FDA Potency Guidance for Cell and Gene Therapy: Implications for Ocular AAV Programs

The FDA's draft guidance, Potency Assurance for Cellular and Gene Therapy Products, represents an important shift in how cell and gene therapy developers should approach potency throughout product development. Although the guidance applies broadly across the field, several recommendations are especially relevant to ocular AAV programs.

Rather than viewing potency as a single laboratory assay, the FDA emphasizes a comprehensive potency assurance strategy that evolves with the program. This strategy brings together product understanding, manufacturing process design and control, material controls, analytical characterization, in-process testing, and potency lot-release assays.

Potency Starts with the Product

The guidance compares potency assurance to sterility assurance. A sterility test does not make a product sterile; it confirms that the facility, process controls, environmental monitoring, and manufacturing practices produced an acceptable lot.

The FDA suggests potency should be approached in the same way. A potency assay remains essential, but it should confirm that a well-understood and well-controlled product consistently retains the biological activity needed to achieve its intended therapeutic effect.

Build the Strategy Early

Developers are encouraged to begin with a clear definition of the intended therapeutic effect and a Quality Target Product Profile (QTPP). From there, potency-related Critical Quality Attributes (CQAs) should be identified, along with the factors that could influence them.

Those factors may include vector design, raw materials, manufacturing variables, storage and shipping conditions, product preparation, and administration. Evaluating these relationships early can reveal where potency may be lost and where controls should be established before problems become more difficult or expensive to correct.

Potency Assurance Should Grow with the Program

The FDA recognizes that early-stage programs will not have every answer at the outset. An initial strategy based on the available product knowledge and data can be appropriate, provided it is refined as the program advances.

As manufacturing experience, nonclinical findings, and clinical data accumulate, the potency strategy should become more mature. By later-stage development, sponsors should have qualified potency assays, scientifically justified acceptance criteria, and evidence that the manufacturing process consistently produces comparable product lots.

Why This Matters for Ocular Gene Therapy

For ocular AAV programs, the guidance reinforces an important principle: product quality cannot be separated from biology. Vector design, manufacturing consistency, dose selection, stability, and analytical characterization can all influence clinical performance.

A stronger understanding of these relationships during preclinical development can improve manufacturing decisions, support clearer regulatory interactions, and strengthen the transition into clinical development. Preclinical studies should do more than demonstrate efficacy; they should also help explain why the product works and identify the attributes most important to consistent performance.

Implications for Ocular AAV Developers

For developers of ocular AAV gene therapies, potency should not be treated as a single assay developed shortly before an IND submission. The FDA's framework encourages a potency assurance strategy that begins early, evolves with product knowledge, and connects manufacturing and analytical controls to biological activity.

Programs that establish this foundation early will be better positioned to identify development risks, justify assay choices, manage manufacturing changes, and prepare for later-stage regulatory and clinical expectations.

Reference

U.S. Food and Drug Administration. Potency Assurance for Cellular and Gene Therapy Products: Draft Guidance for Industry. December 2023.

View the official FDA guidance