FDA Potency Guidance for Cell and Gene Therapy: Implications for Ocular AAV Programs.
Updated: Sep 22
The FDA's 2023 draft guidance, Potency Assurance for Cellular and Gene Therapy Products, represents an important evolution in how cell and gene therapy developers should approach potency throughout product development.
The earlier 2011 guidance focused primarily on developing appropriate potency tests. The newer draft expands this concept into a broader potency assurance strategy that connects product understanding, manufacturing controls, material controls, analytical characterization, in-process testing, and lot-release potency assays.
From Potency Testing to Potency Assurance
A potency assay remains essential. For example, an ocular AAV program may demonstrate throughout preclinical development that the therapy produces the intended biological effect and establish an assay showing that the manufactured product retains relevant biological activity.
The newer framework goes one step further. Developers should also understand why the product remains potent and what factors could cause potency to change.
These factors may include vector design, raw materials, manufacturing conditions, storage and shipping, product preparation, and other variables that can influence biological activity.
The FDA compares potency assurance to sterility assurance. A sterility test does not make a product sterile; it confirms that the manufacturing process and controls produced an acceptable lot.
Potency can be viewed similarly. The potency assay confirms biological activity, while the broader development and manufacturing strategy helps ensure that activity is consistently maintained.
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.
Evaluating these relationships early can help identify where potency may be lost or altered 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 available product knowledge and data can be appropriate, provided it evolves as the program advances.
As manufacturing experience, nonclinical findings, analytical data, and clinical information accumulate, the potency assurance strategy should become more mature.
By later-stage development, sponsors should have appropriately qualified potency assays, scientifically justified acceptance criteria, and evidence that the manufacturing process consistently produces product with the intended biological activity.
Why This Matters for Ocular Gene Therapy
For ocular AAV programs, the guidance reinforces an important principle: product quality cannot be separated from biology.
Demonstrating that the therapy produces the intended effect and establishing an appropriate potency assay remain essential. The newer framework, however, places greater emphasis on understanding which product and manufacturing characteristics help maintain that activity.
A stronger understanding of these relationships during preclinical development can improve manufacturing decisions, support clearer regulatory interactions, and strengthen the transition into clinical development.
Implications for Ocular AAV Developers
For developers of ocular AAV gene therapies, the key evolution is from potency testing toward potency assurance.
The earlier FDA framework already emphasized appropriate potency assays. The newer draft broadens this approach by connecting potency testing more explicitly with product understanding and manufacturing control.
In practical terms, developers should be prepared not only to demonstrate that the product is potent, but also to explain what supports that activity, what could cause it to change, and how those risks are controlled.
Reference
U.S. Food and Drug Administration. Potency Assurance for Cellular and Gene Therapy Products: Draft Guidance for Industry. December 2023.
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