FDA Publishes Draft Guidance on Potency Testing of Active Immunotherapy Products

In August 2026, the U.S. Food and Drug Administration (FDA) published draft guidance on potency testing for Active Immunotherapy Products (ACTIMPs). It is intended for manufacturers and sponsors who must ensure the consistent efficacy of active immunotherapies throughout the entire product lifecycle. The draft is non-binding and is initially being issued for public comment.

Background and Purpose

ACTIMPs treat existing diseases by inducing, stimulating, or modulating immune cells with the help of disease-related antigens. These products include peptide- and protein-based products, viral or bacterial vectors, and cell-based approaches. The draft is particularly relevant to cancer immunotherapies targeting tumor antigens and neoantigens, as well as approaches aimed at inducing immune tolerance in autoimmune diseases.
Assessing potency is challenging because the therapeutic effect depends to a significant extent on the individual patient’s immune response. For personalized products, patient-specific antigens and the limited availability of reagents make it more difficult to develop suitable bioassays. The FDA therefore recommends a science- and risk-based approach that links the mechanism of action (MOA) to critical quality attributes (CQAs). The scope of the draft does not include, among other things, prophylactic vaccines against infectious diseases, bacteriophages, live biotherapeutic products, or fecal microbiota transplantation (FMT) and allergenic products.

Regulatory Framework

The draft applies to biological products regulated under Section 351 of the Public Health Service Act. For these products, it must be demonstrated that they are safe, pure, and potent, and that these properties are maintained over time. Potency assays are therefore particularly relevant for lot release, stability testing, and comparability assessments following process changes. For approved products, the assays must comply with applicable biologics and current good manufacturing practice (cGMP) requirements and must be validated.

For investigational products in the early clinical phases, the FDA permits a phased and iterative approach to establishing potency assurance. The scope and depth of the supporting evidence may depend on the stage of development, study duration, dosage form, and available data. Nevertheless, an adequate potency assessment remains a prerequisite for protecting study participants. The FDA recommends discussing the potency strategy and assay development with the relevant CBER review team at an early stage.

Key Takeaways for Practice

Potency assays should be quantitative and reliably distinguish between sufficiently active and subpotent lots. Depending on the product, biological, physicochemical, or complementary testing approaches may be appropriate. For vectors, both gene transfer and the biological activity of the expressed antigen should be taken into account. For personalized products, a physicochemical assay may be sufficient once the manufacturing process and bioinformatics pipeline have been qualified. For cell-based ACTIMPs, relevant parameters may include cell viability, expression of the antigen or immunomodulator, and relevant cellular functions.
The draft underscores the need for a product- and mechanism-of-action-specific potency strategy that remains linked throughout the product lifecycle to process understanding, material control, stability, and change management.

More details can be found in the Draft Guidance for Industry - Potency Assessment of Active Immunotherapy Products directly.