Potency is a strategy, not a release test: CGT sponsors should write theirs before the pivotal data

The guidance changes what potency means

On 2 November FDA's CBER finalised its guidance on potency assurance for cellular and gene therapy products. It supersedes the January 2011 potency tests guidance. The title change matters. The old document was about tests. The new one sets out a science- and risk-based approach and, according to the agency's announcement, a risk-based Potency Assurance Strategy that runs from development through post-market verification.

My position is simple. Regulatory affairs teams should stop treating potency as a late-stage assay problem owned by quality control. It is now a programme-level strategy, and it belongs in the same planning conversation as endpoints, manufacturing changes and confirmatory commitments.

Why the timing matters

The same day brought a reminder of how CGT products reach the market. FDA granted accelerated approval to Inovio's Voceryq, a plasmid DNA immunotherapy delivered with the CELLECTRA 5PSP device, for adults with recurrent respiratory papillomatosis. The records describe a surgery-frequency endpoint, a 7-in-26 complete response rate, and a required confirmatory study. Separately, FDA accepted uniQure's accelerated approval application for the Huntington's gene therapy AMT-130 with priority review. It tentatively plans an advisory committee discussion and has set an action date of 1 May 2027.

The records do not say that FDA linked these decisions to the potency guidance, and I am not claiming it did. The point is about where the pressure falls. Accelerated pathways rest on evidence that is provisional by design, and the obligation to confirm benefit later runs for years. A product whose biological activity is poorly characterised at approval will be hard to defend through that period. Process changes, scale-up and site transfers will all raise the question of whether the product is still the one that produced the clinical result. A potency strategy that spans development to post-market verification is the answer to that question. A strategy assembled just before filing is not.

What teams should do differently

First, give the potency strategy an owner in regulatory affairs, not only in analytical development. It should be a living document that links the mechanism of action, the clinical endpoint and the release and stability measures, and that is revisited whenever the process changes.

Second, gap-assess existing programmes against the new text now. Programmes designed around the 2011 guidance may be sound, but sponsors should find out where they are not before a reviewer does. Any pre-submission or advisory-committee preparation, such as uniQure's, should expect potency questions.

Third, plan the post-market side from the start. If verification continues after approval, the resources and the data-collection plan need to be budgeted and agreed internally before the approval letter arrives.

The strongest counter-argument

The best objection is that guidance is non-binding and that a risk-based approach offers flexibility, not certainty. Sponsors with small teams and tight cash runways may reasonably argue that a comprehensive strategy document is a luxury, and that it risks becoming a paper exercise that satisfies no one. There is also a fair worry that a lifecycle-wide strategy invites lifecycle-wide scrutiny.

I accept the first point: the guidance is not law, and the records do not detail how reviewers will apply it case by case. But flexibility is exactly why a written strategy matters. A risk-based framework rewards the sponsor that can explain its reasoning and penalises the one that cannot. As for scrutiny, post-market verification is already part of the framework the agency describes. Ignoring it does not make it go away. A strategy that anticipates it is cheaper than one drafted in response to a deficiency.

Our recommendation

Treat the final potency assurance guidance as a planning document, not a reading-list item. Within the next quarter, every CGT programme should have a written potency strategy with a named regulatory owner, tested against the new text and tied to the clinical endpoint and any post-approval commitments. The programmes that do this will find that potency is the easiest part of their evidence to defend. The others may find it is the hardest.

— The VigiEye regulatory desk