03.11.24 -- Overcoming Advanced Therapy Development Hurdles

By working to optimize variables such as plasmid and vector design, yield, analytical development, and production pathway early, and by prioritizing downstream considerations such as final regulatory package as early as possible, drug developers can prevent issues before they arise and avoid the rework and delays that can torpedo timelines and derail development.

Recent breakthroughs in gene editing are revolutionizing research and placing deliverable gene editing therapies within patients' grasp. Realizing this possibility, however, will rely on the effective development and manufacturing of new therapies at scale by partners with proven expertise in areas such as viral vector production and analytics.

Inadequate preclinical planning and process development can stall advanced therapy development, preventing patients from receiving treatment for serious diseases. Leveraging the expertise and capabilities of an experienced partner is a key factor in optimizing AAV processes using DoE, thereby reducing variability and risk.

Major hurdles of manufacturing adeno-associated virus (AAV) vectors are scalability, production yields, and clean feed streams to facilitate effective purification strategies. Review the demands for AAV manufacturing using a suspension process and the DOE-based strategy used to achieve a scalable process in both terms of production and quality of AAV purified.

The optimization necessary to generate a reliable AAV platform that can support scale-up is complex. CDMOs must understand what parameters are necessary to achieve linearity from flask to bioreactor, how differing technologies and approaches influence variability, and how to balance technical considerations with manufacturability.

For any biotherapeutic in development today, a critical element in achieving commercialization is reducing manufacturing risk. Quickly and resourcefully serving as many patients as possible requires particular focus on three key areas: manufacturing, quality control, and process development.