CHALLENGE GRANTS: BIODEFENSE PRODUCT DEVELOPMENT

RELEASE DATE:  June 15, 2004

RFA Number:  RFA-AI-04-029  

EXPIRATION DATE:  January 19, 2005

Department of Health and Human Services (DHHS)

PARTICIPATING ORGANIZATION:
National Institutes of Health (NIH) 
 (http://www.nih.gov)

COMPONENT OF PARTICIPATING ORGANIZATION:
National Institute of Allergy and Infectious Diseases (NIAID) 
 (http://www.niaid.nih.gov) 

CATALOGUE OF FEDERAL DOMESTIC ASSISTANCE NUMBERS:
No. 93.855, Immunology, Allergy, and Transplantation Research
No. 93.856, Microbiology and Infectious Diseases Research

LETTER OF INTENT RECEIPT DATE: December 17, 2004
APPLICATION RECEIPT DATE: January 18, 2005  

THIS RFA CONTAINS THE FOLLOWING INFORMATION

o Purpose of this RFA
o Research Objectives
o Mechanism of Support 
o Funds Available
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirements 
o Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Supplementary Instructions
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations

PURPOSE OF THIS RFA

Research supported and conducted by the National Institute of Allergy and 
Infectious Diseases (NIAID), National Institutes of Health, strives to 
understand, treat and ultimately prevent the myriad infectious, immunologic, 
and allergic diseases that threaten millions of human lives.  The NIAID 
Division of Microbiology and Infectious Diseases (DMID) and the Division of 
Allergy, Immunology and Transplantation (DAIT) support extramural research to 
control and prevent diseases caused by virtually all infectious agents. This 
includes basic biomedical research, such as studies of microbial physiology 
and antigenic structure; immunity; applied research, including the 
development of diagnostic tests; and clinical trials to evaluate experimental 
drugs and vaccines.  

In response to growing concerns about the use of biological agents in acts of 
terrorism, the further clinical development of new vaccines, therapeutics, 
adjuvants, and diagnostics against NIAID Category A, B, and C priority 
pathogens (see http://www.niaid.nih.gov/biodefense/bandc_priority.htm) is a 
high priority.  This program, CHALLENGE GRANTS: BIODEFENSE PRODUCT 
DEVELOPMENT, will support further development of previously identified 
products against NIAID Category A, B, and C high priority pathogens including 
vaccines, adjuvants, therapeutics, and diagnostics. To be responsive to this 
program for the development of biodefense products, the applicant must have 
already demonstrated proof-of-principle for a candidate vaccine, therapeutic, 
adjuvant, or diagnostic method for biodefense. Phases of further development 
eligible for support include, but are not limited to:  early validation; pre-
clinical stages; scale-up; production; and fulfilling regulatory 
requirements. 

NOTE: While clinical development strategies may be included within an overall 
development plan, this RFA will NOT support clinical trials; applications 
requesting support for clinical trials will be viewed as unresponsive to this 
RFA and will be returned without review. Utilization of human derived 
material in pre-clinical studies in support of complying with regulatory 
requirements is considered responsive.

NOTE:  Applications to support basic research or the "discovery" of new 
targets or the identification and validation of protective epitopes for NIAID 
Category A, B, and C priority pathogens will NOT be supported under this RFA, 
but are supported by other NIAID programs (see 
http://www.niaid.nih.gov/biodefense/research/funding.htm).  In addition, 
ancillary research studies that are not directly relevant to development of 
the selected product will not be supported.

Challenge Grants

Under this program, Challenge (UC1) grant awards will be performance based 
for a period of up to three years.  That is, funds can be requested and will 
be awarded in increments based on the attainment of interim research 
objectives (milestones) defined by the applicant and approved following peer 
review by the NIAID.  Because funding will be tied to the attainment of 
interim research objectives (milestones), funding will not be provided 
annually as is traditional for NIH grants, but will be linked to project 
timelines and interim objectives.  Initial release of funds will be to 
support achievement of the first interim objective/milestone.  Release of the 
next funding increment will be based on the achievement of the previous 
interim objective, as determined by NIAID staff.

Partnerships

A key component of this initiative is the development of partnerships between 
the government and industry.  For the purpose of this program, "industry" is 
defined as large and small, domestic or foreign, pharmaceutical, 
biotechnology, bioengineering, and chemical companies.  Since academic 
organizations are often the source of new candidate products, this program 
can also support a partnership between industry and collaborator(s) as 
necessary from academic and non-profit research organizations.  The 
involvement of an academic or non-profit research organization is NOT a 
requirement; therefore, industry does not need an academic collaborator to 
submit an application to this program. 

All projects must demonstrate substantive investment by industry 
participant(s). "Substantive investment" is defined, for the purposes of this 
program, as substantive commitment of any one or more of the following 
resources: personnel, in kind contributions of materials and/or reagents, 
including but not limited to chemical libraries, innovative biotechnology 
platforms (i.e., for screening of drugs and inhibitors), scale up of GMP 
chemical synthesis or production, provision of animal or other laboratory 
models for evaluation, subcontracts, data management resources, regulatory 
support, and alterations/renovations of facilities or provision of equipment 
to address biohazard concerns.  

The Principal Investigator of the project may be affiliated with either 
industry or an academic organization (if academia is part of a partnership 
with industry). See information under ELIGIBLE INSTITUTIONS below.

RESEARCH OBJECTIVES

Background

The National Institutes of Health and other agencies in the Department of 
Health and Human Services (DHHS) are currently supporting research to develop 
new products to protect the public from the health consequences resulting 
from the use of biological threat agents. NIAID has recently convened three 
separate Blue Ribbon Panels to address research priorities.  The three NIAID 
Panels focused on:
          
o NIAID Category A Priority Pathogens 
(February 4-5, 2002; the full report is available at 
http://www.niaid.nih.gov/biodefense/research/biotresearchagenda.pdf 
o NIAID Category B and C Priority Pathogens 
(October 22-23, 2002; the full report is available at 
http://www.niaid.nih.gov/biodefense/research/categorybandc.pdf)
o Immunity and Biodefense (June 17, 2002; the full report is available at 
http://www.niaid.nih.gov/publications/pdf/biodimmunpan.pdf) 

These Panels identified the development of new vaccines, adjuvants, 
therapeutics, and diagnostics as one of the highest priorities.  In addition 
to the NIAID research agenda, the DHHS has identified the highest priority 
products for biodefense preparedness 
(http://www.niaid.nih.gov/biodefense/research/high_priority.htm).

Potential applicants should also be aware of other biodefense research 
programs at NIAID that have different research scopes and requirements from 
those solicited in this program.  A complete list of the biodefense funding 
opportunities currently supported by NIAID can be found at: 
http://www.niaid.nih.gov/biodefense/research/funding.htm.  

To be responsive to this Program: CHALLENGE GRANTS: BIODEFENSE PRODUCT 
DEVELOPMENT, the application must:

o Propose the development of a previously identified candidate vaccine, 
therapeutic, adjuvant, or diagnostic product that has demonstrated proof-of-
concept against any of the NIAID Category A, B, and C priority pathogens 
(listed at http://www.niaid.nih.gov/biodefense/bandc_priority.htm  
o Demonstrate substantial investment by a commercial sector (industry) 
component; and
o Focus on further development of the candidate product(s) or strategy for 
product development by specifying the proposed overall project goal(s) and  
interim objectives (milestones), a detailed timeline for milestone and goal 
attainment, and a detailed budget for each milestone. 

It is recommended that an applicant propose no more than four interim 
objectives/milestones and a final objective (or product).  Ancillary research 
studies that are not directly relevant to development of the selected product 
will not be supported.

VACCINES FOR BIODEFENSE

Vaccines are the most effective method of protecting the public against 
infectious diseases.  The development of vaccines against biological threat 
agents that can be administered quickly and can safely elicit a protective 
response in a broad range of recipients is a high priority.  Research 
approaches should begin with an identified and characterized vaccine 
candidate that has demonstrated proof-of-concept against a NIAID Category A, 
B, or C priority pathogen.  Only applications for vaccine development against 
one of these priority pathogens are responsive to this program.  

NOTE: Applications proposing the development of a vaccine that does not focus 
on a NIAID Category A, B, or C priority pathogen will be deemed unresponsive 
and will be returned to the applicant without review.

All applicants must develop a sound scientific rationale for the forward 
progression of the target or vaccine candidate through the product 
development pathway. A research and development plan must be included that 
defines the potential ultimate product, proposed project goal, interim 
objectives (development milestones), identifies alternative approaches, and 
provides a timeline for milestone and goal attainment.  

Development activities that can be supported under this program include, but 
are not limited to, the following areas:

o Optimization of production methodology including process development;
o Scale up and production of candidate vaccines including GMP production;
o Evaluation of vaccine candidates against a NIAID Category A, B, or C 
priority pathogen formulated with or without adjuvants or immunomodulators;
o Optimization of dose and route of delivery in pre-clinical evaluation; and
o Performing pre-clinical testing for safety and toxicity and efficacy in 
animal models and other benchmarks required for moving candidate vaccines 
into Phase I clinical trials.

NOTE: Clinical trials for vaccines will NOT be supported.

Note: All NIAID Category A, B, and C priority pathogens are responsive to 
this RFA. For applications for vaccine development for Bacillus anthracis, of 
particular interest are projects involving the development of vaccines that 
affect the persistence, germination, clearance, and inactivation (host immune 
response mechanisms) of spores in the lung and/or mediastinal lymph nodes. 
For applications for vaccine development for influenza, of particular 
interest are projects involving the development of vaccines that address 
pandemic influenza issues.

ADJUVANTS FOR BIODEFENSE

The development of an enhanced immune response may require the administration 
or co-administration of an adjuvant or immunostimulatory compound.  
Applications to support the further development or evaluation of molecules 
with documented ability to enhance the immune response are responsive to this 
program, and products capable of safely enhancing an innate immune response 
are particularly encouraged. 

This program supports the further development and evaluation of vaccine 
adjuvants and immunomodulators against all NIAID Category A, B, and C 
priority pathogens (see 
http://www.niaid.nih.gov/biodefense/bandc_priority.htm) that have previously 
demonstrated proof-of-concept. Applications may propose the further 
development of an adjuvant or immunomodulator as either a stand-alone product 
or in conjunction with a licensed or an investigational vaccine against a 
NIAID Category A, B, or C priority pathogen only.  

NOTE: Applications proposing the development of an adjuvant or 
immunomodulator in conjunction with a vaccine that does not focus on a NIAID 
Category A, B, or C priority pathogen will be deemed unresponsive and 
returned to the applicant without review.

Development activities supported under this program may include, but are not 
limited to, one or more of the following areas:

o Testing of previously evaluated adjuvants for their capacity to stimulate 
enhanced immune responses toward specific NIAID category A, B or C priority 
pathogens/toxins; 
o Testing mixtures of adjuvants to evaluate additive or synergistic potential 
to safely stimulate desired immune responses;
o GLP or GMP production;
o Optimization of delivery platform(s), including antigen and adjuvant 
combinations/formulations;
o Optimization of dose, dosing interval, and route of delivery in pre-
clinical evaluation; and
o Performing pre-clinical testing for safety and efficacy in animal models 
and other benchmarks required for moving candidate adjuvants into Phase I 
clinical trials.

NOTE: Clinical trials for adjuvants will NOT be supported. 

The application should comprise a development plan that begins with an 
identified and characterized adjuvant or immunostimulatory compound and 
develops a sound scientific rationale for its forward progression through the 
product development pathway.  A research and development plan must be 
included that defines the potential ultimate product, proposed project goal 
and interim objectives (development milestones); identifies alternative 
approaches; and provides a schedule for milestone and goal attainment.  

THERAPEUTICS FOR BIODEFENSE

The need for safe and effective, broad-spectrum and specific antimicrobials 
for biodefense against highly pathogenic agents or their toxins is a key 
national priority.  Applications for development of novel antivirals, 
antitoxins, immunotherapies, and antibiotics against NIAID Category A, B, and 
C priority pathogens are responsive to this RFA. The further characterization 
of immunotherapeutics such as antimicrobial peptides, antibodies, lectins, or 
immune modulators that provide either broad protection or pathogen specific 
protection against antigens from NIAID category A, B, or C priority pathogens 
are also responsive.

Activities to support the further development of previously identified 
therapeutics may include, but are not limited to, one or more of the 
following areas:

o Lead optimization by structure activity studies, medicinal chemistry, 
molecular modeling and/or library screening to improve the antimicrobial 
activity, pharmacology, and safety of the drug candidate;  
o Synthesis of sufficient quantities of a lead compound(s) for  further 
characterization, including efficacy and toxicity in in vitro or in vivo 
models; 
o Performing preliminary pharmacokinetic and pharmacodynamic analyses; 
assessing bioavailability and mechanism of action;
o Evaluating the potential for the emergence of drug resistance in model 
systems;
o Determining drug interactions in host molecular processes; and
o Performing required benchmarks for moving a drug candidate into Phase I 
clinical trials (http://www.fda.gov/cder/regulatory/default.htm).

NOTE: Clinical trials for therapeutics will NOT be supported.

Applications should focus on the further development and testing of the 
therapeutic identified in one of the above areas deemed responsive to this 
program.  The application should include a sound scientific rationale for the 
further development of the product.  A research and development plan must be 
included that defines the proposed project goal, interim objectives 
(development milestones) and potential ultimate product, and provides a 
timeline for milestone and goal attainment.

NOTE: All NIAID Category A, B, and C priority pathogens are responsive to 
this RFA. For applications for development of therapeutics for Bacillus 
anthracis, of particular interest  are projects involving the development of  
therapeutics that affect the persistence, germination, clearance, and 
inactivation (host immune response mechanisms) of spores in the lung and/or 
mediastinal lymph nodes. For applications for development of therapeutics for 
influenza, of particular interest are projects involving the development of 
therapeutics that address pandemic influenza issues.

DIAGNOSTICS FOR BIODEFENSE

There is an urgent need for rapid, highly sensitive, specific, easy to use, 
and cost-effective diagnostics for public health laboratories, hospital-based 
clinical laboratories, and point-of-care use to identify or diagnose 
individuals exposed to biological threat agents or their toxins. Diagnostic 
tools that will rapidly distinguish whether an individual is infected by a 
biological threat agent or a common infection with similar, generalized 
symptoms and determine drug sensitivities are of high priority, as are 
diagnostic tools for the simultaneous detection and identification of a broad 
range of infectious agents in clinical specimens.  This program supports the 
further development of sensitive, specific, and rapid diagnostics against all 
NIAID Category A, B, and C priority pathogens.  

To be responsive to this program, applications must focus on diagnostic 
assays and technologies that previously have demonstrated proof-of-concept in 
early stages of development. Applications should focus on the further 
development and validation of assays and technologies for NIAID Category A, 
B, or C priority pathogens and include a description of the capabilities of 
the diagnostics; a description of how the diagnostic/technology will be used; 
and plans for determining the sensitivity, specificity and validation of the 
diagnostic.  

NOTE: This program does NOT support applications for the development of 
environmental detection devices or their deployment.  As such, applications 
for the development of environmental detection devices and/or their 
deployment will be deemed unresponsive and returned to the applicant without 
review.
 
Activities to support the further development of diagnostics may include, but 
are not limited to, one or more of the following areas: (we agree this is 
fine and have removed the prior language).

o Technologies capable of high throughput screening using multiple biomarkers 
to identify multiple pathogens simultaneously and/or human immune or other 
physiological response to infection (e.g. platform-based technologies);
o Tests to evaluate antimicrobial resistance, enhanced virulence, or genetic 
manipulation;
o Technologies that integrate multiple methods of parallel measurements for 
detection in the same platform, such as detecting nucleic acids and proteins 
from multiple agents in the same assay;
o Technologies for multiplex rapid nucleic acid or antigen detection using 
novel and improved methodologies and reagents; and
o In vivo imaging methods and development of contrast reagents for 
visualization of pathogens or host immune responses in vivo.

MECHANISM OF SUPPORT

This RFA will use the NIH Challenge Grant - Cooperative Agreement (UC1), an 
"assistance" mechanism, rather than an "acquisition" mechanism, in which 
substantial NIH scientific and/or programmatic involvement with the awardee 
is anticipated during the performance of the activity.  The applicant will be 
solely responsible for planning, directing, and executing the proposed 
project.  This RFA is a one-time solicitation.  Future unsolicited, 
competing-continuation applications based on this project will compete with 
all investigator-initiated applications and will be reviewed according to the 
customary peer review procedures.  The anticipated award date is July, 2005.  
Applications that are not funded in the competition described in this RFA may 
be resubmitted as NEW investigator-initiated applications using the standard 
receipt dates for NEW applications described in the instructions to the PHS 
398 application.  

The NIH UC1 is a cooperative agreement award mechanism in which the Principal 
Investigator retains the primary responsibility and dominant role for 
planning, directing, and executing the proposed project, with NIH staff being 
substantially involved as a partner with the Principal Investigator, as 
described under the section "Cooperative Agreement Terms and Conditions of 
Award." Essential elements of the challenge grant cooperative agreement 
mechanism include:  (1) a single Principal Investigator who will be 
scientifically and administratively responsible for the research and 
development effort; (2) a single applicant organization that will be legally 
and financially responsible for the use and disposition of funds awarded; and 
(3) interim research and development targets upon whose achievement the next 
increment of funds will be released to the awardee.  Recognizing that product 
development is often an iterative and sequential process, and that steps 
early in the process may not be successful and may need to be modified or 
reworked, NIAID staff, through the cooperative agreement grant mechanism, 
will be actively involved as a member of the partnership by evaluating the 
milestones of awardees and determining whether additional investment in the 
development of the product is warranted.

Awards will be made for a period of up to three years and will be 
performance-based.  That is, funds will be awarded in increments based on the 
attainment of interim research objectives defined by the applicant and 
approved by the NIAID (See APPLICATION INSTRUCTIONS and TERMS AND CONDITIONS 
OF AWARD below).  Because funding will be tied to the attainment of interim 
research objectives/milestones, funding will not be provided annually as is 
traditional for NIH grants, but will be linked to the interim research 
objectives.  A separate budget is required for each interim research 
objective/milestone proposed.  Initial release of funds will be to support 
achievement of the first interim objective/milestone.  Release of the next 
funding increment will be based on the achievement of the previous interim 
objective as determined by NIAID staff.  

The total project period for applications submitted in response to this RFA 
may not exceed three years.  At this time, the NIAID has not determined 
whether and how this solicitation will be continued beyond the present RFA.

This RFA uses just-in-time concepts, but not modular grant budgets.  

FUNDS AVAILABLE

The estimated total funds [direct and facilities and administrative (F&A) 
costs] available for all awards for the entire length of the program will be 
$30 million to be awarded in fiscal year 2005.  As a result, in FY2005, the 
NIAID plans to fund approximately 4-8 awards.

It is anticipated that award budgets will vary widely in amount from hundreds 
of thousands to millions of dollars. The NIAID is seeking to fund a range of 
product development projects based on scientific merit and public health 
needs and priorities.  An applicant may request up to $300,000 for major 
equipment.  Although this program is provided for in the financial plans of 
the NIAID, awards pursuant to this RFA are contingent upon the availability 
of funds for this purpose and the receipt of a sufficient number of 
applications of high scientific merit. Continued funding will be contingent 
upon satisfactory progress on timelines and milestones.  At this time, the 
NIAID has not determined whether and how this solicitation will be continued 
beyond this present program.

ELIGIBLE INSTITUTIONS

The applicant may submit (an) application(s) if the institution has any of 
the following characteristics:

o For-profit or non-profit organizations 
o Public or private institutions, such as universities, colleges, hospitals, 
and laboratories 
o Units of State and local governments
o Eligible agencies of the Federal government
o Domestic and foreign institutions/organizations
o Faith-based or community-based organizations
FOREIGN ORGANIZATIONS

Several special provisions apply to applications submitted by foreign 
organizations.
 
o Charge back of customs and import fees is not allowed.
o Format: every effort should be made to comply with the format 
specifications, which are based
 upon a standard US paper size of 8.5" x 11."
o Funds for up to 8% administrative costs can now be requested, 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-01-028.html)
o Organizations must comply with federal/NIH policies on human subjects, 
animals, and biohazards. 
o Organizations must comply with federal/NIH biosafety and biosecurity 
regulations. See TERMS AND CONDITIONS OF AWARD below.

INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS

Any individual with the skills, knowledge, and resources necessary to carry 
out the proposed research is invited to work with their institution to 
develop an application for support.  Individuals from underrepresented racial 
and ethnic groups as well as individuals with disabilities are always 
encouraged to apply for NIH programs.

SPECIAL REQUIREMENTS

This program responds to the urgent public health need to advance new and 
promising high-priority products for biodefense by supporting partnerships 
between the private sector and the Federal Government.  Applications in 
response to this program are limited to the development of vaccines, 
adjuvants, therapeutics and diagnostics against NIAID Category A, B, and C 
priority pathogens that have demonstrated proof-of-concept.  Each application 
must propose a milestone-driven, timeline-based project whose goal is to 
further the development of that product as specified above.  Ancillary 
research studies that are not directly relevant to the development of the 
selected product will not be supported.  

1. Budget  

Because awards made under this program will be performance-based and 
milestone-driven, funding will be tied to the successful attainment of 
interim research objectives (milestones), and may not be provided annually as 
is traditional for NIH grants.  Budget submissions must be linked to the 
interim objectives/milestones and final product(s) rather than the 
traditional annual budget periods requested in NIH grants.  Applicants must 
include separate, complete budget pages (Form Page 4 - Detailed Budget for 
Initial Budget Period) for each interim research objective/milestone, for 
each project.  The initial budget period is defined as the time period needed 
to complete the first interim objective/milestone, and the funds requested 
should be those needed to attain the first interim milestone. In the upper 
right-hand corner of the first Form Page 4, enter the proposed "From" and 
"Through" dates for research to complete the first interim objective. 
Complete the balance of the form based on the efforts to be performed during 
this interval. Initial release of funds will be to support achievement of the 
first interim objective/milestone. The budgets for the second budget period 
should be that needed to attain the second interim objective (or the final 
product if there is no second interim objective), and the third budget period 
shows the funds needed to complete the R&D effort (if there were two interim 
objectives).  Each additional Form Page 4 submitted in support of each 
milestone must also state proposed “From” and “Through” dates for that 
specific milestone.  Release of subsequent funding increments will be based 
on the achievement of the previous interim objective as determined by NIAID 
staff. 

Form Page 5 - Budget for Entire Proposed Period of Support – The budgets for 
each budget period must indicate the funds needed to attain the interim 
objectives/milestones and should not be annually-based on an annual basis.  
Since these budget periods are tied to performance and not to the calendar, 
the budgets can be for periods of more than or less than one year.

2. Product Development Plan

Applicants MUST include a section entitled “Product Development Plan” in the 
application which may not exceed 5 pages.  The Product Development Plan does 
not count towards the page limits for the Research Plan.  This section must 
describe a plan for the further commercial development of the candidate 
product(s).  It must include:

o A clear description of the goal(s) of the project, including one (or more) 
final product(s) or stage(s) of development to be completed during the award 
period.  Some examples could be: an Ebola vaccine candidate requiring scale-
up or an anthrax drug needing toxicity testing.  This section must also state 
all interim milestones to be achieved during the course of the project and 
identify any impediments that could require a revision in the work plan or 
milestones with alternative approaches.  Some examples of interim objectives 
could be: completion of a prototype of a diagnostic tool or animal 
immunogenicity studies.

It is suggested that an applicant propose no more than four interim 
objectives/milestones and a final objective.  An example of an interim 
milestone could be the production of a GMP vaccine candidate or a decision as 
to which drug candidate will advance to pre-clinical testing. This section 
should include information that demonstrates that the applicant understands 
the steps that are required for advancing a candidate product as proposed in 
the application. For additional details on vaccines, see: 
http://www.fda.gov/cber/vaccine/vacappr.htm. For additional details on 
therapeutics, see: http://www.fda.gov/cder/regulatory/default.htm. For 
additional details on diagnostics, see: http://www.fda.gov/cdrh.

o A detailed schedule or timeline for the anticipated attainment of each 
milestone and the overall goal(s).

o Criteria that clearly describe how decisions will be made to advance a 
product through the proposed product development pathway. In other words, 
provide criteria by which "go" or "no go" decisions will be made for each 
milestone.  

3. Physical and/or Facility Security

Applicants must address issues related to physical or facility security and 
biocontainment and biosafety pertinent to the specific pathogens of interest 
in a Biosafety and Biocontainment section of the application. In addition, 
biosafety procedures and personnel biosafety training should be addressed.

4. Good Laboratory Practice

When appropriate, research plans should include an awareness of the 
guidelines that govern GLP as defined by 21 CRF (58) and GMP, as defined by 
21 CRF (211), manufacturing and/or IND enabling studies that will be 
performed with this award as they would be applicable to eventual product 
licensure in the U.S.

5. Intellectual Property

The successful development of high priority products for biodefense will 
require substantial investment and support of private sector industries and 
may also involve collaborations with multiple organizations, including 
academic and/or non-profit research institutions.  It is the intent of this 
initiative to support the formation of the appropriate public-private 
partnerships that are essential to meet these urgent public health needs.  
NIAID recognizes that intellectual property rights are likely to play an 
important role in achieving the goals of this program.  To this end, the 
NIAID requires that at the time of application, all applicants provide a 
letter ("Proprietary Rights Assurance Letter") containing the following 
assurances, which is signed by a representative who is duly authorized to 
provide such assurances on behalf of the applicant organization:

o Applicant is solely responsible for the timely acquisition of all 
proprietary rights, including intellectual property rights, and all materials 
needed for applicant to perform the project;
o Applicant acknowledges that prior to, during, and subsequent to the award, 
the U.S. Government is not required to obtain for applicant any proprietary 
rights, including intellectual property rights, or any materials needed by 
applicant to perform the project;
o Applicant acknowledges the requirement to report to the U.S. Government all 
inventions made in the performance of the project, as specified at 35 U.S.C. 
Sect. 202 (Bayh-Dole Act).

The Proprietary Rights Assurance Letter should be included with the 
application preceding the checklist page.

Apart from the Proprietary Rights Assurance Letter, applicants are encouraged 
to reach early consensus with their proposed partners regarding intellectual 
property and other legal matters that may arise during the project.  In 
addition, applicants are expected to exercise their Bayh-Dole rights in a 
manner that does not conflict with the goals of this award or the intent of 
the Bayh-Dole Act to promote the utilization, commercialization and 
availability of U.S. Government-funded inventions for public benefit. 
Finally, applicants are expected to make new information and materials known 
to the research community in a timely manner through publications, web 
announcements, and reports to the NIAID or other mechanisms.

6. Select Agents

All awardee institutions, foreign and domestic, must confirm that they are in 
compliance with Select Agent regulations (http://www.cdc.gov/od/sap/) and NIH 
Guidelines for Research Involving Recombinant DNA Molecules 
(http://www4.od.nih.gov/oba/rac/guidelines/guidelines.html) to receive 
funding from NIAID. See COOPERATIVE AGREEMENT TERMS AND CONDITIONS OF AWARD 
below.

7. Meetings

A critical determinant of success of the project is likely to be the degree 
of communication among the grantee organization, any collaborating 
institutions (if applicable), and the NIH and/or other U.S. government 
agencies. It is mandatory that the Principal Investigator, one or two key 
personnel designated by the Principal Investigator, two external advisors, 
and the NIAID Program Officer meet once a year to review progress and aid 
program development. To facilitate this mandatory meeting, proposed budgets 
must include funds for travel of the Principal Investigator, key personnel, 
and two external advisors (to be named after award by NIAID in consultation 
with the Principal Investigator) to an annual two-day meeting in Bethesda, 
Maryland, or at a relevant scientific meeting, as determined by NIAID Program 
staff. Names of suggested external advisors should not be included in the 
application.

Where scientifically appropriate, NIAID may ask grant recipients to 
collaborate or cooperate with other NIAID-funded projects and/or US 
government agencies, for example, the Food and Drug Administration, the 
Centers for Disease Control and Prevention, and the United States Department 
of Agriculture.

COOPERATIVE AGREEMENT TERMS AND CONDITIONS OF AWARD

The following terms and conditions will be incorporated into the award 
statement and provided to the Principal Investigator as well as the 
institutional official at the time of award.

These special Terms of Award are in addition to, and not in lieu of, 
otherwise applicable OMB administrative guidelines, HHS Grant Administration 
Regulations at 45 CFR part 74 and 92, and other HHS, PHS, and NIH Grant 
Administration policy statements.

The administrative and funding instrument used for this program is the 
challenge grant cooperative agreement (UC1), an “assistance” rather than an 
“acquisition” mechanism, in which substantial NIH scientific and/or 
programmatic involvement with the awardee is anticipated during the 
performance of the activity. Under the cooperative agreement, the NIH purpose 
is to support and/or stimulate the recipient's activity by involvement in and 
otherwise working jointly with the award recipient in a partnership role, but 
it is not to assume direction, prime responsibility, or a dominant role in 
the activity. Consistent with this concept, the dominant role and prime 
responsibility for the activity resides with the awardees for the project as 
a whole, although specific tasks and activities in carrying out the research 
will be shared among the awardees and the NIAID Program Officer.  

1.  Monitoring Clinical Studies

When clinical studies are a component of the research proposed, NIAID policy 
requires that studies be monitored commensurate with the degree of potential 
risk to study subjects and the complexity of the study. AN UPDATED NIAID 
policy was published in the NIH Guide on July 8, 2002 and is available at: 
http://grants.nih.gov/grants/guide/notice-files/NOT-AI-02-032.html. The full 
policy, including terms and conditions of award, is available at: 
http://www.niaid.nih.gov/ncn/pdf/clinterm.pdf.

2.  Awardee Rights and Responsibilities

Awardees will have primary responsibility for defining the research 
objectives, approaches and details of the projects within the guidelines of 
the RFA and for performing the scientific activity. Specifically, awardees 
have primary responsibility as described below.

Awardees may be from industry or academia; however, the industrial portion of 
the partnership is critical for compliance and substantive investment by 
industry directed to the specific project being proposed must be clearly 
defined.  

The awardee must be in compliance with Select Agent Rule 
(http://www.cdc.gov/od/sap/) and NIH Guidelines for Research Involving 
Recombinant DNA Molecules 
(http://www4.od.nih.gov/oba/rac/guidelines/guidelines.html).

The NIH has established a new policy regarding the use of NIH funds for 
research involving Select Agents. This policy is being implemented using 
Terms of Award that are to be included in any grant, cooperative agreement, 
or contract in which select agents are or will be used.

Award to a U.S. Institution: This award includes research involving Select 
Agents (see 42 CFR 73 for the Select Agent list; and 7 CFR 331 and 9 CFR 121 
for the relevant animal and plant pathogens). Before using NIH funds, the 
awardee must complete registration with CDC (or USDA, depending on the 
agent).  No funds can be used for research involving Select Agents if the 
final registration certificate is denied.

Award to Foreign Institution: This award includes research involving Select 
Agents (see 42 CFR 73 for the Select Agent list; and 7 CFR 331 and 9 CFR 121 
for the relevant animal and plant pathogens). Before using NIH funds for any 
work directly involving the Select Agents, the awardee must provide 
information satisfactory to the NIH that a process equivalent to that 
described in 42 CFR 73 for US institutions is in place and will be 
administered on behalf of all Select Agent work sponsored by these funds. The 
awardee must be willing to address the following key elements appropriate for 
their institutions: safety, security, training, procedures for ensuring that 
only approved/appropriate individuals have access to the Select Agents, and 
any applicable laws, regulations and policies equivalent to 42 CFR 73.

Award to U.S. Institution with Foreign Institution Participation: This award 
includes research involving Select Agents (see 42 CFR 73 for the Select Agent 
list; and 7 CFR 331 and 9 CFR 121 for the relevant animal and plant 
pathogens). Before using NIH funds for any work directly involving the Select 
Agent at the US institution, the awardee must complete registration with CDC 
or USDA, depending on the agent).  No funds can be used for research 
involving Select Agents if the final registration certificate is denied. 
Before using NIH funds for any work directly involving the Select Agents at 
the foreign institution, the US awardee must provide information from the 
foreign institution satisfactory to the NIH that a process equivalent to that 
described in 42 CFR 73 for US institutions is in place and will be 
administered on behalf of all Select Agent work sponsored by these funds. The 
awardee must be willing to address the following key elements appropriate for 
the foreign institution: safety, security, training, procedures for ensuring 
that only approved/appropriate individuals have access to the Select Agents, 
and any applicable laws, regulations and policies equivalent to 42 CFR 73.

The Principal Investigator retains primary responsibility for the performance 
of the scientific activity, and agrees to accept close assistance in 
coordination, cooperation and participation of NIAID staff in scientific and 
technical management of the project in accordance with the terms formally and 
mutually agreed upon prior to the award.  The responsibility for the 
planning, direction, and execution of the proposed project will be solely 
that of the Principal Investigator.

Meetings: One mandatory progress review meeting of the awardees will be held 
annually at the NIAID, or at a site designated by the NIAID Program Officer, 
during which the Principal Investigator and Project Leaders will present 
significant findings. The NIAID Program Officer and External Advisors (when 
applicable) will be present.  A critical determinant of success will be the 
degree of communication between the Principal Investigator, Project Leaders 
and other significantly involved parties. Therefore, in addition to the one 
meeting listed above, additional meetings, which may be necessary for 
coordination of cooperative agreement activities, may be scheduled if 
justified. Regular telephone and written communication with the NIAID Program 
Officer is considered to be very important and is strongly encouraged.

Publications: The Principal Investigator will be responsible for the timely 
submission of all abstracts, manuscripts and reviews (co)authored by members 
of the grant and supported in part or in total under this Agreement. The 
Principal Investigator and Project Leaders are requested to submit 
manuscripts to the Program Officer within two weeks of acceptance for 
publication so that an up-to-date summary of program accomplishments can be 
maintained and joint press conferences and press releases prepared.  
Publications or oral presentations of work performed under this Agreement are 
the responsibility of the Principal Investigator and appropriate Project 
Leaders and will require appropriate acknowledgement of NIAID support. Timely 
publication of major findings is encouraged.

While the NIAID Program Officer has a right of access to the data (see NIAID 
staff responsibilities below) the awardee will retain custody of and right to 
the data. For more information on data sharing go to: 
http://grants.nih.gov/grants/policy/data_sharing/index.htm.  

3. NIAID Staff Responsibilities

The NIAID Program Officer will provide normal stewardship and will have 
substantial scientific/programmatic involvement during the conduct of this 
activity through technical assistance, advice and coordination above and 
beyond normal program stewardship for grants, as described below.

The NIAID Program Officer will serve as a liaison/facilitator between the 
awardee, pharmaceutical and  biotechnology industries, and other government 
agencies (e.g., FDA, USDA, CDC), and will serve as a resource of scientific 
and policy information related to the goals of the awardee's research. The 
NIAID Program Officer will facilitate coordination of project activities 
during the course of the project.

The NIAID Program Officer will assist the awardee with access to other NIAID-
supported resources and services, including resources for preclinical 
development such as animal models, screening facilities, standardized 
research reagents, and a genomics resource center, where available.

4.  Collaborative Responsibilities

The specific timelines, interim objectives and funding levels agreed to by 
the awardee and the NIAID shall be included in the terms and conditions of 
award. Given the nature of product development, it is recognized that 
timelines and interim objectives may require revision and renegotiation 
during the course of the project period. The Principal Investigator and NIAID 
must agree to all such revisions. Release of each funding increment by NIAID 
will be based on a NIAID review of progress towards achieving the previously 
agreed upon interim objective. Where scientifically appropriate, NIAID may 
ask awardees to collaborate or cooperate with other NIAID-funded projects 
and/or US government agencies, for example CDC, FDA, and/or USDA.

5.  Arbitration

Any disagreement that may arise on scientific/programmatic matters (within 
the scope of the award), between award recipients and IC may be brought to 
arbitration.  An arbitration panel will be composed of three members – one 
chosen by the awardee, a second member selected by the IC, and the third 
member selected by the two prior selected members.  This special arbitration 
procedure in no way affects the awardee's right to appeal an adverse action 
that is otherwise appealable in accordance with the PHS regulations at 42 CFR 
Part 50, Subpart D and HHS regulation at 45 CFR Part 16.

These special Terms of Award are in addition to and not in lieu of otherwise 
applicable OMB administrative guidelines, HHS Grant Administration 
Regulations at 45 CFR Parts 74 and 92, and other HHS, PHS, and NIH Grant 
Administration policy statements.

WHERE TO SEND INQUIRIES

We encourage your inquiries concerning this RFA and welcome the opportunity 
to answer questions from potential applicants. Inquiries may fall into three 
areas: scientific/research, peer review, and financial or grants management 
issues:

o Direct inquires regarding general scientific, technical, and programmatic 
issues to:

Dr. Michael Kurilla
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Diseases  
Room 5030, MSC-6603
6610 Rockledge Drive
Bethesda, MD  20892-6603
Telephone:  (301) 496-5305
FAX: (301) 496-8030
E-Mail: mk486x@nih.gov

o Direct your questions about scientific/research issues on VACCINES to:

Dr. Cristina Cassetti 
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Diseases  
Room 5032, MSC-6603
6610 Rockledge Drive
Bethesda, MD  20892-6603
Telephone: (301) 451-3745
FAX:  (301) 496-8030
E-Mail: cc125b@nih.gov

o Direct your questions about scientific/research issues on ADJUVANTS to:

Dr. David Winter  
Division of Allergy, Immunology and Transplantation
National Institute of Allergy and Infectious Diseases  
Room 3014, MSC-6601
6610 Rockledge Drive
Bethesda, MD  20892-6601
Telephone:  (301) 496-7551
FAX: (301) 480-2381
E-Mail: dw322u@nih.gov

o Direct your questions about scientific/research issues on THERAPEUTICS to:

Dr. Mark Challberg
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Diseases  
Room 4095, MSC-6603
6610 Rockledge Drive
Bethesda, MD  20892-6603
Telephone:  (301) 496-7453
FAX:  (301) 480-1594
E-Mail:  mc37e@nih.gov 

o Direct your questions about scientific/research issues on 
IMMUNOTHERAPEUTICS to:

Dr. Alison Deckhut 
Division of Allergy, Immunology and Transplantation
National Institute of Allergy and Infectious Diseases  
Room 3007, MSC-6601
6610-B Rockledge Drive
Bethesda, MD  20892-6601
Telephone:  (301) 496-7551
FAX:  (301) 402-2571
E-Mail:  ad122x@nih.gov 

o Direct your questions about scientific/research issues on DIAGNOSTICS to:

Dr. Maria Giovanni
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Diseases
Room 6007, MSC-6603  
6610 Rockledge Drive
Bethesda, MD  20892-6603
Telephone: (301) 496-5305
FAX: (301) 496-8030 
E-Mail:  mg37u@nih.gov

Direct your questions about peer review issues to:

Dianne Tingley, Ph.D.
Division of Extramural Activities 
National Institute of Allergy and Infectious Diseases
Room 3133, MSC-7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616 (20817 for express mail or courier service)
Telephone: (301) 496-0818
FAX: (301) 402-2638
Email:   mh30x@nih.gov  

o Direct your questions about financial or grants management matters to:  

Ms. Pamela Fleming
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 2119, MSC-7614
6700-B Rockledge Drive
Bethesda, MD 20892-7614
Telephone:  (301) 496-7075
FAX:  (301) 480-3780
E-Mail: pf49e@nih.gov  

LETTER OF INTENT

Prospective applicants are asked to submit a letter of intent that includes 
the following information:

o Descriptive title of the proposed research 
o Name, address, and telephone number of the Principal Investigator
o Names of other key personnel
o Participating institutions
o Number and title of this RFA

Although a letter of intent is not required, is not binding, and does not 
enter into the review of a subsequent application, the information that it 
contains allows IC staff to estimate the potential review workload and plan 
the review.
 
The letter of intent is to be sent by the date listed at the beginning of 
this document. The letter of intent should be sent to:

Dianne Tingley, Ph.D.
Division of Extramural Activities 
National Institute of Allergy and Infectious Diseases
Room 3133, MSC-7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616 (20817 for express mail or courier service)
Telephone: (301) 496-0818
FAX: (301) 402-2638
Email:   mh30x@nih.gov  

SUBMITTING AN APPLICATION

Applications must be prepared using the PHS 398 research grant application 
instructions and forms (rev. 5/2001). Applications must be submitted as new 
applications; revised applications previously submitted in response to former 
RFAs will not be viewed as responsive to this RFA and will be returned. 
Applications must have a DUN and Bradstreet (D&B) Data Universal Numbering 
System (DUNS) number as the Universal Identifier when applying for Federal 
grants or cooperative agreements. The DUNS number can be obtained by calling 
(866) 705-5711 or through the web site at http://www.dunandbradstreet.com/. 
The DUNS number should be entered on line 11 of the face page of the PHS 398 
form. The PHS 398 document is available at 
http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive 
format.  For further assistance contact GrantsInfo, Telephone (301) 435-0714, 
Email: GrantsInfo@nih.gov. 

SUPPLEMENTARY INSTRUCTIONS:

Applications must address each item described under the SPECIAL REQUIREMENTS 
section, as applicable.  In addition, responses to this RFA should follow the 
PHS 398 instructions with the following modifications:

o Form Page 2 – Description – The first sentence of the description should 
identify the primary focus of the work proposed as either Vaccines for 
Biodefense, Adjuvants for Biodefense, Therapeutics for Biodefense, or 
Diagnostics for Biodefense.

o Form Page(s) 4 - Given the anticipated complexity of applications and the 
likelihood for multi-organizational arrangements, applicants should pay 
special attention to the preparation of a detailed budget which provides a 
thorough justification for all key personnel, equipment, consultant costs, 
and travel expenses.  Separate budgets must be submitted for each interim 
objective/milestone (See SPECIAL REQUIREMENTS Section).  Budget materials do 
not count against the page limitations. Continuation pages should be used 
when necessary to provide a complete budget justification. This RFA does not 
use the modular budget format. 

o Research Plan: Must have the following four sections and may not exceed 25 
pages:

1. Specific Aims - What do you intend to do?  What product or products will 
be developed?

2. Background and Significance - Why is the R&D important? What is the 
potential public health benefit? What is the probability of a beneficial 
product?

3. Preliminary Studies - What has already been done? How does this support 
the proposed R&D effort?

4. Research Methods - How are you going to perform the R&D effort?

o The Proprietary Rights Assurance Letter should be included with the 
application preceding the checklist page.

USING THE RFA LABEL: The RFA label available in the PHS 398 (rev. 5/2001) 
application form must be affixed to the bottom of the face page of the 
application. Type the RFA number on the label.  Failure to use this label 
could result in delayed processing of the application such that it may not 
reach the review committee in time for review.  In addition, the RFA title 
and number must be typed on line 2 of the face page of the application form 
and the YES box must be marked. The RFA label is also available at: 
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf.

SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten original of 
the application, including the checklist, and three signed photocopies in one 
package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD  20892-7710
Bethesda, MD  20817 (for express/courier service)

At the time of submission, two additional exact copies of the grant 
application and all five sets of any appendix material must be sent to:

Dianne Tingley, Ph.D.
Division of Extramural Activities 
National Institute of Allergy and Infectious Diseases
Room 3133, MSC-7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616 (20817 for express/courier service)

Applications must be received on or before January 18, 2005. Applications 
that are not received as a single package on the receipt date will be judged 
non-responsive and will be returned to the applicant.

It is highly recommended that the appropriate NIAID program contact be 
consulted before submitting the letter of intent and during the early stages 
of preparation of the application. (See program contact under INQUIRIES).

APPLICATION PROCESSING: 

The Center for Scientific Review (CSR) will not accept any application in 
response to this RFA that is essentially the same as one currently pending 
initial review, unless the applicant withdraws the pending application. 
However, when a previously unfunded application, originally submitted as an 
investigator-initiated application, is to be submitted in response to an RFA, 
it is to be prepared as a NEW application. That is the application for the 
RFA must not include an Introduction describing the changes and improvements 
made, and the text must not be marked to indicate the changes from the 
previous unfunded version of the application. While the investigator may 
still benefit from the previous review, the RFA application is not to state 
explicitly how.

Although there is no immediate acknowledgement of the receipt of an 
application, applicants are generally notified of the review and funding 
assignment within 8 weeks.

PEER REVIEW PROCESS  
 
Upon receipt, applications will be reviewed for completeness by the CSR and 
responsiveness by NIAID. Incomplete and/or nonresponsive applications will be 
returned to the applicant without further consideration.  

Applications that are complete and responsive to the RFA will be evaluated 
for scientific and technical merit by an appropriate peer review group 
convened by the NIAID in accordance with the review criteria stated below.  
Depending on the total number and research topics of applications received in 
response to this RFA, applications may be separated into subgroups for review 
by different peer review committees.  As part of the initial merit review, 
all applications will:

o Undergo a selection process in which only those applications deemed to have 
the highest scientific merit, generally the top half of applications under 
review, will be discussed and assigned a priority score
o Receive a written critique
o Receive a second level review by the National Advisory Allergy and 
Infectious Diseases Council

REVIEW CRITERIA    

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  In 
the written comments, reviewers will be asked to evaluate the application in 
order to judge the likelihood that the proposed research will have a 
substantial impact on the pursuit of these goals. The scientific review group 
will address and consider each of the following criteria in assigning the 
application's overall score, weighting them as appropriate for each 
application. 

o Significance 
o Approach 
o Innovation
o Investigator
o Environment
  
The application does not need to be strong in all categories to be judged 
likely to have major scientific impact and thus deserve a high priority 
score.  For example, an investigator may propose to carry out important work 
that by its nature is not innovative but is essential to move a field 
forward.

o SIGNIFICANCE:  Is this project likely to significantly advance the 
development of a vaccine, adjuvant, therapeutic, or diagnostic against the 
specific biologic threat agent identified in this initiative? If the aims of 
the application are achieved, are important biomedical agents or products 
likely to result?  What will be the effect of these studies on the concepts 
or methods that drive this field? 

o APPROACH:  Does the application clearly articulate the development of a 
candidate product?  Are the conceptual framework, design, methods, and 
analyses adequately developed, well integrated, and appropriate to the aims 
of the project?  Does the applicant acknowledge potential problem areas and 
consider alternative tactics? Is the industry commitment adequate to have an 
impact on the success of the proposed research objectives? Is the likelihood 
of successful project completion high given the current state of research and 
development and the technical approach? Does the application clearly 
delineate appropriate timelines and interim milestones and are they 
appropriate, feasible and technically sound? 

o INNOVATION:  If appropriate, does the project employ novel concepts, 
approaches, or methods?  Are the aims original and innovative?  Does the 
project challenge existing paradigms or develop new methodologies or 
technologies?
NOTE: The NIAID recognizes that the inherent nature and demands of the 
product development process may require funding large, complex grants with 
interdependent specific aims.  Furthermore, some aspects of the product 
development process (e.g., large-scale production) are inherently not 
innovative. 

o INVESTIGATOR:  Is the research and development team appropriately trained 
and experienced and well suited to carry out this work?  Is the work proposed 
appropriate to the experience level of the principal investigator and other 
researchers (if any)? Is there strong evidence of substantive industrial 
commitment?

o ENVIRONMENT:  Does the environment in which the work will be done 
contribute to the probability of success?  Do the proposed experiments take 
advantage of unique features of the scientific environments, including 
partnerships with industry, or employ useful collaborative arrangements?  Is 
there adequate evidence of institutional support?

ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, the following 
items will be considered in the determination of scientific merit and the 
priority score:

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 criteria included in the 
section on Federal Citations, below)
 
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.  Plans for the recruitment and retention of subjects will also be 
evaluated. (See Inclusion Criteria in the sections on Federal Citations, 
below).

CARE AND USE OF VERTEBRATE ANIMALS IN RESEARCH: If vertebrate animals are to 
be used in the project, the five items described under Section f of the PHS 
398 research grant application instructions (rev. 5/2001) will be assessed.  

ADDITIONAL REVIEW CONSIDERATIONS

RFA-specific review criteria:

o The scientific rationale and basis for the candidate product, including the 
strength of existing data on product feasibility, safety, and potential 
efficacy
o The appropriateness of the proposed project in terms of the stage of 
development of the candidate product
o The appropriateness and feasibility of defined objectives/milestones
o Feasibility of future product development
o The appropriateness and feasibility of conducting or field evaluation 
during the period of award.

SHARING RESEARCH DATA: Applicants requesting more than $500,000 in direct 
costs in any year of the proposed research are expected to include a data 
sharing plan in their application. The reasonableness of the data sharing 
plan or the rationale for not sharing research data will be assessed by the 
reviewers. However, reviewers will not factor the proposed data-sharing plan 
into the determination of scientific merit or priority score. (See 
instructions and URL to policy in the Federal Citations, below.)
 
BUDGET:  The reasonableness of the proposed budget and the requested period 
of support in relation to the proposed research.

RECEIPT AND REVIEW SCHEDULE

Letter of Intent Receipt Date:      December 17, 2004
Application Receipt Date:           January 18, 2005
Peer Review Date:                   May, 2005
Council Review:                     June, 2005
Earliest Anticipated Start Date:    July, 2005

AWARD CRITERIA

Award criteria that will be used to make award decisions include: 

o Scientific merit of the proposed project as determined by peer review
o Availability of funds
o Programmatic priorities
o High priority public health needs

In addition, to achieve program balance, NIAID reserves the right to make 
awards to the most meritorious applications in various priority categories, 
including vaccines, therapeutics, adjuvants and diagnostics.
  
REQUIRED FEDERAL CITATIONS 

HUMAN SUBJECTS PROTECTION: Federal regulations (45CFR46) require that 
applications and proposals involving human subjects must be evaluated with 
reference to the risks to the subjects, the adequacy of protection against 
these risks, the potential benefits of the research to the subjects and 
others, and the importance of the knowledge gained or to be gained.  
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm

SHARING RESEARCH DATA: Investigators submitting an NIH application seeking 
more than $500,000 or more in direct costs in any single year are expected to 
include a plan for data sharing or state why this is not possible   
(http://grants.nih.gov/grants/policy/data_sharing). Investigators should seek 
guidance from their institutions, on issues related to institutional 
policies, local IRB rules, as well as local, state and Federal laws and 
regulations, including the Privacy Rule. Reviewers will consider the data 
sharing plan but will not factor the plan into the determination of the 
scientific merit or the priority score.

INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH: It is the policy of 
the NIH that women and members of minority groups and their sub-populations 
must be included in all NIH-supported clinical research projects unless a 
clear and compelling justification is provided indicating that inclusion is 
inappropriate with respect to the health of the subjects or the purpose of 
the research. This policy results from the NIH Revitalization Act of 1993 
(Section 492B of Public Law 103-43).

All investigators proposing clinical research should read the AMENDMENT "NIH 
Guidelines for Inclusion of Women and Minorities as Subjects in Clinical 
Research - Amended, October, 2001," published in the NIH Guide for Grants and 
Contracts on October 9, 2001 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); 
a complete copy of the updated Guidelines are available at
http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm

The amended policy incorporates: the use of an NIH definition of clinical 
research; updated racial and ethnic categories in compliance with the new OMB 
standards; clarification of language governing NIH-defined Phase III clinical 
trials consistent with the new PHS Form 398; and updated roles and 
responsibilities of NIH staff and the extramural community.  The policy 
continues to require for all NIH-defined Phase III clinical trials that: a) 
all applications or proposals and/or protocols must provide a description of 
plans to conduct analyses, as appropriate, to address differences by 
sex/gender and/or racial/ethnic groups, including subgroups if applicable; 
and b) investigators must report annual accrual and progress in conducting 
analyses, as appropriate, by sex/gender and/or racial/ethnic group 
differences.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS: 
The NIH maintains a policy that children (i.e., individuals under the age of 
21) must be included in all human subjects research, conducted or supported 
by the NIH, unless there are scientific and ethical reasons not to include 
them. 

All investigators proposing research involving human subjects should read the 
"NIH Policy and Guidelines" on the inclusion of children as participants in 
research involving human subjects that is available at 
http://grants.nih.gov/grants/funding/children/children.htm

REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS: NIH 
policy requires education on the protection of human subject participants for 
all investigators submitting NIH proposals for research involving human 
subjects.  This policy announcement is in the NIH Guide for Grants and 
Contracts Announcement, dated June 5, 2000, at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of research 
on hESCs can be found at http://stemcells.nih.gov/index.asp and at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html.  Only 
research using hESC lines that are registered in the NIH Human Embryonic Stem 
Cell Registry will be eligible for Federal funding (see http://escr.nih.gov).   
It is the responsibility of the applicant to provide, in the project 
description and elsewhere in the application as appropriate, the official NIH 
identifier(s)for the hESC line(s)to be used in the proposed research.  
Applications that do not provide this information will be returned without 
review. 

PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT: The 
Office of Management and Budget (OMB) Circular A-110 has been revised to 
provide public access to research data through the Freedom of Information Act 
(FOIA) under some circumstances.  Data that are (1) first produced in a 
project that is supported in whole or in part with Federal funds and (2) 
cited publicly and officially by a Federal agency in support of an action 
that has the force and effect of law (i.e., a regulation) may be accessed 
through FOIA.  It is important for applicants to understand the basic scope 
of this amendment.  NIH has provided guidance at 
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.

Applicants may wish to place data collected under this RFA in a public 
archive, which can provide protections for the data and manage the 
distribution for an indefinite period of time.  If so, the application should 
include a description of the archiving plan in the study design and include 
information about this in the budget justification section of the 
application. In addition, applicants should think about how to structure 
informed consent statements and other human subjects procedures given the 
potential for wider use of data collected under this award.

STANDARDS FOR PRIVACY OF INDIVIDUALLY IDENTIFIABLE HEALTH INFORMATION: The 
Department of Health and Human Services (DHHS) 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 
(HIPAA) of 1996 that governs the protection of individually identifiable 
health information, and is administered and enforced by the DHHS Office for 
Civil Rights (OCR).  

Decisions about applicability and implementation of the Privacy Rule reside 
with the researcher and his/her institution. The OCR website 
(http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including 
a complete Regulation Text and a set of decision tools on "Am I a covered 
entity?"  Information on the impact of the HIPAA Privacy Rule on NIH 
processes involving the review, funding, and progress monitoring of grants, 
cooperative agreements, and research contracts can be found at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs IN NIH GRANT APPLICATIONS OR APPENDICES: All applications and proposals 
for NIH funding must be self-contained within specified page limitations. 
Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) 
should not be used to provide information necessary to the review because 
reviewers are under no obligation to view the Internet sites.   Furthermore, 
we caution reviewers that their anonymity may be compromised when they 
directly access an Internet site.

HEALTHY PEOPLE 2010: The Public Health Service (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 
RFA 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. 

AUTHORITY AND REGULATIONS

This program is described in the Catalogue of Federal Domestic Assistance at 
http://www.cfda.gov/ in the following citations: No. 93.855, Immunology, 
Allergy, and Transplantation Research and No. 93.856, Microbiology and 
Infectious Diseases Research. Awards are made under authorization of Sections 
301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) 
and administered under NIH grants policies and Federal Regulations 42 CFR 52 
and 45 CFR Parts 74 and 92. This program is not subject to the 
intergovernmental review requirements of Executive Order 12372 or Health 
Systems Agency review.

The NIH Grants Policy Statement is available at 
http://grants.nih.gov/grants/policy/policy.htm. This document includes 
general information about the grant application and review process; 
information on the terms and conditions that apply to NIH Grants and 
cooperative agreements; and a listing of pertinent offices and officials at 
the NIH.  All awards are subject to the terms and conditions, cost 
principles, and other considerations described in the NIH Grants Policy 
Statement. 

The 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 performed during this interval.

Weekly TOC for this Announcement
NIH Funding Opportunities and Notices

	Office of Extramural Research (OER)			National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892			Department of Health and Human Services (HHS)
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