[Federal Register Volume 63, Number 212 (Tuesday, November 3, 1998)]
[Rules and Regulations]
[Pages 59217-59222]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 98-29391]



[[Page 59217]]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 814

[Docket No. 98N-0171]


Medical Devices; Humanitarian Use of Devices

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA) is issuing a final rule 
amending the regulations governing humanitarian use devices (HUD's). 
These amendments are being made to implement provisions of the Federal 
Food, Drug, and Cosmetic Act (the act) as amended by the Food and Drug 
Administration Modernization Act of 1997 (FDAMA).

EFFECTIVE DATE: February 1, 1999.

FOR FURTHER INFORMATION CONTACT: Joanne R. Less, Center for Devices and 
Radiological Health (HFZ-4dd), Food and Drug Administration, 9200 
Corporate Blvd., Rockville, MD 20850, 301-594-1190.

SUPPLEMENTARY INFORMATION:

I. Background

    In the Federal Register of June 26, 1996 (61 FR 33232), FDA 
published a final rule prescribing the procedures for submitting 
humanitarian device exemption (HDE) applications, amendments, and 
supplements; procedures for obtaining an extension of the exemption; 
and the criteria for FDA review and approval of HDE's. This rule 
amended part 814 (21 CFR part 814) of FDA's premarket approval 
regulations.
    On November 21, 1997, the President signed FDAMA into law (Pub. L. 
105-115). Section 2dd of FDAMA made the following changes to section 
520(m) of the act (21 U.S.C. 360j(m)):
    (1) FDAMA added a new provision to section 520(m) of the act that 
requires FDA to issue an order approving or denying an HDE within 75 
days after receiving the application.
    (2) FDAMA provided for an exemption from the requirement that a HUD 
may not be used without approval from an institutional review board 
(IRB) for cases in which a physician determines in an emergency 
situation that approval cannot be obtained in time to prevent serious 
harm or death to a patient. In such cases, the physician must notify 
the chairperson of the IRB after using the device. The notification 
must include the name of the patient, the date on which the device was 
used, and the reason for the use.
    (3) FDAMA eliminated the requirement that the sponsor of an HDE 
obtain approval for continued use every 18 months. Instead, FDA may 
require a sponsor to demonstrate continued compliance with the 
requirements of section 520(m) of the act, if FDA believes that such a 
demonstration is necessary to protect the public health, or if FDA has 
reason to believe that the criteria for exemption are no longer met.
    (4) FDAMA added a provision to section 520(m) of the act stating 
that FDA may suspend or withdraw an HDE approval only after providing 
notice and an opportunity for an informal hearing.
    (5) FDAMA eliminated the ``sunset'' provision in section 520(m) of 
the act, under which new approvals of HDE's would not have been 
permitted 5 years after the effective date of the rule originally 
implementing section 520(m) of the act.
    Section 2dd of FDAMA became effective on February 19, 1998. In the 
Federal Register of April 17, 1998, FDA published a direct final rule 
(63 FR 19185) and a companion proposed rule (63 FR 19196) on 
humanitarian use devices to amend the existing regulations to conform 
to amendments made by FDAMA to section 520(m) of the act. FDA published 
the direct final rule because the agency anticipated that it would 
receive no significant adverse comments, and because the agency 
believed the rule contained noncontroversial changes. FDA stated that 
if the agency received any significant adverse comment regarding the 
direct final rule, FDA would publish a document withdrawing the direct 
final rule within 30 days after the comment period ended and proceed to 
respond to all the comments under the companion proposed rule using 
usual notice-and-comment procedures. Any comments received under the 
companion proposed rule would be considered as comments regarding the 
direct final rule.
    FDA received significant adverse comment in response to the direct 
final rule. Therefore, FDA withdrew the direct final rule in the 
Federal Register of July 31, 1998 (63 FR 40825), and is publishing this 
final rule, which responds to the comments received and modifies the 
proposal in response to those comments.

II. Highlights of the Final Rule

    The following provisions of the proposed rule have not been 
changed:
    Part 814 has been amended in Sec. 814.100 to implement new section 
520(m)(5) of the act, which provides that FDA may require an HDE 
applicant to demonstrate continued compliance with the HDE 
requirements, if the agency believes that such a demonstration is 
necessary to protect the public health or if FDA has reason to believe 
the criteria for exemption are no longer met. This section of the 
regulation has also been modified to reflect the FDAMA provision that 
requires FDA to provide notice and an opportunity for an informal 
hearing before withdrawing or suspending approval of an HDE.
    Section 814.104 has been amended to repeal the sunset provision for 
submitting an original application as provided for in new section 
520(m)(5) of the act.
    In addition to the changes required by FDAMA, FDA is amending 
Sec. 814.104(b)(5) to allow a sponsor who is charging more than $250 
per HUD, to submit, in lieu of a report by an independent certified 
accountant (CPA), an attestation by a responsible individual of the 
organization, verifying that the amount charged does not exceed the 
device's cost of research, development, fabrication, and distribution. 
The submission of any report or attestation is unnecessary for HUD's 
for which an HDE applicant is charging $250 per HUD or less because, in 
most circumstances, a charge for a HUD that is $250 or less is evidence 
that the charge is unlikely to exceed the cost of research, 
development, fabrication, and distribution. This modification to the 
regulation will decrease the burden associated with submitting an HDE 
application for some devices by eliminating the time and cost 
associated with obtaining a report by a CPA or an attestation by a 
responsible individual in the organization.
    Sections 814.106, 814.108, 814.112, and 814.114 have been amended 
or revised to comply with a new provision of section 520(m) of the act. 
This new provision states that FDA will issue an order approving or 
denying an application 75 days after receiving it. Accordingly, FDA has 
adjusted its extension, review, and response timeframes for 
applications, amendments, and supplements.
    Section 814.116 has also been amended to implement this new 
provision of section 520(m) of the act. This amendment adjusts the 
applicable timeframes in cases where panel review is necessary or an 
applicant has received a not approvable letter.
    Section 814.120 has been revised because the 18-month term and 5-
year sunset provision were repealed by FDAMA. In accordance with new 
section 520(m)(6) of the act, Sec. 814.120 has been revised to provide 
for the

[[Page 59218]]

temporary suspension of approval of an HDE or an HDE supplement only 
after the sponsor has had an opportunity for an informal hearing under 
21 CFR part 16.
    Section 814.124 has been amended in accordance with section 
520(m)(4) of the act, to allow physicians, faced with an emergency 
situation, to administer a HUD prior to obtaining IRB approval if the 
physician determines that the wait will cause the patient serious harm 
or death. The amendment to this section also reflects the requirement 
that physicians who use a HUD in such emergencies must notify the IRB 
of such use and establishes a 5-day timeframe for such notification.
    Section 814.126 has been amended to incorporate section 520(m)(5) 
of the act, which provides FDA the authority to require an HDE 
applicant to demonstrate continued compliance with the HDE 
requirements, if the agency believes that such a demonstration is 
necessary to protect the public health or has reason to believe that 
the criteria for the HDE exemption are no longer met. FDA believes that 
it cannot fulfill its statutory obligation to protect the public health 
unless it obtains certain information about these products from the HDE 
holder. Accordingly, FDA added a reporting requirement that will permit 
the agency to monitor the HDE holder's continued compliance with the 
statutory criteria for exemption. The information required in these 
reports is the same type of information that is required for premarket 
approval applications (PMA's), but it will also contain additional 
information because of the unique nature of these device approvals. If 
these reports or any other information in FDA's possession give the 
agency reason to believe that a particular device raises public health 
concerns or that the criteria for exemption are no longer met, FDA may 
require the HDE holder to submit additional information to demonstrate 
compliance with the HDE requirements.

III. Summary and Analysis of Comments and FDA's Responses

    FDA received significant adverse comment in response to the direct 
final rule. A summary of the comments and FDA's responses to them are 
as follows:
    1. One comment expressed concern regarding the emergency use of a 
HUD before IRB review and approval (Sec. 814.124(a)), without any 
additional provision for the protection of human subjects. The comment 
stated that without additional measures, there may be nothing to 
prevent mistreatment of vulnerable or mentally incompetent subjects. 
The comment urged the agency to provide protection for patients in the 
form of required consultation with an institutional ethicist, 
ombudsman, or other unbiased third party prior to use of the device 
without IRB approval.
    FDA has not changed this provision of the rule. FDAMA specifically 
provided for the use of a HUD without IRB approval in emergency 
situations to protect the life or physical well-being of patients. 
Although FDA encourages the kind of consultation suggested by the 
comment in situations where time and circumstances permit such 
consultation, the agency believes imposing a requirement for such prior 
consultation would be contrary to the intent of this statutory 
provision. The agency further believes that notification of the IRB 
chairperson following the emergency use will provide a measure of 
protection for patients.
    2. The same comment also asked for clarification of the statement 
in Sec. 814.118(e) that FDA will not withdraw approval of an HDE solely 
because it is subsequently determined that the disease or condition for 
which the HUD is intended affects or is manifested in more than 4,000 
people in the United States per year. The comment urged FDA to set a 
distribution limit in order to reduce the possibility that 
manufacturers will abuse the exemption.
    FDA agrees that Sec. 814.118(e) of the proposed rule requires 
clarification. As originally issued in June 1996, that section of the 
regulation included an additional sentence, which explained that a 
determination that more than 4,000 people were affected could be a 
basis for disapproving an extension request for an HDE. When the 
sentence referencing the extension was eliminated in the proposed rule 
to conform with FDAMA's removal of the 18-month term for HDE's, the 
remaining portion of the provision became unclear. Under the statute 
and FDA's implementing regulations, an HDE may be withdrawn if any of 
the criteria for the exemption are no longer met. FDA, therefore, is 
deleting Sec. 814.118(e) from the final rule.
    However, because humanitarian use devices are intended for patient 
populations with limited options, the statute gives the agency 
discretion in determining whether a HUD should be removed from the 
market. FDA does agree with the comment that withdrawal would be 
appropriate when the numbers of devices being sold are so large that 
they indicate a clear abuse of the law. The agency does not believe, 
however, that it would be appropriate in every instance to withdraw 
approval of an HDE solely because the disease or condition has been 
determined to affect more than 4,000 people in the United States per 
year. In determining if the approval for an HDE should be withdrawn, 
FDA will consider all of the statutory criteria as well as the needs of 
the affected patient population.
    3. The second comment objected to the annual reporting requirement 
and suggested that FDA determine the appropriate reporting period at 
the time of product approval rather than always requiring reporting on 
an annual basis.
    FDA has modified the rule in response to this comment. Under the 
June 26, 1996, final rule, an HDE holder was required to obtain 
approval of an extension request every 18 months in order to continue 
marketing the HUD. FDAMA eliminated this requirement but provided that 
FDA may require the holder to demonstrate continued compliance with the 
HDE requirements if the agency believes that such demonstration is 
needed to protect the public health or has reason to believe that the 
criteria for the exemption are no longer met.
    FDA included a provision for annual reporting in the proposed rule 
because the agency believed that annual reporting would be the most 
appropriate mechanism for the agency to monitor whether there is reason 
to question the continued exemption of the device from the act's 
effectiveness requirements. Upon reconsideration, FDA has determined 
that the reporting frequency necessary to protect the public health may 
vary depending upon the device, its intended use, the affected patient 
population, and experience with the device after it is marketed. 
Therefore, Sec. 812.126(b)(1) has been modified in the final rule to 
state that the frequency of the reports will be specified in the 
approval order for the HDE. Ordinarily, FDA does not expect to require 
periodic reports to be submitted more frequently than annually. FDA 
does believe, however, that it may be appropriate to require reports on 
certain HDE's less frequently and that in many cases the frequency of 
required reports will decrease after the device has been marketed for a 
period of time.
    4. The same comment also objected to the ``requirement'' that an 
``HDE holder maintain records in perpetuity * * *'' and suggested that 
a more appropriate timeframe would be 3 calendar years after the 
manufacturer ceases distribution of the product in question.
    Section 814.126(b)(2) of the HDE regulation specifies the types of 
records that should be maintained by the HDE holder, but does not 
specify the timeframe for maintaining such records. FDA agrees that a 
reasonable timeframe

[[Page 59219]]

should be established for maintaining such records and intends to 
specify such timeframes as part of the approval order. Accordingly, FDA 
has modified the regulation to state that records shall be maintained 
in accordance with the approval order for the HDE.
    FDA has also made some changes in the final rule to correct 
typographical errors and citations that were incorrect.

IV. Environmental Impact

    The agency has determined under 21 CFR 25.30(h) that this action is 
of a type that does not individually or cumulatively have a significant 
effect on the human environment. Therefore, neither an environmental 
assessment nor an environmental impact statement is required.

V. Analysis of Impacts

    FDA has examined the impact of this final rule under Executive 
Order 12866 and the Regulatory Flexibility Act (5 U.S.C. 601-612) (as 
amended by subtitle D of the Small Business Regulatory Fairness Act of 
1996 (Pub. L. 104-121)), and the Unfunded Mandates Reform Act of 1995 
(Pub. L. 104-4). Executive Order 12866 directs agencies to assess all 
costs and benefits of available regulatory alternatives and, when 
regulation is necessary, to select regulatory approaches that maximize 
net benefits (including potential economic, environmental, public 
health and safety, and other advantages; distributive impacts; and 
equity). The agency believes that this final rule is consistent with 
the regulatory philosophy and principles identified in the Executive 
Order. In addition, this 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. The rule codifies applicable statutory requirements 
imposed by FDAMA. Because the rule allows physicians more flexibility 
without compromising the public health and reduces the requirements 
imposed on sponsors, it may permit more small competitors to enter the 
marketplace. The agency certifies, therefore, that this final rule will 
not have a significant economic impact on a substantial number of small 
entities. This final rule also does not trigger the requirement for a 
written statement under section 202(a) of the Unfunded Mandates Reform 
Act because it does not impose a mandate that results in an expenditure 
of $100 million or more by State, local, or tribal governments in the 
aggregate, or by the private sector, in any one year.

VI. Paperwork Reduction Act of 1995

    This final rule contains information collection requirements that 
are subject to review by the Office of Management and Budget (OMB) 
under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520). A 
description of the requirements is given below. The title, description, 
and respondent description of the information collection provisions are 
shown below with an estimate of the annual reporting and recordkeeping 
burden. Included in the estimate is the time for reviewing the 
instructions, searching existing data sources, gathering and 
maintaining the data needed, and completing and reviewing each 
collection of information. The description below reflects the changes 
made in the final rule in response to comments, as discussed in section 
III of this document.
    Title: Amendments to Humanitarian Use Device Requirements.
    Description: Section 520(m) of the act was created as an incentive 
for the development of HUD'S for use in the treatment or diagnosis of 
diseases or conditions affecting fewer than 4,000 individuals in the 
United States. FDA is issuing this rule to amend the existing 
regulations governing HUD's, found in part 814, to conform to the 
amendments made by FDAMA to section 520(m) of the act.
    Section 814.124(a) is amended to allow physicians in emergency 
situations to administer a HUD prior to obtaining IRB approval. In such 
situations, the physician is required to provide written notification, 
including the identification of the patient involved, the date of use, 
and the reason for use, to the IRB within 5 days after emergency use. 
FDA anticipates that five physicians will use HUD's in emergency 
situations before obtaining approval from an IRB. FDA estimates that 
notifications under this section will take an average of 1 hour per 
response.
    In response to a comment, FDA is amending proposed 
Sec. 814.126(b)(1) to delete the requirement of an annual report and to 
include instead a periodic reporting requirement that will be 
established by the approval order for the HDE. This change continues to 
permit the agency to obtain sufficient information for it to determine 
whether there is reason to question the continued exemption of the 
device from the act's effectiveness requirements. FDA estimates that, 
due to the nature of some of the devices, initially 15 HDE holders per 
year will be required to submit annual reports. As the agency and 
industry gain experience with HDE's, FDA believes the number of HDE 
holders who will be required to submit annual reports will decrease. 
FDA believes that much of the information will already be in the HDE 
holder's possession, and the agency estimates that the reports will 
take an average of 120 hours per response.
    In addition to the changes required by FDAMA, FDA is amending 
Sec. 814.104(b)(5) to allow a sponsor who is charging more than $250 
per HUD to submit, in lieu of a report by an independent CPA, an 
attestation by a responsible individual of the organization, verifying 
that the amount charged does not exceed the device's cost of research, 
development, fabrication, and distribution. In addition, the amendments 
to Sec. 814.104(b)(5) waive the requirement for submission of any CPA 
report or attestation for HUD's for which an HDE applicant is charging 
$250 or less. FDA anticipates, based on past experience, that 7 of the 
anticipated 15 HDE holders per year will charge less than $250 per HUD, 
and thus be exempt from the requirement altogether. For the remaining 
eight HDE holders, FDA anticipates that all will submit attestations in 
lieu of CPA reports, and estimates that these submissions will require 
2 hours to complete.
    Proposed Sec. 814.126(b)(2) has been modified, in response to a 
comment, to require HDE holders to retain records for a time period 
specified in the approval order, rather than an unlimited time period.
    Description of Respondents: Business or other for profit 
organization.
    FDA estimates the burden for this collection of information as 
follows:

                                  Table 1.--Estimated Annual Reporting Burden1
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                                                      Annual
         21 CFR Section               No. of       Frequency per   Total Annual      Hours per      Total Hours
                                    Respondents      Response        Responses       Response
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 814.104(b)(5)                          8               1               8               2              16

[[Page 59220]]

 814.124(a)                             5               1               5               1               5
 814.126(b)(1)                         15               1              15             120           1,800
 Total                                                                                              1,821
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\1\ There are no operating and maintenance costs or capital costs associated with this information collection.


                                Table 2.--Estimated Annual Recordkeeping Burden1
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                                                      Annual
         21 CFR Section               No. of       Frequency per   Total Annual      Hours per      Total Hours
                                   Recordkeepers   Recordkeeping      Records      Recordkeeper
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 814.126(b)(2)                         15               1              15               2              30
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\1\ There are no operating and maintenance costs or capital costs associated with this information collection.

    The information collection provisions of this final rule have been 
submitted to OMB for review and approved under OMB control number 0910-
dd84. An agency may not conduct or sponsor, and a person is not 
required to respond to a collection of information unless it displays a 
currently valid OMB control number.

List of Subjects in 21 CFR Part 814

    Administrative practice and procedure, Confidential business 
information, 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 814 is amended as follows:

PART 814--PREMARKET APPROVAL OF MEDICAL DEVICES

    1. The authority citation for 21 CFR part 814 continues to read as 
follows:

    Authority: 21 U.S.C. 351, 352, 353, 360, 360c-360j, 371, 372, 
373, 374, 375, 379, 379e, 381.

    2. Section 814.100 is amended by revising paragraphs (a)(2) and (d) 
and by adding paragraph (e) to read as follows:

Sec. 814.100   Purpose and scope.

    (a) * * *
    (2) Marketing approval for the HUD notwithstanding the absence of 
reasonable assurance of effectiveness that would otherwise be required 
under sections 514 and 515 of the act.
* * * * *
    (d) A person granted an exemption under section 520(m) of the act 
shall submit periodic reports as described in Sec. 814.126(b).
    (e) FDA may suspend or withdraw approval of an HDE after providing 
notice and an opportunity for an informal hearing.
    3. Section 814.104 is amended by removing paragraph (b), by 
redesignating paragraphs (c) through (e) as paragraphs (b) through (d), 
and by revising newly redesignated paragraphs (b)(5) and (d) and the 
first sentence in redesignated paragraph (c) to read as follows:


Sec. 814.104   Original applications.

* * * * *
    (b) * * *
    (5) The amount to be charged for the device and, if the amount is 
more than $250, a report by an independent certified public accountant, 
made in accordance with the Statement on Standards for Attestation 
established by the American Institute of Certified Public Accountants, 
or in lieu of such a report, an attestation by a responsible individual 
of the organization, verifying that the amount charged does not exceed 
the costs of the device's research, development, fabrication, and 
distribution. If the amount charged is $250 or less, the requirement 
for a report by an independent certified public accountant or an 
attestation by a responsible individual of the organization is waived.
    (c) Omission of information. If the applicant believes that certain 
information required under paragraph (b) of this section is not 
applicable to the device that is the subject of the HDE, and omits any 
such information from its HDE, the applicant shall submit a statement 
that identifies and justifies the omission. * * *
    (d) Address for submissions and correspondence. Copies of all 
original HDE's, amendments and supplements, as well as any 
correspondence relating to an HDE, shall be sent or delivered to the 
Document Mail Center (HFZ-401), Office of Device Evaluation, Center for 
Devices and Radiological Health, Food and Drug Administration, 9200 
Corporate Blvd., Rockville, MD 20850.
    4. Section 814.106 is revised to read as follows:

Sec. 814.106   HDE amendments and resubmitted HDE's.

    An HDE or HDE supplement may be amended or resubmitted upon an 
applicant's own initiative, or at the request of FDA, for the same 
reasons and in the same manner as prescribed for PMA's in Sec. 814.37, 
except that the timeframes set forth in Sec. 814.37(c)(1) and (d) do 
not apply. If FDA requests an HDE applicant to submit an HDE amendment, 
and a written response to FDA's request is not received within 75 days 
of the date of the request, FDA will consider the pending HDE or HDE 
supplement to be withdrawn voluntarily by the applicant. Furthermore, 
if the HDE applicant, on its own initiative or at FDA's request, 
submits a major amendment as described in Sec. 814.37(c)(1), the review 
period may be extended up to 75 days.
    5. Section 814.108 is revised to read as follows:

Sec. 814.108   Supplemental applications.

    After FDA approval of an original HDE, an applicant shall submit 
supplements in accordance with the requirements for PMA's under 
Sec. 814.39, except that a request for a new indication for use of a 
HUD shall comply with requirements set forth in Sec. 814.110. The 
timeframes for review of, and FDA action on, an HDE supplement are the 
same as those provided in Sec. 814.114 for an HDE.
    6. Section 814.112 is amended by revising paragraph (a) 
introductory text, paragraph (a)(1), and paragraph (b) to read as 
follows:

[[Page 59221]]

Sec. 814.112   Filing an HDE.

    (a) The filing of an HDE means that FDA has made a threshold 
determination that the application is sufficiently complete to permit 
substantive review. Within 30 days from the date an HDE is received by 
FDA, the agency will notify the applicant whether the application has 
been filed. FDA may refuse to file an HDE if any of the following 
applies:
    (1) The application is incomplete because it does not on its face 
contain all the information required under Sec. 814.104(b);
* * * * *
    (b) The provisions contained in Sec. 814.42(b), (c), and (d) 
regarding notification of filing decisions, filing dates, the start of 
the 75-day review period, and applicant's options in response to FDA 
refuse to file decisions shall apply to HDE's.
    7. Section 814.114 is revised to read as follows:

Sec. 814.114   Timeframes for reviewing an HDE.

    Within 75 days after receipt of an HDE that is accepted for filing 
and to which the applicant does not submit a major amendment, FDA shall 
send the applicant an approval order, an approvable letter, a not 
approvable letter (under Sec. 814.116), or an order denying approval 
(under Sec. 814.118).
    8. Section 814.116 is amended by removing the last sentence in 
paragraph (a) and by adding two sentences in its place, by revising the 
last sentence of paragraph (d), and by adding paragraph (e) to read as 
follows:

Sec. 814.116   Procedures for review of an HDE.

    (a) * * * If the HDE is referred to a panel, the agency shall 
follow the procedures set forth under Sec. 814.44, with the exception 
that FDA will complete its review of the HDE and the advisory committee 
report and recommendations within 75 days from receipt of an HDE that 
is accepted for filing under Sec. 814.112 or the date of filing as 
determined under Sec. 814.106, whichever is later. Within the later of 
these two timeframes, FDA will issue an approval order under paragraph 
(b) of this section, an approvable letter under paragraph (c) of this 
section, a not approvable letter under paragraph (d) of this section, 
or an order denying approval of the application under Sec. 814.118(a).
* * * * *
     (d) * * * The applicant may respond to the not approvable letter 
in the same manner as permitted for not approvable letters for PMA's 
under Sec. 814.44(f), with the exception that if a major HDE amendment 
is submitted, the review period may be extended up to 75 days.
    (e) FDA will consider an HDE to have been withdrawn voluntarily if:
    (1) The applicant fails to respond in writing to a written request 
for an amendment within 75 days after the date FDA issues such request;
    (2) The applicant fails to respond in writing to an approvable or 
not approvable letter within 75 days after the date FDA issues such 
letter; or
    (3) The applicant submits a written notice to FDA that the HDE has 
been withdrawn.
    9. Section 814.118 is amended by revising paragraph (a)(8) and 
removing paragraph (e) to read as follows:

Sec. 814.118   Denial of approval or withdrawal of approval of an HDE.

    (a) * * *
    (8) The applicant does not permit an authorized FDA employee an 
opportunity to inspect at a reasonable time and in a reasonable manner 
the facilities and controls, and to have access to and to copy and 
verify all records pertinent to the application; or
* * * * *
    10. Section 814.120 is revised to read as follows:

Sec. 814.120   Temporary suspension of approval of an HDE.

    An HDE or HDE supplement may be temporarily suspended for the same 
reasons and in the same manner as prescribed for PMA's in Sec. 814.47.
    11. Section 814.124 is amended by adding three sentences at the end 
of paragraph (a) to read as follows:

Sec. 814.124   Institutional Review Board requirements.

    (a) * * * If, however, a physician in an emergency situation 
determines that approval from an IRB cannot be obtained in time to 
prevent serious harm or death to a patient, a HUD may be administered 
without prior approval by the IRB located at the facility or by a 
similarly constituted IRB that has agreed to oversee such use. In such 
an emergency situation, the physician shall, within 5 days after the 
use of the device, provide written notification to the chairman of the 
IRB of such use. Such written notification shall include the 
identification of the patient involved, the date on which the device 
was used, and the reason for the use.
* * * * *
    12. Section 814.126 is amended by revising the first sentence in 
paragraph (a) and by revising paragraph (b) to read as follows:

Sec. 814.126   Postapproval requirements and reports.

    (a) An HDE approved under this subpart H shall be subject to the 
postapproval requirements and reports set forth under subpart E of this 
part, as applicable, with the exception of Sec. 814.82(a)(7). * * *
    (b) In addition to the reports identified in paragraph (a) of this 
section, the holder of an approved HDE shall prepare and submit the 
following complete, accurate, and timely reports:
    (1) Periodic reports. An HDE applicant is required to submit 
reports in accordance with the approval order. Unless FDA specifies 
otherwise, any periodic report shall include:
    (i) An update of the information required under Sec. 814.102(a) in 
a separately bound volume;
    (ii) An update of the information required under 
Sec. 814.104(b)(2), (b)(3), and (b)(5);
    (iii) The number of devices that have been shipped or sold since 
initial marketing approval under this subpart H and, if the number 
shipped or sold exceeds 4,000, an explanation and estimate of the 
number of devices used per patient. If a single device is used on 
multiple patients, the applicant shall submit an estimate of the number 
of patients treated or diagnosed using the device together with an 
explanation of the basis for the estimate;
    (iv) Information describing the applicant's clinical experience 
with the device since the HDE was initially approved. This information 
shall include safety information that is known or reasonably should be 
known to the applicant, medical device reports made under part 8dd of 
this chapter, any data generated from the postmarketing studies, and 
information (whether published or unpublished) that is known or 
reasonably expected to be known by the applicant that may affect an 
evaluation of the safety of the device or that may affect the statement 
of contraindications, warnings, precautions, and adverse reactions in 
the device's labeling; and
    (v) A summary of any changes made to the device in accordance with 
supplements submitted under Sec. 814.108. If information provided in 
the periodic reports, or any other information in the possession of 
FDA, gives the agency reason to believe that a device raises public 
health concerns or that the criteria for exemption are no longer met, 
the agency may require the HDE holder to submit additional information 
to demonstrate continued compliance with the HDE requirements.
    (2) Other. An HDE holder shall maintain records of the names and

[[Page 59222]]

addresses of the facilities to which the HUD has been shipped, 
correspondence with reviewing IRB's, as well as any other information 
requested by a reviewing IRB or FDA. Such records shall be maintained 
in accordance with the HDE approval order.

    Dated: October 28, 1998.
 William B. Schultz,
 Deputy Commissioner for Policy.
[FR Doc. 98-29391 Filed 11-2-98; 8:45 am]
BILLING CODE 4160-01-F