Why CMC Is A Key Sticking Point For Cell And Gene Therapies And How To Meet FDA Expectations

By Louis Cicchini, Ph.D, and Michael Day, Ph.D

The complexity of cell and gene therapies (CGTs) has made Chemistry, Manufacturing, and Controls (CMC) a critical focus area for regulators. Recent actions, including the rejection or delay of Biologics License Applications (BLAs), highlight a tightening of FDA scrutiny on manufacturing strategies, with deficiencies frequently noted in process control, analytical methods, and data integrity. The inherent variability of CGT starting materials and processes, from patient-specific cells to viral vector production, creates unique hurdles compared to traditional pharmaceuticals.

To ensure success and avoid costly delays like a Complete Response Letter (CRL), developers must implement robust strategies for potency testing, batch comparability, and facility inspection readiness. This includes ensuring potency assays are definitively linked to the mechanism of action, establishing clear comparability protocols for manufacturing changes, and meticulously adhering to data integrity and GMP standards. Proactively leveraging regulatory guidance, engaging early with the FDA, and establishing a cross-functional governance team are vital steps for de-risking development and navigating the rigorous path to approval. Learn more about mitigating these CMC risks by reading the full article.