Innovation and standardization across borders are essential to facilitate manufacturing solutions that can strengthen the global medicines supply chain, panelists suggested during an April 25 session of the Asia-Pacific Economic Cooperation (APEC) forum’s Medical Product Supply Chain Dialogue, co-hosted by the U.S. FDA and USP in Rockville, Maryland. The panel was titled “Manufacturing Solutions to Strengthen Global Supply Chain Resilience.”
Innovation drives resilience
“Innovation drives resilience. That is my own perspective,” said panelist James Coburn, manufacturing innovation lead for pandemic preparedness at the White House Office of Science and Technology Policy. Facilitating adoption of advanced manufacturing technologies (AMT) such as continuous manufacturing is a “critical” component of building that resilience, Coburn said.
When it comes to the medicines people rely on for their health, innovative AMT like pharmaceutical continuous manufacturing (PCM) are gaining attention from policymakers and other stakeholders as one potential solution to help increase the manufacturing of medicines in more nations and across more regions to bolster supply chain resilience. While over-reliance on sourcing of medicines from a few countries can contribute to global supply chain vulnerabilities and potential disruptions, AMT can enable production efficiencies for many medicines and their ingredients to help increase geographic diversity in sourcing and strengthen the supply chain, alongside increased utilization of excess capacity for traditional batch manufacturing.
Standardization is essential
When considering barriers to adoption of AMT like PCM, typically “it’s not an engineering problem, it’s not a chemistry problem often, and I would even say it’s not necessarily a regulatory problem,” Coburn suggested. “Though the finger would often be pointed to difficulties in the regulatory area,” when it comes to getting products made with [AMT] approved it’s often that “maybe it takes more information, because people are not as familiar with it, and maybe even the people who are doing it are not as familiar with it and they’re not able to provide that information.” Therefore, “it’s standards and validated processes…that are super important” to getting such products approved, Coburn concluded.
Speaking as a fellow panelist at the event, I agreed standardization can have a significant role to play in helping with the regulatory aspects of AMT, particularly when the goal is to advance adoption of such technologies globally. Manufacturers typically seek approval of medicines not just in one country but internationally, magnifying the importance of acceptance of their manufacturing technologies and practices across borders, in-line with quality standards and harmonized regulatory guidance. USP is working to address barriers to AMT adoption through a broad portfolio of quality-focused solutions including standards, analytical laboratory services, and related programs. This dovetails with the efforts of governments and regulators, including through harmonized guidance development, to support AMT adoption.
White House priorities
U.S. government efforts to facilitate manufacturing innovation in support of medicines supply chain resilience include a range of White House initiatives that Coburn outlined during the panel. These include the administration’s issuance of goals and an executive order aimed at advancing U.S. biomanufacturing and biotechnology, as well as a national strategy for advanced manufacturing, each impacting both medical and non-medical products. Coburn spotlighted four related objectives: Increasing manufacturing flexibility while maintaining quality and accountability; improving supply chain visibility; increasing redundancies in suppliers and decreasing supply chain length; and modernizing and optimizing stockpiling.
While not specifically noted during the panel, the U.S. government’s fiscal 2023 funding bill, signed into law in December 2022, included a range of specific provisions to support medicines supply chain resilience, including those supporting development of AMT through creation of national centers of excellence. The legislation also encourages HHS’ Biomedical Advanced Research and Development Authority (BARDA) to support development of novel pharmaceutical manufacturing technologies that aid production of medical countermeasures at lower cost than traditional manufacturing processes, and to partner with domestic manufacturers to enhance the capacity to respond to future public health emergencies.
Innovative business models
Beyond innovation in manufacturing, innovative business models also can provide potential solutions to medicines supply chain vulnerabilities, as evidenced by Civica. The non-profit maker of essential generic medicines was established by a group of U.S. health systems to help address drug shortages, explained panelist Allan Coukell, Civica’s senior vice president of public policy. “The supply of generic drugs has been unreliable for 15 years” in the U.S., Coukell observed. “At any given time, there are dozens or even hundreds of products on the FDA’s drug shortage list.” Addressing a generic drug marketplace defined by tight margins that often can deter competition, Civica was formed four years ago and has since shipped about 120 million vials of medicines across the therapeutic spectrum to serve about 50 million patients. Civica has 55 U.S. health system members that determine which drugs in shortage or at risk of shortage the firm will supply to help address supply chain challenges. The drugs are priced at cost, plus what it takes to run the company, Coukell explained.
“Innovation comes from constraining the system,” opined panelist Frank Gupton, Ph.D., CEO of the Medicines for All Institute and chair, Virginia Commonwealth University – College of Engineering. “If you constrain the system, it will cause people to think differently.” In the case of the Medicines for All Institute that has included working to leverage innovations in drug manufacturing processes to achieve efficiencies, cost savings, and reduced environmental footprints that improve global access to lifesaving medicines, such as those used to treat HIV and tuberculosis, Gupton told meeting attendees. The Institute works to train chemists and engineers, and engages in partnerships with stakeholders around the world, to help make more medicines in more places and bolster supply chain resilience.
Longstanding global medicines supply chain vulnerabilities became even more obvious during the COVID-19 pandemic, noted panelist Juan de Villafranca, executive president, Mexican Association of Pharmaceutical Laboratories (AMELAF). The medicines supply chain “has always been very important,” but “I think a lot of things were taken for granted” before the pandemic, he told attendees. Industry stakeholders “were very comfortable, getting a lot of things from very far away” but with the pandemic there was a “big change in the mentality.” The potential for shortages, increased shipping costs and supply chain disruptions has received increased attention from AMELAF member companies, resulting in more emphasis on risk-analysis, and in some cases additional stockpiling of ingredients and pursuit of additional suppliers. “We are believers of near-shoring, and we need to have more planning to identify potential risks,” he said. Events like the APEC Medical Product Supply Chain Dialogue are “very important because these help us to try to understand where we are heading.”
Beyond innovation and increased geographic diversity in drug sourcing, panelists also noted the potential importance of public-private partnerships, capital investments, financial incentives, and workforce education and development in helping to drive adoption of manufacturing solutions that strengthen global medicines supply chain resilience. Public-private partnerships can be “a really good structure…to bring industry and government together to solve difficult problems,” Coukell said.
USP manufacturing-related initiatives I outlined during the panel aim to identify, characterize, and quantify vulnerabilities in the supply chain; build practical, quality-focused solutions to address related challenges; and scale those solutions to facilitate manufacturing capability building that supports supply chain resilience. Examples of specific USP solutions include development of a PCM knowledge center to facilitate dissemination of knowledge about PCM; creation of guidelines, best practices and quality standards to support PCM adoption; and helping companies realize potential benefits of AMT through related services including education, training, and direct in-laboratory solutions.
In a related keynote presentation at the APEC meeting, USP CEO Ronald Piervincenzi, Ph.D., outlined seven key elements of a strong, global medicines supply chain. They include manufacturing capability, ingredient and product quality assurance, regulatory capability, international cooperation, supply chain security, resilience, and trust.