Manufacturing Challenges Limit Gene Therapy Development

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Moving forward with gene therapy development requires a “quantum leap” in manufacturing capabilities.

The biggest hurdle for advancing gene therapy from treating rare diseases to addressing more common conditions is difficulties in achieving efficient scale-up of production processes, says Peter Marks, director of FDA’s Center for Biologics Evaluation and Research (CBER). Marks noted that there are now more than 700 investigational new drug applications (INDs) filed with the agency, and more arriving daily. But to move forward with development, he observed at Prevision Policy’s Biopharma Congress in Washington in November 2018, requires a “quantum leap” in manufacturing capabilities.

Marks added that FDA often is “very lenient” about companies meeting manufacturing standards for testing gene therapies in Phase I trials. But scaling up to larger production for further studies is difficult and can delay product development for years.

Clinical trials for gene therapies are not a problem, Marks noted. A manufacturer can gain proof of concept in a study of only 10 patients. To more forward, however, requires manufacturing at scale, and few companies can produce the necessary vectors, and they need to do so more efficiently.


While there remain many uncertainties about developing and testing gene therapies, particularly related to concerns about immune reactions to vectors, Marks seeks to avoid “regulatory paralysis” arising from safety concerns. “Things will happen,” he conceded, and sponsors and regulators need to understand the risks and work to develop therapies that patients and providers can trust. The vision, Marks observed, is that gene therapies eventually will provide important treatments for a broader range of diseases, but only if they can be proven to be safe and can be produced efficiently, which also is key to reducing product costs.