Addressing barriers in implementing pharmaceutical continuous manufacturing – Key concepts & challenges in pharmaceutical continuous manufacturing


U.S. Pharmacopeia, Rockville, MD, USA


Pharmaceutical continuous manufacturing (PCM) can reduce production time, decrease labor costs, and optimize process flow and the supply chain. Although some industry leaders have already invested in PCM, its widespread implementation has yet to be achieved. Major challenges to adoption include knowledge gaps in multiple aspects of quality control, workforce capacity limitations with a lack of PCM expertise, logistics, uncertainty around regulations, start-up costs, industry economic dynamics including significant excess batch manufacturing capacity for generic medicines, and low prices for generics that can impede capital investment in PCM. To address these issues, it is necessary to ramp up education on the broader concepts, equip the workforce with the necessary skills, partner with organizations with adequate resources to ascertain quality control, alleviate uncertainty around regulatory review, and facilitate exploration of where PCM may be most impactful in terms of return on investment.

As its name suggests, pharmaceutical continuous manufacturing (PCM) aims to connect discrete steps into a single operational unit so that, in theory, there is no disruption between the start and end of drug production. (1) This goal exists in contrast to the traditional approach to drug manufacturing, or batch manufacturing, which requires discrete steps where samples of an intermediate product are taken to multiple laboratories for different aspects of quality control before sending the entire batch to the next step in manufacturing, which may also be in a different location. All these additional steps increase demands on working capital, strain the supply chain, and require more time and personnel. The batch manufacturing of pharmaceutical drugs can have between 10-20 steps, resulting in an overall production time of at least 12-24 months. Any interruptions in the supply chain, such as those caused by pandemics or geopolitical events, can delay the process. These delays can manifest as a shortage of essential medicines during increased demand. (2) Batch manufacturing can pose critical constraints for the overall product cycle because ...