[Federal Register Volume 67, Number 104 (Thursday, May 30, 2002)]
[Notices]
[Pages 37839-37843]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-13461]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration


Safety and Effectiveness of Products for the Treatment of 
Naturally Occurring Human Plague (Bubonic, Pneumonic, Meningitic, or 
Septicemic); Availability of Grants; Request for Applications

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA), Center for Drug 
Evaluation and Research (CDER), is announcing its Office of Pediatric 
Drug Development and Program Initiatives (OPDDPI) grant program for 
fiscal year (FY) 2002. FDA is announcing the expected availability of 
FY 2002 funds for awarding grants to support clinical trials on the 
safety and effectiveness of drug products for the treatment of human 
plague (bubonic, pneumonic, meningitic, or septicemic) caused by 
Yersinia pestis. This grant program is part of FDA's counter-terrorism 
efforts.

DATES: The application receipt date is July 29, 2002.

ADDRESSES: Application forms are available from, and completed 
applications should be sent to: Rosemary Springer, Grants Management 
Specialist, Division of Contracts and Procurement Management (HFA-522), 
Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857, 
301-827-7182, [email protected]. Application forms can also be found 
at http://www.nih.gov/grants/phs398/forms_toc.html. Please do not send 
applications to the Center for Scientific Review (CSR), National 
Institutes of Health (NIH). Applications mailed to CSR and not received 
by FDA in time for orderly processing will be returned to the applicant 
without consideration. (Note: completed applications that are hand-
carried or commercially delivered should be addressed to 5630 Fishers 
Lane, rm. 2129, Rockville, MD 20857.) FDA is unable to receive 
applications electronically.

FOR FURTHER INFORMATION CONTACT:
    Regarding the administrative and financial management issues of 
this notice: Rosemary Springer (see ADDRESSES).
    Regarding the programmatic issues of this notice: Joanne M. Holmes, 
Office of Pediatric Drug Development and Program Initiatives (HFD-950), 
Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857, 
301-827-2350, e-mail: [email protected].

SUPPLEMENTARY INFORMATION: FDA is announcing the expected availability 
of FY 2002 funds for awarding grants to support clinical trials on the 
safety and effectiveness of drug products for the treatment of human 
plague (bubonic, pneumonic, meningitic, or septicemic). Subject to the 
availability of FY 2002 funds, it is anticipated that $2.1 million 
should be available. FDA anticipates making up to three awards each for 
up to $700,000 (direct and indirect costs). Funding will be provided 
one time at the beginning of the project and will cover both years of 
the project period. The budget and project periods will coincide for 
these awards. These awards will start before September 30, 2002.
    FDA will support the clinical studies covered by this notice under 
the authority of section 301 of the Public Health Service Act (the PHS 
Act) (42 U.S.C. 241). FDA's research program is described in the 
Catalog of Federal Domestic Assistance, No. 93.103. The Public Health 
Service (PHS) strongly encourages all grant recipients to provide a 
smoke-free workplace and to discourage the use of all tobacco products. 
This is consistent with the PHS mission to protect and advance the 
physical and mental health of the American people.
    FDA is committed to achieving the health promotion and disease 
prevention objectives of ``Healthy People 2010,'' a national effort to 
reduce morbidity and mortality and to improve the quality of life. 
Applicants may obtain a hard copy of the ``Healthy People 2010'' 
objectives, vols. I and II, conference edition (B0074) for $22 per set, 
by writing to the Office of Disease Prevention and Health Promotion 
(ODPHP) Communication Support Center (Center), P.O. Box 37366, 
Washington, DC 20013-7366. Each of the 28 chapters of ``Healthy People 
2010'' is priced at $2 per copy. Telephone orders can be placed to the 
Center on 301-468-5690. The Center also sells the complete conference 
edition in CD-ROM format (B0071) for $5. This publication is available 
as well on the Internet at http://www.health.gov/healthypeople/. 
Internet viewers should proceed to ``Publications.''
    PHS policy is that applicants for PHS clinical research grants 
should include minorities and women in study populations so research 
findings can be of benefit to all people at risk of the disease, 
disorder, or condition under study. Special emphasis should be placed 
on the need for inclusion of minorities and women in studies of 
diseases, disorders, and conditions that disproportionately affect 
them. This policy applies to research subjects of all ages. If women or 
minorities are

[[Page 37840]]

excluded or poorly represented in clinical research, the applicant 
should provide a clear and compelling rationale that shows inclusion is 
inappropriate.

I. Program Research Goals

    OPDDPI has as one of its goals the identification and facilitation 
of development of drug products that may be used in the treatment of 
conditions caused by agents released in a terrorist event. These agents 
can be of a pathogenic, radiological, or chemical nature.
    To ensure that the needs of the public health, including special 
populations, are met, it is necessary to have an array of approved drug 
products available and labeled to treat such conditions. One approach 
to facilitating drug product availability is to support clinical 
research to determine if drug products approved for another indication 
are safe and effective for use in an indication related to terrorism 
and to utilize such information to provide appropriate dosing and use 
information in the label. All funded studies are subject to the 
requirements of the Federal Food, Drug, and Cosmetic Act (the act) and 
regulations issued under it.
    Although gentamicin is not FDA approved for treatment of pneumonic 
plague, the Center for Civilian Biodefense Studies Working Group on 
Civilian Biodefense has recommended it along with streptomycin as a 
preferred therapy. FDA obtained from the Centers for Disease Control 
and Prevention (CDC) at Fort Collins, CO, the limited data on all 
reported U.S. pneumonic plague cases, both primary and secondary, from 
the 1950s to the present. Because of multiple confounders in this 
limited population and because no patients received gentamicin alone, 
no conclusions could be reached to support labeling gentamicin as 
monotherapy for pneumonic plague. Therefore, the goal of FDA's OPDDPI 
grant program is the clinical development of products for use in plague 
(bubonic, pneumonic, meningitic, or septicemic). FDA provides grants 
for clinical studies that will either result in or substantially 
contribute to the addition of a plague indication to gentamicin. 
Applicants should keep this goal in mind and must include an 
explanation in the application's ``Background and Significance'' 
section of how their proposed study will either help gain product 
approval of this indication or provide essential data needed for 
product development. The applicant should provide a summary of any 
meetings or discussions about the clinical study that have occurred to 
date with FDA review division staff as an appendix to the application.
    Except for medical foods that do not need premarket approval, FDA 
will only consider awarding grants to support premarket clinical 
studies to find out whether the products are safe and effective for 
approval under the act (21 U.S.C. 301 et seq.) or under section 351 of 
the PHS Act (42 U.S.C. 262). All studies of new drug products must be 
conducted under the FDA's investigational new drug (IND) procedures. 
Although gentamicin is an approved product, studies of approved 
products to evaluate new indications must be conducted under an IND to 
support a change in labeling. (See Program Review Criteria in section 
V.B of this document for important requirements about IND status of 
products to be studied under this grant.)
    Studies proposed for this grant must be in phase 2 or phase 3 of 
investigation. Phase 2 trials include controlled clinical studies 
conducted to evaluate the effectiveness of the product for a particular 
indication in patients with the disease or condition and to determine 
the common or short-term side effects and risks associated with it. 
Phase 3 trials gather more information about effectiveness and safety 
that is necessary to evaluate the overall risk-benefit ratio of the 
product and to provide an acceptable basis for physician labeling.
    Applications must propose a controlled clinical trial of gentamicin 
versus an antibiotic already approved for plague (doxycycline or 
streptomycin) in the treatment of human plague (bubonic, pneumonic, 
meningitic, or septicemic). Historical data from untreated patients 
will be considered as the negative control. A plan to obtain a minimum 
of 30 plague-confirmed patients per arm is required. The diagnosis of 
plague should be confirmed by culture and/or serology. The applicant 
must provide supporting evidence that the product to be studied is 
available to the applicant in the form and quantity needed for the 
clinical trial. The applicant must also provide supporting evidence 
that the patient population has been surveyed and reasonable assurance 
that the necessary number of eligible patients is available for the 
study. Funds may be requested in the budget to travel to FDA for 
meetings with review division staff about the progress of product 
development.

II. Human Subject Protection and Informed Consent

A. Protection of Human Research Subjects

    All institutions engaged in human subject research supported by the 
Department of Health and Human Services (DHHS) must file an 
``assurance'' of protection for human subjects with the Office for 
Human Research Protection (OHRP) (45 CFR part 46). Some activities 
carried out by a recipient under this announcement may be governed as 
well by the FDA Research Involving Human Subjects Committee part 50 (21 
CFR part 50) and (21 CFR part 56). Applicants may wish to visit the 
OHRP Internet site at http://ohrp.osophs.dhhs.gov for guidance on human 
subjects issues. The requirement to file an assurance includes both 
``awardee'' and collaborating ``performance site'' institutions. 
Awardee institutions are automatically considered to be engaged in 
human subject research whenever they receive a direct DHHS award to 
support such research, even where all activities involving human 
subjects are carried out by a subcontractor or collaborator. In such 
cases, the awardee institution bears ultimate responsibility for 
protecting human subjects under the award. The awardee is also 
responsible for ensuring that all collaborating institutions engaged in 
the research hold an approved assurance prior to their initiation of 
the research. No awardee or performance site may spend funds on human 
subject research or enroll subjects without the approved and applicable 
assurance(s) on file with OHRP.
    Existing assurances, multiple project assurances (MPAs), 
cooperative project assurances (CPAs), and single project assurances 
(SPAs), will remain in effect through their current expiration date, or 
December 31, 2003, whichever comes first. However, OHRP no longer 
accepts changes to existing MPAs, CPAs, and SPAs. MPA, CPA, and SPA 
institutions should file a new Federal wide assurance with OHRP if 
changes are necessary. Applicants must provide certification of 
Institutional Review Board (IRB) review and approval for every site 
taking part in the study. However, this documentation need not be on 
file with the grants management officer, FDA before the award. 
Applicants should review the section on human subjects in the 
application kit entitled ``Section C. Specific Instructions--Forms, 
Item 4, Human Subjects'' (pp. 7 and 8 of the application kit), for IRB 
review requirements.

[[Page 37841]]

B. Key Personnel Human Subject Protection Education

    The awardee institution should ensure that all key personnel 
receive appropriate training in their human subject protection 
responsibilities. Within 30 days of award, the principal investigator 
should provide a letter describing the human subjects protection 
training for each individual identified as ``key personnel'' in the 
proposed research. Key personnel include all principal investigators, 
coinvestigators, and performance site investigators responsible for the 
design and conduct of the study. The description of training should be 
submitted in a letter that includes the names of the key personnel, the 
title of the education program completed by each named personnel, and a 
one-sentence description of the program. This letter should be signed 
by the principal investigator and cosigned by an institution official 
and sent to the Grants Management Office. OPDDPI does not prescribe or 
endorse any specific education programs. Many institutions already have 
developed educational programs on the protection of research subjects 
and have made participation in such programs a requirement for their 
investigators. Other sources of appropriate instruction might include 
the online tutorials offered by the Office of Human Subjects Research, 
NIH at http://ohsr.od.nih.gov/ and by OHRP at http://ohrp.osophs.dhhs.gov/educmat.htm. Also, the University of Rochester has 
made available its training program for individual investigators. Their 
manual can be obtained through Centerwatch, Inc., at http://www.centerwatch.com.

C. Informed Consent

    Consent forms, assent forms, and any other information given to a 
subject, should be sent with the grant application. Information given 
to the subject or his or her representative must be in language the 
subject or representative can understand. No informed consent, whether 
verbal or written, may include any language through which the subject 
or representative waives any of the subject's legal rights, or by which 
the subject or representative releases or appears to release the 
investigator, the sponsor, or the institution or its agent from 
liability. If a study involves both adults and children, separate 
consent forms should be provided for the adults and the parents or 
guardians of the children.

D. Elements of Informed Consent

    The elements of informed consent are stated in the DHHS regulations 
at 45 CFR 46.116 and [sect] 50.25 as follows:
1. Basic Elements of Informed Consent
    In seeking informed consent, the following information shall be 
provided to each subject.
    (a) A statement that the study involves research, an explanation of 
the purposes of the research and the expected duration of the subject's 
participation, a description of the procedures to be followed, and 
identification of any procedures that are experimental.
    (b) A description of any reasonably foreseeable risks or 
discomforts to the subject.
    (c) A description of any benefits to the subject or to others that 
may reasonably be expected from the research.
    (d) A discussion of proper alternative procedures or courses of 
treatment, if any, that might be helpful to the subject.
    (e) A statement that describes the extent, if any, to which 
confidentiality of records identifying the subject will be maintained, 
and that notes the possibility that FDA may inspect the records.
    (f) For research involving more than slight risk, an explanation of 
whether any compensation and any medical treatments are available if 
injury occurs and, if so, what they consist of or where further 
information may be gained.
    (g) An explanation of whom to contact for answers to relevant 
questions about the research and research subject's rights, and whom to 
contact if the subject is injured by the research.
    (h) A statement that participation is voluntary, that refusal to 
take part will involve no penalty or loss of benefits to which the 
subject is otherwise entitled, and that the subject may stop 
participation at any time without penalty or loss of benefits to which 
the subject is otherwise entitled.
2. Other Elements of Informed Consent
    When suitable, one or more of the following elements of information 
shall also be provided to each subject:
    (a) A statement that the particular treatment or procedure may 
involve risks to the subject (or the embryo or fetus, if the subject is 
or may become pregnant) that are unforeseeable.
    (b) Anticipated circumstances under which the investigator, without 
regard to the subject's consent, may stop the subject's participation.
    (c) Any costs to the subject that may result from participation in 
the research.
    (d) The consequences of a subject's decision to withdraw from the 
research and procedures for orderly ending of participation by the 
subject.
    (e) A statement that significant new findings developed during the 
research that may affect the subject's willingness to continue 
participation will be provided to the subject.
    (f) The estimated number of subjects involved in the study.
    The informed consent requirements do not intend to preempt any 
applicable Federal, State, or local laws that require other information 
to be disclosed for informed consent to be legally effective. Nothing 
in the notice intends to limit the authority of a physician to provide 
emergency medical care as permitted under applicable Federal, State, or 
local law.

III. Reporting Requirements

    The original and two copies of the annual Financial Status Report 
(FSR) (SF-269) must be sent to FDA's grants management officer at two 
occasions during these projects. The first FSR will be due 15 months 
after date of award and the final FSR will be due 90 days after the end 
of the grant. Failure to file the FSR in a timely fashion will be 
grounds for suspension or termination of the grant. All grants must 
comply with all regulatory requirements necessary to keep active status 
of their IND. This includes, but is not limited to, submission of an 
annual report to the proper regulatory review division within FDA. 
Failure to meet regulatory requirements will be grounds for suspension 
or termination of the grant.
    The program project officer will monitor grantees quarterly and 
will prepare written reports. The monitoring may be in the form of 
telephone conversations or e-mail between the project officer/grants 
management specialist and the principal investigator. Periodic site 
visits with officials of the grantee organization may also occur. The 
results of these reports will be recorded in the official grant file 
and may be available to the grantee on request consistent with FDA 
disclosure regulations.
    In addition to annual reports submitted to the IND according to the 
requirements under 21 CFR 312.33, the grantee must file a final program 
progress report, FSR, and invention statement within 90 days after the 
end date of the project period as noted on the notice of grant award. 
Progress reports throughout the project will be required semiannually 
(every 6 months). These progress reports must be sent to the Grants 
Management Officer and should include the following cumulative and 
incremental counts: Patients enrolled; patients who are

[[Page 37842]]

culture positive for Y. pestis; patients with a positive seroconversion 
to Y. pestis; pneumonic, septicemic, meningitic, and/or bubonic plagues 
cases; patients treated; treatment outcomes; and adverse events 
(categorized by type and severity).

IV. Mechanism of Support

A. Award Instrument

    Support will be in the form of a grant. All awards will be subject 
to all policies and requirements that govern the research grant 
programs of PHS, including the provisions of 42 CFR part 52 and 45 CFR 
parts 74 and 92. The regulations issued under Executive Order 12372 do 
not apply to this program. The NIH's modular grant program does not 
apply to this FDA grant program. All grant awards are subject to 
applicable requirements for clinical investigations imposed by sections 
505, 512, and 515 of the act (21 U.S.C. 355, 360b, and 360e), section 
351 of the PHS Act (42 U.S.C. 262), and regulations issued under any of 
these sections.

B. Eligibility

    These grants are available to any foreign or domestic, public or 
private nonprofit entity (including State and local units of 
government) and any foreign or domestic, for-profit entity. For-profit 
entities must commit to excluding fees or profit in their request for 
support to receive grant awards. Organizations described in section 
501(c)(4) of the Internal Revenue Code of 1968 that engage in lobbying 
are not eligible to receive grant awards.

C. Length of Support

    The length of support will be for 2 years.

D. Funding Plan

    It is anticipated that three new awards will be funded for up to 2 
years each. Before an award will be made, OPDDPI will confirm the 
active status of the protocol under the IND. If the protocol is under 
FDA clinical hold for any reason, no award will be made. Also, if the 
IND for the proposed study is not active and in complete regulatory 
compliance, no award will be made. Documentation of IRB approvals for 
all performance sites must be on file with the Grants Management 
Office, FDA (see ADDRESSES), before research can begin at that site.

V. Review Procedure and Criteria

A. Review Method

    Grants management and program staff will first review all 
applications sent in response to this request for application (RFA). A 
responsive application is defined as being in compliance with the 
program review criteria in section V.B of this document. Applications 
found to be nonresponsive will be returned to the applicant without 
further consideration.

B. Program Review Criteria

    Applicants are strongly encouraged to contact FDA to resolve any 
questions about criteria before submitting their application. Direct 
all questions of a technical or scientific nature to the OPDDPI program 
staff and all questions of an administrative or financial nature to the 
grants management staff. (See the FOR FURTHER INFORMATION CONTACT 
section). Applications considered nonresponsive will be returned to the 
applicant unreviewed. Responsiveness criteria include the following:
    1. The application must propose a clinical trial intended to 
provide safety and efficacy data of gentamicin for plague (bubonic, 
pneumonic, meningitic, or septicemic) compared to either doxycycline or 
streptomycin. There should be a plan to recruit a minimum of 30 plague 
confirmed patients per treatment arm. The diagnosis of plague should be 
confirmed by culture and/or serology.
    2. There must be an explanation in the ``Background and 
Significance'' section of how the proposed study will either contribute 
to approval of gentamicin for plague (bubonic, pneumonic, meningitic, 
or septicemic) or provide essential data needed for product 
development.
    3. The protocol proposed in the grant application must already be 
under an active IND (not under review or on hold) before the grant 
application deadline, described as follows:
    (a) The IND with the proposed clinical protocol must be submitted 
to the FDA IND reviewing division a minimum of 30 days before the grant 
application deadline. The IND must be in active status, in compliance 
with all regulatory requirements and cannot have any type of FDA 
clinical hold placed on it at the time the grant application is 
submitted.
    (b) The number assigned to the IND that includes the proposed study 
must appear on the face page of the application with the title of the 
project.
    (c) The applicant should submit an IND verification with the 
application. The verification includes the IND number, the date the 
subject protocol was submitted to FDA for the IND review, the IND 
serial number (if known), and a statement that the IND contains the 
same protocol as proposed in the grant application and that this IND is 
active (not under review or on hold).
    (d) Protocols that would otherwise be eligible for an exemption 
from the IND regulations must be conducted under an IND to be eligible 
for funding under this FDA grant program.
    (e) If the sponsor of the IND is other than the principal 
investigator listed on the application, a letter from the sponsor 
permitting access to the IND must be submitted. Both the principal 
investigator named in the application and the study protocol must have 
been submitted to the IND.
    (f) Studies of already approved products are also subject to these 
IND requirements.
    4. The requested budget must be within the limits as stated in this 
request for applications. Any application received that requests 
support over the maximum amount allowable for that particular study 
will be considered nonresponsive.
    5. Proposed consent forms, assent forms, and any other information 
given to a subject, should be included in the grant application.
    6. Evidence that the product to be studied is available to the 
applicant in the form and quantity needed for the clinical trial must 
be included in the application. A current letter from the supplier as 
an appendix will be acceptable.
    7. Applicants must follow guidelines named in the PHS 398 (Rev. 5/
01) or (Rev. 4/98) grant application kit.
    Responsive applications will be reviewed and evaluated for 
scientific and technical merit by an ad hoc panel of experts in the 
subject field of the specific application. Consultation with the proper 
FDA review division may also occur during this first review to 
determine whether the proposed study will provide data that could 
result in or contribute to product approval. Responsive applications 
will be subject to a second review by a National Advisory Council for 
concurrence with the recommendations made by the first-level reviewers, 
and funding decisions will be made by the Commissioner of Food and 
Drugs.

C. Scientific/Technical Review Criteria

    The ad hoc expert panel will provide the first review. The 
application will be judged on the following scientific and technical 
merit criteria:
    1. The soundness of the rationale for the proposed study.
    2. The quality and appropriateness of the study design to include 
the rationale for the statistical procedures.
    3. The statistical justification for the number of patients chosen 
for the study

[[Page 37843]]

(to demonstrate superiority of the gentamicin treatment arm to that of 
a no treatment historical control), based on the proposed outcome 
measures and the appropriateness of the statistical procedures for 
analysis of the results.
    4. The adequacy of the evidence that the proposed number of 
eligible subjects can be recruited in the requested timeframe.
    5. The qualifications of the investigator and support staff, and 
the resources available to them.
    6. The adequacy of the justification for the request for financial 
support.
    7. The adequacy of plans for complying with regulations for 
protection of human subjects.
    8. The ability of the applicant to complete the proposed study 
within its budget and within time limits stated in this RFA.
    The priority score will be based on the scientific/technical review 
criteria cited in section V.C of this document. Also, the reviewers may 
advise the program staff about the appropriateness of the proposal to 
the goals of the OPDDPI grant program described under Program Research 
Goals in section I of this document.

VI. Submission Requirements

    The original and two copies of the completed Grant Application Form 
PHS 398 (Rev. 5/01) or (Rev 4/98) or the original and two copies of the 
PHS 5161-1 (Rev. 7/00) for State and local governments, with copies of 
the appendices for each of the copies, should be delivered to Rosemary 
Springer (see ADDRESSES). State and local governments may use the PHS 
398 (Rev. 5/01) or (Rev. 4/98) application form instead of the PHS 
5161-1. The application receipt date is July 29, 2002.
    Other than evidence of final IRB approval, no material will be 
accepted after the receipt date. The mailing package and item two of 
the application face page should be labeled, ``Response to RFA-FDA-
CDER-02-2''.

VII. Method of Application

A. Submission Instructions

    Applications will be accepted during normal working hours, from 8 
a.m. to 4:30 p.m., Monday through Friday, by the established receipt 
dates. Applications will be considered received on time if sent or 
mailed by the receipt dates as shown by a legible U.S. Postal Service 
dated postmark or a legible date receipt from a commercial carrier, 
unless they arrive too late for orderly processing. Private metered 
postmarks shall not be acceptable as proof of timely mailing.
    Applications not received on time will not be considered for review 
and will be returned to the applicant. (Applicants should note the U.S. 
Postal Service does not uniformly provide dated postmarks. Before 
relying on this method, applicants should check with their local post 
office.) Do not send applications to the Center for Scientific Research 
(CSR), NIH. Any application sent to NIH that is then forwarded to FDA 
and received after the applicable due date will be judged nonresponsive 
and returned to the applicant. Applicants should know FDA does not 
adhere to the page limits or the type size and line spacing 
requirements imposed by NIH on its applications. FDA is unable to 
receive applications electronically.

B. Format for Application

    Submission of the application must be on Grant Application Form PHS 
398 (Rev. 5/01) or (Rev. 4/98). All ``General Instructions'' and 
``Specific Instructions'' in the application kit should be followed 
except for the receipt dates and the mailing label address. Do not send 
applications to the CSR, NIH. Applications from State and local 
governments may be sent on Form PHS 5161-1 (Rev. 7/00) or Form PHS 398 
(Rev. 5/01) or (Rev. 4/98). The face page of the application should 
reflect the request for applications number RFA-FDA-CDER-02-2. The 
title of the proposed study should include the name of the product 
(gentamicin versus either doxycycline or streptomycin) and the disease/
disorder (human plague) to be studied and the IND number. The format 
for all following pages of the application should be single-spaced and 
single-sided. Data information included in the application will 
generally not be publicly available prior to the funding of the 
application. Data included in the application may be entitled to 
confidential treatment as trade secret or confidential commercial 
information within the meaning of the Freedom of Information Act (5 
U.S.C. 552(b)(4)) and FDA's implementing regulations (21 CFR 20.61) 
even after funding has been granted. To designate information that an 
applicant believes to be trade secret or confidential commercial 
information that remains exempt from disclosure after funding, sponsors 
should use the legend below. Information collection requirements 
requested on Form PHS 398 (Rev. 5/01) and (Rev. 4/98) has been sent by 
the PHS to the Office of Management and Budget (OMB) and was approved 
and assigned OMB control number 0925-0001.

C. Legend

    Unless disclosure is required by the Freedom of Information Act as 
amended (5 U.S.C. 552) as determined by the freedom of information 
officials of DHHS or by a court, data contained in the portions of this 
application which have been specifically identified by the applicant as 
containing restricted information shall not be disclosed to the public 
or used except for evaluation purposes.

    Dated: May 23, 2002.
Margaret M. Dotzel,
Associate Commissioner for Policy.
[FR Doc. 02-13461 Filed 5-29-02; 8:45 am]
BILLING CODE 4160-01-S