[Federal Register Volume 67, Number 211 (Thursday, October 31, 2002)]
[Notices]
[Pages 66403-66404]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-27769]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Office of Public Health and Science and Food and Drug 
Administration

[Docket No. 02N-0466]


Solicitation of Public Review and Comment on Research Protocol: A 
Multicenter, Randomized Dose Response Study of the Safety, Clinical and 
Immune Response of Dryvax[reg] Administered to Children 2 to 5 Years of 
Age

AGENCY: Office of Public Health and Science and Food and Drug 
Administration, HHS.

ACTION: Notice.

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SUMMARY: The Office for Human Research Protections (OHRP), Office of 
Public Health and Science, Department of Health and Human Services 
(HHS) and the Food and Drug Administration (FDA), HHS are soliciting 
public review and comment on a proposed research protocol entitled ``A 
Multicenter, Randomized Dose Response Study of the Safety, Clinical and 
Immune Response of Dryvax[reg] Administered to Children 2 to 5 Years of 
Age.'' The proposed research would be supported by a contract awarded 
by the National Institutes of Health (NIH) and conducted under an 
Investigational New Drug Application (IND) filed with the FDA. Public 
review and comment is solicited regarding the proposed research 
protocol pursuant to the requirements of HHS regulations at 45 CFR 
46.407 and FDA regulations at 21 CFR 50.54.

DATES: To be considered, written or electronic comments on the proposed 
research must be received on or before 4:30 p.m. December 2, 2002.

ADDRESSES: Submit written comments to the Dockets Management Branch 
(HFA-305), Docket Number 02N-0466, Food and Drug Administration, 5630 
Fishers Lane, Room 1061, Rockville, MD 20852. Submit electronic 
comments to http://www.fda.gov/dockets/ecomments. All comments should 
be identified with the docket number found in brackets in the heading 
of this document. Received comments may be viewed on the FDA Web site 
at: http://www.fda.gov/ohrms/dockets/dockets/02n0466/02n0466.htm or may 
be seen in the Dockets Management Branch between 9 a.m. and 4 p.m., 
Monday through Friday.

FOR FURTHER INFORMATION CONTACT: Dr. Leslie K. Ball, Office for Human 
Research Protection, The Tower Building, 1101 Wootton Parkway, Suite 
200, Rockville, MD 20852; telephone

[[Page 66404]]

301-496-7005; fax 301-402-0527; e-mail: [email protected]; or Ms. 
Patricia M. Beers Block, Office for Good Clinical Practice, OSHC, 
Office of the Commissioner, Food and Drug Administration, 5600 Fishers 
Lane, HF-34, Rockville, MD 20857; telephone 301-827-3340; fax 301-827-
1169; e-mail: [email protected].

SUPPLEMENTARY INFORMATION: All studies conducted or supported by HHS 
which are not otherwise exempt and which propose to involve children as 
subjects require Institutional Review Board (IRB) review in accordance 
with the provisions of HHS regulations at 45 CFR part 46, subpart D. 
Under FDA's Interim Final Rule effective April 30, 2001 (21 CFR part 
50, subpart D), FDA adopted similar regulations to provide safeguards 
for children enrolled in clinical investigations of FDA-regulated 
products.
    Pursuant to HHS regulations at 45 CFR 46.407 and FDA regulations at 
21 CFR 50.54, if an IRB reviewing a protocol conducted or supported by 
HHS for a clinical investigation regulated by FDA does not believe that 
the proposed research or clinical investigation involving children as 
subjects meets the requirements of HHS regulations at 45 CFR 46.404, 
46.405, or 46.406, and FDA regulations at 21 CFR 50.51, 50.52, or 
50.53, respectively, the research or clinical investigation may proceed 
only if the following conditions are met: (a) The IRB finds and 
documents that the research or clinical investigation presents a 
reasonable opportunity to further the understanding, prevention, or 
alleviation of a serious problem affecting the health and welfare of 
children; and (b) the Secretary (HHS) and the Commissioner (FDA), 
respectively, 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 determine 
either:
    (1) That the research or the clinical investigation in fact 
satisfies the conditions of 45 CFR 46.404, 46.405, or 46.406 under HHS 
regulations, and 21 CFR 50.51, 50.52, or 50.53 under FDA regulations, 
or (2) that the following conditions are met: (i) The research or 
clinical investigation presents a reasonable opportunity to further the 
understanding, prevention, or alleviation of a serious problem 
affecting the health or welfare of children; (ii) the research or 
clinical investigation will be conducted in accordance with sound 
ethical principles; and (iii) adequate provisions are made for 
soliciting the assent of children and the permission of their parents 
or guardians, as set forth in 45 CFR 46.408 and 21 CFR 50.55.
    HHS received a request from Harbor-UCLA Medical Center to review a 
protocol entitled ``A Multicenter, Randomized Dose Response Study of 
the Safety, Clinical and Immune Response of Dryvax[reg] Administered to 
Children 2 to 5 Years of Age'' pursuant to the provisions of HHS 
regulations at 45 CFR 46.407. The sponsor of this research, the 
National Institute of Allergy and Infectious Diseases (NIAID), NIH, 
proposes to study the safety and immune response to Dryvax[reg] 
(vaccinia virus vaccine), when administered to children 2 to 5 years of 
age. This study proposes to evaluate Dryvax[reg] at its full, licensed 
strength and at a 1:5 dilution, in children enrolled in a number of 
sites, including Harbor-UCLA Medical Center and Cincinnati Children's 
Hospital Medical Center. Use of Dryvax[reg] in this protocol is being 
performed under an FDA IND primarily because there are no data to 
support the efficacy of the 1:5 dilution of this product in children. 
This protocol was developed by NIAID in the context of current HHS 
bioterrorism preparedness plans, given the potential risk of smallpox 
being used as a weapon of bioterrorism, and has been approved by two 
IRBs.
    However, after reviewing this research proposal, the Harbor-UCLA 
Medical Center IRB determined that this study could not be approved 
under 45 CFR 46.404, 46.405, or 46.406 but was suitable for review 
under 45 CFR 46.407. Because this clinical investigation is regulated 
by FDA, FDA's regulations at 21 CFR part 50, subpart D, apply as well. 
The Harbor-UCLA Medical Center IRB was unable to assess the prospect of 
direct benefit to the participants but found that the research 
presented a reasonable opportunity to further the understanding, 
prevention or alleviation of a serious problem affecting the health or 
welfare of children. NIAID has not initiated this clinical trial 
pending the Secretary's and Commissioner's determination. Experts in 
relevant disciplines have reviewed this protocol (see discussion below 
regarding access to each expert's report), but prior to the Secretary 
and Commissioner making a final determination, public review and 
comment are hereby solicited pursuant to HHS regulations at 45 CFR 
46.407 and FDA regulations at 21 CFR 50.54. In particular, comments are 
solicited on the following questions: (1) What are the potential 
benefits of the research, if any, to the subjects and to children in 
general; (2) what are the types and degrees of risk that this research 
presents to the subjects; (3) are the risks to the subjects reasonable 
in relation to the anticipated benefits, if any, to the subjects, and 
the importance of the knowledge that may reasonably be expected to 
result; and (4) does the research present a reasonable opportunity to 
further the understanding, prevention, or alleviation of a serious 
problem affecting the health or welfare of children?
    All written comments concerning this matter should be submitted to 
FDA's Dockets Management Branch pursuant to 21 CFR 10.20. Received 
comments may be viewed on the FDA Web site at: http://www.fda.gov/ohrms/dockets/dockets/02n0466/02n0466.htm or may be seen in the Dockets 
Management Branch between the 9 a.m. and 4 p.m., Monday through Friday.
    Materials available for review on the OHRP Web page (available at 
http://ohrp.osophs.dhhs.gov/dpanel/dpindex.htm) include: The NIH 
protocol, site-specific protocol application reviewed by the Harbor-
UCLA Medical Center IRB, sample parental permission document, relevant 
package inserts, and reports of each of the experts pursuant to HHS 
regulations at 45 CFR 46.407 and FDA regulations at 21 CFR 50.54. A 
paper copy of the information referenced here is available upon 
request.

    Dated: October 23, 2002.
Lester M. Crawford,
Deputy Commissioner, FDA.
    Dated: October 24, 2002.
Eve E. Slater,
Assistant Secretary for Health.
[FR Doc. 02-27769 Filed 10-30-02; 8:45 am]
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