FDA issues guidance in CGT potency tests

The document is intended to provide manufacturers of CGTs with recommendations regarding the development of tests to measure potency.

Since potency assays are designed specifically for every product the FDA’s guidance does not cover the selection of a test. Instead it focuses on clarifying the information that is needed to support an Investigational New Drug Application (IND) or a Biologics License Application (BLA).

The guidance states: “FDA regulations allow for considerable flexibility in determining the appropriate measurement(s) of potency for each product. Potency is determined based on individual product characteristics; therefore, the adequacy of potency assays is evaluated on a case-by-case basis​.

“All potency assays used for release testing of licensed biological drug products must comply with applicable biologics and current good manufacturing practice (CGMP) regulations​.”

Methods for measuring potency fall into the categories of biological, non-biological analytical and matrix assays. Any of these individually or in combination can be used to measure potency but the matrix assay is particularly useful owing to the complexity of some CGTs.

This is because devising potency tests for CGT products poses some challenges, such as inherently variable starting materials, multiple active ingredients and complex mechanisms of action.

In particular, in products with more than one active ingredient it may be unclear which contributes to potency. The guidance recommends that in these cases tests are devised to determine the potency of all active ingredients.

This is further complicated by the possibility of synergistic interactions between the different active ingredients. Consequently the development of a potency test requires the manufacturer to have an understanding of the products biological properties.

The guidance recommends this information is gained throughout preclinical and clinical testing, giving the manufacturer the time and information to refine the approach to measuring potency.

Consequently the guidance treats CTGs in clinical testing differently, acknowledging that potency tests may evolve throughout the development of the product.

In clinical trials potency measurements are needed for product characterisation testing, comparability studies and stability protocols. These are used to establish that a consistently manufactured product is administered during all phases of clinical investigation.

This is particularly important to provide a way of assessing the comparability of different manufacturing processes that may be tried during a products development. This is another factor that leads the guidance to recommend that potency assay development begins when the product is in preclinical.

The full draft guidance can be found here​.