The US FDA's Center for Biologics Evaluation and Research (CBER) issued draft guidance in August 2026 setting out its recommendations for potency assessment of active immunotherapy products (ACTIMPs), including personalized neoantigen cancer vaccines, vectored immunotherapies, and cell-based antigen-presenting platforms.
The guidance addresses how developers should identify potency-related critical quality attributes (CQAs) and design, validate, and apply potency assays across clinical development and commercialization. It supplements CBER's broader draft guidance on potency assurance for cellular and gene therapy products, while also covering ACTIMPs, such as peptide- and protein-based products, that do not fall within the cell and gene therapy category.
What it covers
FDA defines ACTIMPs as biological products regulated under Section 351 of the Public Health Service Act that treat pre-existing disease by inducing, stimulating, or modulating antigen-specific immune responses. Preventive infectious disease vaccines, live biotherapeutic products, bacteriophages, fecal microbiota transplantation products, and allergenics are outside the guidance's scope.
Recommendations are organized across five product categories: non-personalized peptide/protein products, non-personalized vectored products, personalized peptide/protein products, personalized vectored products, and cell-based ACTIMPs. The guidance addresses selection of bioassays and physicochemical assays, CQA identification, reagent qualification, adjuvant control strategies, lot release, stability testing, and manufacturing comparability.
Personalized products receive particular attention because each patient's antigen composition may differ, making conventional product-specific biological potency testing difficult to implement at scale. For products using bioinformatics pipelines to identify patient-specific epitopes, FDA describes a phase-appropriate approach in which early clinical development may rely on sequence confirmation supported by scientific justification of the antigen-selection process.
As development advances and the bioinformatics and manufacturing processes become appropriately qualified, FDA indicates that potency may in some circumstances be assured using physicochemical testing of relevant CQAs rather than a functional bioassay for every individualized lot. The agency states that physicochemical assays alone may be appropriate when sponsors can demonstrate that they adequately assure product potency.
Why it matters
The guidance addresses a potentially important manufacturing constraint for personalized cancer vaccines. Because each patient's product may encode a different set of tumor neoantigens, requiring a bespoke functional potency assay for every manufactured batch could make large-scale commercial production difficult and slow.
FDA's proposed framework provides a potential regulatory route around that problem: developers can establish and qualify the systems used to select and manufacture individualized antigens, define the CQAs linked to biological activity, and potentially transition toward scalable physicochemical lot-release testing when scientifically justified.
That approach could become increasingly relevant as personalized neoantigen vaccines move into late-stage development. Rather than requiring identical antigen content across patients, potency assurance can focus on demonstrating that the platform used to design and manufacture each individualized product consistently produces material meeting predefined quality and functional expectations.
For cell-based ACTIMPs, FDA also recommends multiple complementary approaches to potency assessment where appropriate and discusses viability and other product characteristics that may function as potency-related CQAs. The agency emphasizes that potency strategies should be tailored to individual products and developed through early interaction with CBER.