FDA/M-CERSI Co-Processed API Workshop

This workshop on co-processed API brought together pharmaceutical researchers, regulatory and materials scientists and manufacturing colleagues from industry, academia, and regulatory agencies on July 13 and 14, 2022, from 8:30 a.m. to 4:30 p.m. (EDT).

This in-person was held at the University of Maryland, Baltimore School of Pharmacy, located at 20 N. Pine St. Baltimore, MD 21202. The event was not recorded. 

This two-day workshop examined recent advances in co-processed API as a technology to improve drug-substance physical-chemical properties and drug product manufacturing process robustness and explore proposals for enabling commercialization of these transformative technologies. Regulatory considerations were also discussed with a focus on regulatory classification, regulatory CMC strategies and CMC documentation supporting the use of this class of materials for clinical studies and commercialization.

This workshop is supported by the Food and Drug Administration (FDA) of the U.S. Department of Health and Human Services (HHS) as part of a financial assistance award U01FD005946 totaling $5,000 with 100 percent funded by FDA/HHS. The contents are those of the author(s) and do not necessarily represent the official views of, nor an endorsement, by FDA/HHS, or the U.S. Government.

Innovations in synthetic chemistry have resulted in improved potency and efficacy of active pharmaceutical ingredients (API), albeit with added molecular complexity. This complexity often comes with challenging physical-chemical properties that cannot be addressed via conventional drug substance processing and particle design routes and ultimately present manufacturing difficulties to drug substance and drug product operations.

A wealth of opportunities to address challenging physical-chemical properties exist through technologies residing at the drug substance-drug product interface. These technologies involve introduction of non-active components (excipients) during drug substance processing to deliver co-processed API, which may have promising implications that stand to transform pharmaceutical manufacturing. The improved physical-chemical properties that co-processed API offer would streamline drug product processing and expand applicability of continuous drug product operations to a wider portion of the development pipeline. Co-processed API has the potential to reduce variability of API properties, improve quality of drug product, enhance the physical and chemical stability of API and maximize the availability of supplies through simplified and robust manufacturing trains. These benefits in total would drive down pharmaceutical cost, and the improved manufacturing robustness stands to reduce drug shortage risks.

Incorporating non-active components during drug substance processing to improve the robustness of the drug product process represents a marked philosophical change to historically separated drug substance and drug product operations. The spectrum of technologies, which have demonstrated success in academic and industry proof of concept arenas, have had limited commercial application thus far. More effective deployment of co-processed API technologies across commercial manufacturing will require a thoughtful and strategic collaboration among academia, industry and regulatory agencies. A combined industry/academic perspective outlining the case for co-processed API, considerations for broader commercial implementation, and some regulatory proposals can be found here (manuscript).

This workshop will present an overview of the changing development pipeline, the need for innovative approaches to improve manufacturing process robustness and assurance of supply, and outline the challenges and promising opportunities afforded by co-processed API with academic and industrial case studies. Importantly, the workshop will outline regulatory and analytical considerations to advance commercialization of co-processed API with opportunities for discussion between attendees. Case studies on co-processed APIs will be presented. The industrial and academic position paper linked above acknowledges that co-processed API may be best suited to manufacture in drug substance facilities due to the need of solvents (and associated HSE constraints) for the most common co-processing technologies. Hence it was proposed that if these materials are manufactured in drug substance facilities, designation of these materials as drug substances (as opposed to drug product intermediates) may be applicable. The workshop will provide opportunities to discuss implications of such designation. Discussions on spray-dried dispersions, which are also constituted of API and excipients were not discussed in the manuscript as they represent an area of precedence of drug product intermediates. However, for the workshop this stance and definition may be relevant for discussion as well as considerations around blurring the DS-DP boundary in context of end-to-end continuous processing.

The format of the workshop will be designed with plenary talks from key thought leaders in the field of co-processing including presentations from the FDA. Ample time for open discussion in panel discussions and breakout sessions with regulatory agencies and the workshop participants will be held to gain insights into strategies for future commercialization opportunities.