Pharmaceutical companies would spend, on average, several billion dollars for every new therapeutic protein that is eventually commercialized. The underlying reason for this huge cost is the exceptionally high rate of failure observed in the development process: approximately 90% of drug candidates failed during clinical trials. Unsatisfactory physical and chemical properties of drug molecules, such as poor solubility, low stability, high viscosity, the propensity of aggregation, and undesirable post-transcriptional modifications, can impact efficacy and even generate immunotoxic reactions, thus finally leading to failure of the project during late-stage development or clinical trials. With full understanding of this, Creative Biolabs provides comprehensive and state-of-the-art CreDA™ developability assessment service for your biopharmaceutical candidates, in order to address the issues that may lead to potential clinical failure.
Why is developability assessment necessary?
For the reasons mentioned above, the direct transition of molecules selected during early discovery stage with suboptimal properties to late-stage development may increase failures or require expensive and time-consuming formulation and development efforts. Therefore, the implementation of a knowledge-based developability assessment and experimental screening of drug candidates to select the developable molecules as early as possible is of crucial importance, as opposed to fixing “badly behaved” molecules in the late-stage development. Developability assessment campaign could de-risk the late-stage failures, with the consequent reduction in attrition rates, lowering development costs and shortening the timeline of the development cycle.
What developability assessment concerns about?
Developability assessment can be considered as the extension of the QbD (quality by design) guidance, providing a bridge between product knowledge and process understanding. It implements comprehensive investigation to assess manufacturing feasibility (productivity, stability, aggregation, etc.), formability for a specific administration route, and compatibility with in vivo environment, such as immunogenicity, off-target effect, and half-life. In short, developability assessment is a kind of risk assessment, through which the best drug candidate can be selected or, if necessary, risk-mitigated to fulfill the manufacturing, formulation, and safety characteristics before expensive development efforts are initiated.
Developability Assessment Service in Creative Biolabs
Creative Biolabs offers comprehensive and state-of-the-art CreDA™ developability assessment services for your drug candidates, in order to address the issues that may lead to potential clinical failure. Through the assessment, the most promising candidate is screened out or engineered to fulfill the manufacturing, formulation, and safety characteristics before further moved to the expensive development process. Our CreDA™ platform consists of mainly two modules: a preliminary screening stage and a comprehensive assessment stage. According to the magnitude of your drug candidates to be evaluated, one or both of the service modules could be chosen to guide your choice of lead candidate for further process development.
Fig.1 CreDA™ Platform for Biologics Developability Assessment.
Antibody discovery by phage display or hybridoma technologies typically results in a considerable number (usually >50) of potential candidates with desirable biological properties. To assess the developability of these large number of candidates, a high-throughput preliminary selection strategy, combine in silico prediction and in vitro assay of the isoelectric point, potential post-transcriptional modifications (PTMs), expression titer, aggregation, and stability, etc., is performed to screen out the top ones (usually <10) that will be ultimately characterized in detail during the comprehensive assessment stage.
Comprehensive Assessment
This module covers the comprehensive and detailed evaluation of the drug candidates, addressing the developability of each candidate from three different but interactive aspects: manufacturability, immunogenicity, and in vivo fitness.
Manufacturability assessment mainly involves in vitro assays (or in some cases in silico predictions) to evaluate the product yield and productivity, physical stability, the propensity of aggregation, chemical stability & PTMs, and pre-formulation. Among them, protein aggregation and PTMs are two particularly important issues that can appear at different stages of the manufacturing process, which can impact not only the yield and cost of the manufacturing but also the target product profile, delivery, and even in vivo safety.
Immunogenicity Assessment of Drug Candidates
Administration of biopharmaceuticals to patients can cause undesired immunogenic reaction, which is considered to be one of the major safety concerns for biotherapeutics and one of the primary causes for attrition during early clinical development. To address this issue, we have developed an advanced immunogenicity assessment system, including antigen presentation assay, T cell proliferation assay, DC-T assay, and other relevant assays, to evaluate your candidates and guide your choice of the lead molecule with low immunogenicity risk for further process development.
Drug candidates that show desirable manufacturability do not necessarily mean an optimal behavior in vivo, given the complicated in vivo environment of the patients. To investigate the potential risks and evaluate the in vivo fitness, several assays, including unspecific binding, FcRn binding, FcγR binding, serum stability, and pharmacokinetics are developed by our research groups, aiming to get a comprehensive understanding of your drug candidates.
Creative Biolabs has been making constant commitment to providing best-in-class developability assessment service, aiming to guide your choice of the most appropriate lead molecule from dozens of candidates for further process development. If you are interested in our service, please contact us for more information and a detailed quote.
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