Clinical Studies of Safety and Effectiveness of Orphan Products; Availability of Grants; Request for Applications, 75198-75203 [05-24164]

Agencies

• Food and Drug Administration
• DEPARTMENT OF HEALTH AND HUMAN SERVICES

[Federal Register Volume 70, Number 242 (Monday, December 19, 2005)]
[Notices]
[Pages 75198-75203]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 05-24164]


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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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I. Funding Opportunity Description

    The Food and Drug Administration (FDA) is announcing changes to its 
Office of Orphan Products Development (OPD) grant program for fiscal 
year (FY) 2007 and FY 2008. This announcement supersedes the previous 
announcement of this program, which was published in the Federal 
Register of January 14, 2005 (70 FR 2642). Please note that there is 
only one receipt date for FY 2007 and one receipt date for FY 2008.

1. Background

    OPD was created to identify and promote the development of orphan 
products. Orphan products are 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 people per year.

2. Program Research Goals

    The goal of FDA's OPD grant program is to support 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 on safety and/or 
effectiveness that will either result in, or substantially contribute 
to, market approval of these products. Applicants must include, in the 
application's ``Background and Significance'' section, documentation to 
support the estimated prevalence of the orphan disease or condition and 
an explanation of how the proposed study will either help gain product 
approval or provide essential data needed for product development. All 
funded studies are subject to the requirements of the Federal Food, 
Drug, and Cosmetic Act (the act) (21 U.S.C. 301 et seq.) and 
regulations issued under it.

II. Award Information

    Except for applications for studies of medical foods that do not 
need premarket approval, FDA will only award grants to support 
premarket clinical studies to determine safety and effectiveness for 
approval under section 505 or 515 of the act (21 U.S.C. 355, or 360e) 
or safety, purity, and potency for licensing under section 351 of the 
Public Health Service Act (the PHS Act) (42 U.S.C. 262).
    FDA will support the clinical studies covered by this notice under 
the authority of section 301 of the PHS Act (42 U.S.C. 241). FDA's 
research program is described in the Catalog of Federal Domestic 
Assistance, No. 93.103.
    Applicants for Public Health Service (PHS) clinical research grants 
are encouraged to include minorities and women in study populations so 
research findings can be of benefit to all people at risk of the 
disease or condition under study. It is recommended that applicants 
place special emphasis on including 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.
    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 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 
designed to reduce morbidity and mortality and to improve quality of 
life. Applicants may obtain a paper copy of the ``Healthy People 2010'' 
objectives, vols. I and II, for $70 ($87.50 foreign) S/N 017-000-00550-
9, by writing to the Superintendent of Documents, P.O. Box 371954, 
Pittsburgh, PA 15250-7954. Telephone orders can be placed to 202-512-
2250. The document is also available in CD-ROM format, S/N 017-001-
00549-5 for $19 ($23.50 foreign) as well as on the Internet at https://
www.healthypeople.gov/. Internet viewers should proceed to 
``Publications'' (FDA has verified the Web site and its address, but we 
are not responsible for subsequent changes to the Web site or its 
address after this document publishes in the Federal Register).

1. 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 National Institutes of Health (NIH) 
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, 
section 351 of the PHS Act, and regulations issued under any of these 
sections.

2. Award Amount

    Of the estimated FY 2007 funding ($14.2 million), approximately $10 
million will fund noncompeting continuation awards, and approximately 
$4.2 million will fund 10 to 12 new awards subject to availability of 
funds. It is anticipated that funding for the number of noncompeting 
continuation awards and new awards in FY 2008 will

[[Page 75199]]

be similar to FY 2007. The earliest expected start date for the FY 2007 
and FY 2008 awards will be November 1, 2006, and November 1, 2007, 
respectively. Grants will be awarded up to $200,000 or up to $350,000 
in total (direct plus indirect) costs per year for up to 3 years. 
Please note that the dollar limitation will be total costs, not direct 
costs as in previous years.
    Applications for the smaller grants ($200,000) may be for phase 1, 
2, or 3 studies. Study proposals for the larger grants ($350,000) must 
be for studies continuing in phase 2 or 3 of investigation. Phase 1 
studies include the initial introduction of an investigational new drug 
or device into humans, are usually conducted in healthy volunteer 
subjects, and are designed to determine the metabolic and 
pharmacological actions of the product in humans, the side effects 
including those associated with increasing drug doses and, if possible, 
to gain early evidence on effectiveness. Phase 2 studies include early 
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 short-term side effects and risks 
associated with it. Phase 3 studies 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 product labeling. Budgets for each year of requested support may 
not exceed the $200,000 or $350,000 total cost limit, whichever is 
applicable.

3. 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 1 year, a second 
or third year of noncompetitive continuation of support will depend on 
the following factors: (1) Performance during the preceding year, (2) 
compliance with regulatory requirements of the investigational new drug 
(IND)/investigational device exemption (IDE), and (3) availability of 
Federal funds.

4. Funding Plan

    In addition to the requirement for an active IND/IDE discussed in 
section V.1.B.(4) of this document, documentation of assurances with 
the Office of Human Research Protection (OHRP) (see section IV.5.A of 
this document) must be on file with FDA's Grants Management Office 
before an award is made. Any institution receiving Federal funds must 
have an institutional review board (IRB) of record even if that 
institution is overseeing research conducted at other performance 
sites. To avoid funding studies that may not receive, or may experience 
a delay in receiving, IRB approval, documentation of IRB approval and 
Federal Wide Assurance (FWA or assurance) for the IRB of record and all 
performance sites must be on file with FDA's Grants Management Office 
before an award to fund the study will be made. In addition, if a grant 
is awarded, grantees will be informed of any additional documentation 
that should be submitted to FDA's IRB. This grant program does not 
require the applicant to match or share in the project costs if an 
award is made.

5. Dun and Bradstreet Number (DUNS)

    As of October 1, 2003, applicants are now required to have a DUNS 
number to apply for a grant or cooperative agreement from the Federal 
Government. The DUNS number is a 9-digit identification number that 
uniquely identifies business entities. Obtaining a DUNS number is easy 
and there is no charge. To obtain a DUNS number, call Dun and 
Bradstreet at 1-866-705-5711. Be certain that you identify yourself as 
a Federal grant applicant when you contact Dun and Bradstreet.

6. Central Contractor Registration

    In anticipation of the grants.gov electronic application process, 
applicants are encouraged to register with the Central Contractor 
Registration (CCR) database. This database is a governmentwide 
repository of commercial and financial information for all 
organizations conducting business with the Federal Government. 
Registration with CCR will eventually become a requirement for grant 
applicants and is consistent with the governmentwide Management Reform 
to create a citizen-centered web presence and build e-gov 
infrastructures in and across agencies to establish a ``single face to 
industry.'' The preferred method for completing registration is on the 
Internet at https://www.ccr.gov (FDA has verified the Web site address, 
but we are not responsible for subsequent changes to the Web site or 
its address after this document publishes in the Federal Register). 
This Web site provides a CCR handbook with detailed information on data 
applicants will need prior to beginning the online registration, as 
well as steps to walk applicants through the registration process. 
Applicants must have a DUNS number to begin registration and should 
call Dun and Bradstreet, Inc., at the number listed in the previous 
paragraph if they do not have one.
    In order to access grants.gov, applicants will be required to 
register with the Credential Provider. Information about this is 
available at https://www.grants.gov/CredentialProvider (FDA has verified 
the Web site address, but we are not responsible for subsequent changes 
to the Web site or its address after this document publishes in the 
Federal Register).

7. Clinical Trials Data Bank (CTDB)

    The Food and Drug Modernization Act of 1997 requires that certain 
information be entered into CTDB for federally and privately funded 
clinical trials conducted under an IND if a drug is being used to treat 
a serious or life-threatening disease or condition and if the trial is 
to test effectiveness (42 U.S.C. 282(j)(3)(A)). Information on 
noneffectiveness trials for drugs to treat conditions not considered 
serious or life-threatening may also be entered into this database, but 
such information is not required.
    This databank provides patients, family members, healthcare 
providers, researchers, and members of the public easy access to 
information on clinical trials for a wide range of diseases and 
conditions. The U.S. National Library of Medicine has developed this 
site in collaboration with NIH and FDA. The databank is available to 
the public through the Internet at https://clinicaltrials.gov (FDA has 
verified the Web site and its address, but we are not responsible for 
subsequent changes to the Web site or its address after this document 
publishes in the Federal Register).
    CTDB contains the following information: (1) Information about 
clinical trials, both federally and privately funded, of experimental 
treatments for patients with serious or life-threatening diseases; (2) 
a description of the purpose of each experimental drug; (3) the patient 
eligibility criteria; (4) the location of clinical trial sites; and (5) 
the point of contact for those wanting to enroll in the trial. OPD 
program staff will provide more information to grantees about entering 
the required information in CTDB after awards are made.

III. Eligibility Information

1. Eligible Applicants

    The grants are available to any foreign or domestic, public or 
private, for-profit or nonprofit entity (including State and local 
units of government). Federal

[[Page 75200]]

agencies that are not part of the Department of Health and Human 
Services (HHS) may apply. Agencies that are part of HHS may not apply. 
For-profit entities must commit to excluding fees or profit in their 
request for support to receive grant awards. Organizations that engage 
in lobbying activities, as described in section 501(c)(4) of the 
Internal Revenue Code of 1968, are not eligible to receive grant 
awards. An application that has received two prior disapprovals is not 
eligible to apply.

2. Cost Sharing or Matching

    Cost sharing is not required.

IV. Application and Submission

1. Addresses to Request Application

    If submitted as a paper copy, application requests and completed 
applications should be submitted to Cynthia Polit, Grants Management 
Specialist, Division of Contracts and Grants Management (HFA-500), Food 
and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857, 301-
827-7180, e-mail: cynthia.polit@fda.hhs.gov or cpolit@oc.fda.gov. 
Applications that are hand-carried or commercially delivered should be 
addressed to 5630 Fishers Lane, rm. 2105, Rockville, MD 20852. 
Applications may also be obtained from OPD on the Internet at https://
www.fda.gov/orphan. Do not send applications to the Center for 
Scientific Research (CSR), NIH.

2. Content and Form of Application

A. General Information
    FDA is accepting new applications for this program electronically 
via www.grants.gov. Applicants are encouraged to apply electronically 
by visiting the Web site www.grants.gov and following instructions 
under ``Apply for Grants.'' The required application, SF 424RR 
(Research and Related Portable Document Formats) can be completed and 
submitted online. The package should be labeled ``Response to RFA-FDA-
OPD-2007'' or ``Response to RFA-FDA-OPD-2008''. If you experience 
technical difficulties with your online submission you should contact 
either the grants.gov Customer Response Center or Cynthia Polit (see 
Addresses to Request Application in section IV.1 of this document).
    To comply with the President's Management Agenda, HHS is 
participating as a partner in the new governmentwide grants.gov Web 
site. Users of grants.gov will be able to download a copy of the 
application package, complete it offline, and then upload and submit 
the application via the grants.gov Web site. We encourage your 
participation in the grants.gov project. When you enter the grants.gov 
Web site, you will find information about submitting an application 
electronically through the Web site.
    In order to apply electronically, the applicant must have a DUNS 
number and register in the CCR database as described in sections II.5 
and II.6 of this document.
    If submitted other than electronically, please call Cynthia Polit 
for guidance (see Addresses to Request application in section IV.1 of 
this document) prior to submission. For hard copies, an original and 
two copies of the completed Grant Application Form PHS 398 (Rev. 5/01) 
with three copies of the appendices must be submitted to Cynthia Polit 
(see Addresses to Request Application in section IV.1 of this 
document). Other than evidence of final IRB approval, FWA or assurance, 
and certification of adequate supply of study product, no material will 
be accepted for inclusion in the grant application after the receipt 
date.
    In unusual circumstances, additional information may be considered, 
on a case by case basis, for inclusion in the ad hoc expert panel 
review. However, FDA cannot assure inclusion of any information after 
the receipt date other than evidence of final IRB approval, FWA or 
assurance, and certification of adequate supply of study product.
    The mailing package and the application face page must be labeled 
``Response to RFA-FDA-OPD-2007'' for FY 2007 and ``Response to RFA-FDA-
OPD-2008'' for FY 2008. If an application for the same study was 
submitted in response to a previous request for application (RFA) but 
has not yet been funded, an application in response to this notice will 
be considered a request to withdraw the previous application. The 
applicant for a resubmitted application should address the issues 
presented in the summary statement from the previous review and include 
a copy of the summary statement itself as part of the resubmitted 
application.
    An application that has received two prior disapprovals is not 
eligible for resubmission.
B. Format for Application
    For FY 2007, if submitted electronically, the application must be 
on SF424 Research and Related Portable Document Format. If submitted in 
paper copy, the application must be submitted on Grant Application Form 
PHS 398 (Rev. 5/01). All ``General Instructions'' and ``Specific 
Instructions'' in the application kit or on OPD's Web site (see 
Addresses to Request Application in section IV.1 of this document) must 
be followed except for the receipt dates and the mailing label address 
in the PHS 398 package. The face page of the application, either 
electronic or paper, should reflect RFA number RFA-FDA-OPD-2007. The 
title of the proposed study must include the name of the product and 
the disease/disorder to be studied and the IND/IDE number. The 
narrative portion of the application may not exceed 100 pages in length 
and must be single-spaced, printed on 1 side, in 12-point font, and 
unbound. The appendices should also not exceed 100 pages in length 
(separate from the narrative portion of the application).
    For FY 2008, all applications must be submitted electronically 
through grants.gov. Exceptions may be made in unusual circumstances and 
on a case-by-case basis. If electronic submission is impossible, please 
contact the Grants Management Office (see Addresses to Request 
Application in section IV.1 of this document). The face page of the 
application should reflect RFA number RFA-FDA-OPD-2008. The title of 
the proposed study must include the name of the product and the 
disease/disorder to be studied and the IND/IDE number. The narrative 
portion of the application may not exceed 100 pages in length and must 
be single-spaced, printed on 1 side, in 12-point font. The appendices 
should also not exceed 100 pages in length (separate from the narrative 
portion of the application).
    For all applications in FY 2007 and FY 2008, applicants have the 
option of omitting, from the application copies (but not from the 
original), specific salary rates or amounts for individuals specified 
in the application budget and Social Security numbers if otherwise 
required for individuals. The copies may include summary salary 
information.
    Applicants should provide as an appendix to the application a 
summary of any meetings or discussions about the clinical study that 
have occurred with FDA review division staff.
    Data and information included in the application generally will not 
be publicly available prior to the funding of the application. After 
funding has been granted, data and information included in the 
application will be given confidential treatment to the extent 
permitted by the Freedom of Information Act (5 U.S.C. 552(b)(4)) and 
FDA's implementing regulations (including 21 CFR 20.61, 20.105, and 
20.106). By accepting funding, the applicant agrees to allow OPD to 
publish specific information about the grant.

[[Page 75201]]

    Information collection requirements requested on Form PHS 398 (Rev. 
5/01) have been sent by PHS to the Office of Management and Budget 
(OMB) and have been approved and assigned OMB control number 0925-0001. 
The requirements requested on Form SF424 Research and Related Portable 
Document Formats were approved and assigned OMB control number 4040-
0001.

3. Submission Dates and Times

    For FY 2007, the application receipt date is March 14, 2006, and 
for FY 2008, the application receipt date is February 7, 2007. Please 
note that there is only one receipt date for FY 2007 and one receipt 
date for FY 2008. Applications submitted electronically must be 
received by the close of business on the established receipt date.
    The protocol in the grant application should be submitted to IND/
IDE no later than February 13, 2006, for FY 2007 and no later than 
January 8, 2007, for FY 2008.
    For FY 2007, if submitted as a paper copy, applications will be 
accepted from 8 a.m. to 4:30 p.m., Monday through Friday, until the 
established receipt date. Applications will be considered received on 
time if hand-carried to the address noted previously (see Addresses to 
Request Application in section IV.1 of this document) before the 
established receipt date, or sent or mailed by the receipt date as 
shown by a legible U.S. Postal Service dated postmark or a legible 
dated receipt from a commercial carrier (applicants should note that 
the U.S. Postal Service does not uniformly provide dated postmarks. 
Before relying on this method, applicants should check with their local 
post office). Private metered postmarks shall not be acceptable as 
proof of timely mailing. If submitted electronically, applications must 
be received by close of business on the published receipt date.
    Applications not received on time will not be considered for review 
and will be returned to the applicant. Please do not send applications 
to CSR at NIH. Any application sent to NIH/CSR that is forwarded to 
FDA's Grants Management Office and not received in time for orderly 
processing will be judged nonresponsive and returned to the applicant. 
Applications must be submitted via U.S. mail or commercial carrier or 
hand-carried as stated previously, unless submitted electronically.

4. Intergovernmental Review

    This program is not subject to review under the terms of Executive 
Order 12372.

5. Funding Restrictions

A. Protection of Human Research Subjects
    All institutions engaged in human subject research financially 
supported by HHS must file an assurance of protection for human 
subjects with OHRP (45 CFR part 46). Applicants are advised to visit 
OHRP's Web site at https://www.hhs.gov/ohrp for guidance on human 
subjects issues (FDA has verified the Web site address, but we are not 
responsible for subsequent changes to the Web site or its address after 
this document publishes in the Federal Register).
    The requirement to file an assurance applies to both ``awardee'' 
and collaborating ``performance site'' institutions. Awardee 
institutions are automatically considered to be ``engaged'' in human 
subject research whenever they receive a direct HHS 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 the responsibility for protecting human 
subjects under the award.
    The awardee institution is also responsible for, among other 
things, ensuring that all collaborating performance site institutions 
engaged in the research hold an approved assurance prior to their 
initiation of the research. No awardee or performance site institution 
may spend funds on human subject research or enroll subjects without 
the approved and applicable assurance(s) on file with OHRP. An awardee 
institution must, therefore, have its own IRB of record and assurance. 
The IRB of record may be an IRB already being used by one of the 
``performance sites,'' but it must specifically be registered as the 
IRB of record with OHRP.
    For further information, applicants should review the section on 
human subjects in the application instructions entitled ``I. Preparing 
Your Application, Section C. Specific Instructions, Item 4, Human 
Subjects'' in the PHS 398 package or as posted on the grants.gov 
application Web site.
    The clinical protocol should comply with ICHE6 ``Good Clinical 
Practice Consolidated Guidance'' which sets an international ethical 
and scientific quality standard for designing, conducting, recording, 
and reporting trials that involve the participation of human subjects. 
Applicants are encouraged to review the regulations, guidances, and 
information sheets on Good Clinical Practice cited on the Internet at 
https://www.fda.gov/oc/gcp/.
B. Key Personnel Human Subject Protection Education
    The awardee institution is responsible for ensuring that all key 
personnel receive appropriate training in their human subject 
protection responsibilities. Key personnel include all principal 
investigators, coinvestigators, and performance site investigators 
responsible for the design and conduct of the study. HHS, FDA, and OPD 
do not prescribe or endorse any specific education programs. Many 
institutions have already 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 https://ohsr.od.nih.gov 
and by OHRP at https://ohrp-ed.od.nih.gov/CBTs/Assurance/login.asp (FDA 
has verified the Web site addresses, but we are not responsible for 
subsequent changes to the Web sites or their addresses after this 
document publishes in the Federal Register).
    Within 30 days of the award, the principal investigator should 
provide a letter to FDA's Grants Management Office that includes the 
names of the key personnel, the title of the human subjects protection 
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 FDA's Grants Management Office.

6. Other Submission Requirements

    Informed Consent
    Consent forms, assent forms, and any other information given to a 
subject are part of the grant application and must be provided, even if 
in a draft form. The applicant is referred to HHS regulations at 45 CFR 
46.116 and 21 CFR 50.25 for details regarding the required elements of 
informed consent.

V. Application Review Information

1. Criteria

A. General Information
    FDA grants management and program staff will review all 
applications sent in response to this notice. To be responsive, an 
application must be submitted in accordance with the

[[Page 75202]]

requirements of this notice and must bear the original signatures of 
both the principal investigator and the applicant institution's/
organization's authorized official if submitted as a paper copy in FY 
2007. The original signature requirement does not apply to applications 
submitted electronically.
    Applications found to be nonresponsive will be returned to the 
applicant without further consideration. Applicants are strongly 
encouraged to contact FDA to resolve any questions about criteria 
before submitting applications. Please direct all questions of a 
technical or scientific nature to OPD program staff and all questions 
of an administrative or financial nature to the grants management staff 
(see Agency Contacts in section VII of this document).
B. Program Review Criteria
    (1) Applications must propose clinical trials intended to provide 
safety and/or efficacy data.
    (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.
    (3) The ``Background and Significance'' section of the application 
must contain information documenting that the prevalence, not 
incidence, of the population to be served by the product is fewer than 
200,000 individuals in the United States. The applicant should include 
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 study protocol proposed in the grant application must be 
under an active IND or IDE (not on clinical hold) to qualify the 
application for scientific and technical review. Additional IND/IDE 
information is described as follows:
    The proposed clinical protocol should be submitted to FDA's IND/IDE 
review division a minimum of 30 days before the grant application 
deadline.
    The number assigned to the IND/IDE that includes the proposed study 
should appear on the face page of the application with the title of the 
project. The date the subject protocol was submitted to FDA for the 
IND/IDE review should also be provided.
    Protocols that would otherwise be eligible for an exemption from 
IND regulations must be conducted under an active IND to be eligible 
for funding under this FDA grant program.
    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 in both the IND/IDE 
and in the grant application. The principal investigator(s) named in 
the application and in the study protocol must be submitted to the IND/
IDE.
    Studies of already approved products, evaluating new orphan 
indications, are also subject to these IND/IDE requirements.
    Only medical foods that do not need premarket approval and medical 
devices that are classified as nonsignificant risk (NSR) are exempt 
from these IND/IDE requirements. Applicants studying an NSR device 
should provide a letter in the application from FDA's Center for 
Devices and Radiologic Health indicating the device is an NSR device.
    (5) The requested budget must be within the limits, either $200,000 
in total costs per year for up to 3 years for any phase study, or 
$350,000 in total costs per year for up to 3 years for phase 2 or 3 
studies. Any application received that requests support over the 
maximum amount allowable for that particular study will be considered 
nonresponsive.
    (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. If negotiations with a sponsor to 
supply the study product are underway but have not been finalized at 
the time of application, please provide a letter indicating such in the 
application. Verification of an adequate supply of the study product 
will be necessary before an award is made.
    (7) The protocol should be submitted in the application. The 
narrative portion of the application should be no more than 100 pages, 
single-spaced, printed on 1 side, with 1/2-inch margins, and in 
unreduced 12-point font. The appendices should also be no more than 100 
pages (separate from the narrative portion of the application). The 
application should not be bound.
C. Scientific/Technical Review Criteria
    The ad hoc expert panel will review the application based 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, including 
the design of the monitoring plans;
    (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 and monitoring; and
    (8) The ability of the applicant to complete the proposed study 
within its budget and within time limits stated in this RFA.

2. Review and Selection Process

    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 phase of the review to 
determine whether the proposed study will provide acceptable data that 
could 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 or his designee.
    A score will be assigned based on the scientific/technical review 
criteria. The review panel may advise the program staff about the 
appropriateness of the proposal to the goals of OPD's grant program.

3. Anticipated Announcement and Award

    Notification regarding the results of the review is anticipated by 
September 30, 2006, for FY 2007 and by September 30, 2007, for FY 2008. 
The earliest expected start date for the FY 2007 awards will be 
November 1, 2006, and for FY 2008 awards, the earliest expected start 
date will be November 1, 2007.

VI. Award Administration Information

1. Award Notices

    If receiving an award, applicants will be notified by FDA's Grants 
Management Office. Awards will either be issued on a Notice of Grant 
Award (PHS 5152) signed by FDA's Chief Grants Management Officer and be 
sent

[[Page 75203]]

to successful applicants by mail or will be transmitted electronically.

2. Administrative Requirements

    Applicants must adhere to the requirements of this notice. Special 
terms and conditions regarding FDA regulatory requirements and adequate 
progress of the study may be part of the award notice.

3. Reporting

A. 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. For continuing 
grants, an annual program progress report is also required. For such 
grants, 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 the status of their IND/IDE ``active'' and ``in 
effect,'' that is, not on ``clinical hold.'' Failure to meet regulatory 
requirements will be grounds for suspension or termination of the 
grant.
B. Monitoring Activities
    The program project officer will monitor grantees periodically. The 
monitoring may be in the form of telephone conversations, e-mails, or 
written correspondence between the project officer/grants management 
officer and the principal investigator. Information including but not 
limited to study progress, enrollment, problems, adverse events, 
changes in protocol, and study monitoring activities will be requested. 
Periodic site visits with officials of the grantee organization also 
may occur. The results of these monitoring activities will be recorded 
in the official grant file and will be available to the grantee upon 
request consistent with applicable disclosure statutes and with FDA 
disclosure regulations. Also, the grantee organization must comply with 
all special terms and conditions of the grant, including those 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.

VII. Agency Contacts

    For issues regarding the administrative and financial management 
aspects of this notice: Cynthia Polit (see Addresses to Request 
Application in section IV.1 of this document).
    For issues regarding the programmatic aspects of this notice: Debra 
Y. Lewis, Director, Orphan Products Grants Program, Office of Orphan 
Products Development (HF-35), Food and Drug Administration, 5600 
Fishers Lane, rm. 6A-55, Rockville, MD 20857, 301-827-3666, e-mail: 
debra.lewis@fda.gov or dlewis@oc.fda.gov.

VIII. Other Information

    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).
    Unless disclosure is required under the Freedom of Information Act 
as amended (5 U.S.C. 552) as determined by the freedom of information 
officials of HHS, by a court, or required by another Federal law, data 
contained in the portions of this application that have been 
specifically identified by page number, paragraph, etc., by the 
applicant as containing restricted information, shall not be used or 
disclosed except for evaluation purposes.

    Dated: December 12, 2005.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 05-24164 Filed 12-16-05; 8:45 am]
BILLING CODE 4160-01-S