[Federal Register: May 25, 2005 (Volume 70, Number 100)]
[Notices]               
[Page 30128-30129]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr25my05-125]                         

-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 2005N-0184]

 
Solicitation of Public Review and Comment on Research Protocol: 
Precursor Preference in Surfactant Synthesis of Newborns

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

ACTION: Notice.

-----------------------------------------------------------------------

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), are soliciting 
public review and comment on a proposed research protocol entitled 
``Precursor Preference in Surfactant Synthesis of Newborns.'' The 
proposed research would be conducted at the St. Louis Children's 
Hospital and supported by the National Heart, Lung and Blood Institute. 
Public review and comment are solicited regarding the proposed research 
protocol under the requirements of HHS and FDA regulations.

DATES: To be considered, written or electronic comments on the proposed 
research must be received on or before 4:30 p.m. on June 17, 2005.

ADDRESSES: Electronic copies of the documents for public review can be 
viewed at the Pediatric Advisory Committee Docket Web site at http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/ohrms/dockets/ac/acmenu.htm.
 (Click on the year 2005 and 

scroll down to Pediatric Ethics Subcommittee meetings.) Submit written 
comments to the Division of Dockets Management (HFA-305), Docket No. 
2005N-0184, 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.
 All comments should be identified with the docket 

number found in brackets in the heading of this document. Received 
comments may be viewed on FDA's Web site at http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/ohrms/dockets/dockets/05n0184/05n0184.htm
, or may be seen in the Division of 

Dockets Management between 9 a.m. and 4 p.m., Monday through Friday.

FOR FURTHER INFORMATION CONTACT: Kevin Prohaska, Office for Human 
Research Protections, The Tower Building, 1101 Wootton Pkwy., suite 
200, Rockville, MD 20852, 301-496-7005, FAX: 301- 402-2071, e-mail: 
kprohask@osophs.dhhs.gov; or Jan N. Johannessen, Office of the 
Commissioner (HF-33), Food and Drug Administration, 5600 Fishers Lane 
(for express delivery, rm. 14C-06), Rockville, MD 20857, 301-827-6687, 
or by e-mail: jjohannessen@fda.gov.

SUPPLEMENTARY INFORMATION: All studies conducted or supported by HHS 
that are not otherwise exempt and that propose to involve children as 
subjects require Institutional Review Board (IRB) review in accordance 
with the provisions of HHS regulations for the protection of human 
subjects in 45 CFR part 46, subpart D. Under FDA's interim final rule 
effective April 30, 2001, FDA adopted similar regulations in part 50, 
subpart D (21 CFR part 50, subpart D) to provide safeguards for 
children enrolled in clinical investigations of FDA-regulated products. 
Because the proposed research, ``Precursor Preference in Surfactant 
Synthesis of Newborns,'' would be supported by NIH, a component of HHS, 
and would be regulated by FDA, both HHS and FDA regulations apply to 
this proposed research.
    Under HHS regulations in 45 CFR 46.407, and FDA regulations in 
Sec.  50.54, if an IRB reviewing a protocol to be conducted or 
supported by HHS for a clinical investigation regulated by FDA does not 
believe that the proposed research involving children as subjects meets 
the requirements of HHS regulations in 45 CFR 46.404, 46.405, or 
46.406, and FDA regulations in Sec. Sec.  50.51, 50.52, or 50.53, the 
research may proceed only if the following conditions are met: (1) IRB 
finds that the research 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 Secretary 
(HHS) and the Commissioner (FDA), after consultation with experts in 
pertinent disciplines (e.g., science, medicine, education, ethics, law) 
and following opportunity for public review and comment, determine 
either: (a) That the research in fact satisfies the conditions of 45 
CFR 46.404, 46.405, or 46.406 under HHS regulations, and Sec. Sec.  
50.51, 50.52, or 50.53 under FDA regulations, or (b) 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

[[Page 30129]]

children and the permission of their parents or guardians, as set forth 
in 45 CFR 46.408 and 21 CFR 50.55.
    HHS has received a request on behalf of the Washington University 
Medical Center IRB to review under 45 CFR 46.407 the protocol entitled 
``Precursor Preference in Surfactant Synthesis of Newborns.'' The 
principal investigator proposes to administer to preterm and full-term 
newborns simultaneous 24-hour infusions of palmitate and acetate 
labeled with the stable (nonradioactive) isotope carbon-13, then 
measure the incorporation of each into surfactant, collected by 
tracheal aspiration. Subjects of the study would include approximately 
10 full-term, intubated infants with normal lungs and 15 to 20 preterm 
(24 to 28 weeks gestational age), intubated infants with respiratory 
distress syndrome.
    The overall goal of the proposed study is to better understand the 
potential differences in precursor preferences in surfactant synthesis 
between preterm infants with immature lungs (requiring mechanical 
ventilation) and full-term infants with normal lung function. The three 
specific aims of the study are to: (1) Determine the rate of surfactant 
synthesis using de novo synthesized fatty acids (acetate), (2) 
determine the rate of surfactant synthesis using preformed fatty acids 
(palmitate), and (3) compare the rates of incorporation in preterm 
infants versus full-term infants with normal lungs.
    The Washington University Medical Center IRB determined that the 
protocol was not approvable under 45 CFR 46.404, 46.405, or 46.406 
because the 24-hour isotope infusion and extra blood draws pose more 
than minimal risks to the subjects, there is no prospect of direct 
benefit to the individual subjects, the interventions or procedures do 
not present an experience to the control group that are reasonably 
commensurate with those inherent in their expected medical situation, 
and the control group does not have the condition or disorder under 
study. Accordingly, the Washington University Medical Center IRB 
forwarded the protocol to OHRP under 45 CFR 46.407 for consideration. 
Because this clinical investigation is regulated by FDA, FDA's 
regulations in part 50, subpart D, specifically Sec.  50.54, apply as 
well.
    In accordance with 45 CFR 46.407(b) and 21 CFR 50.54(b), OHRP and 
FDA are soliciting public review and comment on this proposed clinical 
investigation. In particular, comments are solicited on the following 
questions: (1) What are the potential benefits, 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, and is the 
research likely to result in knowledge that can be generalized about 
the subjects' disorder or condition; 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.
    To facilitate the public review and comment process, FDA has 
established a public docket and placed in that docket information 
relating to the proposed clinical investigation, including the 
following: Correspondence from Washington University Medical Center 
referring the proposed research protocol to HHS for consideration under 
45 CFR 46.407; correspondence from FDA and OHRP to Washington 
University Medical Center regarding the proposed protocol; the research 
protocol; NIH's grant funding the protocol; IRB's deliberations on the 
proposed research; the drug preparation protocol; certificate of 
analysis of the test compounds; the data safety monitoring plan; and 
the parental permission documents. Electronic copies of these documents 
can be viewed at the Pediatric Advisory Committee (PAC) Docket Web site 
at http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/ohrms/dockets/ac/acmenu.htm. (Click on the year 

2005 and scroll down to Pediatric Ethics Subcommittee meetings.) These 
materials are also available on OHRP's website at http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.hhs.gov/ohrp/children/
.

    All written comments concerning this proposed research should be 
submitted to FDA's Division of Dockets Management under 21 CFR 10.20, 
no later than 4:30 p.m. on June 17, 2005. The background materials and 
received comments may be viewed on FDA's Web site at http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/ohrms/dockets/dockets/05n0184/05n0184.htm
 or may be seen in 

the Division of Dockets Management between 9 a.m. and 4 p.m., Monday 
through Friday. The background materials may also be viewed on OHRP's 
Web site at http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.hhs.gov/ohrp/children/.


    Dated: May 19, 2005.
Sheila Dearybury Walcoff,
Associate Commissioner for External Relations.
[FR Doc. 05-10438 Filed 5-24-05; 8:45 am]

BILLING CODE 4160-01-S