Innovative manufacturing techniques can expand the production of drugs and medical supplies in the U.S.
The COVID-19 pandemic caused significant disruptions in global supply chains, and policymakers are now strategizing around how to ramp up U.S. supply chain resiliency. Everything from beef to toilet paper became more difficult to find in U.S. stores, and the pandemic also caused dire shortages of medical supplies and lifesaving treatments. The shortages were caused by the closure of many manufacturing plants in countries like China, and our domestic supply chain was not sufficient to meet the demand gap. In fact, it is estimated that China exports more respirators, surgical masks, and other personal protective equipment than the rest of the world combined. The limited capacity of domestic supply chains – particularly for pharmaceuticals and medical supplies – was a focus for Chair Tammy Baldwin (D, WI) during last week’s Senate Appropriations Subcommittee hearing featuring testimony from Dr. Janet Woodcock, acting commissioner of the Food and Drug Administration (FDA).
The distributed nature of modern manufacturing
The production of goods such as smartphones, medical therapeutics, or kitchen appliances is complex. Manufacturers rely on highly-trained specialists to make different components that are eventually combined into a single product. For example, the manufacture of LCD displays requires obtaining the raw materials, like glass sheets, films, semiconductor chips, and circuit connectors, from other manufacturers around the world, and assembling components inside multi-billion-dollar factories. Specialization in manufacturing allows businesses to develop new, lower-cost technologies, and more easily scale production and design processes. Unfortunately, specialization also results in a layered network of manufacturers relying on yet other manufacturers, and so on, and it becomes very difficult to determine where each component is coming from in the supply chain. The lack of visibility into this process then exacerbates disruptions in manufacturing during crises, such as the COVID-19 pandemic.
Federal partnerships to strengthen the domestic manufacturing base
To protect against future disruptions, implementing advanced manufacturing practices in domestic facilities, and encouraging businesses, particularly those that make critical drugs and medical supplies, to set up new advanced manufacturing plants in the U.S., can make a substantial impact. During last week’s hearing, Senate Appropriations Subcommittee on Agriculture, Rural Development, FDA, and Related Agencies Chair Baldwin began by asking (33:05 mark in video) FDA Acting Commissioner Woodcock about how the agency is helping to strengthen domestic pharmaceutical supply chains with advanced manufacturing.
The implementation of advanced manufacturing is a top priority for the Biden Administration, and earlier this year, the FDA partnered with the National Institute of Standards and Technology (NIST) to develop an advanced manufacturing regulatory framework. The partnership aims 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.” One emerging technology that will be explored by the partnership is the modularization of manufacturing processes. Modularization refers to structuring discrete parts of the manufacturing process in a way that they can be plugged into each other in different combinations and still function properly. With modular processes, reconfiguring the manufacturing floor to produce a different medicine or device could take just hours or days, instead of months. Another example is using artificial intelligence to track production, tweak settings to increase efficiency, and schedule maintenance to reduce the amount of downtime necessary.
In addition to FDA and NIST efforts to implement advanced manufacturing for medical supplies, two Manufacturing USA Institutes – the National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL) and the Bioindustrial Manufacturing and Design Ecosystem (BioMADE) – are pursuing new advanced biomanufacturing solutions. NIIMBL is a public-private partnership supported by industry and NIST to “accelerate biopharmaceutical innovation,” develop standards, and educate the biomanufacturing workforce. Advances in manufacturing processes developed by NIIMBL aid in the production of treatments for debilitating diseases like cancer, autoimmune disorders, microbial infections, and diabetes. BioMADE is one of the newest Manufacturing USA institutes, supported by the Department of Defense and industry partners. It will promote the commercialization of new biomanufacturing technologies by (i) developing predictive models to move products from the lab to production, (ii) de-risking new technologies, and (iii) manufacturing products at pilot and intermediate scales before they are produced at full scale. BioMADE would also help establish best practices for the biofabrication of novel chemicals, enzymes, and other useful biological products.
Advanced manufacturing for on-demand pharmaceuticals
There are already numerous advanced manufacturing technologies that could be leveraged to boost domestic capacity and improve U.S. self-sufficiency in the production of high-priority medicines, such as anesthetics. Building on work that is underway at the federal level, there are additional opportunities for the Executive Branch to form cross-cutting, productive partnerships. A proposal from Dr. Geoffrey Ling – former founding director of the Biological Technologies Office at the Defense Advanced Research Projects Agency, CEO of On Demand Pharmaceuticals, and Day One Project contributor – suggests that the U.S. Government could launch a national adaptive pharmaceutical manufacturing initiative. This initiative would aim to achieve self-sufficiency for the production of medicines in the U.S. by implementing new technologies to establish high-quality and automated systems readily deployed across the country. Action steps would include fostering:
- “Targeted synthetic biology research and development to enable faster manufacturing of low-cost, on-demand vaccines and precision immunotherapies;”
- “Advanced development of green, modular, on-demand small-molecule manufacturing technologies;” and
- “New business models to support the economically sustainable domestic adoption and deployment of new manufacturing technology.”
By convening experts from the public and private sectors, as well as academia, to craft a national strategy for advanced manufacturing, and then supporting its execution, the federal government could help reduce U.S. dependence on foreign pharmaceutical and medical supply manufacturing.
Fundamental research setting the stage for advanced manufacturing
While much of the focus to implement advanced manufacturing technologies is on later-stage experimental development and commercialization, fundamental research is critical to launching these cutting-edge systems. For instance, the National Science Foundation (NSF) spent an estimated $318 million on basic manufacturing research in fiscal year 2021, and is requesting an additional $100 million in funding for its work in fiscal year 2022. In the coming fiscal year, NSF plans to sponsor research in scientific disciplines vital to advanced manufacturing, such as:
- “Highly-connected, adaptable, resilient, safe, and secure cyber-physical systems;”
- “New methods, processes, analyses, tools, or equipment for new or existing manufacturing products, supply-chain components, or chemicals and materials, including replacements for mainstay materials such as plastics that cause environmental harm;”and
- “Next-generation manufacturing infrastructure as part of a broader effort to design and renew national infrastructure.”
Today’s investments in fundamental research into manufacturing are expected to catalyze tomorrow’s breakthrough advanced manufacturing technologies.
The full implementation of new developments in advanced manufacturing has the potential to ensure the resilience of U.S. medical supply chains in future crises. It can also provide other significant benefits, such as improvements in the quality of critical treatments and therapies, the creation of new jobs, and strengthening the economy. As the FDA, NIST, and other federal agencies work together, and Congress explores ways to continue supporting advanced manufacturing, we encourage the CSPI community to continue to serve as a resource to federal officials.
While the U.S. government grapples with the definition of the bioeconomy and what sectors it does and does not contain, another definitional issue needs to be addressed: What does sustainability mean in a bioeconomy?
Federal clearinghouses should incorporate open science practices into their standards and procedures used to identify evidence-based social programs eligible for federal funding.
To better address security and sustainability of open source software, the United States should establish a Digital Technology Fund through multi-stakeholder participation.
Building on existing data and privacy efforts, the White House and federal science agencies should collaborate to develop and implement clear standards for research data privacy across the data management and sharing life cycle.