FDA drafts guidance on assessing potency of immunotherapy products
The US Food and Drug Administration’s (FDA) Center for Biologics Evaluation and Research (CBER) has issued a guidance to assist sponsors in assessing potency assays for active immunotherapy products (ACTIMPs), including cancer vaccines and treatments for autoimmune diseases.
FDA said that when finalized, this guidance will describe its current thinking regarding design, validation, and evaluation of potency tests for ACTIMPs.
The guidance aims to supplement the broader guidance provided for the industry on “Potency Assurance for Cellular and Gene Therapy Products,” which was released in December 2023. It includes additional advice and considerations specifically for ACTIMPs, including those that are based on peptides and proteins but do not fall under the categories of cell or gene therapy products. (RELATED: FDA CGT draft guidance focuses on potency assurance strategy, Regulatory Focus 2 January 2024)
The guidance addresses how sponsors can develop potency assays for ACTIMPS and selecting bioassays for ACTIMPS. It also addresses assessing potency for specific types of ACTIMPs, including non-personalized peptide- and protein-based ACTIMPs, non-personalized vectored ACTIMPs, and cell-based ACTIMPS.
According to FDA, active immunotherapies are designed to treat existing diseases or conditions by inducing, stimulating, or modulating immune effector cells through the introduction of an antigen associated with the specific disease or condition into the immune system.
Preventive vaccines for infectious diseases, bacteriophage products for infectious diseases, live biotherapeutic products, fecal microbiota for transplantation (FMT) products or allergenic products are outside the scope of the guidance.
The guidance states that “recent advances in genomics and new knowledge regarding mutation load in tumor cells have led to rapid improvements in ACTIMPs intended to treat cancer through induction of anti-cancer immune responses. ACTIMPs also include products intended to treat autoimmune disease by inducing immune tolerance against specific antigens associated with that autoimmune disease.”
FDA notes that assessing ACTIMP’s potency is challenging due to its reliance on host immune responses.
To evaluate potency for these products, sponsors should understand the active ingredients and mechanism of action (MOA) of the ACTIMP to identify critical quality attributes (CQAs) related to potency.
Sponsors should also ensure that potency assays are quantitative and are able to reliably discriminate between a product that is actively achieving its intended therapeutic effect and a product that has insufficient activity.
In addition, sponsors should discuss their potency assurance strategy and potency assay development plans with the CBER review team assigned to their Investigational New Drug (IND) application.
The guidance advises sponsors against adding an adjuvant to licensed products unless there is "satisfactory evidence" that it does not impact the product's safety or potency. If an adjuvant is utilized, CBER recommends that sponsors consult with their CBER review team for guidance on the appropriate control strategy for the adjuvant.
The guidance said that the most effective way to assess ACTIMP potency is through a quantitative bioassay. This type of bioassay evaluates the product’s impact on the immune system using living cells, tissues, or animals. “Bioassays can help mitigate risks to a product’s potency that may not be fully addressed through physicochemical assays alone,” states the guidance.
If the potency of an ACTIMP can be adequately assured without a bioassay, sponsors can use physicochemical assays during release testing.
The deadline for submitting comments is 18 November. Comments should be sent to www.regulations.gov and reference Docket No. FDA-2026-D-8561.
