During the clinical development of a cell-based therapy product, changes are often necessary to the manufacturing process, facilities, raw materials, and analytical methods, e.g., to improve the process performance and quality of the final product.
To successfully implement a process change, we must demonstrate the comparability of the pre- and post-process, and the final product, with no significant impact on the product quality and the safety of patients. It is also a prerequisite for manufacturers seeking to advance their products into the clinic, for example, the transfer of the manufacturing process to a commercial site.
However, given the increased number of clinical trials using advanced novel cell-based therapies, much of the regulatory and industry guidance needs to evolve accordingly. This means there is a growing need to establish suitable best practices for demonstrating comparability.
Our new paper, Demonstrating comparability for clinical cell-based therapy products following manufacturing process changes: an industry perspective, meets this need and gives you recommendations for CMC package components to demonstrate product comparability.
These are based on a list of process changes commonly encountered during the development of cell-based therapy products and processes. Changes were assessed based on the potential impact on product safety, identity, strength, purity, and quality (SISPQ) and the recommendations are based on the overall risk of the potential impact.
Our team evaluated over 140 common process, material, and analytical changes derived from the FDA guidance on Chemistry, Manufacturing and Control Changes to an Approved Application: Certain Biological Products. Changes with the potential for a significant impact on cell-based therapy products were assessed for comparability, focusing on the pre-pivotal and pivotal phases.
Being unable to demonstrate comparability can delay or negatively affect your regulatory filings, resulting in detrimental effects on the drug lifecycle. Our recommendations will therefore guide you when approaching changes to your manufacturing processes, materials, or analytical methods during the development and/or clinical trials of cell-based therapy products. They will support the planning of comparability strategies ahead of time based on anticipated changes.
The goal is to robustly demonstrate the comparability of products while efficiently using the resources and product material you have available. Our recommendations are designed to increase your regulatory success when demonstrating comparability associated with filings and approval requests to regulatory agencies.
Designs and/or plans for comparability studies should be shared with regulatory agencies for a potential commercial application or ongoing clinical stages. This approach will reduce potential delays in obtaining regulatory approval, ultimately accelerating the time to advance the cell-based therapy product through its development lifecycle.