Disqualification of a Clinical Investigator, 20575-20588 [2011-8786]

Agencies

• Food and Drug Administration
• DEPARTMENT OF HEALTH AND HUMAN SERVICES

[Federal Register Volume 76, Number 71 (Wednesday, April 13, 2011)]
[Proposed Rules]
[Pages 20575-20588]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2011-8786]


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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: Proposed rule.

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SUMMARY: The Food and Drug Administration (FDA) is proposing to amend 
the regulations to expand the scope of clinical investigator 
disqualification. Under this proposal, when the Commissioner of Food 
and Drugs determines that an investigator is

[[Page 20576]]

ineligible to receive certain test articles (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 products regulated by FDA. This proposal is based 
in part upon recommendations from the Government Accountability Office, 
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: Submit either electronic or written comments on the proposed 
rule by July 12, 2011. See section VII of this document for the 
proposed effective date of a final rule based on this document.

ADDRESSES: You may submit comments, identified by Docket No. FDA-2011-
N-0079 and/or RIN number 0910-AG49, by any of the following methods:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments.

Written Submissions

    Submit written submissions in the following ways:
     FAX: 301-827-6870.
     Mail/Hand delivery/Courier (for paper, disk, or CD-ROM 
submissions): Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.
    Instructions: All submissions received must include the Agency name 
and Docket No. FDA-2011-N-0079 and Regulatory Information Number (RIN) 
for this rulemaking. All comments received may be posted without change 
to https://www.regulations.gov, including any personal information 
provided. For additional information on submitting comments, see the 
``Comments'' heading of the SUPPLEMENTARY INFORMATION section of this 
document.
    Docket: For access to the docket to read background documents or 
comments received, go to https://www.regulations.gov and insert the 
docket number, found in brackets in the heading of this document, into 
the ``Search'' box and follow the prompts and/or go to the Division of 
Dockets Management, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.

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: 

Table of Contents

I. Introduction
II. Background
III. Description of the Proposed Rule
    A. Disqualification Proceedings (Sec. Sec.  312.70(a), 
511.1(c)(1), and 812.119(a))
    B. Ineligibility To Receive Any Test Article (Sec. Sec.  
312.70(b), 511.1(c)(2), and 812.119(b))
    C. Disqualified Investigator's Data in Applications and 
Submissions to FDA (Sec. Sec.  312.70(c), 511.1(c)(3), and 
812.119(c))
    D. Disqualified Investigator's Data in Applications and 
Submissions to FDA--Sponsor Notification, Opportunities, and 
Responsibilities (Sec. Sec.  312.70(d), 511.1(c)(4), and 812.119(d))
    E. Disqualified Investigator's Data in Applications and 
Submissions to FDA--Withdrawal of Product Approval (Sec. Sec.  
312.70(e), 511.1(c)(5), and 812.119(e))
    F. Other Proceedings
    G. Reinstatement (Sec. Sec.  312.70(f), 511.1(c)(6), and 
812.119(f))
    H. Part 511 Definitions (Sec.  511.3)
IV. Regulatory Hearing Before the Food and Drug Administration
V. Environmental Impact
VI. Legal Authority
VII. Proposed Implementation Plan
VIII. Analysis of Impacts
    A. Objective
    B. Background
    C. Baseline
    D. Costs of the Proposed Rule
    E. Benefit
    F. Alternatives
    G. Small Business Impact
IX. Paperwork Reduction Act of 1995
X. Federalism
XI. Request for Comments
XII. References

I. Introduction

    Under current regulations, a clinical investigator disqualified by 
the Commissioner of Food and Drugs (the Commissioner) is ineligible to 
receive a particular type of FDA-regulated test article only; i.e., 
drugs (including biologics) in Sec.  312.70 (21 CFR 312.70); new animal 
drugs in Sec.  511.1(c) (21 CFR 511.1(c)); or devices in Sec.  812.119 
(21 CFR 812.119). The proposed rulemaking will amend Sec. Sec.  312.70, 
511.1(c), and 812.119 to provide that when the Commissioner determines 
that a clinical investigator is ineligible to receive the test article 
under that provision (e.g., drugs in Sec.  312.70), the clinical 
investigator also 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.
    Other proposed revisions are intended to clarify and harmonize the 
clinical investigator disqualification regulations in parts 312, 511, 
and 812 (21 CFR parts 312, 511, and 812). FDA proposes this rulemaking 
to help protect the rights and safety of subjects involved in FDA-
regulated investigations and to help ensure the reliability and 
integrity of the data used to support marketing of products regulated 
by FDA.

II. Background

    FDA inspects the records of a clinical investigator to evaluate the 
quality and integrity of clinical data used to support applications 
under review by FDA and to evaluate whether protections are afforded to 
participating research subjects, where required. FDA may consider 
disqualification of a clinical investigator when FDA has information 
that an investigator has repeatedly or deliberately failed to comply 
with applicable requirements for the conduct of clinical 
investigations, or has repeatedly or deliberately submitted to FDA or 
to the sponsor false information in any required report.
    Disqualification of an investigator is initiated by the appropriate 
FDA Center depending upon the particular type of test article under 
study by the investigator in the clinical investigation. For example, 
the Center for Devices and Radiological Health may pursue 
disqualification of a clinical investigator who conducted a device 
study and allegedly violated the regulations. The regulations provide 
the investigator, who is subject to disqualification, an opportunity to 
be heard and explain the matter(s) complained of; i.e., explain the 
alleged violation(s). If the explanation offered is not accepted by the 
Center, the investigator will be given an opportunity for an informal 
regulatory hearing under part 16 (21 CFR part 16). After evaluating all 
available information, including any explanation presented by the 
investigator, the Commissioner issues a Commissioner's decision 
regarding the eligibility of the investigator to receive a particular 
type of test article. When disqualified by a Commissioner's decision, 
the investigator is no longer eligible to receive the particular type 
of test article (drugs, devices, or new animal drugs) under study when 
the violations occurred. Under current regulations, an

[[Page 20577]]

investigator disqualified by a Commissioner's decision as ineligible to 
receive investigational devices, for example, may still be eligible to 
receive investigational drugs (including biologics), because the 
regulations do not specifically prohibit such an investigator from 
receiving other types of test articles.
    In September 2009, the Government Accountability Office (GAO) 
released a final report on FDA's oversight of clinical investigators 
(Ref. 1). In that report, the GAO recommended, among other things, that 
FDA extend disqualification by a Commissioner's decision to include 
ineligibility to receive drugs, biologics, and medical devices. The GAO 
noted that FDA's disqualification regulations are included in separate 
sets of regulations and, as a result, the regulations as currently 
written limit the types of test articles to which disqualification 
applies and consequently, limits FDA's oversight of clinical 
investigators (Ref. 1 at page 40, under ``FDA's Regulations Allow 
Disqualified Clinical Investigators to Conduct Trials for Other Medical 
Products''). The GAO elaborated, comparing disqualifications that 
resulted from a Commissioner's decision with those resulting from a 
consent agreement between FDA and the investigator. That is, a consent 
agreement may contain ``more extensive restrictions by disqualifying 
the investigator from receiving any FDA-regulated investigational 
products (including drugs, biologics, devices, animal drugs, and food 
additives)'' (Ref. 1 at page 41). 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).
    In past investigator disqualification actions, there is little, if 
any, evidence that an investigator disqualified from receiving one type 
of test article (e.g., drugs) later conducted a clinical investigation 
studying a different type of test article (e.g., devices). Even so, FDA 
agrees with the GAO's recommendation and its underlying rationale to 
expand the scope of articles covered when an investigator is 
disqualified by a Commissioner's decision. This proposed action of 
explicitly extending a disqualified investigator's ineligibility to 
receive any FDA-regulated test article would help to reduce the risk of 
additional violations in other FDA-regulated investigations and thus, 
would help to ensure the integrity of clinical trial data and help 
reduce the risk to human subjects who participate in FDA-regulated 
investigations. This proposed rule may also lead to improved public 
confidence in the clinical data supporting FDA decisions.
    We therefore propose that a clinical investigator disqualified by a 
Commissioner's decision will be ineligible to receive any test article 
under the disqualification regulations in parts 312, 511, or 812, and, 
in addition, the investigator will be ineligible to conduct any 
clinical investigation that supports an application for a research or 
marketing permit for products regulated by FDA. Those products include 
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. To 
effect this change, FDA proposes to amend the current regulations in 
Sec. Sec.  312.70, 511.1(c), and 812.119.

III. Description of the Proposed Rule

    To harmonize the headings for the clinical investigator 
disqualification regulations in parts 312, 511, and 812, FDA proposes 
to change the heading in Sec.  511.1(c) to match those currently in 
Sec. Sec.  312.70 and 812.119. Therefore, we propose to change the 
heading in Sec.  511.1(c) from ``Withdrawal of eligibility to receive 
investigational-use new animal drugs'' to ``Disqualification of a 
clinical investigator''. This revision will help to identify the 
investigator disqualification regulations pertaining to new animal 
drugs.

A. Disqualification Proceedings (Sec. Sec.  312.70(a), 511.1(c)(1), and 
812.119(a))

    FDA proposes to revise the provisions currently in Sec. Sec.  
312.70(a), 511.1(c)(1), and 812.119(a), to clarify, simplify, and to 
harmonize those provisions. Also, for consistency with other proposed 
changes to the disqualification regulations, FDA proposes to change the 
scope of the question addressed during a part 16 hearing, should the 
investigator request and be granted an informal regulatory hearing.
1. Proposed Revisions to Sec.  312.70(a)
     To harmonize the provisions in Sec.  312.70(a) with those 
currently in Sec.  812.119(a), we propose to add ``repeatedly or 
deliberately'' before the reference to submitting false information in 
any required report. The addition of ``repeatedly or deliberately'' 
before ``submitted to FDA or to the sponsor false information in any 
required report,'' codifies FDA's current policies and makes consistent 
the clinical investigator disqualification regulations.
     To harmonize the provisions in Sec.  312.70(a) with those 
currently in Sec.  812.119(a), we propose to add a provision for 
accepting an investigator's explanation concerning the alleged 
misconduct. That is, if the investigator offers an explanation in 
writing or during an informal conference and the explanation is 
accepted by the applicable Center, the Center will discontinue pursuit 
of the disqualification proceeding. This proposed revision clarifies 
FDA's current policies and makes consistent the clinical investigator 
disqualification regulations.
     To simplify the regulations, we propose to change ``Center 
for Drug Evaluation and Research or the Center for Biologics Evaluation 
and Research'' to ``applicable Center'' after ``If an explanation is 
offered but not accepted by the * * *''.
     We propose to add ``of this chapter'' after ``the 
investigator will be given an opportunity for a regulatory hearing 
under part 16 * * *'', for clarity and to harmonize Sec.  312.70(a) 
with the provisions currently in Sec.  812.119(a).
     Regarding the question of whether the investigator is 
entitled to receive test articles, we propose to change ``entitled'' to 
``eligible'' because ``eligible'' is the correct term for this 
provision.
     We propose to change the scope of the question addressed 
during a part 16 hearing, should the investigator request and be 
granted an informal hearing, from whether the investigator is eligible 
to receive ``investigational new drugs'' to 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''. Those 
FDA-regulated products include 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.
2. Proposed Revisions to Sec.  511.1(c)(1)
     To harmonize the investigator disqualification 
regulations, we propose to change the first words in the first sentence 
in Sec.  511.1(c)(1) from ``Whenever the Food and Drug Administration'' 
to ``If FDA''.
     Although already applicable, we propose to add explicit 
provisions in Sec.  511.1(c)(1), consistent with the current 
regulations in Sec.  312.70(a), that a clinical investigator includes a 
sponsor-investigator. Because sponsor-

[[Page 20578]]

investigators must meet an investigator's regulatory responsibilities 
as well as a sponsor's, FDA has consistently considered sponsor-
investigators to be subject to the clinical investigator 
disqualification provisions in studies of drugs, animal drugs, and 
devices.\1\
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    \1\ See, for example, the final rule at 62 FR 46875, September 
5, 1997; clarifying FDA's authority to reach sponsor-investigators 
under the regulations for disqualification of a clinical 
investigator.
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     To harmonize the provisions in Sec.  511.1(c)(1) with the 
provisions currently in Sec.  812.119(a), we propose to add 
``repeatedly or deliberately'' before the reference to submitting false 
information in any required report. The addition of ``repeatedly or 
deliberately'' codifies FDA's current policies and makes consistent the 
clinical investigator disqualification regulations.
     To make the investigator disqualification regulations 
consistent, we propose to change the wording of the first sentence in 
Sec.  511.1(c)(1) to read as follows, ``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.'' For this first sentence, 
this proposal removes the reference to ``in general terms'' concerning 
the Center's written notice of the matter to the investigator. This 
proposal also replaces offering ``him'' with offering ``the 
investigator'' an opportunity to explain. At the end of this first 
sentence, the wording is changed from ``in an informal conference and/
or in writing'' to ``in writing, or, at the option of the investigator, 
in an informal conference.''
     To harmonize the provisions in Sec.  511.1(c)(1) with 
those currently in Sec.  812.119(a), we propose to add a provision for 
accepting an investigator's explanation concerning the alleged 
misconduct. That is, if the investigator offers an explanation in 
writing or during an informal conference and the explanation is 
accepted by the affected Center, the Center will discontinue pursuit of 
the disqualification proceeding. This proposed revision clarifies FDA's 
current policies and makes consistent the clinical investigator 
disqualification regulations.
     For consistency with the regulations currently in 
Sec. Sec.  312.70(a) and 812.119(a), we propose to change in the second 
sentence in Sec.  511.1(c)(1) (the third sentence in this proposal), 
``shall have'' to ``will be given'', and remove after ``an opportunity 
for a regulatory hearing * * *'' the clause, ``before the Food and Drug 
Administration pursuant to * * *'' Also, in this sentence, we propose 
to change the term ``entitled'' to the term ``eligible''.
     We propose to change the scope of the question addressed 
during a part 16 hearing, should the investigator request and be 
granted an informal hearing, from whether the investigator is eligible 
to receive ``investigational new animal drugs'' to 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''. Those FDA-regulated products include 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. Proposed Revisions to Sec.  812.119(a)
     Although already applicable, we propose to add explicit 
provisions in Sec.  812.119(a), consistent with the current regulations 
in Sec.  312.70(a), that a clinical investigator includes a sponsor-
investigator. Because sponsor-investigators must meet an investigator's 
regulatory responsibilities as well as a sponsor's, FDA has 
consistently considered sponsor-investigators to be subject to the 
clinical investigator disqualification provisions in studies of drugs, 
animal drugs, and devices.\2\
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    \2\ See, for example, the final rule at 62 FR 46875, September 
5, 1997; clarifying FDA's authority to reach sponsor-investigators 
under the regulations for disqualification of a clinical 
investigator.
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     To harmonize the provisions in Sec.  812.119(a) with those 
currently in Sec.  312.70(a), we propose to change after repeatedly or 
deliberately submitted ``false information either to the sponsor of the 
investigation or * * *'', to read instead, ``to FDA or to the sponsor 
false information in any required report, * * *''
     To harmonize the provisions in Sec.  812.119(a) with those 
currently in Sec.  312.70(a), we propose to change the matter ``under 
complaint'' to the matter ``complained of''.
     For clarity and consistency with our current procedures 
and the proposed changes to Sec. Sec.  312.70(a) and 511.1(c)(1), we 
propose to change the language in Sec.  812.119(a) from ``the 
disqualification process will be terminated'' to ``the Center will 
discontinue pursuit of the disqualification proceeding.''
     For consistency with the proposed revisions to Sec. Sec.  
312.70(a) and 511.1(c)(1), we propose to add ``applicable'' before 
``Center'' to read, ``If an explanation is offered but not accepted by 
the applicable Center''.
     Regarding the question of whether the investigator is 
entitled to receive test articles, we propose to change the term 
``entitled'' to ``eligible''.
     We propose to change the scope of the question addressed 
during a part 16 hearing, should the investigator request and be 
granted an informal hearing, from whether the investigator is eligible 
to receive investigational devices to 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''. Those 
FDA-regulated products include drugs, biologics, devices, new animal 
drugs, foods, including dietary supplements, that bear a nutrient 
content claim or a health claim, infant formulas, food and color 
additives, and tobacco products.
    In summary, the proposed harmonized provisions in Sec. Sec.  
312.70(a), 511.1(c)(1), and 812.119(a) provide that when FDA has 
information indicating that a clinical investigator, including a 
sponsor-investigator, has repeatedly or deliberately failed to comply 
with the relevant regulatory requirements or has repeatedly or 
deliberately submitted to FDA or to the sponsor of the investigation 
false information in any required report, the applicable FDA Center 
notifies the investigator in writing of the alleged violations. This 
written notice offers the investigator an opportunity to explain the 
matter in writing, or, at the option of the investigator, during an 
informal conference. If the investigator offers an explanation that is 
accepted by the applicable Center, that Center will discontinue pursuit 
of the disqualification proceeding. If, however, the investigator 
offers an explanation not accepted by the applicable Center, the 
investigator will be offered an opportunity to request an informal 
regulatory hearing \3\ under part 16 \4\ on the question of whether the 
investigator is eligible to receive test articles under

[[Page 20579]]

the applicable part and eligible to conduct any clinical investigation 
that supports an application for a research or marketing permit for 
products regulated by FDA. Those FDA-regulated products include 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.
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    \3\ FDA issues to the investigator a ``Notice of Opportunity for 
Hearing''. The investigator must show that there is a genuine and 
substantial issue of fact that warrants a hearing (Sec.  16.26(a)).
    \4\ See part 16, subpart D--Procedures for Regulatory Hearing.
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B. Ineligibility To Receive Any Test Article (Sec. Sec.  312.70(b), 
511.1(c)(2), and 812.119(b))

1. Proposed Revisions to Sec.  312.70(b)
     For consistency, we propose to refer to ``repeatedly or 
deliberately'' in the same order throughout the provision.
     For clarity, we propose to move after ``submitted'' the 
clause, ``to FDA or to the sponsor''. Therefore, the proposed provision 
reads, ``or has repeatedly or deliberately submitted to FDA or to the 
sponsor false information in any required report, * * *''.
     We propose to add a notification to the reviewing 
institutional review board(s) (IRB(s)) about the investigator's 
disqualification. This proposed change will harmonize Sec.  312.70(b) 
with FDA's current procedures along with those provisions currently in 
Sec.  812.119(b). IRBs play a significant role in ensuring that 
clinical investigators meet the applicable statutory and regulatory 
requirements.\5\ We therefore propose to add this provision in Sec.  
312.70(b) to help ensure that any reviewing IRB is aware of the 
clinical investigator's disqualification.
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    \5\ 63 FR 55873 at 55874, October 19, 1998.
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     We propose to change ``entitled'' to ``eligible''.
     FDA proposes to harmonize the disqualification regulations 
by changing the investigator's ineligibility from receiving 
``investigational drugs'' to ineligibility to receive ``test articles 
under this part.'' We are also proposing that an investigator 
disqualified by a Commissioner's decision also 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.
     For clarity and consistency with our procedures, we 
propose to add an explicit reference concerning notification by FDA 
about the investigator's disqualification. That is, the investigator 
and sponsor will be notified about the basis for the disqualification 
determination. The notification to the sponsor, for example, will 
provide a statement of the basis for disqualification such as a list of 
the investigator's violations, and also include instructions concerning 
ongoing studies and any approved products containing the investigator's 
data.
     For consistency with our procedures, we propose to add 
that the reviewing IRB(s) also will be notified about the basis for the 
disqualification determination.
2. Proposed Revisions to Sec.  511.1(c)(2)
     To harmonize the investigator disqualification regulations 
in Sec.  511.1(c)(2) with those currently in Sec. Sec.  312.70(b) and 
812.119(b), we propose to change the first word ``If'' in Sec.  
511.1(c)(2) to read instead, ``After evaluating all available 
information, including any explanation presented by the investigator, 
if the Commissioner determines that * * *''.
     We propose to change the term ``section'' to 
``subchapter''. The disqualification action is pursuant to the 
investigator's failure to comply with the conditions of the exempting 
regulations in subchapter E (21 CFR chapter I, subchapter E)--Animal 
drugs, feeds, and related products. Therefore, we propose ``this 
subchapter'' is the applicable and correct term as opposed to the 
narrower reference currently in Sec.  511.1(c)(2) to ``this section''.
     For clarity and to harmonize Sec.  511.1(c)(2) with the 
proposed investigator disqualification regulations in Sec. Sec.  
312.70(b) and 812.119(b), we propose to move and modify the clause ``to 
the sponsor of an investigation'' and add ``to FDA'' and ``in any 
required report'', to read, ``or has repeatedly or deliberately 
submitted to FDA or to the sponsor false information in any required 
report, * * *''.
     For clarity and to harmonize the investigator 
disqualification regulations, we propose to change ``he'' to ``the 
investigator''.
     We propose to change ``entitled'' to ``eligible''.
     FDA proposes to harmonize the disqualification regulations 
by changing the investigator's ineligibility from receiving 
``investigational use new animal drugs'' to ineligibility to receive 
``test articles under this part.'' We are also proposing that an 
investigator disqualified by a Commissioner's decision also 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.
     For clarity and consistency with our procedures, we 
propose to add an explicit reference concerning notification by FDA 
about the investigator's disqualification. That is, the investigator 
and sponsor will be notified about the basis for the disqualification 
determination. The notification to the sponsor, for example, will 
provide a statement of the basis for disqualification such as a list of 
the investigator's violations, and also include instructions concerning 
ongoing studies and any approved products containing the investigator's 
data.
3. Proposed Revisions to Sec.  812.119(b)
     For consistency, we propose to refer to ``repeatedly or 
deliberately'' in the same order throughout the provision.
     For clarity and to harmonize Sec.  812.119(b) with the 
proposed investigator disqualification regulations in Sec. Sec.  
312.70(b) and 511.1(c)(2), we propose to move and modify the clause 
``to the sponsor of an investigation'', add ``to FDA'', and remove 
``either'', to read, ``or has repeatedly or deliberately submitted to 
FDA or to the sponsor false information in any required report, * * 
*''.
     We propose to change ``entitled'' to ``eligible''.
     FDA proposes to harmonize the disqualification regulations 
by changing the investigator's ineligibility from receiving 
``investigational devices'' to ineligibility to receive ``test articles 
under this part.'' We are also proposing that an investigator 
disqualified by a Commissioner's decision also 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.
     For clarity and consistency with our procedures, we 
propose to add an explicit reference concerning notification by FDA 
about the investigator's disqualification. That is, the investigator, 
sponsor, and reviewing IRB(s) will be notified about the basis for the 
disqualification determination. The notification to the sponsor, for 
example, will provide a statement of the basis for disqualification 
such as a list of the investigator's violations, and also include 
instructions concerning ongoing

[[Page 20580]]

studies and any approved or cleared products containing the 
investigator's data.
    Therefore, as proposed, an investigator determined to be ineligible 
to receive test articles under one part of FDA's regulations also would 
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. This proposal is consistent with the underlying rationale for 
disqualifying a clinical investigator, which is to preserve the 
integrity of study data and to help ensure the safety, rights, and 
welfare of study subjects. As proposed, those principles would apply to 
all test articles and studies; an investigator who is determined to 
have repeatedly or deliberately violated the regulations while 
conducting a study of a particular type of test article sufficient to 
warrant disqualification would thus be ineligible to receive any FDA-
regulated test article or conduct any clinical investigation that 
supports an application for a research or marketing permit for products 
regulated by FDA.

C. Disqualified Investigator's Data in Applications and Submissions to 
FDA (Sec. Sec.  312.70(c), 511.1(c)(3), and 812.119(c))

1. Proposed Revisions to Sec.  312.70(c)
    Currently, Sec.  312.70(c) provides, ``Each IND and each approved 
application submitted under part 314 containing data reported by an 
investigator who has been determined to be ineligible to receive 
investigational drugs will 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 of any 
marketing application.'' FDA proposes to revise the current regulations 
in Sec.  312.70(c) to clarify the applicability of this provision, 
update this provision consistent with Sec. Sec.  312.70(b), 
511.1(c)(2), and 812.119(b) of this proposal, and to harmonize the 
disqualification regulations in Sec. Sec.  312.70(c), 511.1(c)(3), and 
812.119(c). Therefore, we propose to amend Sec.  312.70(c) to change 
``Each IND and each approved application submitted under part 314'' to 
``Each application or submission to FDA under the provisions of this 
chapter''. The ``provisions of this chapter'' refers to chapter I and 
includes INDs and approved applications submitted under part 314. Also, 
we propose to change ``drugs'' to ``FDA-regulated test articles''; 
``continuation of the investigation'' to ``continuation of any 
investigation''; and add after ``essential to the approval of any 
marketing application'' the phrase ``essential to the continued 
marketing of an FDA-regulated product.''
2. Proposed Revisions to Sec.  511.1(c)(3)
    Currently, Sec.  511.1(c)(3) provides, ``Each `Notice of Claimed 
Investigational Exemption for a New Animal Drug' and each approved new 
animal drug application containing data reported by an investigator who 
has been determined to be ineligible to receive investigational-use new 
animal drugs will be examined to determine whether he has submitted 
unreliable data that are essential to the continuation of the 
investigation or essential to the approval of any new animal drug 
application.'' FDA proposes to revise the current regulations in Sec.  
511.1(c)(3) to clarify the applicability of this provision, update this 
provision consistent with Sec. Sec.  312.70(b), 511.1(c)(2), and 
812.119(b) of this proposal, and to harmonize the disqualification 
regulations in Sec. Sec.  312.70(c), 511.1(c)(3), and 812.119(c). 
Therefore, we propose to revise Sec.  511.1(c)(3) to provide, ``Each 
application or submission to FDA under the provisions of this chapter 
and containing data reported by an investigator who has been determined 
to be ineligible to receive FDA-regulated test articles will be 
examined to determine whether the investigator has submitted unreliable 
data that are essential to the continuation of any investigation or 
essential to the approval of any marketing application, or essential to 
the continued marketing of an FDA-regulated product.'' The ``provisions 
of this chapter'' refers to chapter I and includes a notice of claimed 
investigational exemption for a new animal drug and an approved new 
animal drug application.
3. Proposed Revisions to Sec.  812.119(c)
    Currently, Sec.  812.119(c) provides, ``Each investigational device 
exemption (IDE) and each cleared or approved application submitted 
under this part, subpart E of part 807 of this chapter, or part 814 of 
this chapter containing data reported by an investigator who has been 
determined to be ineligible to receive investigational devices will 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.'' 
FDA proposes to revise the current regulations in Sec.  812.119(c) to 
clarify the applicability of this provision, update this provision 
consistent with Sec. Sec.  312.70(b), 511.1(c)(2), and 812.119(b) of 
this proposal, and to harmonize the disqualification regulations in 
Sec. Sec.  312.70(c), 511.1(c)(3), and 812.119(c). Therefore, we 
propose to revise Sec.  812.119(c) to provide, ``Each application or 
submission to FDA under the provisions of this chapter and containing 
data reported by an investigator who has been determined to be 
ineligible to receive FDA-regulated test articles will be examined to 
determine whether the investigator has submitted unreliable data that 
are essential to the continuation of any investigation or essential to 
the clearance or approval of any marketing application, or essential to 
the continued marketing of an FDA-regulated product.'' The ``provisions 
of this chapter'' refers to chapter I and includes investigational 
device exemptions (IDEs), and cleared or approved applications 
submitted under part 812; 21 CFR part 807, subpart E; or part 814 (21 
CFR part 814).

D. Disqualified Investigator's Data in Applications and Submissions to 
FDA--Sponsor Notification, Opportunities, and Responsibilities 
(Sec. Sec.  312.70(d), 511.1(c)(4), and 812.119(d))

1. Proposed Revisions to Sec.  312.70(d)
     In accordance with FDA's procedures and for consistency 
with the provisions currently in Sec.  812.119(d), we propose to add 
``and the reviewing IRB(s)'' after ``shall terminate the IND 
immediately and notify the sponsor * * *''.
     We propose to change ``determination'' to ``termination''. 
This correction is consistent with the regulations currently in 
Sec. Sec.  511.1(c)(4) and 312.44 and, therefore, will harmonize and 
clarify the regulations. This proposal provides, ``If a danger to the 
public health exists * * * the Commissioner shall terminate the IND 
immediately and notify the sponsor and the reviewing IRB(s) of the 
termination.''
     We propose to add a new sentence at the end of Sec.  
312.70(d), to clarify and emphasize the sponsor's responsibilities 
under this provision. That is, we propose to add that when the 
Commissioner determines that an investigation may not be considered in 
support of a research or marketing application, or a notification or 
petition submission, this determination does not relieve the sponsor of 
any obligation under any other applicable regulation to submit to FDA 
the results of the investigation.

[[Page 20581]]

2. Proposed Revisions to Sec.  511.1(c)(4)
     For the purpose of plain language and for consistency with 
the current and proposed investigator disqualification regulations, FDA 
proposes to make corrections to Sec.  511.1(c)(4):
    [cir] Change ``he shall first'' to ``the Commissioner will'',
    [cir] Change ``before the Food and Drug Administration pursuant 
to'' to ``before FDA under'',
    [cir] Remove ``on whether the exemption should be terminated'',
    [cir] Change ``he'' to ``the Commissioner'',
    [cir] Change ``forthwith'' to ``immediately'',
    [cir] Change ``event'' to ``case'',
    [cir] Change ``the Food and Drug Administration pursuant to'' to 
``FDA under'', and
    [cir] Remove ``(see 42 FR 15075, March 22, 1977)''.
     We propose to add a new sentence at the end of Sec.  
511.1(c)(4), to clarify and emphasize the sponsor's responsibilities 
under this provision. That is, we propose to add that when the 
Commissioner determines that an investigation may not be considered in 
support of a research or marketing application, or a notification or 
petition submission, this determination does not relieve the sponsor of 
any obligation under any other applicable regulation to submit to FDA 
the results of the investigation.
3. Proposed Revisions to Sec.  812.119(d)
     We propose to change ``determination'' to ``termination''. 
This correction is consistent with the regulations currently in Sec.  
511.1(c)(4) and therefore will harmonize and clarify the regulations. 
Also, we propose to add ``(s)'' at the end of ``IRB'' because there 
might be more than one reviewing IRB, to provide that ``the 
Commissioner shall terminate the IDE immediately and notify the sponsor 
and the reviewing IRB(s) of the termination.''
     We propose to add a new sentence at the end of Sec.  
812.119(d). As proposed for Sec. Sec.  312.70(d) and 511.1(c)(4), we 
propose to add that when the Commissioner determines that an 
investigation may not be considered in support of a research or 
marketing application, or a notification or petition submission, this 
determination does not relieve the sponsor of any obligation under any 
other applicable regulation to submit to FDA the results of the 
investigation.

E. Disqualified Investigator's Data in Applications and Submissions to 
FDA--Withdrawal of Product Approval (Sec. Sec.  312.70(e), 511.1(c)(5), 
and 812.119(e))

1. Proposed Revisions to Sec.  312.70(e)
    The current investigator disqualification regulations provide that 
if the Commissioner determines, after the unreliable data submitted by 
the investigator are eliminated from consideration, that the continued 
approval of the drug product for which the data were submitted cannot 
be justified, the Commissioner will proceed to withdraw approval of the 
drug product in accordance with the applicable provisions of the 
Federal Food, Drug, and Cosmetic Act as amended (the FD&C Act). We also 
note that the Commissioner would revoke any biologics license approved 
under the Public Health Service Act. To harmonize the investigator 
disqualification regulations in Sec. Sec.  312.70(e), 511.1(c)(5), and 
812.119(e), we propose to remove the reference to ``drug''. To keep the 
investigator disqualification regulations consistent, this proposal 
also changes the reference to the applicable provisions of the FD&C Act 
to a reference to the applicable provisions of the relevant statutes.
2. Proposed Revisions to Sec.  511.1(c)(5)
    The current investigator disqualification regulations in Sec.  
511.1(c)(5) provide that if the Commissioner determines, after the 
unreliable data submitted by the investigator are eliminated from 
consideration, that the ``data remaining are such that a new animal 
drug application would not have been approved, he will proceed to 
withdraw approval of the application in accordance with section 512(e) 
of the act.'' This proposal does not change the meaning of this 
provision, however, for simplicity and to keep the investigator 
disqualification regulations consistent, we propose changes to 
harmonize the investigator disqualification regulations, as follows:
     Change the ``data remaining are such that a new animal 
drug application would not have been approved'' to ``continued approval 
of the product for which the data were submitted cannot be justified'',
     Change ``he'' to ``the Commissioner'',
     Change ``application'' to ``product'', and
     Change ``in accordance with section 512(e) of the act'' to 
``in accordance with the applicable provisions of the relevant 
statutes''.
3. Proposed Revisions to Sec.  812.119(e)
    The current investigator disqualification regulations provide that 
if the Commissioner determines, after the unreliable data submitted by 
the investigator are eliminated from consideration, that the continued 
clearance or approval of the marketing application for which the data 
were submitted cannot be justified, the Commissioner will proceed to 
withdraw approval or rescind clearance of the medical device in 
accordance with the applicable provisions of the FD&C Act. We propose 
to harmonize and simplify the provisions in Sec. Sec.  312.70(e), 
511.1(c)(5), and 812.119(e). Therefore, in Sec.  812.119(e), we propose 
to change ``marketing application'' and ``medical device'' to 
``product'' and change ``in accordance with the applicable provisions 
of the act'' to ``in accordance with the applicable provisions of the 
relevant statutes''. Also, we propose to change the order of ``withdraw 
approval or rescind clearance'' to ``rescind clearance or withdraw 
approval'' to match respectively the order at the beginning of the 
sentence.

F. Other Proceedings

    Although not explicit in the proposed codified, the 
disqualification of an investigator is independent of, and neither in 
lieu of nor a precondition to, other proceedings or actions authorized 
by the FD&C Act. That is, at any time, FDA may, through the Department 
of Justice, institute any appropriate judicial proceedings (civil or 
criminal) and any other appropriate regulatory action, in addition to 
or in lieu of, and before, at the time of, or after, disqualification. 
Also, FDA may refer pertinent matters to another Federal, State, or 
local government agency for any action determined appropriate by that 
agency.

G. Reinstatement (Sec. Sec.  312.70(f), 511.1(c)(6), and 812.119(f))

    FDA proposes minor revisions to the regulations currently in 
Sec. Sec.  312.70(f), 511.1(c)(6), and 812.119(f), to make the 
investigator disqualification regulations consistent. This proposal 
changes the references to an investigator who has been determined to be 
ineligible to receive ``investigational drugs'', ``investigational-use 
new animal drugs'', and ``investigational devices'' currently in those 
provisions to, instead, reference an investigator who has been 
determined to be ineligible under the appropriate paragraph in the 
relevant section (e.g., in proposed Sec.  312.70(f), ``an investigator 
who has been determined to be ineligible under paragraph (b) of

[[Page 20582]]

[Sec.  312.70] may be reinstated as eligible * * *''). This proposal 
also changes the current references to ``parts 50 and 56'' and to ``the 
provisions of this part'' in Sec. Sec.  312.70(f) and 812.119(f), and 
the reference to ``the exempting regulations in this section'' in Sec.  
511.1(c)(6), to ``the applicable provisions of this chapter'' (i.e., 
chapter I). We also added, for consistency with the proposed changes to 
Sec. Sec.  312.70(b), 511.1(c)(2), and 812.119(b), the phrase, ``and 
will conduct any clinical investigation that supports an application 
for a research or marketing permit for products regulated by FDA''. We 
therefore propose that an investigator who has been determined to be 
ineligible under Sec. Sec.  312.70(b), 511.1(c)(2), or 812.119(b), 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 chapter I.

H. Part 511 Definitions (Sec.  511.3)

    FDA proposes to amend part 511 by adding a new section that 
provides definitions for a contract research organization, 
investigator, sponsor, and sponsor-investigator. We propose to add 
those definitions to harmonize part 511 with other regulations for the 
disqualification of a clinical investigator.

IV. Regulatory Hearing Before the Food and Drug Administration

    We propose to add to 16.1(b)(2) an entry for 812.119 and to revise 
the entries for 312.70 and 511.1(c)(1). Also, the list of regulatory 
provisions under which a part 16 regulatory hearing is available (Sec.  
16.1(b)(2)) is incomplete. The provisions for Sec.  58.204(b) (21 CFR 
58.204(b)), relating to disqualifying a testing facility, and 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 
FD&C Act (21 U.S.C. 360l), were inadvertently omitted. We, therefore, 
propose to amend part 16 by adding those provisions.

V. 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.

VI. Legal Authority

    The disqualification of a clinical investigator is a remedial 
measure. 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 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 (DC Cir. 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, 99 S.Ct. 505, 513, 58 L.Ed.2d 484 
(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, 97 S.Ct. 576, 581, 50 L.Ed.2d 494 (1977); 
Udall v. Tallman, 380 U.S. 1, 16, 85 S.Ct. 792, 801, 13 L.Ed.2d 616 
(1965).
    Under section 701(a) of the FD&C Act (21 U.S.C. 371(a)), the 
Commissioner is empowered to promulgate regulations for the efficient 
enforcement of the FD&C Act. Regulations issued by the Commissioner 
under section 701(a) 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.2nd 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 
regarding clinical investigations that require prior FDA authorization 
direct the Commissioner to promulgate 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 proposed rulemaking is 
intended to fulfill those mandates.
    The Commissioner therefore concludes that legal authority to 
promulgate those regulations regarding clinical investigators exists 
under sections 505(i), 512(j), 520(g) and 701(a)

[[Page 20583]]

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).

VII. Proposed Implementation Plan

    FDA proposes that any final rule that may issue based on this 
proposal become effective 30 days after the date of publication of the 
final rule in the Federal Register.

VIII. Analysis of Impacts

    FDA has examined the impacts of the proposed rule under Executive 
Order 12866 and the Regulatory Flexibility Act (5 U.S.C. 601-612), and 
the Unfunded Mandates Reform Act of 1995 (Pub. L. 104-4). Executive 
Order 12866 directs 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). The Agency believes that 
this proposed rule is not a significant regulatory action as defined by 
the Executive order.
    The Regulatory Flexibility Act requires agencies to analyze 
regulatory options that would minimize any significant impact of a rule 
on small entities. Because this proposed rule does not impose new 
requirements on any entity and therefore has no associated compliance 
costs, the Agency proposes to certify 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 $135 million, using the most current (2009) Implicit 
Price Deflator for the Gross Domestic Product. FDA does not expect this 
proposed rule to result in any 1-year expenditure that would meet or 
exceed this amount.

A. Objective

    The objective of the proposed rule is to strengthen the process for 
ensuring the reliability and integrity of the clinical trial data 
supporting FDA decision-making on product applications and to help 
ensure the adequate protection of research subjects participating in 
FDA-regulated clinical investigations. Specifically, this rule would 
expand the scope of FDA's disqualification actions so that a 
disqualified clinical investigator is ineligible to receive any FDA-
regulated test article. That is, an investigator determined to be 
ineligible to receive test articles under parts 312, 511 or 812, 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. This action would help reduce the risk to human subjects who 
participate in FDA-regulated clinical investigations by explicitly 
extending a disqualified investigator's ineligibility to receive any 
FDA-regulated test article. In addition, the proposed rulemaking would 
establish uniform language across the several existing regulations that 
address investigator disqualification.

B. Background

    In 2009, the GAO conducted a study of FDA's oversight of clinical 
investigators who conduct research involving new drugs, biologics and 
medical devices, ``Oversight of Clinical Investigators--Action Needed 
To Improve Timeliness and Enhance Scope of FDA's Debarment and 
Disqualification Processes for Medical Product Investigators'' (Ref 
1.). Among its findings, the GAO recommended that FDA amend its 
regulations to ensure that those clinical investigators who have 
engaged in misconduct sufficient to warrant disqualification for one 
type of investigational medical product are not able to serve as 
clinical investigators for other types of medical products.
    Currently, FDA regulations provide authority to disqualify 
researchers conducting clinical investigations of medical products when 
FDA determines that the investigators have not followed the rules 
intended to protect study subjects, or who have submitted false 
information. The actions to disqualify clinical investigators are 
initiated because FDA has evidence that the clinical investigator 
repeatedly or deliberately violated FDA's regulations governing the 
proper conduct of clinical investigations. However, the regulatory 
language may allow a disqualified investigator to participate in 
clinical investigations as long as the investigational products studied 
are different from the product involved in the disqualification.

C. Baseline

    To develop a baseline of the disqualification actions that would be 
affected by this proposed rule, FDA's Office of Good Clinical Practice 
reviewed all FDA disqualification actions over a 10-year period, 1998-
2007. This time-period was selected to provide a data set large enough 
to analyze and to allow sufficient elapsed time from initiation to 
final action to characterize completed actions. Over this 10-year 
period, FDA has initiated a total of about 60 disqualification actions, 
or an average of 6 per year. Of those 60 disqualification actions, 5 
percent of the investigators were not disqualified. Approximately 75 
percent of clinical investigators entered into a consent agreement or a 
restricted agreement that restricts their ability to investigate other 
FDA-regulated products, i.e., products different from the one in the 
study (or studies) that led to disqualification. A small number of 
clinical investigators, about 20 percent of the disqualification 
actions, were ultimately disqualified following a Commissioner's 
decision. In those matters, FDA does not have regulatory authority to 
prohibit those investigators, who are disqualified by a Commissioner's 
decision, from conducting investigations involving other FDA-regulated 
articles. We have little, if any, evidence that any of the 
investigators to date who have been disqualified via a Commissioner's 
decision have conducted investigations with other types of FDA-
regulated test articles. Nonetheless, the agency agrees with GAO's 
recommendation that FDA have in place uniform and enforceable 
regulatory requirements to prevent clinical investigations in other 
product areas by disqualified clinical investigators.

D. Costs of the Proposed Rule

    We estimate that there may be an average of about 1 or 2 matters 
per year of clinical investigators who are ultimately disqualified via 
a Commissioner's decision. Because the majority of disqualification 
actions are concluded by consent agreements that specifically preclude 
the investigator from investigating other FDA-regulated articles and 
current practices already

[[Page 20584]]

reduce the risk of such occurrences, we do not expect that this 
proposed rule would impose additional costs. Past disqualification 
actions show little, if any, evidence that an investigator disqualified 
from receiving one type of test article later conducted a clinical 
investigation studying a different type of test article. Nonetheless, 
based in part on GAO recommendations, we find that explicit regulatory 
language is needed to ensure that a disqualified investigator cannot 
conduct a clinical investigation with any FDA-regulated test article.
    FDA would realize cost savings if there are future disqualification 
matters involving clinical investigators who are already disqualified 
and then conduct additional research in another FDA-regulated product 
area. There would be no need to bring a second action because the first 
disqualification would prohibit research by the disqualified 
investigator with any test article. We cannot estimate the amount of 
savings, but the legal costs avoided would be considerable for each 
additional product area.

E. Benefit

    The proposed rule would help ensure that disqualified investigators 
cannot receive any FDA-regulated article, i.e., disqualified 
investigators 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. Explicitly expanding a 
disqualified investigator's ineligibility to receive any FDA-regulated 
test article would help to reduce the risk of additional violations in 
other FDA-regulated investigations and would help to ensure the 
integrity of clinical trial data. This action would help reduce the 
risk to human subjects who participate in FDA-regulated investigations. 
This proposed rule may also lead to improved public confidence in the 
clinical data supporting FDA decisions.

F. Alternatives

    This proposed rule constitutes a minor change to existing 
regulations to ensure that FDA has the clear regulatory authority it 
needs to protect human subjects from exposure to research conducted by 
disqualified clinical investigators. We considered not expanding the 
scope of FDA's disqualification actions to include the ineligibility of 
a disqualified clinical investigator to receive any FDA-regulated test 
article. However, this would not meet the objective of helping to 
ensure the adequate protection of human subjects in clinical 
investigations or helping to ensure the reliability and integrity of 
the clinical trial data supporting FDA decision-making on product 
applications. There are no other viable alternatives.

G. Small Business Impact

    The clinical research community, including clinical investigators, 
is composed of many large and small business entities