Demonstrating comparability for clinical cell-based therapy products following manufacturing process changes: an industry perspective

During the clinical development of a cell-based therapy product, quite often, changes to the manufacturing process, facilities, raw materials and analytical methods may be necessary for several reasons. Examples include improving the process performance and quality of the final product, changes to the critical/raw materials used for manufacturing and/or execution of assays, and transfer of the manufacturing process to a commercial site or a site where the required process changes can be implemented.

For a successful implementation of a process change, it is necessary to demonstrate the comparability of the pre- and post-process, as well as the final product, with no significant impact to the product quality and the safety of patients. Moreover, demonstrating product comparability following a process change is a prerequisite for the manufacturer seeking to advance their products into the clinic, to a pivotal phase in the clinical trials or
approaching commercialization with an applicable regulatory agency. Given the increased growth in the number of clinical trials using advanced novel cell-based therapies, which often require accelerated development with limited historical data and experience, much of the regulatory and industry guidance also needs to evolve accordingly. This means there is a growing need to establish a suitable best practices document for demonstrating
comparability as a guide to manufacturers across the biopharmaceutical industry.

This paper provides joint industry recommendations by Subject Matter Experts in the development and manufacturing of cell-based therapy products to demonstrate comparability for some of the common process changes implemented by manufacturers that may occur during the clinical development lifecycle. The experts evaluated over 140 commonly encountered process, material and analytical changes, as derived from the U.S. Food
and Drug Administration (FDA) guidance on Chemistry, Manufacturing and Control Changes to an Approved Application: Certain Biological Products. Changes with the potential for a significant impact to cell-based therapy products were assessed for comparability recommendations, with the focus on the pre-pivotal and pivotal phases. The resulting recommendations are intended to help manufacturers with the design and approach for comparability studies to streamline study design and execution, as well as organization of data for accelerated regulatory agency approvals.

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• Create Date 10th August 2023
• DOI https://doi.org/10.46220/2023CGT009
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