By: Stephen M. Hahn, M.D., Commissioner of Food and Drugs and Colin Rom, Senior Advisor to the Commissioner
Remember in-person meetings? A year ago, would you have thought our world, our homes and offices would be upended and changed so rapidly? Seemingly overnight businesses were adapting to a new reality. We at U.S. Food and Drug Administration adapted as well – we had to. Our mission is so critical, we couldn’t fall behind because too much was, and still is, at risk. At the start of this 21st year of the 21st Century, businesses, manufacturers, the FDA, and patients, are all adjusting to the changing times and adopting new trends. For the day-to-day work of the FDA those changes are focused on advanced manufacturing technologies, digital industry and “Industry 4.0.”
Advanced manufacturing technologies are being adopted by both small businesses and large corporations in ways that are changing the industry and regulatory landscape. The FDA has dedicated significant effort over the past several years to establishing both research and regulatory programs for advanced manufacturing, computational modeling, and other emerging technologies. These efforts have led to updated regulatory processes, guidance documents and dozens of peer-reviewed research publications to identify characteristics of advanced manufacturing processes that can provide regulatory evidence of quality, safety and efficacy. The FDA also encourages use of advanced manufacturing through involvement in new standards development and industry outreach.
The COVID-19 pandemic has shown us that the existing manufacturing structures, with a small number of facilities fed by long and complex supply chains, can be disrupted. This has also been demonstrated in the aftermath of hurricanes in recent years. This can elevate risk and create shortages in the U.S. The reality is that it isn’t enough to just respond to the current pandemic. The FDA and industry have to accelerate the adoption of advanced and smart manufacturing technologies to strengthen the nation’s public health infrastructure. To this end, the FDA is creating a new collaboration with the National Institute of Standards and Technology (NIST) through a memorandum of understanding (MOU). This MOU is intended to increase U.S. medical supply chain resilience and advanced domestic manufacturing of drugs, biological products and medical devices through adoption of 21st century manufacturing technologies. These include smart technologies, such as artificial intelligence and machine learning, and emerging manufacturing processes. The MOU signals alignment between senior leadership at both institutions in recognition of the importance of modernizing regulatory frameworks as well as industry practices to meet public health needs in the U.S.
We envision that this partnership will leverage the complementary skills of the FDA’s regulatory expertise and NIST’s precision characterization and standards. The FDA has unique insight into the broad landscape of medical manufacturing and the regulatory science opportunities presented by emerging technologies. The agency also has expertise in evaluating the quality, safety and efficacy of a wide array of drugs and medical devices. NIST is a globally recognized source of world-class measurement and testing facilities, many of which focus on the processes, controls, and modeling used in modern manufacturing. They have advanced capabilities encompassing a wide range of areas that include precision measurement, computer science, mathematics, statistics, and systems engineering. NIST also works closely with a variety of industry stakeholders through their Advanced Manufacturing National Program Office, which coordinates the 16 Manufacturing Innovation Institutes of the Manufacturing USA Network and the Hollings Manufacturing Extension Partnership Program (MEP) a national network of technical assistance centers and offices located in every state.
The MOU establishes direct points of contact between senior leadership and collaborative links between subject matter experts to accelerate development and implementation of best practices for advanced manufacturing. These include many technologies that are poised to transform industry. For instance, modularization of unit operations entails breaking manufacturing down into parts that can be plugged into each other and still function, much like train cars can connect to any engine. With modularized processes, one has the potential to switch production from one pharmaceutical or regenerative medicine product to another in days or hours, using the same facility. Another example is adaptive process controls for manufacturing, which use artificial intelligence and computational models to monitor a manufacturing line and tweak settings to boost efficiency or schedule maintenance to reduce downtime.
The FDA has also expanded our commitment to advanced manufacturing by starting several new initiatives. These new initiatives supplement ongoing efforts such as the Center for Drug Evaluation and Research’s (CDER) Emerging Technology Program, the Center for Devices and Radiological Health’s (CDRH) Case for Quality, and the Center for Biologics Evaluation and Research’s (CBER) Advanced Technologies Program.
- CDER and CBER have partnered to create a Center of Excellence for Advanced Manufacturing. Knowledge generated from this effort, together with the information provided by sponsors or applicants, will enable science- and risk-based assessments and inspections of drug and biological product manufacturers; establish best assessment and inspection practices; support standard, policy and guidance development; and provide training to staff related to novel manufacturing technologies.
- CDRH is creating an Advanced Manufacturing Technology Clearinghouse as an independent third party that identifies and evaluates promising advanced manufacturing technologies used in the medical device or other industries. These could include high-performance computing, digitalization of production, modeling and advanced robotics. The clearinghouse plans to provide non-confidential information about these technologies and strategies for successful implementation, and publish assessments of the technology to industry and government to promote and facilitate adoption of more effective and efficient means of manufacturing.
- CBER is increasing its efforts to encourage the development and adoption of advanced manufacturing methods for critical vaccines. Advanced manufacturing methods could help the vaccine supply more easily ramp up on short notice or rapidly modify certain vaccines to address emerging infectious diseases.
The FDA has encouraged deployment of advanced technologies in manufacturing and encouraged the renewal of manufacturing assets in the U.S. for many years. This need has been made even more evident by the COVID-19 pandemic and related challenges to critical supply chains. We feel strongly that existing regulatory frameworks and ongoing enhancement programs support this effort, but improved coordination and alignment of programs within the agency, communication with innovators in industry and public-private partnerships and understanding of practical challenges and opportunities in real world manufacturing will further support extension of the innovative practices that have so successfully brought medicines to market.
The FDA’s steadfast focus, collaboration and communication on advanced manufacturing is helping to connect government agencies, decrease regulatory uncertainty, and increase industry adoption of technologies that can address issues raised by the COVID-19 pandemic. We aim to prepare the U.S. to face the rest of the 21st century with a modern and resilient system for pharmaceuticals, biopharmaceuticals, medical devices, and vaccines.