Document ID: FDA-2008-N-0613-0001
Agency: fda
Document Type: Notice
Title: Clinical Studies of Safety and Effectiveness of Orphan Products
Posted Date: 2008-12-18T05:00Z

[Federal Register: December 18, 2008 (Volume 73, Number 244)]
[Notices]               
[Page 77029-77039]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr18de08-63]                         

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2008-N-0613]

 
Clinical Studies of Safety and Effectiveness of Orphan Products

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration's (FDA) Office of Orphan 
Product Development (OPD) is providing notice of a funding opportunity 
announcement for Federal assistance. The goal of the 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 
proposed product will be superior to 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.

DATES: See section IV.E of the SUPPLEMENTARY INFORMATION section for 
application submission dates.

FOR FURTHER INFORMATION CONTACT:
    Scientific/Research Contact: Katherine Needleman, Office of Orphan 
Products Development, Food and Drug Administration (HF-35), rm. 6A-55, 
5600 Fishers Lane, Rockville, MD 20857, 301-827-3666, e-mail: 
katherine.needleman@fda.hhs.gov.
    Financial/Grants Management Contact: Vieda Hubbard, Office of 
Acquisitions & Grant Services, 5630 Fishers Lane (HFA-500), rm. 2104, 
Rockville, MD 20857, 301-827-7177, e-mail: vieda.hubbard@fda.hhs.gov.

SUPPLEMENTARY INFORMATION:

I. Funding Opportunity Description

Research Project Grants (R01)
Request for Application (RFA) Number: RFA-FD-09-001
Catalog of Federal Domestic Assistance Number(s): 93.103

A. Research Objectives

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 prevalence, not incidence, of fewer than 
200,000 people in the United States). Diagnostics and vaccines will 
qualify for orphan status only if the U.S. population to whom they will 
be administered is fewer than 200,000 people per year.
2. Research Objectives
    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 proposed product will be superior 
to 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 (or in the case of a 
vaccine or diagnostic, information to support the estimates of how many 
people will be administered the diagnostic or vaccine annually) and an 
explanation of how the proposed study will either help gain product 
approval or provide essential data needed for product development.
    See section VII.A of this document for policies related to this 
announcement.

II. Award Information

A. Mechanism of Support

    Support will be in the form of a research project (R01) grant. The 
R01 grant is an award made to support a discrete, specified, 
circumscribed project to be performed by the named investigator(s) in 
an area representing the investigator's specific interest and 
competencies, based on the mission of FDA. The Project Director/
Principal Investigator (PD/PI) will be solely responsible for planning, 
directing, and executing the proposed project.
     All awards will be subject to all policies and requirements that 
govern the research grant programs of the Public Health Service (PHS) 
as incorporated in the Department of Health and Human Services (HHS) 
Grants Policy Statement, dated January 1, 2007 (http://www.hhs.gov/
grantsnet/adminis/gpd/index.htm), 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 Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355, 
360b, and 360e), section 351 of the PHS Act, regulations issued under 
any of these sections, and other applicable HHS statutes and 
regulations regarding human subject protection.
    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 Federal Food, Drug, and 
Cosmetic Act or safety, purity, and potency for licensing under section 
351 of the PHS Act. 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 (CFDA) No. 93.103.

B. Funds Available

1. Award Amount
    Of the estimated FY 2010 funding ($14.1 million), approximately $10 
million will fund noncompeting continuation awards, and approximately 
$4.1 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 2011 will be similar to FY 
2010. Grants will be awarded up to $200,000 or up to $400,000 in total 
(direct plus indirect) costs per year for up to 4 years. Please note 
that the dollar limitation will apply to total costs, not direct costs, 
as in

[[Page 77030]]

previous years. A fourth year of funding is available only for phase 2 
or 3 clinical studies. Applications for the smaller grants ($200,000) 
may be for phase 1, 2, or 3 studies. Study proposals for the larger 
grants ($400,000) must be for studies continuing in phase 2 or 3 of 
investigation. Budgets for each year of requested support may not 
exceed the $200,000 or $400,000 total cost limit, whichever is 
applicable.
    Phase 1 studies, including the initial introduction of an 
investigational new drug (IND) 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, and 
the side effects, including those associated with increasing drug 
doses. In some phase 1 studies that include subjects with the rare 
disorder, it may also be possible to gain early evidence on 
effectiveness.
    Phase 2 studies include early controlled clinical studies conducted 
to: (1) Evaluate the effectiveness of the product for a particular 
indication in patients with the disease or condition and (2) 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.
2. 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, 
third, or fourth year of noncompetitive continuation of support will 
depend on the following factors: (1) Performance during the preceding 
year, (2) compliance with regulatory requirements of IND/
investigational device exemption (IDE), and (3) availability of Federal 
funds.
3. Funding Plan
    In addition to the requirement for an active IND/IDE discussed in 
section V.C of this document, documentation of assurances with the 
Office of Human Research Protection (OHRP) (see section IV.F.1 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 for 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.
    Because the nature and scope of the proposed research will vary 
from application to application, it is anticipated that the size and 
duration of each award will also vary. Although the financial plans of 
FDA provide support for this program, awards under this funding 
opportunity are contingent upon the availability of funds.
    FDA grants policies as described in the HHS Grants Policy 
Statement: (http://www.hhs.gov/grantsnet/adminis/gpd/index.htm) will 
apply to the applications submitted and awards made in response to this 
FOA.

III. Eligibility Information

A. Eligible Applicants

1. Eligible Institutions
    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 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.
2. Eligible Individuals
    Any individual(s) with the skills, knowledge, and resources 
necessary to carry out the proposed research as the PD/PI is invited to 
work with his/her organization to develop an application for support. 
Individuals from under-represented racial and ethnic groups as well as 
individuals with disabilities are always encouraged to apply for FDA 
support.
    More than one PD/PI (i.e., multiple PDs/PIs) may be designated on 
the application for projects that require a ``team science'' approach 
and therefore clearly do not fit the single-PD/PI model. Additional 
information on the implementation plans and policies and procedures to 
formally allow more than one PD/PI on individual research projects is 
available at http://grants.nih.gov/grants/multi_pi.\1\ All PDs/PIs 
must be registered in the NIH electronic Research Administration (eRA) 
Commons (hereafter called eRA Commons or the Commons) prior to the 
submission of the application. (See http://era.nih.gov/
ElectronicReceipt/preparing.htm for instructions.)
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    \1\ FDA has verified the Web site addresses throughout this 
document, but FDA is not responsible for any subsequent changes to 
the Web sites after this document publishes in the Federal Register.
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    When multiple PDs/PIs are proposed, FDA requires one PD/PI to be 
designated as the ``Contact'' PI. The ``Contact'' PI will be 
responsible for: (1) All communication between the PDs/PIs and FDA, (2) 
assembling the application materials outlined in section IV of this 
document, and (3) coordinating progress reports for the project. The 
contact PD/PI must meet all eligibility requirements for PD/PI status 
in the same way as other PDs/PIs, but has no other special roles or 
responsibilities within the project team beyond those mentioned in the 
previous sentence.
    The decision of whether to apply for a single PD/PI or multiple PD/
PI grant is the responsibility of the investigators and applicant 
organizations and should be determined by the scientific goals of the 
project. Applications for multiple PD/PI grants will require additional 
information, as outlined in the instructions in section IV of this 
document, and the FDA review criteria for approach, investigator, and 
environment has been modified to accommodate applications involving 
either a single PD/PI or multiple PDs/PIs as indicated in section IV of 
this document. A weak or inappropriate PD/PI can have a negative effect 
on the review. Multiple PDs/PIs on a project share the authority and 
responsibility for leading and directing the project, intellectually 
and logistically. Each PD/PI is responsible and accountable to the 
grantee organization, or, as appropriate, to a collaborating 
organization, for the proper conduct of the project or program, 
including the submission of all required reports. For further 
information on multiple PDs/PIs, please see http://grants.nih.gov/
grants/multi_pi.

B. Cost Sharing or Matching

    This grant program does not require the applicant to match or share 
in the project costs if an award is made.

C. Other Special Eligibility Criteria

    Applicants may submit more than one application, provided each 
application is scientifically distinct.

[[Page 77031]]

IV. Application and Submission Information

    To comply with the President's Management Agenda, HHS is 
participating, as a partner, in the new governmentwide grants.gov 
application site. Applicants should apply electronically by visiting 
the Web site www.grants.gov and following instructions under ``Apply 
for Grants.''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 strongly encourage 
using the ``Tips'' posted on www.grants.gov under the announcement 
number when preparing your submission. This process is similar to the 
R01 Grant Application process currently used at NIH. You can visit the 
following Web site for helpful background on preparing to apply, 
preparing an application, and submitting an application to Grants.gov: 
http://era.nih.gov/ElectronicReceipt/. In order to apply 
electronically, the applicant must have a Data Universal Number System 
(DUNS) number, and register in the Central Contractor Registration 
(CCR) database, in eRA Commons (http://era.nih.gov/ElectronicReceipt/
preparing.htm), and in grants.gov (further explained in the following 
section IV.A of this document).

A. Registration Information

    To download a SF424 (R&R) Application Package and SF424 (R&R) 
Application Guide for completing the SF424 (R&R) forms for this FOA, 
link to http://www.grants.gov/Apply/ (hereafter called Grants.gov/
Apply) and follow the directions provided on that Web site.
    A one-time registration is required for institutions/organizations 
at both:
     Grants.gov (http://www.grants.gov/GetStarted) and
     eRA Commons (http://era.nih.gov/ElectronicReceipt/
preparing.htm).
    A registration process with Grants.gov and eRA Commons is necessary 
before submission and applicants are highly encouraged to start the 
process at least 4 weeks prior to the grant submission date. PDs/PIs 
should work with their institutions/organizations to make sure they are 
registered in the eRA Commons.
    Several additional separate actions are required before an 
applicant institution/organization can submit an electronic 
application, as follows:
    (1) Organizational/Institutional Registration at: http://
www.grants.gov/applicants/get_registered.jsp.
     Your organization will need to obtain a DUNS number 
(https://eupdate.dnb.com/requestoptions/government/ccrreg/) and 
register with the CCR (http://www.ccr.gov/) as part of the Grants.gov 
registration process.
     The DUNS number is a 9-digit identification number that 
uniquely identifies business entities.
     The CCR database is a governmentwide warehouse of 
commercial and financial information for all organizations conducting 
business with the Federal Government.
     If your organization does not have a Taxpayer 
Identification Number (TIN) or Employer Identification Number (EIN), 
allow for extra time. A valid TIN or EIN is necessary for CCR 
registration.
     The CCR also validates the EIN against Internal Revenue 
Service records--a step that will take an additional 1 to 2 business 
days.
     Tips for foreign organization registration are available 
at: http://era.nih.gov/ElectronicReceipt/preparing.htm#4.
     Direct questions regarding Grants.gov registration can be 
directed to the
    Grants.gov Customer Support Center: (http://www.grants.gov/help/
help.jsp), 1-800-518-4726, Monday through Friday, 7 a.m. to 9 p.m., 
e.s.t., e-mail: support@grants.gov.
    (2) Organizational/Institutional Registration on the eRA Commons 
(https://commons.era.nih.gov/commons/registration/
registrationInstructions.jsp)
     To find out if an organization is already Commons-
registered, see the ``List of Grantee Organizations Registered in eRA 
Commons''(http://era.nih.gov/userreports/ipf_com_org_list.cfm).
     Direct questions regarding the Commons registration can be 
directed to: eRA Commons Help Desk, 301-402-7469 or 866-504-9552 (toll 
free), TTY: 301-451-5939, Monday through Friday, 7 a.m. to 8 p.m., 
e.s.t., e-mail: commons@od.nih.gov.
    (3) PD/PI Registration on the eRA Commons Web site at: http://
era.nih.gov/docs/COM_UGV2630.pdf.
     The individual(s) designated as PDs/PIs on the application 
must also be registered in the eRA Commons. In the case of multiple 
PDs/PIs, all PDs/PIs must be registered in the eRA Commons prior to the 
submission of the application.
     Each PD/PI must hold a PD/PI account in the Commons. 
Applicants should not share a Commons account for both an Authorized 
Organization Representative/Signing Official (AOR/SO) role and a PD/PI 
role; however, if they have both a PD/PI role and an Internet Assisted 
Review (IAR) role, both roles should exist under one Commons account. 
When multiple PDs/PIs are proposed, all PDs/PIs at the applicant 
organization must be affiliated with that organization. PDs/PIs located 
at another institution need not be affiliated with the applicant 
organization, but must be affiliated with their own organization to be 
able to access the Commons.
     This registration/affiliation must be done by the AOR/SO 
or their designee who is already registered in the Commons.
     Both the PD/PI(s) and AOR/SO need separate accounts in the 
eRA Commons since both are authorized to view the application 
image.Note that if a PD/PI is already registered in the eRA Commons, 
another registration to apply for an FDA opportunity is not necessary.
    Note that if a PD/PI is also an NIH peer reviewer with an 
Individual DUNS and CCR registration, that particular DUNS number and 
CCR registration are for the individual reviewer only. These are 
different than any DUNS number and CCR registration used by an 
applicant organization. Individual DUNS and CCR registration should be 
used only for the purposes of personal reimbursement and should not be 
used on any grant applications submitted to the Federal Government.
    Several of the steps of the registration process could take 4 weeks 
or more. Therefore, applicants should immediately check with their 
business official to determine whether their organization/institution 
is already registered in both Grants.gov and the Commons (https://
commons.era.nih.gov/commons/). The FDA will accept electronic 
applications only from organizations that have completed all necessary 
registrations.
    If you experience technical difficulties with your online 
submission, you should contact the grants.gov Customer Response Center: 
(http://www.grants.gov/contactus/contactus.jsp. If the Customer 
Response Center is unable to resolve your problem, please contact Marc 
Pitts, Grants Management Specialist, Division of Acquisition Support 
and Grants (DASG), Office of Acquisition & Grant Services (OAGS), Food 
and Drug Administration, 301-827-7162, e-mail: marc.pitts@fda.hhs.gov.

B. Request Application Information

    In FYs 2010 and 2011, all applications must be submitted 
electronically through Grants.gov. Applicants must download the SF424 
(R&R) application forms and the SF424 (R&R) Application Guide for this 
FOA through Grants.gov/Apply.

[[Page 77032]]

    Note: Only the forms package directly attached to a specific FOA 
can be used. You will not be able to use any other SF424 (R&R) forms 
(e.g., sample forms, forms from another FOA), although some of the 
``Attachment'' files may be useable for more than one FOA.
    For further assistance, contact Marc Pitts at 301-827-7162. 
Telecommunications for the hearing impaired: 301-480-0434.

C. Content and Form of Application Submission

    Prepare all applications using the SF424 (R&R) application forms 
along with the SF424 (R&R) Application Guide for this FOA through 
http://www.grants.gov/applicants/apply_for_grants.jsp.
    Note: The following link provides additional information to the 
Adobe transition submission process: (http://era.nih.gov/
ElectronicReceipt/files/adobe_transition.pdf).
    The SF424 (R&R) Application Guide is critical to submitting a 
complete and accurate application to FDA. Some fields within the SF424 
(R&R) application components, although not marked as mandatory, are 
required by FDA (e.g., the ``Credential'' log-in field of the 
``Research & Related Senior/Key Person Profile'' component must contain 
the PD/PI's assigned eRA Commons User ID). Agency-specific instructions 
for such fields are clearly identified in the Application Guide. For 
additional information, see ``Frequently Asked Questions--Application 
Guide, Electronic Submission of Grant Applications'' (http://
era.nih.gov/ElectronicReceipt/faq_prepare_app.htm#1).
    Prepare all applications using the SF424 (R&R) application forms 
along with the SF424 (R&R) Application Guide for this FOA through 
Grants.gov/Apply at: http://www.grants.gov/applicants/apply_for_
grants.jsp.
    Note that the move to electronic applications has brought a change 
in terminology. The new Grants.gov terminology is as follows:
New = New
Resubmission = A Revised or Amended application
Renewal = Competing Continuation
Continuation = Noncompeting Progress Report
Revision = Competing Supplement
    The SF424 (R&R) application has several components. Some components 
are required, others are optional. The forms package associated with 
this FOA in Grants.gov/APPLY includes all applicable components, 
required and optional. A completed application in response to this FOA 
includes the data in the following components:
Required Components
SF424 (R&R) (Cover component)
Research & Related Project/Performance Site Locations
Research & Related Other Project Information
Research & Related Senior/Key Person
PHS398 Cover Page Supplement
PHS398 Research Plan
PHS398 Checklist
PHS398 Research & Related Budget
Research & Related Subaward Budget Attachment(s) Form
Optional Components
PHS398 Cover Letter File
Foreign Organizations--(Non-domestic (non-U.S.) Entity)
    Applications from foreign organizations must:
     Request budgets in U.S. dollars.
     Prepare detailed budgets for all applications (that is, 
complete the Research & Related Budget component of the SF424).
     Not seek charge back of customs and import fees.
     Make every effort to comply with the format 
specifications, which are based upon a standard U.S. paper size of 
8.5'' x 11'' within each portable document format (PDF).
     Comply with Federal/FDA policies on human subjects, 
animals, and biohazards.
     Comply with Federal/FDA biosafety and biosecurity 
regulations. See section VI.B of this document, ``Administrative and 
National Policy Requirements.''
     Indicate in the 398 Research Plan how the proposed project 
has specific relevance to FDA's mission and objectives and has the 
potential for significantly advancing sciences in the United States.
    Proposed research should provide special opportunities for 
furthering research programs through the use of unusual talent, 
resources, populations, or environmental conditions in other countries 
that are not readily available in the United States or that augment 
existing U.S. resources.

D. Special Instructions

1. Applicants Who Are Submitting a Renewal or Revision
    Applicants submitting a renewal or resubmission are required to 
enter the previous grant number into the Federal Identifier field in 
the SF424 (R&R) Cover Component form (box 8). Renewal and 
resubmission applications that do not include this number will receive 
an error message. Applicants should log on to the eRA Commons to obtain 
the previous grant number. If the number is not available in Commons, 
contact Marc Pitts at 301-827-7162 at FDA to get the previous grant 
number in order to submit the application. Visit http://era.nih.gov/
ElectronicReceipt/resubmission_FAQ.htm for additional information. 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 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.
2. Applications With Multiple PDs/PIs
    When multiple PDs/PIs are proposed, FDA requires one PD/PI to be 
designated as the ``Contact'' PI. The ``Contact PI will be responsible 
for: (1) All communication between the PDs/PIs and FDA, (2) assembling 
the application materials outlined below, and (3) coordinating progress 
reports for the project. The contact PD/PI must meet all eligibility 
requirements for PD/PI status in the same way as other PDs/PIs, but has 
no other special roles or responsibilities within the project team 
beyond those mentioned in the previous sentence.
    Information for the Contact PD/PI should be entered in item 15 of 
the SF424 (R&R) Cover component. All other PDs/PIs should be listed in 
the Research & Related Senior/Key Person component and assigned the 
project role of ``PD/PI.'' Please remember that all PDs/PIs must be 
registered in the eRA Commons prior to application submission. The 
Commons ID of each PD/PI must be included in the ``Credential'' field 
of the Research & Related Senior/Key Person component. Failure to 
include this data field will cause the application to be rejected.
    All projects proposing multiple PDs/PIs will be required to include 
a new section describing the leadership of the project.
    Multiple PD/PI Leadership Plan: For applications designating 
multiple PDs/PIs, a new section of the research plan entitled 
``Multiple PD/PI Leadership Plan'' (section 14 of the PHS398 Research 
Plan component), must be included. A rationale for choosing a multiple 
PD/PI approach should be described. The governance and organizational 
structure of the research project should be described, and should 
include communication plans, process

[[Page 77033]]

for making decisions on scientific direction, and procedures for 
resolving conflicts. The roles and administrative, technical, and 
scientific responsibilities for the project or program should be 
delineated for the PDs/PIs, including responsibilities for human 
subjects or animal studies as appropriate.
    If budget allocation is planned, the distribution of resources to 
specific components of the project or the individual PDs/PIs should be 
delineated in the Leadership Plan. In the event of an award, the 
requested allocations may be reflected in a footnote on the Notice of 
Award (NoA).
3. Applications Involving a Single Institution
    When all PDs/PIs are within a single institution, follow the 
instructions contained in the SF424 (R&R) Application Guide: (http://
grants.nih.gov/grants/funding/424/index.htm).
4. Applications Involving Multiple Institutions
    When multiple institutions are involved, one institution must be 
designated as the prime institution and funding for the other 
institution(s) must be requested via a subcontract to be administered 
by the prime institution. When submitting a detailed budget, the prime 
institution should submit its budget using the Research & Related 
Budget component. All other institutions should have their individual 
budgets attached separately to the Research &Related Subaward Budget 
Attachment(s) Form. See section 4.8 of the SF424 (R&R) Application 
Guide for further instruction regarding the use of the subaward budget 
form.
    Information concerning the consortium/subcontract budget is 
provided in the budget justification. Separate budgets for each 
consortium/subcontract grantee are required.

E. Submission Dates and Times

1. Submission, Review, and Anticipated Start Dates
Opening Date: January 4, 2009, for FY 2010 and January 3, 2010, for FY 
2011 (Earliest date an application may be submitted to Grants.gov)
Application Due Date(s): February 4, 2009, in FY 2010 and February 3, 
2010, in FY 2011
Peer Review Date(s): May/June 2009 and 2010 and November/December 2009 
and 2010
Council Review Date(s): September 2009 and September 2010
Earliest Anticipated Start Date(s): November 2009 and November 2010
    Please note that there is only one receipt date for FY 2010 and one 
receipt date for FY 2011 for new and resubmitted 
applications.Resubmissions and applications that were submitted 
previously but were deemed non-responsive to the RFA due to technical 
or IND issues will be allowed to resubmit on October 15, 2009, and 
October 15, 2010. Resubmissions will also be accepted in the February 
receipt dates in both FYs.
    Note: On time submission requires that applications be successfully 
submitted to Grants.gov no later than 5 p.m. local time (of the 
applicant institution/organization). Applications must be received by 
the close of business on February 4, 2009. Late applications may be 
accepted under extreme circumstances beyond the control of the 
applicant. Applications not received on time will not be considered for 
review and will generally be returned to the applicant.
    The protocol in the grant application should be submitted to the 
IND/IDE no later than January 5, 2009, for FY 2010 and no later than 
January 4, 2010, for FY 2011. The current version of the protocol that 
is included in the grant application and is intended to be used if the 
study is funded is the protocol that must be submitted to the IND/IDE 
before the application is reviewed. The date that corresponds with the 
IND/IDE submission/amendment date that corresponds to the protocol in 
the grant application should be reported in the title of the grant with 
the IND/IDE number.
    a. Letter of intent. A letter of intent is not required for the 
funding opportunity.
2. Submitting an Application Electronically to FDA
    To submit an application in response to this FOA, applicants should 
access this FOA via http://www.grants.gov/Apply and follow steps 1 
through 4. Note: Applications must only be submitted electronically.
3. Application Processing
    Applications may be submitted on or after the opening date and must 
be successfully received by Grants.gov no later than 5 p.m. local time 
(of the applicant institution/organization) on the application 
submission/receipt date(s). (See section IV.D.1. of this document.) If 
an application is not submitted by the receipt date(s) and time, the 
application may be delayed in the review process or not reviewed.
    Once an application package has been successfully submitted through 
Grants.gov, any errors have been addressed, and the assembled 
application has been created in the eRA Commons, the PD/PI and the AOR/
SO have 2 business days to view the application image to determine if 
any further action is necessary.
     If everything is acceptable, no further action is 
necessary. The application will automatically move forward for 
processing after 2 business days, excluding Federal holidays.
     Prior to the submission deadline, the AOR/SO can 
``Reject'' the assembled application and submit a changed/corrected 
application within the 2-day viewing window. This option should be used 
if it is determined that some part of the application was lost or did 
not transfer correctly during the submission process, the AOR/SO will 
have the option to ``Reject'' the application and submit a Changed/
Corrected application. In these cases, please contact the eRA Help Desk 
to ensure that the issues are addressed and corrected. Once rejected, 
applicants should follow the instructions for correcting errors in 
section 2.12 of the SF424 (R&R) Application Guide (http://
grants.nih.gov/grants/funding/424/index.htm#), including the 
requirement for cover letters on late applications. The ``Reject'' 
feature should also be used if you determine that warnings are 
applicable to your application and need to be addressed now. Remember, 
warnings do not stop further application processing. If an application 
submission results in warnings (but no errors), it will automatically 
move forward after 2 weekdays if no action is taken. Some warnings may 
need to be addressed later in the process. If the 2-day window falls 
after the submission deadline, the AOR/SO will have the option to 
``Reject'' the application if, due to an eRA Commons or Grants.gov 
system issue, the application does not correctly reflect the submitted 
application package (e.g., some part of the application was lost or 
didn't transfer correctly during the submission process). The AOR/SO 
should first contact the eRA Commons Helpdesk (http://
ithelpdesk.nih.gov/eRA/) to confirm the system error, document the 
issue, and determine the best course of action. FDA will not penalize 
the applicant for an eRA Commons or Grants.gov system issue.
     If the AOR/SO chooses to ``Reject'' the image after the 
submission deadline for a reason other than an eRA Commons or 
Grants.gov system failure, a changed/corrected application still can be 
submitted but it will be subject to the NIH/FDA late policy (http://
grants.nih.gov/grants/guide/notice-files/NOT-OD-05-030.html) guidelines 
and may not be accepted. The reason for this

[[Page 77034]]

delay should be explained in the cover letter attachment. Late 
applications may be accepted under extreme circumstances beyond the 
control of the applicant. In the absence of such extreme circumstances 
beyond the applicant's control, applications not received on time will 
not be considered for review and will generally be returned to the 
applicant.
     Both the AOR/SO and PD/PI will receive e-mail 
notifications when the application is rejected or the application 
automatically moves forward in the process after 2 days.
     In unusual circumstances, the following can occur: 
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.
    Upon receipt, applications will be evaluated for completeness. 
Incomplete applications will not be reviewed.
    There will be an acknowledgement of receipt of applications from 
Grants.gov and the Commons. The submitting AOR receives the Grants.gov 
acknowledgments. The AOR and the PI receive Commons acknowledgments. 
Information related to the assignment of an application to a Scientific 
Review Group is also in the Commons.
    Note: Because e-mail can be unreliable, it is the responsibility of 
the applicant to check periodically on their application status in the 
Commons.
    FDA will not accept any application in response to this FOA that is 
essentially the same as one currently pending initial merit review 
unless the applicant withdraws the pending application. FDA will not 
accept any application that is essentially the same as one already 
reviewed. However, FDA will accept a resubmission application, but such 
application must include an introduction (3 pages maximum) addressing 
the critique from the previous review.

F. Intergovernmental Review

    This initiative is not subject to Intergovernmental Review under 
the terms of Executive Order 12372.

G. Funding Restrictions

    All FDA awards are subject to the terms and conditions, cost 
principles, and other considerations described in the HHS Grants Policy 
Statement http://www.hhs.gov/grantsnet/adminis/gpd/index.htm.
1. 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 Web site at http://www.hhs.gov/ohrp for guidance on 
human subject protection issues. Also refer to section VII of this 
document.
    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. Please see the following link for more on 
Engagement of Institutions in Research http://www.hhs.gov/ohrp/
humansubjects/assurance/engage.htm.
    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 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. All human subject research regulated 
by FDA is also subject to FDA's regulations regarding the protection of 
human subjects (21 CFR parts 50 and 56). Applicants are encouraged to 
review the regulations, guidance, and information sheets on human 
subject protection and good clinical practice available on the Internet 
at http://www.fda.gov/oc/gcp/.
2. Key Personnel and 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 PIs, co-
investigators, 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 http://ohsr.od.nih.gov/ and by OHRP at http://www.hhs.gov/ohrp/
education/.
    Within 30 days of the award, the PI 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 for each key personnel, and a one-sentence description of the 
program. This letter should be signed by the PI and cosigned by an 
institution official and sent to the Grants Management Specialist whose 
name appears on the official Notice of Grant Award (NGA).

H. Other Submission Requirements

1. 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 consent forms should be attached in an appendix 
section. The applicant is referred to HHS and FDA regulations at 45 CFR 
46.116 and 21 CFR 50.25 for details regarding the required elements of 
informed consent.
2. PD/PI Credential (e.g., Agency Login)
    FDA requires the PD/PI(s) to fill in his/her Commons User ID in the 
``PROFILE--Project Director/Principal Investigator'' section, 
``Credential'' log-in field of the ``Research & Related Senior/Key 
Person Profile'' component.
3. Organizational DUNS
    The applicant organization must include its DUNS number in its 
Organization Profile in the eRA Commons. This DUNS number must match 
the DUNS number provided at CCR registration with Grants.gov. For 
additional information, see ``Frequently

[[Page 77035]]

Asked Questions--Application Guide, Electronic Submission of Grant 
Applications'' at: http://era.nih.gov/ElectronicReceipt/faq_prepare_
app.htm#1.
4. PHS398 Research Plan Component Sections
    Page limitations of the PHS398 Research Plan component must be 
followed as outlined in the SF424 (R&R) Application Guide. Although 
each section of the Research Plan component needs to be uploaded 
separately as a PDF attachment, applicants are encouraged to construct 
the Research Plan component as a single document, separating sections 
into distinct PDF attachments just before uploading the files. This 
approach will enable applicants to better monitor formatting 
requirements such as page limits. All attachments must be provided to 
FDA in PDF format, filenames must be included with no spaces or special 
characters, and a .pdf extension must be used.
    All application instructions outlined in the SF424 (R&R) 
Application Guide must be followed. Note: The link below provides 
additional information regarding the Adobe transition submission 
process: (http://era.nih.gov/ElectronicReceipt/files/adobe_
transition.pdf).
5. Appendix Materials
    Applicants must follow the specific instructions on Appendix 
materials as described in the SF424 (R&R) Application Guide. (See 
http://grants.nih.gov/grants/funding/424/index.htm.)
    Do not use the appendix to circumvent the page limitations of the 
Research Plan component. An application that does not observe the 
required page limitations may be delayed in the review process.
6. Resource Sharing Plan(s)
    Not Applicable
7. Foreign Applications(Non-domestic (non-U.S.) Entity)
    Indicate how the proposed project has specific relevance to the 
mission and objectives of FDA and has the potential for significantly 
advancing sciences in the United States.

V. Application Review Information

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.
    Applications found to be non-responsive 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 FOR FURTHER INFORMATION 
CONTACT).
    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 the National Cancer Institute, National 
Cancer Advisory Board (NCAB) 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 to each application 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.
    Applications submitted in response to this FOA will compete for 
available funds with all other recommended applications submitted in 
response to this FOA. The following will be considered in making 
funding decisions:
     Scientific merit of the proposed project as determined by 
peer review,
     Availability of funds, and
     Relevance of the proposed project to program priorities.
    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. In their written critiques, reviewers will be asked to comment 
on each of the following criteria in order to judge the likelihood that 
the proposed research will have a substantial impact on the pursuit of 
these goals. Each of these criteria will be addressed and considered in 
assigning the overall score, and weighted as appropriate for each 
application. Note that an application does not need to be strong in all 
categories to be judged likely to have major scientific impact and thus 
deserve a meritorious priority score.
    Investigators: Assessing the competence of the principal 
investigator(s) and key personnel to conduct the proposed research.This 
includes their academic qualifications, research experiences, 
productivity, and any special attributes.
    Resources and Environment: Evaluating any special attributes or 
deficiencies relevant to the conduct of the proposed studies.
    Budget: Evaluating whether all items of the requested budget are 
appropriate and justified.
    Human Subjects and Monitoring: Evaluating possible physical, 
psychological, or social injury patients might experience as subjects 
in the proposed research. Discussing whether the rights and welfare of 
the individuals will be adequately protected. Assessing the safety-
monitoring plan including the reporting of adverse events. Evaluating 
the informed consent documents as well as the plan to monitor the 
integrity of the data collected and the compliance with the protocol.

B. 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.

C. 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''

[[Page 77036]]

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 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 to whom they will be administered 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 
applicable FDA 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 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 
name(s) of 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 non-significant risk (NSR) are free from 
these IND/IDE requirements. Applicants studying an NSR device should 
provide a letter in the application from FDA's Center for Devices and 
Radiological 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 
$400,000 in total costs per year for up to 4 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 
non-responsive.
    (6) In an appendix to the application, there must be evidence that 
the product to be studied is available to the applicant in the form and 
quantity needed for the clinical trial proposed.A current letter from 
the supplier as an appendix will be acceptable. If negotiations 
regarding the supply of 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 
protocol may be included as an appendix. Page limits, font size, and 
margins should comply with the Application Guide, Electronic Submission 
of Grant Applications (http://era.nih.gov/ElectronicReceipt/faq_
prepare_app.htm#1).

D. Additional Review Criteria

    In addition to the previously mentioned criteria, the following 
items will continue to be considered in the determination of scientific 
merit and the priority score:
Resubmission Applications (formerly ``revised/amended'' applications): 
The adequacy of the responses to comments from the previous scientific 
review group will be assessed including the appropriateness of the 
improvements in the resubmission application.
Protection of Human Subjects from Research Risk: The involvement of 
human subjects and protections from research risk relating to their 
participation in the proposed research will be assessed. See the 
``Human Subjects Sections'' of the PHS398 Research Plan component of 
the SF424 (R&R).
Inclusion of Women, Minorities and Children in Research: The adequacy 
of plans to include subjects from both genders, all racial and ethnic 
groups (and subgroups), and children as appropriate for the scientific 
goals of the research will be assessed. Plans for the recruitment and 
retention of subjects will also be evaluated. See the ``Human Subjects 
Sections'' of the PHS398 Research Plan component of the SF424 (R&R).
Care and Use of Vertebrate Animals in Research: The adequacy of the 
plans for care and use of vertebrate animals to be used in the project 
will be assessed. See the ``Other Research Plan Sections'' of the 
PHS398 Research Plan component of the SF424 (R&R).
Biohazards: If materials or procedures are proposed that are 
potentially hazardous to research personnel and/or the environment, 
determine if the proposed protection is adequate.

E. Additional Review Considerations

Budget and Period of Support: The reasonableness of the proposed budget 
and the appropriateness of the requested period of support in relation 
to the proposed research may be assessed by the reviewers. The priority 
score should not be affected by the evaluation of the budget.
Applications from Foreign Organizations: Whether the project presents 
special opportunities for furthering research programs through the use 
of unusual talent, resources, populations, or environmental conditions 
in other countries that are not readily available in the United States 
or that augment existing U.S. resources will be assessed.

F. Sharing Research Data

    Sharing research data is not applicable.

G. Sharing Research Resources

    Sharing research resources is not applicable.

H. Anticipated Announcement and Award Dates

Earliest anticipated start/award date(s): November 1, 2009, and 
November 1, 2010.

VI. Award Administration Information

A. Award Notices

    After the review of the application is completed, the PD/PI will be 
able to access his or her summary statement (written critique) via the 
eRA Commons.
    If the application is under consideration for funding, FDA may 
request information from the applicant prior to making the award. For 
details, applicants may refer to the HHS Grants Policy Statement: 
(http://www.hhs.gov/grantsnet/adminis/gpd/index.htm).
    A formal notification in the form of a NoA will be provided to the 
applicant organization. The NoA signed by the grants management officer 
is the authorizing document. Once all administrative and programmatic 
issues have been resolved, the NoA will be generated via e-mail 
notification from the awarding component to the grantee business 
official.
    Selection of an application for award is not an authorization to 
begin performance. Any costs incurred before receipt of the NoA are at 
the recipient's risk. These costs may be reimbursed only to the extent 
considered allowable

[[Page 77037]]

pre-award costs. See section IV.G, ``Funding Restrictions.''

B. Administrative and National Policy Requirements

    All FDA grant and cooperative agreement awards include the HHS 
Grants Policy Statement as part of the NoA. For these terms of award, 
see the HHS Grants Policy Statement at: http://www.hhs.gov/grantsnet/
adminis/gpd/index.htm.

C. Reporting

1. Monitoring Activities
    a. OPD monitoring of clinical trials language. These guidelines are 
intended to provide information for principal investigators who are 
conducting clinical trials. The procedures outlined herein are in 
addition to (and not in lieu of) IRB, OHRP, and other FDA requirements.
    It is an OPD policy that data and safety monitoring of a clinical 
trial is to be commensurate with the risks posed to study participants 
and with the size and complexity of the study. In addition, the OPD 
requires that a Grantee and any third party engaged in supporting the 
clinical research be responsible for oversight of data and safety 
monitoring, ensuring that monitoring systems are in place, that the 
quality of the monitoring activity is appropriate, and that the OPD 
Project Officer is informed of recommendations emanating from 
monitoring activities.
    b. FDA requirements for monitoring. The OPD requires that each 
clinical trial it supports, regardless of phase, has data and safety 
monitoring procedures in place to safeguard the well-being of study 
participants and to ensure scientific integrity. Monitoring must be 
performed on a regular basis throughout the subject accrual, treatment, 
and followup periods.
    The specific approach to monitoring will depend on features of the 
clinical trial to be conducted e.g., several levels of monitoring: Data 
and Safety Monitoring Board (DSMB), Study Monitoring Committee (SMC) 
and Independent Medical Monitor.
    Monitoring activities should be appropriate to the study, study 
phase, population, research environment, and degree of risk involved.
    In small, single-site studies, safety monitoring is often performed 
by the independent medical monitor or a safety monitoring committee in 
conjunction with the study statistician. All phase 3 studies and any 
high risk phase 1 or 2 clinical trial will also require a DSMB. It may 
be desirable to utilize a DSMB for:
     Trials involving highly experimental therapies or 
specialized review procedures external to the OPD (e.g., gene therapy 
or xenotransplantation);
     Trials involving substantial risk to study participants 
(e.g., studies with irreversible outcomes); or
     Trials involving particularly vulnerable study 
participants (e.g., children or persons with impaired ability to 
consent).
    c. Study monitoring plan. The OPD requires that the protocol 
document include a section describing the proposed plan for interim 
data monitoring. This section will detail who is to be responsible for 
interim monitoring (i.e., a DSMB, an SMC, or the study investigator), 
what data will be monitored (i.e., performance and safety data only vs. 
efficacy data as well), the timing of the first data review (e.g., 
``the first interim look will occur when the initial 20 participants 
have completed the 6-month followup visit''), and the frequency of 
interim reviews (which will depend on such factors as the study design, 
interventions and anticipated recruitment rate). The plan will specify 
``stopping guidelines'' and other criteria for the monitors to follow 
in their review of the interim data.
    A preliminary monitoring plan must be submitted as part of the 
Research Plan portion of the grant application for a clinical trial. 
The plan will be examined as part of the peer review process, and any 
comments and concerns will be included in an administrative note in the 
summary statement. OPD staff will ensure that all concerns are resolved 
before the grant award is made.
2. Oversight 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 or specialist and the principal investigator. Information 
including, but not limited to, information regarding 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 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 the 
following: (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 applicable FDA and HHS regulatory requirements for the trial.
    In addition to the requirement for an active IND/IDE discussed in 
section V.C of this document, documentation of assurances with the OHRP 
(see section IV.F.1 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 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 (FWA or 
assurance) for the IRB of record for 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.
3. Reporting Requirement
    The grantee must file a final program progress report, financial 
status report, and invention statement within 90 days after the end 
date of the project period as noted on the notice of grant award.
    When multiple years are involved, awardees will be required to 
submit the Non-Competing Grant Progress Report (PHS 2590) annually and 
financial statements as required in the HHS Grants Policy Statement, 
dated October 1, 2006, (http://www.hhs.gov/grantsnet/adminis/gpd/). 
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.
    Awardees will be required to submit the Non-Competing Continuation 
Grant Progress Report (PHS 2590) (http://grants.nih.gov/grants/funding/
2590/2590.htm) annually and financial statements as required in the HHS 
Grants Policy Statement http://www.hhs.gov/grantsnet/adminis/gpd/
index.htm.

[[Page 77038]]

    A listing and a justification for any study changes that occurred 
in the past year must be included in the Non-Competing Continuation 
Grant Progress Report (PHS 2590).
    A final progress report, invention statement, and Financial Status 
Report are required when an award is relinquished when a recipient 
changes institutions or when an award is terminated.

VII. Other Information

A. Required Federal Citations

1. Clinical Trials Data Bank
    The Food and Drug Administration Amendments Act of 2007 (FDAAA) 
contains provisions that expand the current database known as 
ClinicalTrials.gov to include additional requirements for individuals 
and entities, including grantees, who are involved in conducting 
clinical trials that involve products regulated by FDA or that are 
funded by HHS, including FDA. These additional requirements include 
mandatory registration of certain types of clinical trials, as well as 
reporting of results for certain trials for inclusion in the 
ClinicalTrials.gov database. ClinicalTrials.gov, which was created 
after the Food and Drug Administration Modernization Act of 1997, 
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. 
ClinicalTrials.gov is available to the public through the Internet at 
http://clinicaltrials.gov.
    ClinicalTrials.gov contains information about certain clinical 
trials, both federally and privately funded, of drugs (including 
biological products) and medical devices. The types of trials that are 
required to be registered, and for which results must be reported, are 
known as ``applicable clinical trials.'' FDAAA defines the types of 
clinical trials that are ``applicable clinical trials'' and, therefore, 
are subject to the registration and results reporting requirements. The 
registry listing for each trial includes information such as 
descriptive information about the trial, patient eligibility criteria, 
recruitment status, location information on the clinical trial sites, 
and points of contact for those wanting to enroll in the trial. The 
database also contains information on the results of clinical trials. 
More detailed information on the definition of ``applicable clinical 
trial'' and the registry and results reporting requirements can be 
found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-
014.html and http://prsinfo.clinicaltrials.gov/fdaaa.html.
    FDAAA also added new requirements concerning clinical trials 
supported by grants from HHS, including FDA. Under these provisions, 
any grant or progress report forms required under a grant from any part 
of HHS, including FDA, must include a certification that the person 
responsible for entering information into ClinicalTrials.gov (the 
``responsible party'') has submitted all required information to the 
database. There are also provisions regarding when agencies within HHS, 
including FDA, are required to verify compliance with the database 
requirements before releasing funding to grantees.OPD program staff 
will be providing additional information on these requirements, 
including the appropriate means by which to certify that a grantee has 
complied with the database requirements.
2. Data and Safety Monitoring Plan
    Data and safety monitoring may be required for certain types of 
clinical trials. See section VI.C.1.c for more details and other FDA 
monitoring requirements. The establishment of DSMBs is required for 
multi-site clinical trials involving interventions that entail 
potential risk to the participants, and generally for phase 3 clinical 
trials. Although phase 1 and phase 2 clinical trials may also use 
DSMBs, smaller clinical trials may not require this oversight format, 
and alternative monitoring plans may be appropriate.
3. Access to Research Data Through the Freedom of Information Act 
(FOIA)
    FOIA, (5 U.S.C. 552), provides individuals with a right to access 
certain records in the possession of the Federal government, subject to 
certain exemptions. The government may withhold information under the 
exemptions and exclusions contained in the FOIA. The exact language of 
the exemptions can be found in the FOIA. Additional guidance on the 
exemptions and how they apply to certain documents can be found in the 
HHS regulations implementing the FOIA (45 CFR part 5) and FDA 
regulations implementing the FOIA(21 CFR part 20). (Also see the HHS 
Web site: (http://www.hhs.gov/foia/).
    Data included in the application may be considered trade secret or 
confidential commercial information within the meaning of relevant 
statutes and implementing regulations. FDA will protect trade secret or 
confidential commercial information to the extent allowed under 
applicable law.
4. Use of Animals in Research
    Recipients of PHS support for activities involving live vertebrate 
animals must comply with PHS Policy on Humane Care and Use of 
Laboratory Animals (http://grants.nih.gov/grants/olaw/references/
PHSPolicyLabAnimals.pdf) as mandated by the Health Research Extension 
Act of 1985 (http://grants.nih.gov/grants/olaw/references/
hrea1985.htm), and the U.S. Department of Agriculture Animal Welfare 
Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm) as 
applicable.
5. Inclusion of Women And Minorities in Clinical Research
    Applicants for 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.
6. Inclusion of Children as Participants in Clinical Research
    FDA regulations at 21 CFR part 50, subpart D, contain additional 
requirements that must be met by IRBs reviewing clinical investigations 
regulated by FDA and involving children as subjects. FDA is part of 
HHS; accordingly, the research project grants under this program are 
supported by HHS, and HHS regulations at 45 CFR part 46, subpart D also 
apply to research involving children as subjects.
7. Standards for Privacy of Individually Identifiable Health 
Information
    HHS issued final modification to the ``Standards for Privacy of 
Individually Identifiable Health Information,'' the ``Privacy Rule,'' 
on August 14, 2002. The Privacy Rule is a federal regulation under the 
Health Insurance Portability and Accountability Act of 1996 that 
governs the protection of individually identifiable health information, 
and is administered and enforced by the HHS Office for Civil Rights 
(OCR).
    Decisions about applicability and implementation of the Privacy 
Rule reside with the researcher and his/her institution. The OCR Web 
site http://www.hhs.gov/ocr/ provides information on the Privacy Rule.

[[Page 77039]]

8. Healthy People 2010
    PHS is committed to achieving the health promotion and disease 
prevention objectives of ``Healthy People 2010,'' a PHS-led national 
activity for setting priority areas. This FOA is related to one or more 
of the priority areas. Potential applicants may obtain a copy of 
``Healthy People 2010'' at http://www.health.gov/healthypeople.
9. Smoke-Free Workplace
    PHS strongly encourages all grant recipients to provide a smoke-
free workplace and discourage the use of all tobacco products. In 
addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits 
smoking in certain facilities (or in some cases, any portion of a 
facility) in which regular or routine education, library, day care, 
health care, or early childhood development services are provided to 
children. This is consistent with the PHS mission to protect and 
advance the physical and mental health of the American people.
10. Authority and Regulation
    This program is not subject to the intergovernmental review 
requirements of Executive Order 12372. FDA's research program is 
described in the Catalog of Federal Domestic Assistance (CFDA), No. 
93.103 http://www.cfda.gov/.
    FDA will support the clinical studies covered by this notice under 
the authority of section 301 of the PHS Act as amended (42 U.S.C. 241) 
and under applicable regulations at 42 CFR part 52 and 45 CFR parts 74 
and 92. All grant awards are subject to applicable requirements for 
clinical investigations imposed by sections 505, 512, and 515 of the 
Federal Food, Drug, and Cosmetic Act or safety, purity, and potency for 
licensing under section 351 of the PHS Act, including regulations 
issued under any of these sections.
    All human subject research regulated by FDA is also subject to 
FDA's regulations regarding the protection of human subjects (21 CFR 
parts 50 and 56). Applicants are encouraged to review the regulations, 
guidance, and information sheets on human subject protection and Good 
Clinical Practice available on the Internet at http://www.fda.gov/oc/
gcp/.
    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.
    All awards will be subject to all policies and requirements that 
govern the research grant programs of the PHS as incorporated in the 
HHS Grants Policy Statement, dated January 1, 2007, (http://
www.hhs.gov/grantsnet/adminis/gpd/index.htm).
11. Human Subjects Protection
    Federal regulations (45 CFR part 46) require that applications and 
proposals involving human subjects must be evaluated with reference to: 
(1) The risks to the subjects, (2) the adequacy of protection against 
these risks, (3) the potential benefits of the research to the subjects 
and others, and (4) the importance of the knowledge gained or to be 
gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).
12. Human Embryonic Stem Cell Research and Cloning
    Section 498 of the PHS Act places certain restrictions on human 
fetal research.In addition, under currently applicable executive 
orders, HHS funds may not be used to support human embryo research 
under any extramural award instrument. HHS funds may not be used for 
the creation of a human embryo for research purposes or for research in 
which a human embryo is destroyed, discarded, or knowingly subjected to 
risk of injury or death greater than that allowed for research on 
fetuses in utero under 45 CFR 46.204 and 46.207 and subsection 498(b) 
of the PHS Act (42 U.S.C. 289g(b)). The term ``human embryo'' includes 
any organism not protected as a human subject under 45 CFR part 46, as 
of the date of enactment of the governing appropriations act, that is 
derived by fertilization, parthenogenesis, cloning, or any other means 
from one or more human gametes or human diploid cells.
    In addition, HHS is prohibited, by a March 4, 1997, Presidential 
memorandum, from using Federal funds for cloning human beings. In 
implementing this program, FDA will comply with all applicable 
statutes, regulations, presidential memoranda and Executive orders.
    Criteria for Federal funding of research on hESCs can be found at: 
http://www.hhs.gov/faq/research/stemcell/r-0006.html and http://
stemcells.nih.gov/research/registry/eligibilityCriteria.asp.

    Dated: December 9, 2008.
Jeffrey Shuren,
Associate Commissioner for Policy and Planning.
[FR Doc. E8-30061 Filed 12-17-08; 8:45 am]

BILLING CODE 4160-01-S