Federal Register, Volume 63 Issue 74 (Friday, April 17, 1998)

[Federal Register Volume 63, Number 74 (Friday, April 17, 1998)]
[Rules and Regulations]
[Pages 19185-19190]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-9637]

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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: Direct final rule.

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SUMMARY: The Food and Drug Administration (FDA) is amending the
regulations governing humanitarian use devices. 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). Elsewhere in this issue of the
Federal Register, FDA is publishing a companion proposed rule, under
FDA's usual procedures for notice and comment, to provide a procedural
framework to finalize the rule in the event the agency receives any
significant adverse comment and withdraws the direct final rule.

DATES: This rule is effective August 31, 1998. Submit written comments
on or before July 1, 1998. Submit written comments on the information
collection provisions on or before June 16, 1998. If FDA receives no
significant adverse comments within the specified comment period, the
agency intends to publish a document confirming the effective date of
the final rule in the Federal Register within 30 days after the comment
period on this direct final rule ends.

ADDRESSES: Submit written comments on the direct final rule to the
Dockets Management Branch (HFA-305), Food and Drug Administration,
12420 Parklawn Dr., rm. 1-23, Rockville, MD 20857.

FOR FURTHER INFORMATION CONTACT: Joanne R. Less, Center for Devices and
Radiological Health (HFZ-403), Food and Drug Administration, 9200
Corporate Blvd., Rockville, MD 20857, 301-594-1190.

SUPPLEMENTARY INFORMATION:

I. Background

The Safe Medical Devices Act of 1990 (Pub. L. 101-629) added
section 520(m) to the act (21 U.S.C. 360j(m)). Section 520(m) creates
an incentive for the development of humanitarian use devices (HUD) for
use in the treatment or diagnosis of diseases or conditions affecting a
small number of individuals. Section 520(m) authorizes FDA, by
regulation, to exempt a HUD from the effectiveness requirements of
section 514 and 515 of the act (21 U.S.C. 360d and 360e) (i.e.,
``reasonable assurance that the device is effective'') provided that:
(1) The device is to be used to treat or diagnose a disease or
condition that affects fewer than 4,000 individuals in the United
States; (2) the device would not be available to a person with such a
disease or condition unless the exemption is granted; (3) no comparable
device (other than a device that has been granted such an exemption) is
available to treat or diagnose the disease or condition; and (4) the
device will not expose patients to an unreasonable or significant risk
of illness or injury, and the probable benefit to health from using the
device outweighs the risk of injury or illness from its use, taking
into account the probable risks and benefits of currently available
devices to alternative forms of treatments.
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 regulations.
On November 21, 1997, the President signed into law FDAMA (Pub. L.
105-115). Section 203 of FDAMA made the following changes to section
520(m) of the act:
(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

[[Page 19186]]

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, after
use of the device, notify the chairperson of the IRB. 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).
Section 203 of FDAMA became effective on February 19, 1998, and
FDA is implementing the statute as of that date. FDA is issuing this
direct final rule to amend the existing regulations to conform to
certain amendments by FDAMA to section 520(m) of the act.

II. Highlights of Part 814--Subpart H--Humanitarian Use Devices

Section 814.100 has been amended 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 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. FDAMA also allows FDA to withdraw or
suspend approval of an HDE after providing notice and an opportunity
for an informal hearing if any conditions of the HDE are no longer met.
Section 814.104 has been amended to repeal the sunset provision
for submitting an original application, as provided 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
public 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 does not 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 revised
or amended 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. In accordance with
the new provision, FDA has adjusted its extension, review, and response
timeframes for applications, amendments, and supplements.
Section 814.116 also has been amended to implement the new
provision of section 520(m) of the act and to incorporate the 75-day
provision. This section is amended to adjust the applicable timeframes
in cases where panel review is necessary or an applicant has received a
not approvable letter.
The last sentence of Sec. 814.118 has been amended because
extensions are no longer required under new section 520(m)(6) of the
act.
Section 814.120 has been revised because the 18-month term and 5-
year sunset provision were repealed by FDAMA. Under new section
520(m)(6) of the act, Sec. 814.120 has been revised to provide for the
temporary suspension of approval of an HDE or an HDE supplement after
the sponsor has had an opportunity for an informal hearing under 21 CFR
part 16.
Section 814.124 is 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 patient serious harm or death. This
section has also been amended to reflect the requirement that
physicians who use a HUD in such emergencies must notify the IRB
following such use.
Section 814.126 has been amended to incorporate the provision of
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 FDA 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 on a regular
basis. Prior to FDAMA, HDE's were approved for a period of 18 months.
Under the amended provision, marketing authorization is no longer
temporary. Accordingly, FDA is adding an annual reporting requirement
that will permit the agency to obtain sufficient information for the
agency to determine whether there is reason to question the continued
exemption of the device from the act's effectiveness requirements. The
submission of annual reports is consistent with the premarket approval
application (PMA) reporting requirements for other marketed devices,
but the HDE annual reports will contain additional information because
of the unique nature of these device approvals. The information
required in these annual reports is the same type of information that
was previously required in requests for extensions. If these annual
reports or any other information in FDA's possession give FDA reason to
believe that a particular 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
compliance with the HDE requirements.

III. Rulemaking Action

In the Federal Register of November 21, 1997 (62 FR 62466), FDA
described when and how it will employ direct final rulemaking. FDA
believes that this rule is appropriate for direct final rulemaking
because FDA views this rule as making noncontroversial amendments to an
existing regulation, incorporating amendments to section 520(m) of the
act made by FDAMA; and FDA anticipates no significant adverse comments.
Consistent with FDA's procedures on direct final rulemaking, elsewhere
in this issue of the Federal Register FDA is publishing a companion
proposed rule to amend the existing HUD regulations. The companion
proposed rule is identical to the direct final rule. The companion
proposed rule provides a procedural framework within which the rule may
be finalized in the

[[Page 19187]]

event the direct final rule is withdrawn because of any significant
adverse comments. The comment period for the direct final rule runs
concurrently with the comment period of the companion proposed rule.
Any comments received under the companion proposed rule will be
considered as comments regarding the direct final rule.
FDA is providing a comment period on the direct final rule of 75
days after April 17, 1998. If the agency receives any significant
adverse comments, FDA intends to withdraw this final rule by
publication of a notice in the Federal Register within 30 days after
the comment period ends. A significant adverse comment is defined as a
comment that explains why the rule would be inappropriate, including
challenges to the rule's underlying premise or approach, or would be
ineffective or unacceptable without change. In determining whether a
significant adverse comment is sufficient to terminate a direct final
rulemaking, FDA will consider whether the comment raises an issue
serious enough to warrant a substantive response in a notice-and-
comment process. Comments that are frivolous, insubstantial, or outside
the scope of the rule will not be considered significant or adverse
under this procedure. For example, a comment requesting the inclusion
of HDE applications for HUD's intended to benefit patients in the
treatment and diagnosis of diseases or conditions that affect more than
4,000 individuals per year in the United States (Sec. 814.102(a)(5))
will not be considered a significant adverse comment because it is
outside the realm of the rule. On the other hand, a comment
recommending an additional change to the rule may be considered a
significant adverse comment if the comment explains why the rule would
be ineffective without the additional change. In addition, if a
significant adverse comment applies to part of a rule and that part can
be severed from the remainder of the rule, FDA may adopt as final those
parts of the rule that are not the subject of a significant adverse
comment.
If FDA withdraws the direct final rule, all comments received will
be considered under the companion proposed rule in developing a final
rule under the usual notice-and-comment procedures under the
Administrative Procedure Act (5 U.S.C. 552 et seq.). If FDA receives no
significant adverse comments during the specified comment period, FDA
intends to publish a confirmation notice in the Federal Register within
30 days after the comment period ends. FDA intends to make the direct
final rule effective 30 days after the date the confirmation notice is
published in the Federal Register.

IV. Environmental Impact

The agency has determined under 21 CFR 25.30(h) that this action
is of a type that does not 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 direct 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 of available regulatory alternatives and,
when regulatory action 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 direct
final rule is consistent with the regulatory philosophy and principles
identified in the Executive Order. In addition, this direct 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 the 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 that this direct final
rule will not have a significant economic impact on a substantial
number of small entities. This direct 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 1
year.

VI. Paperwork Reduction Act of 1995

This direct final rule contains information collection provisions
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). 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.
FDA invites comments on: (1) Whether the proposed collection of
information is necessary for the proper performance of FDA's functions,
including whether the information will have practical utility; (2) the
accuracy of FDA's estimate of the burden of the proposed collection of
information, including the validity of the methodology and assumptions
used; (3) ways to enhance the quality, utility, and clarity of the
information to be collected; and (4) ways to minimize the burden of the
collection of information on respondents, including through the use of
automated collection techniques, when appropriate, and other forms of
information technology.
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.
FDA is amending Sec. 814.126(b)(1) to delete the requirement for a
final report and to include an annual reporting requirement for HDE
holders that will 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.

[[Page 19188]]

FDA estimates that 15 HDE holders will submit annual reports. FDA
believes that much of the information will already be in the HDE
holder's possession, and the agency estimates that 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 Sec. 814.104(b)(5) 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.
Section 814.126(b)(2) modifies the current recordkeeping
requirement for HDE holders to require that HDE holders retain records
indefinitely instead of only for the duration of the period for which
the HUD is approved for marketing. FDA believes that this change will
not affect the total time required to maintain the records.
Description of Respondents: Business or other for profit
organizations.
FDA estimates the burden for this collection of information as
follows:

Table 1.--Estimated Annual Reporting Burden
----------------------------------------------------------------------------------------------------------------
Annual
21 CFR Section No. of Frequency per Total Annual Hours per Total Hours
Respondents Response Responses Response
----------------------------------------------------------------------------------------------------------------
814.104(b)(5) 8 1 8 2 16
814.124(a) 5 1 5 1 5
814.126(b)(1) 15 1 15 120 1,800
Total 1,821
----------------------------------------------------------------------------------------------------------------

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

As provided in 5 CFR 1320.5(c)(1), collections of information in a
direct final rule are subject to the procedures set forth in 5 CFR
1320.10. Interested persons and organizations may submit comments on
the information collection requirements of this direct final rule by
June 16, 1998 to the Dockets Management Branch (address above).
At the close of the 60-day comment period, FDA will review the
comments received, revise the information collection provisions as
necessary, and submit these provisions to OMB for review. FDA will
publish a notice in the Federal Register when the information
collection provisions are submitted to OMB, and an opportunity for
public comment to OMB will be provided at that time. Prior to the
effective date of the direct final rule, FDA will publish a notice in
the Federal Register of OMB's decision to approve, modify, or
disapprove the information collection provisions. 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.

VII. Comments

Interested persons may by July 1, 1998, submit written comments
regarding this rule to the Dockets Management Branch (address above).
This comment period runs concurrently with the comment period for the
companion proposed rule. Two copies of any comment are to be submitted,
except that individuals may submit one copy. Comments are to be
identified with the docket number found in the brackets in the heading
of this document. Received comments may be seen in the office above
between 9 a.m. and 4 p.m., Monday through Friday. All comments received
will be considered comments regarding the proposed rule and this direct
final rule. In the event the direct final rule is withdrawn, all
comments received regarding the companion proposed rule and the direct
final rule will be considered comments on the proposed rule.

List of Subjects 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 new 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 an annual report as described in Sec. 814.126(b).

[[Page 19189]]

(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) and
redesignating paragraphs (c) through (e) as paragraphs (b) through (d),
by revising redesignated paragraph (b)(5) and the first sentence in
redesignated paragraph (c), and by revising redesignated paragraph (d)
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 above
requirement will be 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 have been 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 the introductory text of
paragraph (a) and by revising paragraph (b) to read as follows:

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:
* * * * *
(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 will
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 revising the last sentence in
paragraph (a), adding a sentence to the end of paragraph (a), revising
the last sentence of paragraph (d), and 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 (e) to read as
follows:

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

* * * * *
(e) Unless FDA otherwise determines that continued marketing under
the HDE is inconsistent with the intent of section 520(m) of the act,
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.
10. Section 814.120 and the heading 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:

[[Page 19190]]

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 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) Annual report. An HDE applicant is required to submit an
annual report on the anniversary date of marketing approval. The annual
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. 814.102(c)(2), (c)(3), and (c)(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 803 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
annual 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
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.

Dated: March 31, 1998.
William B. Schultz,
Deputy Commissioner for Policy.
[FR Doc. 98-9637 Filed 4-16-98; 8:45 am]
BILLING CODE 4160-01-F}