Navigating the Unique Complexities of CMC Challenges for Cell Therapies

Cell therapies are extremely complex in comparison to small molecule therapies and many other biological approaches and as such present unique chemistry, manufacturing and control (CMC) challenges. The complex manufacturing processes and highly variable starting materials associated with cell-based therapies alongside sometimes unknown mechanisms of action can collectively make it difficult to ensure consistent cell therapy products from lot to lot. Indeed, the CMC portion of an IND submission for a cell therapy is often the weakest section and can pose one of the biggest stumbling blocks for Agency review and carry a high risk of triggering a clinical hold. This session will offer brief presentations highlighting these unique CMC challenges during development and approval of cell therapies. Issues that will be covered include ensuring suitability of starting material (allogeneic or autologous), analytical testing strategy, product characterization strategy, and comparability throughout lifecycle. In addition, this session will offer insights around the current trends observed as well as the regulatory framework and opportunities for engagement with FDA, EMA and PMDA to advance productive exchange of information around CMC issues. Following this, the unique challenges and successful navigation of opportunities for engagement with regulatory agencies will be illustrated through a few examples/case studies in both early- and late-stages of development. The session will conclude with a summary of lessons learned in this space regarding how to successfully navigate unique CMC challenges for cell therapies.