On Jan. 31, 2020, the Department of Health and Human Services (HHS) declared a public health emergency (PHE) related to the global COVID-19 pandemic. The declaration of a PHE enabled FDA to issue a declaration regarding the appropriateness of utilizing emergency use authorizations (EUA). FDA may also utilize enforcement policies to signal its willingness to permit the marketing of unapproved products.
FDA has taken advantage of the EUA and enforcement priority pathways to address the COVID-19 pandemic, issuing approximately 450 device EUAs and 17 medical device enforcement policies. Most of the devices receiving EUAs are in vitro diagnostic tests for COVID-19.
On December 22, 2021, FDA published two draft guidances describing FDA’s proposed transition from the PHE (“Transition Plan for Medical Devices Issued Emergency Use Authorizations (EUAs) During the Coronavirus Disease 2019 (COVID-19) Public Health Emergency” and “Transition Plan for Medical Devices That Fall Within Enforcement Policies Issued During the Coronavirus Disease 2019 (COVID-19) Public Health Emergency.”) Under both of these transition plans, FDA will expect complete adherence to all regulatory requirements, except that premarket submissions (e.g., premarket approval (PMA) submission, substantial equivalence premarket notification (510(k) notification), or de novo classification request) need only be accepted by FDA at least 180 days after the implementation date.
There are many additional commonalities between the two draft guidances:
- The purpose of these policies is “to facilitate an orderly and transparent transition back to normal operations . . . taking into account . . . the manufacture, distribution, and use of devices in the context of the COVID-19 PHE.”
- For certain reusable life-supporting or life-sustaining devices, FDA recommends the submission during the transition period of information on a manufacturer’s intent to continue marketing after the transition period. Having this information will assist FDA in resource planning.
FDA requests that a manufacturer not planning to continue marketing after the transition period provide, among other information, “its plans to discontinue distribution of the device, to restore the device to a previously FDA-cleared or -approved version, to provide a physical copy or electronic updated labeling, and any other efforts to address or mitigate potential risks of devices that remain distributed after the EUA termination date.”
- As part of the marketing submission, manufacturers should include a transition implementation plan that “addresses the manufacturers’ plans both for dealing with devices already distributed in the case of a positive decision or in the case of a negative decision on the marketing submission.” The plan should include an assessment of the “benefit-risk based plan for disposition of already distributed product in the event of a negative decision on the marketing submission.” The plan should also include an explanation of the manufacturers’ plans for addressing already-distributed product in the event of a positive decision on the marketing submission. The plan should address how users (including patients, healthcare providers, and distributors) will be notified of the regulatory status of the already-distributed devices, how labeling will be distributed, a maintenance plan for distributed devices, and where appropriate for a negative decision, how the device will revert to a prior FDA-cleared or approved version.
- With the exception of premarket review requirements, all other regulatory requirements will apply at the completion of the transition period. Nevertheless, FDA acknowledges that many manufacturers may have trouble meeting the requirements of the Quality System Regulation (QSR; FDA’s medical device good manufacturing practice regulation), and FDA encourages manufacturers to consider seeking exemption or variance from QSR.
- Once FDA reaches a negative decision for a marketing submission or the marketing submission is withdrawn by a manufacturer, FDA expects the device to cease being distributed.
- If a manufacturer does not intend to continue to distribute a device after EUA termination or the enforcement policy is withdrawn, FDA will not generally require already-distributed devices to be removed from the market if the device is:
- Single use, non-life-supporting/non-life-sustaining.
- Reusable, non-life-supporting/non-life-sustaining (e.g., remote patient monitoring devices) and either:
- It has been restored to a previously cleared or approved version, or
- The manufacturer has “publicly available labeling that accurately describes the product features and regulatory status (i.e., that the product lacks FDA clearance or approval).”
- Reusable life-supporting/life-sustaining (e.g., ventilators, extracorporeal membrane oxygenation systems, continuous renal replacement therapy systems) and either:
- It has been restored to a previously cleared or approved version, or
- The manufacturer has “both publicly available and a physical copy of labeling that accurately describes the product features and regulatory status (i.e., that the product lacks FDA clearance or approval).”
- An in vitro diagnostic (IVD) test to be used for no more than two years after EUA termination or expiration date, whichever is less.
The primary differences between the proposed transition plans for those devices on the market under an EUA versus an enforcement policy are the timing and triggers for the transition period.
Because FDA must provide advance notice via publication in the Federal Register that an EUA declaration will be terminated, FDA will publish its intent to end the EUA declaration at least 180 days before termination of the EUA declaration. During the transition period, the conditions for authorization under the EUA will continue to apply.
There is a 180-day transition period, consisting of three phases, starting on the implementation date of the transition plan. If the transition plan is finalized before the termination of the PHE, the implementation date will be the date the PHE ends. If the PHE ends before the finalization of the transition plan, the implementation date will be at least 45 days after the transition plan is finalized.
The first phase begins on the implementation date, and manufacturers must follow the adverse event reporting requirements in 21 CFR Part 803 starting in Phase 1.
Phase 2 begins 90 days into the transition period, and during this phase manufacturers must begin to adhere to the reporting requirements for device corrections and removals in 21 CFR Part 806 in addition to meeting the requirements in Part 803. For those manufacturers intending to keep their products on the market at the end of the transition period, the manufacturers must also register their facilities (if not already registered) and list the product consistent with 21 CFR Part 807 Subparts B-D.
At the 180-day mark of the transition period, Phase 3 begins. As noted above, FDA will expect the removal of all devices unless FDA has accepted a premarket review submission. With the exception of having a marketing order (approval or clearance), FDA will expect all regulatory requirements to be met for marketed devices.
Note that all the enforcement policies the transition plan would apply to indicate that they will expire at the conclusion of the PHE. The proposed transition plan would extend each of these policies until the end of the transition period (at least 180 days after the conclusion of the PHE).
FDA has encouraged industry for well over a year to begin transitioning to “normal” by submitting marketing applications. These proposed transition plans are FDA’s further attempt to continue planning for a post-pandemic world.
Though the number of cases of COVID-19 have recently spiked, it is important for manufacturers to begin planning for the end of the PHE. Not only does FDA expect immediate adherence to certain regulatory requirements once the transition period begins, it may take greater than 180 days to generate data and draft a premarket submission. Additionally, for certain devices additional input from FDA may be required to prepare an effective premarket submission. Obtaining a meeting with FDA can take several months once requested – further adding to the time required to prepare a successful premarket submission.
Considerations in developing the premarket submission include:
- For most Class II and some Class I devices, a 510(k) clearance will be required. A 510(k) submission will require identification of a predicate device against which applicants must demonstrate equivalence. It is therefore critically important to select the appropriate predicate. If a predicate cannot be identified, manufacturers may utilize the de novo classification process to demonstrate to FDA that the device will be safe and effective without a premarket application (generally requiring clinical studies).
- Much of the information required for a 510(k) or de novo may have been generated as part of an EUA request or in the development of a product that will meet an enforcement policy, but to ensure that all required information is supplied to FDA, it is important to have the advice of experienced regulatory professionals.
- In some cases, especially for novel devices, FDA guidance may leave open questions about the submission. In such a circumstance, it may be beneficial to have a pre-submission meeting with FDA. A pre-submission meeting request will result in a written response within 70 days or a meeting within approximately 75 days preceded by a written response (after either 70 days after the meeting is requested or five days before the meeting, whichever is sooner). A pre-submission request should include background information on the device as well as questions for which the manufacturer is seeking FDA input. It is important to carefully construct the meeting package to ensure that FDA’s advice fully addresses the manufacturer’s questions.