FDA finalises potency rules for cell and gene therapies, starting at IND

It's tempting to treat potency as a pre-BLA problem. The FDA's final guidance on potency assurance says it starts at the IND. RAPS reported the guidance on 2 November, finalising a draft from December 2023 and replacing the agency's 2011 guidance on potency tests for these products.

What it asks for

The core idea is a potency assurance strategy: a plan, built on quality risk management, for showing that a product is potent and stays that way through its shelf life. Sponsors should describe that strategy in the CMC section of their IND, with more detail expected as development moves through each phase.

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For a BLA, every lot needs a potency test, run after all the manufacturing steps that could affect potency. Alternatives are allowed if they give the same or better assurance. Manufacturing changes have to be assessed for any effect on potency, and stability data during clinical development should include phase-appropriate potency assessments.

The guidance covers raw material variability, in-process testing, lab potency tests, short-shelf-life products, viral vector gene therapies and individualised therapies. It uses the familiar quality-by-design toolkit: target product profile, critical quality attributes, critical process parameters and a control strategy.

The sharp end

RAPS notes the FDA may put an IND on hold if it lacks the potency information needed to assess risk to participants. A Phase 2 or 3 study can also be held if its design can't meet its stated objectives.

"Patients who receive cellular and gene therapies are often battling serious or life-threatening conditions" Karim Mikhail, director of CBER, as quoted by RAPS

What changed from the draft

According to RAPS, the final version adds advice on fitting potency assurance into existing quality systems, more detail on risk assessment, recommendations on engaging with regulators, new examples and tidied terminology. The agency encourages sponsors to talk to it early about their potency strategy and assays.

The bigger picture

This sits alongside the FDA's recent work on individualised gene editing, which we covered last week. The direction is consistent. The agency is opening faster routes for rare disease genetic medicines, and asking for strong manufacturing and analytical evidence in return.

Our view: for early-stage companies, this moves analytical development up the hiring list. Potency now has to be planned from the first IND, not added later.

What it means for hiring

Potency assay development and analytical leadership become IND-stage hires, not pre-BLA ones. In our view, early cell and gene therapy companies that haven't built this function yet will start looking.
Regulatory CMC specialists who can write and defend a potency assurance strategy will be in demand, especially those who have handled CBER interactions on viral vector or individualised products.
Quality leaders with risk management experience (control strategies, CQAs, comparability) become more central as manufacturing changes need a documented potency assessment.

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