Principal Scientist Amgen Thousand Oaks, California
Protein aggregation is a critical quality attribute that is closely monitored during biologic candidate selection and process development. Aggregation is often observed under accelerated stress conditions such as thermal stress, agitation and freeze-thaw processes. This talk will delve into the relatively rare stability issues encountered during long-term storage of proteins in the frozen state. Specifically, the presentation will provide a high-level overview of the possible mechanisms of frozen state protein aggregation and will highlight case studies on the higher order structure characterization of frozen aggregates in novel modalities. Potential mitigation strategies to control frozen aggregation such as formulation development will also be discussed. Finally, the implications of frozen state instability on drug substance and drug product analytical development will be addressed.
Learning Objectives:
Identify possible routes of degradation for novel biologic modalities after long-term frozen storage
Define appropriate formulation development strategies to mitigate frozen state degradation
Understand structural liabilities responsible for aggregation that could be addressed during early stages of molecule development
