Federal Register / Vol. 77, No. 83 / Monday, April 30, 2012 / Rules and Regulations 25353 

FDIC has sought to present the Final 

Rule in a simple and straightforward 

manner. 

List of Subjects in 12 CFR Part 380 

Holding companies, Insurance 

companies, Mutual insurance holding 

companies. 

For the reasons stated above, the 

Board of Directors of the Federal 

Deposit Insurance Corporation amends 

part 380 of title 12 of the Code of 

Federal Regulations as follows: 

PART 380—ORDERLY LIQUIDATION 

AUTHORITY 

■ 1. The authority citation for part 380 

is revised to read as follows: 

Authority: 12 U.S.C. 5383(e); 12 U.S.C. 

5389; 12 U.S.C. 5390(s)(3); 12 U.S.C. 

5390(b)(1)(C); 12 U.S.C. 5390(a)(7)(D). 

■ 2. The heading for subpart A is 

revised to read as follows: 

Subpart A—General and Miscellaneous 

Provisions 

■ 3. Amend § 380.1 by adding 

definitions of Intermediate insurance 

stock holding company, Mutual 

insurance company, and Mutual 

insurance holding company in 

alphabetical order to read as follows: 

§ 380.1 Definitions. 

* * * * * 

Intermediate insurance stock holding 

company. The term ‘‘intermediate 

insurance stock holding company’’ 

means a corporation organized either at 

the time of, or at any time after, the 

organization of the mutual insurance 

holding company that: 

(1) Is a subsidiary of a mutual 

insurance holding company; 

(2) Holds a majority of the issued and 

outstanding voting stock of the 

converted mutual insurance company 

created at the time of formation of the 

mutual insurance holding company; and 

(3) Holds, as its largest United States 

subsidiary (as measured by total assets 

as of the end of the previous calendar 

quarter), an insurance company. 

Mutual insurance company. The term 

‘‘mutual insurance company’’ means an 

insurance company organized under the 

laws of a State that provides for the 

formation of such an entity as a nonstock mutual corporation in which the 

surplus and voting rights are vested in 

the policyholders. 

Mutual insurance holding company. 

The term ‘‘mutual insurance holding 

company’’ means a corporation that: 

(1) Is lawfully organized under state 

law authorizing its formation in 

connection with the reorganization of a 

mutual insurance company that 

converts the mutual insurance company 

to a stock insurance company, and— 

(2) Holds either: 

(i) A majority of the issued and 

outstanding voting stock of the 

intermediate insurance stock holding 

company, if any, or 

(ii) If there is no intermediate 

insurance stock holding company, a 

majority of the issued and outstanding 

voting stock of the converted mutual 

insurance company. 

* * * * * 

■ 4. Add § 380.11 to read as follows: 

§ 380.11 Treatment of mutual insurance 

holding companies. 

A mutual insurance holding company 

shall be treated as an insurance 

company for the purpose of section 

203(e) of the Dodd-Frank Act, 12 U.S.C. 

5383(e); provided that— 

(a) The company is subject to the 

insurance laws of the state of its 

domicile, including, specifically and 

without limitation, a statutory regime 

for the rehabilitation or liquidation of 

insurance companies that are in default 

or in danger of default; 

(b) The company is not subject to 

bankruptcy proceedings under Title 11 

of the United States Code; 

(c) The largest United States 

subsidiary of the company (as measured 

by total assets as of the end of the 

previous calendar quarter) is an 

insurance company or an intermediate 

insurance stock holding company; and 

(d) The assets and investments of the 

company are limited to the securities of 

an intermediate insurance stock holding 

company, the securities of the converted 

mutual insurance company and other 

assets and securities of the type 

authorized for holding and investment 

by an insurance company domiciled in 

its state of incorporation. 

Dated at Washington, DC, this 23rd day of 

April 2012. 

By order of the Board of Directors. 

Federal Deposit Insurance Corporation. 

Robert E. Feldman, 

Executive Secretary. 

[FR Doc. 2012–10146 Filed 4–27–12; 8:45 am] 

BILLING CODE 6714–01–P 

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. 

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 


srobinson on DSK4SPTVN1PROD with RULES
25354 Federal Register / Vol. 77, No. 83 / Monday, April 30, 2012 / Rules and Regulations 

1See, 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). 

2See, 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://

www.fda.gov/RegulatoryInformation/FOI/ 

ElectronicReadingRoom/ucm143242.htm). 

3See, 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://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://www.fda.gov/ 

downloads/RegulatoryInformation/FOI/ 

ElectronicReadingRoom/UCM143906.pdf). 

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://

www.fda.gov/RegulatoryInformation/FOI/ 

ElectronicReadingRoom/ucm143242.htm). 

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 § 312.70, part 511 (21 

CFR part 511) in § 511.1(c), and part 812 

(21 CFR part 812) in § 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 § 16.1(b)(2) an entry for 

§ 812.119; 

• Revising the entries for §§ 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: 

Æ § 58.204(b) (21 CFR 58.204(b)), 

relating to disqualifying a testing 

facility, and 

Æ § 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 §§ 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 §§ 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 § 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

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

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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Federal Register / Vol. 77, No. 83 / Monday, April 30, 2012 / Rules and Regulations 25355 

5See, 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://

www.fda.gov/downloads/RegulatoryInformation/ 

FOI/ElectronicReadingRoom/UCM144019.pdf. 

6On June 18, 2008, Dr. Gentry was determined 

ineligible to receive investigational drugs. See 

http://www.fda.gov/downloads/ 

RegulatoryInformation/FOI/ 

ElectronicReadingRoom/UCM143906.pdf. 

7 Id. at pages 20–21. 

8See http://www.fda.gov/RegulatoryInformation/ 

FOI/ElectronicReadingRoom/ucm092185.htm. 

9See http://www.fda.gov/RegulatoryInformation/ 

FOI/ElectronicReadingRoom/ucm143240.htm. 

10See http://www.fda.gov/ICECI/ 

EnforcementActions/ 

DisqualifiedRestrictedAssuranceList/ 

ucm131681.htm. 

11See http://www.fda.gov/ScienceResearch/ 

SpecialTopics/RunningClinicalTrials/ 

ComplianceEnforcement/default.htm. 

reckless disregard for whether his or her 

conduct may result in a regulatory 

violation may be found to have 

deliberately violated the regulations. 

Decisionmakers in part 16 

proceedings have interpreted the term 

‘‘deliberately’’ in § 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

* * * 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 FDAapproved 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 FDAregulated product. (See §§ 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 §§ 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 productapproval 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. 

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. 

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 

§§ 312.70(b), 511.1(c)(2), and 

812.119(b)). 

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., §§ 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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25356 Federal Register / Vol. 77, No. 83 / Monday, April 30, 2012 / Rules and Regulations 

12See 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. 

13See http://www.fda.gov/ICECI/ 

EnforcementActions/ 

DisqualifiedRestrictedAssuranceList/ 

ucm131681.htm. 

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. 

(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). 

(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 §§ 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 §§ 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, § 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-bycase 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

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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Federal Register / Vol. 77, No. 83 / Monday, April 30, 2012 / Rules and Regulations 25357 

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 


srobinson on DSK4SPTVN1PROD with RULES
25358 Federal Register / Vol. 77, No. 83 / Monday, April 30, 2012 / Rules and Regulations 

14See http://www.reginfo.gov/public/do/ 

PRAViewICR?ref_nbr=200905-0910-005 (accessed 

on March 30, 2012). 

15See http://www.reginfo.gov/public/do/ 

PRAViewICR?ref_nbr=200711-0910-003 (accessed 

on March 30, 2012). 

16See http://www.reginfo.gov/public/do/ 

PRAViewICR?ref_nbr=200806-0910-005 (accessed 

on March 30, 2012). 

17See http://www.reginfo.gov/public/do/ 

PRAViewICR?ref_nbr=201001-0910-010 (accessed 

on March 30, 2012). 

clinical trial data. This final rule will 

help to reduce the risk to human 

subjects who participate in FDAregulated 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 § 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 § 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 § 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 § 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. 

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://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://

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://

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 

■ 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. 

■ 2. Section 16.1 is amended in 

paragraph (b)(2) by numerically adding 

entries for ‘‘§ 58.204(b)’’, ‘‘§ 812.119’’, 

and ‘‘§ 822.7(a)(3)’’, and by revising the 

entries for ‘‘§ 312.70’’ and 

‘‘§ 511.1(c)(1)’’ to read as follows: 

§ 16.1 Scope. 

* * * * * 

(b) * * * 

(2) * * * 

* * * * * 

§ 58.204(b), relating to disqualifying a 

testing facility. 

* * * * * 

§ 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. 

* * * * * 

§ 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. 

* * * * * 


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§ 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. 

* * * * * 

§ 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 

■ 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. 

■ 4. Section 312.70 is revised to read as 

follows: 

§ 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 FDAregulated 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 

■ 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. 

■ 6. Section 511.1 is amended by: 

■ 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). 

■ b. Revising paragraph (c). 

The revisions read as follows: 

§ 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 


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25360 Federal Register / Vol. 77, No. 83 / Monday, April 30, 2012 / Rules and Regulations 

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 FDAregulated 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. 

* * * * * 

■ 7. Section 511.3 is added to read as 

follows: 

§ 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 sponsorinvestigator. 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 

■ 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. 

■ 9. Section 812.119 is revised to read 

as follows: 

§ 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 


srobinson on DSK4SPTVN1PROD with RULES
Federal Register / Vol. 77, No. 83 / Monday, April 30, 2012 / Rules and Regulations 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 FDAregulated 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 

DEPARTMENT OF HOMELAND 

SECURITY 

Coast Guard 

33 CFR Part 165 

[Docket No. USCG–2012–0199] 

RIN 1625–AA00 

Safety Zone; Chicago Harbor, Navy 

Pier Southeast, Chicago, IL 

AGENCY: Coast Guard, DHS. 

ACTION: Notice of enforcement of 

regulation. 

SUMMARY: The Coast Guard will enforce 

the Navy Pier Southeast Safety Zone in 

Chicago Harbor during various periods 

from July 4, 2012 through July 28, 2012. 

This action is necessary and intended to 

ensure safety of life on the navigable 

waters of the United States immediately 

prior to, during, and immediately after 

fireworks events. Enforcement of this 

safety zone will establish restrictions 

upon, and control movement of, vessels 

in a specified area immediately prior to, 

during, and immediately after various 

fireworks events. During the 

enforcement period, no person or vessel 

may enter the safety zones without 

permission of the Captain of the Port, 

Sector Lake Michigan. 

DATES: The regulations in 33 CFR 

165.931 will be enforced at various 

times between 9:00 p.m. on July 4, 2012 

through 10:30 p.m. on July 28, 2012. 

FOR FURTHER INFORMATION CONTACT: If 

you have questions on this notice, call 

or email MST2 Rebecca Stone, 

Prevention Department, Coast Guard 

Sector Lake Michigan, Milwaukee, WI at 

414–747–7154, email 

Rebecca.R.Stone@uscg.mil. 

SUPPLEMENTARY INFORMATION: The Coast 

Guard will enforce the Safety Zone; 

Chicago Harbor, Navy Pier Southeast, 

Chicago, IL listed in 33 CFR 165.931 for 

the following events: 

(1) Navy Pier Fireworks; on July 4, 

2012 from 9:00 p.m. through 11:00 p.m.; 

on July 7, 2012 from 10:00 p.m. through 

10:30 p.m.; on July 11, 2012 from 9:15 

p.m. through 9:45 p.m.; on July 14, 2012 

from 10:00 p.m. through 10:30 p.m.; on 

July 18, 2012 from 9:15 p.m. through 

9:45 p.m.; on July 21, 2012 from 10:00 

p.m. through 10:30 p.m.; on July 25, 

2012 from 9:15 p.m. through 9:45 p.m.; 

and on July 28, 2012 from 10 through 

10:30. 

All vessels must obtain permission 

from the Captain of the Port, Sector Lake 

Michigan, or his or her on-scene 

representative to enter, move within or 

exit the safety zone. Vessels and persons 

granted permission to enter the safety 

zone shall obey all lawful orders or 

directions of the Captain of the Port, 

Sector Lake Michigan, or his or her onscene representative. While within a 

safety zone, all vessels shall operate at 

the minimum speed necessary to 

maintain a safe course. 

This notice is issued under authority 

of 33 CFR 165.931 and 5 U.S.C. 552(a). 

In addition to this notice in the Federal 

Register, the Coast Guard will provide 

the maritime community with advance 

notification of these enforcement 

periods via broadcast Notice to Mariners 

or Local Notice to Mariners. The 

Captain of the Port, Sector Lake 

Michigan, will issue a Broadcast Notice 

to Mariners notifying the public when 

enforcement of the safety zone 

established by this section is suspended. 

If the Captain of the Port, Sector Lake 

Michigan, determines that the safety 

zone need not be enforced for the full 

duration stated in this notice, he or she 

may use a Broadcast Notice to Mariners 

to grant general permission to enter the 

safety zone. The Captain of the Port, 

Sector Lake Michigan, or his or her onscene representative may be contacted 

via VHF Channel 16. 


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