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Volume 33, Issue 5
Policy makers seek to ensure supplies of new therapies and to limit shortages.
Concerns about access to medicines and diagnostics critical to containing the coronavirus pandemic (COVID-19) and treating infected patients have broadened support for advanced pharmaceutical manufacturing and test methods. FDA officials have long pressed industry to adopt continuous manufacturing and online testing methods able to scale up quality production quickly and efficiently. The current pandemic has boosted support for such initiatives, as global health organizations and US policy makers recognize the importance of being able to produce millions of doses of any promising new treatments.
While the lack of personal protective gear and respirators has dominated the headlines since the pandemic outbreak, potential difficulties in ensuring sufficient supplies of newly discovered therapies and anticipated vaccines have moved to center stage. China’s prominence in producing key APIs for antibiotics and many common medicines, plus a recent move by the Indian government to halt the export of multiple drugs and drug ingredients, heightened concerns about the United States’ dependence on global supply chains. Rumors that an existing malaria treatment might be effective against COVID-19, for example, created a run on the drug, leading to notable shortages at some manufacturers.
These concerns have spurred calls for greater US investment in high-tech biopharma production systems. In announcing the COVID-19 Therapeutics Accelerator in early March to advance treatments for the pandemic, the Bill and Melinda Gates Foundation cited the need to quickly build up manufacturing capacity to test a variety of drugs. Gates further emphasized that the federal government should provide suppport for building production facilities now, as making such investments before knowing that a product will be used is excessively risky for manufacturers.
Funds to advance efficient drug manufacturing systems to ensure access to vital therapies and prevent shortages due to supply disruptions from China and elsewhere were included in the initial $8.3-billion emergency coronavirus funding package enacted March 5, 2020. FDA gained $61 million to support the development of new medical countermeasures and vaccines, of advanced manufacturing for medical products, and for monitoring medical product supply chains (1). The subsequent $2-trillion coronavirus aid and relief package approved March 27, 2020 similarly provided an added $80 million to FDA to advance the development and approval of medical countermeasures and vaccines (2). The legislation also directed FDA to use some of the funds to further the adoption of advanced manufacturing systems for medical products and to monitor supply chains for potential threats to access to medicines and APIs imported from abroad. To help FDA anticipate looming supply problems, Congress instructed manufacturers to send FDA information on where interruptions in supply affect APIs as well as drugs and extended such requirements to medical device makers during this public health emergency. To further address these issues, Congress provided $1.5 million for the National Academies of Sciences, Medicine, and Engineering (NASEM) to prepare a study on ways to strengthen the manufacturing supply chain for drugs and devices to avoid shortages.
Added support for establishing advanced biopharma manufacturing facilities is found in sections of the pandemic relief legislation, which provides some $30 billion for federal health agencies to develop countermeasures and vaccines, plus platform technologies to advance US production of new therapeutics, diagnostics, vaccines, and medical supplies. Congress specified that a portion of $3.5 billion for the Biomedical Advanced Research and Development Authority (BARDA) should be used to construct or renovate US-based next-generation manufacturing facilities. Similar directions are included in providing added funds for the Defense Research Advanced Projects Agency (DARPA) in the Department of Defense, building on its research programs related to advancing biopharma manufacture. Among other things, these initiatives have supported the development of RNA and DNA vaccines to fight infectious diseases such as Chikungunya and Ebola and to overcome manufacturing challenges to faster scale-up.
The pandemic legislation also provides $27 billion for the Public Health & Social Services Emergency Fund managed by the Secretary of Health and Human Services (HHS) to develop countermeasures and vaccines in response to the pandemic. This includes building the Rapid Aseptic Packaging of Injectable Drugs (RAPID) consortium with a network of up to eight domestic facilities to rapidly fill and finish millions of prefilled syringes for delivering vaccines and therapies for COVID-19 (3). An innovative syringe developed by ApiJect Systems utilizes existing blow-fill-seal technology plus an interlocking needle hub to provide low-cost, easy-to-use injectables for the Strategic National Stockpile.
Similarly, additional funding for the National Institute of Standards and Technology (NIST) supports programs to accelerate production of critical materials, build additional production facilities, ensure supply chains for vital ingredients, develop and train manufacturing workers, and return to the US the manufacture of critical conventional drugs (4). NIST has worked with biotech firms for several years to address challenges in developing more efficient and reliable ways to produce high quality cell and gene therapies.
These and other projects stand to assist manufacturers on accelerated timelines for testing promising COVID-19 therapies and vaccines looking to establish systems for fast, reliable manufacturing scale-up capabilities. At a “virtual summit” in March sponsored by the Biotechnology Innovation Organization (BIO), industry leaders cited the challenge in needing to expand manufacturing capabilities before knowing they have a viable product, and the fast launch of clinical trials for candidate vaccines aggravates those difficulties.
On many fronts, industry is rising to the challenge, with pharma companies partnering with smaller biotechs and federal agencies that offer innovative drug and vaccine candidates for established firms to test and produce. In March, Johnson & Johnson announced that a $1-billion partnership of its Janssen unit with BARDA planned to rapidly scale up vaccine manufacturing capacity to be able to supply over one billion doses of vaccine globally (5). Such fast expansion of production capacity will be needed for clinical trials slated to begin this fall and then to provide emergency use access to any promising product.
1. H.R. 6074, 116th Congress, Public Law 116–123-Mar. 6, 2020, Coronavirus Preparedness and Response Supplemental Appropriations Act, 2020.
2. Amendment H.R. 748, “An Act to amend the Internal Revenue Code of 1986 to Repeal the Excise Tax on High Cost Employer-Sponsored Health Coverage,” US Senate, March 21, 2020.
3. HHS, “HHS Announces New Public-Private Partnership to Develop US-Based, High-Speed Emergency Drug Packaging Solutions,” Press Release, March 18, 2020.
4. NIST, “NIST Funding Manufacturing Institutes to Support Pandemic Response,” Press Release, March 31, 2020.
5. J&J, “Johnson & Johnson Announces a Lead Vaccine Candidate for COVID-19; Landmark New Partnership with US Department of Health & Human Services; and Commitment to Supply One Billion Vaccines Worldwide for Emergency Pandemic Use,” Press Release, March 30, 2020.
Volume 33, Number 5
When referring to this article, please cite it as J. Wechsler, "Modern Drug Manufacturing Key to COVID-19 Response," BioPharm International 33 (5) 2020.