[Federal Register Volume 82, Number 248 (Thursday, December 28, 2017)]
[Rules and Regulations]
[Pages 61443-61446]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2017-27973]


=======================================================================
-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 16 and 511

[Docket No. FDA-2011-N-0079]
RIN 0910-AH64


New Animal Drugs for Investigational Use; Disqualification of a 
Clinical Investigator

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA, the Agency, or we) is 
issuing a final rule amending the regulations for new animal drugs for 
investigational use to expand the scope of clinical investigator 
disqualification to include ineligibility to conduct nonclinical 
laboratory studies. Under this final rule, when the Commissioner of 
Food and Drugs (the Commissioner) determines that an investigator is 
ineligible to receive a new animal drug for investigational use, the 
investigator also will be ineligible to conduct any nonclinical study 
intended to support an application for a research or marketing permit 
for a new animal drug. This final rule will help ensure adequate 
protection of animal research subjects and the quality and integrity of 
data submitted to FDA.

DATES: This rule is effective January 29, 2018.

ADDRESSES: 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 final rule into 
the ``Search'' box and follow the prompts,

[[Page 61444]]

and/or go to the Dockets Management Staff, 5630 Fishers Lane, Rm. 1061, 
Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Vernon Toelle, Center for Veterinary 
Medicine (HFV-230), Food and Drug Administration, 7519 Standish Pl., 
Rockville, MD 20855, 240-402-5637, [email protected].

SUPPLEMENTARY INFORMATION: 

Table of Contents

I. Executive Summary
    A. Purpose of the Final Rule
    B. Summary of the Major Provisions of the Final Rule
    C. Legal Authority
    D. Costs and Benefits
II. Background
    A. Need for the Regulation
    B. Summary of Comments to the Proposed Rule
III. Legal Authority
IV. Comments on the Proposed Rule and FDA Response
V. Effective Date
VI. Economic Analysis of Impacts
VII. Analysis of Environmental Impact
VIII. Paperwork Reduction Act of 1995
IX. Federalism

I. Executive Summary

A. Purpose of the Final Rule

    The regulations in Sec.  511.1(c) (21 CFR 511.1(c)) provide that a 
disqualified clinical investigator is ineligible to conduct any 
clinical investigation that supports an application for a research or 
marketing permit for products regulated by FDA. However, the animal 
drug regulations permit the same clinical investigator to conduct both 
nonclinical laboratory studies as well as clinical investigations. We 
have proposed changes to these regulations (81 FR 57812, August 24, 
2016) that would prevent disqualified clinical investigators from 
conducting nonclinical laboratory studies intended to support an 
application for a research or marketing permit for a new animal drug, 
thus enhancing protection of animal research subjects and ensuring the 
quality and integrity of data submitted to FDA in support of a new 
animal drug approval.

B. Summary of the Major Provisions of the Final Rule

    This final rule expands the clinical investigator disqualification 
regulations in Sec.  511.1(c) to include the ineligibility of a 
disqualified investigator to conduct any nonclinical laboratory study 
intended to support an application for a research or marketing permit 
for a new animal drug. We received one comment, and it supported the 
proposed amendment.

C. Legal Authority

    FDA is issuing these regulations based on its authority under the 
new animal drug provisions in section 512 of the Federal Food, Drug, 
and Cosmetic Act (FD&C Act) (21 U.S.C. 360b) and under section 701(a) 
of the FD&C Act (21 U.S.C. 371(a)), which gives the Agency general 
rulemaking authority to issue regulations for the efficient enforcement 
of the FD&C Act.

D. Costs and Benefits

    FDA believes this final rule is not a significant regulatory action 
as defined by Executive Order 12866 and certifies that it will not have 
a significant economic impact on a substantial number of small 
entities. FDA and applicants will not incur additional costs by 
expanding the scope in part 511 for disqualification of a clinical 
investigator. The benefit of preventing a disqualified clinical 
investigator from performing both nonclinical laboratory studies as 
well as clinical investigations will be enhanced protection of animal 
research subjects and data integrity submitted to FDA in support of a 
new animal drug approval.

II. Background

    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 (e.g., new 
animal drug for investigational use) under study by the investigator in 
the clinical investigation. For example, the Center for Veterinary 
Medicine (CVM or the Center) may pursue disqualification of a clinical 
investigator who conducted a new animal drug clinical investigation and 
allegedly submitted to FDA or the sponsor false information in a 
required report.
    The regulations provide the investigator who is subject to 
disqualification an opportunity to be heard and explain the matter 
complained of, i.e., explain the alleged violations. 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 (e.g., a new animal drug 
for investigational use). When disqualified by a Commissioner's 
decision, the investigator is no longer eligible to receive the 
particular type of test article under study when the violations 
occurred (e.g., new animal drugs). Also, an investigator disqualified 
by a Commissioner's decision is ineligible to conduct any clinical 
investigation that supports an application for a research or marketing 
permit for products regulated by FDA.
    Because CVM regulates drugs for animal use, the study subjects are 
animals in both clinical investigations and nonclinical laboratory 
studies intended to support the approval of a new animal drug. 
Nonclinical laboratory studies such as those for target animal safety 
and human food safety may be essential in determining whether to 
approve an application for a research or marketing permit for a new 
animal drug. For animal drug products regulated by CVM, the same 
investigator may conduct both clinical investigations and nonclinical 
laboratory studies. For example, CVM's two most recent clinical 
investigator disqualification matters involved investigators who were 
also study directors on nonclinical laboratory studies submitted to CVM 
in support of applications for a new animal drug. In addition, CVM is 
aware of multiple persons who conduct both clinical investigations and 
nonclinical laboratory studies intended to support an application for a 
research or marketing permit for a new animal drug. Therefore, CVM 
proposed (81 FR 57812) that it have authority to disqualify an 
investigator from conducting nonclinical laboratory studies intended to 
support an application for a research or marketing permit for a new 
animal drug when that same investigator is disqualified from conducting 
clinical investigations.

A. Need for the Regulation

    Expanding the regulations to include that a disqualified 
investigator is ineligible to conduct any nonclinical laboratory study 
intended to support an application for a research or marketing permit 
for a new animal drug helps to ensure adequate protection of animal 
research subjects and data integrity. This action also leads to 
improved public confidence in the nonclinical and clinical data 
supporting FDA decisions for new animal drug approvals.

[[Page 61445]]

B. Summary of Comments to the Proposed Rule

    We received one comment to the proposed rule. The comment supports 
the proposal. Therefore, we are finalizing the proposal without 
revision.

III. Legal Authority

    We are issuing this final rule under section 512(j) of the FD&C 
Act, which authorizes FDA to issue regulations for exempting from the 
operation of section 512 of the FD&C Act new animal drugs intended 
solely for investigational use by experts qualified by scientific 
training and experience to investigate the safety and effectiveness of 
animal drugs, and section 701(a) of the FD&C Act, which authorizes FDA 
to issue regulations for the efficient enforcement of the FD&C Act. An 
investigator who repeatedly or deliberately submits to FDA or the 
sponsor false information in a required report would not be considered 
a qualified expert with the experience required to conduct nonclinical 
laboratory studies intended to support an application for a research or 
marketing permit for a new animal drug. FDA therefore concludes that 
legal authority to promulgate this rule exists under sections 512(j) 
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 201, 501, 502, 503, 512, and 701 of the FD&C Act (21 
U.S.C. 321, 351, 352, 353, 360b, and 371).

IV. Comments on the Proposed Rule and FDA Response

    We received no adverse or substantive comment and are finalizing 
without change.

V. Effective Date

    This rule is effective January 29, 2018.

VI. Economic Analysis of Impacts

    We have examined the impacts of the final rule under Executive 
Order 12866, Executive Order 13563, Executive Order 13771, 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 us 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). Executive Order 13771 
requires that the costs associated with significant new regulations 
``shall, to the extent permitted by law, be offset by the elimination 
of existing costs associated with at least two prior regulations.'' 
This final rule is not a significant regulatory action as defined by 
Executive Order 12866.
    The Regulatory Flexibility Act requires us to analyze regulatory 
options that would minimize any significant impact of a rule on small 
entities. Because this rule does not impose new requirements on any 
entity and therefore has no associated compliance costs, we certify 
that the final rule will not have a significant economic impact on a 
substantial number of small entities.
    The Unfunded Mandates Reform Act of 1995 (section 202(a)) requires 
us to prepare a written statement, which includes an assessment of 
anticipated costs and benefits, before issuing ``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 $148 
million, using the most current (2016) Implicit Price Deflator for the 
Gross Domestic Product. This final rule will not result in an 
expenditure in any year that meets or exceeds this amount.
    This rule expands the scope in part 511 of disqualification of a 
clinical investigator to include ineligibility to conduct nonclinical 
laboratory studies intended to support an application for a research or 
marketing permit for a new animal drug. A final rule published on April 
30, 2012 (77 FR 25353), prevents a disqualified investigator from 
conducting any clinical investigation, and therefore applies explicitly 
to clinical investigations. However, that rule was silent on 
nonclinical laboratory studies. Thus, before this final rule, a 
disqualified investigator could conduct a nonclinical laboratory study 
intended to support an application for a research or marketing permit 
for a new animal drug. Because the reason for disqualification in part 
511 is typically the repeated or deliberate submission of false 
information to us or to sponsors in a required report, preventing a 
disqualified clinical investigator from performing both nonclinical 
laboratory studies and clinical investigations is essential to adequate 
protection of animal research subjects and data integrity.
    We will not incur additional costs by expanding the scope in part 
511 for disqualification of a clinical investigator because we already 
post the names of any disqualified investigator on FDA's internet site 
at https://www.accessdata.fda.gov/scripts/SDA/sdNavigation.cfm?sd=clinicalinvestigatorsdisqualificationproceedings&previewMode=true&displayAll=true. Similarly, industry will not incur 
additional costs because the rule does not require applicants to 
perform additional tasks. For instance, upon disqualification, we post 
the respective investigator's name on FDA's internet site, which helps 
mitigate the employment of a disqualified investigator for clinical 
investigations or nonclinical laboratory studies intended to support an 
application for a research or marketing permit for a new animal drug. 
The benefit of preventing a disqualified clinical investigator from 
performing both nonclinical laboratory studies and clinical 
investigations will be enhanced protection of animal research subjects 
and data integrity.

VII. Analysis of Environmental Impact

    We have 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.

VIII. Paperwork Reduction Act of 1995

    This final rule contains no collection of information. Therefore, 
clearance by the Office of Management and Budget under the Paperwork 
Reduction Act of 1995 is not required.

IX. Federalism

    We have 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, we conclude 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.

List of Subjects

21 CFR Part 16

    Administrative practice and procedure.

21 CFR Part 511

    Animal drugs, Medical research, Reporting and recordkeeping 
requirements.


[[Page 61446]]


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

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

0
1. The authority citation for 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. In Sec.  16.1, in paragraph (b)(2), revise the numerically sequenced 
entry for Sec.  511.1(c)(1) to read as follows:


Sec.  16.1  Scope.

* * * * *
    (b) * * *
    (2) * * *
    (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; and 
any nonclinical laboratory study intended to support an application for 
a research or marketing permit for a new animal drug.
* * * * *

PART 511--NEW ANIMAL DRUGS FOR INVESTIGATIONAL USE

0
3. The authority citation for part 511 continues to read as follows:

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


0
4. In Sec.  511.1:
0
a. Revise the section heading;
0
b. Revise the last sentence in paragraph (c)(1);
0
c. Add paragraphs (c)(1)(i) and (ii);
0
d. Revise the last sentence in paragraph (c)(2);
0
e. Add paragraphs (c)(2)(i) and (ii); and
0
f. Revise paragraph (c)(6).
    The revisions and additions read as follows:


Sec.  511.1  New animal drugs for investigational use exempt from 
section 512(a) of the Federal Food, Drug, and Cosmetic Act.

* * * * *
    (c) * * *
    (1) * * * 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 question of whether the investigator is eligible to receive test 
articles under this part and eligible to conduct:
    (i) Any clinical investigation that supports an application for a 
research or marketing permit for products regulated by FDA; and
    (ii) Any nonclinical laboratory study intended to support an 
application for a research or marketing permit for a new animal drug.
    (2) * * * The notification also will explain that an investigator 
determined to be ineligible to receive test articles under this part 
will be ineligible to conduct:
    (i) 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; and
    (ii) Any nonclinical laboratory study intended to support an 
application for a research or marketing permit for a new animal drug.
* * * * *
    (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 and 
any nonclinical laboratory study intended to support an application for 
a research or marketing permit for a new animal drug, solely in 
compliance with the applicable provisions of this chapter.
* * * * *

    Dated: December 21, 2017.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2017-27973 Filed 12-27-17; 8:45 am]
BILLING CODE 4164-01-P