On September 20, 2018, the U.S. Food and Drug Administration (“FDA”) released draft guidance “Civil Money Penalties Relating to the ClinicalTrials.gov Data Bank” (“Guidance”). The purpose of this Guidance is to explain FDA’s protocol in (1) determining how the centers will identify whether responsible parties failed to comply with submission and certification requirements to the ClinicalTrials.gov or submitted false or misleading documents to the data banks and (2) deciding when, why, and what civil monetary penalties will be assessed against the responsible parties or submitters. The new guidance seeks to address requirements of responsible parties involved in the performance of clinical research and submission of applications for marketing authorizations to register their trial, submit clinical results information and make certain certifications regarding their compliance with these requirements.  In order to mitigate their risk of civil money penalties in accordance with this guidance,  sponsors and researchers should (1) have policies and procedures that ensure correct clinical trial information is submitted to the ClinicalTrials.gov data bank, (2) have policies and procedures that ensure routine monitoring for missing or inaccurate clinical trial information in the data bank, (3) make timely submissions of the required information, and (4) remain responsive to any inquiries by FDA concerning clinical trial data and/or certifications to FDA.

Background

Under section 801 of the Food and Drug Administration Amendments Act of 2008 (the “FDAAA”), which amended section 402(j) of the Public Health Service Act (42 U.S.C. 282(j)(5)(B)), responsible parties engaged in certain clinical research activities are required to submit registration and results information to the ClinicalTrials.gov data bank. Additionally, submitters of certain applications and other items to FDA regarding drug, biological, and medical device products are required to certify to FDA that all requirements of section 402(j) have been met. Similarly, the FDAAA amended section 301(jj) of the Food Drug and Cosmetics Act (the “FD&C Act”) to prohibit: (1) the failure of submitting or knowingly submitting a false certification to FDA, (2) the failure to submit required clinical trial information, and (3) submitting false or misleading clinical trial information to the ClinicalTrials.gov data bank. Further, the FDAAA amended section 303(f)(3) of the FD&C Act, authorizing FDA to assess civil monetary penalties against the person committing the prohibited acts.

Identifying Noncompliant Responsible Parties and Submitters

In this Guidance, FDA states its intention to utilize evidence collected during FDA’s Bioresearch Monitoring Program (“BIMO”) inspections to assess compliance with registration and results reporting requirements as described in Form FDA 2438 – Chapter 48 – Bioresearch Monitoring (Apr. 19, 2017). FDA also intends to identify violations as a result of complaints received by the Agency, which may entail reviewing public and non-public information, including, but not limited to information submitted to the ClinicalTrials.gov data bank and to FDA.

It is in the best interest of sponsors, researchers, and other parties subject to an obligation to submit clinical trial registration, information, results, and/or certifications to FDA to have policies and procedures in place to ensure correct information is submitted to ClinicalTrials.gov data bank. Policies and procedures should also include periodic review of the data bank to monitor for any missing or inaccurate clinical trial information. Developing and implementing these policies and procedures will mitigate the risk of enforcement for noncompliance with registration and clinical trial results reporting requirements, as outlined in the Guidance.

Determining When to Seek Civil Monetary Penalties

Under Guidance, FDA intends to provide the responsible parties with an opportunity to remedy any prohibited acts under section 301(jj) of the FD&C Act and corresponding regulations (42 CFR Part 11) before initiating an action to recover penalties. Pursuant to the procedures detailed in the Guidance, when FDA determines that when submissions are not timely filed or inaccurate, FDA will generally send the responsible party or submitter a Preliminary Notice of Noncompliance Letter describing the potential violation. The responsible party or submitter will have thirty (30) calendar days to remedy the violation. Should FDA conduct further review and find further or continued noncompliance with the applicable clinical trial requirements, the agency will then issue a Notice of Noncompliance, giving the responsible party or submitter another thirty (30) days to remedy noncompliance after receipt of the notice.

It is in the best interest of sponsors and researchers to promptly respond to any FDA inquiries and notices concerning registration, clinical trial information or certification issues related to the ClinicalTrials.org data bank. Failure to comply within the thirty (30) days of receipt of Notice of Noncompliance will result in FDA escalating regulatory action, including civil monetary penalties, of up to $10,000 for all violations adjudicated in a single proceeding.  Additional penalties of up to $10,000 each day may be included if the violation continues and if said violation is not corrected within thirty (30) days following notification. FDA may also pursue injunction and/or criminal prosecution.

In determining monetary penalties, the FDA will evaluate the circumstances, nature, extent, and gravity of the violation(s) with respect to the individual.  Other factors will include the violator’s ability to continue conducting business, any prior history of such violations, and the degree of culpability in the matter.

Responding To Civil Monetary Penalties by FDA

If FDA seeks civil monetary penalties, according to 21 CFR Part 17, the responsible party or submitter has the opportunity to either: (1) pay the penalty prescribed in the complaint or (2) file an Answer, contesting the allegations either in part or in whole, within thirty (30) days of date of service.

Should the responsible party or submitter contest the allegations by submitting an Answer, generally settlement discussions with FDA are entered into, providing the responsible party or submitter to present mitigating evidence to FDA for purposes of reducing the penalty amount. If a settlement is not reached before a decision on appeal, a presiding officer will make an initial decision, followed by the usual administrative appeal process (e.g., Department of Health and Human Services Departmental Appeal Board and then the U.S. Court of Appeals for the District of Columbia or any other circuit in which the responsible party or submitter resides or conducts business), should either party appeal the initial decision.

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A recent BMJ article, “Compliance with requirement to report results on the EU Clinical Trials Register: cohort study and web resource,” reported that for approximately half of the clinical trials, the responsible person did not report results on the EU register while a 2015 New England Journal of Medicine article, “Compliance with Results Reporting at ClinicalTrials.gov,” reported that approximately 20% of industry trials did not report results when required to do so, and 50% of NIH-sponsored research went unreported. While the registration, reporting, certification requirements, and the penalties for noncompliance are not new, FDA’s release of this Guidance should be taken as a signal to sponsors and researchers of its plan to enforce those requirements more rigorously. Therefore, sponsors and researchers should take this opportunity to evaluate the sufficiency of their policies and procedures for compliance with registration and reporting requirements and audit their submissions to ensure they are up-to-date.  Comments are due by November 20, 2018.