A leading biotechnology company developing a gene transfer therapy for Duchenne muscular dystrophy required Chemistry, Manufacturing, and Controls (CMC) regulatory expertise to prepare for a Type B Meeting with the U.S. Food and Drug Administration (FDA).

The meeting would focus on changes to the master cell banks, viral vectors, and the manufacturing process as the product progressed into late-stage clinical and commercial manufacturing.

To ensure a successful and productive FDA interaction, the client sought guidance on the preparation of the FDA Meeting Request and Briefing Book.

G&L Healthcare Advisors was engaged to provide expert CMC regulatory support and strategic input to refine the documentation and prepare the client’s team.

Challenges

Issues encountered included:
Complex regulatory pathway: The client faced a complex CMC development pathway for a novel gene transfer therapy in late-stage clinical trials, which required a clear and robust regulatory strategy.
Gaps in data: Gaps in supporting data related to potency assays and comparability protocols posed risks for FDA queries that could delay the product’s development timeline.
Documentation revisions: The initial structure and content of the FDA Meeting Request and Briefing Book needed significant revisions to align with FDA expectations for clarity and data presentation.

G&L’s Approach and Solution

Within this engagement, G&L took the following steps to ensure a comprehensive and well-prepared FDA interaction:
CMC expert evaluation and strategy: G&L assigned a dedicated CMC expert specializing in gene therapies to evaluate the client's draft Meeting Request and Briefing Book. This review identified several areas where the content could be strengthened and restructured for better alignment with FDA guidance.
Restructuring the Briefing Book: To ensure clarity and adherence to FDA expectations, G&L recommended a re-structuring of the Briefing Book’s content. This included a clear presentation of the changes to the master cell banks, virus vector, and manufacturing process, ensuring that the rationale behind these changes was well documented and scientifically supported.
Addressing data gaps: G&L identified critical gaps in the supporting data, particularly around potency assays and comparability protocols. These gaps posed a significant risk to the success of the FDA meeting and the development timeline. G&L recommended the generation of additional critical data to de-risk the FDA interaction.
Guidance and collaboration: G&L led the client's Subject Matter Experts (SMEs) through the process of rewriting the FDA Meeting Request and Briefing Book, ensuring that all necessary data and justifications were included and structured in a way that would facilitate a productive discussion with the FDA.

Impact and Outcomes:

With G&L's expertise, the following was achieved:
Comprehensive data presentation: G&L’s strategic input ensured that all necessary supporting data was generated and included in the Meeting Request and Briefing Book before the FDA meeting.
Successful FDA interaction: With G&L’s guidance, the client had a more productive discussion with the FDA, which helped to de-risk the development plan for the gene transfer therapy. This proactive approach prevented potential delays in the eventual Biologics License Application (BLA) filing.
Regulatory milestones secured: The successful engagement with the FDA, facilitated by G&L’s support, allowed the client to continue their late-stage clinical and commercial manufacturing process without disruption, keeping the project on track for future regulatory submissions.