[Federal Register Volume 62, Number 50 (Friday, March 14, 1997)]
[Rules and Regulations]
[Pages 12087-12096]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-6475]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES
21 CFR Part 812

[Docket No. 92N-0308]


Investigational Device Exemptions; Disqualification of Clinical 
Investigators

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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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 Sec. 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 
Sec. 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 Sec. 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 
Sec. 312.70 (21 CFR 312.70). FDA stated that if comments persuaded the 
agency to revise the proposed rule to follow Sec. 312.70 precisely or 
closely, the agency might issue a final rule which parallels 
Sec. 312.70.
    FDA received three comments stating an explicit preference for 
rules governing disqualification of investigators of drugs as specified 
in Sec. 312.70, over the rules that had been proposed for 
disqualification of investigators of devices. Two other comments that 
did not specifically mention Sec. 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 Sec. 312.70 to the proposed regulation 
because Sec. 312.70 does not contain the perceived flaws found in the 
proposed regulation. These comments stated, e.g., that the threshold 
for disqualification in Sec. 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 Sec. 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 Sec. 312.70. 
Therefore, the comment recommended that FDA propose a rule similar to 
Sec. 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 Sec. 312.70 (as well as the regulation for 
disqualification of investigators of animal drugs at Sec. 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 Sec. 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 
Sec. 312.70 * * *

[[Page 12088]]

the agency may issue a rule that parallels Sec. 312.70.''( 58 FR 
52144).)
     In response to the concern that medical device companies and 
investigators of medical devices are unfamiliar with Sec. 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 Sec. 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 Sec. 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 Sec. 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 Sec. 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 Sec. 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 
Sec. 812.30(c)(2).)
    In accordance with Sec. 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 Sec. 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 Sec. 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

[[Page 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 Sec. 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 (Sec. 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 (Sec. 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 
(Sec. 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 (Sec. 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 
Sec. 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 Sec. 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 Sec. 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 Sec. 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 Sec. 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, Sec. 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 Sec. 812.119(c).) If the Commissioner determines, after the

[[Page 12090]]

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 Sec. 812.119(d).)
    Thus, in accordance with Sec. 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 Sec. 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 Sec. 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 Sec. 812.119(a)

    2. One comment requested that Sec. 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 
Sec. 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 Sec. 812.119(a)(1)

    3. One comment noted that the use of the term ``necessarily'' in 
proposed Sec. 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 
Sec. 812.119(a)(1) to ensure that a disqualification decision would not 
affect these areas of the investigator's life.
    Proposed Sec. 812.119(a)(1) has not been adopted in the final 
regulation. However, under Sec. 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 Sec. 812.119(b)(1)

    4. Proposed Sec. 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 
Sec. 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 
Sec. 812.119(a) ensures against such situations.
    In accordance with Sec. 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 Sec. 812.119(b)(3)

    5. Five comments suggested modifying the language in proposed 
Sec. 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 Sec. 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 Sec. 812.119(a), which parallels, with minor modifications, 
Sec. 312.70(a). Section Sec. 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 Sec. 812.119(a). Section 
812.119(a) provides the investigator with an opportunity to explain the

[[Page 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 Sec. 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 
Sec. 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 
Sec. 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 Sec. 812.119(b), which parallels the 
language used in Sec. 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 
Sec. 812.119(d), which parallels the language used in Sec. 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 Sec. 812.119(c)(1) and (d)

    7. A comment suggested that the written notice in 
Sec. 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 Sec. 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 Sec. 812.119(c)(2)

    8. Proposed Sec. 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 
Sec. 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 
Sec. 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 Sec. 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 Sec. 812.119(a) by 
inserting the term ``alleged'' in the regulatory text is unnecessary 
because Sec. 812.119(a), unlike proposed Sec. 812.119(c)(2), does not 
indicate that a final noncompliance determination will be made at this 
preliminary stage.

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

    9. A comment requested that the terms ``FDA'' and ``agency'' in 
Sec. 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 Sec. 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.

[[Page 12092]]

J. Proposed Sec. 812.119(d)

    10. A comment stated that the text of proposed Sec. 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 
Sec. 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 Sec. 812.119(f)(1)

    11. Under Sec. 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 Sec. 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 Sec. 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 Sec. 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 Sec. 812.119(g)

    13. One comment said that proposed Sec. 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 
Sec. 812.119(g).
    The agency has addressed these concerns with the adoption of 
Sec. 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 Sec. 812.119(e), which parallels Sec. 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 Sec. 812.119(g)(2)

    14. A comment suggested that proposed Sec. 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 Sec. 812.119(d), which, like 
Sec. 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 Sec. 812.119(g)(2) and proposed Sec. 812.119(b). The comment 
stated that, under Sec. 812.119(b), the Commissioner must base a 
disqualification order upon findings that address only limited factual 
issues. In contrast, Sec. 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 Sec. 812.119(b) related to ``the risks of the

[[Page 12093]]

subjects from suspension of the study,'' and yet FDA, under 
Sec. 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 Sec. 812.119(b), which 
parallels Sec. 312.70(b) and by the elimination of proposed 
Sec. 812.119(g) in the final rule. Under Sec. 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 Sec. 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 Sec. 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 Sec. 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 Sec. 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, Sec. 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 Sec. 812.119(g)(2)(v)

    19. One comment stated that proposed Sec. 812.119(g)(2)(v) was too 
restrictive. Various comments suggested that Sec. 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 Sec. 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 life-threatening 
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 Sec. 812.119(g)(3)

    20. Under proposed Sec. 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 
Sec. 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 Sec. 312.70(c).)
    The agency agrees with the comments and has adopted 
Sec. 812.119(c), which parallels the language used in Sec. 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 
Sec. 312.70. Under Sec. 812.119(c), each regulatory submission 
containing data reported by a

[[Page 12094]]

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 Sec. 312.70. Under Sec. 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 Sec. 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 Sec. 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, Sec. 812.119(e) parallels Sec. 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 
Sec. 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 Sec. 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 Sec. 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 Sec. 812.119(g)(4)

    26. Under proposed Sec. 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., Secs. 812.40 and 812.150, must be maintained to provide adequate 
protection for subjects.

T. Proposed Sec. 812.119(h)(1)

    27. Proposed Sec. 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 
Sec. 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

[[Page 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 Sec. 812.119(h)(1), which is addressed in this comment, 
has not been adopted. However, under Sec. 812.119(b), a 
disqualification notice is provided that states that the investigator 
is disqualified and the basis for such determination. Final 
Sec. 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 Sec. 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 Sec. 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 Sec. 812.119(b), which 
parallels Sec. 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 Sec. 812.119(h)(3)

    29. According to a comment, proposed Sec. 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 Sec. 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 Sec. 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 Sec. 812.119(j) addressed in these two comments has not 
been adopted in the final rule. However, Sec. 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

[[Page 12096]]

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:

Sec. 812.2  Applicability.

* * * * *
    (c) Exempted investigations. This part, with the exception of 
Sec. 812.119, does not apply to investigations of the following 
categories of devices: * * *
* * * * *
    3. New Sec. 812.119 is added to subpart E to read as follows:

Sec. 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