FDA Finalizes Rules on Clinical Investigator Disqualification

By Nisha P. Shah –

FDA issued a final rule that amends the regulations to expand the scope of disqualification of clinical investigators.  77 Fed. Reg. 25353 (Apr. 30, 2012).  We previously reported on the proposed rule issued in April 2011, and there are no substantive changes between the proposed and final rules.  Under the final rule, a clinical investigator, including a sponsor-investigator, disqualified pursuant to 21 C.F.R. Parts 312 (drugs and biologics), 511 (animal drugs), or 812 (devices) will be ineligible to conduct any clinical investigation supporting an application for a research or marketing permit for FDA-regulated products, including “drugs, biologics, devices, new animal drugs, foods, including dietary supplements, that bear a nutrient content claim or a health claim, infant formulas, food and color additives, and tobacco products.”  In other words, the amended rule closes a gap in the regulations.  An investigator who is disqualified and ineligible to receive one type of investigational product (e.g., drugs) will now be ineligible to conduct clinical studies that support marketing applications for other types of products regulated by FDA.  The rule is effective May 30, 2012. 

The procedural steps for disqualifying investigators essentially remain the same.  Certain changes are meant to harmonize the investigator disqualification regulations across the FDA-regulated industries.  For instance, similar to the medical device regulations, FDA adds to 21 C.F.R. Parts 312 (drugs and biologics) and 511 (animal drugs) that the applicable FDA Center will initiate disqualification proceedings when the Center has information indicating that a clinical investigator has “repeatedly or deliberately” failed to comply with the relevant requirements or has “repeatedly or deliberately” submitted to FDA or to the sponsor of the investigation false information in any required report.  Previously, the drug and animal drug regulations applied the “repeatedly or deliberately” qualifier to the failure to comply allegations, but not to the submission of false information allegations. 

FDA will continue to issue to the investigator written notice of the allegations, and allow the investigator to respond in writing or in an informal conference.  If the response is unsatisfactory to the applicable Center, the investigator will be given an opportunity for a regulatory hearing under 21 C.F.R. Part 16.  The final rule adds a notification to reviewing institutional review boards (“IRBs”) about the investigator’s disqualification, in addition to the current notification requirements to the investigator and sponsor.  The preamble explains that FDA will provide a redacted copy of the investigator’s notice of initiation of disqualification proceedings and opportunity to explain (“NIDPOE”) letter to the study sponsor and IRBs.  77 Fed. Reg. at 25355.  If an investigator is deemed to be disqualified, a notification will be sent to the investigator, study sponsors, and reviewing IRBs that explains the basis for FDA’s determination.  This notice is also posted on FDA’s website.

Significantly for study sponsors, the final regulations will continue to permit the Commissioner to examine whether continued approval or clearance of a product for which data were submitted by the disqualified investigator is not justifiable and that approval or clearance of the product be withdrawn.  In the preamble, FDA explains that all products for which the investigator submitted data are subject to scrutiny, not only those products that caused the disqualification.  77 Fed. Reg. at 25356.  FDA also clarifies that products that have been on the market for a long period of time without significant safety concerns “would probably remain on the market if sufficient reliable product-approval data support the continued approval of the product.”  77 Fed. Reg. at 25355.  To support continued marketing of a product, the Agency may request from study sponsors statistical analyses of study results after eliminating the disqualified investigator’s data.  77 Fed. Reg. at 25356.  Further, FDA may take steps to terminate studies conducted by the disqualified investigator. 

Finally, a disqualified investigator may be reinstated as eligible to receive a test article when the Commissioner determines that the investigator has presented adequate assurances that the investigator will use test articles and conduct clinical investigations in compliance with the applicable clinical trial regulations.  FDA stated it will notify interested parties of the reinstatement and will post a list of these investigators on its website.