Federal Register / Vol. 76, No. 71 / Wednesday, April 13, 2011 / Proposed Rules 20575 

21 5 U.S.C. 601–612 (2006). 

22 5 U.S.C. 605(b) (2006). 

23 5 U.S.C. 601(3) (citing section 3 of the Small 

Business Act, 15 U.S.C. 623 (2006)). Section 3 

defines a ‘‘small-business concern’’ as a business 

which is independently owned and operated and 

which is not dominant in its field of operation. 

C. Regulatory Flexibility Act 

20. The Regulatory Flexibility Act of 

1980 (RFA) 21 generally requires a 

description and analysis of final rules 

that will have significant economic 

impact on a substantial number of small 

entities. The Commission is not 

required to make such an analysis if 

proposed regulations would not have 

such an effect.22 Most companies 

regulated by the Commission do not fall 

within the RFA’s definition of a small 

entity.23

21. The rule proposed herein should 

have no significant negative impact on 

those entities, be they large or small, 

subject to the Commission’s regulatory 

jurisdiction under the NGA. Most 

companies to which the rules proposed 

herein, if finalized, would apply, do not 

fall within the RFA’s definition of small 

entities. In addition, the proposed rule 

is only triggered if more than one 

affiliate of the same entity participates 

in an open season for pipeline capacity 

in which the pipeline may allocate 

capacity on a pro rata basis, and each 

affiliate does not have an independent 

business reason for submitting a bid. 

Therefore, the rule would only affect a 

limited number of small entities. The 

rules proposed herein, if finalized, will 

not have a significant economic effect 

on these small entities because the rule 

does not impose any reporting or 

recordkeeping requirements. Therefore, 

the Commission certifies that the 

proposed rules will not have a 

significant economic effect on a 

substantial number of small entities. 

D. Comment Procedures 

22. The Commission invites interested 

persons to submit comments on the 

matters and issues proposed in this 

notice to be adopted, including any 

related matters or alternative proposals 

that commenters may wish to discuss. 

Comments are due 45 days from 

publication in the Federal Register. 

Comments must refer to Docket No. 

RM11–15–000, and must include the 

commenter’s name, the organization 

they represent, if applicable, and their 

address in their comments. 

23. The Commission encourages 

comments to be filed electronically via 

the eFiling link on the Commission’s 

Web site at http://www.ferc.gov. The 

Commission accepts most standard 

word processing formats. Documents 

created electronically using word 

processing software should be filed in 

native applications or print-to-PDF 

format and not in a scanned format. 

Commenters filing electronically do not 

need to make a paper filing. 

24. Commenters that are not able to 

file comments electronically must mail 

or hand deliver an original copy of their 

comments to: Federal Energy Regulatory 

Commission, Secretary of the 

Commission, 888 First Street, NE., 

Washington, DC 20426. 

25. All comments will be placed in 

the Commission’s public files and may 

be viewed, printed, or downloaded 

remotely as described in the Document 

Availability section below. Commenters 

on this proposal are not required to 

serve copies of their comments on other 

commenters. 

E. Document Availability 

26. In addition to publishing the full 

text of this document in the Federal 

Register, the Commission provides all 

interested persons an opportunity to 

view and/or print the contents of this 

document via the Internet through 

FERC’s Home Page (http://www.ferc.gov) 

and in FERC’s Public Reference Room 

during normal business hours (8:30 a.m. 

to 5 p.m. Eastern time) at 888 First 

Street, NE., Room 2A, Washington, DC 

20426. 

27. From FERC’s Home Page on the 

Internet, this information is available on 

eLibrary. The full text of this document 

is available on eLibrary in PDF and 

Microsoft Word format for viewing, 

printing, and/or downloading. To access 

this document in eLibrary, type the 

docket number excluding the last three 

digits of this document in the docket 

number field. 

28. User assistance is available for 

eLibrary and the FERC’s Web site during 

normal business hours from FERC 

Online Support at (202) 502–6652 (toll 

free at 1–866–208–3676) or e-mail at 

ferconlinesupport@ferc.gov, or the 

Public Reference Room at (202) 502– 

8371, TTY (202)502–8659. E-mail the 

Public Reference Room at 

public.referenceroom@ferc.gov. 

List of Subjects in 18 CFR Part 284 

Continental shelf, Natural gas, 

Reporting and recordkeeping 

requirements. 

By direction of the Commission. 

Kimberly D. Bose, 

Secretary. 

In consideration of the foregoing, the 

Commission proposes to amend part 

284, Chapter I, Title 18, Code of Federal 

Regulations, to read as follows: 

PART 284—CERTAIN SALES AND 

TRANSPORTATION OF NATURAL GAS 

UNDER THE NATURAL GAS POLICY 

ACT OF 1978 AND RELATED 

AUTHORITIES 

1. The authority citation for part 284 

continues to read as follows: 

Authority: 15 U.S.C. 717–717w, 3301– 

3432; 42 U.S.C. 7101–7352; 43 U.S.C. 1331– 

1356. 

2. Section 284.15 is added to read as 

follows. 

§ 284.15 Bidding by affiliates in open 

seasons for pipeline capacity. 

(a) Multiple affiliates of the same 

entity may not participate in an open 

season for pipeline capacity conducted 

by any interstate pipeline providing 

service under subparts B and G of this 

part, in which the pipeline may allocate 

capacity on a pro rata basis, unless each 

affiliate has an independent business 

reason for submitting a bid. 

(b) If more than one affiliate of the 

same entity participates in an open 

season subject to paragraph (a) of this 

section, none of those affiliates may 

release any capacity obtained in that 

open season to any affiliate, or 

otherwise allow any affiliate effectively 

to obtain the use of the allocated 

capacity. 

(c) For purposes of this section, an 

affiliate is any person that satisfies the 

definition of affiliate in §§ 358.3(a)(1) 

and (3) of this chapter with respect to 

another entity participating in an open 

season subject to paragraph (a) of this 

section. 

[FR Doc. 2011–8915 Filed 4–12–11; 8:45 am] 

BILLING CODE 6717–01–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: Proposed rule. 

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 


srobinson on DSKHWCL6B1PROD with PROPOSALS
20576 Federal Register / Vol. 76, No. 71 / Wednesday, April 13, 2011 / Proposed Rules 

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: http:// 

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 http://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 http:// 

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 

(§§ 312.70(a), 511.1(c)(1), and 812.119(a)) 

B. Ineligibility To Receive Any Test Article 

(§§ 312.70(b), 511.1(c)(2), and 

812.119(b)) 

C. Disqualified Investigator’s Data in 

Applications and Submissions to FDA 

(§§ 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 (§§ 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 

(§§ 312.70(e), 511.1(c)(5), and 812.119(e)) 

F. Other Proceedings 

G. Reinstatement (§§ 312.70(f), 511.1(c)(6), 

and 812.119(f)) 

H. Part 511 Definitions (§ 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 § 312.70 (21 CFR 312.70); 

new animal drugs in § 511.1(c) (21 CFR 

511.1(c)); or devices in § 812.119 (21 

CFR 812.119). The proposed rulemaking 

will amend §§ 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 § 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 FDAregulated 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 


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Federal Register / Vol. 76, No. 71 / Wednesday, April 13, 2011 / Proposed Rules 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 FDAregulated 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 FDAregulated 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 

§§ 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 

§ 511.1(c) to match those currently in 

§§ 312.70 and 812.119. Therefore, we 

propose to change the heading in 

§ 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 

(§§ 312.70(a), 511.1(c)(1), and 

812.119(a)) 

FDA proposes to revise the provisions 

currently in §§ 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 § 312.70(a) 

• To harmonize the provisions in 

§ 312.70(a) with those currently in 

§ 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 

§ 312.70(a) with those currently in 

§ 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 § 312.70(a) with the 

provisions currently in § 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 § 511.1(c)(1) 

• To harmonize the investigator 

disqualification regulations, we propose 

to change the first words in the first 

sentence in § 511.1(c)(1) from 

‘‘Whenever the Food and Drug 

Administration’’ to ‘‘If FDA’’. 

• Although already applicable, we 

propose to add explicit provisions in 

§ 511.1(c)(1), consistent with the current 

regulations in § 312.70(a), that a clinical 

investigator includes a sponsorinvestigator. Because sponsorVerDate Mar<15>2010 18:03 Apr 12, 2011 Jkt 223001 PO 00000 Frm 00010 Fmt 4702 Sfmt 4702 E:\FR\FM\13APP1.SGM 13APP1

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20578 Federal Register / Vol. 76, No. 71 / Wednesday, April 13, 2011 / Proposed Rules 

1See, 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. 

2See, 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. 

3FDA 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 (§ 16.26(a)). 

4See part 16, subpart D—Procedures for 

Regulatory Hearing. 

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

• To harmonize the provisions in 

§ 511.1(c)(1) with the provisions 

currently in § 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 § 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 

§ 511.1(c)(1) with those currently in 

§ 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 §§ 312.70(a) and 

812.119(a), we propose to change in the 

second sentence in § 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 § 812.119(a) 

• Although already applicable, we 

propose to add explicit provisions in 

§ 812.119(a), consistent with the current 

regulations in § 312.70(a), that a clinical 

investigator includes a sponsorinvestigator. Because sponsorinvestigators 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

• To harmonize the provisions in 

§ 812.119(a) with those currently in 

§ 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 

§ 812.119(a) with those currently in 

§ 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 §§ 312.70(a) and 511.1(c)(1), 

we propose to change the language in 

§ 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 §§ 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 §§ 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 


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Federal Register / Vol. 76, No. 71 / Wednesday, April 13, 2011 / Proposed Rules 20579 

5 63 FR 55873 at 55874, October 19, 1998. 

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. 

B. Ineligibility To Receive Any Test 

Article (§§ 312.70(b), 511.1(c)(2), and 

812.119(b)) 

1. Proposed Revisions to § 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 § 312.70(b) with FDA’s 

current procedures along with those 

provisions currently in § 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 § 312.70(b) to help 

ensure that any reviewing IRB is aware 

of the clinical investigator’s 

disqualification. 

• 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 § 511.1(c)(2) 

• To harmonize the investigator 

disqualification regulations in 

§ 511.1(c)(2) with those currently in 

§§ 312.70(b) and 812.119(b), we propose 

to change the first word ‘‘If’’ in 

§ 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 

§ 511.1(c)(2) to ‘‘this section’’. 

• For clarity and to harmonize 

§ 511.1(c)(2) with the proposed 

investigator disqualification regulations 

in §§ 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 § 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 

§ 812.119(b) with the proposed 

investigator disqualification regulations 

in §§ 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 


srobinson on DSKHWCL6B1PROD with PROPOSALS
20580 Federal Register / Vol. 76, No. 71 / Wednesday, April 13, 2011 / Proposed Rules 

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 FDAregulated 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 

(§§ 312.70(c), 511.1(c)(3), and 

812.119(c)) 

1. Proposed Revisions to § 312.70(c) 

Currently, § 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 

§ 312.70(c) to clarify the applicability of 

this provision, update this provision 

consistent with §§ 312.70(b), 511.1(c)(2), 

and 812.119(b) of this proposal, and to 

harmonize the disqualification 

regulations in §§ 312.70(c), 511.1(c)(3), 

and 812.119(c). Therefore, we propose 

to amend § 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 § 511.1(c)(3) 

Currently, § 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 § 511.1(c)(3) to clarify the 

applicability of this provision, update 

this provision consistent with 

§§ 312.70(b), 511.1(c)(2), and 812.119(b) 

of this proposal, and to harmonize the 

disqualification regulations in 

§§ 312.70(c), 511.1(c)(3), and 812.119(c). 

Therefore, we propose to revise 

§ 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 § 812.119(c) 

Currently, § 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 § 812.119(c) to clarify the 

applicability of this provision, update 

this provision consistent with 

§§ 312.70(b), 511.1(c)(2), and 812.119(b) 

of this proposal, and to harmonize the 

disqualification regulations in 

§§ 312.70(c), 511.1(c)(3), and 812.119(c). 

Therefore, we propose to revise 

§ 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 FDAregulated 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 (§§ 312.70(d), 

511.1(c)(4), and 812.119(d)) 

1. Proposed Revisions to § 312.70(d) 

• In accordance with FDA’s 

procedures and for consistency with the 

provisions currently in § 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 §§ 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 § 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. 


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Federal Register / Vol. 76, No. 71 / Wednesday, April 13, 2011 / Proposed Rules 20581 

2. Proposed Revisions to § 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 § 511.1(c)(4): 

Æ Change ‘‘he shall first’’ to ‘‘the 

Commissioner will’’, 

Æ Change ‘‘before the Food and Drug 

Administration pursuant to’’ to ‘‘before 

FDA under’’, 

Æ Remove ‘‘on whether the exemption 

should be terminated’’, 

Æ Change ‘‘he’’ to ‘‘the Commissioner’’, 

Æ Change ‘‘forthwith’’ to 

‘‘immediately’’, 

Æ Change ‘‘event’’ to ‘‘case’’, 

Æ Change ‘‘the Food and Drug 

Administration pursuant to’’ to ‘‘FDA 

under’’, and 

Æ Remove ‘‘(see 42 FR 15075, March 

22, 1977)’’. 

• We propose to add a new sentence 

at the end of § 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 § 812.119(d) 

• We propose to change 

‘‘determination’’ to ‘‘termination’’. This 

correction is consistent with the 

regulations currently in § 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 § 812.119(d). As proposed 

for §§ 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 

(§§ 312.70(e), 511.1(c)(5), and 

812.119(e)) 

1. Proposed Revisions to § 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 

§§ 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 § 511.1(c)(5) 

The current investigator 

disqualification regulations in 

§ 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 § 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 §§ 312.70(e), 

511.1(c)(5), and 812.119(e). Therefore, 

in § 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 (§§ 312.70(f), 

511.1(c)(6), and 812.119(f)) 

FDA proposes minor revisions to the 

regulations currently in §§ 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 § 312.70(f), ‘‘an 

investigator who has been determined to 

be ineligible under paragraph (b) of 


srobinson on DSKHWCL6B1PROD with PROPOSALS
20582 Federal Register / Vol. 76, No. 71 / Wednesday, April 13, 2011 / Proposed Rules 

[§ 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 

§§ 312.70(f) and 812.119(f), and the 

reference to ‘‘the exempting regulations 

in this section’’ in § 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 §§ 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 §§ 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 (§ 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 (§ 16.1(b)(2)) is incomplete. 

The provisions for § 58.204(b) (21 CFR 

58.204(b)), relating to disqualifying a 

testing facility, and § 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) 


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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 FDAregulated 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 


srobinson on DSKHWCL6B1PROD with PROPOSALS
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6See http://www.reginfo.gov/public/do/

PRAViewICR?ref_nbr=200905-0910-005 (accessed 

on February 4, 2011). 

7See http://www.reginfo.gov/public/do/

PRAViewICR?ref_nbr=200711-0910-003 (accessed 

on February 4, 2011). 

8See http://www.reginfo.gov/public/do/

PRAViewICR?ref_nbr=200806-0910-005 (accessed 

on February 4, 2011). 

9See http://www.reginfo.gov/public/do/

PRAViewICR?ref_nbr=201001-0910-010 (accessed 

on February 4, 2011). 

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 FDAregulated 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 FDAregulated 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 FDAregulated 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 decisionmaking 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. Clinical investigators 

may be associated with government and 

academic research institutions, contract 

research organizations, site-management 

organizations, or independent 

researchers. Investigational product 

research is often sponsored by FDAregulated firms that seek to bring a new 

product to market. 

The proposed rule is not expected to 

have a significant economic impact on 

a substantial number of small entities as 

previously discussed in this document. 

As stated above in this section of this 

document, we do not expect that the 

proposed rule would impose additional 

new costs. This proposed rule is 

expected to affect an average of about 1 

to 2 clinical investigators per year. 

Affected investigators are disqualified 

because FDA has evidence that the 

clinical investigator repeatedly or 

deliberately violated FDA’s regulations 

governing the proper conduct of clinical 

investigations. FDA is not imposing any 

additional requirements for the conduct 

of clinical investigations used to 

support marketing applications. It is 

clarifying its regulatory authority over 

disqualified investigators. Under this 

proposed rule a disqualified investigator 

would explicitly be ineligible to 

conduct any studies of FDA-regulated 

articles. We have little, if any, evidence 

that a disqualified investigator has 

conducted a clinical investigation 

studying a different type of test article. 

For the reasons stated above, we 

propose to certify that this proposed 

rule would not have a significant 

economic impact on a substantial 

number of small entities. 

IX. Paperwork Reduction Act of 1995 

This proposed 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 number 0910–0014; 

expiration date August 31, 2011.6 The 

notification of IRB(s) in proposed 

§ 312.70 is approved under OMB control 

number 0910–0130—Protection of 

Human Subjects; Recordkeeping 

Requirements for Institutional Review 

Boards (IRBs); expiration date December 

31, 2010 (renewal pending at OMB).7

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 number 0910–0117; 

expiration date August 31, 2011.8 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 part 812, OMB 

control number 0910–0078; expiration 

date February 28, 2013.9 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, 

part 814, are approved under OMB 

control number 0910–0231. 

X. Federalism 

FDA has analyzed this proposed rule 

in accordance with the principles set 

forth in Executive Order 13132. FDA 

has determined that the proposed rule, 

if finalized, would not contain policies 

that would 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 tentatively 

concludes that the proposed 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. 


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XI. Request for Comments 

Interested persons may submit to the 

Division of Dockets Management (see 

ADDRESSES) either electronic or written 

comments regarding this document. It is 

only necessary to send one set of 

comments. It is no longer necessary to 

send two copies of mailed comments. 

Identify comments with the docket 

number found in brackets in the 

heading of this document. Received 

comments may be seen in the Division 

of Dockets Management between 9 a.m. 

and 4 p.m., Monday through Friday. 

XII. References 

The following reference has been 

placed on display in the Division of 

Dockets Management, Food and Drug 

Administration, 5630 Fishers Lane, rm. 

1061, Rockville, MD 20857 and may be 

seen by interested persons between 

9 a.m. and 4 p.m., Monday through 

Friday. We have verified the Web site 

address, but we are not responsible for 

any subsequent changes to the Web site 

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 

(accessed on February 4, 2011). 

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, it is proposed that 

21 CFR parts 16, 312, 511, and 812 be 

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 adding in numerical 

sequence 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. 

* * * * * 

§ 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 of this 

chapter, 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 pursuit of 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 of this 

chapter, 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 board 

(IRB(s)) that the investigator is not 

eligible to receive test articles under this 

part. The notification to the investigator, 

sponsor, and IRB(s) will provide a 

statement of the basis for such 


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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 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 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 IRB(s) 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 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 

revising paragraph (c) to 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 pursuit of 

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 

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 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 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 of this chapter 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. 


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(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. Part 511 is amended by adding 

§ 511.3 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 FDA. 

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 of this 

chapter, 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 pursuit of 

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 of this 

chapter, 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 IRB(s) that the 

investigator is not eligible to receive test 

articles under this part. The notification 

to the investigator, sponsor, and IRB(s) 

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 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 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 IDE 

immediately and notify the sponsor and 

the reviewing IRB(s) 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 


srobinson on DSKHWCL6B1PROD with PROPOSALS
20588 Federal Register / Vol. 76, No. 71 / Wednesday, April 13, 2011 / Proposed Rules 

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 7, 2011. 

David Dorsey, 

Acting Deputy Commissioner for Policy, 

Planning and Budget. 

[FR Doc. 2011–8786 Filed 4–12–11; 8:45 am] 

BILLING CODE 4160–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

21 CFR Chapter I 

[Docket No. FDA–2011–N–0251] 

FDA Food Safety Modernization Act: 

Focus on Preventive Controls for 

Facilities; Public Meeting 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice of public meeting; 

request for comment. 

SUMMARY: The Food and Drug 

Administration (FDA) is announcing a 

public meeting entitled ‘‘FDA Food 

Safety Modernization Act: Focus on 

Preventive Controls for Facilities.’’ The 

purpose of the public meeting is to 

provide interested persons an 

opportunity to discuss implementation 

of the preventive controls for facilities 

provisions of the recently enacted FDA 

Food Safety Modernization Act (FSMA). 

FDA is seeking information on 

preventive controls used by facilities to 

identify and address hazards associated 

with specific types of food and specific 

processes. The public will have an 

opportunity to provide information and 

share views that will inform the 

development of guidance and 

regulations on preventive controls for 

food facilities that manufacture, process, 

pack or hold human food or animal food 

and feed (including pet food). 

DATES: See ‘‘How to Participate in the 

Meeting’’ in the SUPPLEMENTARY

INFORMATION section of this document. 

FOR FURTHER INFORMATION CONTACT: 

Patricia M. Kuntze, Office of External 

Affairs, Food and Drug Administration, 

10903 New Hampshire Ave., Bldg. 32, 

rm. 5322, Silver Spring, MD 20993, 

301–796–8641, 

Patricia.Kuntze@fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: 

I. Background 

FSMA (Pub. L. 111–353) amends the 

Federal Food, Drug, and Cosmetic Act 

(the FD&C Act) to establish the 

foundation for a modernized, 

prevention-based food safety system and 

gives FDA for the first time a legislative 

mandate to require comprehensive, 

science-based preventive controls across 

the food supply. 

In particular, section 103 of FSMA 

requires the owner, operator, or agent in 

charge of a facility that is required to 

register under section 415 of the FD&C 

Act (21 U.S.C. 350d) to take certain 

preventive actions, including to 

evaluate the hazards that could affect 

food manufactured, processed, packed, 

or held by the facility, and to identify 

and implement preventive controls to 

significantly minimize or prevent the 

occurrence of such hazards. FDA is 

required to develop regulations to 

establish science-based standards for 

conducting a hazard analysis, 

documenting hazards, implementing 

preventive controls, and documenting 

their implementation. 

In addition, FDA is required to issue 

guidance with respect to hazard analysis 

and preventive controls. Given the 

diversity of registered facilities and 

regulated foods, FDA will use the 

guidance to assist the food and feed 

industries in complying with the 

preventive controls regulations, when 

they are finalized. FDA will leverage, 

where appropriate, best practices for 

hazards and controls identified by 

industry for specific types of food and 

feed and specific methods in 

manufacturing, processing, packing, and 

holding food and feed. FDA is interested 

in making appropriate best practices 

publicly available. FDA is particularly 

interested in preventive control 

practices that are applicable and 

practical for small and very small 

businesses to implement. 

II. Purpose and Format of the Meeting 

If you wish to attend and/or present 

at the meeting scheduled for April 20, 

2011, please register by e-mail at 

http://www.blsmeetings.net/ 

FDAPreventiveControls by April 15, 

2011. FDA is holding the public meeting 

on section 103 of FSMA to receive input 

from the public to inform the 

development of the regulations and 

guidance identified previously in this 

document. FDA will also consider input 

it has received previously through its 

engagement of stakeholders as part of 

the process to examine and update 

current good manufacturing practice 

requirements and to develop an animal 

feed safety system. 

In general, the meeting format will 

include introductory presentations by 

FDA. Listening to our stakeholders is 

the primary purpose of this meeting. In 

order to meet this goal, FDA will 

provide multiple opportunities for 

individuals to actively express their 

views by making presentations at the 

meeting, participating in a total of three 

75-minute break-out sessions on the 

provisions discussed at the meeting, and 

submitting written comments to the 

docket within 30 days after this 

meeting. (Participants can select up to 

three of the following five break-out 

sessions: Preventive Controls Guidance, 

On-Farm Manufacturing and Small 

Business, Product Testing and 

Environmental Monitoring, Training 

and Technical Assistance, and 

Preventive Controls and the 

Relationship to cGMPs.) There will be 

an interactive Webcast; see section III of 

this document, ‘‘How to Participate in 

the Meeting.’’ In order to provide 

Webcast participants with information 

before and after the meeting, we request 

attendees provide their name, their 

affiliation, and email when registering. 

III. How To Participate in the Meeting 

Stakeholders will have an opportunity 

to provide oral comments. Due to 

limited space and time, FDA encourages 

all persons who wish to attend the 

meeting, including those requesting an 

opportunity to make an oral 

presentation during the time allotted for 

public comment at the meeting, to 

register in advance and to provide the 

specific topic or issue to be addressed 

and the approximate desired length of 

their presentation. Depending on the 

number of requests for such oral 

presentations, there may be a need to 

limit the time of each oral presentation 

(e.g., 3 minutes each). If time permits, 

individuals or organizations that did not 

register in advance may be granted the 

opportunity for such an oral 

presentation. FDA would like to 

maximize the number of stakeholders 

who make a presentation at the meeting 

and will do our best to accommodate all 

persons who wish to make a 

presentation or express their views at 

the meeting. FDA anticipates that there 

will be several opportunities to speak in 

break-out sessions and an interactive 

Webcast will also be available for 

stakeholders who are not onsite. 

FDA encourages persons and groups 

who have similar interests to 

consolidate their information for 

presentation through a single 

representative. After reviewing the 

presentation requests, FDA will notify 

each participant before the meeting of 

the amount of time available and the 


srobinson on DSKHWCL6B1PROD with PROPOSALS