FDA touts new flexible approach to reviewing cell and gene therapies

The US Food and Drug Administration (FDA) has announced it will take a flexible approach to reviewing all new cell and gene therapy (CGTs) biologics license applications (BLAs) to expedite the development of these products, rather than applying its flexibilities on a case-by-case basis.

The agency announced the new policy in a statement posted on Sunday. “Regulatory flexibility must be tailored for cell and gene therapies. These are common-sense reforms that will address the unique characteristics of cell and gene therapies and foster more innovation,” FDA Commissioner Marty Makary said.

Vijay Kumar, acting director of the Office of Therapeutic Products (OTP) in FDA’s Center for Biologics Evaluation and Research (CBER), concurred. “CBER is proactively communicating about regulatory flexibilities that were previously applied case-by-case to select CGT therapies. By communicating these approaches broadly, we aim to expedite product development across the CGT field. It is vital that every sponsor, no matter the CBER reviewer team they engage with, understand what types of regulatory flexibility may be scientifically acceptable,” he said.

Over the last decade, the CBER has approved nearly 50 CGTs. The agency said that “the transformative potential of these therapies has captured the imagination of the patient community and ignited product development.”

CBER Director Vinay Prasad said “there has been tremendous enthusiasm amongst product developers resulting in an explosive growth of cell and gene therapy submissions, many of which target serious or life-threatening conditions with an unmet medical need. CBER is eager for stakeholders to know that our effectiveness at exercising greater regulatory flexibility around chemistry, manufacturing and control requirements furthers innovative product development.”

FDA said it will grant regulatory flexibility to CGTs in three areas: clinical development, commercial specifications and process validation. In clinical development, manufacturers will not be expected to comply with Good Manufacturing Practices (GMPs) under 21 CFR part 211 in Phase 1 trials. FDA also said it will be flexible in establishing product release specifications and that such specifications should be consistent with the nature of the product and should be appropriately justified by sponsors. Also, FDA will not impose “overly strict and onerous comparability data” as products move from Phase 1 to Phase 3 studies.

FDA said its approach to specifications “is based on the need to ensure product quality and compliance while also recognizing that the small patient populations targeted by CGT therapies do not necessarily allow for a large number of manufacturing lots to support the product release specifications.”

The agency will also be flexible in establishing product release specifications in BLAs “consistent with the nature of the products and process and when appropriately justified.”

In the process validation area, FDA said it will not require three process performance qualification (PPQ) lots for process validation. Instead, FDA’s review “may consider whether PPQ protocols justify the appropriate number of lots based on overall process understanding.”

Mo Heidaran, chief regulatory scientist for Cellx Inc. Consulting, and a former reviewer with CBER, told Focus in an email that he does not see any new policy changes at FDA regarding these products but rather indicates how FDA’s OTP “has interpreted existing regulation in the framework of products developed for rare diseases.”

Heidaran stated that information regarding FDA’s expectations for CGTs can be found in a draft guidance issued in November 2024. (RELATED: FDA drafts Q&A guidance on cell and gene therapy development, Regulatory Focus 19 November 2024)

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FDA touts new flexible approach to reviewing cell and gene therapies

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