The Food and Drug Administration (FDA) announced a final guidance that describes the current thinking of the Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER), and Center for Devices and Radiological Health (CDRH) (the Centers) on the assessment of civil money penalties (authorized under Section 303(f)(3) of the Federal Food, Drug, and Cosmetic Act (FD&C Act)) against responsible parties and/or submitters of applications and submissions to FDA regarding drug products, biological products and device products (products) who fail to submit clinical trial registration and/or results information to the ClinicalTrials.gov data bank and/or certain certifications to FDA.
The Food and Drug Administration Amendments Act of 2007 (FDAAA) amended the FD&C Act to require that responsible parties (i) submit clinical trial registration and results information to the ClinicalTrials.gov data bank for certain “applicable clinical trials” and (ii) certify to FDA that all applicable regulatory requirements have been met when submitting certain applications and submissions regarding products.
The FDAAA also amended the FD&C Act to prohibit the (i) failure to submit or the knowing submission of a false certification to FDA, (ii) failure to submit required clinical trial information, and (iii) submission of clinical trial information to the ClinicalTrials.gov data bank that is false or misleading.
The FDAAA authorized FDA to assess civil money penalties against a person who commits prohibited acts.
Scope of Guidance
How will FDA identify whether responsible parties have (i) failed to submit required information to the ClinicalTrials.gov data bank, (ii) submitted false or misleading information to the data bank, (iii) failed to submit to FDA the required certification, or (iv) knowingly submitted a false certification to FDA?
- Generally, FDA will identify violations of the FD&C Act’s requirements relating to the ClinicalTrials.gov data bank through evidence collected during inspections conducted as part of FDA’s Bioresearch Monitoring Program (BIMO), as well as complaints received by the agency about potential violations of FDA requirements. In evaluating complaints, FDA may review any public and nonpublic information available to FDA, including information submitted to the ClinicalTrials.gov data bank.
Under what circumstances may a Center decide to seek civil money penalties against a responsible party?
FDA will utilize a risk-based approach to determine the situations in which Pre-Notice Letters will be issued, focusing on the following areas:
- Responsible parties who have failed to submit required clinical trial registration and/or results for applicable clinical trials of products that may pose a higher risk to human subjects or applicable clinical trials of products intended to address significant public health needs. These include applicable clinical trials of a product that has not previously been approved, licensed or cleared by FDA and is intended to treat a serious and/or life-threatening disease or condition as well as applicable clinical trials involving vulnerable populations (such as pediatrics), rare diseases or emergency research conducted without informed consent under 21 CFR 50.24.
- Responsible parties who have had a pattern of previous noncompliance with the requirements to submit clinical trial information and/or certifications.
- Applicable clinical trials for which noncompliance exists in conjunction with noncompliance with other statutory and/or regulatory requirements pertaining to the conduct of the trial (for example, the failure to retain clinical trial records or the failure to obtain informed consent).
Based on this review, FDA will send Pre-Notice Letters to a responsible party. After the 30-calendar-day period for any necessary action has passed, FDA will review the information submitted to the ClinicalTrials.gov data bank for that applicable clinical trial, the application/submission in FDA files and/or any other information available to the agency in order to determine whether a violation exists. If the Center determines that a responsible party failed to submit required clinical trial information to the ClinicalTrials.gov data bank, submitted information that is false or misleading in any way, failed to submit the required certification to FDA, or knowingly submitted a false certification, the agency will issue a Notice of Noncompliance to the submitter.
- A Notice of Noncompliance will give the responsible party an opportunity to remedy the noncompliance within 30 calendar days after the notification. If the responsible party does not remedy the noncompliance, FDA will seek civil money penalties, taking into account the type of noncompliance and the circumstances associated with the lack of remediation.
What procedures apply when a Center seeks civil money penalties?
- FDA will send the respondent a complaint including allegations of liability, the specific violations that are the basis for the alleged liability, the reasons the respondent is responsible for the violations, and the amount of penalties and assessments FDA seeks.
- The respondent must either (i) pay the penalty sought in the complaint or (ii) file an answer with the Division of Dockets Management and contest some or all of the allegations within 30 days after the date of service of the complaint.
- If the respondent files an answer within the time prescribed, the respondent is entitled to a hearing according to the procedures established in FDA’s regulations governing civil money penalty proceedings.
What civil money penalty amounts may be assessed for (i) failing to submit required clinical trial registration and/or results information to the ClinicalTrials.gov data bank, (ii) submitting false or misleading information to the data bank, (iii) failing to submit the required certification to FDA, or (iv) knowingly submitting a false certification to FDA?
- The maximum penalties under the FD&C Act for committing prohibited acts do not exceed $10,000 for all violations adjudicated in a single proceeding. If a violation is not corrected within 30 days following notification, an additional civil money penalty of not more than $10,000 may be assessed for each day the violation continues after such period until the violation is corrected. FDA will consider certain factors in determining the penalty, including the nature, circumstances, extent and gravity of the violations; the responsible party’s ability to pay; the effect on its ability to continue to do business; any history of such violations; the degree of culpability; and other relevant matters.