[Federal Register Volume 71, Number 90 (Wednesday, May 10, 2006)]
[Notices]
[Pages 27264-27266]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E6-7058]


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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Draft Guidance for Clinical Investigators, Institutional Review 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availability of a draft guidance entitled ``Guidance for Industry; 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draft guidance describes the procedures FDA generally intends to follow 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DATES: Submit written or electronic comments on the draft guidance by 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ADDRESSES: Submit written requests for single copies of the draft 
guidance to the Office of Policy (HF-11), Office of the Commissioner, 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    Submit written comments on the draft guidance to the Division of 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://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INFORMATION section for electronic access to the draft guidance 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://www.fda.gov/cder/guidance/index.htm or 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]
BILLING CODE 4160-01-S