Introduction
On 4 February 2020, the Secretary for the Department of Health and Human Services (DHHS) declared a significant public health threat in the US from the novel coronavirus, now known as SARS-CoV-2,the causative agent in COVID-19 illness. This declaration resulted in the facilitation of expedited reviews and issuance of EUAs for use of unapproved medical products to address a Public Health Emergency (PHE) to mitigate threats from chemical, biological, radiological, and nuclear and emerging infectious disease agents. In preparation for the cessation of PHE operations, revocation of hundreds of EUAs,and withdrawal of enforcement discretion policy guidances, the FDA published two guidance documentsto support stakeholders.
The Federal Food, Drug, and Cosmetic Act (FD&C Act) has been amended to align with current public health needs. One such instance was with the 2013 amendment, the Pandemic and All-Hazards Preparedness Act of 2006 (PAHPA),which allowed the FDA commissioner to facilitate expedited reviews, and issue EUAs for use of medical products for risks of public health emergencies involving chemical, biological, radiological, and nuclear and emerging infections disease agents. The Agency plans to take a phased approach to support medical device industry stakeholders to adjust to FDA policies and operations after the PHE is over and more stringent review requirements are reinstated.
Enforcement discretion versus EUA
The FDA has the authority to create, implement, and enforce regulations that carry the weight of law. The Agency also publishes guidance documents to facilitate understanding of its policy and/or enforcement strategy around a regulatory issue.
Enforcement discretion
The FDA may use its enforcement discretionwhen the risk to patients is deemed low. That means that, at the order of the commissioner, the Agency may elect to not enforce certain regulatory requirements for the medical devices within its purview. Generally, this has been for products that have an existing product code and for which submissions have already been reviewed and cleared by the agency. During the COVID-19 PHE, the FDA has exercised discretion by allowing unreviewed medical devices, deemed substantially equivalent to currently marketed devices, to be distributed for the continuity of patient care and to avoid disruption of the supply chain.
Emergency Use Authorization (EUA)
EUAs are for unapproved products that address a specific need for which there is no appropriate solution. These products would typically require a De Novo classification request and some of them could be automatic Class III, high-risk medical devices under different circumstances. However, under section 564 of the FD&C Act, the FDA may issue EUAs during a PHE, such as the current global pandemic. Authorization under EUA permits manufacturers to market and distribute unapproved medical devices to meet an urgent, unmet need with a lowered threshold for the standard of effectiveness relative to market clearance or authorization under 510(k) or premarket approval submission processes.
Different transition plans
The agency issued multiple guidance documents for enforcement discretion during the COVID-19 PHE for medical devices, including noninvasive digital health devices for psychiatry, electronic thermometers, ventilators, and coagulation measurement systems. These enforcement discretion policies will be lifted once the PHE operations are transitioned back to normal operations and the guidance documents will be withdrawn, ostensibly, at the same time.
The EUA declaration under Section 564 of the FD&C Act is not dependent on the PHE declaration under Section 319 of the Public Health Services Act. An EUA may remain in effect until the FDA chooses to revoke its declaration. Therefore, EUAs may remain in place beyond the declared PHE.
In summary, the FDA has the authority to end either of these forms of enforcement discretion based on its assessment of the need and availability of adequate, approved alternatives.
What manufacturers need to know
The timeline
It is not clear exactly when the EUA declaration will be terminated. However, HHS is required to publish advance notice in the Federal Register. From that time on, the FDA has expectations mapped out in the guidances with the caveat of FDA’s authority to withdraw the guidances and/or EUAs at the Agency’s discretion.
EUAs will end when the declaration has been terminated, after the advance notice. Guidances for enforcement discretion will be withdrawn 180 days after the EUA declaration has terminated.
Notification of intent
The FDA recommends that manufacturers of certain types of medical devices notify the Agency of their intent to submit or not submit a marketing application. If a manufacturer is not planning to submit a marketing submission, the notification should contain plans for:
- Discontinuing distribution of the medical device;
- Restoring the medical device to a previously FDA-cleared or -approved version;
- Providing a physical copy or electronic updated labeling; and
- Addressing and/or mitigating potential risks of medical devices that remain distributed after the EUA termination date.
Medical devices within the scope of this expectation are listed in both guidances are gas anesthesia, portable oxygen generators, ventilators, and ventilator-related medical devices.
Products continuing to be marketed after EUA termination
FDA expects manufacturers planning to continue distributing products beyond the termination date should plan to submit marketing applications sufficiently early to get the refuse-to-accept and/or accept-and-file process through before the withdrawal date.
Once the FDA terminates an EUA declaration, the labeling for distributed medical devices should be updated during the review period of the marketing submission to reflect its regulatory status, that is, it was authorized under an EUA during the COVID-19 PHE and is under FDA review for clearance or approval. If a manufacturer has an accepted submission to FDA, those medical devices may remain in the market and agency does not intend to object to continued distribution if it has not acted on the submission on the termination date.
Unique content for these submissions includes a transition implementation plan, which should include the estimated number of medical devices distributed under an EUA.
In case of a negative FDA decision, additional information should include:
- Disposition plan for already distributed medical devices;
- Benefit-risk information for disposition plan;
- Process for notifying patients, consumers, healthcare facilities, providers, and distributors of the device’s regulatory status, “not reviewed or cleared by FDA”;
- Process and timeline for restoring distributed medical devices to the previously cleared or approved version of the devices, labeling updates publicly; and
- Description of maintenance plan for distributed medical devices.
For a potential positive FDA decision, additional information should include the process outline and timeline for providing users of previously distributed medical devices updated labeling or components that reflect any changes made to the cleared or approved device.
Products not being marketed post EUA termination
After submitting a notification of intention to stop marketing a product after EUA termination, the FDA will not require market removal of certain types of medical devices that had been distributed under enforcement discretion policies or EUAs. However, at the EUA declaration termination date, distribution of these medical devices by the manufacturer should be halted. Medical devices that were distributed before the EUA termination date may remain in the field until they have been used up, restored to the previously cleared/approved version, or have labeling updated to describe the regulatory status as discussed in previous paragraphs. In vitro diagnostics may remain in the field 2 years after EUA termination date or until the expiry date, whichever occurs sooner.
Scenarios not covered within the guidances
Recognizing that there are iterative or scenarios that are not covered within the guidances should be addressed with the FDA via the Q-submission process.
Conclusion
FDA is gearing up for return to normal operations as supply chains settle and continuity of patient care is less of a concern. These guidances provide transparent, salient, expectations for industry stakeholders to continue to provide safe and effective medical devices for patient care in the US. This transition for manufacturers will be one requiring increased scrutiny under marketing applications from the lowered standard of “may be effective” for EUAs and various enforcement discretion expectations to requirements to provide objective evidence of safety and effectiveness. It will be interesting to see how many of the EUA medical devices continue to be sold and distributed after termination of the EUA declaration and the impact on the variety of medical devices on the market. Only long-term post market data will determine the impact, if any, on the COVID-19 PHE and patients from the use of EUA medical devices during the pandemic.
Abbreviations
EUA, emergency use authorization;
FDA, [US] Food and Drug Administration;
FD&C [Act], Federal Food, Drug, and Cosmetic Act;
PHE, public health emergency; and
US, United States.
REFERENCE: RAPS (Regulatory Focus, News Articles 2022 5); 23 MAY 2022; Ashley Clark, MS, RAC