Medical Devices; Humanitarian Use of Devices; Companion to Direct Final Rule

Proposed Rules

Federal Register

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Proposed Rules

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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; Companion to Direct

Final Rule

AGENCY: Food and Drug Administration, HHS.

ACTION: Proposed rule.

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SUMMARY: The Food and Drug Administration (FDA) is proposing to amend

certain regulations governing humanitarian use devices. This proposed

rule is a companion document to the direct final rule published

elsewhere in this issue of the Federal Register. The 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). This companion proposed rule is

being issued under FDAMA and the act as amended.

DATES: Comments must be received on or before July 1, 1998. Comments on

the information collection requirements must be received on or before

June 16, 1998.

ADDRESSES: Submit written comments on the companion proposed 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.

SUPPLEMENTARY INFORMATION:

I. Background

mit written comments on the companion proposed 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.

SUPPLEMENTARY INFORMATION:

I. Background

This proposed rule is a companion to the direct final rule

published in the final rules section of this issue of the Federal

Register. The direct final rule and this companion proposed rule are

substantively identical. FDA is publishing the direct final rule

because the rule contains noncontroversial changes, and FDA anticipates

that it will receive no significant adverse comments. A detailed

discussion of this rule is set forth in the preamble of the direct

final rule. If no significant comment is received in response to the

direct final rule, no further action will be taken related to this

proposed rule. Instead, FDA will publish a confirmation notice within

30 days after the comment period ends confirming that the direct final

rule will go into effect on August 31, 1998. Additional information

about FDA's direct final rulemaking procedures is set forth in a

guidance published in the Federal Register of November 21, 1997 (62 FR

62466).

If FDA receives any significant adverse comment regarding this

rule, FDA will publish a document withdrawing the direct final rule

within 30 days after the comment period ends and will proceed to

respond to all of the comments under this companion proposed rule using

usual notice-and-comment procedures. The comment period for this

companion proposed rule runs concurrently with the direct final rules's

comment period. Any comments received under this companion proposed

rule will also be considered as comments regarding the direct final

rule

the comment period ends and will proceed to

respond to all of the comments under this companion proposed rule using

usual notice-and-comment procedures. The comment period for this

companion proposed rule runs concurrently with the direct final rules's

comment period. Any comments received under this companion proposed

rule will also be considered as comments regarding the direct final

rule.

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 a 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 adverse under this procedure. For example, a comment

recommending a rule change in addition to the rule will not be

considered a significant adverse comment, unless the comment states 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.

This action is part of FDA's continuing effort to achieve the

objectives of the President's ``Reinventing Government'' initiative,

and it is intended to reduce the burden of unnecessary regulations on

medical devices without diminishing the protection of public health.

Section 520(m) of the act (21 U.S.C. 360j(m)) was added by the Safe

Medical Devices Act of 1990 (Pub. L. 101-629)

e comment.

This action is part of FDA's continuing effort to achieve the

objectives of the President's ``Reinventing Government'' initiative,

and it is intended to reduce the burden of unnecessary regulations on

medical devices without diminishing the protection of public health.

Section 520(m) of the act (21 U.S.C. 360j(m)) was added by the Safe

Medical Devices Act of 1990 (Pub. L. 101-629). 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) of the act authorizes FDA,

by regulation, to exempt a HUD from the effectiveness requirements of

sections 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 or 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 FDAMA into law

pliance 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 that FDA

may 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).

FDA is issuing this companion proposed rule to amend the existing

regulations to conform to revised section 520(m) of the act. For a

discussion of the specific provisions of the regulation, see the

preamble to the direct final rule published elsewhere in this issue of

the Federal Register.

II. Environmental Impact

The agency has determined under 21 CFR 25.30(h) that this proposed

action is of a type that does not individually of cumulatively have a

significant effect on the human environment. Therefore, neither an

environmental assessment nor an environmental impact statement is

required.

III. Analysis of Impacts

FDA has examined the impact of this companion proposed 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)

), and the Unfunded Mandates

Reform Act of 1995 (Pub. L. 104-4). Executive Order 12866 directs

agencies to assess all costs and benefits of available regulatory

alternatives and, when regulation is necessary, to select regulatory

approaches that maximize net benefits (including potential economic,

environmental, public health and safety and other advantages;

distributive impacts; and equity). The agency believes that this

proposed rule is consistent with the regulatory philosophy and

principles identified in the Executive Order. In addition, the proposed

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 companion proposed 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, therefore, certifies that this

proposed rule if issued, will not have a significant economic impact on

a substantial number of small entities. In addition, this proposed rule

will not impose costs of $100 million or more in either the private

sector or State, local, and tribal governments in the aggregate, and

therefore a summary statement of analysis under section 202(a) of the

Unfunded Mandates Reform Act of 1995 is not required.

IV. Paperwork Reduction Act of 1995

ficant economic impact on

a substantial number of small entities. In addition, this proposed rule

will not impose costs of $100 million or more in either the private

sector or State, local, and tribal governments in the aggregate, and

therefore a summary statement of analysis under section 202(a) of the

Unfunded Mandates Reform Act of 1995 is not required.

IV. Paperwork Reduction Act of 1995

This companion proposed 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 (the PRA) (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

g 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 propose amending 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) would allow physicians in emergency situations

to administer a HUD prior to obtaining IRB approval. In such

situations, the physician would be 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 proposing to amend 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. 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 proposing to

amend Sec

the continued exemption of the device from the act's

effectiveness requirements. 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 proposing to

amend 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.

In addition, the proposed

amendments to Sec. 814.104(b)(5) would 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) would modify 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:

olders 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

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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

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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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.

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.

For consistency with the direct final rule to which this proposed

rule is a companion, FDA is following the PRA comment procedures for

direct final rules in this proposed rule. 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 provisions of this proposed 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 the 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.

V. Submission of Comments

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.

V. Submission of Comments

Interested persons may, on or before July 1, 1998, submit to the

Dockets Management Branch (address above) written comments regarding

this proposal. This comment period runs concurrently with the comment

period for the direct final rule. Two copies of any comments are to be

submitted except that individuals may submit one copy. Comments are to

be identified with the docket number found in 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 as comments regarding the direct final rule and this

proposed rule. In the event, the direct final rule is withdrawn, all

comments received will be considered comments on this 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.

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).

(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 $250.00, 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

$250.00 or less, the above requirement will be waived.

ards 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

$250.00 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.

he 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.

n 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.

le 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 two sentences at the end

of paragraph (a) to read as follows:

Sec. 814.124 Institutional Review Board requirements.

he 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 two 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 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:

icable, 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

s 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. 98-9638 Filed 4-16-98; 8:45 am]

BILLING CODE 4160-01-F