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Jill Wechsler is BioPharm International's Washington Editor, firstname.lastname@example.org.
Manufacturers and regulators accelerate R&D and production of new vaccines and therapies.
The imperative to prevent, treat, and cure the deadly COVID-19 virus has generated new research and manufacturing strategies, bolstered by unprecedented support from the federal government, private investors, and timely regulatory guidance and advice. Aware of intense pressure and great opportunity, industry moved quickly to identify compounds with potential to treat ill patients and to mitigate the virus’ lethal effects. The federal government poured billions into drug and vaccine development and production through its Operation Warp Speed (OWS) task force. At the same time, FDA struggled to meet often divergent and unclear requests and mandates from the White House and the Department of Health and Human Services (HHS), developments that have undermined public confidence in the agency’s independence.
FDA’s first crisis involved confusion over the development and approval of diagnostic tests for the COVID-19 pathogen, a situation that resulted in notable delays in public access to products able to reliably identify infected individuals. While FDA was not solely responsible for the situation, knowledgeable observers believe that more proactive leadership from the agency could have accelerated advances in this critical area.
The agency’s new commissioner, Stephen Hahn became further entangled in administration efforts to promote certain unproven COVID-19 therapies and to demand that FDA issue Emergency Use Authorizations (EUAs) for potentially harmful treatments. Hahn’s initial support for such authorization alienated agency staffers and medical authorities alike and raised concerns about the agency’s ability to fully test and vet promising vaccines and other critical therapies.
These issues came to a head in October as vaccine experts within FDA and from leading medical institutions emphasized the importance of obtaining sufficient safety and efficacy data on any vaccine prior to approving it for administration to millions of individuals. This approach was considered critical to offset growing public “vaccine hesitancy” arising from fears that companies and regulators were taking shortcuts to speed the development of COVID-19 vaccines for political purposes. Vaccine manufacturers supported the call for adequate test data to obtain results that could generate public support in the coming months.
The accelerated development of several COVID-19 vaccines highlighted the critical role of FDA’s Center for Biologics Evaluation and Research (CBER). In May 2020, CBER Director Peter Marks opted to remain at FDA instead of shifting over to the administration’s OWS task force, as did Janet Woodcock, director of the Center for Drug Evaluation and Research (CDER), who moved temporarily to lead OWS therapy development efforts. Under Marks’ leadership, CBER issued critical guidance in June clarifying the requirements for developing and testing new vaccines to protect against COVID-19 infection, with an emphasis on the need for large, randomized, placebo-based clinical trials to provide adequate safety and efficacy data, as well as upfront manufacturing information (1). Further guidance in October specified similar approaches for gaining FDA EUA for a new vaccine (2).
Many of these clinical development programs benefited from OWS funding, as did early production of large quantities of test vaccines—a marked change from the usual practice of delaying investment in scale-up and production until clinical testing showed results. The aim was to provide sufficient quantities of any preventive as soon as testing demonstrated an immune response. FDA guidance emphasized the need for early chemistry, manufacturing, and controls (CMC) data, while providing leeway in batch stability records (1). Vaccine sponsors signed up contract manufacturers and other firms to be prepared for fast scale-up when authorized. OWS also supported added production of glass vials and injectors critical for vaccinating hundreds of millions of individuals.
While shifting many staffers to operations involved in COVID-19 product development and review, FDA also worked overtime to maintain support and approval of new therapies for the usual broad spectrum of serious medical conditions. Innovative biomedical R&D faced added challenges from delays in many new and ongoing clinical trials due to pandemic complications. Moreover, FDA had to cancel regulatory inspections, particularly those involving foreign firms. Instead, the agency looked to evaluate the quality status of an operation producing a new drug or vaccine through greater reliance on compliance history, production records, analysis of actual products, and inspection reports from other trusted regulatory authorities.
Supply chain security for drugs and medical products emerged as a critical issue, as the global pandemic raised fears about reliable access to medicines and their components produced overseas. Shortages in certain vital therapies for treating hospitalized patients, including antibiotics and sedatives, prompted FDA to bolster efforts to detect pending shortages in advance and to support alternative production activities, including broader drug compounding and the administration’s “buy American” campaign to expand production of drugs and medical products in the United States. These developments highlighted the importance of manufacturers’ ability to establish modern, more reliable pharmaceutical manufacturing operations able to maintain high quality, reliable production with well-documented internal oversight.
The pandemic slowed but did not derail a range of FDA initiatives designed to improve the regulatory process. CDER finalized the overhaul of its Office of New Drugs, with an expanded number of offices and divisions implementing a new team-based “integrated review” approach for assessing new drug applications.
In addition to focusing on vaccine development, CBER’s Office of Tissues and Advanced Therapies (OTAT) continued to experience a surge in proposals for developing new cellular and gene therapies and regenerative medicines. Hundreds of investigational new drug applications flooded OTAT, many raising challenging and unique medical and technical issues, including concerns about ensuring product quality, purity, and strength. In expediting development programs, FDA focused on clarifying strategies for product characterization, process validation, scale-up, and ensuring stability.
FDA has approved more than 40 innovative medicines this past year and worked hard to meet user fee time frames for prescription drugs, generics, and biosimilars. Those numbers may drop in the coming months, as sponsors face continued difficulties in launching new clinical trials and in documenting quality manufacturing operations. With the coronavirus again surging across the nation and the world as this historic year draws to a close, the only certainty is that both obstacles and opportunities will continue to challenge biopharmaceutical companies, regulatory authorities, and the research community in the months ahead.
1. FDA, Development and Licensure of Vaccines to Prevent COVID-19, Guidance for Industry (CBER, June 2020).
2. FDA, Emergency Use Authorization for Vaccines to Prevent COVID-19 Guidance for Industry (CBER, October 2020).
Jill Wechsler is BioPharm International’s Washington editor, email@example.com.
Vol. 33, No. 12
When referring to this article, please cite it as J. Wechsler, "Pandemic Brings Major Changes to FDA and Drug Development in 2020," BioPharm International 33 (12) 2020.