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36758 - Session V - Potency Assays

‐ Jun 7, 2022 11:30am

Potency is a critical quality attribute (CQA) for cell and gene therapy (CGT) medicinal products. Assays that measure potency are required for multiple purposes, including product release, stability, characterization, as well as assessing process comparability, batch-to-batch consistency, and structure-activity relationships. A quantitative assay where potency is analyzed relative to a reference standard and is relevant to the mechanism of action (MOA)/clinical response remains the golden standard, like protein biologics. The MOAs of several CGT medicinal products are not well understood or fully known and are often too complex with the many quality attributes involved to be modeled by a single in vitro assay. The small size of batches and their limited number, the frequent lack of reference standards, the need of multiple analytical methods and the rapid development of the manufacturing process create additional challenges. Several products are highly specific, for example AAV-based GT medicinal products with capsids targeting specific cell types and/or transgenes with tissue specific promoters. These products may require genetic engineering to create permissive cell lines to analyze their potency or rely on the use of in vivo assays. Given these challenges, potency is often assessed using a surrogacy- or a matrix of orthogonal assay-based approach. These assays should be developed early during product development and correlated as soon as possible with functional assays or pre-clinical and clinical studies.
This session will be focused on generating a robust discussion between the audience, presenters, and panel members. The objective is to explore various approaches to potency assay development and discuss potential strategies when Sponsors/Applicants are faced with difficulties in the establishment of robust potency assays for CGT medicinal products. Questions that will be discussed may include:
1. What are the regulatory requirements for potency testing CGT medicinal products at various development stages?
2. What are critical deficiencies observed by regulators when reviewing potency assays?
3. Some Sponsors/Applicants perform complex in vivo studies to confirm product potency, does this add value?
4. How do we re-evaluate the use of infectivity assays to measure AAV-based medicinal products potency?

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