Breakthrough Therapies Raise Manufacturing Issues

FDA officials are working with drug manufacturers to ensure that accelerated development of new breakthrough therapies yields high-quality products for patients. A risk is that evaluations based on limited stability data and “provisional” specifications could mask safety issues. These challenges were discussed at the November ISPE annual meeting, along with innovative manufacturing strategies that can accelerate quality production, such as continual manufacturing systems, using a clinical manufacturing site for initial commercial production, or producing clinical supplies in a commercial site.

Sarah Miksinski, acting director of the Division of New Drug Quality Assessment 2 in the Office of New Drug Quality Assessment, emphasized the importance of manufacturers discussing such options with the agency early in development so that the agency can anticipate a filing with limited data and form an appropriate CMC review team. Early discussion of development plans also permits FDA to assess the potential manufacturing site to determine if an inspection will be needed, while also learning of any new technologies or quality-by-design approaches.