Subject/Title:

PINICILLIN/ CEPHALOSPORIN DECONTAMINATION OF FACILITIES

1.0 PURPOSE
1.1 To define the minimum basic technical and regulatory requirements for penicillin or
cephalosporin decontamination to render a facility suitable for use for non-lactam production.
This document is to be used for one-time decontamination of facilities. There may be
additional requirements or more appropriate methods based on local regulations. This
document does not preclude, but rather supports, the need for site specific change control
documentation.
1.2 The analytical standard for demonstrating adequate Penicillin (beta-lactam antibiotic)
decontamination of facilities, separation within the same building, or measurement of
cross-contamination of facilities is codified at CFR 211.176.
2.0 SCOPE
2.1 Any manufacturing facilities undergoing decontamination for penicillin or
cephalosporin.
3.0 RESPONSIBILITIES
3.1 Quality & Compliance - Quality Operations
3.1.1 Reviewing decontamination plans and protocols.
3.1.2 Reviewing decontamination data submitted by the local facility.
3.1.3 Providing technical assistance with the decontamination upon request.
3.2 Engineering/Production Operations
3.2.1 Generate SOPs for the decontamination and sampling process.
3.2.2 Obtain the resources for performing the actual decontamination and
sampling, and assure that the SOPs for these activities are followed and that all
activities are documented.
3.2.3 Carry out the routine (3-lactam monitoring program (Section 13.0)
3.3 Validation Group
3.3.1 To ensure overall adherence to this guideline during the decontamination program.
Specific responsibilities include:
3.3.1.1 Preparation of the decontamination and sampling protocol.

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Subject/Title:
PINICILLIN/ CEPHALOSPORIN DECONTAMINATION OF FACILITIES

3.3.1.2 Preparing a swab sampling plan for post-

decontamination testing.
3.3.1.3 Accumulating, compiling and evaluating all test results.
3.3.1.4 Preparing the decontamination report and
circulating it for approval (Refer to Attachment II).
3.3.1.5 Submitting decontamination data to Quality &
Compliance Quality Operations upon completion of the
decontamination program.
3.4 Quality Control or Approved Laboratory
3.4.1 Conducting the assays required for the decontamination program.
3.5 Quality Assurance
3.5.1 Reviewing and approving the decontamination protocol and report.
3.5.2 Assure that a program is established for continued monitoring of the
facility for trace -lactam materials.
4.0 DEFINITION OF AREA TO BE DECONTAMINATED
It is important to take time in defining the exact extent of the penicillin or cephalosporin
decontamination. The areas must include but may not be limited to any area where the
product is formulated, packaged, stored, tested, or otherwise handled or held. In addition, any
ancillary equipment or area such as desks, tables, chairs, etc. must be considered. Besides
the actual rooms, cross contamination caused by employees carrying powder from one room
to another, shared facilities such as cafeterias, washing areas, weighing areas, etc., and
shared air systems all must be considered.
Each area undergoing decontamination should be defined and documented (See
Attachment I) under one of the following categories (include as-built drawings and
schematics to define demolition, removal and construction):
4.1 Critical Items
4.1.1 Weighing, processing and primary packaging rooms that are exposed to
penicillin or cephalosporin active drug substance and dosage forms.
4.2 Non-Critical Items
4.2.1 This would cover all other items not having product contact:
4.2.1.1 Rooms sharing the same air system,
4.2.1.2 Walls/floors/ceilings of corridors,
4.2.1.3 Packaging areas (where product is not exposed),
4.2.1.4 Sinks, desks, chairs, ancillary equipment (scales and
balances), warehouse racks, light fixtures,

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Subject/Title:
PINICILLIN/ CEPHALOSPORIN DECONTAMINATION OF FACILITIES
 4.2.1.5Rooms shared by employees e.g. offices, cafeterias, wash
areas, laboratories, etc.
4.2.1.6 Personal equipment (typewriters, calculators), file cabinets, etc.
4.3 Items to be Discarded
4.3.1 Depending on the scope of the decontamination, ceilings and even walls and
floors may be marked for removal. Certain items cannot be subjected to
complete decontamination and would have to be discarded. This would include
the following:
4.3.1.1 Air handling ducts.
4.3.1.2Filter media for HVAC systems including pre-filters,
dust-collecting filters, and HEPA filters.
4.3.1.3Porous materials such as insulation, ceiling tiles, fiber drums,
wooden pallets, and wooden boxes.
4.3.1.4Paper work which must be retained should be placed in plastic
bags, sealed and moved to a storage site or archive. All other paper
work should be discarded.
4.3.1.5All clothing, including shoes, previously worn or stored in the
penicillin or cephalosporin area.
4.3.1.6Some structural material, e.g. cinder block or porous concrete
surfaces are not suitable for decontamination but may not be
replaceable either. This type of item must be cleaned as thoroughly
as possible, sealed by painting with an epoxy paint and then
decontaminated.
Note: Quality & Compliance Quality Operations must be notified and give approval for any exceptions prior
to initiation of the decontamination program.
Note: All replacement parts, equipment, etc. must be kept off site until the decontamination is
completed and approved.
5.0 PRE-DECONTAMINATION PROCEDURE
5.1 Remove all items which have been identified as Items to be Discarded (Section 4.3), to
an appropriate disposal site.
5.2 The area should be disassembled to its most basic form.
5.3 The preparation, cleaning and decontamination procedures should be performed
working from the upper areas to the lower areas, e.g. start from the roof area to the
mezzanine; proceed to the upper most and then to the lower floors. Within a room or
area, begin with stationary equipment followed by the ceiling, walls and finally the floor.

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Subject/Title:
PINICILLIN/ CEPHALOSPORIN DECONTAMINATION OF FACILITIES

6.0 PREPARATION OF EQUIPMENT AND AREAS

6.1 Certain items cannot, by their nature, be soaked with an aqueous decontamination agent.
Therefore, these items should be cleaned as thoroughly as possible with
vacuum/compressed air and wiped with the decontaminating agent where possible.
These items would then be wrapped in plastic and sealed for the remainder of the
 operation. Since vacuum/air blowing moves dust readily, this must be done in advance of
the general cleaning/decontaminating operation.
6.2 Any area which is not routinely cleaned should be cleaned thoroughly. These areas
should be cleaned starting with the "cleanest" section and moving towards the "dirtiest"
section.
6.3 Electrical boxes, switch boxes, and other areas which are not readily accessible to routine
cleaning must be vacuumed clean, blown with compressed air, and wiped if possible with
the decontamination solution.
Note: Compliance to established safety procedures is required throughout the decontamination
process.
7.0 CLEANING OF AREAS
All areas and items must be cleaned as per routine SOP using the specified detergent and
grade of water. If an area or item is not covered by an SOP, a "generic" cleaning method must
be formulated, documented and followed.
8.0 DECONTAMINATION METHOD
Note: Refer to Appendix I for documentation requirements.
8.1 The decontamination of all areas/items should proceed following the sequence as
identified in 4, 5, 6, and 7 above.
8.1.1 A suitable decontamination agent should be prepared (e.g., Alcojet, 5%
ammonia or sodium hydroxide with pH = 12). There must be documented
evidence of the effectiveness of the agent selected, at the concentration and
hold time to be used.
8.2 Actual Decontamination Procedure
8.2.1 The method of application must be specified. Methods include the following:
8.2.1.1 Spraying: Walls, ceilings, floors, tables, laminar flow curtains, storage racks, etc.

8.2.2 8.2.1.2
Wiping: Electrical components. Wipes must be disposable, non-linting if in a
sterile area, and changed with each major item change.
8.2.1.3 Soaking: Utensils, tools, etc.
Contact Time
8.2.2.1 The exposure time before rinsing is at least 2 hours and must be supported by agent
effectiveness studies.
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Subject/Title:
PINICILLIN/ CEPHALOSPORIN DECONTAMINATION OF FACILITIES

8.3 A rinsing procedure adequate to remove all the decontaminating agent should be
performed.
9.0 SAMPLING (SWABBING) PLAN FOR TRACE PENICILLIN/CEPHALOSPORIN
9.1 A Swabbing Procedure for Sampling Surfaces for Trace Residues is provided as
Appendix II and describes the swabbing method which should be used (other methods
may be used when validated).
9.2 Swab recovery studies must be done to determine levels of contamination that can be
recovered from the various surfaces within the facility. The minimum recovery efficiency
will be specified as part of method validation.
9.3 Critical versus non-critical areas/items must be recognized when designing the sample
plan. The most difficult to clean areas should be swabbed; this should include horizontal
surfaces, hard to clean areas on motors and at surface intersections. The exact location
of each swab must be documented. A swab may be used to sample related items
(minimum sample area 5 cm x 5 cm, or as per other validated method) as long it is
understood that a positive test result will require re-decontamination of all items swabbed
with that individual swab. It must be kept in mind that a swab will represent a predefined
area or item.
9.3.1 Critical Areas/Items
9.3.1.1 All areas/items designated critical must be swabbed.
Areas/items may require multiple swabs based on size.
9.3.1.1.1 Walls 1 swab per 100 square feet. Minimum of 1
swab/each wall (include an upper corner of the room).
9.3.1.1.2 Floors 1 swab per 100 square feet. Minimum of 2
swabs/room.
9.3.1.1.3 Ceilings 1 swab per 100 square feet.
Minimum of 2 swabs/room.
9.3.2 Non-Critical Areas/Items
9.3.2.1 The number of points sampled should be determined after the
area/item list is reviewed.
9.3.2.1.1 Walls 1 swab per 400 square feet. Minimum of 1
swab/room.
9.3.2.1.2 Floors 1 swab per 400 square feet. Minimum of 1
swab/room.
9.3.2.1.3 Ceilings 1 swab per 400 square feet.
Minimum of 1 swab/room.
9.3.2.1.4 All Other A minimum of 10% of the total
number of items listed as the most difficult to clean
non-critical equipment must be swabbed.
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Subject/Title:
PINICILLIN/ CEPHALOSPORIN DECONTAMINATION OF FACILITIES
10.0 TEST METHOD
FDA-By-Lines N:3
11.0 LIMITS
The Limits which apply for the testing must be designated in the protocol and SOP.
11.1 Critical Items Negative to test.
11.2 Non-Critical Items Negative to test.
12.0 ACTION PLAN FOR AREAS OR ITEMS WHICH EXCEED THE LIMITS
For both critical and non-critical items, the unit to be re-decontaminated is defined based
on how the swab areas were defined (Attachment I). Even if there is more than one swab
for a particular surface, each swab sample is representative of an entire surface area of a
wall, floor, ceiling, or other item. Therefore, when a swab sample exceeds the limits, the
decontamination process for the entire surface area must be repeated followed by swab
sampling.
12.1 For example, if a floor sample is out of specification, the entire floor area and any
other affected floor areas must be re-decontaminated; if a table has an area out of
specification, the entire table must be re-decontaminated.
12.2 The first pass minimum decontamination effectiveness must be indicated as part
the facility cleaning protocol. The decontamination procedure used may require
revision if deemed inadequate for the decontamination of the facility.
13.0 ROUTINE MONITORING
13.1 Following satisfactory decontamination of a facility, a program of routine swab
monitoring must be established. This program must provide an assessment of the
facility and equipment on an ongoing basis.
13.2 Following introduction of non-beta-lactam products, testing of these products for
the presence of beta-lactam residue must be conducted on a batch-by-batch basis.
13.3 A program to control and monitor for future demolition and construction activities
for the decontaminated facility must be in place to ensure these interventions do not
create contamination potential by disturbing previously undisturbed structures and
fixtures.

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Subject/Title:
PINICILLIN/ CEPHALOSPORIN DECONTAMINATION OF FACILITIES

APPENDIX I

The following documentation must be prepared and maintained for the decontamination
program:
1. A statement indicating that all areas and items were prepared and cleaned as per SOP.
The SOP number and title should be listed.
2. A list of areas/items which were decontaminated. This list should indicate the specific
area or item, whether the item is critical or non-critical as defined in 4.1 and 4.2, the
decontamination date, the swab sampling date and result (if applicable), and any re-
decontamination/ resample/ retest and the dates performed if applicable (See
Attachment I).
3. A schematic diagram of the area including dimensions, room numbers, functions of the
rooms, and air system. The air system should indicate everything from intake to room
feeds. If the system is shared, the shared area should be included.
4. A list of items which were discarded as in 4.3.
5. Sampling protocols must clearly define exact sampling locations so that they can be
identified at a later date.
6. Swab method and analytical procedures and analysis and validation reports.
7. Swab recovery studies for each material to be cleaned.
8. Decontamination effectiveness study indicating agent, concentration and the minimum
effective hold times.
9. Any deviation investigations that were relevant to the decontamination process should
indicate root cause and corrective actions.

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Subject/Title:
PINICILLIN/ CEPHALOSPORIN DECONTAMINATION OF FACILITIES
 APPENDIX II

SWABBING PROCEDURE FOR SAMPLING SURFACES FOR TRACE RESIDUES

Note: this procedure was validated. Alternative validated procedures may be employed. Swab
recovery from the surfaces sampled must be validated.

PURPOSE:
To present a swabbing procedure that may be used to monitor decontamination activities.

RESPONSIBILITY
Personnel taking swab samples must adhere to this procedure when decontamination procedures are
being performed.

PROCEDURE:
1. Each sample requires application to each sample area of 2 sterile swabs (e.g. sterile, cotton
tipped applicator Pur-Wraps). The first swab applied to the sample area is pre-moistened with 1%
Potassium Phosphate buffer solution pH 6.0. The second swab applied to the sample area is
applied dry.
2. Carefully and permanently mark a tube containing 4 ml sterile 1% Potassium Phosphate buffer
solution pH 6.0 with an identifying number. A numbered worksheet should be prepared ahead
of time so the sample locations can be recorded.
3. Using the pre-moistened swab, swab the chosen location firmly over a 5 cm X 5 cm (2" x 2") area
(25 sq. cm. or 4 sq. inches). By rolling the swab as you contact the surface, the contact surface of
the swab will be maximized. Following contact immerse this swab in the pre-numbered tube.
Using the dry swab, swab the same area until visible residual moisture on the sample surface is
absent. Immerse this swab in the same tube as the first swab. Assay both swabs simultaneously
as one sample.
4. A minimum of one unexposed swab should be included for each 50 samples taken as a
control.
5. The swabs in the pre-numbered tubes are held (refrigerated at 2-8C) until tested as per the
applicable test, but for no longer than 24 hours.

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 COMPLIANCE REPORT
PENICILLIN/CEPHALOSPORIN DECONTAMINATION
OF FACILITIES

ATTACHMENT I

REFERENCE # 1 2 3 4 5

ROOM #

ITEM

SWAB LOCATION

CRIT./NONCRITICAL

DECON. DATE

SWAB DATE

TEST DATE

RESULT (per swab)

RE-DECON. DATE

SWAB DATE

TEST DATE

RESULT (per swab)

For additional Re-
decontamination, go to page:

REFER 6 7 8 9 0
ENCE #
ROOM #
ITEM
SWAB LOCATION
CRIT./NONCRITICAL

DECON. DATE
SWAB DATE
TEST DATE
RESULT (per swab)
RE-DECON. DATE
SWAB DATE
TEST DATE
RESULT (per swab)
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 COMPLIANCE REPORT
PENICILLIN/CEPHALOSPORIN DECONTAMINATION
OF FACILITIES

COMPLETED EXAMPLE OF ATTACHMENT I

REFERENCE # 141 142 143 144 145

ROOM # 110 110 110 110 110

ITEM Ceiling South Wall North Wall East Wall East

SWAB LOCATION at diffuser bottom right top left middle left middl

CRIT./NONCRITICAL C C C C C
DECON. DATE 1/Jul/90 1/Jul/90 1/Jul/90 1/Jul/90 1/Jul

SWAB DATE 1/Jul/90 1/Jul/90 1/Jul/90 1/Jul/90 1/Jul

TEST DATE 2/Jul/90 2/Jul/90 2/Jul/90 2/Jul/90 2/Jul/

RESULT (per swab) .05 mcg BDL BDL BDL BDL

RE-DECON. DATE 4/Jul/90

SWAB DATE 4/Jul/90

TEST DATE 4/Jul/90

RESULT (per swab) BDL

For additional Re-
decontamination, go to page:

REFERENCE # 146 I 147 I 148 I 149 I 150

ROOM # 110 110 110 125 125

ITEM Scale Table Air wall return File cabinet Desk

SWAB LOCATION ft. top shield side south wall, middle drawer, rt. m
center side
CRIT./NONCRITICAL C C C NC NC

DECON. DATE 1/Jul/90 1/Jul/90 2/Jul/90 2/Jul/90 1/Jul

SWAB DATE 1/Jul/90 1/Jul/90 2/Jul/90 2/Jul/90 N/A

TEST DATE 2/Jul/90 2/Jul/90 3/Jul/90 3/Jul/90

RESULT (per swab) BDL 1.5 mcg BDL 0.85 mcg

RE-DECON. DATE 4/Jul/90

SWAB DATE 4/Jul/90

TEST DATE 4/Jul/90

RESULT (per swab) 0.2 mcg
For additional Re- 56
decontamination, go to page:

BDL = Below Detectable Limit of Assay

Report Number:
Page of .
 COMPLIANCE REPORT
PENICILLIN/CEPHALOSPORIN DECONTAMINATION OF
EQUIPMENT

ATTACHMENT II

DECONTAMINATION APPROVAL

Name / Title Author

Date

Name / Title Local Validation Group

Date

Name / Title Local Quality Assurance

Date
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