FDA Opens the Pre-Sub Program to Compliance Actions, Including Form 483s and Warning Letters

Considering the tight timeline for preparing responses to FDA compliance actions coupled with the agency’s expectation for timely implementation of corrective and preventive actions, the benefit of obtaining feedback through the Q-submission program (also referred to as a “pre-submission”) may be limited.

To start off the new calendar year, FDA issued a revised version of its guidance document on the Q-submission program on January 6, 2021, “Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program.” Changes made to the guidance document since its last publication on May 7, 2019 are as follows:

• Obtaining feedback on submissions that may qualify for FDA’s recently announced Safer Technologies Program (STeP), also launched on January 6, 2021 (see Guidance Document). The STeP Program provides an expedited review and authorization process for certain device and device-led combination products that are reasonably expected to significantly improve the safety of currently available treatments or diagnostics that target an underlying disease or condition associated with morbidities and mortalities less serious than those eligible for the Breakthrough Devices Program.

• Obtaining feedback related to compliance actions. The updated guidance document provides as an example requesting feedback from FDA in preparing a response to inspectional observations listed on a Form 483. Although not explicitly included, the Q-submission process appears to also be available for other types of compliance actions, such as untitled letters, Warning Letters, and “It has come to our attention” letters.

FDA’s Other Published Mechanisms for Obtaining Feedback

The updated Q-submission guidance provides yet another option for device companies to obtain feedback for compliance actions that may be more appealing than prior FDA programs. Less than a year ago, and due to a mandate from the FDA Reauthorization Act of 2017 (FDARA), FDA published a guidance document that launched a pathway for obtaining feedback from FDA on compliance actions. The guidance document, “Nonbinding Feedback After Certain FDA Inspections of Device Establishments” released on April 22, 2020, allowed companies to obtain nonbinding feedback from the agency so long as

• the request was made no later than 15 business days after issuance of the Form 483; and
• the company documents in its request a justification that the inspectional observations “involve a public health priority,” “implicate systemic or major actions”, or “relate to emerging safety issues (as determined by [FDA])”[1]. FDA provided three examples in the guidance document that met this criteria. All three examples included a determination that the observations suggest that the company’s quality system, if left unaddressed, could lead to public harm (i.e., death or serious injuries).

If the company demonstrates to FDA that it meets both criteria, FDA is required to provide nonbinding feedback to the company within 45 calendar days of the agency’s receipt of the request.

Companies have been reluctant to use the nonbinding feedback program because the company must justify to FDA that the inspectional observation(s) demonstrate a breach in the company’s quality system that can cause significant harm to the public. The guidance document does not place any limits on how FDA could use such self-incriminating statements against the company in additional compliance actions (e.g., Warning Letters, Consent Decrees, Criminal and Civil Penalty proceedings). Moreover, plaintiff lawyers could use the company statements in class actions as evidence that the devices are misbranded and/or adulterated.

Practical Implications of Using the Q-Submission Program for Obtaining Feedback

The Q-submission guidance document does not include criteria as to the types of compliance actions the agency is willing to provide feedback on. However, because in the Q-submission program the agency has up to 90 days to provide feedback to the requestor (which it usually takes), FDA’s feedback may be untimely in preparing a response to a compliance action or executing an action plan. Specifically:

• Companies generally have 15 business days to respond to a Form 483 or Warning Letter (the most common FDA compliance actions). Within the 15 days, FDA generally expects companies to develop an action plan that fully addresses the agency’s concerns and begin execution of that plan (at least for those issues that may have a public safety component). FDA has routinely found company responses to be inadequate (and thus trigger additional FDA enforcement) if action plans are not fully developed and/or immediate action has not been initiated by the time the first response is submitted to the agency. Indicating in a response that a company will develop an action plan once it receives feedback from the agency through the Q-submission program may not be enough to convince an FDA compliance officer that additional enforcement is not necessary.
• FDA expects companies to implement corrective and/or preventive actions in a timely, expedient manner. If long periods of time are required to implement permanent corrective and/or preventive action, FDA generally expects companies to implement interim actions to avoid continual noncompliant behavior. Because the agency has up to 90 days to provide feedback on Q-submission requests, delaying the implementation of actions because of wanting to receive feedback from the agency through the pre-submission before implementation may not be acceptable to an FDA compliance officer.

Nonetheless, the Q-submission program may provide some benefit when dealing with compliance actions. For example:

• When determining the extent of a retrospective review activity, obtaining feedback from the agency before execution may be helpful to confirm the adequacy of the company’s planned activity.
• When there are legitimate questions regarding the reportability of information pursuant to 21 CFR Parts 803 (MDR) and 806 (recalls), the Q-submission program can be used to pressure-test reporting rationales.
• When there are legitimate technical questions regarding whether a process does in fact require validation, the Q-submission program can be used to obtain feedback on a company’s rationale.

Should a company use the Q-submission program to obtain feedback, the company should consider committing to FDA interim actions to address the FDA concerns while the feedback is under review. Committing to interim actions should demonstrate to the FDA compliance officer that the company understands action is required; however, the nature and extent of that action will be fully determined once feedback has been obtained.

Compliance Outlook Under the Biden Administration

After a 90% decrease in Warning Letters between 2015 and 2019, coupled with a pause/significant reduction of FDA’s inspection program due to COVID-19, we anticipate an increase in FDA enforcement activity under the Biden administration. While during the pandemic FDA is discussing the use of “virtual inspections,” we expect FDA’s inspection cadre to be fully engaged in conducting in-person inspections once it is safe to do so. Accordingly, actions being taken by companies today will likely be reviewed by FDA in the future. Noncompliant activity that would have been handled through nonpublic, informal correspondence under the Trump administration could likely trigger formal, public enforcement actions (e.g., Warning Letters, Consent Decrees) under the Biden administration.

While companies should be taking steps today to ensure that they are operating in compliance with their quality system processes and regulatory requirements, should a company be subject to a compliance action, the Q-submission program may (in limited scenarios as noted above) be helpful in developing and implementing action plans.

HOW WE CAN HELP

Morgan Lewis helps companies around the world and across industries assess the impact of the legal and regulatory issues described above. We have assisted numerous clients with navigating FDA policies and guidance related to medical device and digital health products, both before and during the COVID-19 pandemic, including support for evaluating how or whether such technologies are regulated by FDA, the preparation and submission of EUAs, and other premarket submissions. We also routinely counsel companies on postmarket compliance, including the development of quality system procedures and the preparation/defense of companies before FDA inspections.

CONTACTS

If you have any questions or would like more information on the issues discussed in this LawFlash, please contact any of the following Morgan Lewis lawyers:

Washington, DC
Dennis Gucciardo
Michele Buenafe

[1] Section 704(h)(2)(B)(ii) of the Federal Food Drug and Cosmetic Act