Vous êtes sur la page 1sur 4

Technical Bulletin

Cell Culture Media Manufactured in the


imMEDIAte ADVANTAGETM Pin Mill
Demonstrates Chemical Equivalency to Media
Manufactured in the Small Scale Pin Mill and
Continuous Pin Mill
Introduction • Process flow: pre-blend, pin mill, post-blend
• Nitrogen gas: utilized to cool the mill and transport components
In July 2008, SAFC Biosciences imMEDIAte ADVANTAGE™
TM
after particle size reduction
(IA) group installed a state-of-the-art, small-scale pin mill • Milling temperature: criteria is monitored: <40 C
capability for the manufacture of quick-turnaround, non-cGMP
dry powder cell culture media (DPM). This latest pin mill Pin mills are a type of high-speed impact mills consisting of
addition, termed the IA Pin Mill, provides seamless scale-up a feed inlet, a set of two disks with concentric rings of pins
of non-cGMP prototype formulations to the cGMP Small Scale and a product outlet. The pre-blended media components
Pin Mill (SSPM) and large-scale commercial Continuous Mill are fed into the mill and enter the center of the disk where
(CM). The IA Pin Mill is capable of producing 0.50 kg to they are centrifugally propelled outward and reduced in size
10 kg of non-cGMP DPM. by the rotating intermeshing pins. The raw materials are mixed
in a blender both before entering and after leaving the pin
The IA Pin Mill consists of the same stainless steel pin mill mill chamber to ensure a consistent feed into the mill and a
design as its large-scale cGMP counterparts along with the homogenous final product after being milled. Figure 1 shows
same: a photograph of the IA Pin Mill equipment, which is a Universal
Mill, model 6H, manufactured by Kemutec (Bristol, PA).

Figure 1. The Kemutec Universal Mill,


model 6H.

United States Europe Asia Pacific


SAFC Biosciences, Inc. SAFC Biosciences Ltd. SAFC Biosciences Pty. Ltd.
13804 W. 107th Street Smeaton Road, West Portway 18-20 Export Drive
Lenexa, Kansas 66215 Andover, Hampshire SP10 3LF Brooklyn, Victoria 3025
USA UNITED KINGDOM AUSTRALIA
Phone
Toll free-USA
Fax
+1 913-469-5580
1 800-255-6032
+1 913-469-5584
Phone
Fax
E-mail
+44 (0)1264-333311
+44 (0)1264-332412
info-eu@sial.com
Phone
Toll free-AUS
Fax
+61 (0)3-9362-4500
1 800-200-404
+61 (0)3-9315-1656
www.safcbiosciences.com
E-mail info-na@sial.com E-mail info-ap@sial.com
As part of the qualification of the IA Pin Mill it was necessary variation between samples in a given population (the
to demonstrate that the DPM it manufactured was chemically magnitude of the %RSD value is inversely proportional to the
homogeneous and comparable to the cGMP SSPM- and CM- homogeneity of the product). There will be an inherent
manufactured DPM. This was established via chemical analysis amount of variability present due to sample preparation and
comparing two different lots (of disparate sizes) of IA Pin Mill- the analytical method itself, which will be larger for
produced DPM against the SSPM and CM control DPM. components which are present in smaller quantities. Therefore,
based on preliminary work and information from the testing
Homogeneity laboratories regarding assay variability, an acceptance criterion
To demonstrate that the IA Pin Mill manufacturing process fully of <10% RSD for the amino acids and vitamins and <15% RSD
and uniformly blends a medium’s components to achieve a for the trace metal zinc was chosen to indicate a homogeneous
homogeneous product (i.e., any given component is present product.
at the same concentration at any given location throughout
the batch), multiple samples (6 - 14 aliquots) throughout the Figures 2 and 3 show the homogeneity results obtained as
lot were pulled, hydrated and sent for quantitative analysis of part of the validation for a SAFC Biosciences proprietary
amino acids, vitamins and zinc, one of the trace metals in chemically defined medium (EX-CELL™ CD CHO Serum-Free
the medium at a very low level of ~20 ppm). Percent relative Medium for CHO Cells) at two different batch sizes — a
standard deviation (standard deviation divided by the mean 600 g batch size representing the low end of the IA Pin Mill
and multiplied by 100%, or %RSD) was chosen as the pass/fail capacity and an 11 kg batch size, representing the high end
metric to assess homogeneity, and was used to quantify the of the capacity.

Figure 2

Amino Acid Homogeneity


115

110

105
Amount (%)

100

95

90

85
Thr

Tyr
Ile

Trp
Ser
Asp

Asn
Glu
Pro

Ala

Cystine

Leu

Phe

Arg
Val

Met
Gly

Lys
His

Amino Acids
Figure 2: Amino acid homogeneity (%RSD) of IA Pin Mill batches versus batches produced via
the cGMP SSPM and CM; Key: blue-IA Pin Mill (large lot); lavender-IA Pin Mill (small lot), red-
SSPM; black-CM.

www.safcbiosciences.com
Figure 3

Vitamin and Trace Metal Homogeneity


120

115

110

105
Amount (%)

100

95

90

85

80
Media Components
Pyridoxine Riboflavin Thiamin Nicotinamide Folic Acid Vitamin B12 Zinc

Figure 3: Vitamin and trace metal homogeneity (%RSD) of IA Pin Mill batches versus batches
produced via the SSPM and CM; Key: blue-IA Pin Mill (large lot); lavender-IA Pin Mill (small lot),
red-SSPM; black-CM.

All of the components met the %RSD criteria for being Summary
homogeneously distributed throughout the IA Pin Mill media The IA Pin Mill provides an application/milestone-specific
independent of batch size. The data demonstrate that the manufacturing site for customers requiring a quick-turnaround
manufactured media formulation will contain the same prototyping manufacturing process and/or smaller lot sizes.
amounts of individual components, within the normal assay Upon evaluation of the analytical studies, it has been
variability range, regardless of being produced via the IA Pin demonstrated that the IA Pin Mill is an effective and scaleable
Mill (0.50 kg to 10 kg), cGMP Small Scale Pin Mill manufacturing option that can produce quality, homogenous
(10 kg to 100 kg) or large-scale cGMP Continuous Mill cell culture media equivalent to the large-scale Continuous Mill-
(300 kg to 4000 kg). produced media.

www.safcbiosciences.com
Warranty, Limitation of Remedies
SAFC Biosciences warrants to the purchaser for a period of one year from date of delivery that this product conforms to
its specifications. Other terms and conditions of this warranty are contained in SAFC Biosciences’ written warranty, a
copy of which is available upon request. ALL OTHER WARRANTIES, EXPRESSED OR IMPLIED, INCLUDING THE IMPLIED
WARRANTY OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE, ARE EXCLUDED. In no case will SAFC
Biosciences be liable for any special, incidental, or consequential damages arising out of this product or the use of this
product by the customer or any third party based upon breach of warranty, breach of contract, negligence, strict tort,
or any other legal theory. SAFC Biosciences expressly disclaims any warranty against claims by any third party by way of
infringement or the like. THIS PRODUCT IS INTENDED FOR PURPOSES DESCRIBED ONLY AND IS NOT INTENDED FOR
ANY HUMAN OR THERAPEUTIC USE.
Additional Terms and Conditions are contained in the product Catalog, a copy of which is available upon request.

SAFC Biosciences TM, the SAFC Biosciences logo, imMEDIAte ADVANTAGE TM and
EX-CELLTM are trademarks of Sigma-Aldrich Biotechnology L.P.

© 2008 SAFC Biosciences, Inc.

Issued October 2008 T101

United States Europe Asia Pacific


SAFC Biosciences, Inc. SAFC Biosciences Ltd. SAFC Biosciences Pty. Ltd.
13804 W. 107th Street Smeaton Road, West Portway 18-20 Export Drive
Lenexa, Kansas 66215 Andover, Hampshire SP10 3LF Brooklyn, Victoria 3025

www.safcbiosciences.com USA
Phone
Toll free-USA
+1 913-469-5580
1 800-255-6032
UNITED KINGDOM
Phone
Fax
+44 (0)1264-333311
+44 (0)1264-332412
AUSTRALIA
Phone
Toll free-AUS
+61 (0)3-9362-4500
1 800-200-404
Fax +1 913-469-5584 E-mail info-eu@sial.com Fax +61 (0)3-9315-1656
E-mail info-na@sial.com E-mail info-ap@sial.com

Vous aimerez peut-être aussi