Takeaways from the 7th Annual FDA Liaison Meeting

ASGCT convened its seventh annual Liaison Meeting with the Food and Drug Administration’s (FDA) Center for Biologics Evaluation and Research’s (CBER) Office of Therapeutic Products (OTP) in February. This meeting brought together Society experts and Agency leadership for a focused dialogue on key regulatory issues in cell and gene therapy (CGT). The meeting featured two ASGCT-led presentations addressing challenges and opportunities in regulatory policy for CGT development. ASGCT appreciates FDA’s time and continued engagement in these discussions, which help advance shared goals in the field. Dr. Kristin Van Goor, Chair of ASGCT’s Regulatory Affairs Committee, served as the meeting’s moderator. 

ASGCT Presentation 1: Accelerated Approval Considerations for Cell and Gene Therapy 

Presenters: 

• Jeffrey Chamberlain, PhD, Immediate Past President, ASGCT; Professor and McCaw Endowed Chair in Muscular Dystrophy, University of Washington 

• Angela Whatley, PhD, Senior Director of Regulatory Affairs, Prime Medicine 

• Kristin Van Goor, PhD, Chair, ASGCT Regulatory Affairs Committee; Executive Director, US Head of Global Regulatory Policy and Innovation, Takeda 

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ASGCT’s first presentation focused on the application of the Accelerated Approval (AA) pathway to CGTs and the role of platform technologies in streamlining product development. 

Dr. Chamberlain opened the presentation by outlining three distinct CGT development scenarios in which the AA pathway could be applied. He emphasized that biological plausibility should serve as the foundation for regulatory decision-making and that AA should be the primary regulatory pathway for CGTs in cases where strong empirical evidence supports pharmacologic activity. 

Dr. Chamberlain urged FDA to provide clearer expectations regarding the weight assigned to different types of clinical and biomarker evidence when evaluating CGT products under AA. He noted that CGTs often have distinct mechanisms of action.  Therefore, early engagement between FDA and sponsors is critical to ensure appropriate data collection and regulatory alignment. 

Dr. Whatley then presented how platform technologies can enhance regulatory efficiency in CGT development and facilitate AA. She explained that platform-based approaches can: 

• Reduce development timelines and regulatory burden. 

• Increase manufacturing efficiencies and decrease costs by standardizing production processes. 

• Minimize redundant studies by applying knowledge across programs. 

Dr. Whatley acknowledged FDA’s Platform Designation Program as an important tool and noted that greater clarity is needed as to how sponsors can leverage platform-generated data to meet regulatory expectations. 

She presented ASGCT’s key recommendations for FDA, including: 

• Hosting multi-stakeholder workshops to advance platform-based regulatory approaches. 

• Providing case studies—real or hypothetical—to illustrate how prior data can support AA across CMC, pharmacology/toxicology, and clinical development. 

• Clarifying regulatory pathways for integrating platform-generated data into AA decisions. 

• Offering substantive, early advice on platform utilization prior to the first Biologics License Application (BLA) submission. 

Dr. Whatley emphasized that FDA’s flexibility in applying platform data can streamline development and reduce regulatory uncertainty. 

Dr. Kristin Van Goor concluded the presentation by discussing the application of the "Meaningful Advantage" standard to CGTs. She explained that in many cases, FDA evaluates whether a new therapy offers a meaningful advantage over existing treatments, but this evaluation should be adapted for CGTs. 

She noted that while traditional regulatory frameworks focus on direct clinical benefit, CGTs offer additional advantages that warrant consideration, such as reducing the number of clinic visits and overall treatment burden, improving long-term quality of life, and enabling earlier access to potentially curative therapies. 

Dr. Van Goor emphasized that earlier access to CGTs, even by months or years, can be highly beneficial, particularly for patients with progressive diseases. ASGCT recommended that FDA remain flexible in defining "meaningful advantage" in the CGT context to avoid unnecessary delays in access to life-changing therapies. 

She also highlighted that FDA should continue engaging with patient groups and clinical experts to ensure the meaningful advantage standard reflects real-world patient experiences and unmet medical needs. 

ASGCT also expressed appreciation to FDA for its continued efforts to develop and support the Accelerated Approval pathway, including the Agency’s sustained engagement with developers and patient communities to ensure the pathway remains scientifically robust, patient-centered, and responsive to the evolving CGT landscape. 

ASGCT Presentation 2: Risk-Based Manufacturing Standards for CGTs in Rare Diseases 

Presenters: 

• Sadik Kassim, PhD, Chief Technology Officer and Chief Scientific Officer, Danaher Genomic Medicines 

• Brian Shy, MD, PhD, Assistant Professor, University of California, San Francisco 

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The second ASGCT presentation focused on the challenges associated with manufacturing CGTs for rare and ultra-rare diseases and the need for a risk-based regulatory approach to ensure both feasibility and safety. 

Dr. Sadik Kassim opened by discussing the significant barriers to CGT manufacturing for ultra-rare diseases, noting that while CGTs offer potentially curative treatments, current regulatory expectations do not account for the realities of extremely small patient populations. He explained that applying large-scale commercial manufacturing requirements to ultra-rare indications creates unnecessary burdens, delaying access to life-saving therapies. He emphasized that many CGTs have demonstrated safety and efficacy but lack commercial viability due to high production costs, limited patient populations, and regulatory complexity. 

Dr. Brian Shy presented a case study on ART-SCID (Artemis-deficient Severe Combined Immunodeficiency), an ultra-rare genetic disorder. He described how a lentiviral gene therapy has successfully treated 17 patients over six years, but the lack of commercial interest has required UCSF to pursue a BLA within an academic setting. Despite its success, the regulatory burden of scaling production for such a small population is disproportionate to the actual manufacturing needs. 

Dr. Kassim then introduced a second case study focused on CRISPR-based gene editing and the need for harmonization around guide RNA (gRNA) sourcing and quality. He explained that inconsistent quality definitions among vendors create regulatory uncertainty and inefficiencies, and that gRNA purity directly impacts potency and functional efficiency, requiring more material to achieve the same editing outcomes when purity is lower. He noted that off-target effects were not significantly impacted by gRNA purity, suggesting that regulatory standards should be adapted accordingly. 

Dr. Shy closed the presentation by outlining ASGCT’s key recommendations, including: 

• A risk-based approach for critical starting materials to ensure regulatory expectations align with product safety and efficacy, rather than applying one-size-fits-all manufacturing requirements. 

• Expansion of FDA’s platform designation program to include non-BLA holders, enabling academic and small biotech sponsors to benefit from platform-based regulatory frameworks. 

• Regulatory alignment with EMA standards, including harmonized risk-based approaches to raw materials and differentiated expectations for active substances versus critical starting materials. 

• Greater clarity from FDA on expectations for small patient populations, including flexibility in GMP requirements based on disease prevalence, manufacturing scale, and clinical need. 

Dr. Shy emphasized that challenges with critical starting materials are delaying progress for both established and next-generation CGTs and that a risk-based approach and platform-based manufacturing strategies could reduce regulatory burden while maintaining safety and efficacy. He reiterated that FDA guidance on these topics would provide much-needed clarity and help incentivize innovation in the CGT space. 

ASGCT thanked FDA for the opportunity to engage in thoughtful dialogue on the manufacturing challenges unique to CGT development and closed the meeting by expressing appreciation for the Agency’s continued collaboration across these critical areas of science and policy. The Society looks forward to ongoing engagements with FDA to support regulatory approaches that enable timely, safe, and equitable access to transformative therapies. 

Andrew is ASGCT's Senior Manager of Regulatory Affairs.