Clinical Studies of Safety and Effectiveness of Orphan Products; Availability of Grants; Request for Applications, 2642-2646 [05-762]

Agencies

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

[Federal Register Volume 70, Number 10 (Friday, January 14, 2005)]
[Notices]
[Pages 2642-2646]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 05-762]


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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) 2006. This announcement supercedes the previous announcement 
of this program, which was published in the Federal Register of August 
8, 2003 (68 FR 47340). Please note that there are new submission 
requests and requirements for this grant program. These include, but 
are not limited to, a requested letter of intent, a change in funding 
levels, a change in number of receipt dates, and changes in review 
criteria.
1. Background
    The 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 a 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 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. 331 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, 512, or 515 of the act (21 U.S.C. 355, 
360b, or 360eet seq.) 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.
    The 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 
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/. (FDA has verified the Web site address, but we 
are not responsible for subsequent changes to the Web site after this 
document publishes in the Federal Register). Internet viewers should 
proceed to ``Publications.''
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 the 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 fiscal year (FY 2006) funding ($13.2 million), 
approximately $9.2 million will fund noncompeting continuation awards, 
and approximately $4 million will fund 10 to 12 new awards subject to 
availability of funds. The expected start date for the FY 2006 awards 
will be June 1, 2006.
    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 beginning in FY 2006, 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

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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
    The number of studies funded will depend on the quality of the 
applications received and the availability of Federal funds to support 
the projects. Resources for this program are limited. Therefore, if two 
applications propose duplicative or similar studies, FDA may support 
only the study with the better score. Funds may be requested in the 
budget to travel to FDA for meetings with OPD or reviewing division 
staff about the progress of product development.
    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 or if the IND/IDE for the proposed study is not 
active and in regulatory compliance, no award will be made. 
Documentation of Assurances with the Office of Human Research 
Protection (OHRP) (see section IV.4.A of this document) must be on file 
with the FDA 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 the FDA 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)
    Beginning October 1, 2003, applicants are 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 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 
warehouse of commercial and financial information for all organizations 
conducting business with the Federal Government. Registration with CCR 
will eventually become a requirement and is consistant 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 a registration is through the World Wide Web at https://
www.ccr.gov. This Web site provides a CCR handbook with detailed 
information on data you will need prior to beginning the online 
registration, as well as steps to walk you through the registration 
process. You must have a DUNS number to begin your registration. Call 
Dunn & Bradstreet, Inc., at the number listed in the previous paragraph 
if you do not have a DUNS number.
    In order to access grants.gov an applicant will be required to 
register with the Credential Provider. Information about this is 
available at https://www.grants.gov/CredentialProvider.

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 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
    Application requests, letters of intent, 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.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
    The original and two copies of the completed Grant Application Form 
PHS 398 (Rev. 5/01) or the original and two copies of PHS 5161-1 (Rev. 
7/00) for State and local governments, with three copies of the 
appendices must be submitted to Cynthia Polit (see Addresses to Request 
Application in section IV.1 of this document). State and local 
governments may use the PHS 398 (Rev. 5/01) application form in lieu of 
the PHS 5161-1. Other than evidence of final IRB approval, FWA or 
assurance, and certification of adequate supply of study product, no 
material will be accepted after the receipt date. The mailing package 
and item two of the application face page must be labeled ``Response to 
RFA-FDA-OPD-2006.'' If

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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.
    Applicants must follow guidelines named in the PHS 398 (Rev. 5/01) 
grant application instructions. An application that has received two 
prior disapprovals is not eligible to apply.
B. Format for Application
    Submission of the application must be on Grant Application Form PHS 
398 (Rev. 5/01). Applications from State and local governments may be 
sent on Form PHS 5161-1 (Rev. 7/00) or Form PHS 398 (Rev. 5/01). All 
``General Instructions'' and ``Specific Instructions'' in the 
application kit or on the OPD 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. The face page of 
the application should reflect the request for applications number RFA-
FDA-OPD-2006. 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).
    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 reviewing division staff.
    Data and information included in the application will generally 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.
    Information collection requirements requested on Form PHS 398 (Rev. 
5/01) have been sent by the 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 PHS 5161-1 (Rev. 7/00) were approved 
and assigned OMB control number 0348-0043.
3. Submission Dates and Times
    For FY 2006, the application receipt date is April 19, 2005. Please 
note that there is only one receipt date for FY 2006.
    The protocol in the grant application should be submitted to the 
IND/IDE no later than March 18, 2005.
    A letter of intent to submit a grant application is requested and 
should be sent to Cynthia Polit, Grants Management Specialist (see 
Addresses to Request Application in section IV.1 of this document) by 
March 18, 2005.
    The letter of intent should include the name of the drug, biologic, 
device, or food; the disease/condition; a brief summary of the proposed 
project; and the possible study sites. The letter of intent is not 
binding on the applicant or the agency. That is, the applicant may 
choose not to submit an application even if a letter of intent has been 
submitted previously. Submission of a letter of intent does not change 
any of the requirements and due dates outlined in this RFA.
    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 delivered 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. 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 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). Please do not send applications to the CSR at NIH. Any 
application sent to NIH/CSR that is forwarded to the FDA 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 delivered 
as stated previously. Currently, FDA is unable to receive applications 
electronically.
4. 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 the OHRP (45 CFR part 46). Applicants are advised to 
visit the OHRP Internet site at https://ohrp.osophs.dhhs.gov/ 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 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 the OHRP.
    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'' for further 
information.
    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,

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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.osophs.dhhs.gov/educmat.htm. (FDA has 
verified the Web site address, but we are not responsible for 
subsequent changes to the Web site after this document publishes in the 
Federal Register.)
    Within 30 days of the award, the principal investigator should 
provide a letter to the FDA 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 the Grants Management Officer.
5. 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 requirements of 
this notice and must bear the original signatures of both the principal 
investigator and the applicant institution's/organization's authorized 
official. 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 their application. Please 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 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 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 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 the FDA IND/
IDE reviewing 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 
the 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 free from 
these IND/IDE requirements. Applicants studying an NSR device should 
provide a letter in the application from the FDA 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 adequate supply of 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;

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    (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 the OPD grant program.
3. Anticipated Announcement and Award
    Notification regarding the results of the review is anticipated by 
May 31, 2006. The expected start date for the FY 2006 awards will be 
June 1, 2006.

VI. Award Administration Information

1. Award Notices
    If receiving an award, applicants will be notified by the FDA 
Grants Management Office. Awards will either be issued on a Notice of 
Grant Award (PHS 5152) signed by the FDA Chief Grants Management 
Officer and be sent 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, study monitoring activities will be requested. 
Periodic site visits with officials of the grantee organization may 
also 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 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

    Clinical Trials Data Bank
    The Food and Drug Modernization Act of 1997 requires that certain 
information be entered into the Clinical Trials Data Bank (CTDB) for 
federally and privately funded clinical trials conducted under an IND 
application 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 address, but we are not responsible for 
subsequent changes to the Web site after this document publishes in the 
Federal Register).
    The 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.
    The OPD program staff will provide more information to grantees 
about entering the required information in the CTDB after awards are 
made.

    Dated: January 6, 2005.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 05-762 Filed 1-13-05; 8:45 am]
BILLING CODE 4160-01-S