Are You At Risk For An FDA ClinicalTrials.gov-Related Monetary Penalty?

The FDA has historically not initiated formal actions to enforce the statutory requirements to register and provide clinical trial data to the ClinicalTrials.gov data bank.  However, industry is now on notice that the FDA is about to change its approach. The agency released new guidance in August giving notice that that it will soon be taking action when companies fail to comply with the ClinicalTrials.gov data bank transparency obligations imposed on sponsors and principal investigators.

Background On History And Requirements Under ClinicalTrials.gov

The National Institutes of Health (NIH) created the ClinicalTrials.gov website in response to a Congressional mandate in the Food and Drug Administration Modernization Act of 1997 (FDAMA) to create and maintain a registry of clinical trial information and to make it publicly available.  Section 801 of the FDA Amendments Act of 2007 (FDAAA) added the requirement that sponsors and investigators submit study results for certain trials.  In 2016, the Department of Health and Human Services (HHS) issued the Final Rule for Clinical Trials Registration and Results Information Submission (42 CFR Part 11), which clarified the new registration and results information submission requirements found in section 801 of FDAAA. 

Of note, the final rule issued by HHS exempted certain clinical trials conducted between 2007 and 2017 from the FDAAA’s section 801 reporting requirement. However, that exemption was challenged in federal district court and overturned. See Seife v. U.S. Department of Health and Human Services, 440 F. Supp. 3rd 254 (S.D.N.Y. 2020). HHS has chosen not to appeal. Instead, the FDA and NIH posted a letter on the ClinicalTrials.gov website, directing sponsors and investigators to submit as soon as possible those results that the rule would have exempted from submission.

With that letter, it appears that the government has thrown in the towel and is no longer trying to defend the exemption it created by regulation. Thus, there is now almost a decade’s worth of clinical trial results for products that had not received marketing authorization at the time of trial completion that should now be submitted to ClinicalTrials.gov. 

FDA’s Notice That It Will Begin Enforcing The ClinicalTrials.gov Data Bank Requirements

Significantly, section 801 established penalties for failing to register or submit the results of trials, and HHS delegated the enforcement authority to the FDA. While HHS was going through its rulemaking exercise, the FDA chose not to pursue any enforcement actions. However, with the issuance of a final guidance titled Civil Money Penalties Relating to the ClinicalTrials.gov Data Bank, the FDA has clarified that it will soon begin enforcing this new provision and has provided insight into how it will do so. This guidance finalizes the draft guidance issued in September 2018.

The new guidance explains that prohibited acts related to the submission requirements for the ClinicalTrials.gov data bank that can be penalized include: (1) failing to submit or knowingly submitting a false certification to FDA of compliance with ClinicalTrials.gov data bank requirements; (2) failing to submit required clinical trial information to the data bank; and (3) submitting clinical trial information that is false or misleading. According to the new guidance, the FDA intends to utilize a risk-based approach to enforcement, with priority for enforcement in the following areas: (1) clinical trials that may pose a higher risk to human subjects or that are intended to address significant public health need; (2) where there is a pattern of previous noncompliance; and (3) where there is noncompliance with other statutory or regulatory requirements, such as failure to retain clinical trial records or failure to obtain informed consent. 

The FDA will look for evidence of compliance when it is conducting inspections such as good clinical practice (GCP) inspections conducted as part of the Bioresearch Monitoring Program. The FDA also will consider and appropriately investigate complaints of noncompliance that it receives from other sources. However, in response to comments on the draft guidance, the FDA has clarified that that it does not intend to include on its Lists of Inspectional Observations, Forms FDA 483, any inspectional observations regarding potential violations relating to the ClinicalTrials.gov data bank. However, information that is collected by an investigator regarding potential violations of such requirements will be included in an Establishment Inspection Report and provided to the relevant FDA center for further evaluation.

Companies can take some comfort in the fact that FDA, consistent with statutory requirements, will notify the sponsor or principal investigator of potential noncompliance before taking any enforcement action.  According to the guidance, the FDA will issue a Preliminary Notice of Noncompliance (Pre-Notice) letter that allows the recipient 30 days to correct the potential violation. If the sponsor or principal investigator fails to come into compliance, the FDA’s next step will be to issue and publicly post a Notice of Noncompliance. If the sponsor or principal investigator does not remedy the noncompliance within 30 days after receiving the Notice of Noncompliance, the FDA “generally intends to seek civil money penalties, taking into account the type of noncompliance and the circumstances associated with the lack of remediation.” Once the FDA has formally launched a civil money penalty action, the respondent to the action will have an opportunity request a hearing to challenge the imposition of the penalty. The statute provides for an initial penalty of not more than $10,000, but if the violation is not corrected within 30 days after the conclusion of the civil money penalty adjudication, the statute allows additional penalties of up to $10,000 per day until the violation is corrected.  In addition to seeking civil money penalties, the government also may seek an injunction and/or criminal prosecution. 

What Does This Mean For Sponsors?

Thus, it appears sponsors must be alert to this new statement by the FDA and ensure they are in compliance with the ClinicalTrials.gov data bank requirements.  ClinicalTrials.gov provides an informative Q&A that you can use to help determine if you are in compliance. It is particularly important to review records in the past decade, when sponsors may have not posted information based on an exemption that HHS initially endorsed but now has removed in response to the Seife decision. The FDA’s new guidance will help sponsors assess which trials may be most vulnerable to the FDA’s enforcement efforts and thus prioritize those trials as top priority for bringing into compliance.

About The Authors:

Cynthia Schnedar is executive VP of regulatory compliance at Greenleaf Health. She was formerly director of the Office of Compliance for the FDA’s CDER. During her time at the FDA, she spearheaded efforts to protect the American public from unsafe and ineffective drug products by ensuring companies comply with federal standards for quality and safety. Among her many duties, Schnedar advised the FDA commissioner, the CDER director, and other senior FDA officials on significant enforcement issues. Schnedar spent more than two decades at the Department of Justice, where she specialized in compliance and enforcement issues and served as acting inspector general. She earned a B.A. from the University of New Mexico and a J.D. from the University of Texas School of Law. You can connect with her on LinkedIn.

Kate Cook is executive VP of drug and biological products at Greenleaf Health, Inc. She joined Greenleaf after a long career at the FDA, including 15 years in the Office of Chief Counsel, five years in the Office of the Center Director at the FDA’s Center for Biologics Evaluation and Research, and one and a half as associate director for regulations and policy at the FDA’s Center for Devices and Radiological Health. You can connect with her on LinkedIn.