Potency assay development for cellular therapy products: an ISCT∗ review of the requirements and experiences in the industry

Abstract

The evaluation of potency plays a key role in defining the quality of cellular therapy products (CTPs). Potency can be defined as a quantitative measure of relevant biologic function based on the attributes that are linked to relevant biologic properties. To achieve an adequate assessment of CTP potency, appropriate in vitro or in vivo laboratory assays and properly controlled clinical data need to be created. The primary objective of a potency assay is to provide a mechanism by which the manufacturing process and the final product for batch release are scrutinized for quality, consistency and stability. A potency assay also provides the basis for comparability assessment after process changes, such as scale-up, site transfer and new starting materials (e.g., a new donor). Potency assays should be in place for early clinical development, and validated assays are required for pivotal clinical trials. Potency is based on the individual characteristics of each individual CTP, and the adequacy of potency assays will be evaluated on a case-by-case basis by regulatory agencies. We provide an overview of the expectations and challenges in development of potency assays specific for CTPs; several real-life experiences from the cellular therapy industry are presented as illustrations. The key observation and message is that aggressive early investment in a solid potency evaluation strategy can greatly enhance eventual CTP deployment because it can mitigate the risk of costly product failure in late-stage development.

From production to patient: challenges and approaches for delivering cell therapies

“…It is important that these issues are resolved, because without a potency assay cell therapy shelf-life cannot be determined. Thus, the International Society for Cellular Therapy recently released a comprehensive review of some of the challenges the industry faces with respect to these issues and provides some case studies where they have been overcome (Bravery et al, 2013). Notably, although red blood cell transfusion has been used for decades, it is known that a number of molecular changes, so called 'storage lesions' can occur within the cells.…”

Cell and gene therapy manufacturing: the necessity for a cost-based development approach

“…It is anticipated that the adoption of automated manufacture will decrease variability in the quality of manufactured cell products, resulting in more consistent clinical outcomes that exhibit both reproducibility and, importantly, dose-responsiveness. Poor understanding of the link between potency and product characteristics makes it challenging to develop a series of assays which reliably predict the result of a batch in vivo [27,28]. This situation is further complicated by the fact any assays of a fresh-preserved product must be completed rapidly as non-frozen cell-based products are not stable.…”

“…Current analytical quality control systems are often limited by the rate of throughput of samples and many are destructive or sample-altering in nature. A range of measuring systems for cell-and tissue-based products are needed that are non-destructive and near real-time in measurement [27].…”

The Early Career Researcher’s Toolkit: Translating Tissue Engineering, Regenerative Medicine and Cell Therapy Products

“…The CMAs help guide towards defining the critical quality attributes (CQAs) of the product -product characteristics that must be within specified limits to ensure safety, identity, purity and potency, e.g. cell marker expression or proliferative capacity [8][9][10].…”