Clinical Investigator Administrative Actions - Disqualification: Guidance for Institutional Review Boards, Clinical Investigators, and Sponsors

Administrative guidance, not enacted legislation. This captured publisher edition preserves the listed document and attachments; later developments are not independently consolidated.

Contains Nonbinding Recommendations
Clinical Investigator
Administrative Actions
– Disqualification
Guidance for Institutional
Review Boards, Clinical
Investigators, and Sponsors
Document issued in December 2022
Document originally issued in May 2010
This document supersedes the Information Sheet - Clinical Investigator Administrative
Actions – Disqualifications issued March 2014.
Additional copies are available from:
Office of Clinical Policy
Food and Drug Administration
10903 New Hampshire Ave, WO32-5103
Silver Spring, MD 20993
Phone: 301-796-8340
Email: gcpquestions@fda.hhs.gov
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/clinical-trials-
guidance-documents
U.S. Department of Health and Human Services
Food and Drug Administration
Office of Clinical Policy

Contains Nonbinding Recommendations
Clinical Investigator
Administrative Actions
– Disqualification
Guidance for Institutional
Review Boards, Clinical
Investigators, and Sponsors
NOTE: FDA made the following updates to the guidance in December 2022:
 	In Section D and footnote 12, updated the reference to the recently published
FDA Staff Manual Guide on disqualification proceedings.
 	In the References Section, updated references and website links to reflect current
versions of the referenced documents.
For questions regarding this document, please contact gcpquestions@fda.hhs.gov.
U.S. Department of Health and Human Services
Food and Drug Administration
December 2022
Good Clinical Practice

Contains Nonbinding Recommendations
TABLE OF CONTENTS
I. 	INTRODUCTION............................................................................................................. 1
II. 	DISCUSSION .................................................................................................................... 1
A. 	The Disqualification Process ......................................................................................................... 1
1. Notice of Initiation of Disqualification Proceedings and Opportunity to Explain .......................... 2
2. Consent Agreement .......................................................................................................................... 2
3. Notice of an Opportunity for Hearing on Proposed Disqualification ............................................. 3
4. Part 16 Hearing and Final Decision on Disqualification ............................................................... 3
5. Actions upon Disqualification.......................................................................................................... 4
B. 	Criminal Prosecutions ................................................................................................................... 5
C. 	Disclosure of Information Regarding Disqualification Proceedings ......................................... 5
D. 	Reinstatement of a Disqualified Investigator .............................................................................. 6
III. 	REFERENCES.................................................................................................................. 6

Contains Nonbinding Recommendations
Clinical Investigator Administrative Actions – Disqualification
Guidance for Institutional Review Boards, Clinical Investigators,
and Sponsors1
This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on
this topic. It does not establish any rights for any person and is not binding on FDA or the public. You
can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations.
To discuss an alternative approach, contact the FDA staff responsible for this guidance as listed on the
title page.
I. 	INTRODUCTION
This guidance document is intended to inform institutional review boards (IRBs), clinical
investigators, and sponsors about the administrative action of disqualifying a clinical investigator
from participating in studies involving investigational new drugs (including biologics) or
devices.1 FDA may disqualify a clinical investigator from receiving investigational drugs
(including biologics) and devices if FDA determines that the investigator has repeatedly or
deliberately violated the agency’s regulations, or has repeatedly or deliberately submitted false
information to the sponsor or FDA in any required report.2
In general, FDA’s guidance documents do not establish legally enforceable responsibilities.
Instead, guidances describe the Agency’s current thinking on a topic and should be viewed only
as recommendations, unless specific regulatory or statutory requirements are cited. The use of
the word should in Agency guidances means that something is suggested or recommended, but
not required.
II. 	DISCUSSION
A. 	The Disqualification Process
1 This guidance has been prepared by the Office of Clinical Policy (OCliP), in coordination with the Office of
Medical Policy in the Center for Drug Evaluation and Research (CDER), the Center for Biologics Evaluation and
Research (CBER), the Center for Food Safety and Applied Nutrition (CFSAN), Center for Devices and Radiological
Health (CDRH), and Center for Tobacco Products (CTP) at the Food and Drug Administration; however,
disqualification actions may also be initiated for investigators who conduct studies in support of Investigational New
Animal Drug Applications (INAD) or New Animal Drug Applications (NADA) under 21 CFR 511.1.
2 See 21 CFR 312.70 and 812.119. Disqualification of clinical investigators conducting studies to support INADs or
NADAs is authorized in 21 CFR 511.1(c).
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Contains Nonbinding Recommendations
1. 	Notice of Initiation of Disqualification Proceedings and Opportunity to Explain
FDA’s field staff conduct on-site inspections of clinical investigators involved in the
investigation of FDA-regulated products. FDA performs these inspections of clinical
investigators to evaluate their practices and procedures to determine compliance with applicable
regulations. FDA conducts many such routine (i.e., “surveillance”) inspections each year. In
addition, FDA may receive information about potential misconduct, and typically conducts an
inspection of an investigator’s site to determine the investigator’s compliance.3
If, as a result of the inspection, FDA notes repeated or deliberate violations or potential repeated
or deliberate violations, the FDA Center4 having jurisdiction over the product used in the study
may initiate the investigator disqualification process by issuing a Notice of Initiation of
Disqualification Proceedings and Opportunity to Explain (NIDPOE). Generally, the Center will
consider issuing a NIDPOE when (1) subjects under the care of the investigator would be or have
been exposed to an unreasonable and significant risk of illness or injury; or (2) subjects’ rights
would be or have been seriously compromised; or (3) data integrity or reliability is or has been
compromised. The NIDPOE describes the alleged noncompliance and/or alleged submission of
false information and offers the investigator an opportunity to explain in writing or, at the option
of the investigator, at an informal conference with FDA. The NIDPOE specifies certain time
frames for the investigator to respond to FDA.
If the investigator requests an informal conference, it will be held at the Center as soon as
possible following the request. The investigator may bring an attorney. The informal conference
may be transcribed, but the meeting is informal, and no prescribed format is required or
suggested. After the meeting, the Center will review any new evidence or explanation and decide
whether to proceed with the matter. In the event the Center accepts the investigator’s
explanation, the Center will notify the investigator in writing of this decision.
2. 	Consent Agreement
The Center provides a consent agreement to the investigator with the NIDPOE. Rather than
contest the allegations set forth in the NIDPOE, the clinical investigator may opt to enter into a
consent agreement. In general, the terms of a consent agreement provide that the investigator
agrees that he or she will no longer conduct studies with investigational products.
The investigator may sign the consent agreement at any time during the disqualification process
including up to the issuance of a Commissioner’s decision.5
Consent agreements generally take one of two forms: (1) the investigator agrees to be
disqualified and is no longer eligible to receive investigational products. This agreement has the
same effect as a disqualification after a Part 16 hearing and terminates the disqualification
administrative proceeding; or, (2) the investigator, after discussions with the FDA, including an
3 See “Guidance For IRBs, Clinical Investigators, and Sponsors:
FDA Inspections of Clinical Investigators,” at https://www.fda.gov/media/75185/download.
4 Center for Drug Evaluation and Research, Center for Devices and Radiological Health, or Center for Biologics
Evaluation and Research.
5 The Commissioner issues his or her decision pursuant to 21 CFR 16.95, and 21 CFR 312.70 or 812.119.
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Contains Nonbinding Recommendations
explanation of the alleged violations in writing or at an informal conference, agrees to specific
restrictions in the use of investigational products, such as oversight of the investigator’s conduct
of an investigational study by an individual acceptable to both the investigator and FDA. If the
investigator violates the restricted consent agreement, FDA can reinitiate the disqualification
proceeding.
3. 	Notice of an Opportunity for Hearing on Proposed Disqualification
If the investigator’s explanation (either in writing or during an informal conference) is not
accepted by FDA or if the investigator fails to respond to the NIDPOE within the specified time
period, FDA will offer the investigator an opportunity for an informal regulatory hearing under
21 CFR part 16 (Part 16 hearing) to determine whether the investigator should remain eligible to
receive certain investigational products. FDA initiates a Part 16 hearing by sending the
investigator a Notice of Opportunity for Hearing (NOOH).
The NOOH specifies the facts and other relevant information that are the subject of the Part 16
hearing. If the investigator does not respond within the time period specified in the NOOH, FDA
considers the offer for a hearing to have been waived, and no informal Part 16 hearing will be
held (see 21 CFR 16.22(b)). The Commissioner will consider the information in the
administrative record to determine whether to disqualify the investigator.
4. 	Part 16 Hearing and Final Decision on Disqualification
If the investigator requests a Part 16 hearing and there is a genuine and substantial issue of fact
that warrants a hearing,6 the Commissioner will designate a presiding officer to schedule and
conduct the hearing.
Once the hearing is granted, either party (i.e., the Center or the clinical investigator) may move
for summary decision on any or all of the issues. The presiding officer reviews any motions filed,
issues a summary decision on the issues raised, and determines whether there exists any genuine
and substantial issue of fact to be decided at a hearing. (See 21 CFR 16.26(b)). The summary
decision issued will be incorporated into a presiding officer’s report.
In the alternative, if a hearing is scheduled pursuant to 21 CFR 16.24, the Center and the
investigator will, if feasible, exchange written notices of any published articles or written
information to be presented or relied upon at the hearing (21 CFR 16.24(g)).
6 “A request for a hearing may be denied, in whole or in part, if the Commissioner or the FDA official to whom
authority is delegated to make the final decision on the matter determines that no genuine and substantial issue of
fact has been raised by the material submitted.” (21 CFR 16.26(a)). A hearing will not be granted on issues of policy
or law; or mere allegations or denials of the moving party’s evidence but must present evidence of its own that
establishes a genuine issue of fact. If there are no genuine disputes of fact, summary decision is appropriate.
An example of a genuine and substantial issue of fact that might warrant a hearing is whether an investigator’s
repeated changes to data were legitimate corrections as asserted by the investigator or whether the changes were
made fraudulently to alter the outcome of the clinical trial. In this example, the presiding officer might assess during
the part 16 hearing the veracity of the investigator’s statements about the legitimacy of changes to the data.
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Contains Nonbinding Recommendations
Part 16 hearings are informal, and the rules of evidence do not apply. This means any participant
may comment upon or rebut all data, information, and views presented (21 CFR 16.60(c)). The
hearing begins with Center staff/counsel giving a full and complete statement of the action that is
the subject of the hearing and describing the information and reasons supporting disqualification.
Center staff/counsel 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. The hearing consists primarily of the presentation of oral or
written information, and direct and reasonable cross-examination. (See 21 CFR 16.60(b)).
After the hearing, the presiding officer prepares a written report of the hearing (see 21 CFR
16.60(e)). All written material presented at the hearing will be attached to the report and
becomes part of the administrative record along with the hearing transcript (see 21 CFR 16.80).
The presiding officer’s report includes a recommended decision and the reasons for the
recommendation. When time permits, the parties are given the opportunity to review and
comment on the presiding officer’s report (21 CFR 16.60(e)).
The report and any comments of the parties are transmitted to the Commissioner who considers
them as part of the administrative record to determine whether the investigator should be
disqualified. The Commissioner then issues a written decision giving the basis for the final
action taken. (See 21 CFR 16.95(b)).
5. 	Actions upon Disqualification
If the Commissioner or his or her designee determines that the investigator has repeatedly or
deliberately failed to comply with the applicable regulatory requirements, or has repeatedly or
deliberately submitted to FDA or to the sponsor false information in any required report, the
Commissioner will disqualify the investigator, and:
(a) Notify the investigator, the sponsor of any investigation in which the investigator has
been named as a participant, and the reviewing IRBs that the investigator is not eligible to
receive certain investigational products. The notification to the investigator, sponsor, and
IRBs will provide a statement of the basis for this determination. The notification also
will explain that an investigator determined to be ineligible to receive those
investigational products will be ineligible to conduct any clinical investigation that
supports an application for a research or marketing permit for products regulated by
FDA. (21 CFR 312.70(b) and 812.119(b)).
(b) Notify the sponsor(s) of studies involving the investigational drug or device, and the
sponsors of each approved or cleared application submitted under 21 CFR parts 314, 814,
or 807, subpart E, containing data reported by the disqualified investigator, that each
investigational new drug application (IND), investigational device exemption (IDE), and
each approved and cleared application will need to be examined to determine whether the
investigator has submitted unreliable data that are essential to the continuation of the
investigation or essential to the approval or clearance of any marketing application, or
essential to the continued marketing of an FDA-regulated product. (21 CFR 312.70(c)
and 812.119(c)).
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Contains Nonbinding Recommendations
(c) Determine whether the studies involving the investigational drug or device may
continue.7 If the Commissioner determines, after unreliable data submitted by the
disqualified investigator are eliminated from consideration, that the data remaining are
inadequate to support a conclusion that it is reasonably safe to continue the investigation,
the Commissioner will notify the sponsor who 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 and the
reviewing IRBs of the termination.8 The sponsor will then have an opportunity for a Part
16 regulatory hearing to determine whether the IND or IDE should be reinstated.9 (21
CFR 312.70(d) and 21 CFR 812.119(d)).
(d) Determine whether the continued approval of the product is justified (e.g., any approved
product for which the investigator’s data were pivotal to FDA decision-making). If
continued approval is not justified, the Commissioner will proceed to withdraw approval
of the product in accordance with applicable provisions of the Federal Food, Drug, and
Cosmetic Act. (21 CFR 312.70(e) and 812.119(e)).
B. 	Criminal Prosecutions
A disqualification does not preclude initiation of criminal proceedings against an investigator.
Those investigators referred for criminal investigation are generally clinical investigators who
have knowingly or willfully violated the regulations or statutes.
C. 	Disclosure of Information Regarding Disqualification Proceedings
When FDA issues a NIDPOE to a clinical investigator, the agency provides a copy of the letter
to the reviewing IRB and study sponsor. In addition, if the clinical investigator is disqualified,
FDA will disclose the disqualification action to the IRB and sponsor.10 IRBs and sponsors play a
significant role in ensuring that clinical investigators meet applicable statutory and regulatory
requirements. This disclosure is necessary and appropriate for IRBs and sponsors to be aware of
findings indicating violations or potential violations of the laws and regulations enforced by
FDA.
In some cases, evidence of a violation or potential violation may implicate more than one of the
clinical investigator’s studies. If so, FDA may, where appropriate, share information concerning
a violation or potential violation with the sponsors and IRBs of any of the clinical investigator’s
studies.
7 FDA may determine that further use of the investigational product should be suspended at the investigator’s site
(or a more broad suspension, depending on the circumstances). However, if this suspension could create a life-
threatening situation for a subject under the disqualified investigator’s care, FDA may permit that subject to
continue to receive or use an investigational product. Matters where a subject may be at risk if the study is
suspended, among other relevant matters, may be brought to the agency’s attention during the regulatory hearing.
8 Note: A danger to 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.
9 The determination that an investigation may not be considered in support of a research or marketing application, or
a notification or petition submission does not, however, relieve the sponsor of any obligation under any other
applicable regulation to submit to FDA the results of the investigation. (21 CFR 312.70(d) and 21 CFR 812.119(d)).
10 See 63 Federal Register, October 19, 1998, at 55873.
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Contains Nonbinding Recommendations
In accordance with the above, FDA posts on FDA’s Web page11 a listing of investigators who:
 	are ineligible to receive FDA-regulated investigational products or have agreed to some
restricted use of FDA regulated investigational products,
 	have had restrictions removed,
 	were issued NIDPOEs,
 	were issued NOOH letters, and
 	were the subject of presiding officer reports and Commissioner’s decisions in clinical
investigator disqualification proceedings.
The Web page is updated regularly. FDA encourages IRBs and study sponsors to consult this
listing for information about clinical investigators’ compliance with FDA regulations.
D. 	Reinstatement of a Disqualified Investigator
An investigator who has been disqualified may be reinstated if the Commissioner determines that
the investigator has presented adequate assurances that the investigator will employ all
investigational products and will conduct any clinical investigation that supports an application
for a research or marketing permit for products regulated by FDA solely in compliance with
FDA regulations. For more information, please see the Agency’s reinstatement guidelines,
entitled “FDA Consideration of Reinstatement Requests from Disqualified Clinical
Investigators.”12
III. 	REFERENCES
1. 	FDA/ORA Compliance Program Guidance; Program 7348.811, Chapter 48 – Bioresearch
Monitoring; Subject: Clinical Investigators and Sponsor-Investigators, issued July 20,
2020; available at
http://www.fda.gov/downloads/ICECI/EnforcementActions/BioresearchMonitoring/ucm1
33773.pdf.
2. 	Regulatory Procedures Manual, Chapter 5 – Administrative Actions, section 10 –
Disqualification of Clinical Investigators; available at
https://www.fda.gov/media/77026/download.
3. 	FDA Staff Manual Guides, Volume IV – Agency Program Directives, Compliance
Activities, Disqualification of a Clinical Investigator: The Hearing Process, SMG 7711
(effective Aug. 25, 2014, and changed on Jan. 16, 2020); available at
https://www.fda.gov/media/80788/download.
11 See Clinical Investigators – Disqualification Proceedings, at http://www.fda.gov/disqualificationproceedings.
12 See FDA Staff Manual Guides, Volume IV – Agency Program Directives, Compliance Activities, FDA
Consideration of Reinstatement Requests from Disqualified Clinical Investigators, SMG 7715, (Sep. 2, 2021) at
https://www.fda.gov/media/151976/download.
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