Medical Devices; Humanitarian Use of Devices

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