Guidance for Institutional Review Boards and Clinical Investigators

This information sheet focuses on the applicability of regulatory sanctions to clinical investigators participating in studies involving investigational new drugs, antibiotics, biologics, medical devices, medical foods or food additives. [Note: Although this information sheet refers to human subjects in the context of an Investigational New Drug Application (IND), analogous principles apply to animal subjects in an Investigational New Animal Drug Application (INAD).]

Regulations do not state that hearings will be held at FDA headquarters. Investigators may suggest another location. Hearings can be denied if investigators fail to submit any information that raises any question of fact.

The Disqualification Process

Informal Conference or Written Explanation

FDA may disqualify clinical investigators from receiving investigational drugs, biologics and devices only when the investigator has repeatedly or deliberately violated the Agency's regulations, or has submitted false information to the sponsor in a required report. The appropriate FDA Center will send the investigator a written notice describing the noncompliance or false submission and offer the investigator an opportunity to respond to the notice at an informal conference or in writing. The Agency will specify a time period within which the investigator must respond. While the conference is informal, a transcript may be made, and the investigator may have legal representation.

If the investigator offers a timely and satisfactory explanation for the noncompliance, and the Center accepts, the process is terminated and the investigator is so notified in writing. If, however, the investigator offers an explanation that the Center rejects, or if the investigator fails to respond within the specified time period, FDA will offer the investigator an opportunity for an informal regulatory "Part 16" hearing under the Agency's regulations [21 CFR part 16] to determine whether the investigator should remain eligible to receive investigational test articles.

Notice of an Opportunity for Hearing on Proposed Disqualifications

FDA initiates a Part 16 hearing when it sends the investigator a written Notice of Opportunity for Hearing. The Notice specifies the allegations and other relevant information that is the subject of the hearing. If the investigator does not respond within the time period specified in the letter, FDA considers the offer to have been refused, and no informal hearing will be held. The Commissioner will then consider the information available to FDA to determine whether the investigator should be disqualified.

If a hearing is requested, the Commissioner will designate a presiding officer from the Office of Health Affairs (OHA), and the hearing will take place at a mutually agreeable time at FDA headquarters. If agreement cannot be reached, however, the presiding officer will designate a hearing date acceptable to FDA.

Part 16 Hearing and Final Order on Disqualification

Before the hearing, FDA gives the investigator notice of the matters to be considered at the hearing which includes a comprehensive statement of the basis for the proposal to disqualify the investigator and a general summary of the information that the Center will present. The Center and the investigator exchange written notices of any published articles or written information to be presented or relied upon at the hearing. If it seems unreasonable to expect the other party to have, or to be able to obtain, a copy of a particular document, a copy of the document is provided. The investigator or the Center may each file a motion for summary decision.

Part 16 hearings are informal, and the rules of evidence do not apply. Any participant may comment upon or rebut all data, information, and views presented. The presiding officer conducts the hearing. The hearing begins with Center staff giving a complete statement of the action that is the subject of the hearing and describing the information and reasons supporting disqualification. They may present any oral or written information relevant to the hearing. The investigator, who may be represented by legal counsel, then may present any oral or written information relevant to the hearing.

After the hearing, the OHA presiding officer prepares a written report. This report includes a recommended decision and the reasons for the recommendation. The administrative record of the hearing includes all written material presented at the hearing and the hearing transcript. The parties are given the opportunity to review and comment on the presiding officer's report. The report and the comments of the parties are transmitted to the Commissioner who considers them along with the administrative record to determine whether the investigator should be disqualified. The Commissioner issues a written decision giving the basis for the action taken.

Actions Upon Disqualification

If the Commissioner determines that the investigator has repeatedly or deliberately failed to comply with the regulatory requirements, or has deliberately or repeatedly submitted false information to the sponsor in any required report, the Commissioner will:

(1) Notify the investigator and the sponsor(s) of any investigation(s) in which the investigator has participated that the investigator is not entitled to receive investigational drugs, biologics or devices. The notification will include a statement explaining the basis for this determination.
(2) Notify the sponsors of studies conducted under each IND, IDE or each approved application containing data reported by the investigator that the Agency will not accept the investigator's work in support of claims of safety and efficacy without validating information establishing that the study results were unaffected by the investigator's misconduct.
(3) After the investigator's data are eliminated from consideration, determine whether the data remaining can support a conclusion that studies under the IND or IDE may continue. If the Commissioner determines that the remaining data are inadequate, the sponsor will be notified and will have an opportunity for a regulatory hearing under 21 CFR part 16. If a danger to public health exists, however, the Commissioner will terminate the IND or IDE immediately and notify the sponsor of the determination. The sponsor will then have an opportunity for a Part 16 regulatory hearing to determine whether the IND or IDE should be reinstated.
(4) After the investigator's data are eliminated from consideration, determine whether the continued approval of the product is justified. If it is not, the Commissioner will move to withdraw approval in accordance with the applicable provisions of the Federal Food, Drug, and Cosmetic Act.

The action to be taken with regard to an ongoing clinical investigation conducted by a disqualified investigator is made on a case-by-case basis. FDA considers the nature of the clinical investigation, the number of subjects involved, the risks to the subjects from discontinuation of the study, and the need for involvement of an acceptable investigator. If another investigator accepts responsibility for the investigation, FDA may allow an investigation to continue. If not, further use of the test article is deferred until another investigator is identified. If this deferment could create a life-threatening situation, FDA may permit a subject to continue to receive or use a test article without a further written statement from the disqualified investigator. The investigator can bring such cases to the Agency's attention during the regulatory hearing, so that the Commissioner may consider this option.

Public Disclosure of Information Regarding Disqualification

A danger to the public health includes not only the subjects' safety in any study in question, but also the safety of subjects in other studies in which the investigator is involved.

The Notice of Opportunity for a Hearing letter is available under the Freedom of Information provisions but is not placed on public display. FDA will notify other government agencies of a proposed disqualification whenever the Agency deems such notification to be appropriate.

If the Agency notifies other parties of its preliminary findings prior to final disqualification, FDA will provide a description of these findings, state that the Agency has yet to reach a final decision on whether the investigator should be disqualified, and will not recommend that action be taken by the third party. If the disqualification proceeding does not result in a disqualification or a consent agreement, FDA will so advise those third parties that had been contacted. A copy of each notification will be sent to the investigator.

If the Agency gives notice of the disqualification of a specific investigator to a third party, FDA will provide a copy of the final disqualification order, explain its legal meaning, and state that FDA is not advising or recommending that the person notified take any action upon the matter. A copy of each notification will be sent to the investigator. The list of investigators who are ineligible to receive investigational new drugs, biologics and devices or who have agreed to some restriction of use of investigational drugs, biologics and devices (see below) is not considered to be a "notice" as discussed above.

Reinstatement of a Disqualified Investigator

Investigators who have been disqualified may be reinstated if the Commissioner determines that the investigators have presented adequate assurances that they will employ investigational drugs, biologics and devices in compliance with FDA regulations. The Agency's reinstatement guidelines, entitled "Procedures for Reinstating Eligibility of Disqualified Clinical Investigators to Receive Investigational Articles" are available by writing to the FOI Staff at the address given below.

Consent Agreements

In addition to an opportunity for an informal conference or to respond in writing to Center allegations, the Center for Drug Evaluation and Research, the Center for Biologics Evaluation and Research, and the Center for Devices and Radiological Health offer investigators the opportunity to enter into a consent agreement whereby the investigator agrees to meet certain conditions mutually acceptable to both FDA and the investigator. This agreement obviates the need to proceed further with the disqualification process. Consent agreements generally take one of two forms: (1) the individual agrees to refrain from further studies with FDA regulated test articles or (2) the individual agrees to specific restrictions in the use of investigational products, such as oversight by an individual acceptable to both the investigator and to the Agency. The consent agreement option remains available to the clinical investigator at all stages of the disqualification process. Most actions have been settled by consent agreements.

Criminal Prosecutions

After a Part 16 proceeding, a final order or entry into a consent agreement constitutes final Agency administrative action. This, however, does not preclude institution of criminal proceedings against an investigator. Those investigators referred for criminal prosecution are generally clinical investigators who have knowingly or willingly submitted false information to a research sponsor.

Additional Information

FDA maintains a list of investigators who are ineligible to receive FDA regulated test articles or who have agreed to some restriction of use of FDA regulated test articles. This list is regularly updated and is not considered to be a "notice" of disqualification (see above). The list is available to the public by writing to the following FDA office.

Freedom of Information Staff (HFI-35)
Food and Drug Administration
5600 Fishers Lane
Rockville, MD 20857.

The list is also available on the internet at: www.fda.gov/ora/compliance_ref/bimo/dis_res_assur.htm