Expression and Production
BD Select™ CD1000
A High-Performance Platform Media
112
BioProcess International
0 Control
6 g/L Blend
Yeast + Wheat
3 g/L Blend
Yeast + Soy + Wheat
17 g/L Yeast
9 g/L Yeast
3 g/L Yeast
50
Figure 4: BD Select CD1000 evaluation of CHO and NS0 cell lines feed
strategy using chemically defined supplements
350
300
GS CHO Line #2
CD Feed #1
GS CHO Line #2
CD Feed #2
NSO Line
CD Feed #3
250
200
0
Industry Yearbook 2009
Daily Feed
50
Day 3 Feed
100
Day 0 Feed
150
Daily Feed
Control
100
Day 3 Feed
0
150
Day 0 Feed
50
Yeast = BD Difco™
TC Yeastolate UF
200
Daily Feed
100
NS0
150
Hybridoma
200
GS CHO #2
Antibody Yield %
(Normalized to Control)
250
250
Antibody Yield %
(Normalized to Control)
Figure 2: BD Select CD1000 evaluation of multiple cell types with
hydrolysate supplementation; 0% line represents Select CD1000 without
hydrolysate supplementation
Figure 3: BD Select CD1000 evaluation of GS CHO #2 feed strategy
using hydrolysates; 0% line is Select CD1000 without hydrolysate feed
Day 3 Feed
0
Select CD1000
w/Days 0 and 3 Yeast
(in Bioreactor)
50
Select CD1000
w/Day 0 Yeast
100
Select CD1000
150
Select CD1000
w/Days 0 and 3 Yeast
200
Control
Antibody Yield %
(Normalized to Control)
250
Stacy Holdread is with BD Biosciences—Advanced Bioprocessing,
54 Loveton Circle, Sparks, MD 21152; 1-410-316-3628, fax 1-410-316-3690;
[email protected]. BD, the BD logo, and all other trademarks are
property of Becton, Dickinson and Company, ©2009.
Day 0 Feed
Figure 1: BD Select CD1000 development overview (GS CHO Line #1
evaluation); 0% line represents a commercially available CD medium
CHO, NS0, and hybridoma cell lines after only one round of
hydrolysate optimization.
Further process optimization (including feed supplement
identification) is critical to achieving peak performance. Even
higher yields can be achieved with feed supplements and
strategies. In Figure 3, a GS-CHO line was evaluated with various
individual and blended feed supplements. All flasks that
received a hydrolysate feed showed a significant increase in
protein production, with the 17-g/L TC Yeastolate UF feed
producing >200% increase.
Chemically defined feeds are also effective for achieving
rapid protein production increases. Three different CD feeds
were evaluated in Figure 4, and each resulted in significantly
increased protein yields, with GS-CHO Line #2 achieving >300%
yield increase through daily feeding with CD Supplement #1.
The versatility of BD Select CD1000 to support multiple cell
types and supplementation strategies makes it an ideal platform
medium for rapid, cost-effective process optimization. c
Antibody Yield %
(Normalized to Control)
E
very cell line has unique nutritional requirements that
must be properly balanced to achieve peak
performance. However, production demands and tight
timelines can make it challenging to conduct a base medium
optimization for each individual cell line. To address this issue,
BD has developed Select CD1000, a new, chemically defined
platform medium using the proven methods of the BD
AutoNutrient™ Media Design Service (AMDS) including design
of experiments (DOEs) developed specifically for
biopharmaceutical cell lines.
BD Select CD1000 is a high-performance base medium that has
also been optimized for further supplementation to enable
increased process yield during scale-up and production. In Figure
1, protein production increased when a hydrolysate was added to
Select CD1000. This increase was further enhanced with the
addition of a hydrolyate feed at both the shaker flask and
bioreactor scale. In under three months, protein production was
increased nearly 250% over the original, nonoptimized formulation.
BD Select CD1000 is a versatile platform medium that can be
used across multiple cell types, including CHO, NS0, and
hybridoma cells. Such versatility results in reduced media
optimization time, resources, and costs because only one
formulation is needed to support all potential applications.
Figure 2 demonstrates significant production increases with
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