Creative Biolabs can offer CreDA™ platform to prepare protein materials for comprehensive developability assessment by stable expression in the CHO cell line. Two important aspects of the candidates, expression titer and purification yield, are particularly evaluated to guide our clients’ selection of candidates that can be prepared in a low-resource platform process.
For detailed characterization of drug candidates in the comprehensive developability assessment stage, protein materials are prepared by stable expression in the CHO cell line, because the production of gram quantities of candidates that are needed to perform all tests is only feasible by using a stable expression system already at this stage. Transfected CHO cells are first cultivated as cell pools, and candidate protein recovered from the cultivated cell pools is utilized for profiling. In parallel to cell pools cultivation, the cells are cloned to identify the final clone for clinical and commercial manufacturing. Therefore, the process to generate the final manufacturing cell line and the comprehensive developability assessment of candidates run in parallel and are fully integrated. This approach makes it possible to relate the selection of the manufacturing cell line to the best product profile.
Fig.1 CHO production, expression titer, and purification yield assessment of drug candidates.
Fitness to the downstream process
In the CreDA™ platform, purification of the CHO-expressed proteins (mainly antibodies) is performed in a scaled-down version of the standard purification platform process. After purification by protein A chromatography column, the pH of the eluate is lowered to mimic the virus inactivation step, and different ion-exchange chromatography resins and requirements are tested to identify optimal conditions to polish the protein. During the production and purification processes, two important aspects of the candidates, expression titer and purification yield, are particularly addressed by our developability evaluation, allowing to assess whether a candidate can most likely be prepared in a low-resource platform process or needs to be handled in a more resource-intense non-platform approach.
Low product titers are particularly a concern if the clinic treatment requires a high therapeutic dose, as they can have an impact on how the cost of goods and manufacturing contributes into the overall lead candidate selection. During our developability assessment campaign, candidates are compared using the same production process to directly visualize the impact of the molecule on expression, aiming to increase the potential to select molecules that have overall greater productivity, in contrast to identification based on biological activity alone.
Product quality attributes can be impacted by a variety of factors, such as expression titer and conditions in the purification processes, which include pH ranges, resin loading, resin type, and buffer condition. While expression titer is an important initiating criterion for candidate selection, those that exhibit the highest expression are also required to exhibit good purification efficiency, low aggregation levels, and high stability. Therefore, our developability assessment also addresses the purification procedure that produces a high-quality product and isolates a homogenous, non-aggregated protein at high yield.
In terms of our Ph.D. level seasoned scientists and years of experience in the field of drug development, the CHO productivity assessment service at Creative Biolabs will help your selection of molecule with high productivity for further process development. Please contact us for more information and a detailed quote.