Viral vector-based gene therapy products are the fastest growing segment of the gene therapy field, with adeno-associated virus (AAV)-based vectors dominating the landscape. The possibility of a one-time injection, and a relatively low-risk safety profile, increased demand for application of AAV-based vectors for the treatment of rare, serious, and life-threatening diseases. As sponsors scale-up and scale-out to meet the increasing demands and implement changes to optimize manufacturing process productivity and performance, it is imperative to effectively design and carry out comparability studies.

A well thought out comparability study is critical for demonstrating that the product attributes indicative of quality, safety and efficacy are similar pre and post change. Data derived from a robust comparability study also ensures that the preclinical and clinical data derived pre-change can be leveraged for future clinical studies and/or for supporting licensure without the need for repeat studies with post change product to demonstrate comparability. Implementing manufacturing changes to meet the demands of clinical supply and commercialization has presented challenges when evaluating comparability of the pre- and post-change product. For example, transition from an adherent to a suspension process may increase output while simultaneously impacting process- and product-related impurities. Limitations in the current understanding of how structure impacts function thus limits our ability to know which product quality attributes are important when making manufacturing changes. Inadequate comparability studies can lead to delays and misalignment of the clinical and CMC development and sometimes to the stalling of promising clinical programs.

This session will include case studies that illustrate the challenges and the strategies used for assessing comparability at different stages of development of viral vector-based gene therapies, and a discussion of the key considerations in the design of comparability studies.

Session Speakers:

Case Study: Comparability between AAV manufactured by Triple-plasmid transfection/HEK293 and Double-baculovirus/Sf9 Processes

Garrett Daniels, Prevail Therapeutics

Analytical Comparability – Evolution of Analytical Methods & Case Study for Late-Stage Change

Phillip Ramsey, Sangamo Therapeutics

De-Risking Analytical Comparability for an AAV Manufacturing Process Change in Late Development

Taro Fujimori, Ultragenyx

Assessing Comparability: It’s More Than Just Numbers

Julia O'Neill, Direxa Consulting

Leslie Nash

Appearances

Session 1: Comparability Considerations for Viral Vector-Based Gene Therapies

Session Chairs

Speakers