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FDA expects more than 200 investigational new drug applications for cell and gene therapies by 2020, causing the agency to strengthen its regulatory program.
In anticipation of a continued surge in the development of cutting-edge medical treatments, FDA officials are strategizing how the agency assesses and reviews these products. This involves expanding the cadre of experts tasked with evaluating innovative cell and gene therapies, clarifying policies governing this field, and promoting new production methods that support innovation. FDA estimates that sponsors and investigators will file more than 200 investigational new drug applications (INDs) for these products by 2020, adding to the more than 800 applications currently on file for cell-based or directly administered gene therapy applications. FDA predicts that this pipeline will lead to the approval of 10 to 20 new products in this area by 2025 (1). Analysis by academics and research organizations are similarly enthusiastic. The MIT Focus Project, which seeks to devise new methods to pay for innovative, but costly, cell and gene therapies, predicts the approval by 2030 of 40–60 important curative treatments in this area, which will reach approximately 50,000 patients and cost more than $200 billion a year (2).
These advances reflect a “turning point” in the development of this new technology, observed FDA Commissioner Scott Gottlieb and Peter Marks, director of the Center for Biologics Evaluation and Research (CBER)(1). Their information aims to update the biomedical research community on agency initiatives designed to encourage research and development in this area. They note similarities to the acceleration in discovering antibody drugs in the 1990s, citing the importance of developing safe and effective vectors for delivering gene therapies to patients in enabling further discoveries. A specific plan is to add 50 reviewers in the coming years to expand the staff of CBER’s Office of Tissues and Advanced Therapies (OTAT) and related offices.
Additional guidance documents will further advance innovation in this area. FDA plans to outline how sponsors may use expedited review programs, including the regenerative medicine advanced therapy (RMAT) designation and accelerated approval programs, to facilitate the development of gene therapy products that offer meaningful improvements over available treatments for serious or life-threatening conditions. New guidance on developing gene therapies will target neurodegenerative disorders and on inherited blood disorders such as hemophilia. With accelerated approval approaches, FDA also will require post-market, follow-up studies to assess risks and possible side effects that cannot be determined prior to approval.
A critical challenge, add these FDA leaders, is to address the “complexities associated with manufacturing these products in a safe, reliable, and cost-effective way.” Gottlieb and Marks are concerned that sponsors may avoid implementing innovative manufacturing processes for fear regulators will demand additional clinical trials, which are sometimes required with post-approval changes and create additional costs. Guidance that promotes a better understanding of the critical quality attributes and other factors related to product manufacturing of CAR-T and other cellular therapies will aim to clarify what are minor and major manufacturing changes and explain how innovators may adopt advances in manufacturing without the need to confirm safety and quality in additional clinical investigations.
Further guidance documents will examine when minor manufacturing changes can be made without additional bridging studies and where limited bridging studies and additional real-world data may be sufficient to document the safety and effectiveness of treatments following production changes that implement advanced technologies. FDA plans to hold a public meeting for agency and industry experts to discuss further ways to expedite bridging studies when more than minor changes are made in manufacturing processes, but those changes fall short of fundamental product transformation.
At the same time, FDA officials look to crack down on organizations and clinicians administering gene therapies not vetted by the agency and thus raising serious safety concerns. FDA intends to expand enforcement actions to rein in manufacturers that fail to comply with regulatory policies. Additional guidance from the agency, moreover, will seek to encourage compliance by small firms and academic investigators by outlining innovative trial designs that permit researchers to pool clinical data for products using a common manufacturing protocol and product quality specifications.
1. FDA, “Statement from FDA Commissioner Scott Gottlieb, M.D. and Peter Marks, M.D., PhD, Director of the Center for Biologics Evaluation and Research on new policies to advance development of safe and effective cell and gene therapies,” Press Release, Jan. 15, 2019.
2. MIT NEWDIGS FoCUS Project,
(MIT, Oct. 29, 2018).
Vol. 32, No. 3
When referring to this article, please cite it as J. Wechsler, "Cell and Gene Therapies Gain Streamlined FDA Oversight," BioPharm International 32 (3) 2019.