Crime and Punishment

Are you aware of your responsibilities in complying with the rules and laws of the FDA?

By Dorothy B. Abel

To view the tables related to this article, please refer to the print version of our September issue, page 84.

The views and opinions in this article are those of the authors and do not necessarily reflect those of the US FDA, the US Department of Health and Human Services, or the Public Health Service.

Whether you’re an investigator participating in a clinical study, a manufacturer of medical devices, or a clinician who uses medical devices, there are rules (laws, no less) that apply to you. Although there has been no recent change in these laws, current events suggest that a refresher is warranted. The responsibilities, monitoring of compliance with the laws, and the consequences of noncompliance are covered in this article.

Each investigator participating in a clinical investigation that requires an approved investigational device exemptions (IDE) application should receive a copy of the “Investigators’ Responsibilities for Significant Risk Device Investigations.” Responsibilities outlined in this document include conducting the investigation in accordance with the signed agreement, the investigational plan, and applicable FDA regulations; protecting the rights, safety, and welfare of subjects; controlling devices under investigation; obtaining informed consent from each subject; and not beginning the investigation until both FDA and institutional review board (IRB) approvals have been obtained. The types of records that must be maintained are specified; that is, correspondence with another investigator, an IRB, the sponsor, a monitor, or the FDA; records regarding device disposition (eg, receipt, use, return, disposal); patient information; the protocol; and information on protocol deviations. Submission of reports to sponsors and IRBs is also covered—topics such as the reporting of unanticipated adverse device effects, progress reports, and failure to obtain informed consent. Rules regarding promotion of investigational devices are also summarized.

Responsibilities of IDE sponsors are outlined in the ?Sponsor’s Responsibilities For Significant Risk Device Investigations.? These responsibilities are similar to those of the investigators, with additional requirements for submitting the IDE and appropriate supplements, selecting qualified investigators, and monitoring the study. Also, reporting requirements for IDE sponsors are more extensive than those for investigators and include reports to investigators, the IRBs, and the FDA. The responsibilities for record keeping and reporting are summarized in Tables 1 and 2.

After a device is approved for marketing, different rules apply, including requirements for reporting adverse events. All manufacturers of medical devices must report to the FDA whenever they become aware of information from any source that reasonably suggests that a device may have caused or contributed to a death or serious injury or has malfunctioned, and if the malfunction were to recur, would likely cause or contribute to a death or serious injury. User facilities (eg, hospitals) are required by law to report suspected medical-device related deaths to both the FDA and to the manufacturer, if known, and serious injuries to the manufacturer. If the manufacturer is unknown, reports of serious injuries are to be sent directly to the FDA.

The majority of these responsibilities is specified in the medical device regulations, that is, they are required by law. The law also specifies that the FDA can inspect the investigational site. And they will. Inspections focus on all of the responsibilities outlined above and in the specific regulations, with particular emphasis on those related to patient safety, such as adverse event reporting and documentation of informed consent.

Inspections of manufacturers are understandably broader and more complicated and may take place both pre- and post-market. With respect to adverse event reporting, for example, the regulations specify that the manufacturer must report all information from any source. This includes information obtained through case support and proctoring, whether part of training or per standard company procedures. Inspections may therefore include examining records to determine whether all adverse events from such sources have been appropriately reported.

If during an inspection the FDA finds that an investigator or a manufacturer has not met their responsibilities, several actions or sanctions may be taken or applied. These actions may be directed at an individual or a corporation. Issuance of a Form 483, ?Inspectional Observations,? is common and requires that the issues identified during an inspection be addressed, primarily through process modifications. A Warning Letter is a public document that warns the recipient of the more severe sanctions that the FDA may impose if the violations described are not corrected. These sanctions may include a citation, which is a formal warning of the FDA’s intention to prosecute if violations are not corrected; criminal prosecution; seizure of a product by the FDA; and civil monetary penalties. Another action that may be warranted, depending on the circumstances, is a device recall, which is a procedure where a hazardous or potentially hazardous product is removed from the marketplace. Recalls may either be FDA-initiated or voluntary.

An investigator may face disqualification if they have repeatedly or deliberately fail to comply with the requirements or have repeatedly or deliberately submitted false information either to the sponsor of the investigation or in any required report. This sanction is in addition to those listed above. For manufacturers that have used the disqualified investigator, any and all pending submissions or past approvals could be affected by the disqualification. If, for example, the investigator was responsible for providing data to support a PMA application, the FDA may determine that the data were not valid and would not give the manufacturer approval to market the device.

Recently, there have been several warning letters issued to clinicians based on inspectional observations. In addition, the Office of Criminal Investigations and the Department of Justice have been investigating both individuals and corporations for noncompliance with the Medical Device Regulations (MDRs). The Guidant Corporation (Indianapolis, IN) ANCURE case has gotten the most press, with the case so far resulting in a more than $90 million settlement and removal of the device from the market. In this case, the company failed to submit MDR reports to the FDA regarding observations made by its case support staff who were present at virtually every implant procedure. It was the failure to submit the MDRs and not the performance of the device that led to the case against the manufacturer and the eventual removal of the product from the market. Lessons learned: (1) breaking the rules in and of itself can lead to the actions described above, irrespective of device performance; and (2) manufacturers are responsible for determining whether events observed by their personnel qualify as reportable events, in parallel with the clinicians’ decision as to whether to report the event to the manufacturer.

Also of interest is that a number of the allegations in other cases are related to potential violations that occurred many years ago. Corrective actions that have been put into place since the time of any deviation from the rules may be considered by the FDA in determining whether to impose additional sanctions. However, correction of the problem(s) does not obviate the potential for actions against the offender. Lessons learned: (1) it is not too late to get into trouble for mistakes made years ago (eg, during the early days of endovascular grafting); and (2) it is a good idea to conduct an internal audit to determine whether there is a need to address even old offenses.

In summary, it is critical for all involved in the manufacture and use of medical devices to be aware of their legal responsibilities and of the potential for significant legal consequences if these responsibilities are not met. 

Dorothy B. Abel, is the Convener of the ISO Vascular Prostheses Working Group and a Regulatory Review Scientist with the US FDA Center for Devices and Radiologic Health in Rockville, Maryland. She is also a regular columnist for Endovascular Today. Ms. Abel may be reached at (301) 443-8262; ext. 165;

Thanks to Jarin Kratzberg, an intern at the FDA, for providing research support.


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