[Federal Register Volume 66, Number 166 (Monday, August 27, 2001)]
[Notices]
[Pages 45048-45053]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-21622]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration


Clinical Studies of Safety and Effectiveness of Orphan Products; 
Availability of Grants; Request for Applications

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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[[Page 45049]]

SUMMARY: The Food and Drug Administration (FDA) is announcing changes 
to its Orphan Products Development (OPD) grant program for fiscal year 
(FY) 2002. This announcement supersedes the previous announcement of 
this program, which was published in the Federal Register of August 8, 
2000.

DATES: The application receipt dates are October 17, 2001, and March 5, 
2002.

ADDRESSES: Application forms are available from, and completed 
applications should be sent to: Maura Stephanos, Grants Management 
Specialist, Division of Contracts and Procurement Management (HFA-522), 
Food and Drug Administration, 5600 Fishers Lane, rm. 2129, Rockville, 
MD 20857, 301-827-7183, [email protected]. Applications may also be 
obtained at OPD on the Internet at http://www.fda.gov/orphan. (Note: 
completed applications that are hand-carried or commercially delivered 
should be addressed to 5630 Fishers Lane, rm. 2129, Rockville, MD 
20857.)

FOR FURTHER INFORMATION CONTACT:
    Regarding the administrative and financial management issues of 
this notice: Maura Stephanos (address and telephone number cited 
above).
    Regarding the programmatic issues of this notice: Debra Y. Lewis, 
Office of Orphan Products Development (HF-35), Food and Drug 
Administration, 5600 Fishers Lane, rm. 15A-08, Rockville, MD 20857, 
301-827-3666, [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 products for a rare disease or condition 
(that is, one with a prevalence, not incidence, of fewer than 200,000 
people in the United States). Depending on FY 2002 funding, $12.5 
million should be available, of which approximately $8.5 million will 
be for noncompeting continuation awards. This will leave $4 million for 
funding 12 to 15 new applications. The first part of the funding cycle 
will award about $1 million to successful applications received on the 
October 17, 2001 due date. These awards would start after March 1, 
2002. All approved applications not funded in the first part of the 
funding cycle will remain in competition for the second part of the 
funding cycle. The expected start date for these applications will be 
September 30, 2002. Applications submitted for the first due date may 
be withdrawn and resubmitted for the second due date.
    Any phase clinical trial is eligible for up to $150,000 in direct 
costs a year, plus applicable indirect costs, for up to 3 years. Phase 
2 and 3 clinical trials are eligible for up to $300,000 in direct costs 
a year, plus applicable indirect costs, for up to 3 years.
    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 activity to 
reduce morbidity and mortality and to improve the quality of life. 
Applicants may obtain a hard copy of the Healthy People 2010 
objectives, Volumes 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, 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 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

    OPD was created to identify and promote the development of orphan 
products. The OPD grant program defines orphan products as drugs, 
biologics, medical devices, and foods for medical purposes that are 
indicated for a rare disease or condition (that is, one with a 
prevalence, not incidence, of fewer than 200,000 people in the United 
States). Diagnostic tests and vaccines will qualify only if the U.S. 
population of intended use is fewer than 200,000 a year.
    One way to make orphan products available is to support clinical 
research to find out whether the products are safe and effective. All 
funded studies are subject to the requirements of the Federal Food, 
Drug, and Cosmetic Act (the act) and regulations issued under it.
    The goal of FDA's OPD grant program is the clinical development of 
products for use in rare diseases or conditions where no current 
therapy exists or where the product will improve the existing therapy. 
FDA provides grants for clinical studies that will either result in or 
substantially contribute to approval of these products. 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 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 with FDA reviewing 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 and biological 
products must be conducted under the FDA's investigational new drug 
(IND) procedures and studies of medical devices must be conducted under 
the investigational device exemption (IDE) procedures. Studies of 
approved products to evaluate new orphan indications are also 
acceptable; however, these also must be conducted under an IND or IDE 
to support a change in labeling. (See section V.B of this document 
(Program Review Criteria) for important requirements about IND/IDE 
status of products to be studied under these grants.)
    Studies proposed for the larger grants ($300,000) must be 
continuing 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

[[Page 45050]]

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. Studies proposed for the 
smaller grants ($150,000) may be phase 1, 2, or 3 trials. Budgets for 
all years of requested support may not exceed the $300,000 or $150,000 
direct cost limit, whichever is applicable.
    Applications must propose a clinical trial of one therapy for one 
indication. 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 reviewing 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). 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 Federalwide 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 prior to 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.

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, 
co-investigators, 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 co-signed by an institution 
official and sent to the Grants Management Office. OPD 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, National Institutes of Health (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 21 CFR 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

[[Page 45051]]

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 within 
90 days of the budget period end date of the grant. Failure to file the 
FSR in a timely fashion will be grounds for suspension or termination 
of the grant. For continuing grants, an annual program progress report 
is also required. The noncompeting continuation application (PHS 2590) 
will be considered the annual program progress report. Also, all new 
and continuing grants must comply with all regulatory requirements 
necessary to keep active status of their IND/IDE. 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. Also, the grantee organization must comply with 
all special terms and conditions, which state that future funding of 
the study will depend on recommendations from the OPD project officer. 
The scope of the recommendations will confirm that: (1) There has been 
acceptable progress toward enrollment, based on specific circumstances 
of the study; (2) there is an adequate supply of the product/device; 
and (3) there is continued compliance with all FDA regulatory 
requirements for the trial.
    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.

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 lobby are not 
eligible to receive grant awards.

C. Length of Support

    The length of support will depend on the nature of the study. For 
those studies with an expected duration of more than one year, a second 
or third year of noncompetitive continuation of support will depend on: 
(1) Performance during the preceding year; (2) Federal funds 
availability; and (3) compliance with regulatory requirements of the 
IND/IDE.

D. Funding Plan

    The number of studies funded will depend on the quality of the 
applications received and the Federal funds available to support the 
projects. Before an award will be made, OPD will confirm the active 
status of the protocol under the IND/IDE. If the protocol is under FDA 
clinical hold for any reason, no award will be made. Also, if the IND/
IDE 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 (address above), 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 
following program review criteria. 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 OPD program 
staff and all questions of an administrative or financial nature to the 
grants management staff. (See FOR FURTHER INFORMATION CONTACT section 
of this document.) 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/or efficacy data of one therapy for one orphan 
indication.
    2. There must be an explanation in the ``Background and 
Significance'' section of how the proposed study will either contribute 
to product approval or provide essential data needed for product 
development.

[[Page 45052]]

    3. The prevalence, not incidence, of the population to be served by 
the product must be fewer than 200,000 individuals in the United 
States. The applicant should include, in the ``Background and 
Significance'' section, a detailed explanation supplemented by 
authoritative references in support of the prevalence figure. 
Diagnostic tests and vaccines will qualify only if the population of 
intended use is fewer than 200,000 individuals in the United States per 
year.
    4. The protocol proposed in the grant application must already be 
under an active IND or IDE (not under review or on hold) before the 
grant application deadline, as described below:
    (a) The IND with the proposed clinical protocol must be submitted 
to the FDA IND/IDE reviewing division a minimum of 30 days before the 
grant application deadline. The IND/IDE 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/IDE 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/IDE verification with the 
application. The verification includes the IND/IDE number, the date the 
subject protocol was submitted to FDA for the IND/IDE review, the IND 
serial number (if known), and a statement that the IND/IDE contains the 
same protocol as proposed in the grant application and that this IND/
IDE 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/IDE to be 
eligible for funding under this FDA grant program.
    (e) If the sponsor of the IND/IDE is other than the principal 
investigator listed on the application, a letter from the sponsor 
permitting access to the IND/IDE must be submitted. Both the principal 
investigator named in the application and the study protocol must have 
been submitted to the IND/IDE.
    (f) Studies of already approved products, evaluating new orphan 
indications, are also subject to these IND/IDE requirements.
    (g) Only medical foods that do not need premarket approval are free 
from these IND/IDE requirements.
    5. The requested budget must be within the limits (either $150,000 
in direct costs for each year for up to 3 years for any phase study, or 
$300,000 in direct costs for each year for up to 3 years for phase 2 or 
3 studies) 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.
    6. Proposed consent forms, assent forms, and any other information 
given to a subject, should be included in the grant application.
    7. 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.
    8. Applicants must follow guidelines named in the PHS 398 (Rev. 5/
01) 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, 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 OPD grant program described in section I (Program 
Research Goals) of this document.

D. Award Criteria

    Resources for this program are limited. Therefore, should FDA 
approve two or more applications that propose duplicative or similar 
studies, FDA will support only the study with the best score.

VI. Submission Requirements

    The original and two copies of the completed Grant Application Form 
PHS 398 (Rev. 5/01) 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 Maura 
Stephanos (address above). State and local governments may use the PHS 
398 (Rev. 5/01) application form instead of the PHS 5161-1. The 
application receipt dates are October 17, 2001, and March 5, 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-OPD-
2002.'' If an application for the same study was submitted in response 
to a previous RFA but has not yet been funded, an application in 
response to this RFA will be considered a request to withdraw the 
previous application. Resubmissions are treated as new applications; 
therefore, the applicant may wish to address the issues presented in 
the summary statement from the previous review, and include a copy of 
the summary statement itself.

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

[[Page 45053]]

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. Application 
forms can be found on the Internet (address http://www.fda.gov/orphan). 
However, as noted above, do not mail applications to NIH. 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.

B. Format for Application

    Submission of the application must be on Grant Application Form PHS 
398 (Rev. 5/01). 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). The 
face page of the application should reflect the request for 
applications number RFA-FDA-OPD-2002. The title of the proposed study 
should include the name of the product and the disease/disorder to be 
studied and the IND/IDE 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) 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: August 21, 2001.
Margaret M. Dotzel,
Associate Commissioner for Policy.
[FR Doc. 01-21622 Filed 8-22-01; 2:46 pm]
BILLING CODE 4160-01-S