[Federal Register Volume 63, Number 74 (Friday, April 17, 1998)]
[Proposed Rules]
[Pages 19196-19200]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-9638]
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Proposed Rules
Federal Register
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This section of the FEDERAL REGISTER contains notices to the public of
the proposed issuance of rules and regulations. The purpose of these
notices is to give interested persons an opportunity to participate in
the rule making prior to the adoption of the final rules.
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Federal Register / Vol. 63, No. 74 / Friday, April 17, 1998 /
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
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.
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). 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. Section
203 of
[[Page 19197]]
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 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. This 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 after 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 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). 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
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. 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. 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
[[Page 19198]]
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:
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.
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
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.
(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) * * *
[[Page 19199]]
(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.
(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 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
[[Page 19200]]
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. 98-9638 Filed 4-16-98; 8:45 am]
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