Expectations for Phase-Appropriate Drug Substance and Drug Product Specifications for Early-Stage Protein Therapeutics.

Early phase specifications are established to ensure that materials used in clinical studies have appropriate product quality, reducing the risk of harm to patients. Currently, guidance is available for specification setting practices at commercial phase. With very limited data and manufacturing experience available, it is not possible to fully align to these expectations at the start of clinical trials. A survey was performed among 19 biopharmaceutical companies to gather information about the current practices for setting specifications in early phase development. The results indicate that most companies develop platform approaches to support setting specifications at the first-in-human (FIH) clinical trial stage of development. Based on shared learning across multiple companies, example specification approaches for monoclonal antibodies (mAbs) and antibody-drug conjugates (ADCs) are included. General principles of the example specifications can also be applied to other protein therapeutics and vaccines. Strategies for justification of acceptance criteria are described, along with discussion of considerations for some specific tests. Options for use of non-numerical acceptance criteria are also discussed. While specifications for each molecule must be set considering available molecule specific information the presented information leverages shared learning from multiple companies, to provide guidance for early phase specification setting strategies.