Parallel Session 5B - Immunogenicity Risk and Control

Peptides, proteins and oligonucleotide are becoming essential medical treatments for many progressive, debilitating, or life-threatening diseases. However, the development of these potential therapies can be derailed by product immunogenicity as it can impact on safety and efficacy. Establishment of validated methods to measure anti-drug antibody responses during clinical trials is currently used to identify potential immunogenicity-related adverse outcomes and intervene early on. However, this approach is limited by incidence and study size particularly when there is low frequency of occurrence for many unwanted immunogenic outcomes.  As a result, understanding of product immunogenicity risk is often still incomplete late in development and during early commercialization.  Moreover, this also limits the information yielded by abbreviated regulatory paths for follow-on products such as complex generics and biosimilars.   To mitigate this risk, sponsors are increasingly utilizing analytical, in silico, and in vitro tools to compare and control product attributes such as propensity to aggregate, likelihood to undergo post-translational modifications, and presence of product and process related impurities that could act as adjuvants to reduce the failure risk in their product target selection.  Unfortunately, studies linking the result of these studies in the context of clinical results are rarely shared, even with the regulatory agencies, which is an important missed opportunity to connect critical quality attributes with clinical outcomes.  Thus, currently, our understanding of the levels of product and process related impurities that can impact on immunogenicity risk are frequently based on analytical and process capabilities rather than safety considerations, which can result in unnecessary burdens on development and lead to delay in getting potential therapies to patients.   This session will focus on emerging strategies to connect product quality attributes to immunogenicity risk, and how they could inform not only product selection and development but also the regulatory process for new products as well as for follow on products such as complex generic peptides, oligonucleotides and biosimilars. 

Session Speakers: 

Tiered, Data-driven Approach for Assessing the Safety of Product-Related Impurities in Support of Commercial Control Strategy Development

Robert Siegel, Eli Lilly and Company

Additional Panelists: 

Andrea Ferrante, Eli Lilly and Company

Mark Schenerman, CMC Biotech-MAS Consulting   

Jayda Siggers, Health Canada