The U.S. Food and Drug Administration has finalized its guidance for industry, Potency Assurance for Cellular and Gene Therapy Products. Issued by the Center for Biologics Evaluation and Research (CBER), the final guidance supersedes the agency’s January 2011 guidance, Potency Tests for Cellular and Gene Therapy Products, and finalizes the draft of the same title that FDA released for comment in December 2023.

From Potency Testing to Potency Assurance

The title change signals the substance of the update. The 2011 guidance treated potency largely as a question of test design: pick a biological assay, validate it, and use it to release lots. The new final guidance asks sponsors to build a full potency assurance strategy that spans the product lifecycle, combining manufacturing process design, process control, material control, in-process testing, and lot release assays, so that release testing is one safeguard among several rather than the sole proof of potency.

That strategy is built on a now-familiar quality risk management vocabulary: a Quality Target Product Profile that captures the product’s potency-related characteristics, Critical Quality Attributes tied to mechanism of action, Critical Process Parameters that can move those attributes, and ongoing risk assessment and risk reduction across the product’s life. The guidance also lays out five illustrative, product-specific approaches, for cellular products, for products with an extremely short shelf life, for viral vector gene therapies intended for direct administration, for vector-transduced patient-specific cell therapies, and for tissue-engineered medical products, each with its own practical recommendations.

What’s New Since the December 2023 Draft

Sponsors who have already built a strategy around the 2023 draft will find the final guidance familiar. The overall structure, section headings, and most of the text carry over unchanged. The refinements worth noting:

  • Risk assessments must now consider product-class-specific factors, such as cell viability, functionality, and phenotype for cell therapies, and transduction ability, surface adsorption, aggregation, and degradation for gene therapies.
  • Alternative risk assessment approaches, including surrogate materials and in silico modeling, are now explicitly permitted when testing material is limited, as long as sponsors justify the choice.
  • Reference materials can now be sourced from drug substance as well as drug product, with new flexibility for products where limited batch size or short shelf life rules both out.
  • Citations to companion guidances were updated to reflect ones finalized since 2023, including the now-final Q14 Analytical Procedure Development guidance.
What This Means for CGT Developers

For a program still working from the 2011 framework, this final guidance effectively raises the bar from having a validated potency assay to documenting a full, risk-based control strategy, with a defined QTPP, CQAs, and CPPs built in from early development. FDA is explicit that potency assurance should start before clinical investigations begin and progress through each phase, with specific expectations for what belongs in Module 2 and Module 3 of the CTD at each stage. Programs on compressed timelines get their own recommendation: develop, qualify, and implement potency assays before clinical investigations start, rather than catching up later.

Avance Biosciences supports cell and gene therapy developers through exactly this kind of potency assurance work, with CGMP, GLP, and CLIA analytical and bioanalytical testing built around a product’s mechanism of action and control strategy. Developers navigating this transition are welcome to reach out to discuss how Avance Biosciences can support their potency assurance strategy.

Source: U.S. Food and Drug Administration (FDA)

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