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 advertorial
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