We separately summarize online here the implications for Medicare and federal health care policies affected by the transition out of the COVID-19 PHE.
As FDA winds down its COVID-related policies, there are several areas where pharmaceutical and biological product manufacturers can expect lasting changes based on COVID-19 policies, specifically around facility inspections, supply chain disruptions, and clinical trial operations:
During the pandemic, FDA was unable to conduct in-person facility inspections and adopted numerous policies to foster remote interactions around facility compliance. It adopted “remote regulatory assessment” tools to facilitate livestreaming of operations, video conferencing and remote document sharing to conduct certain types of mandatory oversight. In 2022, FDA made several of these approaches permanent through draft guidance.
Supply chain and shortage concerns have decreased over the last year but issues persist. FDA has noted that although its COVID-19 guidance on the Drug Supply Chain Security Act will expire, FDA will retain authority to grant waivers and exemptions to allow for continued distribution of covered products, such as drugs in shortage due to the pandemic. And, although President Biden is ending the PHE, vaccines and treatments for COVID-19 remain important and we expect FDA to continue to develop policies to spur their development and approval.
During the early phase of the pandemic, many clinical trials faced the prospect of significant disruptions and potential early termination due to the challenges posed by quarantines, travel limitations, site closures, supply chain disruptions, and the lack of sufficient medical personnel at sites. As a result of these challenges, FDA issued guidance recognizing that a certain level of flexibility as well as new approaches to conducting clinical trials were needed to minimize the risks to human subjects and the integrity of ongoing trials. Among other things, FDA took meaningful steps toward accelerating the adoption of decentralized clinical trial tools such as remote monitoring of study subjects, expanded use of home health visits, direct-to-patient delivery of investigational product, and the use of wearables and other digital health platforms to collect data and perform remote assessments. Even after FDA withdraws its COVID-era guidance documents, we anticipate that the agency will continue to embrace the decentralized clinical trial tools that gained widespread acceptance during the pandemic. Notably, many of these approaches may also aid sponsors in recruiting more diverse study populations by making participation in clinical research less burdensome for many patients.
Although FDA is no longer issuing emergency use authorizations (EUAs) for COVID-19 vaccines, FDA is still interested in companies developing innovations and alternatives in this area because of the possibility that annual COVID-19 epidemics will persist. Vaccine development may include new delivery mechanisms and routes of administration, as well as vaccines that are more effective in preventing transmission. In order to improve the government’s response to future pandemics, the agency may provide extra support and guidance to innovations aimed at further increasing the speed and reliability of developing vaccines against new infectious diseases, including new strains of SARS-CoV-2.
During the pandemic, FDA created more leniency for certain requirements regarding donated plasma due to decreased blood donation during the pandemic, such as by shortening the quarantine hold period for source plasma from 60 to 45 calendar days before being manufactured into injectable products. FDA may decide to extend some or all of these leniencies permanently, perhaps eventually through regulation changes. This could provide an opportunity for FDA to reconsider other requirements that may be modified to increase the availability and decrease the cost of this raw material without compromising product safety. There could also be implications for companies developing innovative cellular products that require forms of apheresis to obtain raw biological materials needed for their products.
Background on FDA’s COVID-19 emergency authorities
On January 31, 2020, the Biden Administration declared a PHE under Section 319 of the Public Health Service Act (PHSA), relating to COVID-19. The U.S Health and Human Services Department (HHS) said it plans to let this PHE declaration expire on May 11, 2023.
Separately, on February 4, 2020, HHS made a COVID-19-related determination of a public health emergency pursuant to Section 564 of the Federal Food, Drug, and Cosmetic Act (FDCA), which is not subject to the May 11, 2023 expiration. Under this same Section 564 authority, FDA has authorized EUAs for certain COVID-19-related tests, treatments, and vaccines—all of which can remain in effect beyond the May 11, 2023 expiration of the Section 319 PHE.
FDA authorized the EUAs pursuant to four separate EUA declarations, which include one for in vitro diagnostics, one for personal respiratory protective devices, one for medical devices, and one for drugs and biological products. This article summarizes FDA’s plans for the transition away from the fourth EUA declaration, relating to drugs and biologics.
Additionally, during the PHE, FDA provided product-specific accommodations to drug sponsors to help overcome pandemic-related challenges in the administration of approved drugs. For example, at least one drug sponsor received FDA authorization to permit the self-administration of its injectable drug product during the PHE, despite being originally approved only for administration by a healthcare provider. FDA made this accommodation in view of challenges patients were facing in accessing healthcare providers to administer the injectable as a result of the pandemic. FDA authorized temporary Instructions for Use that included the self-administration accommodation, that were to remain valid for the duration of the PHE. It remains unclear whether these kinds of accommodations may be renewed or otherwise extended.
FDA policy for COVID-19 EUA termination
On March 10, FDA updated its FAQ web page on “What happens to EUAs when a public health emergency ends,” emphasizing that the end of the Section 319 PHE declaration will not affect FDA’s ability to authorize COVID-19-related treatments or vaccines for emergency use.
It is not clear when the COVID-19 Section 564 EUA declarations will be terminated, but when they are, all EUAs issued pursuant to those declarations will cease to be in effect on the date of the termination, with one exception: patients using unapproved products pursuant to EUAs will be able to continue their treatment after the relevant EUA expirations to the extent deemed necessary by the patients’ physicians.
In addition to potential EUA terminations resulting from the end of the Section 564 determination, FDA may revoke individual EUAs (prior to termination of the EUA declaration supporting it) if the agency concludes:
- The circumstances justifying issuance no longer exist,
- The criteria for its issuance are no longer met, or
- Other circumstances make revocation appropriate to protect the public health or safety.
However, even when an EUA declaration is terminated, the government is required to take certain steps to provide “time for manufacturers, health care facilities, providers, patients, and other stakeholders to transition away from EUA products and the policies that support them” including providing transition periods for compliance with certain requirements. FDA is also actively working with sponsors to minimize disruptions in the supply of COVID-19 related products including ensuring there is an adequate number of COVID-19 vaccines available for U.S. patients. For example, HHS has stated, “Access to COVID-19 vaccinations and certain treatments, such as Paxlovid and Lagevrio, will generally not be affected” by the wind down of the COVID-19 policies.
CDER/CBER guidance ending with the PHE
In conjunction with updating its EUA FAQ web page on March 10, 2023, FDA issued a Notice summarizing which of its COVID-19-related guidance documents will no longer be in effect after the Section 319 COVID-19 PHE declaration expires on May 11, 2023 and which guidance documents FDA is revising to temporarily remain in effect after that date. The full list of those documents is online here, but we have spotlighted below some of the guidances affected by the PHE determination that may be most relevant for pharmaceutical and biological product manufacturers.
Most notably, FDA’s March 10, 2023 Notice specifies that the following guidance documents from the Center for Drug Evaluation and Research (CDER) will no longer be in effect upon the expiration of the PHE declaration:
Resuming Normal Drug and Biologics Manufacturing Operations During the COVID-19 Public Health Emergency. This guidance is intended to help drug manufacturers evaluate and prioritize current good manufacturing practice (CGMP) activities as they transition from operations that were necessarily delayed or otherwise modified during the PHE in order to maintain the drug supply, back to normal manufacturing operations. Companies will no longer be able to rely on certain “flexibilities” that FDA permitted under the guidance for GMP deviations.
Statistical Considerations for Clinical Trials During the COVID-19 Public Health Emergency. This guidance provides recommendations on statistical considerations to address the impact of COVID-19 on meeting trial objectives for clinical trials conducted during the PHE to help ensure that the trial will provide interpretable findings with correct statistical quantification of uncertainty.
Temporary Policy on Prescription Drug Marketing Act Requirements for Distribution of Drug Samples During the COVID-19 Public Health Emergency. This guidance addresses questions FDA received during the PHE regarding enforcement of certain requirements relating to the distribution of drug samples under the Prescription Drug Marketing Act of 1987 (PDMA).
COVID-19 Public Health Emergency: General Considerations for Pre-IND Meeting Requests for COVID-19 Related Drugs and Biological Products. This guidance assists clinical trial sponsors in preparing pre-investigational new drug application (pre- IND) meeting requests for COVID-19 related drugs during the PHE.
Exemption and Exclusion from Certain Requirements of the Drug Supply Chain Security Act During the COVID-19 Public Health Emergency (summarized above).
Additionally, one guidance document issued by the Center for Biologics Evaluation & Research (CBER) will also lose effect when the PHE ends: “Manufacturing Considerations for Licensed and Investigational Cellular and Gene Therapy Products During COVID-19 Public Health Emergency.” This guidance provides manufacturers of licensed and investigational cellular therapy and gene therapy (CGT) products with risk-based recommendations to minimize potential transmission of COVID-19.
CDER guidance that will end 180 days after the PHE
CDER is revising three guidance documents to continue in effect for 180 days after the COVID-19 PHE declaration expires, listed below. For these policies, FDA said that the 180-day wind-down period is necessary to allow for “an orderly transition,” but they will be no longer be in effect after November 7, 2023. The full list of those documents is online here, but most notably being withdrawn is the guidance:
- Policy for Certain REMS Requirements During the COVID-19 Public Health Emergency. This guidance communicates FDA’s temporary policy for certain risk evaluation and mitigation strategies (REMS) requirements, including certain elements to assure safe use (ETASU), during the PHE. It states that FDA will not take enforcement action against drug makers that don’t conduct certain laboratory testing and imaging studies required under risk evaluation and mitigation strategies (REMS). Therefore, after November 7, 2023, drug makers must ensure they are conducting lab testing and imaging studies required under REMS agreements.
CDER/CBER to retain other guidance policies revised after PHE ends
The third group of COVID-19-related guidances listed in FDA’s Notice outline policies that FDA said it intends “to retain with appropriate changes after expiration of the COVID-19 PHE declaration,” meaning FDA is revising the guidance documents to continue in effect for 180 days after the COVID-19 PHE declaration expires, and then superseding those guidance documents with final revised versions. There are five such documents from CBER, with the most notable being:
Emergency Use Authorization for Vaccines to Prevent COVID-19. This guidance provides recommendations for the data needed to support an EUA for investigational COVID-19 vaccines during the PHE. FDA makes clear that it has stopped issuing new EUAs for COVID-19 vaccines to manufacturers who had not already received EUAs. Companies now developing such vaccines will need to pursue traditional biologics licensure, including large clinical trials in US populations, which can be challenging.
Alternative Procedures for Blood and Blood Components During the COVID-19 Public Health Emergency. The purpose of the guidance was to help address concerns about the availability of donated plasma due to decreased blood donation during the pandemic. The guidance created more leniency in certain requirements, such as by shortening the quarantine hold period for source plasma from 60 to 45 calendar days before being manufactured into injectable products.
This third category also includes 11 guidance documents from CDER. Most notably, FDA plans to revise these guidance documents:
FDA Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Public Health Emergency. This guidance (issued March 2020; updated August 2021) provides general considerations to assist sponsors in assuring the safety of trial participants, maintaining compliance with good clinical practice (GCP), and minimizing risks to trial integrity during the PHE. This guidance provides numerous recommendations on how to conduct certain aspects of clinical trials remotely. For example, the guidance discusses remote monitoring of clinical trial participants, remotely conducting clinical outcome assessments, and using electronic platforms to conduct remote data assessments. Even after this guidance is no longer in effect, companies likely will continue to utilize its recommendations as the remote conduct of clinical trials may improve patient access to medical care, increase clinical trial enrollment, decrease economic burdens on both the companies and the participants, and improve overall efficiency in trial conduct.
Institutional Review Board (IRB) Review of Individual Patient Expanded Access Requests for Investigational Drugs and Biological Products During the COVID-19 Public Health Emergency. This guidance provides recommendations regarding the key factors and procedures IRBs should consider when reviewing expanded access submissions for individual patient access to investigational drugs for treating COVID-19.
Notifying FDA of a Permanent Discontinuance or Interruption in Manufacturing Under Section 506C of the FD&C Act Guidance for Industry. This guidance addresses notice to FDA about changes in the production of certain drugs and biological products to allow the Agency to prevent or mitigate shortages of such products.
COVID-19: Master Protocols Evaluating Drugs and Biological Products for Treatment or Prevention. This guidance provides recommendations to sponsors of master protocols evaluating drugs for the treatment or prevention of COVID-19.
Remote Interactive Evaluations of Drug Manufacturing and Bioresearch Monitoring Facilities During the COVID-19 Public Health Emergency Guidance for Industry. This guidance describes how FDA would request and conduct voluntary remote interactive evaluations at facilities where drugs are manufactured, processed, packed, or held; facilities covered under FDA’s bioresearch monitoring (BIMO) program; and outsourcing facilities registered under Section 503B of the FDCA, during the PHE.
Postmarketing Adverse Event Reporting for Medical Products and Dietary Supplements During a Pandemic. This guidance provides recommendations regarding postmarketing adverse event reporting for drugs, biologics, medical devices, combination products, and dietary supplements during the pandemic.
FDA’s March 10 COVID-19 Notice comes after HHS announced that the coronavirus PHE declared under Section 319 of the PHSA is set to expire on May 11, 2023, and this date is quickly approaching. If you have any questions about transitioning your company’s practices in order to ensure regulatory compliance as FDA winds down its temporary COVID-19-related policies, please contact any of the authors of this alert or the Hogan Lovells attorney with whom you generally work.
Authored by Meredith Manning, Eman Al-Hassan, Robert Church, Lowell Zeta, and Michael Druckman
 On March 15, 2023, HHS expanded the determination to include a public health emergency, or “a significant potential for a public health emergency,” according to a Notice issued March 20. The determination will therefore continue to be applicable even as COVID-19 related conditions improve.