilizes vials used in the processing of aseptically processed drug product with this equipment. on ' -basis. However. for routine runs. there The ~I lndicalors through the is no_ monitoring. The equipment does not display or record_ exhibited during each cycle. Furthermore, there is no chart or data recording made f~
b)
water s stem located in the ISO 8 Prep room supplies water to the finn's There is no written SOP outlining the use and maintenance of the water system. The water system is maintaincd_ by an outside con_ does ~ d uct any sampling and testing of the water quality produced by th, - ~ater sy stem .
AM ENDM ENT 2
DATE ISSl.E D
J oe y V. Qui t a n ia , I n ves t i ga to r
Sorll a R. Pe terso n , I nve s t i ga t o r

INSP ECnOl"4AL OBSERVAl IO:\."
02/2512 013
PAGE J Of 6 PAGES
DEPARTM ENT OF IIEALlll A!\l) HUMAN SF.R\'ICF..S

DmRCTACORESS INJ PHONf: NiJiilllR
FOOD ~ORUO ADt.UNlSTRA TION
19701 Fairchild Irv ine . CA 92 612 (9 4 9 ) 608-2 9 0 0 Fa x : ( 949 ) 6 08 - 4 4 17
02/ 19/2013 - 02/25/2013'

1'1:. NUMBER
3 0 0 63 4530 5
Indust ry In f ormat i on : www. f da . gov / oc / ind us t ry

NA."'E o'.N) T. 'uo ............ ... ,Du.....Tv ............. PlI:M.JPI ' IS:>ul:l.I
TO:
"U~ _E
us i 1 , Pharm . D. , Che if Execut i ve Of f icer I Founde r J ohn O. M

s m EETADORESS
CITY . STATE,lP ecce.cournn'
Avel la of Dee r Val lev, Inc . Phoenix , AZ

8 5 085-0621
2 3620 N 20th Or Ste 12

saee
, ~CTaJ
Producer of Ste rile DruQ Produc ts
OBSERVATION 4 Procedures designed to prevent micro biological contaminat ion of drug products purporting to be sterile do not include validation of the sterilization process. Speci fica lly, a) Media fills conducted by the finn within the ISO 5 Environments on ' -frequency are inadequate in that Ihe firm does not record the results of the positive control to indica te the med ia was able to support growth. In addition, the media fill record does not include sufficient detail to establi sh that the conditions mimic those that occur dur ing routine production, (such as numb er of individuals in the room, equipment placement, doors opening and closing. etc). The total time to comp letion of the media fill is not record ed. Furthermore, there is no documentation made of which ISO 5 Enviro nment or room was used to conduct each media fill. In April 20 12, certificat ion conducted hy an outside contrac tor for the finn' s ISO 5 and ISO 7 env ironments used to aseptically process dru g produc ts yielded out ofsp ecifica tion results in the finn's IV Cleanroo m in (3) three locations for non-viable particulate air. The followin g results were reported : Sampling Location ISO 7 IV Room Samole 5 IV Room Samole 6 IV Room Sarnole 7
S.OI! per mJ - Result
(Specification _ j ,O "., per tTl )
h)
4,250 particulates 3,536 narticulates 3,286 nartieulates
There was no re-sampling of the locations performed. Although these locations exceeded the specificat ion at the static condition, the room was still certified.
c)
Certification conducted by an outside contractor for the finn ' s ISO 5 environments used to aseptically process dru g products includes performing smoke studies to demonstrate the air flow within the Biosafety Cabinet or Air Flow Hood. There is no recordin g made o f the smoke study to conf irm that the airflow is smooth, laminar, and withou t turbul ence. It was explained that during certi fication, there is no firm representative involved to view the air flow smoke patterns. The smoke studies are conducted at static conditions.
OBSERVATION 5 Individual equipment logs do not show time, date, product, and lot numb er of eac h batch processed. Specifically,
AMENDMENT 2
t MP\.OY(S) SIG ~ TUlE.
SEE REVERS E OF TH IS PAGE

t1) IU I Jo-oA
oil) 10t0't1,
Jo e y V. Qu i tani a , I nve st igator Son i a R. Pet er son , Invest i gator

rltt\'lOOS EllfTON (BSOl..ElE
~
(
OATE I8SUED
::
0 212 5 / 20 13
r AGE4 Of 6 PAGES
INSP F.CT IO NAI.. OHSt:RVAT IONS
ro:siRICT AOCAESSJoN[) PHONEMJWiER
DEI)ARTMENT OF II EALlll AND IIUM AN SF-RVleE-1ii FOODANDDRUG ADM1NI~~:DON D '" ''
1 97 0 1 Fai rc h i l d I r v i ne . CA 92 612 ( 9 4 9) 608-2900 Fa x : ( 94 9) 608 -44 17 Indust ry I nformati on : www . f d a . go v / oc / i nd us t r y

N,tJ,FE AM> HlU 0'
0 2/1 912 0 13 - 02/25/20 13'

FI""-'UIER
TO:
FIRM NAMf
usi l , Pharrn . D. , Che U J o hn D. M
.."",,, .
300 634 5305
Execu t i ve Of f ice r / Fo unde r

STREETADDRESS
CITY, snre. ZIPCODE ,COlHTRY
Avel l a o f De er Va l l ey , I nc. Phoe n ix , AZ 8 508 5- 0 62 1
23 620 N 20 t h Dr St e 12
Pl:E6TA
onD
Produc e r of Ste r ile Dr ug Pr od u c t s
The finn does not maintain a use log for each of the _ I S O 5 units used 10 produce sterile drug products. The ISO 5 units (B iosafety Cabinets and Laminar Air Flow hoods) located within the firm's Cbemo room and IV room are not dedicated. There is no documentation to show what products were produced within the units and the equipment is not recorded on the individual product fonnu lation sheets.
OB S ERVATION 6 Batch production and control records do not include the specific identification of each batch of component used for each batch of drug product produced. Specifically,
For example, Compound Log Worksheets did not include lot information for the following items used in production of sterile products: used in tbe production of Progeslerone 12-20 121201 @119 whicharesterilized in you, a)
_Is
h)
Components used in production and packaging of sterile products including:
i. Bupivacaine HCL/Lidocaine HClJllyaluronidase (Peribulbar) 0.3611 O/oI2.5UIML (Injectahle) ii. Povidone Iodine 5% (Ophthalmic)
DUALITY SYSTEM OBSERVATION 7 Written records arc not always made of investigations into unexplained discrepancies. Specifically, a) _ The finn manually reads and records the pressure differentials of the cleanroom suit Pressure differential excursions offow pressure observed in February 2011, August 20 1I, September 2011, October 201 I, November 2011, Deeember2011, January 20 12, February 20 12, and February 2~ appear to be investigated. These excursions occurred in the finn's ante-room (ISO 7). Specification H20 ; results recorded were low a~ HtJ. There was no investigation conducted in response to these out of specification results. Furthermore. there are some notes recorded on the forms referencing service calls of repair to
AMENDMENT 2
EMP\.OVIE(&) &JGWlTUlIE
SEE RE VERSE OF THIS P AGE

t'OR.'" rnA W
(~')
J oey v . Quitani a , I n ve s t i g a t o r Sonia R. Pe t e r s o n , I nve stigator

f'lI.ElIlOtJS UllTOH 08SCUl1E
DAl E ISSUED
02/25/ 201 3
PAGE S0I'6 .....GES
IJ' 'IISI' ECTIONA L OnSERVAT IO SS

DISTRICT ADDRESS AND PHONE NUMBER DATE(S) OF INSPECTION
19701 Fairchild Irvine, CA 92612 (949) 608-2900 Fax: (949) 608-4417 Industry Information: www.fda.gov/oc/industry
NAME AND TITLE DF INDIVIDUAL TO WHOM REPORT ISSUED
02/19/2013 - 02/25/2013*
FEI NUMBER
3006345305
TO:
FIRM NAME
John D. Musil, Pharm.D., Cheif Executive Officer / Founder

STREET ADDRESS
Avella of Deer Valley, Inc.

CITY, STATE, ZIP CODE, COUNTRY
23620 N 20th Dr Ste 12

Phoenix, AZ
85085-0621
the air handling units. There is no current review by the Quality department of the air handling equipment maintenance records or on-demand repair records, b) During the walkthrough on 02/19/13, we observed an instance where the operator's glove tore exposing bare skin during aseptic processing within the ISO 5 environment of Hood 4 during the mixing ofBupivacaine HCV Cyclopentolate/ Flurbiprofen/ Gentamicin! Phenylephrine/Tropicamide Ophthalmic, Lot# 12-20131802@21. The glove tore during the mixing operation and the operator immediately exited the cleanroom to change gloves, then reentered the cleanroom to continue the aseptic processing operation in Hood 4. In the presence of the finn's Quality Assurance manager, Pharmacist, and finn management, there was no action initiated by the operator or those present to assess product impact for the lot. After the operator's glove tore, bare skin was potentially exposed within the ISO 5 environment during the mixing step of this product. When asked whether or not the incident would be documented within the batch sheet, the finn's Quality Assurance manager indicated that it is not a requirement. There was no investigation initiated at that time. Furthermore, the finn's SOP 03 S-32, "Personnel Hand Hygiene and Gowning for Cleanroom Entry", Revision 10-17-12 does not provide any instruction to contact management or assess to product impact in the event of a glove integrity breach during aseptic processing of drug products. The operator re-entered the cleanroom after changing gloves and completed the operation.
* DATES OF INSPECTION:
02/19/2013(Tue), 02/20/2013(Wed), 02/22/2013(Fri), 02/25/2013(Mon)
AMENDMENT 2
EMPLOYEE(S) SIGNATURE DATE ISSUED

FORM FDA 483 (09/08)
Joey V. Quitania, Investigator Sonia R. Peterson, Investigator

PREVIOUSEDmON OBSOLETE
02/25/2013
PAGE 6 OF 6 PAGES
INSPECnONAL OBSERVAnONS
DEPARTMENf OF IIEALTII
AJIo1) 11UMA. ~
SERVICES
FOOD AND DRUG ADMINlSfRATION
5 55 Winde r l e y Pl a c e , Sui t e 200 Mait l a n d , FL 3275 1 (4 0 7 ) 47 5-4 7 0 0 Fa x : (4 07 ) 47 5-4 7 6 8 I n dust r y I n f or ma t i on: www . fda.gov / oc /indu st ry
W.... E ""' D TIT'LE OF .. ~ TD"""OM REPORTISSUED
0 2/ 1 9/2 0 1 3 - 0 2/ 2 2 / 2013
FE' NUt.o BE/l
30 0 4483463
TO :
Jacob J . Be cke l , CEO

ecce, COUOlTIlY
Ana za ohea 1 t h Corporati o n

CITY. $ TAT!t ZIP
Ta rr.pa , FL
33 634 -5339
Pr o du ce r o f ster i l e p roduc ts
This document lists observations made by the FDA representativefs] during the inspection of your facility. They are inspectional observations, and do DO( representa final Agency determination regarding your compliance. If you have an objection regarding an observation, or have implemented, or plan to implement, corrective action in response to an observation, you may discuss the objection or action with the FDA representative(s) during the inspection or submit this information to FDA at the address above. If you have any questions, please contact FDA at the phone number and address above.
DURING AN INSPEC TION OF YOUR FIRM WE OBSER VEO:
OBSERVATION 1
Procedures de signed to prevent microbiological contaminatio n of dru g products purporting to be sterile are not established, written, and followed Specifically, The Pain Management media fills do not simulate production proce sses under no rmal operating conditions. Some deficiencies include but are not limited to: a) SO P P-403 "Pain Man agement Premix proc ess verificat ion of sterile compounding fill" and SOP P-402.2 "Pain Management Media Fill and Process Verification" is deficient in tha t: 1. The operator mixes the non-sterile (b) (41 media powder in an unco ntrolled area instea d of th e ISO 7 area where non- sterile powders are handled during rou tine productio n. 2. The filled beaker where this med ia is prep ared is sanitizeC(b)(41 times with (b)14) and (b) (4) prior to entering it into the ISO 7 area and ISO 5 hoods thus expo sing the open media to disinfectants. 3. Growth promotion tests are not conducted on the media used for media fills. 4. As per SO P P403, no environmental monitoring, i.e. fingertip, air and surface, is conducted during media fills. 5. SOP P-402.2 requ ires the removal of the 'lbH4J sterilizing filte r during medi a fills of "Medium risk" prod ucts th us not representing actua l productio n operations. 6. The medi a fills did not incorp orate worst case cond itions such as longer process times, extended exposure of components, interruptions/breaks, or othe r appli cab le routine situat ions that could potentia lly impact the sterility of the product. b) SOP P-4 03. 1 "Pa in Management High Volume Process Ver ification Media Fill" is de ficient forthe same reasons as stated above (a). In addition, the 10 ml sterile vials (commercia lly purc hase d) used in media fills do not represent th e larger 50 ml via ls used in regular production. Furthermo re, the 50 ml via ls and stoppers used in regu lar production are not app ropriatel y sterilized an d lb)f4 Ii. c) Procedures and log book s/forms governin g th e use of (bl (4}" " do not state the prescribe d sterilization param eters (time, ~H4J~~ load, etc.] of any kind; no s uch work instructions were posted or readily available. It was
AMENDMENT 1
Et.oPUlYEE(S} S>CliATU.... DATE ' SW ED
1--------"------------#~tJt/J, ' ;:=_-~~-1

FOR.\f FDA 483 (09 '08)
CDR I l e a n a Ba r ret o-Pet t it ~ I nve~ t l aor~ .. Robe r t C. Steyer t , Lnve s t Lq at. o r ,_ Le s l e y K. Satte r whi t e , M i c r obi a l i st
L'SP UTlO;";Al OBSERVATIO;,,;S
_ /a "";;<:::;::;-- I-- '-' ..'

~
0 2/2 2/2 013
'f
P~ Ci El0F7r", CiES
DJ::PARntJ::~T
DlSTIlICTADOftES S .oIlO _
N""l M ~
OF IIEALll lA'IrlDII UMA.""i SERYICES

DA TE(S) Of' INSPECTJC::*j
FOOD AND DRUG ADMINISlRAnON
55 5 W i n d e r l e y Pla c e , Sui t e 20 0 Mai t l a nd , FL 327 51 ( 4 07 ) 47 5- 47 00 Fa x : ( 40 7) 4 7 5- 4 7 68 I nd us t r y In fo r ma tion : www . fda.go v /oc/ indus t r y

......sAN::> Tm.f Of' I N ~",ouo.L TO WtOM ~EPOR T IlJW
0 2/ 1 9/2013
f EI N......S E ~
- 02/2 2 /20 13
30 0 448 34 6 3
TO:
f lRl,I 'lMl.
J acob J. Be c kel , CEO

STRf;ET AOOIIESS
An a za ohea l th Co rporat i o n
e rrv, 51ATE. ZIP CODE. CO\!I<f RY
5710 Ho o v e r Blvd
lY?E E sTA I!LIS~ENT INSl'ECTEO
Ta mp a ,
FL
3363 4- 533 9
Prod ucer of s ter i le p r o ducts
observed ~ i;cians used the ....Tong sterilization parameters for "wrapped" utensils ol(b) (4)(4 for minutes insteadof (b)(4) ~~~ minutes as established by your finn. These utensils are used in the ISO 5 LAFW . d) Some of the )(4 " Tapped glassware and utensils available for aseptic operations were observed with brown sta ins, tears, and not identified with dale of sterilization. oj Bottles of sterile are re-filled in house with non-sterile in the nuclear clean room without obliterating the original "sterile" label o f the bottle. These typ e of bottles were observed in ISO 7 & & areas of the nuclear and pain management clean rooms. It was not possible to differentiate betwee n bottles containing sterile )(.( from those containing non-ster ile f) Prior to transfer into the clean rooms, package s of components, containers, closures and utensils are disinfected with I=:\b}r~~lspray; however, it was observed that the components were then wiped off with a d irty rag. lbH4 supplies are not identified with a unique number for each "'l:D" .( J" load/batch, and "Tapp ed supplies g) mayo r may not be identified with a date o f steriliza tion. conse~~i(~pa in Management Pharma cy): J( runs had been used in sterile preparation I. There is no assurance as to whethe r supplies from failed areas. 2. It co uld not be determined whether the firm 's prescribe d exp iration dater(bH~l l had been exceeded for undated wrapped sterile supplies used (of the dated supplies availa ble, some were expired).
'"
"
'"
OBSERVATION 2
Procedures designed to prevent microbiological contamination of drug products purporting to be sterile do not include validation of the sterilization process. Specifica lly.
(l5l J~"" , .. products produced by a) Your firm fa iled to validate thf (O) (4)' filters used to sterilize your firm from non-sterile com ponents. In addition, your firm has not established pre-filtration bioburden limits in order to determ ine if it exceeds the maximum retention capability of the filter.
b) r" l:Dl(4J, sterilizat ion process parameters in use for liquid nuclear preparations differ from the validated processing parameters, in some cases (exttmHHlknown,-peaSiRg-reeeipt-ofaddition31reoor4s-00 2 22 13). Sterilization time and I ~)(.()..... we re both decreased, while (in some cases) container sizes and volumes were increased and "pig" shields were added. Further, the time and ~) (.(r - - t 'param eters used val]' significantly from batch -to-batch, depend ing on which I "'l:D" .( J" unit is used. The se chang es have not been validated to ensure sterility and other product quality attributes. c)r-t:"H4f""1 sterilization process parameters for dry supplies (beakers, stoppers) have not been validated. in some cases, depend ing on which~)(.()'" unit is used . Sa id supplies are used in sterile IS0 5 processing areas. d) Some r
lb) (4)-,
sterilization process validat ions (where performed) only demon strated a 3-log kill (biological indicator
AMENDMENT 1
EIO "I. Oi'U.(S) S,GN,O.T....E
CDR I le ana Ba r r eto- Pe tti t ,

FORM FD A
Robe r t C. St e yert , Inves ti g at o r Le s l e y K. Satt erwh i t e , M icrobi o l og s t ~

PREVlOC 'S EO m ml O~ <a.ErE
Inves~~r
DA l e I& SOe D
02/ 22/2013
on
(09IOS)
J:liSPECTIOSAL OBSF RVATlO:\S
PAGF 1 OF 7 PA(iF~
OISTROCT !oDDRSSANllI'ftOOE
N~E~
Dt:PARTMENT OF H t:ALTH AND HUMAt"'lSt:RVICr .s FOOD AA "DDRUGADWNISlRATiON

DATE! S) CI' I NSPECT IO ~
555 Win d e r le y Pl a c e, Suite 2 0 0 Mait land, FL 3 2 75 1 (407 ) 4 7 5-4 70 0 Fa x : ( 407) 47 5- 4768 I ndus try I n f o r mati o n : www . fd a .gov / o c / i n d ustry
NOM! ND TlTLI!! oj'NPI;;'~TO ViI'POM ~UOFl.T ISSuED
02/1 9 /2 013
ea
N\lM6E~
02/2 2 /2013
300 448 34 63
TO :
"' ..... """'e
Ja c ob J. Be c ke l , CEO
STRETIIOOl':I!:SS
Ana z a ohea l th Corporation

CITY , ST~T"E . ZIP COQf, COUNl'lY
571 0 Hoover Bl v d
TYPl! ESTII9lJs"",eNT 1 M_ClEO
Tampa , FL
33 634 - 533 9
Produce r of st e r i le p r odu c ts
population: 2.0 x 10"2), and initial bioburden has not been determined for the associated
till (4l
injectable preparatio ns.
OBSERVATION 3
Samp les taken of dru g products for determination of con formance to written specifications are not representati v e. (bJ1~.J .. ,..~' prior to trans fer into Speci fically, sterility samp les are collected from a bulk stock solution in a beaker into syringes. No fin ished drug product testing in its final container closure 'o_lb) (4) system is performed.
OBSERVATION 4
Aseptic processing areas are deficient regarding the system for monitoring environmental conditions. Specifica lly, a) Surface and air monitoring of the 150-5 classified laminar airflow workstations (LAFW) is not conducted at least daily, despite production of sterile dru g products. b) Perso nnel monitoring, incl uding fingertip sampling, o f operators involved in sterile operations of intrathecal drug products in the ISO-5 LAF W is not conducted at least daily. c) The fum failed to investigate excurs ions in their environmental monitoring program whereby viable air samples within the ISO 7 classified compoun ding pharmacy were found to exceed Action Levels.

f OR" f D II 4 3 (lnlOl j
CDR Il eana Barreto -Pet tit, Inv~:at or ~~ Robe r t C . St e yert , Inve st i g a to Les le y K. S a t t e rwhit e, Mi cro b i a s t~
PO.fVlOl'5 mlTT<lN""5OLeTE
~ """'OVEe("1 SIOWITUR!':
AMENDMENT 1
OATE
I s s~eD
02/2 2/ 20 13
I....SPECf lO;.J AL OB SER VATl O~S
P1lG I; J OP 7 1'....OU
"""'D<iffliir AOOF:E.SS AND?HONE OIIJmIER
DEPARTM ENT OF UEALTII AND HUMA. "i SERVIC ES FOOD ANDDRUGADMrnISTRATION

CAn($) OF I ~ ~T O "
55 5 Winderley Place , Suite 200 Ma i t l and, FL 32751 (407) 47 5-4 7 00 Fax : (407 ) 47 5- 47 68 Industry I n f or :na t i on: ~ww .fda .gov / o c /industry
flAAI E ANDTInE OF '~;lMDI.W. TO I'/HOUR(~ 'SSUEC
02 / 19/2 013 - 02/22/2 013

,~ ,_ evo
3004483 463
TO ;
f '........... S
J acob J . Becke l , CEO

STREH ADDRESS
~~ zao hea l t h
Corporat ion
571 0 Hoove r Bl vd
TYPESTAflUSHM8<T
' ~ SPE C T E D
CIT\', STATE, ZI' CODE. CO\.JtmlY
Tamp a , FL
33634-53 39
Prod'..lcer o f steri le p roducts
OBSERVATION 5
Clothing of personnel engaged in the proc essing of drug products is not appropriate for the duties they per form. Specifically, a) Operators performing aseptic operations in ISO 5 hoods re-use sterile cloth gowns throughout a product ion day. As sampling o f sleeves is not performed, your firm has no assurance that the sterility of the sleeves is mainta ined. b) Large ope n p ackages containing multiple pairs of gloves were observed in the nuclear ISO 8 gowning (b) (4) area. These gloves are used in the nuclear clean rooms to perform aseptic operations. The bag is dated when opened but there are no control s to prevent their use in aseptic opera tions once sterility is comprom ised.
OBSERVATION 6
Aseptic processing areas are deficient regarding the system for cleaning and disinfecting the room and equipment to produce aseptic conditions. Specifically, a) The suitability, efficacy, and limitations of d isinfecting agents and procedures has not been assessed to ensure potential contaminants arc adequately removed from surfa ces in the ISO e1assified areas. b) Routine cleaning proc edures ofthe at established frequencies.
ISO~5
classified LAF W do not include the use of a qualified sporicidal cleaning agent
c) Non-steri le wipes are used to clean the ISO 5 LA FWs.
AMENDMENT 1
;;r~~o,,,,~ .~ru~

FO R M
ro ~
CDR Il eana 3arret o -Pe t tit , I nves}f9at or Rob e r t C. gt e ye r t; , I n v e s t i g at o r Les l ey K. Satt e rwhite , M i c rOb iO l O91S ~
--
I
C:o.TE ISSLJED
fi!.:-
.f?Y
02 / 2 2/2 013
P.o, GE 4 OF 7 PAGES
41) (09 '01 )
PREVlOI!S EllmQN cesoisrs
L'iSPECTI OSAL OBSERVAfl OS S
DEPARTMENT OF REALm A. ' lffilruMAN SERVICES

DlsrR>CT .o.:lCftESS "Nt"P;'i5iNii~"BE~
FOOD AND DRUG ADMINlSlRATJON

DATE(S) Of INSPl;CTION
555 W i nde r l e y P l a ce , Suite 2 00 M a i t l a n d , FL 3 2 7 51 (4 07 ) 47 5-4 7 00 Fa x: : ( 40 7) 475-476 8 I n d u s t r y In for mat i o n : www.fda . gov/oc/ indust ry
~ E .....o TITle
~~ !19/2 013
FEI........S131.
02/ 2 2 / 2 013
3 0 0 4483 463
01' IND<V1tILIAl TO WHOM IlEI'ORTISSUl'O
TO: Jacob J . Be c ke l, CEO ~~ NA"f Ana zaohe a l th Corpor a tion

CITY . STUI' , loP OOOE ,COUN'!Rl'
5TREl:TAOORE5S
57 1 0 Ho ov er Bl v d
TYPI': EST""'-'SI4lENT I><SJ'ECH 0
Tamp a , FL
33634- 533 9
Pr o d u c e r o f s t eri le p rodu cts
OBSERVATION 7 Time limits are not established when appropriate for the completion of each production phase to assure the quality of the drug product. Speci fically, your firm lacked adequate data to support the 5-month expiration date (hold time) of the bulk sterile pre-mix bags for the preparation of intrathecal drugs.
OBSERVATION 8 Drug products do not bear an expiration date determined by appropriate stability data to assure they meet applicable stan dards ofideruiry, strength, quality and purity at the time of use. Specifically, your firm assigns a 90-day expiration date to all intrathecal drug products without adequate stability data tested with stability-indicating methods,
OBSERVATION 9 Drug produ ct containers and closures were not clean and sterilized and proce ssed to remove pyrogenic properties to assure that they are suitable for their intended use, Spe cifically, a) There is no data to demonstrate that the non-sterile 50cc amb er glass vials and rubber stoppers repackaged by your finn in uncontrolled areas for steri lization by (0) (4-) : ::::1 -are sterile and free ofpyro gens and particulates prior to being filled with Phosphatidylcholine solution for injection. b) Rubber stoppers are routinely sprayed directly with (b)(4 , in ISO 5 hoods prior to use in sterile operations to cap product vials of injectable drug products. There is no data to demonstrate thalJ~) residue on the prod uct contact surfaces of the stoppers would not alter the quality, purity and strength of the sterile drug product.
AMENDMENT 1
fORM FDA UJ
O ~1\l8)
CDR I l e a n a Ba rre t o - Pe t t it , I n v e s ti g at o r ~ Robe r t C . S t eye rt, I nve st igat o~ 1 st ~ Le s l e y K. Sat t erwhit e , Mi c r ob l

w.EVlOVS rnmON
Oll~
Er..t01.0'IEE(S} SrGNATu FlE
DA TE ISSUEC
02 /2 2 /2013
I)OS PECTIOSAL O BSERVA-no x s
PA(jEIOF1PAGES
DEPART~ENT
DlSTIlICTAOORESS ""J PHDIE ..... "' 8 ~
OF llEALTR Al\D HUMAN SERVICES

DAniS) OF INSPEcTION
FOOD A.'IDDRUG ADMINISTRATION
555 W i n d e r ley Pl a c e, Su ite 200 Mai t l a nd, FL 3 2751 (407 ) 475- 4 700 Fa x: (407 ) 4 7 5-4 76 8 Indus t r y Info rmat i o n : www . f da . g ov/ oc / i ndust ry
~AND T1nE OF I"DMDIJAL 10 'NK:JfI R~T ISSUED
0 2/ 19/ 2013
fE l NU"eE R
0 2/ 22/2013
3004483 46 3
TO :
F""" .........
Jacob J. Be cke l , CEO

STI'EE"T " OOFlE SS
Anaz a oh e a l th Corpora t ion

CITY, $ T"'rE . ZIP CODE,COUN'TflV
5 710 Ho ov e r Blvd
TYPEEST"BLII ,_ NT 'NSPEcTED
Tamp a , FL
33634 -533 9
Pr o d u cer of s t erile p roduct s
OBSERVATION 10
Written procedures are lacking which describe in sufficient detail the receipt, identification, storage, handling, samp ling, testing, approval. and rejection ofcomponents, drug prod uct conta iners, and c losures. Specifically, your finn accepts components (excipienls), containers (glass vials, bags, syringes ), and closures (rubber stoppers) without sampling and examination to ensure they are adequate for their intended use. In addition, your firm lacked written procedures and specifications for the contro l and acceptance ofall containers and closures.
OBSERVATION 11
Test procedures relative to appropriate laboratory testing for pyrogens are not written and followed. Specifically, a) Each lot of intended.
(b)(4)
cartridges for endotoxin testing is not qua lified upon receipt to demonstrate it performs as
b) Non -depyrogena ted glass vials and rubber stoppers are used in the performance ofendotoxin testing of all sterile injectable drug products.
OBSERVATION 12
Routine calibration and inspection of mecha nical and electro nic equipment is not performed according to a written program designed to assure proper performance . Speci fically,
'f' a) techni cian during
~,:" .ca1i brationlte st ing
(bH~J
is not required by the firm's proc edures, and was not performed by the service
certifications.
b) "'lbH~"" timers have not bee n checked/calibrated, as required by the finn's procedure.
c) The calibration ot thermomerers used in Refrigerators # 5 & 6 in the nuclear processing areas expired on 3/24112. These refrigerators were observed as containing mu ltiple batches of sterile inj ectable products in glass vials awaiting test results or
AMENDMENT 1
EMf'l. O'tf.E (")
""""'~ E

FD K. ' I F D... OS J (09/M)
CDR Il eana Ba rre t o -Pe t ti t, InV~g a t o r Robert C. s t e yer t , I nve s t i ga t o 'it Le s l e y K. Sa t t erW h i t e, Microb io is t
"""VlOU' FDITJ<l!'IOBOOlJ!n<
.nr/
M'E ISSVEO
02/ 2 2/20 13
lNs r ECT IONAL OUSERVATIO~S
PAGF. 60F 1P...GF -S
DISTRICTNXIRES8 AND ~ Huwe ~~
DEFARTMEJlrli OF HEALTH A."IjD H U~tA,~ SERVICES FOOD A."'ID DRUGADMINISTRATION

[lA' ~ l)!'
l"SPoCTlON
5 55 Win d e rl e y Pl ace, S ui t e 2 0 0 M a i t l a nd , FL 3 2 75 1 ( 40 7) 4 75 - 4 70 0 F a x : (4 0 7 ) 47 5 - 4768
0 2/ 1 9/2 0 1 3
F I >lUI>lllER
0 2 /221 20 13
300 44 83 4 63
I ndu s try I nformati on : w ww. fda . gov/oc /indu s t ry

....,;0;: ANDTmE OF1 'Ill 'VI 0U\.!.TO \Miot.l REPORT ISSi)ED
TO:
r-r,R>J """'IE
J a c ob J . Bec ke l , CEO
STR E ET ~SS
Anaz a ohea l t h Co rp ora t ion

CI1Y, S
"TE , "' ~ COO
5 710 Hoove r Bl vd
TYPE ES TAaUBHMEl<T INSPECTED
. COlJOITR'l'
Tampa , FL
3 3 634 - 5 3 3 9
Produc e r o f st er i le pr oduc t s
prescriptions before dispensing.
d) The thermometers in refrigerators located in the pain management area were not identified and lacked calibration dates.
AMENDMENT 1
~~ -
E......OVEE{S) SI<; .....TUFlE
see REVERSE
OF THIS PAGE
roR"l F D" 413 (0910 8)
CDR I l e a na Ba r ret o -Pet t it , I nv~

Rob ert C . St e y e rt , Inv e s t i q a t o r
--...-:::
TE ISSUED
Lesl e y K. Sat t e rwhi te, M i c r obiol

wf"' '''-'! rnm<l ""<01.1'"
' S~
'"
0 2/2 2 !?O13-
I
P"GE 1 OF 1 PA GES
INSPFCTIO/'lo'AL OBSF:R\'Artoss
ilii,RICT
-,-TO:
J ac kso n Bl vd S uite 1 5 0 0 Chi c a clO . l L 60 66 1-4 11 6 (3 1 2 ) 353 - 58 6 3 Fax: : ( 3 1 2) 5 96 - 41 B7 Indu strv I n f o r ma tio n : www.fd a.gov / o c / i nctustrv 5 50
~
"'' liiii' NO """' '''-''
DU'ARTMmr O.UUI:rH AND Itl JMAN St:RVICES FOODANDDRUGADMOOSTRATIa:.

'~ilDi' MJlt.
f lOOo
02/19/2 013
~
02/22/2013
1 0 0 03 0589 3
ro _
Edqa r L. aenceco a , Di r e c to r o f Qu a l it y Assurance
Centra l Admi xtu re Pha r r.tacv Service s In c. Chica ao ,

IL
6 062 2 ~ 5 4 24
B21 N Les s i n g St
TrPIE ESf"IlIJ8M,IfNf ~ e:TfO
gf'f. ST"~_lP
Producer of St e ri le Dr u c Produ c ts
This document lists observations made: by the FDA represenlalivc(s) during the inspection of your facility. They are inspectional observations, and do not represent a final Agency determination regarding your compliance. If you have an obj ection regarding an observation, or have implementt.d, OT plan to implement. corrective action in response 1 0 IlII observarien, you may discuss the objection or action with the FDA representalive(s) during the inspection or submit this information to FDA aI the eddress above. If yOli have lilly questions, please contact FDA at the phooe nwnb and ad dress above.
DURING AN INSPECTlON OF YOUR FIRM WE OBSERVED :
OBSE RVATION 1 There is a failur e to thorough ly review the fail ure of a batch or any of its components to meet any of its specifications whe ther or not the batch has been already distributed. Speci fically, The firm does not always recognize and investigate trends in qua lity deficiencies in a timely manner. a. Since February 20 10 the film has been aware of recurring leaks in sterile inj ectable Total Paren teral Nutritio n (TPN) bags at all of its facilities. yet the firm did not open an investigat ion into the tren d until Augus t 20 12. For ex ample. at thi s facility there were 22 complaints for leaking TPN bags from 21112012 to 2/ 1912013. Furthermore, the firm has Dot fully eva luated potential corrective and pre...entlve actions to deal with these leaks . For exam p le, it has mainly tried to pers uade the manufacturer of the sterile bags it uses to inve stigate pote ntial causes and pursu e corrections, yet it has not e valuated its own process of checking TPN bags for leaks before releasing them. b. Since Febru ary 20 12 the firm has rej ected three out of thc. batehes of Sodi um Citrate 40% Solution it has produced for testin g belo w the potency specificatio n. yet it bas not opened an investigation into this tre nd .
OBSERVAT ION 2 Asep tic processing areas are defi cient regar ding the system for mon itorin g environm ental condition s. Specifica lly, For steri le dru g processing in the 150 -5 zo nes (in accordance with SOP-CAPS -4iilliiivironmental Mon itorin g," ver. 9.0, sections # 4.8 2 and 4.9.1 and 4.11.3.A and 4.7. 1.E): air bioburd eo sampling and surra_ en sampling and g love fingertip bioburden sampling and air parti culate matter .sampling arc performed on a basis, instead of dai ly.
EMPu>n(6)
_T\.O<E
SEE REVERS E OF THIS PA GE

POllMm,UJ _
Russ ell K. Rile y , Inve s t iga tor c c ul l o ugh , I nve s t i ga t or Br uce H. M

"!'YlOI.'S I'!l'<TD" ,,",'IOU!''''
f/v<'t/(. 1/"1
DAre IB8UrD
.{'>~II.~
02/22/20 13
P"GE I
L'lSPECfIONAL O BSERVATI O NS
on
P" GEi
DEP ARUU NT OF' HEA LTI.I A.. "'lD II UMA."'l SERVIC ES FOODAND I>RL'GADMrNlSTR.A11ON
~
""'rq8l C F _o;:r_
._TO:
5 50 w. Jac kso n Bl vd . , Suite 1 5 0 0 Ch i caao . IL 60 6 61 - 4116 ( 312 ) 353 -58 63 Fax : ( 3 12 1 596 - 418 1 Indu s trv Inform at ion : www .fd a . q o v / o c / i n du s try
TO WHOIIlIlEl'Olll T ~
02/ 19/20 13 - 0 2/22/20 13

~
1 0 0 0 3 0 58 9 3
_ N C I Tn.E
EdQa r L . Mendaro s . Di rec to r of Qual i ty Assurance

~
Ce nt ra l Admi xtu re Pharmac v Se rvices Inc.
,.
1"o'Pl: E S l _ N f _
~n
N_ Le s s i ng St
eTa)
Ch Lc aq o ,
IL
60 622 - 5 4 2 4
Produ ce r of St eril e Dr ua Produc ts
OBSERVATION 3
C lothing of personnel engage d in the processing of drug produ cts is not appropriate for the duties they perfonn. Spec ificall y,
In accordance wi th 5QP-CAPS-4000 171, "Gowning Requiremen ts," ver. 5.0, the apparel worn by personnel work ing in the 150-7 c1eanrooms sti ll leaves exposed skin areas on the forehead, around the eyes. and on the necks of tbe workers . Hoods and goggles are not used. The helmets, beard cov ers, and face masks worn in the 150 -7 cleanrooms are non -steri le ap parel.
OBSERVATION 4
There was a failure to handle and store components at all times in a manner to pre vent contamination. Speci fica lly,
On 2119120 13 I ( RKR) obse rved a bag ofCitric Ac id 101
tored in the warehouse wi th a hole in the bag which expo sed the citric ac id inside to the unclassi fied air. The warehouse also has a dock door where materials are picked up A. Solution, sterile drug whic h is and delivered by truc k. Citri c Acid is a component in the production of Sodi um Citrate 4()O used in the production of steri le injectable dru gs.
OBSERVATION 5
Ase ptic proce ssing ar eas are deficient regarding air supp ly that is filtered through high-efficiency part iculate air filters under positive pressure. Spec ifica lly, The firm does not contin uously monitor air pressure di ffere ntials during production of sterile injectable drug products.
OBSERVATION 6
Procedures designed to pre vent microbiological contam ination of drug products purporting to be sterile do not include adequate validation of the sterilization process. Spec ifically, The firm has D ot challenged w ith product-specific bacterial retention stu dies the filters used to steri lize sterile injec table drug
Ul?lCNEWl s-a<o.

J'O R~
Rus s ell K. Ril e y , Invo s t i g at or Bruce H. Mccu llou gh , Inve st igator

!'VVIOl" I'IlfT'(lO< ~
f.jU'
~
0 212 212 013

PAGl! 1 OP 1
"'OI' ~
IOU" ] ! _ I
INSPH'TIONAI. OB."i[RVAT10:'olS
_ _ 1Il.IOO8OI
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~19/2013
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( 312) 3 5 3 - 5863 Fax: ( 312) 596 - 4 18 7 Indust r y I nformat i on: www .fda . g ov/ o c /industrv
TO:
10 0 0 3 0 5 B9 3
Ed g a r L . Mend a ros . Di r ector of Qual it y As s u ranc e

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Ce ntra l Admi xture Pharma c v Servi ces Inc .
a St N Lessin 82 ! ..._ ..... WlIP Produ cer of Ster ile Dr uQ Pr o d u c ts
cnrce co,
IL
6 062 2-54 24
products made from non-sterile components.
OBSERVATION 7
An adequate number ofbatehes of each dru g product are not te sted to determine an ap propriate expiration date.
Spec ifically,
The finn does not ha ve recent Stability da ta supporting the Beyond Use Dates (B UD) of so me of its sterile injectable dru g products. a. The mos t recent stability data for Trornethamine O.6 M Solution is from 2000. The HUD for this product is 9 1 days at 2-8
c.
b. Th e most recent ste rility, endo toxin, and part iculal:e matter stab ility data for Cardioplegi a solutions is from 2002. The BUD for these products varies between 14 and 30 days (de pending on the formula) at 2 8 C.
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Ru:ssell K. Ri l ey, Inves t igator Br uce H. M c c u l l o u gh, I n vesti g a to r

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INSI"CTIONAI, OBSUV AnONS

FOOD AND DRUG ADMINlSlRATION
DISTRICT ADDRESS AND PHONE NUMBER DATE(S) OF INSPECTION
404 BNA Dr., Bldg. 200, Ste. 500 Nashville, TN 37217-2597 (615) 366-7801 Fax: (615) 366-7802 Industry Information: www.fda.gov/oc/industry
NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT ISSUED
02/20/2013 - 02/22/2013
FEINUMBER
3004153061
TO:
FIRM NAME
Timothy P. Rinks, General Manager

STREET ADDRESS
PharMEDium Services, LLC.

CITY. STATE, ZIP CODE, COUNTRY
913 N Davis Ave

Cleveland, MS
38732-2106
This document lists observations made by the FDA representative(s) during the inspection of your facility. They are inspectional observations, and do not represent a final Agency determination regarding your compliance. If you have an objection regarding an observation, or have implemented, or plan to implement, corrective action in response to an observation, you may discuss the objection or action with the FDA representative(s) during the inspection or submit this information to FDA at the address above. If you have any questions, please contact FDA at the phone number and address above. '
OBSERVATION 1
The production area air supply lacks an appropriate air filtration system. Specifically, there is no documentation for; a) the air flow studies (smoke studies) performed on the horizontal laminar flow hoods (Ill..AF) or in the clean room where sterile injectable drug products are processed, b) the performance of processing activities in the :m..AF, either routine or non-routine, taking place during the dynamic smoke studies, c) the raw data for the HEPA filter integrity testing for these hoods and clean room.
OBSERVATION 2
Each batch of drug product purporting to be sterile and pyrogen-free is not laboratory tested to determine conformance to such requirements. Specifically, failure to perform endotoxin testing on all finished sterile injectable drug products.
OBSERVATION 3
Procedures designed to prevent microbiological contamination of drug products purporting to be sterile do not include adequate validation ofthe sterilization process. Specifically, media, fills are performed by the firm for equipment/process validation and employee qualification/monitoring validation. The media fills performed do not represent the continuous processes of pooling, subassembly, finished container filling, and packaging. Each media fill is performed only on one processing stage at a time and does not simulate the entire processing from the start of processing to finished packaging. Each process stage is tested separately for microbiolical growth.
1
EMPLOYEE(S) SIGNATURE DATE ISSUED

FORM FDA 483 (09/08)
Marvin D. Jones, Investigator Dell S. Moller, Investigator

".
02/22/2013
,
PAGE I OF 4 PAGES
PREVIOUS EDmON OBSOLE1E
INSPECTIONAL OBSERVA nONS
DEPARTM ENT OF IIt:.ALlll Al' IiD n UftolAN SEHVlC fS

FOOD AND DROO ADMINIS TRATION
n,
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'0' RNA Dr . , Bl dg. 200 , Ste . 500 Na shv i l l e , TN 37217- 25 9 7 (6 15 ) 366- 7801 Fa x : ( 6 1 5) 366 - 7802 I n d u s t r y I n f o rm a t i o n : www .fd a .qov ! o c !ind u st r y
02/20!2013 - 02 /2 2/ 2 013 3 00 41 530 6 1
,-CITY , aT"
-~ TO: Ti mo thv P. Rink s ,
anaae r Ge nera l M
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PharM EDium Services , LLe .

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913 N Davi s Ave

Tl'f'!iEsr-..-
Cleve lan d , MS
38732 -2 106
Pr oduce r o f S t e r ile DruQ Pr od u ct s
Also,
~,("r-o,is used to simulate the drug product instead of microbiologica l growth media.
OBSERVATION 4
Testing and release of drug product for distribution do not include approp riate laboratory determination of satisfactory conformance to the identity and strength of each active ingredient prior to release. Specifically , fa ilure to perfonn finished product potency and sterility testing on each lot of finished sterile injectable drug product processed/distributed. Testing is only performed on a random basis per product family.
OBSERVATION 5
Procedure s designed to prevent microbio logica l contamination of drug products purporti ng 1 0 be sterile are not established. Specifically, there is no sterile filtration perfonned during the aseptic pro cessing of sterile injectable drug products.
OBSERVATION 6
Equipment and utensils are not mainta ined at appropriate intervals to prevent contam ination that would alter the safety, identity, strength, quality or puri ty of the drug product. Specifically, on 2120/ 13 we noted a rust colo red build up o f material behind the HEPA filter screen near the screen retaining bolts of hood #13.
OBSERVATION 7
Equipment used in the manufacture, processing, packing or holding of drug products is not suitably located to facilitate operations for its intended use. Specifically, on 21201 13 we observed equipment and various ite ms blocking or partially blocking the return airflow vents for the ISO 7 clean roo m which con tains the firm's ISO S hoods. Items blocking these vents included trash cans, sharps containers, and meter ing pumps .

FOIlM nM.
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Marvin D. J one s , I nve s t igat o r oller , I nve s t i g a t or Dell S . M

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' 0 ' BNA Dr ., Bldg . 200 , Ste . 500 Nas hvil l e . T N 372 17- 2 597 (615 ) 366-78 01 Fax : (6 15) 366 -7 802 I ndust r v Informa t i on : www . f da. aov / o c / i nd us trv
OU'ARTMENT 010 ' IIF .A.Llll AND HUMAN SERV ICE S FOOD ANDDRUG ADMTNISTRA TION -~
02 / 20 / 2013 - 0 2/ 22 / 2013
~~
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M:II'o'IOl.W. 'ro lO<fol ~T lSSUED
TO:
Ti mothv P. Ri n ks , General M ana a er
PharMEDium Se r vi ces , LLC.
w-._
913 N Davi s Ave

TVI'l! UT.o.BUSHtoIEHT INSPE<:
Cle ve l a nd , M S
38732-2106
Produce r of St e ri l e Drug Products
OBSERVATION 8
Build ings used in the processing of a dru g product are not main tained in a good. state of repair. Speci fically, OD 2120113 we observed various holes, approximately 1/4 inch in diameter, in the wall near laminar airflow hoods 6 and 3 where aseptic processin g occurs. We also observed an off white colored res idue on this same wall, where an air return flow vent for the firm's clean roo m HEPA air filtrati on system was located.
OBSERVATION 9
Labo ratory co ntrols do not include the establishment of scientifically so und and appropriate test procedures design ed to ass ure that dru g prod ucts conform to appro priate stan dards of identity, strength, qu ality and purity. Specificall y, a) failure to utilize positive and used in the mo nitoring,. and me dia fills.
ne,g~;e
co ntro ls or conduct growth promoti on testing for the microbiological growth media mon itori ng oflam inar airflow hoods, perso nne l glove monitoring, environm ental
b) the procedure CPS-7 07, "MICROBIOLOOICAL AND ENVIRONMENTAL TESTING ", implemented 9118112, does not include specific sampling locations for the If sampling of microbiological environmental hood surfaces and hood air sam ples.
OBSERVATiON 10
Container closure systems do not provid e adequate protection against foreseeable external factors in storage and use that can cause deterioration or contam ination of the dru g product . Specifical ly, seve ral of the firm 's finished dru g prod ucts conta in activ e dru g ingredi ents that the manufa cturer's label declares to prot ect from light. Th ese finished dru g prod ucts processed by this fum are placed into clear plastic containers . Th e finn has no testi ng/stability data to support that these co ntain ers prov ide protection from light and do not aUow degredation of the finish ed drug pr oduct .
OBSERVATION 11
Th e written stability program for dru g produ cts does not inc lude meaningful and specific test method s. Specifically, the stability test me thods used to assign expiration dating of fmshed steri le inj ectab le drug products are not
E.... O'>U(1ll S'GNATURf

FO R ~
Marvi n D. Jones , I nves t i gat or o l l er , I nve s tigat or Dell S. M

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DEP ARTJl.1 ENT OF HEALTI IAND HUMAN SE RVICES FOOD ANDDRUGADMINISTRA TION
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. 0 . BNA Dr . , Bl dg . 20 0 , St e . 50 0 Na s hv ille . TN 3 72 17 - 2 5 97 ( 615 ) 366-7 80 1 Fax : ( 6IS ) 366- 7802 Indus try Info r ma t i o n: www. f d a . a o v / o e / i n d u s t r v
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TO:
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Timo thy P. Rinks, Genera l M a na ge r

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Pha r M EDi um Se rvi c e s, LLe.

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9 13 N Da v i s Ave
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387 32- 21 06
Pr oducer o f S te rile Druo Pr oduc ts
stability indicating . The finn's stability test ing procedures do not include steri lity, impurity , or degredant product testing. For example the finn as signs a 90 day expiration date for the sterile injectable drug prod uct. Morphine Sulfate Img/m l in 0.9% Sodium Chloride packaged in a Monoject Barrel syringe.
OBSERVATION 12
Containers and closures are not tested for conformance with all appropriate written procedures.
Specifically, the firm does Dot conduct any samplingltesting upon receipt of sterile finished injectable drug product containers or closures, they are approved/released without any testing.
OBSERVATION 13
Written production and process control procedures are no t followed in the execution of production and process control functions. For example on 2120113, we observed; a) the finn's failure to follo w procedure CPS-30OS, "PERSON NEL GO WNING AND ASEPTIC TECHNIQUE AND CONTROLS", implemented 1216112; in regards to; I) multiple personnel leanin g inside of the front edge of the laminar airflow hood s during the processing of sterile injectable drug produ cts, 2) eq uipment not being used, such as the [b j(4 sterile injectable drug produ cts, located inside the laminar airflow bood during the processing of
Also, we noted an employee draggi ng a full trash bag across the clean room floor with laminar air flow hoods located on each side where aseptic processing activities occurring. b) the firm's failure to follow procedure CPS-748. "OPERATION OF THErbII4 1I2n000 , in regards to envi ronmental air monitoring of the laminar airflow hood, in which the {b) (4) directly in front of the HEPA screens, which appeared to be, approximate ly 3 inches, instead of the procedure.
(bl (4)
r::,~ vice placed uired by this
implemented
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Th e observations of objectionable conditions and practices listed on the front of this form are reported :
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Section 704(b) of the Federal Food , Drug. and Cosme tic Ac t (21 USC 374(b provides: ,,' .. ; '1, , ' ,' j, : ., .j" .' . ,' .... " ,,: ' . ' f' 'trpon completion of any such Inspection of a factory, warehouse, consulting laboratory. or other estabfishmen t, and prior to leaving the premises, the officer or employee "!qking the inspection shall give to the owner. operator, or agent in charge a report ln - writing setting). forth" any , conditions .or .r practlcee observe d by him which. in his judgement, Indicate that any food" drug , device, ,or cosmetic in such establishment ( 1) consis ts In whole or in part of anyfilthy, putrid. or decomposed SUbstance, or (2) has been prepared, packed, or held unde r Insanitary conditIons whereby It may have become contaminated with filth, or whereby it may have been rendered lnlurlcu s to health, A coov of such reoort shall be sent orom otlv to the Secretarv." . '.
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02 /19 /20 13 - 02/ 21/201 3

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(2 14 ) 2S3 -5200
Fa x : ( 2 14) 253 -531 4 I nd us t r v I nforma ti on : ~dW .fda . q ov / o c li nd u s t r TO:
3002596 670
W arren B. Lee , Pre s i d ent and Owne r

4300 Grand Ave
Le e an d COI:IDanv dba L ee s he rmecv , I nc .

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Fo rt Smi th , AR
72904 - 7028
Producer of St erile u ruc Product s
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This doc ument IiSIS obSCf\ations made b)' me FDA rqJres.cntative(s) during (he inspection of)our facility. Tbey an: inspecticna t observations, and do not n:presenl a final Agenq' delenn ination regardi ng your com pliance. If yo u have an obj tion regarding an obse rvation, or have impleme nted. or plan 10 implemen t. corrective action in response 10 an observauon , )'00 may discuss the obje crion action with the FDA rcpre SCltllltive(s) during the inspection or submitt his infonnatio n 10 FDA al!he address ebove. lf you have any question$, please OOIltael FDA a1 1he phone number and addrns above.
Of
DURING AN INSPECTlON OF YOU R ARM WE OBSERVED :
OBSERVATION 1
Aseptic processing areas are deficient regarding the system for monitoring environmental conditions. Specifically,
A) Your firm's procedur es for monitoring the ISO Class S are not suitable to ensure the quality of air. For exam ple. yOW" firm conducts no monitoring for v iable and non-viable panicles during aseptic filling of sterile drug products. The current pract ice of your finn is to conduct personne l monilorin8 ~mon i lor viable particulates via settling and contact plate. and monitor for non-via e parncu ales all in static conditions.
B) Your firm lacks studies under dynam ic conditions to ensur e the flow pattern of filtered air in the ISO Class S area.
OBSERVATION 2
Procedures designed to preve nt microbiological conta mination of drug products purporting to be sterile do not include validation of the sterilization process. Specificall y,
A)
no udies or to slen IU \ '13 S, septums, eqU ipments, _ been validated.
Y~.ny q",l; r"'t;O" """ ;" on yow !!l!!!!!!!l!l!! F"' ~'"
stud ies Uti Inn s current mg patterns. used et. Furthe r. the process of sterilizing suspensions han not
B) Your firm has not established the process for sterilization of empty vials and septums (stoppers) intended for aseptically filling with sterile drug products. For examp le, there is no data to support the critical parameters o f time exposure necessary to render the materials sterile. Moreover, there is a lack o f establishing the load ing pattern for vials and sepnens in ~
SEE REVERS E
OF THIS PAGE
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To r rance J . S l a y ton , I nv e s t i g a t o r Jos e E . Melende z , I n v e s tiga t o r

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40 40 Nort h Cent r al Express wa y , Sui t e 3 0 0 Da ll as , TX 75204 (214 ) 253 - 5200 f a x : (2 14) 253-5 314 Lndus t r v In f or mat i on: www . fda . oov / oc /i nd us trv
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02/1 9/201 3
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- 02/ 21/20 13
300 259 66 70
W arren B. Le e , Pre s i den t a nd Owner

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Le e and Company dba Le e Pha r macy , In c .

B',," Tt , lIP CODE. COUIfTRV
4300 Grand Ave

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fo rt Smi t h, AR
72 90 4-702 8
Pr oduc e r of Ste r i l e Dr ua Pr oduc t s
OBSERVATION 3
Proced ures designed to prevent microb iological contamination of drug products purpo rting to be sterile are not established. Specifically, A) Your finn has no written proced ures that estab lish aseptic technique of the opera tor w hile working in the aseptic areas during aseptic filling operations. For exa mple, there are no directions for the changing of sterile gloves or the frequency of san itization of sterile gloves duri ng set-up and filling operations.
Bj Your firm's SO P #7.1, approved 2121 10, Validation of the Aseptic Techn* rovides for fillin~ ml clear ials during asepli tions., and vials with med ia and incubating. However. your firm ro utinely fills up t fills 2. 10, 30 and 50 ml vials. and nonn ally uses amber colored vials. Therefore. your current media fill studies do not represent actual aseptic filling operations.
OBSERVATION 4
There are no written procedures for prod uction and process controls designed to assure that the drug products have the identity, strength, quality, and purity they purport or are represented to possess. Specifically, there is no assurance that your firm has adequ ate process controls to prevent failures of your sterile drug prod uct. For example. the sterilization processes for suspensions and so lutions have not been design following a scientific sterilized in bulk prior to the aseptic filling proce ss and solutions are filter sterilize d with a ratioM nsions an steril filter.
OBSERVATION 5 There is no written testing program des igned to assess the stability characteristics of drug products. Specifically, A) Your firm has no scientific data to j ustify the ass igned BUD (six months) at room temperature for any sterile inj ectable drug prod uct, all of wh ich contain a preservative. None of the formu lations that you produce were placed on a stability program to determin e an appropriate BUD period.
B) _
err B
pen
ny anti-microbial effect ive testing to determi ne whethe effectively inhibits microbial growt h in your sterile inj ectable drug products through ese preservatives are used in the manufacture of all of your sterile drug products.

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'ro r r a n ce J . S layton , Ln v e s t i.q a t o r
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4040 No rth Cent r al Expr e s sway , Sui t e 300 Dallas , TX 7 5 2 0 4 (2 14 ) 253 - 52 00 Fax : (2 14) 253 - 5314 Indus trv I nformat i on : www .fda .oov / oc /indus trv
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3002 596670
TO:
Lee
Wa rren B. Lee , Pr esi d e n t a nd Owne r
an d C
a n y dba Lee Pha r mac y,
I nc.
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43 00 Gr an d Ave
Fo rt Smi t h , AR
729 0 4- 70 28
Pr od uce r o f St e r il e nruc Produ c t s
OBSERVATION 6
Establishment of the reliability of the component supplier's report of analyses is deficient in that 1M test results an: not appropriately validated at appropriate intervals. Specifically, your firm has no prog ram for the evaluation of suppliers test results. Further. you conduct no independent testing of any raw materia l prior to use in producing sterile drug products.
OBSERVATION 7
The responsibilities and procedures applicable 10 the quality control unit are not fully followed.
Specifically, SOP #9.5. approved 1122103, Visual Examination ofStcrilc Preparation, requires that ~ injectablc preparat ion will be inspected after filling into the sterile vial. However, your finn' s current pnetice ISto only visually inspect the bulk product while contained in a IV bag while located in the ISO Class 5 hood.
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"Upon completion of any such inspection of a factory, warehouse, consultinq laboratory, or other establishment, and prior to leaving the premises, the officer or employee making the inspection shall give to the owner, operator, or agent in charge a report in writing sell ing forth any conditions or practices observed by him which, in his jUdgement, indicate that any food, drug, device, or cosmetic in such establishment (1) consists in whole or in part of any filthy, putrid, or decomposed substance, or (2) has been prepared, packed, or held under insanitary conditions whereby it may have become contaminated with filth, or whereby it may have been rendered injurious to health. A copy of such report shall be sent promptly to the Secretary."
OEPA,nIlENT OF HEAL TH AND HUMAN SERVIC E S FOOD AND DRUG ADI.4INISTRAlION OISTRICT OffIC E AOOREsSNooOPHOIIE MJM9ER
OATE(s IOF I~SPECTH)N
10 waterv iew B lvd. 3rd Floor Parsippany , NJ 07054 (973 ) 3 3 1-4900 Industry Information : wwwjda. govrocrmdustry
Wl MEAND TITLE ~ INDI\II DVAL TO WHOM REPORT IS ISSUED
1119. 12, 14-16, 19, 271201 2; 01/04. 07. 08, 10 11. 14, 16, 17120 13; 0211112013
~I NUUBER
300 1779702
TO: Anthon y Grzib, R_Ph. Pharm acist in Charge

FIR", ..... ",!" STREET A.IlORESS
Wedgewood Village Pharm acy, Inc .
40 5 Heron Drive, Suite 200

TYPE OF ESTABUStW:DoT I"ISPECTEO
crrr. ST"TE AHOZP CODE

S....edesboeo, NJ 08 085
Com pounding Pharm acy
THIS DOCUMENT U STS OBSERV,.,T10 N$ MADE 8'1' THE FDA REPRESENTAT1VE(S) DURING THE INSPECTION OF YOUR FACIlITY. THtY AAE INSPECTIONAL OBSERVATIONS: AND DO NOT REPRESENT A Frw,l"'O ENCY DETERMINATION REGARDING YOUR COMPLIANCE. IF YOU HAVE AN OBJECTiON REGARDING AN OBSERVATION. OR H,.,VE IMPLEMNT Eo . OR PlAN TO IMPLEMENT CORRECTIVE ACTION IN RESPONSE TO AN OBSERV,.,TlON, YOU M,/lY OISCUSS TIlE 0 9.JECTlO N OR ACTION WITH THE FDA REPRESENT,.,rlVE(5) OURING THE INSPECTION OR SUBMIT THIS INFORMATION TO FDA"'T THE ADDRESS ABOVE. IF YOU IiAVE ANY QUEST IONS. PLEASE CONTACT FOA AT n- e PHONE N!JM6E R AND ADDRESS ABOVE. OURlNGAN INSPECn ON OFYO~ F'IRIJI(I) ~ Oe SERVED:
Observation I During the inspection, personnel practices, gowning, and env ironmental condit ions were observed that have the potentia l for compromising the sterility of sterile aseptically filled human and/or veterinary compounded drug s. For example: A) On 0 110412013, we observed a roll of IVA seals for multi-dose vials and an IV bag used in compounding suspended from hooks hanging d irectly on the back surface of the ISO-S horizontallaminar flow (HLF) hood within aseptic compo unding Roo Sodium Ch loride Injection 0.90/ 0., Preservative Free, in glass vial, lot 20130104@1 36 (Exp: 07/0312013. human), was being aseptically filled at that time . The roll o f seals was observed at the same location on 0 1/08(20 13 and 01117120 13. There is no assuran ce that the placement of these items doc s not block unidirectional airflow and comprom ise asept ic conditions. B) On 11 /1612012, the techn ician compound ing Cyc losporine I % Ophthalmic Solution in MCT Oil. lot 20 121115@237(Exp: 05/ 14!20 13, veterinary) was observ ed leaning hislher upper torso inside the ISO-5 HLF hood directly above open containers being filled and stoppered. We observed the technician exiting the 150 -6 room to the ISO 7 Gowning Ante-room to retrieve packaging components three times once the operation had begun. The compounding batch log sheet (paper) and pen were also observed being manipulated with gloved hands by the technician between operations inside the 150-5 HLF hood ; however, the technici an was not observed sanitizing his/her hands every time before returni ng to the hood . " of the 150-6 rooms (Rooms leaves areas at the neck and top of feet/shoes exposed. Gow ning consists o f shoe covers, sterile coveralls, bouffan t cap, surgical mask, safety glasses . and sterile gloves.
C) The gown ing worn by techn icians whi le compounding sterile dru gs in all
(Ii
D) Improper gowning practices were observed , such as : hair not comp letely covered by the bouffant cap (01/ 11120 13, Ol /I7/20 13).jewelry such as large hoop earr ings worn (01/1612013), holes in gowning of a
E~ Sl~"'!.UR'E
S
RE"'RS
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PAGE
f ORM fDA 483 (91081
z..
EUP LOYEE(Sl NAME ~ TfTLE (F'nn' O"TnoeI
DATEISS\.)
h~
l"icholas ViolMd, Illvestigator Barbua Wilimcryk..J,b cri, Investigator lhomas Friel, Inve.<.rigiltOl' Juanila Versace, Microbiologist:
02111120 13
PREVIOUS EOI t IONOBSOLE r a
INSPEcnONAl OBSERVATtONS
Page 1 of 14
DEP ....RTMENT OF HE ALTH .... N D HUMAN SERVICES FOO O A ND DRUG ADM INISTRATION D1 STf< ICT cence ADDRESSAND PHONE NUMBER DATE(S) OF INSPECTION
10 Waterview Blv d., 3rd Floor Pars ippany, NJ 07054 (97 3) 331-4900
Il f9, 12, 14- 16, 19, 2712012; 0 1/04, 07 ,08, 10-11,14, 16, 1712013; 0211112013
FEINU"'9E ~
Industry Information: ww'WJ dagov/oc/mdllStl)'

NM'lE AN:} TITt,.E OF IHOl\I'C)UAl TO ....... O'>' REPOR T IS ISSlED TO :
300 l n 9702
Anthony Grzi b, R.Ph., Pharm acist in Charge

STREET " OORES S
FIRM N,O, ~E
Wedge wood Villag e Pharmacy, Inc.

CITY. STATE"'~ZI PCOOE
405 Heron Drive, Suite 200

TYPE OF ESTABLlsHMErff INSPECTED
Swede sboro, NJ 08085
Compound ing Pharmacy
technician prior to beginning an operation in Roo (150-6, containing 150-5 Biosafety Cabinet) (0 111 112013), and in-ear headphones hangin g outside of a technician 's gown to the waist level during the clean ing (0 1/1012013). Notably, the cord and earpieces of'the of the ISOS B iosafcty Cabinet (BSC) in Room headphones were observed touching the edges of the ISO-5 BSC near the working surface. While cleaning the drug transfer device, which is intended for usc inside the ISO-S DSC, the technician removed the equipment and held it against hislher body and the headphones as they were clean ing, then replaced the equipment back inside the cleaned sse, E) There is no minor in Room the ISO-1 gowning room to ens4) J!2C i ,donning of the bouffant cap; nor in " ( b) (4 where sterile coveralls, surgical Room e ISO-7 Ante-room outside IS()..6 rooms ~ mask, safety glasses, and sterile gloves are donned . Additionally, SOP COM-AC-518.2, Working Within the Clean Room Complex and Hood(s), docs not describe whether any part ofthe sterile coveralls may touch the ground while donni ng. On 0 1/08120 13 and 0 1/16/20 13. techn icians demonstrated donning of sterile coveralls, during which parts of the coverall touched the ground. F) On 01/0412013, during the sterile ""' o f Sod ium Chloride Inj ection 0.9%, Preservative Free, in glass vial, lot 20 130104@136 (Exp: 07/03120 13 , human in the ISO-S HLF hood, a product leak was observed at the sterile outlet. The technician completed the filling operation and tubing set where it attached to the sterilizing wiped up the produ ct, but did not document the leak in the compounding batch log sheet or elsewhere. G) It docs not appear that all materials arc routinely sanitized immed iately before enter ing either: one ofthe 6 , ISO-S lILF aseptic compounding hoods, or ISO-6 ase ptic co mpounding rooms (Room IS0-5 biosafety cabinets. SOP COMAC-518 .2, Working Within the Clean Room Complex and Hood(s), does not have any provisions for this. On 0110412013, pouches of sterilized closure s; aluminum crimp caps; a manual cap crimper; a redlblack screwdriver; and the spray bottle ofl!l' (4 ere observed being used and placed inside the ISO-5 HLF hood in Roo:"-b-W4~uring the compo unding of Sodium Chloride Injection 0.9%. Preservative Free. in glass vial. lot 20 130 104@136 (Exp: 07/03120 13, human) . We did not observe any of these items being sanitized immediately before entry into the hood,
EIIPLOYEE(S) Sl(;t.;.\~
REVERSE
OF TH/S PAGE
EMPLoYEE(Sl NoUlE AND TITlE (PIld (J' T_ J
SEe
~.
D"TE ISSUED
J5~ ~<.--
fORM FDA 413 1'108)
..
-.
Nicbc d... ~ V;oland, Investigator Barbara Wilimcrylc-Macri, InvC$tigator l bomas Friel, Investigator
Juan ita Ver:; ace, Microbiologist
OVl 1l2013
S E TION OBSOt.ETi<
INSPEcnONAL OBSERVATIONS
Page 2 of 14
DEPARTMENT OF HEALTH AND HUM AN SERVICES FOOD AND DRUG A DMINISTRATION DISTRICT OFFICE ADDRESSANDPHONE NUMBER DATE(S) OF INSPECTION
10 Waterview Blvd., Jrd Floor Parsippany, NJ 07054 (973) 3314900

Industry Infonn ation: ",ww.fda-gov/oc/industry
~ EAN0 1'J'I'(E
1119,12, 14-16,19, 271201 2; 01/04,07, 08, 10- 11,14, 16, 1712013 ; 02111 12013
FEl NUlEER
JOO l n 9702
OF rNOlVlC:llW.TO WHOU REPOQT JS ISSUED
TO :
Anth ony Grzib, R.Ph.,Pharmacist in Charge

STREET ADDRESS
FIRM NAME
wedgewood Village Pharmacy, Inc.

TYPE OF e STABUSHMENT INSPECTED
CrrY. STATE AND ZIP CODE

Swedesboro, NJ 080RS
CompoundingPharmacy
On 11 / 16f20 12, pouches of ste riliz ed containers and closures, and a' screwdriver were observed being used and placed inside the ISO5 HLF hood in Room during the compo unding ofCyclospo rine I % Ophthalm ic 01 201 2 11 15@237 (Ex p : 0 5/1 4/2 0 I3 , veterinary). We did not observe any of the se items Sol utio n in MCT O il, 1 being sanitize d immediately before entry into the hood . The po uches of sterilized co ntainers, closures, and tubing are not routin ely sanitized be fore be ing transferred into one o f th e 150-6 aseptic compound ing rooms from the stock o f open storage s helves in the IS0-7 An te-room . Th e storage shelves are located adjacent to the handwashing sink and go wni ng donn ing/removal area. Th is is also not done for the compounding batch log sheets (pape r) that are brought into the 150-6 rooms from the uncontrolled corridor. On 1111 612012 and 0 1/04f20 13, pouche s o f co mponents and compounding batch log sheets were observed in use in 15 0 -6 Room during the compound ing o f Cyclospo rine 1% Ophthalmic Solution in MCT O il, lot 20 121 115@2 37(Exp: 0511 412013 , veterinary), and Sodium C hloride Injection 0.9%, Pre serv ativ e Free, in glass v ial, lot 20 130104@ 136 (Exp: 0710312013, hu man ), respec tiv ely. H) On 0 110412013, di ffic ult-to-sani tize item s were obse rved in the ISO-6 aseptic compounding Room such as an ope n lapto p computer and RF scanner, compo unding batch log sheet (pa per), adhesive paper notes. stan dard push-button cal cu lator, vacuum pum p intended for sterile filter integrity test, and two plast ic/rubber handled screwdrivers. Wi thin the 150-5 H LF hood , a ro ll of IVA seal s for mul ti-dose via ls was han ging at the back of the hood. Sodium Ch loride Injection 0.9%, Preservat ive free , in glass vial, lot 20130 104@ 136(Exp: 07/03120 13, human ) was being com pounded. Some o f these items, such as the vacuum pump , screwdrivers, and roll of l YA seals, were observed within t he room again on 0110812013 and 01/ 17120 13, in addition to a plastic handled box cutter, ma nua l stap ler, cardboard co ntai ners holding glass via ls, and a metal binder clip attached to cart 4. I) On 0 1104120 13. wh ile a single techn ician was aseptically filling Sod ium Ch loride Injection 0.9%, Preservative Free , in glass vial , lot 2013 0 104@ 136 (Exp: 0 7/03120I3, human)in the ISO-5 HL F hood in 150 -6 Room we obse rved a second technician op en the door to the 150-6 roo m and walk acro ss the room to use the laptop comp uter and RF scanner located on the tabl e in front of the observation window . The seco nd techn ician wa lked back to the door and held it op en,leaving an open path between the 150-6 and ISO- 7 classi fied areas, in order to con tinue a co nversat ion with the first tech nician that was performi ng the aseptic fill.
J) According to SOP COM-AC-51 8.2, Working Within the Clean Roo m Com plex and Hood{s), Section 23,
' EE
R~R SE
E~~
~~ J1/V~- ----PREVIOUSEDmON OeSOLfTE
EMPlOYEE{S)NAME AND TTflE (P/WIl or Type,
DATEOSUB>
OF THIS
PAGE
Violand.lnvcstigator Barbara WilimU)'kMacri, Investigator Thomas Friel, Investigator Juanita Versace, Microbinlngist
~icholas
02111/2013
FORM FDA 483 (91081
IN$PECnONAL OBSERVATIONS
Pil9E'3 of 14
DEPARTMENT O F HEALTH AND HU MAN SERVI CES f OOD AND ORUG A DMINISTRATIO N DISTRICT OfR(;E AOORESS " NO PHO~ NUIoIaER OA.TE(S) OF INSPECTK)"l
10 Waterview Bl vd., l Td Floo r Parsippany, NJ 0705 4 (973) 33 1-4900
lI J9, 12, 14-16, 19,271101 2; 0 1/04, 07, 08, 10- 11, 14, 16,1 7110 1] ; 02111120 13
FEI N.NBER
Industry Intormanon: www fda.gov/oc/ind ustry

NA.ME AND TITLE OF INDIVIDUALTO"""'OM RPORT IS ISSUED
300 ITI9702
TO: Anthony Gl7i b, R.Ph., Pharmacist in Charge

FlF:l:U NAME
sre ser ADOI:tESS

405 Heron Drive, Sui te 200
TYPE OF ESTA9l.lSHU EHT INSPECTED
Wed gewood Vill age Pharmacy , Inc.

CITY. STATE M>ZJP COClE
Swedesboro, NJ 08085
Co mpounding Phannacy
gow ns may be removed in the ante-room and hung up inside-out, so that they may be re-worn again. A lthough the re-use of gowns was verbally descr ibed as limited to one shift, the procedu re does not limit how many time s this may be done or a timeframe for re-use. There has been no evaluation o f this practice to ensure re-w om gowns do not contribute to potential contamination of sterile preparations.
---
Observatio n 2 Steri le veterinary compounds are not routinely tested for sterility and endotox in limit, regardless of quanti ty produced or method of preparation. Veterinary compounds represen t over o f orders d ispensed between 101112012 and I n I2013. Specifi cally: units (2ml vials) o f Am ikacin Preservative Free Injecti on, 250 mg/ml, lot A) Approximately 20 121112@270 (Exp: 05/11/2013), were aseptically filled on or about 11 /2912012. No sterility or endotoxin limit testing was performed . nits ( 1000 ml IV bags) of Guaifcnesin 5% (in Dextrose 5%) Solution for IV Infusion, lot B) Approximately 20 130 104@363 (Exp: 04/0412013), were aseptically filled on or about 01 /071201 3. No sterility or endotoxin limit testin g was performed.
C) Approximately H' nits (30ml vials) of Medro xyproge sterone Acetate 200mg/ml Suspension for Inj ection,lot sterilized by n or about 09/ 18120 l2. No sterility 20120917@310 (Exp: 03/1 612013), were or endotoxin limit testing was performed.
------- --- - ----- -------- ------- ------ -._---- - - --
units (5 gram tubes) of Edetate Disod ium 1% Ophthalmic Ointment, lot 20 130107@ I2 2 D) Approximately , sterilized bYl on o r about 01/0712013. No sterility or endotoxin limit (Exp: 0710612013), wereI testing was performed .
---_..------------------------EMPLOYEE(S) SIGNATURE
- -- ---- OATE ISSUED
O bservation 3 Steril e human compounds are not always tested for sterility, even when made from non-steri le ingredients. Section 2.4 of SOP COM-AC-5 70.l , Sterility Testing of Human Preparation s, requires sterility testing for all highEMPlOYEE(S) NAME AND n TLE (Prinf or T~J
--
REVERSE OF "'S
PA GE
SEE
6 ""-~
::;:;;?--~'- --.-/
PREVIOUSWI TlON O B
w0 ''2.' ---no
Nicholas Violand, Investigator Barbara WilimCZ)'k-Macri,lnvestigallll' 1bomas Frjel, lcvest igater Juanit~ versece, Miaobiologist
INSPECTlONAL O BSERVATIONS
02' 1112013
Page 4 of 14
FORN FDA "I:S (M)8)
DEPAR,...EH T OF HE A L TH AND HUMAN SERVIC ES eooo ... "IO DRUG AOMINISmATlON DISTRICT
~E
ADDRESS A"l) Pt10NE NUMBER:
OI' lEtSI OF INSPECTlOO
10 Waterview Blv d., 3rd Pars ippany , NJ 07054 (973) 3 31-4900
Floor
1119, 12, 14- 16, 19, 27120 12; 0 1/04, 07, 08, 10- 11,14,16,171201 3; 02 /1 112013
FEI NUMBER
Industry Information: www.fda.govze crindustry

NAME }H) nTLE OF tNOIVIOUAl. TO tM-/OU REPORTI S IS::;l.E D TO :
300 1779702
Anthon)' Grzi b. R-Ph" Phann acist in Charge

STREET AOORESS
FIRM NAME
Wedgewood Villag e Phannacy,lnc.

CITY. s r "TE " !I/O ZIP CODE

TYPE OF ESTAalJ SHMENT 1 t.'SPECTtO
Swedes boro, NJ 08 085
Compounding Pharmacy
risk leve l compo unded sterile prod ucts intended for ~_~umans that are produced
I I-. ' I A
(bn 4r
.,
ore ocmg stennzeo. r- or example :
A) Naltrexonc 1.4gm Pellct (implantable) is
Ibll41 I and sterilized bvl 0112011 , this preparation has been made in batches of up to approximatel y=- units, but no sterility or endotoxin testi ng has ever been performed for this product. Lots 20 1 20822@ 1 2~ Q ,units) and 20 120425@150 units) ' were produced in 20 12 and rema in within their expiry (08/1712013 and 4120/2013, respectively).
B) Sodium Bicarbonate 8.4% Preservative Free Injection, lot 201212 11@1 33 (Exp: 06/09(2013), was sterile units (50mJ single -use vial). Sterility or endotoxin and asept ically filled on or about 1211112012 a limit te sting was not performed .
---- - -
--------- --
Ob servation 4 There is a lack ofassurance of sterility for compounded sterile human and veterinary drug s, including injectable, implan table and ophthalmic prod ucts. Not all methods of sterilization for these products have been fully evaluated for effec tiveness andlor consistency. Specifically: Ster ilization: There is no assuran ce the ste rilization process o f the is reachin the se~., for the du ration 0 The is not calibrated for {1i '" r point 0 time on any rout ine basis. The sterilization process has not been supported by actual sterility tests on product sterilized at worst case conditions (e.g., varied loading patterns and quantity of units being Examples o f products prepared by sterilization include: Medroxyprogesterone Acetate 200mglml Suspension for Inj ection (veteri nary), Estrone 5mglmJ Suspen sion for 1M Injection (veterinary) and Cyclosporine I % Aqueous Ophtha lmic Suspension (huma n). I for assurance ofPJ {>1J~ntegrity after aseptic fill is not and Asept ic Fill: The '" B) Sterile l always fully documented. The technician is to circle "pass" or "fail" and record a pressure reading at which the was tested; however, instances were seen in w fich this information was not recorded at all. Examples
A) r-""
'"
EMf'loYEE{SJSIGNI\TURf:
REVERSE
OF " 'S
SEE
p ,,,,,
6-_ ____ "- ;l . ---;yv PREVIOUS EOl T"lON C8W<8E
--
E~LOV EE(S}
NAIo'E A/'.OTIllE {PI'iri or T)l)e/
coe rsecec
0211112013
Nicholas Violaod, Investigator Barbara Wilimczyk.M Kr'i. In~ c ~gillor 1llotrnL'l Friel. Investigator JuanilllVersace, Microbiologist
FORM FDA 41S3 {${OI}
Pag@50f 14
OEPARTNE NT OF HEALTH AND HU MAN SERVI CE S FOOD A ND DRUG ADM INISTAAn ON DISTRICT OfTICE AOORESS ANOPHONE NUMBER DATE(S) OF INSPECTION
10 Wa terview Blvd., 3rd Floor Parsi ppany, NJ 0705 4 (97 3) 3 31_4 900 Industry Information: ~"WJda.go"'odindu stry
NAJ.'lE Af'CI TITlE OF II'>OlVICJl..IA TO WHON REPoR T IS ISSUED
1119, 12, 14. 16, 19, 2712012; 01104,07, 08, 10- 11,1 4,1 6, 17/201); 0211112013
FE! MJUBER
300177970 2
TO:
Anthony Grzib, R.rh., Pharmac ist in Charge

STREET ADDRESS
FIRM NAME
Wedgewood Village Pharmacy, Inc .

CITY. STATE MlO ZIP CODE
405 Heron Drive , Su ite 200

~
OF ESTAauSHMENT INSPECTED
Swedesboro, NJ 0 808S
include : Pentosan Injection Solut ion 250m glml , lot 20121224 @202, exp : 061221201~~nits, veterinary); FHS Ferr ic Hydrox ide/Sucrose 20mglml Inj ection, lot 20 121203@269.exp: 0 6/0 1120 13 ( nits, veterinary); and its, hum Inr hese examples include Papaverine 30mglm l Injection. Jot 20 12 1I l 5@249, exp : 0311 512013 the technician's init ials in the . box, but no indication of integr ity tes t results.
i~s calibrated for (IIX'" but there is no assurance the C) Steril ization: The l process is reaching th e......, . )(~) . and that. it is. ma intained within a tolerance fO~ ~'1~i fied exposure 1c Ointm ent, lot 20130101@I 22,wa trea ted on time . For example, Edetate Disodium 1% 0f~m ~ The rack location in the is recorded, but no verification 01l01!2 013 from approximatel of the actual ;~i~ci s recorded, nor is there assuran~~~f. ~::':'::';:'as maintained for the spec ified time of ex In addition, there is no procedure for I ' sterilization to describe capacity, loading patterns and operation ofthe
D) The finn provided a theoretlc~r log reduction calculation for a particular organism ~ however, actual product sterility is not routinely for the minimum do se used by the contrac demonstrated through sterility testing. Cert ificates of proces sing receiv ed from the contract show the dose used ; however, worst case conditions (e.g., lowest poss ible dose, load ing pattern) have not been supported by actual ste rility tests on ] I product. Naltrexone IAgm Pel let (Implantable, human) is sterilized by I
------- ------------- - --- - -- - - --- --
--------._--- -_.--------------- [ sterilized products
Observation 5 Steps to control routin e biohurd cn in raw materials and/or compone nts to be used in . are not always taken. For exam ple:
A) Raw materials that will be used in a sterile prod uct are not always stored in a manner to reduce potential contam ination. For example : unfilled (bulk) preservative frcc ophthalmic ointment, lot 20 120928@230, exp. 09/2312013, was observed in aisle (sterile preparations aisle) of the raw material warehouse on 0 1/04120 13 and 0 1/111201 3 in a plastic bucket with metal hand le. Accordi ng to management, the bucket is unlined, is not received as steri le, and is not treate d prior to u:.~n addition, Carbome r Gel for Cycl osporin Gel,lot 20120806@1 56,exp: 0210112013, was also observed in aisle on 0111712013, in a clear plast ic tub . The lid of the tub appeared to have
SEE REVERSE OF mlS PAGE
~~? 7~
____
k.~
EMPlOYEE(S) tuoue ANO TITlE (PIn or r~
IlATE ISSUE:>
Nicholas Violand, Investigator

Harbara Wilimczyk_MacTi , Investigator
__ - ,.-t-
Thomas Friel, Investigator

Juanita Versace, Microbiolog ist
INSPECnONAL OBSERYATIONS
0211112013
FORM FDA 4&3 (Wll) _ PREVIOUS EDlnoN OI!SOLETE
Page6of1 4
DE PARTMEN T OF HEALTH A ND H UMAN SERVICES FOO D A ND DRUG ADM INISTRAnON DISTRICT OFFICE AODRESSAND P!-KlNE NUMBER DATE\S) OF INSPECTION
10 Waterv iew Blvd., 3rd Floor Pars ippa ny, NJ 07054 (973) 33 1-4900
Industry Information: _
1l/9, 12, 14-16, 19,27120 12; 011 04, 07, 08, 10-11, 14, 16, 1712013; 02111120 13
FEI NV"'BEFt
Jda.govlocJmdustry
300 l n 9 702
NAME ANO TlTLE OF lNOMCll.lAl. TO 'M-IOM REPORT IS ISSlJO TO ;
Anth ony Grzib , R.Ph., Pharmacist in Charge

STREET ADDRESS
FIRM NAME
Wedgewood Village Pharmacy, Inc.


TYPE OF ESTAII USHMENT NSPECTEIl
Swedesboro, "'J 08085
Compounding Pharma cy
liq uid co ndensation on the inner surface and the tub did not appear to be lined . B) Prep aration of vial stoppers for products that will be term inally ster ilized is performed by rinsing wi th purch ased sterile water for inj ect ion (WFI), drying with a lint- free cloth, and transporting to the multi-pu rpo se general compound ing room (Room rbTr4' in a plastic weigh boat. Th is cleaning process is performed ins ide the washroom , which has many act ivities occurr ing, such as ~'-I glassware wash ing! an d incubatio n of bacterial growth media and t no-mdrcators. The rinsing/preparation o f the sto ppers should be performed in an env ironme nt that is less like ly to contri bute to bioburden on the con tai nerclosu re sys tem. which has direct contact with prod uct This process was verbally described, and is not in a wri tten proc edure .
--- - - -_._----- - ~ - ~ ~ - - - -~~ - - _ . _ -----_._-_ ._- --- - -
....
_-_ ....._ ---_ ....
_ ~ - - - . - . _ - - - - - . - .-
Obse rvat ion 6 Raw materials s uch as bu lk act ive ingred ients are not routinely tested for identity, and raw materials being used in sterile compounded drugs are not evaluated for rout ine bioburden . Altho ugh qu ality agreements are ma intai ned with suppliers of active ingredients. sampling and test ing has never been per formed for any active or inacti ve ingred ients. There arc no identity tests performed for any materials. For example: of raw material Medroxy progesterone Acet ate was received with a certificate of ana lysis A) Lot and checked into inv entory on or about 08/08/20 12. No sam pl ing or testing was perform ed for the material, wh ich was used to com po und Medroxy progesteron c Acetate Suspe nsion for Inj ection 20Omglml, lot 20 12 1219@273 sterilized by . (Exp: 06/ 17120 13), which was Th is raw material has not been assessed for routine biobu rden .
~r""'nf raw materi al Sod ium Bicarbo nate Powder, USP wa s rece ived with a certificate of ana lysis B) Lot an d che cked into inventory on or a bout 06/ 18120 12. No sampling or tes ting was performed for the material, which was used to com pound Sodium B icar bonate 8.4 % Preservat ive Free Injection, lot 20 1212 11@133 (Exp : 06/0912013), whi ch was steri l~-rilr;-and aseptically filled. Thi s raw material has not been assessed for routine biobu rden .
REV RSE
OF'THrs PAGE
.
EIIPLOYEE(SI NAIolE AND TITL (Prit'tv T_ J
...
DATE ISSUED
02/11I20 13
Page 7 of 14
SEE
EM~~TU~
~/'
~? "--' Jv:L/
PI'I!::VIOUS EDITION oaSOLETE
Nicholas Viollnd, Investigator Barblra Wn imeryl:.~Macri , l nvestigeior

Thom as Frie l, Investigator Juani ta Versace, Micro bio logist
IN SPECTIONAL OBS
fOR M F OA 4 J I910e
ER VATIoN s
DEPARTMENT OF HEALTH AND HUMAN SERVIC ES FOOOAN D DRUG ADMINISTRATTON DISTRICT OFFICE .-.ooRESS..NOF'l-tO"IE NU"' 9ER OA TEl SJOF
INS~CTION
10 waterview B lvd., 3rd Floo r
Parsippany, N J 07054
(97]) 331-4900
1119, 12, 14- 16, 19,27120 12; 0 1104, 07, 08, IO-J I, 14, 16, 17120 13; 0111112.013
fEI NUMBER
IndUSU)' Information: wwwJda.govloclindusuy

NAMEAND TITLE OF tNDMDlJil,L TOWHOM REPORT IS ISsuED
3001n9702
TO: Anthony Grzib, R.Ph., Pharmacist in Charge

FIR'" NAME
STReer~SS
Wedgewood Village Pharmacy, Inc.

cnv . STATE A")Zlf" CO~E
4US Heron Drive, Suite200

lYJ>E OF ESTA3l.ISHMENT-.sPECTEO
Swedesboro, N J 08085
Observation 7 Reports of adverse eve nts and complaints relating to potential quality or labeling defects are not trended and eva luated for possible systemic issue s that co uld affe ct more than one produ ct. Quality Event Investi gation s (QE ls) are gen erated for cus tomer complaints and adverse events. These typ ically de scribe trending for the same product (i tem code) or speci fic lot number; however, rev iew for similar adverse events/complaints am on g different item codes is not typically included in the QEI or in any other doc ument . (Between 11/0 112011 and 10/31 1201 2, ~ unique human and veteri nary item codes were prod uced .) For ex ampl e: approxima tely A) Between 01/01 12012 and 12fJ 112.0 12, approximately 30 report s were rece ived, acro ss multiple sterile injectable or im plantable human or veterinary co mpo unds , de scribing reacti on s whi ch include but are not limited to: injectionlimplant site reaction ; infection, abscess, redness, or swelling at injection site; inflammation ; death; or other non-specific reactions. General trends for adverse ev ents such as inject ion site reaction or othe r types of reaction s following adm inistrat ion of any injectable or impla ntable compounded steri le preparation are not noted in the Q E ls or e lsew here. Examp les include:
i. QE I case 00 0 19 139, opened 10129120 12, describes that a horse administered M edroxyprogesteronc co mpound (item co de: MEDROX-INJ005VC, veterinary) was found dead approx imately 30 minutes aftcr receiving the injec tion; and an autopsy found the ca use of death to be anaphylax is. The investigation notes that two possible produ ct lots may ha ve been administered to the horse (20 120 807@286 , 201209 17@3 1O); and no other issues were rep orted for th ose lots, and no other co mplaints of that nature had been received for that item code in the last year. T he QEI was closed on 11/0 1/2012 , without any chemical or microbiological testing being performed.
ii . QEI case 0001 54 36, opened 0412012012, describes that th ree patients that had received the Naltrcxone implant s (item code: NALTRE-PEL003HC, lot 201 11208@02 0,hurnan)were experiencing infection, with swelling and redness at the incision site. Case 000 15129 had been opened on 04/0212012, in which the same reporter described three of five pati ents compla ined of white chalky fluid leaking from the site of implant, for the same lot (201 11208@020). These were pre sumed but not confirmed to be the same pat ients . Th e investigations did not include any testing or possible root cause determination, and concluded that a lack of other complaints indicated the lot was accep tab le . QEI 000 15 129 was close d on 04/02/2012; and no closure date is included for Q EI 000 15436, which was cancelled .
REVERSE
"" ,",$
""
EMPl~-=~r/
H APlOYEE(Si NAME AND Til l!" (Pri rtt o! Typ.)
DATE ISSUED
Nicho las
Violand, Investigator
0211112013
Page 8 of 14
PAGE.
FORMFDA 13(
....
. ~ j<~/' ,/7-,,' ~
I'RVlOUS EOlT1ON OSSOl.ETt.
Barbara Wilimczyk-Macri, Investigator thomas Friel, ~gator Juanita V~, M jcrobtolog~t

IN SPEcnONA L OBSERVAnONS

DISTRICT OFFICE ADDRESS AND PHONENUMBER
DATE(S) OF INSPE CTI ON
10Waterview Blvd., 3rd Floor Parsippany, NJ 07054 (973) 331-4900

Industry Information: www.fda.gov/oc/indu stry
NAME AND TITLE OF INDIVIDUALTO VVHOM REPORT IS ISSUED
1119, 12, 14-16, 19,2712012; 01104, 07,08, 10-11, 14 , 16, 17 12013; 0211112013
FEINUMBER
3001779702
TO :
Anthony Grzib, R.Ph., Pharmacist in Charge

STR EET ADDRESS
FIRM NAME
Wedgewood Village Pharmacy.Jnc.

CITY . S1ATE ANDZIP CODE

TYPE OF ESTABLISHMENTINSPECTED
iii. QEI case 00013604, opened 01/05/2012 , describes that numerous horses experienced abscesses at the injection site after administration of glucosamine sulfate 250mg/ml (item code: GLUSUL-INJOOI ve, lot 20111116@043 , veterinary). The investigation concluded that a lack of other complaints for this lot and item code indicated the product was acceptable. The QEI was closed on 01/06/2012, without a possible root cause or any testing being performed. B) Between 01101 /2012 and 12/3112012, approximately 18 reports were received across multiple sterile ophthalmic veterinary compounds, describing reactions that include but are not limited to : redness; irritation; swelling; discharge; bacterial conjunctivitis; soreness; ulcer, or other non-specific reactions. General trends for adverse events following administration of any sterile ophthalmic product are not noted in the QEls or elsewhere. Examples include: i. QEI case 00017680, opened 08/17/2012, describes "the eye gets 'excessively' irritated and 'lost a lot of skin ' and now appears to have an ulcer" following administration of edetate disodium ophthalmic ointment (item code: EDEDIS-OPH027Ve, lot 20 120706@278, veterinary). The investigation concludes that the product is acceptable, as no other complaints of this nature had been received for the lot and item code. The QEI was closed on 08121/2012, without any possible root cause being proposed or testing being performed. ii. QEI case 00017910, opened 08/29/2012, describes that the patient's eyes became sore and watery following the administration of Idoxuridine ophthalmic solution (item code: IDOXUROPHOOI VC, lot 20120618@364, veterinary). The complainant notes the patient had used the same product previously with no issues, and "wanted to know if this was a 'bad batch' ." Theinvestigation concludes that the produ ct is acceptable, as no other complaints of this nature had been received for this lot and item code . The QEI was closed on 08/3012012, without any possible root cause being proposed or testing being performed . iii. QEI case 00014790, opened 031l012012, describes that the patient's eye swelled and turned red following one application ofDiclofenac ophthalmic ointment 0.1 % (item cod e: DICLOF-OPH002VC, lot 20 120229@106 , veterinary). The investigation concludes that the product is acceptable, as no other complaints of this nature had been received for th is lot and item code. The QEI was closed on 03/12/2012, without any possible root cause being proposed or testing being performed.
EMPLOYEE(S) SIGNATU~
SEE REVERSE
OF THIS
~. .-
EMPlOYEE(S) NAMEAND Tine (Print or Type)
DATEISSUED
PAGE
5~ y~//
Of PREVIOUS EDITION OBSOLETE
'
/ 7
_.
Nicholas Violand, Investigator Barbara Wilim czyk-Macri, Investigator Thomas Friel, Investigator Juanita Versace, Microbiologist
0211112013
Page 9 of 14
FORM FDA 483 (9/08)

FOOD AND DRUG ADMINI$ TRAnov DISTRICT OFFICE ADDRESS AND PHONE NUMBER
DATE(S) OF INSP ECTIO N
10 Waterview Blvd., 3rd floor Parsippany, NJ 07054 (973) 331-4900

Industry Information: www.fda.gov /odindustry
NAME AND TITl E OF INDIVIDUAL TO 'M-lOM REPORT IS ISSUED
1l/9, 12, 14-16, 19, 27/201 2; 01104,07,08, 10-11 ,14, 16,17/2013; 0211112013
FEI NUMBER
3001779702
TO:
Anthony Grzib, R.Ph., Pharmacis t inCharge

STREET ADDRESS
FIRM NAME
WedgewoodVillagePharmacy, Inc.
CITY , STATE ANDZ!? CODE

TYP E OF ESTABLISHMENT INS PEClEO
C) From the log ofQEIs initiated between 0110112012 and 12/31/2012 for human and veterinary compounds, approximately 28 examples of cas e files were rev iewed that categorize the issue as "NO BIOLOGICAL RESPONSE". Additi onal entries in the log descri be issues such as the subject product(s) did not work or did not produce the expected response . Reports categorized as "NO BIOLOGICAL RESPONSE" and/or reports of lack of effect are not trended in the QEI s or elsewhere, for any potential associations with a specific dosage form, process/procedure, technician(s), equipment, or raw material. Examples include;
i. QEI case 00018405, opened 09/20/2012 , is categorized as "NO BIOLOGICAL RESPONSE" for Methimazole Suspension (item code; METHIM-SUS5 IOVC, vete rinary) . It states the patient' s thyroid level "is now above 23 after 2 months of therapy and [the complainant] fee ls that this methimazole was not compounded correctly." The patient was noted to have been on the same compounded product with no issues. The QEI conclude s the product is acceptable, as only 2 other complaints of this nature have been received for this item code in the last year. The QEI wa s closed on 09/2 112012, without any testing or root cause analysis being performe d. ii. QEI case 00016 374, opened 06/13/20 12, is categorized as "NO BIOLOGICAL RESPONSE " for Tri-mix Inj ection (item code : TRIMIX-INJ005HC, lot 2012 0507@071, human). The patient reported lack of effect. The QE1 concludes the product is acceptable as only 2 complaints for this lot and 19 for this item code of this nature had been received. The QE1 was clo sed on 06/14/2012, without any testing or root cause analysis being performed. iii. QEI case 00016395, opened 06/14/2012, is categorized as "NO BIOLOGICAL RESPONSE " for Corticotrophin Injecti on (item code: CORTIC-INJ002VC, lot 20120503 @055, veterinary). The reporter notes the patient's ACTH test results "were erra tic." As per the reporter, the patient was not on any other medication that could interfere or interact. The QEI concludes that the product is acceptable, as only 6 complaints of this nature have been received for this item code. The QEI was closed on 06/ 1512012, without any testing or root cause analysis being performed.
D) Between 01/0112012 and 12/31/2012, approximately 31 complaints across multiple human and veterinary compounds were received, describing eith er incorrect labeling or receipt of incorrect order. General trend s for labeling and shipment errors are not noted in the QEl s or any other report, for any potential associations with a specific process/procedure or technician(s)/pharmacist(s). Specific complai nts include:
. SEE REVERSE
OF THIS
EMPLO~U~
EMPLOYEE(S) NAMEAND TITLE (Printor Type)
DATE ISSUED
PAGE
-z;'.-z.
1/7 ~
",>
Nicholas Violand, Investigator Barbara Wil imczyk-Macri, Investigator Thomas Friel, Investigator . Juanita Versace, Microbiologist
INSPECTIONAL OBSERVA TIONS
02l t 112013
M<!
FORM FDA 48 3 (9/08)
--
Page l 0 0f
/'1 1.-111{1}
DEPARTJ,lENT OF HEALTH A ND HUMAN SERVICES FOOD AN D DRUG ADMINISTRATI ON DISmlCT OFFICE ADDRESS AND PHONE NUMBER D'\'TE(S)OF INSPECTION
10 Waterview Blvd., 3rd Floor Parsippany, XJ 07054 (973)3 31-4900 Industry Information: ....'WWJdagovfodindustry
NAl,lE AM) TITtE OF Ii'IIlMOUAt. TO Wi:;)',l REPORT IS iSSlJEO TO;
11 19, 12, 14-16, 19, 27/2012; 0 1/04, 07, 08, 10-1I, 14, 16, 1712013; 02/1112013
FE! NUUBEl\
3001779702
Anthony Grzib, R.Ph., Pharmacist in Charge

STReET ADDRESS
FIRM NAME
Wedgewood VillagePharmacy, Inc.

CITY, STATE ANOZIP CODE
405 HeronDrive, Sune200

TYPE OF ESTABU SHMENT INSPECTED
S....edesborc, NJ 08085
CompoundingPharmacy
i. QEI case 000 19218 , opened 1I /03fl Ol2, descri bes that the complainan t was "confused about the bottl es and labels. [He/She] said there was a bottle labeled DES tiny tabs, but there were capsules in the bott le. [He/She} pee led back the label and the label underneath sai d Pren isolonctretracycline caps." ii. QE I case 00013 579, opened 0 1l0412012. describe s that the complainan t rec eived all the items in their order, with an additional item labeled for a different pat ient. iii. QEI case 000 16859, opened 07/09n.0 12, describes the rece ipt o f an inc orre ct item. It states "The requ est from the doctor wasfor slow release caps (once daily) but. the technical notes were taken inco rrectly and the capsu les were form ulated as the immediate rel ease."
-----------------------_.----- --------------------------.-------------- _.._ .._-----------------Observation 8 Efforts to preven t cross contamination o f allergens such as cep halo sporins and potent materials such as horm ones have not been evaluated for effectiveness . Cephalospo rin an d hormone co ntai ning compounds may be produced from powders in the general com pounding room (Room under non-d edicated containment hoods. using nondedicated compounding equipment. Routine cleaning o f the hood s and other eq uipment has not been demonstrated to be effective at removing traces of s uch ma teria ls, nor are there any specific instructions or wr itten proc edu res for cle aning following thc comp oundi ng of such ma teria ls. For example:
A) Cephalexin IOOmg Chew Treat. lot 20130 108@23 1 (veterinary), was co mpounded on or about 0 1/0812013 und er an unspecifi ed hood. using a beaker, glass stir rod, and anim al treat mold . There are no spec ific instructions or docu mentation in the compounding batch log sheet for cleaning following co mpound ing of this cephalosporin containing produc t.
B) Cefadrox il IOOmg Capsules, lot 20130109@2 47 (veterinary). wa s comp ounded on or about 01109/2013 under an unspecified hood. using a mortar and pestle and unspeci fied encap sulat ion equipment. There arc no specific instructions or documentation in the compounding ba tch log sheet for clean ing following co mpounding o f this cephalosporin containing produ ct.
REVE RSE
'""''' ~ ~.---/' /i.?'~~'-P'GE

PREVIOUS EDITION 06S0LETE
'"
EW'l~~~
~ _.
EU PLOYEECS) ~"'E AN) TTnE (Prin' or T",e)
DA TEISSueD
Nicholes Viol and, Investigator Barbara Wilimc:yk-Macri , ln vestiglltot

~mil5
Friel, Investigator
0211112013
Page 11 of
Ju anita
V ersace, Microbiologist
FORM FD A 483 (9108)
INSPECTl ONAL OBSERVATIONS
1'1
1 .{(if1 )
...
DEPARTMEN T OF HEAL TH AN D HUM A N SER VIC ES FOOD AN D DRUG ADMl NI5TRATl ON DISTRIC T OfTlCE '-DOI'lESS AM) PI<lNE MAlBER
OATE(Sl OF I"'IS PECTION
10 WaterviewBlvd., 3rd Floor Parsippany, NJ 07054

(97]) 331-4900
1119. 12. 1416, 19, 2712012; 011 04. 01. 08, 10-11, 14, 16. 171201] ;021 1112013
F'E1~BEM
Industry Information: www.fda.gcv/oc/induetry

NAJo'E At.V m u: OF INDIVIDUAL TO WiON REPOR'T IS ISStEO
3001779702
TO: Anthony Grzib. R.Ph_. Pharmacist in Charge:

FFtIol t.A ... a
STREET "DOl'lESS
Wedgewood Village Pharma cy.Tnc .

CITY. 57" T A r.tI ZIP CODE
405 Heron Drive. Suite 200

TYPE OF ESTABUSHMENT INSPECTfD
Swedesboro. NJ 08085
C) Medroxypro geste ronc Acetate Su spe nsion for Inj ection, 200mglm L lot 20121 219@273 (veteri nary), was compounded on or about I W O n.O12 under an unspe cified hood. u sing a glas s mortar and pestle. beaker, and unspe cified stirring and equipment. There are no specific instruction s or documentation in the compo unding batch log sheet for cleaning following compound ing of this hormone contai nin g product.
D) Hydroxyprogesterone Caproate 2 50mg/ml in Castor Oil Soluti on for Inj ection. Jot 20 1212 l4@ 199 (human), was compounded approx imately on I undcr an unspecified hoo d, usi ng an unspeci fied container and stirring equipment before being sterile ...... 'and aseptically filled . There are no specific instructions or
docum enta tion in thc compou nding batch log sheet for cleaning following compounding of this ho rmon e containing product. Additionally, SOP CO M-GE N-0 89. I, Qua lity Assessment ofE qu ipmcnt, Section 2.2, states "All equipmen t is to be co nstructed so that surfaces that conta ct pharmaceutical co mpo nents, in-proc ess materials, or finished medicati ons arc no t re active, additive, or absorptive in order to pre vent adversely affecting the safety, identity, strength, quality, or pu rity of the preparations." It is uncle ar how assurance o f this procedural requ irement is accom plished .
-- - ---
Ob servation 9 There is no assurance that testing per form ed by co ntract laboratories on finished compounded drugs is adequately and appro priately performed . No documented efforts are made to evaluate the services provided by these organiz ations. Th ere are at least three different contract laboratories used for finished product tests, which incl ude potency , sterility an d en dotoxin limit test ing for sterile hu man co mpounds . Prod ucts tested by these laboratories include: Hydroxyprogesterone Caproa te 250mglmllnjecti on in Castor Oil, Sod iwn Chlo ride 0.9% in plastic via ls (human), and Tri-mix Standa rd Injecti on (Prostaglandin E, Papaverine, Phento lamine) (hum an).
- - - ---- - --- ---
---- - ---
- --- - --.---- - ------- ---
------ -- --
-------
Obse rvat ion 10 The foll owing defi cien cies we re observed during rev iew of compounding ba lch log sheets (batch records ): A) There is no traceab ility of sterile co mpo nents used throughout the compo unding process, suc h as sterile tub ing EIolPlOYEE(Sj ..mE AND TlTtE (PI"'" or r)peJ Oo'TE ISSUED EMPL OYEE(S) SIG/IlA,TURe ~ :-JichoiltS ViolaJId. [n~ rni gal or
REVERSE OF ,"" PM;
FORM FDA
,..
fi-
~ --
~- -U - - y:;......._ ~. . .-0:...- .--?
wi. - .-
Barban. WilirnuylMacri. lnvcstigator Thornil" Frid , Investigator Juanita Versace, Microbiologist
O2JllflOI3
4U ('
m.)
PREVIOUS EDI TION OBSOLETE
IN SPECn ONAL OBSERVA no NS
Page 12of 1 4
....' 1./"/1}
DEPAR TM ENT O F HEALTH AND HUMAN SERVIC ES FOOD AND D RIJG "OM1NI$ TRATl ON DISTRICT OFfiCE ADDRESS ANO PHONE NUMBER O....TE(Sj OF INSPECTION
10 Waterv iew m-e. 3rd Floor Parsippan y, NJ 07054 (913)33 1-4900 Industry Information: .......w JdagovlocJindustry
NAtJE..o.NO
11/9, 12. \ 4- 16, 19, 2712012; 01104, 07, 08, 10.1\.1 4, 16,1 712013 ; 02111120 13
FEI '"lIUBER
300 1179702
nne Of' lro.uMOUAl. TO ...........eN- REPORT IS lSsta>

STREET ADDRES S
TO:
Anthony Grzlb, R.Ph., Ph armacist in Charge 40 5 Heron Dri ve, Sui te 200
TYPE OF ESTABlISl-I MENT INSPECTEO
FIRM NAME
wedge wco d Villag e Phar macy,lnc.

CITY. ST"TE " NO ZIP CODE
Swedesboro, NJ OS085
Compoundi ng Pltannacy
l as the lot and expiry date s of actual components used are not recorded . In some instances, and sterilizing )" compo nent lots are listed in log sheets from 2012 , with expiry dates from as early as 2009 . For example: i. Hyd roxyprogestcrone Caproate Inject ion 250mglmJ in Castor Oil , Preservative Free, lot 20121015@348 (Bxp: 04/13/20 13, human ), was compounded on or about 10/16/20 12. The compounding log sheet lists approximately eleven di fferent components wi~6r(~~atcs prior to 1011612012. which include "BAG, STERJLE CONTAINE R 4000ML DEVICE" lot expiry 0913012009; , ,,4 ~ 4 J DEVICE" lot 4 expiry 0413012010, and "TImE SET, STERILE (I b) IA DEVICE" lot ~~ expiry 1013112011.
ii . These same three lots of expired device components arc also listed in the compound ing log sheet for Medetomidine Hel l mglml Inj ection Solution, lot 2012 1218@393 (Bxp: 06/ 16/ 13, veterinary), compounded on or about 1211 91201 2.
B) Compounding batch log sheets do not contain adequate details of the actu al compounding process as performed, to ensure proper execution and lot-to-lot consistency. Compounding log sheets for human and veterinary solutions and suspensions do not routinely require the documentation of mixing speeds, mixing tim es. and spe cific equipment (or type) used througho ut the process. For examp le:
i. The compounding log sheet for Medroxyprogesteronc Acetate Sus pension for Injection, 200mglml. lot 20 1212 19@273 (Exp: 06/l712013, veterinary) requires the technician to perform activities such as:
(1)1(4>
(bl<4l
etar s regar mg vesse SlZC, mixing speeds and nm es, duration and speed of and actual pump speed were recorde d by the techn ician in the record.
ii . Th e compounding log sheet for Guaifcnesin 5% (in Dextrose 5%) Solution for IV Infusion, Preservati ve Free, IOOOml, lot 201301 04@363 (Exp: 04/04/201 3, veterin ar~ requires the technician to perfonn activities such as..i..-
0fI
lOll_I
REVERSE OF 11-/1$
SE'
I NO details regarding initial volume settmg usee, SIZe or oeaxcr ana vessel used , o rder of add ition of ingredie nts, mixing EIolPLOYEE(S) NAIJ AND TTT1. (PtMtor rypel oere escec EIII~~Tl.RE r-; icholas viotaed, Investigator ~ .. Barbara Wilimczyk-Macri, Investigator
(tI) (.()
j u se c , =
PAGE
~ ~ ~4;?--PREVIOUS EDITION O8"tA-JO I E
Thomas Friel, Investigator Juanita Versace, Microbiologist

0211112013
FOR M FOA 483 9108
Page 13 of 1'1
DEPARTMENT O F HEAI,.TH AND HUMAN SERVICES 1'000 MIO DR UG ADMINISTRATIO N DI STRiCT OFFICE ....ODRESS ANO PHONE NUMBER O....TE(Sj OF INSPr;.CTION
10 Waterview Blv d ., J rd Floor Parsi pp any, NJ 070 S4 (9 73) 33 1-4900 Industry Information: www Jda.gov/oclindustry
NAME .... "IO TTTI.E OF INDNIClUAL. TO W10M RU'ORT IS ISSUED
1119, 12, 14- 16, 19,27120 12; 0 1104, 07, 08. 10- 11, 14, 16, 17120 13; OVI J120l J
FEl NU\l8E~
J OO ln9702
. Pharmac ist in Charge TO : Anthon y Grzi b, R .Ph_

FIRM NAME STREET AOORESS
Wedg ewood Village Pharmacy, Inc.

CITY. STATE ~ ZIP COOE

TYPe: OF ESTA8U SHNENT INS~CTED
Swedesboro, NJ 0808S
Compou nding Pharmacy
speeds, and mixing times were recorded by the technician in the record .
.---
------ ----- ----- ---- - ----------------- ---------------------
Observation I] The syste m used to manage changes to formulation s and processes is not always effective . Formul ation Change Request 1875 was implemented approximately on 3t2612012. to modify the formulation o f Medroxypro gesterone Acetate Suspension for Inj ection. 200mglml, following the compounding ofbatcbes that could not be filled into vials. Multiple ingre dients were changed, including the preservative system, from -I Although the compounding batch log sheet was updated to reflect the formula change, the preservatives listed on the label for the product were not subsequently changed to reflect the difference . More than 7 month s later and after the initiation of this inspection, Change Request 2027 was issued (11/1512012), to correct the labeling; however. approximately 22 lots with potentia lly incorrect labeling have been produced and remain within expiry.
EMPLOYEE(S) ~TURE
R~RSE
SEE
OF""S
P<GE
---;;;;;:;~
fMPLOYEE(S) NAI,lE AN~ TITlE (PMI or Type}
DATEISSlD
4 -
f/ tA"0' 4 ~
m
Nicholas v loland, Investigator Barbara WilimCl:yk~acri , Investigator Thomas Friel, Investigator Ju""ita Versace, Microbiologist
0211112013
FORM FOA 48J; (91OS)
PREVIOUS EO!TIO
Page 14 of
DEPA RTM ENT OF HEALTH A ND HUM A N SERVICES FOOD A ND DRUG ADMINIST RAT IO N DISTRICT OFFICE ADDRESS AND PHONE NUMBER. DATE(S) OF
I ~ SPE CT I O N
60 Eighth Street, NE Atlanta, GA 30309 Industry Infonnation: www.fda.gov/oc/industry

NAME AND TITLE OF INDIVIDUAL TO WH O~ REPORT IS ISSUED TO:
1211 0- 13, 18,20/20 12; 1/4, 11, 16,1812013

FEI NUMBER
3009925820
Patr ica Stephens, R.Ph - Pharmaci st in Charge/Owner

STREET ADDRESS
FIRM NAME
Medi-Fare Drug & Hom e Health Center, Inc .

CITY, STATE AND ZIP CODE
300 W. P ine Stree t

Blacksburg, SC 29702
Compou nding Pharm acy
THIS DOCUMENT LISTS OOSERVATIONS MADE B'f THE FDA REPRESENTATIVE\Sj DURING THE INSPECTION OF 'fOUR FACILITY. THEY ARE INSPECTIONAL OBSERVATIONS; AND DO NOT REPRESENT A FINAL AGENCY DETERMINATION REGARDING YOUR COMPLIANCE, IF YOU HAVE AN OBJECTION REGARDING AN OBSERVATiON, OR HAVE IMPLEMENTED, OR PLAN TO IMPLEMENT CORRECTIVE ACTION IN RESPONSE TO AN OBSERVATION. YOU MAY DISCUSS THE OBJECTION OR ACTION 'M TH THE FDA REPRESENTATIVEISj DURING THE INSPECTION OR SUBMIT THIS INFORMATION T O FDA AT THE .... DDRESS ABOVE, rr YOU HAVE ANy QUESTIONS. PLEASE CONTACT FDA AT THE PHO~E NU\.lIB ER AND ADDRESS ABOVE. DURING AN INSPECTION OF YOUR FIRM (I) (\!VE) OBSERVED;
Observation I. The re is no assuran ce that containers, closures, and drug products are free from objectionab le microorganisms. Specifically, (a). There is no documentatio n available of the _ validations conduc ted to ensure appro priatene ss for use prior to_ g l a s sware and finished product. (b). Section 5.3 of your ' ', P&P 8.040. dated 9/15/03 require that "moni toring data from each cycle shall be recorded to ensure that processes are performed prop e~t all critical parameters are within specified limits during proces sing". Your firm does not m aintain ~y cl e printouts to show the cycle parameters were met. During the inspection, sterilization cyc le printouts were requested but never received. In addition your "_ U s e , C lean ing & Spore Testing Log" docs not list the lot number of the articles being sterilized, lot number of bio logical indicators used within the load or document cycle parameters. (c). There are no records documentin rocedures were followed in the _ erification of you C c le Verification", SOP No. E.023. 1, dated 1/ 11/12 . D u ri n ~ cycle, per your proce dure entitled, , inspection, management stated that a biological indicator is placed into a load cycle and at the. of that cycle, the BI is sent to. or verification . H~re are no records documenting when this verification cycle was performed, what articles were _ _ in the load, or the lot number of the biologica l indicator challenged. In addition, the written procedures for verifi cation of your _ ycle do not reflect current operations. Observation 2 : Sterility assurance parameters were not met due to your failure to adequately evaluate your define appropriate parameters for drug product sterilizat ion, and maintain documentation of sten izauon . For example, the following products require _ sterilization per your firm 's formula ry
E~f>~O YEE(S)
NAME AND TITLE (Pnnl oc
rype)
DATE ISSUED
FO RM FD A 483 (9/ Cl8)
INSPECTI ONA L OBS ERVA TIO NS
Page l of 5
DEPARTMENT OF HEA LT H AN D HUMAN SERVIC ES

FOOD AND DRUG A DV lN lSTRATION
OillE(S) OF II\SPeC Il O..,
60 Eighth Street, l\"E Atlanta, GA 30309

Industry Information: ",,,,, w .fdaBovfodindustry
M IolE '" 1TlE OF INOIV1CUJl ~ TO "'MO\l
RE~T
12110-13 ,1 8,2 012012; 1/4 ,11,1 6,1812013
3009 925820
IS ISSUED
TO: Patrica Stephens. R .Ph Pharmacist in Charge/Owner

STREET .o.coR.E SS
Medi F are Drug & Home Health Center , Inc.

CIT'l' _STATE "' ,,"0 ZIP
300 W. Pine Street

TYPE OF ESTABlISH"' ENT INSPECTEO
ccoa
Compoundi ng Phar macy
worksheets; howev er no records exist documenting their sterilizat ion: Dexamethasone Acetat e, LOl20120222 @ 3 Tes tosterone Aqueou s Sus pension, Lot 201 205 15@ 3 Tri amci nolone Acetonid e Inj ection 40 mg/ml, Lot 201205 30@ 1 Ciprotloxacin/Oexamctb ascne Sterile Inj., Lot 20 l20726@9 Obs ervat ion 3: Distribution of the Te stosterone Aqueous Suspension 50mglm l inj ., Lot 20 1205 15@3 occurred prior to receipt of final product test resul ts. It was shipped on 5/23/12 and 6/2 1/12 from your firm, however prel iminary results from your contract testing lab were not reported unti!lO/S/]2 . Observation 4: Vials used in fillin sterilized prep arations have not been rendered free from viable microbes ycle. Management stated that such articles art_ using th roueh the use of a validate th~ycl e of the ir This cycle has not been challenged to ensure l~ ach ieving at least a 3log re netIon In en otoxi n levels. Obse rvat ion 5: Records d ocumenting the dates, load cycle, and lot numbe r of via ls wa shed and not been being maintained . Observation 6: The current system for mon itoring environmen tal cond itions existing within the asepti c proces sing areas is deficient.
Specifically, (a). Your proced ure entitled, "3.060 Environmental Mon itorin g of the Aseptic Compound ing Area: Microbial Orga nisms", dated 1/4/06, d oes not describe wheth er sampling is performed under dynamic conditions; descr ibed samp ling locations do not corres pond to the areas actually sampled; nor does the proce dure describe wha t type of media should be used for incubating such samples.
(b) . Personnel monitoring and env ironmen tal samp ling is not perform ed and documented during aseptic processing. In addition, gloved fingert ip monitoring is only ~ ed as part of employee validations. Env ironmental sampling is performed, - EM"tOYEE1SJ "(,U ,lE"'''O TITlE (PrJ.'Il or Twe)
Rf' VER$E
OA.TE ISSlED
OF THIS
PIl G~
'"
1]./1,:f/t S &r5/;~f hd ju. 1-/'0-)3

PREVIOU S EOlTIO!'1 OSS Ol.ETE
f O RM f DA 483 19108)
INSPECTIONA L OBSERVA TIONS
Page 2 0f S
DEP ARTMEN T OF H EA L. T H AN D H UMAN SERVI CES FOO D M D DRUG .-.CMINISTRAnON

OIS T~ICT
OFFICE AOORESS AAO PH "'-E MJUBER
O.-.TE(SJ OF J~CTlON
60 E ighth Street, NE Atlanta, GA 30309 Induslry Information: www.fda go...lodindustry

NAI,I ANO TiTl E OF INON I AL 0 'MtOM REPORT S ISSlJ D
12110- 13. 18,20120 12; 11 4, 11,16,18/20 13

FEI Nl..M8ER
3009925820
TO: Parrica Stephens, R,Ph Pha rmacist in Charg e/Owner

FIRM NAME
STREET ADClRES S
Medi- Fare Drug & Home Health Center , lnc.

CITY. STATE Al.lD ZIP CODE
300 W. Pine Stre et

TYP1"OF ESTABLlS-W ( NT INSPECTED
Bla cksbu rg, SC 29 702
Compou nding Pharma cy
(e). Envi roTesr Monitoring Lo gs da ted 12127/ 10- 1215/ 12 do not includ e inclu sive incub ation times, med ia type and expiration, or doc ument the length of time settlin g plates were exp ose d to the enviro nment. (d). Neutralizing agen ts are not added to the med ia, to ensure that th e growth potent ial o f such media is not inh ibited due to disinfectan ts applie d to surfaces within the clean rooms. (e). Media to support the growth o f fung i (suc h as Malt Extract Agar) is not being used in high-risk level sterile pre para tions as part o f your clean room enviro nmental monitoring program . (f). Nonsterile med ia is used to prepare solutions used in
"
media tills.
(g) . Re sults of repeat ed mic rob ial test ing o f envir onmental samples are not docu mented in instances were CF U co unts> I were foun d. For example, on 8/ 15/12 . cru co unts of 4 were noted in the ante room, 14 counts W CI C noted in outer room sink. and 15 counts were noted in the outer room floor . The comments denoted "clean and ret est", however no additional re sults were recorded . (h). Records docu menting incubated personnel touch plates do not identify media lot used or incubation times.
( i). Full identification o f microorganisms found within the ante roo m was not made in the fo llowing instance when environme ntal act ion limits were exceeded : On 812 5/1 2, Sample #4 (anteroom, ISO 7) showed 13 CF U mic rob ial co unts, where the act ion limit is > IOcfu's . Sect ion 5.2.8 afSOP, 3.060 Environm ent al M onitor ing of the Aseptic Compounding Area, states that "any CF U's must be identifi ed" .
viable particle co unt reports provided by your contract testing company. do not indicate whether such tes ting is performed under dy nam ic co nditio ns. Suc h report s are also no t being reviewed, evaluated and approv ed by QA. (k). Th~onti nuous environm ental monitoring so ftware sy stem has not bee n properly validated to ensure data is continuou sly captured and saved. For examp le, monitoring data requested for October 1-7 20 12 cou ld not be provided during the inspection . According to mana gement. the system automatically overrides such da ta aft er _dala po ints arc co llected.
REVERSE
OF TH iS
PA GF.
S /:
1-16-13
PREVIOUS EDITION D650 LE: 1/:0
F ORM F DA 483 (9108)
INSPECTIONAL OBS ERVA TIONS
Page 30f S
DEPARTMENT OF HEAL TH AND HUMAN SERVI CES FOOD ....ND ORUG .... DMINISTRATION DISTRICT OFFICE ACDR<:SS "" 0 PHONE NU~8E:~ DATt(Sl OF INS....t=CTION
60 Eighth Street. ':\'t Atlanta, GA 30309
12Jl o-I3,18.2OJ2012 ; 1/4,l l ,16,ISn 0 13

FE! Nt. v BER
- ,'" " Patrice Ste phens, R.Ph - Pharmacist in Charge/Owner

If\.CM DIJ,oIl,l TO IMiC~ R TO : FIR'" NAJ,lE STREET AOORrSS
Industry Information: www.fd a.gcvzocsmdusey
3009925820
Medi-Fare Drug & Home Health Cente r, Inc.

CITY.
STA~E
300 W. Pine: Street

TYPE OF ESTABlI S"''-'ENT INSPECTED
ANO ZIP CCCE
(1) . Growth promotion testing is not perfor med on any purchased media used for environme nta l mo nitoring and
ste rility testing of products [0 ensure such media is capable of supporting growth. (m). Media fills do not simulate rout ine aseptic manufacturing operatio ns that inco rporate worst case activities and conditions that may provide a challenge to your aseptic operations (such as; max im um batch sizes, max imum personnel, interven tions, container/closure systems, etc). Currently, you r med ia fills are only performed as part of
employ~uali fications.
(n). No smoke stud ies have been conducted to verify the unidirectiona l airflow and air turb ulences wit hin clean room critica l areas were sterilized drug products, containers, and closures are exposed to environm enta l condi tions . Observa tion 7: The re is no docum enta tion that sup ports the extension of the BUD dates outside of the duration of ther apy . Your procedu re entitled," Beyond-Use Dating (BUD )ofCompo undcd Prep arat ions" , SOP 9.050, sec 9.4 states that," for all othe r form ulations , a B UD is no later than the intended durat ion of therapy or 30 days, whic hever is earlier". For exam ple: "Testosterone Aqueous Suspension, Lot # 20 120515@ 3, BUD of 5/ 15/13; '" Zinc sulfate I mg/ml injecta ble Lot # 20 120319@ 12 made on 3/19/ 12 w ith BUD
of 6117/12;
'" Ctonidine/Bupivlcaine /Baclofe n PfIntra thecallot 201 103 15@4madeon 311 5/ 11 w ith BUD of 511 411 1. Observat ion 8: Your firm cites USP <797> and USP <7 1> as their gu idanc e for sterility and endotoxin testing requirements . As such, sufficient samples in relation to the form ulation batch s ize are not routinely sent to your contract resting lab. For instance: Glycopyrrclate 0.2mg/ml (5ml MDV ); Lot no. 20 12 1030@8 - . vials ; 2-5ml vials sent to lab; Ketorolac Tromethamine 30mglm l: Lot no. 20 120 113@4 -_ vials;3- lm l vialssent to lab: Furosem ide Inj . IOmg/ml; Lot no. 201220S04@3- ~s ; J vlm l vials sent to lab; nits: 4-2ml via ls Me toclopra mide Inj lOmg/ml ; Lot no. 20120912@.6 REVERSE OF THIS
PilG E
SEE
~:;rI.R~
I
PREVlOUS ECITIQN OIl S0 LTE
~:~r;N;.'~J:t:~w:"~
INSPE CTIONAL OBSERVAT IONS
COoTE ISSUE::>
l-JH 3
Paqe e ot S
FORM F DA "83l911:l 81
DE P.... RT M EN T OF HE....l TH AN D H UMAN SE RVICES FOO D AN D DR UG ...OUI Nl STRATION DISTRICT OFFICE MXlF!ESS AND PHONE MoNgER DATE(S) OF I""SPECTlON
60 E.ighth Street, :"IE

Atl anta, GA 30309
Ind ustry Information : www.fdagov/o clindustr)'
W. ...E AND TITlE. OF ~OMOU"' L TO WiOJII
RE~T
12110.13, 18,2012012; 11 4, 11, 16,181201]

FE! NtH9ER
300992 5820
IS ISS1.JEO
TO: Patrica Stephens , R_Ph - Pharmacist in ChllTgd Ownc:r

FR "'NAME
STREET ADDRE SS
Medi-Fare Drug &. Home Health Center, Inc.

CITY. STA TE AND ZIP CODE
300 W. Pine Street

TYPE OF ESTABUSH '<IENT INSPECTED
Blacks burg , SC 297 02
Compou nding Pharmacy
In add ition, there are no quality control procedures addre ssing the statis tical criteria used to j ustify such sampling size. Observat ion 9: Formul ation w orkshee ts are not sufficie ntly reviewe d to ensure accu rate and comple te information is recorded . The following errors we re consistently made with out justification: I . Lot number and expiration dates of chemicals are not recor ded or incorrectly recorded; 2. Device lot numbers are no t recorded for vials, stoppers, filters used ; 3. Form ulat ion instructions were incomplete; 4. Exp ired che mica ls used in formul ations, and use of chemicals due to expire prior to the Beyond -Use Date of the finished prod uct. Observation 10: (a).Your finn failed to thoroughly investigate the QREs (Quality Related Eve nts) for Epinephrine 1:1000 PF Su lfite Free Injectable lots 2012 1018@9 and 20 12 1024 @8 and dispe nsed from 11f2-1 I n / 12 w ith reported pink discoloration, whi ch resul ted in the recall of both lots . No units were sent to the contract testing lab for further testing, nor in vestigation into previous lots were made to determine root cause and imp lement corrective actions to preve nt reo ccurrence. ~o l 21f I s @5 %< I})~ (b) .Sod ium Bicarbonate 50 ml vial 8.4% inj., lot 20J'21 1~ was found w ith visible part iculate '. The formulatio n work sheet however does not matter, and vials of suc h lot wer e bagged and labeled '_ denote the presence o f partic ulates, and no additiona l investigations into the root cause o f this quality prob lem were made. Continuo us part icu late matter has been noted in additional formulations without any laboratory evaluations.
I,)
Observation 11: There is no documen tation of any investigations con ducted for over 150 compounded preparat ions and raw material s that were ident ified as being "O ut of Spec", "Not Pas s QN', or " Rej ected" on d estruction logs dated 1214-7/ 12. Observa tion 12: There ar e no written procedures and documentatio n thereof add ressing the subsequent stability, microbia l and poten cy characteristics of stock solutions th roughout their labeled Beyond-Use Date, from which multiple aliquots are withdrawn to prepare add itional steri le fonnu lations.
E !,jF\.OYEE(S)N.lIIolE"'''01TTl.E (Ptint~J
E,,.,;L ,, ~. ~),t1sk'i .ll"lfPSbr

FORM F DA 4 83 ( 9/0 8) PRE\IlO\JS EOITION OBSOLETE
.1
DATE lS5LEO
H S'-13
Page 5 0f 5

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