FDA CGT draft guidance focuses on potency assurance strategy

The US Food and Drug Administration has proposed a guidance that would update its policy on how sponsors can provide information on potency assurance for cell and gene therapy (CGT) products. If finalized, it would update a previous guidance that was less broad and focused on testing, which the agency acknowledged can be burdensome.

On 28 December 2023, FDA published a draft guidance on potency assurance for CGT products that the agency says takes a risk-based total product lifecycle (TPLC) approach. When finalized, the guidance is meant to replace a 2011 final guidance on potency tests for CGT products.

FDA also published a short video presented by Matthew Klinker, a branch chief at FDA's Office of Cellular Therapy and Human Tissues, alongside the draft guidance explaining the proposed updates. The branch chief noted that the biggest takeaway from the draft guidance is to encourage sponsors to develop potency assurance strategies that ensure that every lot of their product has the potency required to be effective and uses quality risk management principles. By comparison, he noted that the previous guidance was focused on potency testing, which can be burdensome for sponsors.

FDA said that the potency assurance strategy should be comprehensive and is meant to reduce the risk of the potency of a CGT product by factoring in the manufacturing process design, manufacturing process control, material control, in-process testing, and outcomes from potency lot release assays.

“As with some other aspects of CGT product manufacturing, our expectations are that you'll refine your potency assurance strategy as your product proceeds through each stage of clinical development,” said Klinker. He also noted that the broader approach using a potency assurance strategy is the main difference between the proposed guidance and the 2011 guidance, which focused on potency tests for CGT products.

Klinker added that the potency assurance strategy should be based on the sponsor's understanding of the characteristics of their CGT product that ensures that the product is effective, and recommended they develop a quality target product profile (QTPP) based on the product's mechanism of action, intended clinical indication and the route of administration. Furthermore, he added that FDA wants sponsors to identify the potency-related critical quality attributes (CQA) of their product that are needed to demonstrate the product’s intended therapeutic effect.

"The overall goal of a potency assurance strategy is to make sure that these potency-related CQAs fall into an appropriate range,” said Klinker. “So, identifying these attributes is a crucial step in developing a potency assurance strategy.”

Klinker added that after identifying potency-related CQAs, sponsors should conduct a risk assessment to identify risks that could affect the CQAs, figure out how likely they are to occur, and what steps can be taken to mitigate them. Ultimately, he noted that while the proposed guidance may be broader, it is also meant to be more flexible than the draft guidance.

“If there are limitations in one aspect of your potency assurance strategy, other aspects of the strategy may be able to compensate for those limitations,” Klinker added.

Stakeholders can comment on the draft guidance on www.regulations.gov under docket no. FDA-2023-D-4299 through 27 March.

Draft potency assurance guidance
2011 potency test guidance

FDA CGT draft guidance focuses on potency assurance strategy

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