Potency is a critical attribute of any cell therapy, as it confirms that the product possesses a biological function that is relevant to treating the clinical indication. However, in a recent review by the FDA, less than half of all cell therapy IND submissions described bioactivity assays, even though drug potency assays are required to be validated prior to the start of registrational clinical trials, which for rare disease indications can be as early as the first clinical trial.
Specifically, the FDA interprets potency as defined in 21 CFR600.3 and 21CFR610.10as an assay that: 1) demonstrates the functional bioactivity relevant to a known or postulated mechanism of action, 2) is appropriate for product lot release, 3) is specific to the product, 4) is quantifiable, 5) can demonstrate lot-to-lot consistency, 6) has been validated, 7) is compared to reference standards.
However, in recent guidance offered to the industry, the FDA has acknowledged that cell therapies present developers with a number of unique challenges, particularly when it comes to developing assays that accurately measure potency. Some of those challenges include the inherent variability of the starting materials; the limited lot size available for testing; the limited stability of the material; a lack of appropriate reference standards; multiple active ingredients, and the potential for interference or synergy between components of the product.
Enough information is required at each phase of an investigation to ensure proper potency assessment; the amount of information will vary with the phase of the investigation. Because each cell therapy is likely to require a unique potency assay or set of assays, the responsibility falls on the developer to provide ample data to support the proposed potency method and may require multiple assays.