Manufacturing & Analytical Characterization
Luke Schenck
Principal Scientist
Merck & Co., Inc.
Rahway, New Jersey
.jpg "Maria Cruanes, PhD Chemistry (she/her/hers) photo")
Maria Cruanes, PhD Chemistry (she/her/hers)
Director Analytical Chemistry
Organon
Spring House, Pennsylvania
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: https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.0c00198.
This presentation will include 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. Co-processed API presents immediate opportunity to development pipelines, and unique potential towards optimization of pharmaceutical manufacturing in the context of end-to-end continuous processing. Regulatory and analytical considerations to advance commercialization of co-processed API will be briefly presented.