[Federal Register: May 10, 2006 (Volume 71, Number 90)]
[Notices]
[Page 27264-27266]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr10my06-70]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 2006D-0172]
Draft Guidance for Clinical Investigators, Institutional Review
Boards, and Sponsors; Process for Handling Pediatric Referrals to the
Food and Drug Administration: Additional Safeguards for Children in
Clinical Investigations
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
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SUMMARY: The Food and Drug Administration (FDA) is announcing the
availability of a draft guidance entitled ``Guidance for Industry;
Process for Handling Pediatric Referrals to FDA: Additional Safeguards
for Children in Clinical Investigations.'' This guidance is intended to
assist clinical investigators, institutional review boards (IRBs),
sponsors, and other interested parties in understanding FDA's process
for handling clinical investigations that include children as subjects
and that have been referred to FDA for review under FDA regulations on
additional safeguards for children in clinical investigations. The
draft guidance describes the procedures FDA generally intends to follow
in handling clinical investigations referred for review under these
regulations and in reaching final determinations in accordance with
these regulations.
DATES: Submit written or electronic comments on the draft guidance by
July 10, 2006. General comments on agency guidance documents are
welcome at any time.
ADDRESSES: Submit written requests for single copies of the draft
guidance to the Office of Policy (HF-11), Office of the Commissioner,
Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857.
Send one self-addressed adhesive label to assist that office in
processing your requests. Submit telephone requests to 800-835-4709 or
301-827-1800.
Submit written comments on the draft guidance to the Division of
Dockets Management (HFA-305), Food and Drug Administration, 5630
Fishers Lane, rm. 1061, Rockville, MD 20852. Submit electronic comments
to http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/dockets/ecomments. See the SUPPLEMENTARY
INFORMATION section for electronic access to the draft guidance
document.
FOR FURTHER INFORMATION CONTACT: Erik Mettler, Office of Policy (HF-
11), Food and Drug Administration, 5600 Fishers Lane, Rockville, MD
20857, 301-827-3360.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of a draft guidance entitled
``Guidance for Industry; Process for Handling Referrals to FDA Under 21
CFR 50.54: Additional Safeguards for Children in Clinical
Investigations.'' FDA issued 21 CFR part 50, subpart D, ``Additional
Safeguards for Children in Clinical Investigations,'' (part 50, subpart
D) as an interim final rule on April 24, 2001 (66 FR 20598). Under
these regulations, an IRB must review clinical investigations involving
children as subjects and covered by subpart D and approve only those
clinical investigations that satisfy the criteria described in
Sec. Sec. 50.51, 50.52, or 50.53, as well as the conditions of all
other applicable sections in subpart D.
Under Sec. 50.54, if an IRB does not believe that a clinical
investigation within the scope described in Sec. Sec. 50.1 and 56.101
(21 CFR 56.101) and involving children as subjects meets the
[[Page 27265]]
requirements of Sec. Sec. 50.51, 50.52, or 50.53, the clinical
investigation may proceed only if the following occurs: (1) The IRB
finds and documents that the clinical investigation presents a
reasonable opportunity to further the understanding, prevention, or
alleviation of a serious problem affecting the health or welfare of
children; and (2) the Commissioner of Food and Drugs, after
consultation with a panel of experts in pertinent disciplines (for
example: science, medicine, education, ethics, law) and following
opportunity for public review and comment, determines either of the
following: (1) The clinical investigation in fact satisfies the
conditions of Sec. Sec. 50.51, 50.52, or 50.53, as applicable, or (2)
the following conditions are met: (A) The clinical investigation
presents a reasonable opportunity to further the understanding,
prevention, or alleviation of a serious problem affecting the health or
welfare of children; (B) the clinical investigation will be conducted
in accordance with sound ethical principles; and (C) adequate
provisions are made for soliciting the assent of children and the
permission of their parents or guardians as set forth in Sec. 50.55.
The draft guidance describes the procedures FDA generally will
follow in handling clinical investigations referred for review under
Sec. 50.54 and in reaching final determinations under that regulation.
The draft guidance is based in part on FDA's experience to date with
such referrals. The Department of Health and Human Services (HHS) has
human subject protection regulations that also govern research
involving children as subjects and supported or conducted by HHS. (See
45 CFR part 46, subpart D.) The draft guidance also addresses
situations in which a clinical investigation is subject to both 21 CFR
50.54 and 45 CFR 46.407.
This draft guidance is being issued consistent with FDA's good
guidance practices regulation (21 CFR 10.115). The draft guidance, when
finalized, will represent the agency's current thinking on the process
for handling referrals to FDA under 21 CFR 50.54. It does not create or
confer any rights for or on any person and does not operate to bind FDA
or the public. An alternative approach may be used if such approach
satisfies the requirements of the applicable statutes and regulations.
II. The Paperwork Reduction Act of 1995
Under the Paperwork Reduction Act (44 U.S.C. 3501-3520) (the PRA),
Federal agencies must obtain approval from the Office of Management and
Budget (OMB) for each collection of information they conduct or
sponsor. ``Collection of information'' is defined in 44 U.S.C. 3502(3)
and 5 CFR 1320.3(c) and includes agency requests or requirements that
members of the public submit reports, keep records, or provide
information to a third party. Section 3506(c)(2)(A) of the PRA (44
U.S.C. 3506(c)(2)(A)) requires Federal agencies to provide a 60-day
notice in the Federal Register concerning each proposed collection of
information before submitting the collection to OMB for approval. To
comply with this requirement, FDA is publishing notice of the proposed
collection of information set forth below.
With respect to the following collection of information, FDA
invites comment on these topics: (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 on respondents, including through the use of automated
collection techniques, when appropriate, and other forms of information
technology.
The draft guidance is intended to assist clinical investigators,
IRBs, sponsors, and other interested parties in understanding the FDA's
process for handling clinical investigations that include children as
subjects and that have been referred to FDA for review under 21 CFR
part 50, subpart D.
Title: Draft Guidance for Industry; Process for Handling Referrals
to FDA Under 21 CFR 50.54: Additional Safeguards for Children in
Clinical Investigations.
Burden Estimate: The information that must be submitted to FDA by
sponsors for approval of clinical investigations involving children is
contained in the investigational new drug application (IND) and
investigational device exemption (IDE) regulations (21 CFR parts 312
and 812 (parts 312 and 812), respectively) and is approved under OMB
control number 0910-0014 (expires March 31, 2009) for INDs and under
OMB control number 0910-0078 (expires August 31, 2006) for IDEs. In
addition to the collections of information already required under parts
312 and 812, the draft guidance requests that an IRB submitting a
clinical investigation for consideration under Sec. 50.54 include with
that submission/referral the documentation of its finding under Sec.
50.54(a) that the clinical investigation presents a reasonable
opportunity to further the understanding, prevention, or alleviation of
a serious problem affecting the health or welfare of children.
Under Sec. 50.54(a), IRBs must find and document that the clinical
investigation presents a reasonable opportunity to further the
understanding, prevention, or alleviation of a serious problem
affecting the health or welfare of children. The requirement to
``document'' the finding is a recordkeeping requirement. IRB
recordkeeping requirements are set forth in FDA regulations on IRBs
(part 56) at Sec. 56.115, and are approved under OMB control number
0910-0130 until November 30, 2007. Thus, only the submission to FDA of
the IRB's finding would not already be required under Sec. 50.54(a).
FDA estimates that each submission would take no more than 15 minutes
because, as required by the regulation, the IRB will already have
prepared and documented the finding, and the IRB would only have to
send the documentation of that finding to FDA.
The draft guidance also contains a second collection of
information. The introductory paragraph to Sec. 50.54 states that if
an IRB does not believe that a clinical investigation within the scope
described in Sec. Sec. 50.1 and 56.101 and involving children as
subjects meets the requirements of Sec. Sec. 50.51, 50.52, or 50.53,
the clinical investigation may proceed only if certain conditions set
forth in Sec. 50.54 are met. The draft guidance requests that the IRB
include, when submitting its finding under Sec. 50.54 that the
clinical investigation presents a reasonable opportunity to further the
understanding, prevention, or alleviation of a serious problem
affecting the health or welfare of children, an explanation why the IRB
does not believe that the clinical investigation meets the requirements
of Sec. Sec. 50.51, 50.52, or 50.53. FDA believes that in most cases
this explanation will already be part of the IRB meeting minutes.
Because the IRB may need to summarize these minutes in order to send
them to FDA, FDA estimates that each explanation would take
approximately 1 hour to prepare.
According to a 1998 Office of the Inspector General (OIG) report,
there are 3,000 to 5,000 IRBs in the United States, and most are
associated with hospitals and academic centers (see Department of
Health and Human Services, Office of the Inspector General,
Institutional Review Boards: A Time for Reform, page
[[Page 27266]]
3, June 8, 1998). However, based on FDA's experience to date with IRB
referrals under Sec. 50.54, only a very small percentage of IRBs
(approximately 5 per year) are expected to refer a clinical
investigation to FDA under 21 CFR part 50, subpart D.
The information collection resulting from the draft guidance that
is not already approved by OMB is summarized as follows:
Table 1.--Estimated Annual Reporting Burden\1\
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Number of Number of Responses Total Annual Hours per
Respondents per Respondent Responses Response Total Hours
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Submission of finding required under Sec. 5 1 5 15 min. 1 hour, 15 minutes
50.54(a)
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Explanation why investigation does not meet 5 1 5 1 5
Sec. Sec. 50.51, 50.52, or 50.53
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Total 6 hours, 15 minutes
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\1\ There are no capital costs or operating and maintenance costs associated with this collection.
III. Comments
Interested persons may submit to the Division of Dockets Management
(see ADDRESSES) written or electronic comments regarding this document.
Submit a single copy of electronic comments or two paper copies of any
mailed comments, except that individuals may submit one paper 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
Division of Dockets Management between 9 a.m. and 4 p.m., Monday
through Friday.
IV. Electronic Access
Persons with access to the Internet may obtain the document at
either http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/cder/guidance/index.htm or http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www
.fda.gov/ohrms/dockets/default.htm.
Dated: May 2, 2006.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. E6-7058 Filed 5-9-06; 8:45 am]
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