Stronger Unapproved Stem-Cell Enforcement Accompanies FDA Center for Biologics’ Cell and Gene Therapy Advancement Efforts

Over the last few years, FDA has ramped up its efforts to protect the public from unapproved and potentially dangerous stem cell products, while striving to create a regulatory framework and approach that is as supportive as possible for the advancement of the entire cell and gene therapy (CGT) field.

In this five-part story, IPQ explores the various ways in which the agency has been seeking to fulfill these two complementary sides of its mission in the CGT arena.

Included are insights provided over the past year at various forums from CBER leaders on the dimensions of the CMC challenges involved and the approaches being taken to address them.

● Part I – Comparing the Stem-Cell and Gene Therapy Landscapes: The story begins with a review of the opening presentation by CBER Director Peter Marks at an April 2020 Food and Drug Law Institute (FDLI) conference on regenerative medicine in which he provided an overview of and comparison between the regulatory issues and developments for stem-cell versus gene therapies. The Q&A that followed offered Marks the chance to elaborate on some of the key issues he had discussed.

● Part II – The Evolving Regulatory Framework for HCT/Ps: Explored more deeply in the next three parts of the story are the evolving regulatory framework in which CGT sponsors are working to bring new therapies forward and the supporting pathways and interaction opportunities that the agency offers. Following Marks at the FDLI April conference, CBER Chief of Staff Julia Tierney focused on the human cells, tissues, and cell and tissue-based products (HCT/Ps) – including the regulatory tiers that come into play, the guidance documents that have been issued, the expedited program designations and engagement pathways, and the compliance and enforcement activity. Tierney discusses the strong interest sponsors have shown in the Regenerative Medicine Advanced Therapies (RMAT) designation program.

● Part III – Gene Therapy Challenges and Regulatory Developments: Also addressing the FDLI meeting, Wilson Bryan from CBER’s Office of Tissues and Advanced Therapies (OTAT) discussed the gene therapy guidance series issued in January and the workshop held around the same time on the manufacturing issues for adeno-associated virus (AAV). The industry comments on CBER’s January draft guidance on interpreting sameness of gene therapy products for the purposes of orphan-drug determinations are reviewed. Included also is a review of Bryan’s presentation at the ISPE biomanufacturing conference in June in which he delved further into the upsurge in gene therapy investigational new drug applications (INDs) and biologics license applications (BLAs), and compared the traditional development paradigm with the sped-up process that is possible for gene therapies.

● Part IV – The Broader CBER, FDA and International Supporting Efforts: In focus in this part of the story is the keynote presentation at the 2019 CASSS CGT conference by CBER Deputy Director Celia Witten on CBER’s evolving regulatory process for CGTs and how it fits in with the broader regulatory program at CBER and FDA. Included is the engaging discussion that the presentation generated at the conference. After reviewing the tools provided by the 21st Century Cures Act and gene therapy developments, Witten highlighted the efforts to support advanced therapies through international regulatory sharing and harmonization – a subject that was explored further in the subsequent Q&A. Also commented on by Witten were CBER’s engagement in the FDA efforts to support advanced manufacturing and medical product/clinical development, and CBER’s overall strategic priorities for FY 2019.

● Part V – CBER Enforcement in the Stem Cell Therapy Arena: The concluding section takes a deeper dive into CBER’s compliance and enforcement efforts, where unapproved stem cell use has been a key focus. Included is a review of the enforcement landscape and developments in FY 2019 by Maria Anderson – a branch chief in CBER’s Office of Compliance and Biologics Quality (OCBQ) – at the PDA/FDA conference in September 2019. Updates are included on the HCT/P compliance activity by OCBQ Deputy Director Melissa Mendoza at the annual FDLI December enforcement conference and at the FDLI April regenerative medicine meeting, and by CBER Director Marks in an FDA release at the end of July 2020.

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