PhRMA Seeks Specificity for Cell Product Potency Guide
Pharmaceutical Research and Manufacturers of America (PhRMA) says FDA’s recent draft guidance titled “Potency Assurance for Cellular and Gene Therapy Products” needs additional specificity and considerations for particular development phases. “Accordingly, PhRMA recommends including additional detail regarding phase-appropriate implementation and how the guidance would be applied to different modalities or products of varying complexity (e.g., autologous CAR-T (Chimeric Antigen Receptor-T cell), gene-edited autologous, gene-edited allogeneic, iPSC (induced Pluripotent Stem Cells) products),” the group says in just-posted comments to the agency.
PhRMA’s comments urge FDA to include specific examples where recommendations for different modalities may vary. “For example,” it says, “PhRMA recommends including guidance on empty-full ratio, which may impact a gene therapy to a larger extent than a cell therapy, and guidance on establishing reference materials for cell therapy products.”
FDA published the draft guidance in 12/2023, describing a potency assurance strategy as “a multifaceted approach that reduces risks to the potency of a product through manufacturing process design, manufacturing process control, material control, in-process testing, and potency lot release assays. The goal of a potency assurance strategy is to ensure that every lot of a product released will have the specific ability or capacity to achieve the intended therapeutic effect.”
PhRMA’s comments recommend allowing flexibility to establish potency assurance when the mechanism of action (MoA) is not clearly understood. It says that for many cell-based therapies, animal studies may not always be sufficient to assess the MoA. “Therefore, PhRMA suggests including in-vitro approaches such as in silico modeling or organs-on-a-chip in lieu of animal studies to determine the MoA when trying to gain product and process understanding,” the comments say.
“In trying to establish a relationship between critical-to-quality attributes (CQA) and potency,” the comments continue, “PhRMA recommends adding examples of a statistical relationship, such as correlation or dose response, between product attribute and non-clinical and clinical outcome that could suggest if an attribute is relevant to potency.”
“The 2011 Guidance for Industry, ‘Potency Tests for Cellular and Gene Therapy Products,’ contains information not included in the new draft guidance,” the group says. Because the draft guidance is intended to supersede the 2011 document, PhRMA requests certain sections in the previous guidance that outline potency test strategies be included in the new document. “Specifically, PhRMA recommends including guidance on establishing the correlation between potency and clinical effectiveness and how potency assurance is considered at all phases of clinical development,” it says.