Cell therapy products: focus on issues with manufacturing and quality control of chimeric antigen receptor T‐cell therapies

Abstract

Recent accelerated approvals of Chimeric AntigenReceptor T-cell (CAR-T) therapies targeting refractory haematological malignancies underscore the potential for this novel technology platform to provide new therapeutic options for oncology areas with high unmet medical needs. However, these powerful 'living drugs' are markedly different to conventional small molecule and biologic therapies on several levels. The highly complex nature and varied composition of CAR-T based products still requires considerable investigation to resolve the best approaches to ensure reproducible and cost-effective manufacture, clinical development, and application. This review will focus on key issues for manufacturing and quality control of these exciting new therapeutic modalities, preceded by a brief description of CAR principals and clinical development considerations.

Cellular Metrology: Scoping for a Value Proposition in Extra- and Intracellular Measurements

“…On the other hand, existing and emerging regulatory policies emphasize the lack of suitable standards that limit the use of advanced therapies (EC/1394/2007; EC/2001/83). These factors expose persistent gaps in the availability of higher order reference measurement procedures and reference materials that are necessary to facilitate the translation of innovation into cost-effective products (Eyles et al, 2018). Different organizations have stood up efforts to begin to fill these gaps (e.g., ISO 20391-1:2018, ASTM F2739), while the life sciences community is placing a stronger focus on cell and gene therapies.…”

Rethinking Cancer Immunotherapy by Embracing and Engineering Complexity

“…This highlights the difficulty in manufacturing and supplying ACT therapies where artificial and biological components intertwine. Current ACT protocols typically follow a centralised approach tailored for large-scale ex vivo bioprocessing at often distant sites, before reinfusion into hospitalised patients [42]. Accessibility and scalability are hampered by high costs, space requirements, error susceptibility, product variability and slow turnaround [43].…”

Single cell migration profiling on a microenvironmentally tunable hydrogel microstructure device that enables stem cell potency evaluation

“…One important need in the cell therapy field is the standardization and quality control of therapies, cell products and manufacturing of cell products. 43,44 Migration has been previously proposed as an important cell function in the mechanism of action of different cell therapy-based treatments, 45,46 and it has been proposed as a potency test. 47 Since cell migration is a complex cellular function that comprises a myriad of biological functions within the cells and in the interaction with their environment, its evaluation through quick testing could be an excellent approach to control the fitness level and therapeutic quality of cell dose along the different steps of manufacturing and cell delivery to the patient.…”