Federal Register / Vol. 62, No. 50 / Friday, March 14, 1997 / Rules and Regulations 12087

monensin, salinomycin, narasin,

semduramicin, and lasalocid) as adverse

reactions may occur. If signs of toxicity

occur, discontinue use. Withdraw 2

days before slaughter. As

chlortetracycline calcium complex,

Type A medicated articles containing

the equivalent of 50 to 100 grams per

pound of chlortetracycline

hydrochloride provided by 000004 and

046573 in § 510.600(c) of this chapter.

Dated: February 6, 1997.

Stephen F. Sundlof,

Director, Center for Veterinary Medicine.

[FR Doc. 97–6476 Filed 3–13–97; 8:45 am]

BILLING CODE 4160–01–F

21 CFR Part 812

[Docket No. 92N–0308]

Investigational Device Exemptions;

Disqualification of Clinical

Investigators

AGENCY: Food and Drug Administration,

HHS.

ACTION: Final rule.

SUMMARY: The Food and Drug

Administration (FDA) is amending its

medical device regulations to include

provisions for the disqualification of

clinical investigators. These amended

regulations parallel, with minor

exceptions, the regulations for

disqualification of clinical investigators

of drugs, biologics, and animal drugs.

The agency is finalizing this regulation

to further implement its plan for

consistent bioresearch monitoring

procedures for all products regulated by

FDA and to improve the remedies

available to deal with clinical

investigators who violate the law. This

action is being taken under the Medical

Device Amendments of 1976.

DATES: Effective May 13, 1997.

FOR FURTHER INFORMATION CONTACT:

Rodney T. Allnutt, Center for Devices

and Radiological Health (HFZ–310),

Food and Drug Administration, 2094

Gaither Rd., Rockville, MD 20850, 301–

594–4718.

SUPPLEMENTARY INFORMATION:

I. Background

FDA has long intended to have

clinical investigator disqualification

procedures available for medical device

investigations. Although the

investigational device exemption (IDE)

regulation part 812 (21 CFR part 812)

allows FDA to initiate regulatory action

against a study sponsor due to a

noncompliant investigator, such as

terminating the sponsor’s IDE or

imposing additional restrictions under

the IDE, the IDE regulation did not

expressly provide for clinical

investigator disqualification. The

proposed IDE regulation, published in

the Federal Register of August 20, 1976

(41 FR 35282 at 35311), contained

disqualification provisions for clinical

investigators in proposed § 812.119 that

were not included in the final IDE

regulations published on January 18,

1980 (45 FR 3732), which apply to

device investigations generally.

Disqualification provisions were

included, however, in part 813 (21 CFR

part 813) on investigational exemptions

for intraocular lenses (IOL’s) in

§ 813.119 (42 FR 58874, November 11,

1977). The preamble to the final IDE

regulation, published in the Federal

Register of January 18, 1980 (45 FR 3732

at 3749), noted that proposed § 812.119

was being removed and would be

addressed in FDA’s final agency-wide

regulation on the obligations of clinical

investigators, which had been proposed

in the Federal Register of August 8,

1978 (43 FR 35186). This agency-wide

regulation, however, was never

finalized.

In the Federal Register of October 6,

1993 (58 FR 52142), FDA issued a

proposed rule to remove part 813, the

regulation on investigational

exemptions for IOL’s. FDA received two

comments in response to the proposed

rule. These comments were addressed

in the preamble to the rule that removed

part 813, which was published in the

Federal Register of January 29, 1997 62

FR 4164.

In the Federal Register of October 6,

1993 (58 FR 52144), FDA also published

a proposed rule governing

disqualification of clinical investigators

of medical devices, to be added to part

812. The proposed rule was virtually

identical to the regulation for

disqualification of clinical investigators

of IOL’s, which would be removed with

the proposed removal of part 813. In the

proposed rule, however, FDA expressly

invited comments on whether the

procedures for disqualification of

clinical investigators of medical devices

should be identical, or virtually

identical to the regulation for the

disqualification of clinical investigators

of drugs and biologics in § 312.70 (21

CFR 312.70). FDA stated that if

comments persuaded the agency to

revise the proposed rule to follow

§ 312.70 precisely or closely, the agency

might issue a final rule which parallels

§ 312.70.

FDA received three comments stating

an explicit preference for rules

governing disqualification of

investigators of drugs as specified in

§ 312.70, over the rules that had been

proposed for disqualification of

investigators of devices. Two other

comments that did not specifically

mention § 312.70 nevertheless suggested

changes to the proposed rule that would

make it more consistent with the drug

investigator disqualification rule. The

other three comments FDA received did

not address this issue.

Two comments preferred § 312.70 to

the proposed regulation because

§ 312.70 does not contain the perceived

flaws found in the proposed regulation.

These comments stated, e.g., that the

threshold for disqualification in

§ 312.70 is set much higher and the

terms are more clearly defined than in

the proposed regulation. One of these

comments requested that the Center for

Devices and Radiological Health (CDRH)

adopt § 312.70 in its entirety because of

the perceived flaws in the proposed

rule. That comment also noted that most

medical device companies and

investigators of devices are unfamiliar

with § 312.70. Therefore, the comment

recommended that FDA propose a rule

similar to § 312.70 and give interested

parties a chance to comment on the

reproposal. The third comment stated

that the regulation for disqualification of

investigators of investigational new

drugs is a better model because it is a

relatively simple and clear regulation, it

does not impose unfair and potentially

harmful presumptions, and it would

give FDA the immediate consistency it

desires among product lines.

FDA has been persuaded by the

comments that the regulation governing

disqualification of investigators of

medical devices should parallel the

regulation for disqualification of

investigators of drugs and biologics in

§ 312.70 (as well as the regulation for

disqualification of investigators of

animal drugs at § 511.1(c) (21 CFR

511.1(c))). This rule for disqualification

of investigators of medical devices,

therefore, adopts regulations that are

basically the same as those governing

disqualification of investigators of

drugs, biologics, and animal drugs, with

minor exceptions.

The agency has concluded, however,

that a reproposal is unnecessary because

the agency received sufficient and

adequate comments to make a reasoned

determination about the final rule and

because the agency provided clear

notice to interested persons that a final

regulation paralleling § 312.70 would be

adopted if the comments persuaded the

agency that this approach represented

the best option. (See the Federal

Register of October 6, 1993, that stated

‘‘FDA is giving notice that, if comments

persuade the agency to revise the

proposed rule to follow § 312.70 * * *
12088 Federal Register / Vol. 62, No. 50 / Friday, March 14, 1997 / Rules and Regulations

the agency may issue a rule that

parallels § 312.70.’’( 58 FR 52144).)

In response to the concern that

medical device companies and

investigators of medical devices are

unfamiliar with § 312.70, the agency

notes that this rule is consistent with

FDA’s regulatory program for

investigators of drugs, which has existed

for more than 30 years, and that

interested persons were provided

explicit notice in the proposal that the

same disqualification procedures might

be adopted for investigators of devices.

Interested parties who may be

unfamiliar with FDA’s bioresearch

monitoring activities for clinical

investigations may find useful the

description of the agency’s investigator

disqualification process that is provided

in an FDA publication entitled ‘‘Food

and Drug Administration

INFORMATION SHEETS for

Institutional Review Boards and Clinical

Investigators’’ (October 1995 revision),

which is currently available from the

Office of the Associate Commissioner

for Health Affairs.

This document explains why FDA

was persuaded by the comments to

adopt the approach being codified and

also describes the ways in which the

rule has been modified from the

proposal in order to incorporate the

changes suggested by the comments. In

addition, this document identifies

comments that are now moot because

the agency adopted disqualification

procedures that parallel § 312.70.

Finally, this document also explains

FDA’s basis for not including other

suggestions.

II. Summary of the Final Rule

The final rule consists of the

following provisions:

A. Grounds for Disqualification

Section 812.119(a) establishes that

disqualification proceedings will only

begin if FDA has information indicating

that the investigator has: (1) Repeatedly

or deliberately failed to comply with the

requirements of this part, part 50 (21

CFR part 50), or part 56 (21 CFR part

56); or (2) repeatedly or deliberately

submitted false information either to the

sponsor of the investigation or in any

required report.

B. Informal Conference or Written

Explanation and Opportunity for a

Hearing on Proposed Disqualification

In accordance with § 812.119(a), when

FDA determines that one of the grounds

for disqualification may exist, CDRH

will furnish the investigator written

notice of the matter under complaint

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 CDRH, the

disqualification process will be

terminated. If an explanation is offered

but not accepted by CDRH, the

investigator will be given an

opportunity for a regulatory hearing

under part 16 (21 CFR part 16) on the

question of whether the investigator is

entitled to continue to receive

investigational devices.

C. Notification of Disqualification

In accordance with § 812.119(b), after

evaluating all available information,

including any explanation presented by

the investigator, if the Commissioner of

Food and Drugs (the Commissioner)

determines that the investigator has

repeatedly or deliberately failed to

comply with the requirements of this

part, part 50, or part 56, or has

repeatedly or deliberately submitted

false information either to the sponsor

of the investigation or 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), that the investigator is not

entitled to receive investigational

devices. The notification will provide a

statement of the basis for such

determination.

D. Actions Upon Disqualification

Under § 812.119(c), FDA shall

examine each IDE and each cleared or

approved application submitted under

subpart E of part 807 (21 CFR part 807)

or part 814 (21 CFR part 814),

containing data reported by an

investigator who has been determined to

be ineligible to receive investigational

devices to determine whether the

investigator has submitted unreliable

data that are essential to the

continuation of the investigation or

essential to the clearance/approval of

any marketing application.

Under § 812.119(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. If a danger to the public

health exists, however, the

Commissioner shall order withdrawal of

approval of the IDE before any hearing.

In such case, the sponsor shall have an

opportunity for a regulatory hearing

under part 16 on the question of

whether the IDE should be reinstated.

(See § 812.30(c)(2).)

In accordance with § 812.119(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 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 act and the

agency’s regulations.

E. Reinstatement of a Disqualified

Investigator

Under § 812.119(f), a disqualified

investigator may be reinstated when the

Commissioner determines that the

investigator has presented adequate

assurances, through written

submissions, that the investigator will

employ investigational devices solely in

compliance with the provisions of parts

812, 50, and 56.

F. Scope

The final rule clarifies that the

provisions for disqualification of

investigators of devices apply to all

cleared or approved and pending device

applications containing or relying upon

any clinical investigations performed by

the disqualified investigator. Such

applications include IDE’s, premarket

notifications (510(k)’s), and premarket

approval applications (PMA’s).

Subsequent to publication of the

proposed rule, FDA discovered that

510(k)’s were inadvertently omitted

from proposed § 812.119(a). Because the

provisions for disqualification of a

clinical investigators are intended to

apply to all device applications

containing or relying upon any clinical

investigations performed by the

disqualified investigator, this final rule

clarifies that such provisions apply to

510(k)’s, IDE’s, and PMA’s.

The final rule also clarifies that no

clinical investigator of medical devices

is exempt from the disqualification

regulations. The exemptions and

abbreviated requirements described in

part 812 for certain investigations are

intended to relate to those procedures

and requirements under part 812

associated with submitting an IDE

application or obtaining an IDE prior to

conducting an investigation. Section

812.2 is not intended to eliminate the

responsibility of clinical investigators of

devices to abide by procedures and

standards associated with good

scientific practice. Whether or not an

investigation requires an IDE, every
Federal Register / Vol. 62, No. 50 / Friday, March 14, 1997 / Rules and Regulations 12089

clinical investigator whose work may be

considered in connection with a

marketing application is expected to

comply with the agency’s regulations

and scientific standards relating to

informed consent, IRB oversight,

inspections, adherence to

investigational protocols, and pertinent

reports and recordkeeping. The final

rule amends § 812.2 to clarify that the

provisions governing disqualification of

investigators apply to all clinical

investigations of devices, including

those that do not require FDA approval

of an IDE, e.g., clinical investigations

involving nonsignificant risk devices,

and those categories of exempted

devices identified in the IDE regulation.

III. Identification and Explanation for

the Differences Between the Regulation

for Disqualification of Investigators of

Devices and the Regulation for

Investigators of Drugs and Biologics

Section 812.119(a) establishes that

FDA may begin the disqualification

process ‘‘if FDA has information

indicating that an investigator has

repeatedly or deliberately submitted

false information either to the sponsor

of the investigation or in any required

report.’’ This language is somewhat

different from the parallel provision for

investigators of drugs and biologics

(§ 312.70(a)), which states that a

disqualification process may begin

when there is information that the

investigator ‘‘has submitted to the

sponsor false information in any

required report.’’ (The parallel

regulation for investigators of animal

drugs (§ 511.1(c)), requires FDA to have

information indicating that the

investigator ‘‘has submitted false

information either to the sponsor of the

investigation or in any required

report.’’) FDA believes that the language

in the final rule for disqualification of

investigators of devices more clearly

states the intent of both the drug and

animal drug provisions.

As discussed in section IV. of this

document, several comments raised

concern that investigators would be

unfairly penalized for submitting false

information inadvertently or when it

was beyond their individual control.

The agency does not intend isolated or

inadvertent failures to be the basis for

disqualification and the addition of the

phrase ‘‘repeatedly or deliberately’’

clarifies that the agency’s threshold for

taking action against a clinical

investigator requires the submission of

false information to be either deliberate

or frequent enough to call into question

the individual’s eligibility to continue

the investigation.

Section 812.119(b) establishes that, in

addition to notifying the investigator

and the sponsor of any investigation in

which a disqualified investigator has

been named as a participant

(§ 312.70(b)), FDA will also notify the

reviewing IRB of a final disqualification

determination. FDA has made this

addition in response to several

comments received on the proposed

rule and after concluding that this

notification will better enable the

reviewing IRB to meet an obligation for

continuing review to ensure the

protection of the rights and well-being

of the subject.

Section 812.119(d) establishes that in

addition to notifying the sponsor of any

investigation (§ 312.70(d)), FDA will

also notify the reviewing IRB that the

Commissioner has determined that a

danger to public health exists and has

ordered withdrawal of approval of the

IDE. FDA has considered the comments

received on the proposed rule that

prompted the adoption of notification of

IRB’s as provided under § 812.119(a),

and has concluded that this notification

will better enable IRB’s to monitor an

investigation that is ordered terminated

to ensure continued protection of the

rights and well-being of the subject.

FDA believes that these changes

improve the medical device regulations

for disqualification of clinical

investigators without creating

significant discrepancies between those

procedures and the regulations that are

now in place for clinical investigators of

drugs, biologics, and animal drugs. FDA

intends to consider making similar

changes to § 312.70 in order to make the

investigator disqualification regulations

as consistent as possible.

IV. Comments

FDA published a proposed rule to

revise its medical device regulations to

include provisions for the

disqualification of clinical investigators

(58 FR 52144). Because of an

inadvertent error, the date for

submission of comments was

incorrectly published as November 5,

1993, even though the preamble to the

proposed rule provided an opportunity

for interested persons to submit

comments on the proposed rule until

December 6, 1993. A correction notice

was published in the Federal Register of

October 14, 1993 (58 FR 53245).

Subsequently, in the Federal Register of

December 6, 1993 (58 FR 64209), FDA

extended the comment period for the

proposed rule from December 6, 1993,

until January 5, 1994, in response to a

request for an extension from a trade

association.

The agency received a total of eight

comments from trade associations,

manufacturers, law offices, a medical

device consultant, a medical center, and

FDA’s Center for Drug Evaluation and

Research (CDER). A summary of the

comments and the agency’s response to

them is provided below:

A. Secondary Studies; Proposed

§ 812.119(a)(2)

1. A comment suggested that the

proposed provisions authorizing

disqualification of secondary studies,

i.e., clinical studies by the same

investigator other than the one in which

misconduct is shown, should be

limited. The comment recommended

that limits should be placed on

retrospective disqualification of

secondary studies because FDA has

authority to monitor the integrity and

performance of secondary studies. For

instance, FDA has the opportunity to

inspect clinical study sites, to review

sponsor’s monitoring of studies, and to

analyze the results of studies. Because

the agency already has the authority to

monitor the integrity and performance

of secondary studies, the comment

requested FDA to establish the

following provisions relating to

disqualification of secondary studies: (1)

Secondary studies should be

disqualified only when there is specific,

demonstrable basis for a charge of

misconduct; (2) the burden of proof

relative to disqualification of a

secondary study should be with FDA;

(3) sponsors of secondary studies should

be notified of disqualification of

investigators; and (4) the basis for

disqualification of a secondary study

should be limited to issues which

represent ongoing threats to the safety of

current or future users of the product.

Another comment suggested that

proposed § 812.119(a)(2) should not

apply to other ongoing IDE’s in which

the investigator is involved, unless

particular information establishes that a

potential problem exists with respect to

that specific clinical investigation.

The agency agrees with these

comments and is persuaded that the

approach set forth in § 312.70 and now

being adopted in part 812 is preferable

to the proposal because it addresses

these concerns. The final rule does not

automatically disqualify all IDE’s or

secondary studies. Instead, § 812.119

establishes that FDA will examine each

IDE to determine whether the

disqualified investigator has submitted

unreliable data that are essential to the

continuation of any investigation in

which the investigator has been named

a participant. (See § 812.119(c).) If the

Commissioner determines, after the
12090 Federal Register / Vol. 62, No. 50 / Friday, March 14, 1997 / Rules and Regulations

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. (See § 812.119(d).)

Thus, in accordance with § 812.119(c)

and (d), FDA may terminate

‘‘secondary’’ clinical investigations in

which the disqualified investigator has

been involved only after FDA: (1) Has

determined that the disqualified

investigator has submitted unreliable

data that are essential to the

continuation of any investigation in

which the investigator has been named

a participant; (2) eliminates the

unreliable data from consideration and

determines that the data remaining are

inadequate to support a conclusion that

it is reasonably safe to continue the

investigation; and (3) provides the

sponsor with an opportunity for a

regulatory hearing.

In accordance with § 812.119(d), the

initial burden of proof relative to

disqualification of secondary studies/

IDE’s rests with the agency. If FDA’s

initial determination is that the data

remaining are inadequate to support a

conclusion that it is reasonably safe to

continue the investigation, the sponsor

will be provided with an opportunity to

challenge FDA’s findings during a

regulatory hearing.

The comment’s suggestion that

sponsors of secondary studies be

notified of the disqualification of

investigators has already been

incorporated into § 812.119(b), which

requires, among other things,

notification of the sponsor of any

clinical investigation in which the

disqualified investigator has been

named as a participant.

B. Proposed § 812.119(a)

2. One comment requested that

§ 812.119(a), which was drafted to apply

to the disqualification of an investigator

‘‘who has failed to comply with any’’ of

the regulations applicable to clinical

investigators, be changed to apply only

to investigators who have engaged in

serious violations.

The agency agrees with the basic

concern raised by this comment and

believes that the decision to adopt a

final regulation that parallels § 312.70

has addressed this concern. Section

812.119(a) replaces ‘‘has failed to

comply with any of the regulations set

forth in this part’’ with ‘‘has repeatedly

or deliberately failed to comply with the

requirements of this part, part 50, or

part 56 * * *.’’ An investigator’s failure

to repeatedly or deliberately comply

with the requirements of this part, part

50, or part 56 constitutes a serious

violation.

C. Proposed § 812.119(a)(1)

3. One comment noted that the use of

the term ‘‘necessarily’’ in proposed

§ 812.119(a)(1) implies that a

disqualification decision may or may

not constitute a finding or

recommendation that the investigator is

not qualified to practice or teach

medicine or should be subject to other

sanctions by third parties. The comment

suggested that these areas are outside

the disqualification proceeding

purview. As a result, the word

‘‘necessarily’’ should be omitted from

§ 812.119(a)(1) to ensure that a

disqualification decision would not

affect these areas of the investigator’s

life.

Proposed § 812.119(a)(1) has not been

adopted in the final regulation.

However, under § 812.119(b), the

disqualification notification issued by

the agency constitutes only a finding

that the investigator is not entitled to

receive investigational devices and a

statement of the basis for a

determination by the agency that the

investigator is disqualified from

participation in clinical investigations.

The agency’s disqualification does not

constitute any other finding.

D. Proposed § 812.119(b)(1)

4. Proposed § 812.119(b)(1) provided

that an investigator could be

disqualified if he or she ‘‘caused false

information to be submitted’’ to FDA or

a sponsor. According to one comment,

this language allows an investigator to

be held responsible even if the

investigator were unaware that the

information was false. The comment

said that this provision fails to recognize

that all clinical studies have some

degree of unavoidable error. Another

comment stated that an investigator

should not be disqualified because he or

she submitted false information

generated by a third person, unless the

investigator knew of the falsehood. A

third comment requested that proposed

§ 812.119(b)(1) be rewritten as follows:

An investigator should be disqualified if

‘‘the investigator deliberately caused

false information to be submitted to

FDA or to the sponsor of a study with

the understanding that information may

be submitted to FDA.’’

It is not FDA’s intention to disqualify

an investigator for a single submission

of false data for which the investigator

was not responsible. The agency would

not seek to disqualify investigators

under such circumstances and FDA

believes that the adoption of

§ 812.119(a) ensures against such

situations.

In accordance with § 812.119(a), an

investigator may be disqualified ‘‘If FDA

has information indicating that an

investigator has * * * deliberately or

repeatedly submitted false information

either to the sponsor of the investigation

or in any required report, * * *.’’

Requiring submission of false

information to be ‘‘deliberately’’

submitted ensures that investigators will

not be held responsible for a single

submission of false information if the

investigator were unaware that the

information was false.

Although the ‘‘repeated submission of

false information’’ basis for

disqualification does not ensure that an

investigator will not be disqualified for

the submission of false information if

the investigator were unaware that the

information was false, FDA believes that

such a basis for disqualification is

necessary. A clinical investigator who

repeatedly causes false information to

be submitted to FDA, whether through

carelessness or mismanagement,

jeopardizes the integrity of the study

and safety of the patients. The agency

believes that investigators who

repeatedly submit false information

should be disqualified from

participation in such investigations.

E. Proposed § 812.119(b)(3)

5. Five comments suggested

modifying the language in proposed

§ 812.119(b)(3) in order to clarify the

grounds for disqualification and to

afford clinical investigators and FDA a

less severe remedy than disqualification

for less serious violations. One comment

recommended that FDA incorporate the

standard used in § 312.70, which states

that investigators may be disqualified

for repeated or deliberate failures to

comply with regulations.

The final rule addresses the concerns

raised by these comments by adopting

§ 812.119(a), which parallels, with

minor modifications, § 312.70(a).

Section § 812.119(a) states that clinical

investigators may be disqualified only

under the following situations: (1)

Repeated or deliberate failure to comply

with the requirements of parts 812, 50,

or 56; or (2) repeated or deliberate

submission of false information either to

the sponsor of the investigation or in

any required report.

The agency believes that the concern

regarding affording clinical investigators

a remedy other than disqualification for

less serious violations has also been

addressed in § 812.119(a). Section

812.119(a) provides the investigator

with an opportunity to explain the
Federal Register / Vol. 62, No. 50 / Friday, March 14, 1997 / Rules and Regulations 12091

matter in writing, or in an informal

conference with the center. FDA

believes that this opportunity is the

appropriate time for a clinical

investigator to dispute or explain any of

the allegations cited in the written

notice proposing disqualification. Based

on the explanation given, CDRH may

determine that the investigator’s

disqualification is not necessary and

terminate the proceeding. The clinical

investigator also may decide to enter

into a consent agreement with the

agency that terminates the

disqualification proceeding.

F. Proposed § 812.119(c) and (d)

6.A comment requested that, in

addition to the investigator receiving

written notice, the sponsor of the

clinical investigation, as well as IRB,

should be informed about any written

notice by FDA to the clinical

investigator of an allegation involving

noncompliance with regulations that

may be grounds to justify

disqualification of the investigator.

Another comment requested that FDA

be required to notify the sponsor, IRB,

and other sponsors who are employing

or have previously employed the

investigator to conduct clinical studies

requiring prior FDA review, that a

potential problem exists at the same

time FDA notifies the investigator about

the opportunity for a written

explanation, an informal conference, or

a hearing. The comment contended that

giving such notification will allow the

sponsors to take actions to minimize the

potential effect of disqualification.

One comment suggested adding the

following provision to § 812.119(c):

The written notice to the investigator will

be copied to the sponsor of the investigation,

as well as the IRB reviewing the

investigation. Sponsors of other clinical

studies requiring prior FDA review which are

being or have been conducted by the

investigator will also be notified. FDA will

issue this notice to the IRB and sponsors

within 15 working days after the notice is

issued to the clinical investigator.

Furthermore, it was requested that the

disqualification process termination

notice to the clinical investigator,

provided for in § 812.119(c)(2), be

required to be copied to the sponsor of

the investigation, the IRB reviewing the

investigation, and sponsors of other

clinical studies requiring prior FDA

review which are being or have been

conducted by the investigator.

The agency does not believe that

additional notification of preliminary

findings should be required routinely as

part of the investigation of an

investigator who may be disqualified

because further investigation may

determine the investigator to be in

compliance with the relevant

regulations, and also because sponsors

and IRB’s have access to Form FD–483

and warning letters relating to their

clinical investigators. The agency does

recognize, however, that there are times

when it is reasonable or necessary for

FDA to notify the sponsor of a study and

the reviewing IRB prior to a final

disqualification determination in order

to ensure the integrity of a study or the

rights and well-being of a subject. While

there are circumstances that may

warrant early notification to sponsors or

IRB’s, this final regulation, like its

counterparts for investigators of drugs,

biologics, and animal drugs, does not

explicitly address this issue. However,

separate from this rulemaking, the

agency is establishing a working group,

representing all FDA centers, to

establish a uniform policy on the issue

of prior disclosure to sponsors and

IRB’s.

The agency has adopted § 812.119(b),

which parallels the language used in

§ 312.70(b) of the investigational new

drug (IND) regulations for

disqualification of investigators, and

provides that ‘‘any sponsor of an

investigation in which the investigator

has been named as a participant and the

reviewing IRB’’ shall be notified of the

agency’s final decision on the

disqualification of the investigator and

the basis for the disqualification. The

agency has also adopted § 812.119(d),

which parallels the language used in

§ 312.70(d) of the IND regulations, and

provides that sponsors and IRB’s shall

be notified and sponsors given an

opportunity for a hearing, when FDA

intends to withdraw approval for an

IDE, or if a danger to public health

warrants immediate termination of an

investigation, that the Commissioner

shall order the immediate withdrawal of

approval of the IDE and the sponsor

shall be offered an opportunity for a

hearing on whether the IDE should be

reinstated.

G. Proposed § 812.119(c)(1) and (d)

7. A comment suggested that the

written notice in § 812.119(c)(1) and (d)

should describe the noncompliance

with sufficient detail and particularity

so that the investigator is informed fully

of the alleged violation. An investigator

cannot provide an informed response

unless sufficient detail is provided.

The agency agrees with the concern

expressed by this comment and has

adopted § 812.119(a), which establishes

the agency’s responsibility to provide

adequate details. Section 812.119(a)

provides that ‘‘* * * the Center for

Devices and Radiological Health will

furnish the investigator written notice of

the matter under complaint * * *.’’

FDA intends that such notices include

a full description of the alleged

violation(s) that are the basis for

disqualification.

H. Proposed § 812.119(c)(2)

8. Proposed § 812.119(c)(2) provides

for the termination of the proceeding if

the investigator offers an explanation for

the noncompliance that is accepted by

FDA. One comment suggested that

§ 812.119(c)(2) be rewritten to allow for

the termination of the proceeding if the

investigator demonstrates that no

regulatory violations actually occurred.

Another comment recommended that

the term ‘‘alleged’’ be placed before the

word noncompliance in § 812.119(c)(2)

to indicate that a noncompliance

determination has not been made at this

preliminary stage.

The agency believes that these

modifications are unnecessary with the

adoption of the final rule. In accordance

with § 812.119(a), when FDA furnishes

the investigator with a written notice of

the matter under complaint, FDA will

also offer the investigator an

opportunity to explain the matter in

writing, or at the option of the

investigator, at an informal conference.

If an explanation is offered by the

investigator and accepted by CDRH, the

disqualification process will be

terminated. The scope of an

investigator’s explanation is not limited

and may include a showing that no

regulatory violations actually occurred.

The agency also believes that

modifying § 812.119(a) by inserting the

term ‘‘alleged’’ in the regulatory text is

unnecessary because § 812.119(a),

unlike proposed § 812.119(c)(2), does

not indicate that a final noncompliance

determination will be made at this

preliminary stage.

I. Proposed § 812.119(c)(2) and (c)(3)

9. A comment requested that the

terms ‘‘FDA’’ and ‘‘agency’’ in

§ 812.119(c)(2) and (c)(3) be replaced

with ‘‘Center for Devices and

Radiological Health,’’ in order to clarify

that informal conferences would not be

held at the Commissioner’s level.

The concern raised by this comment

has been addressed with the adoption of

§ 812.119(a), which references CDRH,

FDA. Also, FDA is taking this

opportunity to notify interested persons

that CDRH’s Division of Compliance

Operations has been eliminated through

reorganization. The informal

conferences will be held by the Division

of Bioresearch Monitoring, Office of

Compliance, CDRH.
12092 Federal Register / Vol. 62, No. 50 / Friday, March 14, 1997 / Rules and Regulations

J. Proposed § 812.119(d)

10. A comment stated that the text of

proposed § 812.119(d) failed to mention

that an opportunity for a hearing exists

for an investigator who has received a

proposed notice of disqualification.

This concern also has been addressed

with the adoption of § 812.119(a).

Section 812.119(a) specifically states, ‘‘If

an explanation is offered but not

accepted by the Center for Devices and

Radiological Health, the investigator

will be given an opportunity for a

regulatory hearing under part 16

* * *.’’

K. Proposed § 812.119(f)(1)

11. Under § 812.119(a) and paragraph

(f)(1) as proposed, a hearing on the

disqualification of an investigator shall

be conducted in accordance with the

requirements for a regulatory hearing as

set forth in part 16. One comment

maintained that conducting a regulatory

hearing under part 16 does not

adequately protect the investigator’s due

process rights. The comment requested

FDA to follow the procedures set forth

in part 12 (21 CFR part 12) for a formal

evidentiary public hearing when

determining whether an investigator

should be disqualified.

The agency disagrees with the

comment that a part 16 regulatory

hearing does not provide adequate due

process. A part 16 regulatory hearing is

initiated by a notice of opportunity for

hearing from FDA. This notice specifies,

among other things, the facts and the

action that are the subject of the hearing

and states the time in which a hearing

may be requested. In accordance with

part 16, if a hearing is requested, the

Commissioner will designate a

presiding officer, and the hearing will

take place at a time and location agreed

upon by the party requesting the

hearing, FDA, and the presiding officer.

A part 16 regulatory hearing, therefore,

adequately protects an investigator’s

due process rights by providing the

investigator with notice and an

opportunity to be heard. Moreover, FDA

has had extensive experience in the use

of part 16 hearings for disqualification

proceedings of clinical investigators of

new drugs under part 312. FDA’s

experience has established that part 16

hearings are appropriate in these

circumstances and protect the

investigator’s due process rights.

Finally, a part 16 regulatory hearing is

more streamlined than a part 12

evidentiary public hearing and will

provide a quicker resolution of issues

for both FDA and the investigator.

L. Proposed § 812.119(f)(3)

12. Section 812.119(f)(2) provides that

a final order disqualifying a clinical

investigator will be copied to the

sponsor of each clinical investigation

subject to requirements for prior

submission to FDA that was or is being

conducted by the investigator. A

comment suggested adding a similar

provision to § 812.119(f)(3) so that

sponsors will be notified of any final

order terminating the disqualification

proceeding. Additionally, the comment

suggested that FDA provide a copy of

such orders to IRB’s as well.

The agency has adopted § 812.119(b),

which provides for notification of the

interested parties after the

Commissioner has made a final

determination that an investigator is

disqualified. After a final

disqualification decision has been

made, the investigator, the sponsors of

any investigations in which the

investigator was named as a participant,

and the reviewing IRB shall be notified

that the investigator is disqualified.

The agency’s response to comments

concerning notification of interested

parties prior to a final disqualification

decision has been provided previously.

(See the response to comment 6 in

section IV.F. of this document.)

M. Proposed § 812.119(g)

13. One comment said that proposed

§ 812.119(g), actions upon

disqualification, may be interpreted to

mean that the Commissioner is

authorized to make decisions that

directly affect the rights and

responsibilities of sponsors even though

sponsors may not be aware of the

disqualification process or be given the

opportunity to participate in the

disqualification decisions. Another

comment maintained that this section

may violate sponsors’ due process

rights. The comment recommended that

sponsors be given the opportunity to

present their views before the agency

takes any of the actions described in

proposed § 812.119(g).

The agency has addressed these

concerns with the adoption of

§ 812.119(d), which provides sponsors

with the opportunity to participate in

proceedings regarding termination of

clinical investigations. Under this

section, if the Commissioner

determines, after the unreliable data

submitted by the disqualified

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. If a danger to the public

health exists, however, the

Commissioner shall terminate the

clinical investigation immediately and

notify the sponsor of that determination.

In such case, the sponsor shall have an

opportunity for a regulatory hearing

under part 16 on the question of

whether the clinical investigation

should be reinstated.

The agency’s adoption of § 812.119(e),

which parallels § 312 .70(e), also

addresses the concerns about sponsors’

rights raised by these comments. This

new section provides that if the

Commissioner determines, after the

unreliable data submitted by the

disqualified investigator are eliminated

from consideration, that the continued

clearance or approval of the device for

which the data were submitted cannot

be justified, the Commissioner will

proceed to rescind clearance or

withdraw approval of the marketing

application in accordance with the

applicable provisions of the act and

regulations. These provisions provide

adequate due process protections to the

sponsor whose clinical investigations

are subject to termination and/or whose

marketing applications are subject to

rescission of clearance or withdrawal of

approval following disqualification of

clinical investigators.

N. Proposed § 812.119(g)(2)

14. A comment suggested that

proposed § 812.119(g)(2) was overly

broad because it would allow FDA to

terminate an entire study based on the

disqualification of a single investigator.

The agency believes that the concern

raised by this comment has been

addressed with the adoption of

§ 812.119(d), which, like § 312.70(d),

provides a sponsor with notification

that the Commissioner has determined

that the data are inadequate to support

a conclusion that it is reasonably safe to

continue the investigation, and an

opportunity for a hearing under part 16,

as indicated previously. (See the

response to comment 13 in section

IV.M. of this document.)

15. A comment suggested that there

was an inconsistency between proposed

§ 812.119(g)(2) and proposed

§ 812.119(b). The comment stated that,

under § 812.119(b), the Commissioner

must base a disqualification order upon

findings that address only limited

factual issues. In contrast,

§ 812.119(g)(2) directed FDA to consider

information that goes beyond the scope

of the administrative record created

during the disqualification proceedings.

For example, nothing in proposed

§ 812.119(b) related to ‘‘the risks of the
Federal Register / Vol. 62, No. 50 / Friday, March 14, 1997 / Rules and Regulations 12093

subjects from suspension of the study,’’

and yet FDA, under § 812.119(g)(2),

would consider that factor. The

comment recommended that this

inconsistency be rectified.

The agency believes that the

inconsistency indicated by this

comment has been addressed with the

adoption of § 812.119(b), which

parallels § 312.70(b) and by the

elimination of proposed § 812.119(g) in

the final rule. Under § 812.119(b), a

disqualification decision will be based

upon the Commissioner’s determination

that the investigator has repeatedly or

deliberately failed to comply with the

requirements of this part, part 50 or part

56, or has deliberately or repeatedly

submitted false information either to the

sponsor or in any required report, after

evaluating all available information,

including any explanation presented by

the investigator.

O. Proposed § 812.119(g)(2)(i)

16. One comment stated that the

meaning of the phrase ‘‘another

investigator accepts responsibility for

the clinical investigation’’ was unclear

in this proposed section.

Proposed § 812.119(g)(2)(i) was not

adopted in the final rule, thus

eliminating any need for clarification

indicated by this comment. However,

FDA believes that if continuation of an

investigation is warranted after an

investigator is disqualified, the sponsor

of the investigation is responsible for

selecting a qualified investigator who

shall be responsible for the continuation

of the investigation at that site. (See,

also, the response to comment 18 in

section IV.P. of this document.)

17. A comment expressed concern

that proposed § 812.119(g)(2)(i) could be

interpreted as broad FDA authority to

suspend or terminate an entire clinical

investigation, rather than the portion of

the investigation conducted by the

disqualified investigator. In order for the

regulation to be explicit on this issue,

this comment suggested that the phrase

‘‘under control of the disqualified

investigator’’ should be added after

‘‘clinical investigation.’’ Additionally,

another comment requested that

‘‘clinical investigation’’ should be

defined as that part of an investigation

directly under the control of the

disqualified investigator. Furthermore,

the comment asked FDA to add the

following sentence to this section for

clarity: ‘‘Disqualification of an

investigator or termination of a clinical

investigation under control of a

disqualified investigator shall not affect

any investigation not under control of

the disqualified investigator.’’

The agency has previously addressed

other comments concerning the

termination of an entire investigation or

other investigations conducted by the

disqualified investigator. (See the

responses to comments 1 and 14 in

sections IV.A. and N. of this document.)

P. Proposed § 812.119(g)(2)(iii)

18. One comment stated that it is

inappropriate for a disqualified

investigator to continue monitoring

subjects. Instead, this comment

recommended that another investigator

be appointed to monitor the subject, or

the subject should be withdrawn from

the study.

The agency agrees that it is

inappropriate for a disqualified

investigator to continue monitoring

clinical trial subjects who are either

continuing to receive the test device or

are in the followup phase of the trial.

An investigator who is disqualified from

eligibility to receive investigational

devices is disqualified from

participation in conducting

investigations, including monitoring the

subjects of investigations. Therefore,

§ 812.119(b) provides that once the

Commissioner makes a final

disqualification determination, the

Commissioner will notify the sponsor of

any investigation in which the

investigator has been named as a

participant and the reviewing IRB that

the investigator is disqualified.

Furthermore, the agency believes that if

subjects are currently enrolled or

receiving followup visits at the

disqualified investigator’s site, the

sponsor is responsible for selecting, as

soon as possible, a qualified investigator

who shall be responsible at the site for

completing the investigation, including

subject followup.

Q. Proposed § 812.119(g)(2)(v)

19. One comment stated that

proposed § 812.119(g)(2)(v) was too

restrictive. Various comments suggested

that § 812.119(g)(2)(v) be expanded to

allow continued use if discontinuing

use would cause a life-threatening

problem, an immediate health problem,

or involve significant risks to the

person’s health.

The agency has not adopted the

provision that was the basis for this

comment. However, under § 812.119(c)

and (d), the Commissioner will

determine whether the remaining data

are adequate to support a conclusion

that it is reasonably safe to continue an

investigation, or whether approval

should be withdrawn. If there is

credible evidence that discontinuing an

investigation would cause a lifethreatening problem, an immediate

health problem, or involve significant

risks to the health of a subject, this type

of evidence will be considered in

support of such determination.

R. Proposed § 812.119(g)(3)

20. Under proposed § 812.119(g)(3),

once an investigator is disqualified,

FDA would examine approved and

pending applications relying on the

work of this disqualified investigator.

FDA would determine whether the

investigation ‘‘is acceptable,’’

notwithstanding the disqualification.

According to several comments,

proposed § 812.119(g)(3) was vague and

unfair for various reasons. One

comment suggested that FDA

incorporate the language used in the

IND regulations for disqualification of

investigators, which provides that an

application 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.’’ (See

§ 312.70(c).)

The agency agrees with the comments

and has adopted § 812.119(c), which

parallels the language used in

§ 312.70(c) of the IND regulations, for

disqualification of investigators.

21. Another comment said that the

wording,

Any investigation done by an investigator

before or after disqualification may be

presumed to be unacceptable, and the person

relying on the investigation may be required

to establish that the clinical investigation was

not affected by the circumstances which led

to disqualification of the investigator, * * *.

has many flaws. First, the terminology

‘‘any investigation done by an

investigator before or after

disqualification may be unacceptable’’

is too broad. The comment

recommended that the regulation state

that an investigator’s data will not be

accepted to support a marketing

application only if the evidence shows

that the data are unreliable. The sponsor

should then be given the opportunity to

validate the data if possible, after

exclusion of the adversely affected data.

The comment also said that a

‘‘presumption’’ of invalidity for any

investigation done by an investigator

before or after disqualification is

inappropriate because, under the

proposed rule, that presumption would

apply to any clinical investigation

performed by the investigator.

The agency believes that the concerns

expressed by this comment have been

minimized with the adoption of a final

rule that parallels § 312.70. Under

§ 812.119(c), each regulatory submission

containing data reported by a
12094 Federal Register / Vol. 62, No. 50 / Friday, March 14, 1997 / Rules and Regulations

disqualified investigator 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. It is not

unreasonable, however, for FDA to

presume that other work done by a

disqualified investigator should be

reviewed. Because this final rule states

that a sponsor is entitled to a hearing

before any particular investigation or

approval is terminated, the opportunity

to validate data will be available to

sponsors.

22. Another comment stated that the

use of the phrase ‘‘the person relying on

the investigation may be required to

establish that the investigation was not

affected,’’ improperly shifts the burden

of proof to the sponsor; just because an

investigator has failed to comply with

the regulations in one study does not

imply that all other studies are tainted.

This comment recommended that, once

FDA determines that an investigator has

acted improperly, FDA should conduct

an investigation to determine whether

other clinical investigations conducted

by the disqualified investigator are

unreliable.

This recommendation is incorporated

into the final rule, which parallels

§ 312.70. Under § 812.119(c), each IDE

and each approved marketing

application submitted under part 807 or

814 in which the disqualified

investigator has been a participant will

be examined by FDA. In essence, final

§ 812.119(c) places on FDA the initial

burden of determining whether any

unreliable data have been submitted by

the disqualified investigator that are

essential to the continuation of any

other investigation or to the approval or

clearance of any marketing application.

(See the agency’s responses to

comments 1, 13, and 14 in sections

IV.A., M., and N. of this document.)

23. A comment urged that an approval

should not be withdrawn unless there is

evidence that the device is unsafe or

ineffective. If the device is found to be

safe and effective, the device should

remain available, regardless of

irregularities in the investigation which

led to the disqualification of an

investigator.

The agency does not intend to

withdraw approval or rescind clearance

of devices under § 812.119(e) unless the

Commissioner determines, after the

unreliable data submitted by the

investigator are eliminated from

consideration, that the continued

approval or clearance of the marketing

application for which the data were

submitted cannot be justified. By its

very nature, unreliable data bring into

question the safety and effectiveness of

the device. If the marketing application

contains data, other than the

disqualified data, that support

substantial equivalence or safety and

effectiveness, FDA would have no

reason to remove the device from the

market. The course of action taken by

FDA with respect to that device will be

commensurate with the results of the

agency’s review, and may include

withdrawal of approval of a PMA or

recision of a 510(k) if that is deemed

necessary. Furthermore, as stated in

response to comment 13 in section IV.

M. of this document, § 812.119(e)

parallels § 312.70(e) and provides

sponsors with the opportunity to

participate in proceedings regarding

withdrawal of approval or recession of

clearance of a marketing application.

24. A comment suggested that the

regulation should include a reasonable

time limit in which a sponsor must

validate the data used in a study in

which an investigator was disqualified.

The agency agrees with this comment.

In accordance with § 812.119(d) and (e),

when FDA has reviewed the remaining

data after the disqualified investigator’s

data are eliminated and the

Commissioner has determined that the

remaining data are inadequate to

support continued approval or clearance

of an investigation or marketing

application, the Commissioner will

notify the sponsor, who shall have an

opportunity for a regulatory hearing

under part 16. The sponsor may request

a hearing to present to FDA any new or

additional factual information which

challenges the determination, including

any information that validates the

disqualified investigator’s data or that

indicates the remaining data are

adequate to support approval or

clearance. The time limit for providing

such information is governed by the

procedures for conducting a regulatory

hearing under part 16.

25. Another comment pointed out that

§ 812.119(d) and (e) requires a sponsor,

in certain circumstances, to submit

validating information to show that an

IDE or PMA containing or relying upon

a clinical investigation performed by a

disqualified investigator is not adversely

affected. This comment suggested that

FDA should offer the sponsor periodic

opportunities, i.e., quarterly, monthly,

etc., to present validating information

for any potentially adversely affected

clinical investigation through segregated

analysis, adding additional sites, or

verification of existing data. According

to this comment, offering such periodic

opportunities to validate existing data

would allow the sponsor to salvage

portions of valid data without having to

gather clinical data through new

investigations.

The agency agrees that such an

opportunity may be appropriate. As part

of FDA’s examination under final

§ 812.119(c) to determine whether the

disqualified investigator has submitted

unreliable data that are essential to the

continuation of an investigation or

essential to the approval of any

marketing application, FDA may request

that sponsors submit to the agency, on

a periodic basis, validating information

for a potentially adversely affected

clinical investigation or marketing

application. Sponsors will receive

written notification of such a request.

S. Proposed § 812.119(g)(4)

26. Under proposed § 812.119(g)(4),

the determination that a clinical

investigation may not be considered in

support of an application would not

relieve the applicant of any obligation

under the statute to submit the results

of the clinical investigation to FDA. A

comment urged that an applicant should

not be required to submit the results of

the clinical investigation to FDA

because, once a determination has been

made that the clinical investigation will

not be considered in support of an

application, the usefulness of the

clinical investigation is questionable.

The agency disagrees with this

comment. Although the final rule no

longer includes this explicit provision,

it is imperative for FDA to review all

available information collected on the

investigational device, particularly

information that may affect the rights,

safety, or welfare of the subjects

enrolled. Therefore, regardless of

whether the clinical data will be used to

support a marketing application, the

reporting requirements described in

other parts of the IDE regulation, e.g.,

§§ 812.40 and 812.150, must be

maintained to provide adequate

protection for subjects.

T. Proposed § 812.119(h)(1)

27. Proposed § 812.119(h)(1) would

have required the notice of

disqualification to state that the results

of any investigations conducted by the

investigator may not be considered by

FDA in support of any IDE or PMA.

According to one comment, proposed

§ 812.119(h)(1) would not permit

validating information to be presented

by a sponsor to save the IDE or PMA.

Because of this, the comment requested

that the contents of the disqualification

notice not automatically reflect a

determination that the study results are

not to be considered in support of an

IDE or PMA. Instead, the comment
Federal Register / Vol. 62, No. 50 / Friday, March 14, 1997 / Rules and Regulations 12095

requested that the contents of the

disqualification notice state that the

results will be evaluated by FDA to

determine the effect of disqualification,

if any, on the IDE or PMA.

Proposed § 812.119(h)(1), which is

addressed in this comment, has not

been adopted. However, under

§ 812.119(b), a disqualification notice is

provided that states that the investigator

is disqualified and the basis for such

determination. Final § 812.119(c), (d),

and (e) establish that FDA will review

any IDE’s, 510(k)’s or PMA’s that

contain data submitted by the

disqualified investigator. If the agency

finds that a withdrawal of approval is

warranted, the sponsor of the

application will be notified and offered

an opportunity for a hearing under part

16. The sponsor may request a part 16

hearing to provide relevant information,

such as validating information, which

may influence a final decision.

28. Under proposed § 812.119(h)(1),

upon issuance of a final order

disqualifying an investigator or upon

entry of a consent decree, FDA would

have discretion to notify all or any

interested persons. A comment

recommended that it be a mandatory

requirement that sponsors receive notice

of an investigator disqualification both

when FDA issues a final order and

when FDA has reason to believe that an

investigator may be subject to

disqualification. Another respondent

asked FDA to include in the regulation

a provision requiring the notification of

the sponsor by FDA when a consent

agreement is executed, with a copy of

the consent agreement included in the

sponsor’s notification. Three other

respondents suggested that FDA, upon

disqualification of a clinical

investigator, inform the approving IRB

that the investigator has been

disqualified.

Proposed § 812.119(h)(1), which is

addressed by these comments, has not

been adopted in the final rule. However,

FDA agrees with these comments in

general and has adopted final

§ 812.119(b), which parallels

§ 312.70(b). This final rule provides that

FDA will give notification of

disqualification to the investigator who

is disqualified, the sponsor of any

investigation in which the investigator

has been named a participant, and the

reviewing IRB.

The agency’s response to comments

concerning notification of interested

parties prior to a final disqualification

decision has been provided previously.

(See response to comment 6 in section

IV.F. of this document.) Records relating

to disqualification proceedings, such as

inspectional findings, disqualification

determinations, administrative records

of determinations and hearings, consent

agreements, and reinstatement

determinations are disclosable to the

public upon request, subject to the

provisions of part 20 (21 CFR part 20).

U. Proposed § 812.119(h)(3)

29. According to a comment,

proposed § 812.119(h)(3) would not give

sponsors notice that an investigator is

facing disqualification proceedings.

This comment requested that the

regulation be revised to require FDA to

notify the sponsor if one of its

investigators may be facing

disqualification.

A similar comment suggested the

following wording:

Whenever FDA has reason to believe that

an investigator may be subject to

disqualification, the agency will so notify the

sponsor of the clinical investigation in

question, as well as the sponsor of each

clinical investigation subject to requirement

of prior submission to FDA that was or is

being conducted by the investigator, and the

IRB’s under which the investigation(s) were

conducted. This notification shall occur

simultaneously with the agency’s notice to

the investigator describing the

noncompliance and request for an

explanation of the noncompliance under

paragraph (c) of this section.

Proposed § 812.112(h)(3) addressed in

these two comments has not been

adopted in the final rule. However, the

agency’s response to similar comments

concerning notification of interested

parties prior to a final disqualification

decision has been provided previously.

(See response to comment 6 in section

IV.F. of this document.)

V. Proposed § 812.119(j)

30. This proposed section would have

required sponsors to notify FDA any

time an investigator is removed from

further participation in a clinical

investigation. One comment stated that

there is no need to require a sponsor to

notify FDA when an investigator is

removed from a study for nonregulatory

reasons. Another comment maintained

that requiring sponsors to report a

termination, for whatever reasons, could

inhibit sponsors from terminating

investigators because of the reporting

requirements.

Proposed § 812.119(j) addressed in

these two comments has not been

adopted in the final rule. However,

§ 812.40 of the existing IDE regulation

currently requires sponsors to inform

the agency of significant new

information about an investigation,

including any changes in or

terminations of clinical investigators.

W. Publication of a List

31. A comment requested that

disqualified investigators be added to a

single list maintained by CDER or the

Office of Health Affairs in FDA so that

IRB’s and sponsors are not required to

search two (or more) separate lists.

Although the proposed rule did not

specifically state that CDRH would

maintain a list of clinical investigators

who have been disqualified under this

authority, FDA intends to compile such

a list. This list will be combined with

CDER’s and the Center for Biologics

Evaluation and Research’s (CBER’s) list

of disqualified investigators. The newly

combined disqualified clinical

investigator list will be maintained by

FDA’s Office of Regulatory Affairs. This

list is disclosable to the public under

part 20. A request for the list should be

sent in writing to the Freedom of

Information Staff (HFZ–35), Food and

Drug Administration, 5600 Fishers

Lane, rm. 12A–16, Rockville, MD 20857.

V. Environmental Impact

The agency has determined under 21

CFR 25.24(a)(8) 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. Analysis of Impacts

FDA has examined the impacts of the

final rule under Executive Order 12866

and the Regulatory Flexibility Act (5

U.S.C. 601–612). 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 final rule is consistent

with the regulatory philosophy and

principles identified in the Executive

Order. In addition, the final rule is not

a significant regulatory action as defined

by the Executive Order and so is not

subject to review under 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 the final rule specifies

the procedures to be followed for

investigator disqualification, the rule

does not impose any burden on

regulated industry. Procedures

themselves are protections and do not
12096 Federal Register / Vol. 62, No. 50 / Friday, March 14, 1997 / Rules and Regulations

impose significant costs beyond what

the underlying statute imposes. Thus,

the agency certifies that the final rule

will not have a significant economic

impact on a substantial number of small

entities. Therefore, under the Regulatory

Flexibility Act, no further analysis is

required.

Lists of Subjects in 21 CFR Part 812

Health records, Medical devices,

Medical research, Reporting and

recordkeeping requirements.

Therefore, under the Federal Food,

Drug, and Cosmetic Act and under

authority delegated to the Commissioner

of Food and Drugs, 21 CFR part 812 is

amended as follows:

PART 812—INVESTIGATIONAL

DEVICE EXEMPTIONS

1. The authority citation for 21 CFR

part 812 continues to read as follows:

Authority: Secs. 301, 501, 502, 503, 505,

506, 507, 510, 513–516, 518–520, 701, 702,

704, 721, 801 of the Federal Food, Drug, and

Cosmetic Act (21 U.S.C. 331, 351, 352, 353,

355, 356, 357, 360, 360c–360f, 360h–360j,

371, 372, 374, 379e, 381); secs. 215, 301, 351,

354–360F of the Public Health Service Act

(42 U.S.C. 216, 241, 262, 263b–263n).

2. Section 812.2 is amended by

revising the introductory text of

paragraph (c) to read as follows:

§ 812.2 Applicability.

* * * * *

(c) Exempted investigations. This part,

with the exception of § 812.119, does

not apply to investigations of the

following categories of devices: * * *

* * * * *

3. New § 812.119 is added to subpart

E to read as follows:

§ 812.119 Disqualification of a clinical

investigator.

(a) If FDA has information indicating

that an investigator has repeatedly or

deliberately failed to comply with the

requirements of this part, part 50, or

part 56 of this chapter, or has repeatedly

or deliberately submitted false

information either to the sponsor of the

investigation or in any required report,

the Center for Devices and Radiological

Health will furnish the investigator

written notice of the matter under

complaint 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 Devices and

Radiological Health, the disqualification

process will be terminated. If an

explanation is offered but not accepted

by the Center for Devices and

Radiological Health, 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 entitled to receive

investigational devices.

(b) After evaluating all available

information, including any explanation

presented by the investigator, if the

Commissioner determines that the

investigator has repeatedly or

deliberately failed to comply with the

requirements of this part, part 50, or

part 56 of this chapter, or has

deliberately or repeatedly submitted

false information either to the sponsor

of the investigation or 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 that the investigator

is not entitled to receive investigational

devices. The notification will provide a

statement of basis for such

determination.

(c) 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.

(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 of the determination.

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.

(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 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 act.

(f) An investigator who has been

determined to be ineligible to receive

investigational devices may be

reinstated as eligible when the

Commissioner determines that the

investigator has presented adequate

assurances that the investigator will

employ investigational devices solely in

compliance with the provisions of this

part and of parts 50 and 56 of this

chapter.

Dated: March 3, 1997.

William B. Schultz,

Deputy Commissioner for Policy.

[FR Doc. 97–6475 Filed 3–13–97; 8:45 am]

BILLING CODE 4160–01–F

DEPARTMENT OF THE TREASURY

Internal Revenue Service

26 CFR Part 1

[TD 8560; TD 8597; TD 8660]

RIN 1545–AQ69; 1545–AT58; 1545–AT51

Consolidated Returns; Consolidated

and Controlled Groups; Correction

AGENCY: Internal Revenue Service,

Treasury.

ACTION: Correcting amendments.

SUMMARY: This document contains

technical corrections to final regulations

[TD 8560; TD 8597; TD 8660] which

were published in the Federal Register

on Monday, August 15, 1994 (59 FR

41666); Tuesday, July 18, 1995 (60 FR

36671); and Thursday, March 14, 1996

(61 FR 10447); respectively. The final

regulations amend the consolidated

return investment adjustment

provisions, intercompany transaction

provisions and the provisions limiting

losses and deductions from transactions

between members of a nonconsolidated

controlled group.

DATES: The correcting amendments

affecting §§ 1.267(f)–1, 1.1502–

13(f)(2)(ii), (g)(5), (l)(1), 1.1502–20,

1.1502–32(b), and 1.1502–80(b) are

effective July 18, 1995. The correcting

amendments affecting §§ 1.1502–11,

1.1502–19, 1.1502–32(f), 1.1502–43,

1.1502–76 and 1.1502–80(d)(1) are

effective January 1, 1995. The correcting

amendments affecting § 1.1502–13(f)(6)

are effective March 14, 1996. For dates

of applicability see §§ 1.267(f)–1(l),

§ 1.1502–11(b)(5), 1.1502–13(l)(1),

1.1502–13(f)(6)(v), 1.1502–19(h),

1.1502–32(h), 1.1502–76(b)(5), 1.1502–

80(d), and other relevant provisions.

FOR FURTHER INFORMATION CONTACT:

William Barry of the Office of Assistant