Medicines supply chain challenges underscored by the COVID-19 pandemic have raised concerns about geographic over-concentration of global pharmaceutical manufacturing facilities and emphasized the need to make more medicines in more places to help ensure supply chain resilience. At the same time, pharmaceutical continuous manufacturing (PCM) technology has gained increased attention from industry and policymakers as one way to help expand domestic manufacturing of essential medicines in the U.S. and other countries to achieve this goal.
I recently had a conversation with pharmaceutical manufacturing consulting services provider Pharmatech Associates’ CEO Bikash Chatterjee about what he’s hearing from his customers about PCM and what drug makers need to know to advance its adoption.
What’s most important for manufacturers to understand about PCM?
Within the next decade, PCM is poised to become an industry staple alongside traditional batch manufacturing for the production of both innovative and generic pharmaceuticals and biologic products. Innovation always brings opportunities and challenges. PCM is no different. Obstacles and misperceptions remain. My company – Pharmatech – was acquired by USP in July 2021 but remains a separate entity, and provides consulting services that can help manufacturers through the decision-making process on PCM adoption, production line development and related regulatory processes.
Do medicines made with PCM face bigger regulatory hurdles?
Some manufacturers have been hesitant to adopt PCM in part due to perceptions of increased regulatory risks. They’re concerned about potential pre-market delays, greater inspectional scrutiny and post-market hurdles. However, a recent FDA self-audit comparing PCM to batch manufacturing regulatory outcomes showed manufacturers that submitted PCM applications actually “had relatively shorter times to approval and market as compared to similar batch applications…translating to an estimated $171-537M in early revenue benefit.” The assessment also found “no substantial regulatory barriers” for PCM applications related to manufacturing process changes or pre-approval inspections.
What are the key differences between PCM and batch manufacturing?
Unlike batch manufacturing, where active pharmaceutical ingredients (APIs) or finished medicines are made in intermittent steps that often take place in many different locations, PCM allows each element of manufacturing to take place in a continuous process in a single facility. Accordingly, PCM technology can help increase output and efficiency, lower costs, cut environmental footprints, accelerate production and scale-up in response to emergencies, and reduce dependence on foreign suppliers. These benefits can help make it possible to expand domestic manufacturing. Nine out of 10 U.S. physicians believe more medicines need to be made in the U.S. to help prevent shortages.
Can you expand on PCM’s impact on medicine supply in terms of bringing products to market?
One advantage PCM provides is the ability for a drug sponsor to respond rapidly to market opportunities. PCM can easily accommodate scale-up and post-approval changes, including increases in lot size by simply running longer. For competitive market situations where there may be drug shortages, this can be a tremendous advantage, allowing a manufacturer to acquire additional market share immediately with little to no disruption to operations or quality understanding.
What are you hearing from manufacturers about PCM?
Companies like Pfizer, Eli Lilly, Glaxo SmithKline and others have proven PCM’s commercial success. There are already over a half-dozen medicines made using PCM that are approved in the U.S. An additional handful are available overseas. Semi-continuous manufacturing is also growing in popularity. Regulators are attempting to push PCM along with harmonized guidance development. With enabling technology, regulatory developments and commercial products, PCM is making tremendous progress. Nevertheless, manufacturers face economic and workforce capacity challenges associated with PCM start-up activities, upfront investment costs, as well as regulatory uncertainties in certain geographies.
How can barriers to PCM adoption be overcome?
Solutions include accelerating scientific and technical knowledge, investment and additional incentives. As you know, USP is helping by collaborating with stakeholders to address PCM knowledge gaps, including through education and training programs that will help develop the next generation of experts on PCM; providing standards that define what quality looks like and exploring where there is a need and opportunity to develop new guidelines, best practices and quality standards; and working with partners to certify and validate related manufacturing processes. Meanwhile, the Biden administration has supported increased funding of PCM to help shore up the pharmaceutical supply chain, and bipartisan legislative proposals in the House and Senate have included provisions to expedite development and review of novel drug manufacturing approaches. In addition, the House-passed version of the America COMPETES Act has provisions for PCM centers of excellence to facilitate collaboration on knowledge sharing and workforce training that hopefully will be included in the final legislation.
Why are quality standards so important when it comes to PCM innovation and adoption?
Quality standards help pharmaceutical manufacturers and regulators ensure that medicines are safe, work as intended, and are available when needed to support public trust. The same goes for medicines made with PCM technology. USP standards and related programs support innovative, advanced manufacturing technology like PCM by helping stakeholders define the requirements for demonstrating process understanding and quality in order to bring more quality-assured products to market faster and more efficiently to improve global health.
Thank you, Bikash. Readers can learn more about USP’s efforts to advance quality-focused solutions for a stronger medicines supply chain.