FDA Issues Draft Guidance on Potency Tests for Cellular and Gene Therapy Products

FDA recently published a new draft guidance document on potency tests for cellular and gene therapy (“CGT”) products.  The FDC Act requires that all biological products meet agency requirements for safety, purity, and potency before such products will be approved, but historically the agency and IND sponsors have faced challenges in establishing appropriate standards for potency testing for these complex types of products.  In the early years of CGT development, some pivotal clinical studies for CGT products were placed on clinical hold for lack of appropriate potency tests.  In the ensuing years, FDA and industry have learned a great deal about developing such tests for these products.  The draft guidance seeks to provide sponsors with the benefit of this learning.

The draft guidance makes clear that FDA recognizes that measuring potency of CGT products is a complex and evolving process.  Thus, the draft guidance recommends “an incremental approach to product characterization testing, including the development of potency assays,” and explains that the potency measurement “may change significantly” as the product is developed.  Although clinical study data “is not a practicable quantitative measure of potency,” FDA states that a manufacturer may use clinical study results “to establish a correlation between the product’s clinical efficacy and a potency measurement.”  FDA further recommends that manufacturers begin considering potency early and gather and evaluate data throughout the preclinical and clinical development of the product in order to determine the best method for measuring potency. 

The guidance also provides recommendations for determining what criteria to use to measure potency and the types of methods that may be able to make these measurements.  First, FDA states that manufacturers should develop potency measurements that “reflect the relevant biological attributes” of the product.  FDA uses a gene therapy vector to illustrate this recommendation, explaining that potency tests for a gene therapy vector should incorporate both the measure of “the ability to transfer a genetic sequence to a cell and the biological effect of the expressed genetic sequence.”  Second, FDA outlines three possible assays for measuring potency, including biological assays, non-biological analytical assays, and an assay matrix, and provides details on the types of data that should be gathered for those assays.   

Adequate potency testing becomes a critical issue for manufacturers in Phase 3 of CGT product development.  The draft guidance states that a manufacturer’s “potency assay design and acceptance criteria should be sufficient to assure that a well-characterized, consistently manufactured product was administered during your pivotal study(ies).”  Therefore, it is important that manufacturers develop appropriate potency testing.      

Although the draft guidance does not create any new regulations and “does not operate to bind FDA or the public,” it is evidence of FDA’s current thinking on CGT product approval.  The draft guidance applies only to CGT products that are reviewed by FDA’s Office of Cellular, Tissue, and Gene Therapies, but it signals FDA’s increasing comfort with for these products.  With luck, this draft guidance will help more manufactures bring these important products to market.

By Susan J. Matthees