
[Federal Register Volume 77, Number 83 (Monday, April 30, 2012)]
[Rules and Regulations]
[Pages 25353-25361]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2012-10292]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 16, 312, 511, and 812

[Docket No. FDA-2011-N-0079]
RIN 0910-AG49


Disqualification of a Clinical Investigator

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA) is amending the 
regulations to expand the scope of clinical investigator 
disqualification. Under this rulemaking, when the Commissioner of Food 
and Drugs (the Commissioner) determines that an investigator is 
ineligible to receive one kind of test article (drugs, devices or new 
animal drugs), the investigator also will be ineligible to conduct any 
clinical investigation that supports an application for a research or 
marketing permit for other kinds of products regulated by FDA. This 
final rule is based in part upon recommendations from the Government 
Accountability Office (GAO), and is intended to help ensure adequate 
protection of research subjects and the quality and integrity of data 
submitted to FDA. FDA also is amending the list of regulatory 
provisions under which an informal regulatory hearing is available by 
changing the scope of certain provisions and adding regulatory 
provisions that were inadvertently omitted.

DATES: This rule is effective May 30, 2012.

FOR FURTHER INFORMATION CONTACT:  Kathleen E. Pfaender, Office of Good 
Clinical Practice, Food and Drug Administration, 10903 New Hampshire 
Ave., Bldg. 32, Rm. 5129, Silver Spring, MD 20993, 301-796-8340.

SUPPLEMENTARY INFORMATION: 

I. Background

    In the Federal Register of April 13, 2011 (76 FR 20575), FDA 
proposed to amend its regulations to expand the scope of clinical 
investigator disqualification (the April 2011 proposed rule). As 
discussed in greater detail in the preamble to the proposed rule (76 FR 
20575 at 20576 to 20585), when disqualified by a Commissioner's 
decision under one part of the former regulations a clinical 
investigator continued to be eligible to receive other types of test 
articles and conduct

[[Page 25354]]

clinical investigations studying those other test articles.
    The GAO, in its September 2009 final report on FDA's oversight of 
clinical investigators (Ref. 1), recognized FDA's regulatory 
limitations regarding clinical investigator disqualification. In its 
September 2009 final report, the GAO recommended, among other things, 
that FDA extend disqualification by a Commissioner's decision to 
include ineligibility to receive unapproved drugs, biologics, and 
medical devices. The GAO concluded that it is ``critical for FDA to 
take action--and to have the authority to take action--to prevent 
clinical investigators * * * who engaged in serious misconduct from 
doing so again, whether in research that involves drugs, biologics, or 
devices'' (Ref. 1, at page 42). Among other amended provisions, this 
final rule responds to that GAO report and prevents clinical 
investigators who are disqualified by a Commissioner's decision 
(whether related to drugs, biologics, devices, or animal drugs) from 
conducting any clinical investigations that support an application for 
a research or marketing permit for products regulated by FDA. The other 
amended provisions in this final rule provide for clarity and 
harmonization of the clinical investigator disqualification regulations 
and the addition of inadvertently omitted regulatory provisions under 
which a part 16 (21 CFR part 16) regulatory hearing is available.

II. Overview of the Final Rule

    This final rule amends part 312 (21 CFR part 312) in Sec.  312.70, 
part 511 (21 CFR part 511) in Sec.  511.1(c), and part 812 (21 CFR part 
812) in Sec.  812.119) to provide that when the Commissioner determines 
that a clinical investigator is ineligible to receive the test article 
under that part (e.g., new animal drugs in part 511 or drugs in part 
312), the clinical investigator also is ineligible to conduct any 
clinical investigation that supports an application for a research or 
marketing permit for products regulated by FDA, 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.
    Other amendments in this final rule, as explained in the preamble 
to the proposed rule, help to clarify and harmonize the clinical 
investigator disqualification regulations in parts 312, 511, and 812 
(21 CFR part 812). Also, this final rule amends certain provisions in 
part 16 (21 CFR part 16) by:
     Adding to Sec.  16.1(b)(2) an entry for Sec.  812.119;
     Revising the entries for Sec. Sec.  312.70 and 
511.1(c)(1); and
     Adding to the list of regulatory provisions under which a 
part 16 regulatory hearing is available, provisions for:
    [cir] Sec.  58.204(b) (21 CFR 58.204(b)), relating to disqualifying 
a testing facility, and
    [cir] Sec.  822.7(a)(3) (21 CFR 822.7(a)(3)), relating to an order 
to conduct postmarket surveillance of a medical device under section 
522 of the Federal Food Drug and Cosmetic Act (FD&C Act) (21 U.S.C. 
3601).
    On its own initiative, FDA modified the codified language published 
in the April 2011 proposed rule (76 FR 20575), to remove ``pursuit of'' 
from the proposed provisions in Sec. Sec.  312.70(a), 511.1(c)(1), and 
812.119(a). FDA made this change to clarify the rule and eliminate 
unnecessary language. In this final rule, therefore, the relevant 
language is ``If an explanation is offered and accepted by the 
applicable Center, the Center will discontinue the disqualification 
proceeding'' (see in this document codified Sec. Sec.  312.70(a), 
511.1(c)(1), and 812.119(a)).
    This final rule helps to protect the rights and safety of subjects 
involved in FDA-regulated investigations, and helps to ensure the 
reliability and integrity of the data used to support marketing of 
products regulated by FDA.

III. Comments on the Proposed Rule

    FDA received two comments on the proposed rule: One from a 
healthcare professional and the other from regulated industry. Both 
submissions supported the proposal to help ensure adequate protection 
of research subjects and the quality and integrity of data submitted to 
FDA. The healthcare professional supported the proposal and had no 
other comment. The following comments and responses summarize and 
address the issues found in the submission from regulated industry:
    (Comment 1) The comment suggests that FDA either clarify or define 
the terms ``repeatedly or deliberately'' or alternatively consider 
removing the language from Sec.  812.119(a). The comment further asks 
that FDA consider how much data or what frequency constitutes 
``repeatedly''; and for ``deliberately'', how FDA proposes to determine 
deliberate actions. The comment requests examples.
    (Response) The interpretations of the terms ``repeatedly'' and 
``deliberately'' in FDA's regulations governing disqualification of 
clinical investigators are well established. The term ``repeatedly'' 
means, simply, more than once.\1\ A violation occurs ``repeatedly'' if 
it happens more than once.\2\
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    \1\ See, e.g., Commissioner's Decision, In the Matter of William 
H Ziering, M.D. (2008), at page 7. ``The term `repeatedly,' as it is 
used in 21 CFR 312.70(b), is given its plain meaning, such that a 
clinical investigator may be found to have acted `repeatedly' if he 
or she engages in proscribed conduct `more than once.' '' (http://www.fda.gov/downloads/RegulatoryInformation/FOI/ElectronicReadingRoom/UCM144019.pdf).
    \2\ See, In The Matter of James A. Halikas, Jr., M.D., 
Commissioner's Decision (January 17, 2001); In The Matter of Huibert 
M Vriesendorp, M.D., Commissioner's Decision (December 31, 2001). 
See also, Commissioner's Decision, In the Matter of William H 
Ziering, M.D. (2008). (http:[sol][sol]www.fda.gov/
RegulatoryInformation/FOI/ElectronicReadingRoom/ucm143242.htm).
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    FDA may consider disqualification if a clinical investigator 
commits a regulatory violation more than one time within a single study 
(e.g., enrolling in a single study two study subjects who were 
ineligible because of concomitant illnesses that put those subjects at 
greater risk) or one time in each of two studies (e.g., enrolling in 
each of two studies, a study subject who was ineligible because of a 
concomitant illness putting the subject at greater risk). The 
Commissioner, in past decisions, has determined that multiple 
violations within a single study constitute repeated violations 
sufficient to support disqualification from receipt of test 
articles.\3\
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    \3\ See, e.g., Commissioner's Decision, In the Matter of James 
A. Halikas (2001), at page 23 (``[T]o interpret repeatedly to mean 
transgressions in more than one study would permit an investigator 
to commit as many violations of the regulations as he/she wished 
without possibility of disqualification as long as that investigator 
limited his/her violations to one study. Such a result * * * would 
be absurd.'') (http:[sol][sol]www.fda.gov/RegulatoryInformation/FOI/
ElectronicReadingRoom/ucm143242.htm). See also Commissioner's 
Decision, In the Matter of Layne O. Gentry (2008), at page 23. 
(http:[sol][sol]www.fda.gov/downloads/RegulatoryInformation/FOI/
ElectronicReadingRoom/UCM143906.pdf).
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    The term ``deliberately'' includes conduct that is ``willful'' as 
well as conduct demonstrating reckless disregard.\4\ Accordingly, when 
a clinical investigator knowingly fails to comply with FDA's 
regulations, the clinical investigator may be found to have 
deliberately violated the regulations. FDA could pursue the 
disqualification of a clinical investigator, for example, if the 
investigator changed a study's results by altering a data field on a 
case report form to include false data. Likewise, an investigator who 
shows a

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reckless disregard for whether his or her conduct may result in a 
regulatory violation may be found to have deliberately violated the 
regulations.
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    \4\ In The Matter of James A. Halikas, Jr., M.D., Commissioner's 
Decision (January 17, 2001); In The Matter of Huibert M. 
Vriesendorp, M.D., Commissioner's Decision (December 31, 2001); In 
The Matter of Layne O. Gentry, M.D., Presiding Officer Report 
(September 12, 2001). (See http:[sol][sol]www.fda.gov/
RegulatoryInformation/FOI/ElectronicReadingRoom/ucm143242.htm).
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    Decisionmakers in part 16 proceedings have interpreted the term 
``deliberately'' in Sec.  312.70(b) as roughly synonymous with the 
``deliberate indifference'' or ``willful'' standard of intent.\5\ This 
standard does not require specific knowledge that behavior, such as 
submission of false data to a study sponsor, violates the law, but 
reckless disregard for what the regulations require. The Commissioner's 
decision In the Matter of Layne O. Gentry \6\ provides a useful 
discussion of the standard for ``deliberate'' behavior in a 
disqualification proceeding: \7\
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    \5\ See, e.g., Commissioner's Decision, In the Matter of William 
H Ziering, M.D. (2008), at page 8 (``A clinical investigator may be 
found to have acted `deliberately' * * * if he or she knowingly or 
willfully engaged in conduct that violates FDA's regulations or if 
the investigator engaged in conduct that demonstrated a reckless 
disregard for compliance with FDA's regulations.'') See 
http:[sol][sol]www.fda.gov/downloads/RegulatoryInformation/FOI/
ElectronicReadingRoom/UCM144019.pdf.
    \6\ On June 18, 2008, Dr. Gentry was determined ineligible to 
receive investigational drugs. See http:[sol][sol]www.fda.gov/
downloads/RegulatoryInformation/FOI/ElectronicReadingRoom/
UCM143906.pdf.
    \7\ Id. at pages 20-21.

* * * the term ``deliberate,'' when used to describe a category of 
violations that might lead to legal consequences, does not 
necessarily require a showing of subjective intent on the part of 
the person in question. * * * the purpose of [disqualification] is 
to protect the safety of patients and to preserve the integrity of 
the data needed to assess the safety and effectiveness of drugs 
before being sold to the general public through disqualifying 
investigators who do not fulfill the responsibilities imposed on 
them.
    In the context of such a remedial, as opposed to punitive, 
scheme, an objective standard for ``deliberate'' or ``deliberately'' 
is a better fit because the inquiry should focus on preventing risk 
rather than imposing punishment for culpable conduct. Even if the 
investigator did not intend for the violations to occur, conduct 
demonstrating a reckless disregard for the regulatory requirements 
calls into question the investigator's fitness for conducting 
clinical trials. * * *

    Therefore, to sustain a finding of repeated or deliberate 
submission of false information, FDA must show that the clinical 
investigator repeatedly submitted to the sponsor or to FDA false 
information, whether in a single study or in multiple studies, or 
submitted false information to the sponsor or FDA knowingly or 
willfully or with reckless disregard for the truthfulness of the data 
submitted.
    (Comment 2) The comment asks how far back FDA will investigate FDA-
approved products with a disqualified investigator's data; and requests 
an explanation of how FDA handles products that have been on the market 
for a longer period of time without significant safety concerns.
    (Response) FDA uses its best efforts to identify each application 
and submission to FDA that may include data from a disqualified 
clinical investigator. FDA does not place limits on how far back FDA 
will investigate to find those applications and submissions that may be 
affected by a disqualified investigator who conducted trials with FDA-
regulated test articles.
    Each application or submission identified as containing data 
reported by a disqualified investigator is subject to examination to 
determine whether the investigator has submitted unreliable data that 
are essential to the approval of a marketing application or essential 
to the continued marketing of an FDA-regulated product. (See Sec. Sec.  
312.70(c), 511.1(c)(3), and 812.119(c)). This examination may be 
undertaken by FDA or the study sponsor. If the Commissioner determines, 
after the unreliable data submitted by the investigator are eliminated 
from consideration, that the continued approval of the product for 
which the data were submitted cannot be justified, the Commissioner 
will proceed to rescind clearance or withdraw approval of the product 
in accordance with the applicable provisions of the relevant statutes. 
(See Sec. Sec.  812.119(e), 511.1(c)(5), and 312.70(e)).
    Often, there may be sufficient data from sources other than the 
disqualified investigator's data to support the continued approval of 
the product. Those products that have been on the market for a longer 
period of time without significant safety concerns, even though a 
disqualified investigator contributed to the data relied on for 
approval, would probably remain on the market if sufficient reliable 
product-approval data support the continued approval of the product.
    (Comment 3) The comment asks that FDA promptly inform affected 
sponsors of an investigator's disqualification.
    (Response) FDA agrees that sponsors should be informed promptly 
about the disqualification of a clinical investigator. Indeed, FDA 
informs sponsors at several stages of the disqualification process. 
When FDA initiates a disqualification action, FDA sends to the clinical 
investigator a notice of initiation of disqualification proceedings and 
opportunity to explain (NIDPOE) letter. Following confirmed receipt of 
the NIDPOE letter by the clinical investigator, FDA provides a redacted 
copy of the letter to the study sponsor and reviewing institutional 
review boards (IRBs) (see Ref. 2, section II.C., at page 8), and posts 
the redacted NIDPOE letter on FDA's Web site.\8\ The posted NIDPOE 
letter is intended to inform sponsors and others who may have an 
interest that FDA is initiating an administrative proceeding to 
determine whether the clinical investigator should be disqualified from 
receiving test articles.
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    \8\ See http:[sol][sol]www.fda.gov/RegulatoryInformation/FOI/
ElectronicReadingRoom/ucm092185.htm.
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    If the investigator's explanation is not accepted by FDA or if the 
investigator fails to respond to the NIDPOE letter within the specified 
time period, FDA offers the investigator an opportunity for an informal 
regulatory hearing under part 16 to determine whether the investigator 
should remain eligible to receive test articles. FDA initiates a part 
16 hearing by sending to 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 (see Ref. 2, 
id.). FDA posts on its Web site \9\ the names of clinical investigators 
who have been issued a NOOH concerning a disqualification proceeding 
along with the redacted NOOH.
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    \9\ See http://www.fda.gov/RegulatoryInformation/FOI/ElectronicReadingRoom/ucm143240.htm.
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    If the investigator is disqualified, after receiving confirmation 
that the investigator has been notified of his or her disqualification, 
FDA promptly posts on its Web site \10\ the investigator's name and the 
date of the disqualification action. In addition, FDA notifies the 
study sponsor and reviewing IRBs, in writing, about the 
disqualification action (Ref. 2, id.). This notification provides a 
statement of the basis for the Commissioner's disqualification 
determination (see Sec. Sec.  312.70(b), 511.1(c)(2), and 812.119(b)).
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    \10\ See http://www.fda.gov/ICECI/EnforcementActions/DisqualifiedRestrictedAssuranceList/ucm131681.htm.
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    FDA recommends that sponsors routinely check FDA's compliance and 
enforcement Web sites \11\ for information about investigator 
disqualification proceedings that might affect the sponsor's studies. 
Further, in compliance with a sponsor's responsibilities (see, e.g., 
Sec. Sec.  312.53(a), 511.1(b)(7)(i), and 812.43(a)), a sponsor must 
select only investigators qualified by training and experience as 
appropriate experts to investigate the study. A sponsor therefore must 
perform

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due diligence to ensure that an investigator is eligible to receive the 
test article. FDA considers checking FDA's Web site for investigator 
disqualification to be part of a sponsor's due diligence effort before 
selecting a clinical investigator to conduct a sponsor's study.
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    \11\ See http://www.fda.gov/ScienceResearch/SpecialTopics/RunningClinicalTrials/ComplianceEnforcement/default.htm.
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    (Comment 4) The comment recommends that FDA consider the impact of 
investigator disqualification on the submission of results from failed 
investigations to ClinicalTrials.gov.
    (Response) The comment is beyond the scope of this rulemaking as 
the National Institutes of Health (NIH) has the statutory 
responsibility for implementing the provisions under the Public Health 
Service Act, section 402(j), 42 U.S.C. 282(j)--Expanded Clinical Trial 
Registry Data Bank. The NIH proposes to issue new regulations \12\ that 
will prescribe procedures for registering and reporting the results of 
clinical trials at ClinicalTrials.gov in accordance with section 801 of 
the Food and Drug Administration Amendments Act of 2007 (FDAAA, Pub. L. 
110-85, September 27, 2007).
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    \12\ See the Fall 2011 Unified Agenda, Expanded Registration and 
Results Reporting at ClinicalTrials.gov (RIN 0925-AA55), at http://reginfo.gov/public/do/eAgendaViewRule?pubId=201110&RIN=0925-AA55.
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    (Comment 5) The comment recommends that FDA seek input from 
affected sponsors regarding the impact of a clinical investigator's 
disqualification on the validity of clinical trial or marketed product 
data.
    (Response) As discussed in response to Comment 2 in this document, 
upon disqualification of a clinical investigator, each application or 
submission to FDA containing data reported by a disqualified 
investigator is subject to examination (see Sec. Sec.  312.70(c), 
511.1(c)(3), and 812.119(c)). We agree that FDA may seek input from an 
affected study sponsor; for example, FDA may request from the study 
sponsor statistical analyses of study results after eliminating from 
the database the disqualified investigator's data.
    (Comment 6) The comment asks FDA to clarify whether the rule 
applies to ``all sponsors for whom the investigator did work, or only 
those that were subject to the problem that caused the 
disqualification.''
    (Response) This final rule applies to all sponsors who selected the 
clinical investigator to conduct their studies. FDA will assess the 
reliability of any data developed by a disqualified clinical 
investigator.
    (Comment 7) The comment recommends that, because clinical 
investigator disqualification by a Commissioner's decision is a lengthy 
proceeding, FDA consider instituting a process similar to a clinical 
hold ``to prevent these individuals from continuing to conduct clinical 
trials while the disqualification process is underway.''
    (Response) FDA agrees that the use of a clinical hold following 
clinical investigator misconduct may be appropriate in some situations 
and has issued a guidance document indicating this (see Ref. 3). For 
example, FDA may impose a clinical hold on studies where the hold is 
necessary to protect human subjects in the study from an unreasonable 
and significant risk of illness or injury. In such a case, FDA may 
impose a clinical hold based on credible evidence that a clinical 
investigator conducting the study has committed serious violations of 
FDA regulations on clinical trials of human drugs and biologics, 
including parts 312, 50, and 56 (21 CFR parts 50 and 56), or has 
submitted false information to FDA or the sponsor in any required 
report. Such a clinical hold may be imposed on the study in which the 
misconduct occurred or on other studies of drugs or biological products 
in which the clinical investigator is directly involved or proposed to 
be involved if FDA determines that the investigator's misconduct poses 
an ongoing threat to the safety and welfare of such subjects. (See 
Sec. Sec.  312.42(b)(1)(i), 312.42(b)(2)(i), 312.42(b)(3)(iii), and 
312.42(b)(4)(i)) (Ref. 3).
    For medical devices, Sec.  812.30(b) allows for withdrawal of 
approval of an application for an investigational device exemption 
(IDE). Under this provision, FDA may withdraw approval of an 
application if FDA determines that continuation of testing under an IDE 
will result in an unreasonable risk to subjects.
    (Comment 8) The comment recommends that FDA issue guidance on how a 
disqualified investigator's data in applications and submissions to FDA 
is to be handled, segregated, analyzed, and reported.
    (Response) Because each situation is different, FDA evaluates on a 
case-by-case basis the best course of action for handling a 
disqualified clinical investigator's data in applications and 
submissions. For this reason, FDA does not intend to issue guidance to 
address how a disqualified investigator's data should be handled.
    (Comment 9) The comment recommends that FDA state explicitly in the 
rule that when an investigator is disqualified by FDA from studies of 
veterinary drugs the investigator should also be ineligible to 
participate in studies of veterinary biologics regulated by the U.S. 
Department of Agriculture (USDA) under Title 9 of the Code of Federal 
Regulations; and, likewise, that ``USDA should codify a companion rule 
to state that investigators disqualified from participation in studies 
of goods regulated by FDA will also be disqualified from investigations 
of veterinary biologics.''
    (Response) As stated in the preamble to the proposed rule, FDA may 
refer pertinent matters to another Federal, State, or local government 
agency for any action determined appropriate by that agency. Although 
FDA agrees that affected agencies should be aware of judicial 
proceedings and regulatory actions taken involving clinical 
investigators, FDA does not have authority to draft a companion rule to 
be administered by USDA.
    (Comment 10) The comment recommends that FDA notify sponsors when a 
disqualified clinical investigator has been reinstated.
    (Response) We agree that FDA should notify interested parties when 
a clinical investigator is reinstated as eligible to receive FDA-
regulated test articles. Because FDA has no way of knowing who, in 
particular, may be interested in the reinstatement of a certain 
investigator, FDA lists on its Web site those investigators who have 
been reinstated.\13\
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    \13\ See http://www.fda.gov/ICECI/EnforcementActions/DisqualifiedRestrictedAssuranceList/ucm131681.htm.
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IV. Environmental Impact

    The agency has determined under 21 CFR 25.30(h) that this action is 
of a type that does not individually or cumulatively have a significant 
effect on the human environment. Therefore, neither an environmental 
assessment nor an environmental impact statement is required.

V. Legal Authority

    The purpose of disqualifying investigators who violate the 
regulations is to preserve the integrity of data needed to assess the 
safety and effectiveness of an FDA-regulated product before the product 
is made available to the public, and to protect the safety of study 
subjects during the conduct of a clinical investigation and patient 
safety after the approval or clearance of a marketing application.
    Although the concept of disqualification is not explicitly 
mentioned in the FD&C Act, FDA has

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the authority to disqualify clinical investigators who violate FDA's 
regulations. The Supreme Court in Weinberger v. Bentex Pharmaceuticals, 
Inc., 412 U.S. 645, 653 (1973) has recognized that FDA has authority 
that ``is implicit in the regulatory scheme, not spelled out in haec 
verba'' in the statute. As stated in Morrow v. Clayton, 326 F.2d 36, 44 
(10th Cir. 1963): ``[I]t is a fundamental principle of administrative 
law that the powers of an administrative agency are not limited to 
those expressly granted by the statutes, but include, also, all of the 
powers that may fairly be implied therefrom.''
    See Mourning v. Family Publications Service, Inc., 411 U.S. 356 
(1973), and National Petroleum Refiners Association v. FTC, 482 F.2d 
672 (DC Cir. 1973). See also Weinberger v. Hynson, Westcott & Dunning, 
Inc., 412 U.S. 609 (1973); National Nutritional Foods Association v. 
Weinberger, 512 F.2d 688, cert denied, 423 U.S. 827 (1975); United 
States v. Nova Scotia Food Products Corp., 568 F.2d 240, 246-248 (2d 
Cir. 1977); American Frozen Food Institute v. Mathews 413 F.Supp. 548 
(D.D.C. 1976) aff'd per curiam, 555 F.2d 1059 (DC Cir. 1977); National 
Confectioners Association v. Califano, 569 F.2d 690 (DCCir. 1978); and 
National Association of Pharmaceutical Manufacturers v. FDA, 637 F.2d 
877 (2d Cir. 1981).
    ``[R]egulatory acts should be given a practical construction, and 
one which will enable the agency to perform the duties required of it 
by Congress.'' Federal Deposit Ins. Corp. v. Sumner Fin. Corp., 451 
F.2d 898, 904 (5th Cir. 1971). Congressional inaction on proposed 
legislation that would state expressly an agency's authority to act 
does not support an inference that the agency lacks implicit authority 
to act under existing legislation. Red Lion Broadcasting Co. v. FCC, 
395 U.S. 367, 381-382 n. 11 (1969). See also Leist v. Simplot, 638 F.2d 
283, 318 (2d Cir. 1980), affirmed sub nom. Merrill Lynch, Pierce, 
Fenner & Smith v. Curran, 456 U.S. 353 (1982). The Supreme Court has 
often recognized ``the construction of a statute by those charged with 
its administration is entitled to substantial deference.'' United 
States v. Rutherford, 442 U.S. 544 (1979). Board of Governors of FRS v. 
First Lincolnwood, 439 U.S. 234, 248 (1978) (the Court's conclusion 
``is influenced by the principle that courts should defer to an 
agency's construction of its own statutory mandate, Red Lion 
Broadcasting Co. v. FCC, 395 U.S. at 381; Commissioner v. Sternberger's 
Estate, 348 U.S. 187, 199 (1955), particularly when that construction 
accords with well established congressional goals.'' 439 U.S. at 251); 
Bayside Enterprises, Inc. v. NLRB, 429 U.S. 298, 304 (1977); Udall v. 
Tallman, 380 U.S. 1, 16 (1965).
    Under section 701(a) of the FD&C Act (21 U.S.C. 371(a)), the 
Commissioner is empowered to issue regulations for the efficient 
enforcement of the FD&C Act. Regulations issued by the Commissioner 
under section 701(a) of the FD&C Act for determining whether a clinical 
investigation of a drug intended for human use, among other things, was 
scientifically reliable and valid to support approval of a new drug, 
have been upheld by the Supreme Court (Weinberger v. Hynson, Westcott & 
Dunning, Inc.); see also Upjohn Co. v. Finch, 422 F.2d 944 (6th Cir. 
1970); and Pharmaceutical Manufacturers Association v. Richardson, 318 
F.Supp. 301 (D.Del. 1970)).
    Furthermore, sections 505(i), 512(j) and 520(g) of the FD&C Act (21 
U.S.C. 355(i), 360b(j), and 360j(g)) regarding clinical investigations 
that require prior FDA authorization direct the Commissioner to issue 
regulations to protect the public health in the course of those 
investigations. Also, sections 505(i)(1), 512(j), and 520(g)(2)(A) of 
the FD&C Act require that investigations be conducted by ``experts 
qualified by scientific training and experience.'' An investigator who 
repeatedly or deliberately violates the regulations or who repeatedly 
or deliberately submits false information would not be considered a 
qualified expert with the experience required to conduct investigations 
of FDA-regulated articles. Among other stated objectives, the final 
rulemaking is intended to fulfill those mandates.
    The Commissioner therefore concludes that legal authority to issue 
those regulations regarding clinical investigators exists under 
sections 505(i), 512(j), 520(g) and 701(a) of the FD&C Act, as 
essential to protection of the public health and safety and to 
enforcement of the Agency's responsibilities under sections 409, 502, 
503, 505, 506, 510, 512, 513, 514, 515, 518, 519, 520 and 801 of the 
FD&C Act (21 U.S.C. 348, 352, 353, 355, 356, 360, 360b, 360c, 360d, 
360e, 360h, 360i, 360j and 381), as well as the responsibilities of FDA 
under section 351 of the Public Health Service Act (42 U.S.C. 262).

VI. Analysis of Impacts

    FDA has examined the impacts of the final rule under Executive 
Order 12866, Executive Order 13563, the Regulatory Flexibility Act (5 
U.S.C. 601-612), and the Unfunded Mandates Reform Act of 1995 (Pub. L. 
104-4). Executive Orders 12866 and 13563 direct Agencies to assess all 
costs and benefits of available regulatory alternatives and, when 
regulation is necessary, to select regulatory approaches that maximize 
net benefits (including potential economic, environmental, public 
health and safety, and other advantages; distributive impacts; and 
equity). In accordance with Executive Order 12866, FDA has previously 
analyzed the potential economic effects of this final rule. As 
announced in the proposal, the Agency has determined that the rule is 
not a significant regulatory action as defined by Executive Order 
12866. The Agency has not received any new information or comments that 
would alter its previous determination.
    The Regulatory Flexibility Act requires Agencies to analyze 
regulatory options that would minimize any significant impact of a rule 
on small entities. Because this final rule does not impose new 
requirements on any entity and therefore has no associated compliance 
costs, the Agency certifies that the final rule will not have a 
significant economic impact on a substantial number of small entities.
    Section 202(a) of the Unfunded Mandates Reform Act of 1995 requires 
that Agencies prepare a written statement, which includes an assessment 
of anticipated costs and benefits, before proposing ``any rule that 
includes any Federal mandate that may result in the expenditure by 
State, local, and tribal governments, in the aggregate, or by the 
private sector, of $100,000,000 or more (adjusted annually for 
inflation) in any one year.'' The current threshold after adjustment 
for inflation is $136 million, using the most current (2010) Implicit 
Price Deflator for the Gross Domestic Product. FDA does not expect this 
final rule to result in any 1-year expenditure that would meet or 
exceed this amount.

Synopsis

    This rule expands the scope of FDA's disqualification actions so 
that a disqualified clinical investigator is ineligible to receive any 
FDA-regulated test article and ineligible to conduct any clinical 
investigation that supports an application for a research or marketing 
permit for products regulated by FDA. We estimate that there is an 
average of about one matter per year in which clinical investigators 
are ultimately disqualified via a Commissioner's decision, and we do 
not expect that this final rule will impose additional costs. Non-
quantifiable benefits of this final rule would include helping to 
reduce the risk of additional violations in other FDA-regulated 
investigations and helping to ensure the integrity of

[[Page 25358]]

clinical trial data. This final rule will help to reduce the risk to 
human subjects who participate in FDA-regulated investigations, and may 
lead to improved public confidence in the clinical data supporting FDA 
decisions. The full analysis of impacts is presented in Ref. 4 of this 
document.

VII. Paperwork Reduction Act of 1995

    This final rule contains no new collections of information. 
Therefore, clearance by the Office of Management and Budget under the 
Paperwork Reduction Act of 1995 is not required.
    The information collection in Sec.  312.70 pertaining to the 
disqualification of a clinical investigator and an investigator's 
opportunity to respond to FDA is approved under the investigational new 
drug regulations, OMB Control No. 0910-0014; expiration date February 
28, 2013.\14\ The notification of IRBs in Sec.  312.70 is approved 
under OMB Control No. 0910-0130--Protection of Human Subjects; 
Recordkeeping Requirements for Institutional Review Boards (IRBs); 
expiration date April 30, 2014.\15\ The information collection in Sec.  
511.1(c) pertaining to the disqualification of a clinical investigator 
and an investigator's opportunity to respond to FDA is approved under 
the new animal drugs for investigational use regulations OMB Control 
No. 0910-0117; expiration date August 31, 2011 (renewal pending at 
OMB).\16\ The information collection in Sec.  812.119 pertaining to the 
disqualification of a clinical investigator and an investigator's 
opportunity to respond to FDA is approved under the investigational 
device exemptions reports and records in 21 CFR part 812, OMB Control 
No. 0910-0078; expiration date February 28, 2013.\17\ In addition, INDs 
and new drug applications are approved under OMB control number 0910-
0416; animal drug applications, 21 CFR part 514, are approved under OMB 
control number 0910-0032; premarket notification submissions 510(k), 
subpart E, are approved under OMB control number 0910-0120; and 
premarket approvals of medical devices, 21 CFR part 814, are approved 
under OMB control number 0910-0231.
---------------------------------------------------------------------------

    \14\ See http://www.reginfo.gov/public/do/PRAViewICR?ref_nbr=200905-0910-005 (accessed on March 30, 2012).
    \15\ See http://www.reginfo.gov/public/do/PRAViewICR?ref_nbr=200711-0910-003 (accessed on March 30, 2012).
    \16\ See http://www.reginfo.gov/public/do/PRAViewICR?ref_nbr=200806-0910-005 (accessed on March 30, 2012).
    \17\ See http://www.reginfo.gov/public/do/PRAViewICR?ref_nbr=201001-0910-010 (accessed on March 30, 2012).
---------------------------------------------------------------------------

VIII. Federalism

    FDA has analyzed this final rule in accordance with the principles 
set forth in Executive Order 13132. FDA has determined that the rule 
does not contain policies that have substantial direct effects on the 
States, on the relationship between the National Government and the 
States, or on the distribution of power and responsibilities among the 
various levels of government. Accordingly, the Agency has concluded 
that the rule does not contain policies that have federalism 
implications as defined in the Executive order and, consequently, a 
federalism summary impact statement is not required.

IX. References

    The following references have been placed on display in the 
Division of Dockets Management (HFA-305), Food and Drug Administration, 
5630 Fishers Lane, Rm. 1061, Rockville, MD 20852, and may be seen by 
interested persons between 9 a.m. and 4 p.m., Monday through Friday. 
(FDA has verified the Web site addresses, but FDA is not responsible 
for any subsequent changes to the Web sites after this document 
publishes in the Federal Register.)

1. GAO Report to Congressional Requesters--Oversight of Clinical 
Investigators, Action Needed to Improve Timeliness and Enhance Scope 
of FDA's Debarment and Disqualification Processes for Medical 
Product Investigators; GAO-09-807. See http:[sol][sol]www.gao.gov/
new.items/d09807.pdf.
2. See ``Information Sheet Guidance for Institutional Review Boards, 
Clinical Investigators, and Sponsors: Clinical Investigator 
Administrative Actions--Disqualification,'' May 2010, at 
http:[sol][sol]www.fda.gov/downloads/RegulatoryInformation/
Guidances/UCM214008.pdf.
3. See ``Guidance for Industry and Clinical Investigators: The Use 
of Clinical Holds Following Clinical Investigator Misconduct,'' 
September 2004, at http:[sol][sol]www.fda.gov/downloads/
RegulatoryInformation/Guidances/UCM126997.pdf.
4. Full Analysis of Impacts of Final Rule.

List of Subjects

21 CFR Part 16

    Administrative practice and procedure.

21 CFR Part 312

    Drugs, Exports, Imports, Investigations, Labeling, Medical 
research, Reporting and recordkeeping requirements, Safety.

21 CFR Part 511

    Animal drugs, Medical research, Reporting and recordkeeping 
requirements.

21 CFR Part 812

    Health records, Medical devices, Medical research, Reporting and 
recordkeeping requirements.

    Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, 21 CFR parts 
16, 312, 511, and 812 are amended as follows:

PART 16--REGULATORY HEARING BEFORE THE FOOD AND DRUG ADMINISTRATION

0
1. The authority citation for 21 CFR part 16 continues to read as 
follows:

    Authority: 15 U.S.C. 1451-1461; 21 U.S.C. 141-149, 321-394, 
467f, 679, 821, 1034; 28 U.S.C. 2112; 42 U.S.C. 201-262, 263b, 364.


0
2. Section 16.1 is amended in paragraph (b)(2) by numerically adding 
entries for ``Sec.  58.204(b)'', ``Sec.  812.119'', and ``Sec.  
822.7(a)(3)'', and by revising the entries for ``Sec.  312.70'' and 
``Sec.  511.1(c)(1)'' to read as follows:


Sec.  16.1  Scope.

* * * * *
    (b) * * *
    (2) * * *
* * * * *
    Sec.  58.204(b), relating to disqualifying a testing facility.
* * * * *
    Sec.  312.70, relating to whether an investigator is eligible to 
receive test articles under part 312 of this chapter and eligible to 
conduct any clinical investigation that supports an application for a 
research or marketing permit for products regulated by FDA, 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.
* * * * *
    Sec.  511.1(c)(1), relating to whether an investigator is eligible 
to receive test articles under part 511 of this chapter and eligible to 
conduct any clinical investigation that supports an application for a 
research or marketing permit for products regulated by FDA 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.
* * * * *

[[Page 25359]]

    Sec.  812.119, relating to whether an investigator is eligible to 
receive test articles under part 812 of this chapter and eligible to 
conduct any clinical investigation that supports an application for a 
research or marketing permit for products regulated by FDA 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.
* * * * *
    Sec.  822.7(a)(3), relating to an order to conduct postmarket 
surveillance of a medical device under section 522 of the act.
* * * * *

PART 312--INVESTIGATIONAL NEW DRUG APPLICATION

0
3. The authority citation for 21 CFR part 312 continues to read as 
follows:

    Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 360bbb, 371; 
42 U.S.C. 262.


0
4. Section 312.70 is revised to read as follows:


Sec.  312.70  Disqualification of a clinical investigator.

    (a) If FDA has information indicating that an investigator 
(including a sponsor-investigator) has repeatedly or deliberately 
failed to comply with the requirements of this part, part 50 or part 56 
of this chapter, or has repeatedly or deliberately submitted to FDA or 
to the sponsor false information in any required report, the Center for 
Drug Evaluation and Research or the Center for Biologics Evaluation and 
Research will furnish the investigator written notice of the matter 
complained of and offer the investigator an opportunity to explain the 
matter in writing, or, at the option of the investigator, in an 
informal conference. If an explanation is offered and accepted by the 
applicable Center, the Center will discontinue the disqualification 
proceeding. If an explanation is offered but not accepted by the 
applicable Center, the investigator will be given an opportunity for a 
regulatory hearing under part 16 of this chapter on the question of 
whether the investigator is eligible to receive test articles under 
this part and eligible to conduct any clinical investigation that 
supports an application for a research or marketing permit for products 
regulated by FDA.
    (b) After evaluating all available information, including any 
explanation presented by the investigator, if the Commissioner 
determines that the investigator has repeatedly or deliberately failed 
to comply with the requirements of this part, part 50 or part 56 of 
this chapter, or has repeatedly or deliberately submitted to FDA or to 
the sponsor false information in any required report, the Commissioner 
will notify the investigator, the sponsor of any investigation in which 
the investigator has been named as a participant, and the reviewing 
institutional review boards (IRBs) that the investigator is not 
eligible to receive test articles under this part. The notification to 
the investigator, sponsor, and IRBs will provide a statement of the 
basis for such determination. The notification also will explain that 
an investigator determined to be ineligible to receive test articles 
under this part will be ineligible to conduct any clinical 
investigation that supports an application for a research or marketing 
permit for products regulated by FDA, 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.
    (c) Each application or submission to FDA under the provisions of 
this chapter containing data reported by an investigator who has been 
determined to be ineligible to receive FDA-regulated test articles is 
subject to examination to determine whether the investigator has 
submitted unreliable data that are essential to the continuation of an 
investigation or essential to the approval of a marketing application, 
or essential to the continued marketing of an FDA-regulated product.
    (d) If the Commissioner determines, after the unreliable data 
submitted by the 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 shall have an opportunity for a regulatory 
hearing under part 16 of this chapter. If a danger to the public health 
exists, however, the Commissioner shall terminate the IND immediately 
and notify the sponsor and the reviewing IRBs of the termination. In 
such case, the sponsor shall have an opportunity for a regulatory 
hearing before FDA under part 16 on the question of whether the IND 
should be reinstated. 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.
    (e) If the Commissioner determines, after the unreliable data 
submitted by the investigator are eliminated from consideration, that 
the continued approval of the product for which the data were submitted 
cannot be justified, the Commissioner will proceed to withdraw approval 
of the product in accordance with the applicable provisions of the 
relevant statutes.
    (f) An investigator who has been determined to be ineligible under 
paragraph (b) of this section may be reinstated as eligible when the 
Commissioner determines that the investigator has presented adequate 
assurances that the investigator will employ all test articles, 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 the applicable provisions of this chapter.

PART 511--NEW ANIMAL DRUGS FOR INVESTIGATIONAL USE

0
5. The authority citation for 21 CFR part 511 continues to read as 
follows:

    Authority: 21 U.S.C. 321, 351, 352, 353, 360b, 371.


0
6. Section 511.1 is amended by:
0
a. Removing ``the Food and Drug Administration'' and adding in its 
place ``FDA'' in paragraph (b)(4) introductory text, and paragraphs 
(b)(5)(iii), (b)(6), (b)(8)(ii), (b)(9)(i), (d)(2), and (f)(1).
0
b. Revising paragraph (c).
    The revisions read as follows:


Sec.  511.1  New animal drugs for investigational use exempt from 
section 512(a) of the act.

* * * * *
    (c) Disqualification of a clinical investigator. (1) If FDA has 
information indicating that an investigator (including a sponsor-
investigator) has repeatedly or deliberately failed to comply with the 
conditions of these exempting regulations or has repeatedly or 
deliberately submitted to FDA or to the sponsor false information in 
any required report, the Center for Veterinary Medicine will furnish 
the investigator written notice of the matter complained of and offer 
the investigator an opportunity to explain the matter in writing, or, 
at the option of the investigator, in an informal conference. If an 
explanation is offered and accepted by the Center for Veterinary 
Medicine, the Center will discontinue the disqualification proceeding. 
If an explanation is offered but not accepted by the Center for 
Veterinary Medicine, the investigator will be given an opportunity for 
a regulatory hearing under part 16 of this chapter on the

[[Page 25360]]

question of whether the investigator is eligible to receive test 
articles under this part and eligible to conduct any clinical 
investigation that supports an application for a research or marketing 
permit for products regulated by FDA.
    (2) After evaluating all available information, including any 
explanation presented by the investigator, if the Commissioner 
determines that the investigator has repeatedly or deliberately failed 
to comply with the conditions of the exempting regulations in this 
subchapter, or has repeatedly or deliberately submitted to FDA or to 
the sponsor false information in any required report, the Commissioner 
will notify the investigator and the sponsor of any investigation in 
which the investigator has been named as a participant that the 
investigator is not eligible to receive test articles under this part. 
The notification to the investigator and sponsor will provide a 
statement of the basis for such determination. The notification also 
will explain that an investigator determined to be ineligible to 
receive test articles under this part will be ineligible to conduct any 
clinical investigation that supports an application for a research or 
marketing permit for products regulated by FDA, 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.
    (3) Each application or submission to FDA under the provisions of 
this chapter containing data reported by an investigator who has been 
determined to be ineligible to receive FDA-regulated test articles is 
subject to examination to determine whether the investigator has 
submitted unreliable data that are essential to the continuation of an 
investigation or essential to the approval of a marketing application, 
or essential to the continued marketing of an FDA-regulated product.
    (4) If the Commissioner determines, after the unreliable data 
submitted by the 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 shall have an opportunity for a regulatory 
hearing under part 16 of this chapter. If a danger to the public health 
exists, however, the Commissioner shall terminate the exemption 
immediately and notify the sponsor of the termination. In such case, 
the sponsor shall have an opportunity for a regulatory hearing before 
FDA under part 16 on the question of whether the exemption should be 
reinstated. 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.
    (5) If the Commissioner determines, after the unreliable data 
submitted by the investigator are eliminated from consideration, that 
the continued approval of the product for which the data were submitted 
cannot be justified, the Commissioner will proceed to withdraw approval 
of the product in accordance with the applicable provisions of the 
relevant statutes.
    (6) An investigator who has been determined to be ineligible under 
paragraph (c)(2) of this section may be reinstated as eligible when the 
Commissioner determines that the investigator has presented adequate 
assurances that the investigator will employ all test articles, 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 the applicable provisions of this chapter.
* * * * *

0
7. Section 511.3 is added to read as follows:


Sec.  511.3  Definitions.

    As used in this part:
    Contract research organization means a person that assumes, as an 
independent contractor with the sponsor, one or more of the obligations 
of a sponsor, e.g., design of a protocol, selection or monitoring of 
investigations, evaluation of reports, and preparation of materials to 
be submitted to the Food and Drug Administration.
    Investigator means an individual who actually conducts a clinical 
investigation (i.e., under whose immediate direction the drug is 
administered or dispensed to a subject). In the event an investigation 
is conducted by a team of individuals, the investigator is the 
responsible leader of the team. ``Subinvestigator'' includes any other 
individual member of that team.
    Sponsor means a person who takes responsibility for and initiates a 
clinical investigation. The sponsor may be an individual or 
pharmaceutical company, governmental agency, academic institution, 
private organization, or other organization. The sponsor does not 
actually conduct the investigation unless the sponsor is a sponsor-
investigator. A person other than an individual that uses one or more 
of its own employees to conduct an investigation that it has initiated 
is a sponsor, not a sponsor-investigator, and the employees are 
investigators.
    Sponsor-Investigator means an individual who both initiates and 
conducts an investigation, and under whose immediate direction the 
investigational drug is administered or dispensed. The term does not 
include any person other than an individual. The requirements 
applicable to a sponsor-investigator under this part include both those 
applicable to an investigator and a sponsor.

PART 812--INVESTIGATIONAL DEVICE EXEMPTIONS

0
8. The authority citation for 21 CFR part 812 continues to read as 
follows:

    Authority: 21 U.S.C. 331, 351, 352, 353, 355, 360, 360c-360f, 
360h-360j, 371, 372, 374, 379e, 381, 382, 383; 42 U.S.C. 216, 241, 
262, 263b-263n.


0
9. Section 812.119 is revised to read as follows:


Sec.  812.119  Disqualification of a clinical investigator.

    (a) If FDA has information indicating that an investigator 
(including a sponsor-investigator) has repeatedly or deliberately 
failed to comply with the requirements of this part, part 50, or part 
56 of this chapter, or has repeatedly or deliberately submitted to FDA 
or to the sponsor false information in any required report, the Center 
for Devices and Radiological Health, the Center for Biologics 
Evaluation and Research, or the Center for Drug Evaluation and Research 
will furnish the investigator written notice of the matter complained 
of and offer the investigator an opportunity to explain the matter in 
writing, or, at the option of the investigator, in an informal 
conference. If an explanation is offered and accepted by the applicable 
Center, the Center will discontinue the disqualification proceeding. If 
an explanation is offered but not accepted by the applicable Center, 
the investigator will be given an opportunity for a regulatory hearing 
under part 16 of this chapter on the question of whether the 
investigator is eligible to receive test articles under this part and 
eligible to conduct any clinical investigation that supports an 
application for a research or marketing permit for products regulated 
by FDA.
    (b) After evaluating all available information, including any 
explanation presented by the investigator, if the Commissioner 
determines that the investigator has repeatedly or deliberately failed 
to comply with the

[[Page 25361]]

requirements of this part, part 50, or part 56 of this chapter, or has 
repeatedly or deliberately submitted to FDA or to the sponsor false 
information in any required report, the Commissioner will notify the 
investigator, the sponsor of any investigation in which the 
investigator has been named as a participant, and the reviewing 
investigational review boards (IRBs) that the investigator is not 
eligible to receive test articles under this part. The notification to 
the investigator, sponsor and IRBs will provide a statement of the 
basis for such determination. The notification also will explain that 
an investigator determined to be ineligible to receive test articles 
under this part will be ineligible to conduct any clinical 
investigation that supports an application for a research or marketing 
permit for products regulated by FDA, 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.
    (c) Each application or submission to FDA under the provisions of 
this chapter containing data reported by an investigator who has been 
determined to be ineligible to receive FDA-regulated test articles is 
subject to examination to determine whether the investigator has 
submitted unreliable data that are essential to the continuation of an 
investigation or essential to the clearance or approval of a marketing 
application, or essential to the continued marketing of an FDA-
regulated product.
    (d) If the Commissioner determines, after the unreliable data 
submitted by the 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 shall have an opportunity for a regulatory 
hearing under part 16 of this chapter. If a danger to the public health 
exists, however, the Commissioner shall terminate the investigational 
device exemption (IDE) immediately and notify the sponsor and the 
reviewing IRBs of the termination. In such case, the sponsor shall have 
an opportunity for a regulatory hearing before FDA under part 16 of 
this chapter on the question of whether the IDE should be reinstated. 
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.
    (e) If the Commissioner determines, after the unreliable data 
submitted by the investigator are eliminated from consideration, that 
the continued clearance or approval of the product for which the data 
were submitted cannot be justified, the Commissioner will proceed to 
rescind clearance or withdraw approval of the product in accordance 
with the applicable provisions of the relevant statutes.
    (f) An investigator who has been determined to be ineligible under 
paragraph (b) of this section may be reinstated as eligible when the 
Commissioner determines that the investigator has presented adequate 
assurances that the investigator will employ all test articles, 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 the applicable provisions of this chapter.

    Dated: April 24, 2012.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2012-10292 Filed 4-27-12; 8:45 am]
BILLING CODE 4160-01-P


