On April 13, 2011, the FDA published a proposed rule to expand the scope of disqualification for clinical investigators involved in drug, biologics, animal drug, and medical device clinical trials.1 The FDA employs its disqualification authority, along with other types of enforcement action, to ensure adequate protection of research subjects and the quality and integrity of clinical data submitted to the FDA.2 The proposed rule addresses recommendations made in a 2009 Government Accountability Office (GAO) report about FDA oversight of clinical investigators.3 Comments on the proposed rule must be submitted by July 12, 2011.
The proposed rule makes changes to existing regulations to help ensure consistency across the disqualification procedures of the FDA Centers (CDER, CBER, CDRH, and CVM). More importantly, the proposed rule would make a disqualified investigator "ineligible to conduct any clinical investigation that supports an application for a research or marketing permit for products regulated by FDA."4 Under current regulations, a disqualified investigator is only prohibited from working on clinical trials with products covered by the specific regulation under which the investigator was disqualified. For example, an investigator who is disqualified under 21 C.F.R. § 312.70 – which only applies to investigations for drugs and biologics – is not disqualified from serving as an investigator on a clinical trial for medical devices.
The proposed rule does not change the current standard for disqualification; the FDA will initiate the disqualification process if the agency has information that an investigator (1) has repeatedly or deliberately failed to comply with applicable requirements for the conduct of clinical investigations, or (2) has repeatedly or deliberately submitted false information in any required report to the FDA or to the sponsor. The proposed rule is consistent with recently issued guidance from the FDA explaining the disqualification process.5
However, under the proposed rule, the consequences of disqualification – both for the investigator and for sponsors – is expanded in two important respects. First, disqualified investigators would be ineligible to conduct any clinical investigations that support an application for a research or marketing permit for any products regulated by the FDA.6 This would include all applications for a research or marketing permit for any new drug, biologic, device, new animal drug, food or dietary supplements that bears a nutrient content claim or a health claim, infant formula, food and color additive, and tobacco product.
Second, under the amended rule, the FDA would examine each application for any new product that contains data reported by a disqualified investigator to determine whether the investigator has submitted unreliable data that are essential either to the continuation of any investigation, the approval or clearance of any marketing application, or the continued marketing of an FDA-regulated product.7
If the proposed rule is made final, clinical trial sponsors would need to ensure that their screening procedures for investigators identify all individuals involved in FDA disqualification procedures, not only those disqualified for violations related to a particular class of product.8 The FDA reports that it initiates an average of six new disqualification proceedings each year. Sponsors should also be aware that a Good Clinical Practices (GCP) violation under the jurisdiction of one FDA Center by an investigator used by the company may prompt FDA action on investigations and approvals or clearances under the jurisdiction of another FDA Center.9
Finally, as recommended by the GAO report on oversight of clinical investigators, it is possible that in the future the FDA may pursue expanded statutory authority to debar individuals involved in felonies or misdemeanors related to medical device research or marketing applications. Under FDA's existing statutory authority, the agency can administratively debar an individual from performing services in any capacity in the pharmaceutical industry if, among other things, the individual has been convicted of a criminal violation related to the development or approval of a pharmaceutical product.10 The GAO report recommended that the FDA "pursue debarment authority for medical devices that is consistent with the current debarment authority for drugs and biologics and prohibit any debarred individual from involvement with drugs, biologics, and medical devices."11 The FDA's current debarment authority is limited to prohibiting conduct involving drug or biologic applications and food importation.12