[Federal Register Volume 63, Number 85 (Monday, May 4, 1998)]
[Notices]
[Pages 24553-24556]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-11743]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration


Research Studies to Support Microbial Risk Assessment Modeling; 
Availability of Cooperative Agreements; Request for Applications

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA), Center for Food Safety 
and Applied Nutrition (CFSAN) is announcing the availability of 
approximately $800,000 for research funds for fiscal year (FY) 1998 to 
conduct research to support the development of risk assessment dose-
response models for microbiological hazards associated with food. FDA 
anticipates making two to three awards at $250,000 to $400,000 (direct 
and indirect costs) per award per year. Support of these agreements may 
be up to 3 years. The number of agreements funded will depend on the 
quality of the applications received and the availability of Federal 
funds to support the project. After the first year, 2 additional years 
of noncompetitive support are predicated upon performance and the 
availability of Federal FY funds.

DATES: Submit applications by June 18, 1998. If the closing date falls 
on a weekend, it will be extended to Monday; if the date falls on a 
holiday, it will be extended to the following workday.

ADDRESSES: Application forms are available from, and completed 
applications should be submitted to: Robert L. Robins, Grants 
Management Officer, Division of Contracts and Procurement Management 
(HFA-520), Food and Drug Administration, Park Bldg., 5600 Fishers Lane, 
rm. 3-40, Rockville, MD 20857, 301-443-6170. Applications hand-carried 
or commercially delivered should be addressed to Park Bldg., 12420 
Parklawn Dr., rm. 3-40, Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT:
    Regarding the administrative and financial management aspects of

[[Page 24554]]

this notice: Robert L. Robins (address above).
    Regarding the programmatic aspects of this notice: Wes R. Long, 
Food Safety Initiative Risk Assessment Lead, Center for Food Safety and 
Applied Nutrition, Food and Drug Administration (HFS-301), 200 C St. 
SW., Washington, DC 20204, 202-205-4064.

SUPPLEMENTARY INFORMATION: FDA will support the research studies 
covered by this notice under section 301 of the Public Health Service 
Act (42 U.S.C. 241). FDA's research program is described in the Catalog 
of Federal Domestic Assistance, No. 93.103.
    The Public Health Service (PHS) strongly encourages all award 
recipients to provide a smoke-free workplace and to discourage the use 
of all tobacco products. This is consistent with the PHS mission to 
protect and advance the physical and mental health of the American 
people.
    PHS urges applicants to submit work plans that address specific 
objectives of ``Healthy People 2000.'' Potential applicants may obtain 
a copy of ``Healthy People 2000'' (Full Report, stock No. 017-0010-
0474-0) through the Superintendent of Documents, Government Printing 
Office, Washington, DC 20402-9325, 202-512-1800.

I. Background

    FDA is mandated by the President's Food Safety Initiative (FSI) to 
develop risk assessment tools to help assure the microbiological safety 
of foods. Even though the American food supply is among the safest in 
the world, millions of Americans are stricken by illness each year 
caused by the food they consume, and some 9,000 Americans a year, 
primarily the very young and elderly, die as a result. The goal of FSI 
is to further reduce the incidence of food borne disease to the 
greatest extent possible. Risk assessment helps promote this goal by 
determining the likelihood that exposure to a hazard, such as a food 
borne pathogen, will result in harm or disease. Risk assessment methods 
help characterize the nature and size of risks to human health 
associated with food borne hazards and assist regulators in making 
decisions about where in the food chain to allocate public resources to 
reduce those risks that have the greatest consequences for human 
health. Carefully formulated risk assessments based on the best 
available data generated from research lead to more informed risk 
management and better decisions. The President's FSI requires that 1998 
funds be used to develop better data and modeling techniques to assess 
the exposure of the population to microbial contaminants and the range 
of health consequences of that exposure.
    Research is needed to develop improved methods and models that will 
make it possible to perform quantitative microbial risk assessments to 
the degree of complexity needed for most food-safety issues. Such 
research requires an integration of work in the biological sciences, 
predictive microbiology, and applied mathematics. Risk assessment's FSI 
activities focus on developing models for improving risk assessments. 
Fundamentally, however, additional data is needed to assist in the 
development of these models. For dose-response models--that is, 
determining the quantity of a virulent organism ingested and the likely 
outcome of that event--there are numerous data needs. Risk assessors 
have mostly relied on qualitative or semi-quantitative criteria, such 
as outbreak reports or surveillance data, to develop these models. 
Significant improvements in modeling dose-response relationships for 
the human population could be realized from a coordinated research 
effort that leverages completed, ongoing, or planned human clinical 
trials funded by the National Institutes of Health (NIH), the 
Environmental Protection Action (EPA), the Department of Defense (DOD), 
and others and emphasizes expansion of clinical studies to include the 
acquisition of data needed in the areas of dose-response relationships 
at low-dose levels, assessment of potential biomarkers of infection 
caused by food borne pathogens, and the effects of food matrices on 
dose-response; also the development of correlative dose-response data 
from relevant animal surrogates.

II. Research Goals and Objectives

    The specific objective of this program of research will be to 
conduct research to complement the use, development, or improvement of 
dose-response models for use in risk assessment.
    Applications that fulfill the following specific project objectives 
will be considered for funding. Collaborations among researchers with 
complementary capabilities are encouraged.

A. Project Objectives

    To generate dose-response data from human clinical studies and 
develop correlative dose-response data from relevant animal surrogates. 
The FDA seeks to support research to complement completed, ongoing, and 
planned controlled clinical infection studies, such as those supported 
by NIH, EPA, or DOD, for the purpose of providing data on the dose-
response relationship in humans ingesting food borne pathogenic 
microorganisms.
    Research would be conducted to expand clinical studies to include 
additional strains and/or lower-dose levels to facilitate dose-response 
modeling. It may also include collection and use of subject samples 
(e.g., stools, peripheral blood) in the development of in vitro or ex 
vivo correlates (biomarkers) of human susceptibility, and/or expansion 
of clinical studies to collect data on food matrix effects.
    In addition, the research must include the development of 
correlative dose-response data from relevant animal surrogates using 
the same bacterial strains, prepared under the same conditions, as used 
in the human dosing experiments, utilizing an appropriate dose range to 
allow extrapolation to low doses. Oral dose-response in animals will be 
required. Research may include both normal animals and 
immunocompromised animals. Applicable models of compromised host 
subpopulations include, but are not limited to, animals with defined 
defects of the innate or acquired immune system or with disruption of 
the composition and/or diversity of the indigenous gut microflora.

B. Protection of Human Research Subjects

    Some activities carried out by a recipient under this announcement 
may be governed by the Department of Health and Human Services' (DHHS) 
regulations for the protection of human research subjects (45 CFR part 
46). These regulations require recipients to establish procedures for 
the protection of subjects involved in any research activities. Prior 
to funding and upon request of the Office for Protection from Research 
Risks (OPRR), prospective recipients must have on file with OPRR an 
assurance to comply with 45 CFR part 46. This assurance to comply is 
called an Assurance document. It includes the designated Institutional 
Review Board for review and approval of procedures for carrying out any 
research activities occurring in conjunction with this award. If an 
applicable Assurance document for the applicant is not already on file 
with OPRR, a formal request for the required Assurance will be issued 
by OPRR at an appropriate point in the review process, prior to award, 
and examples of required materials will be supplied at that time. No 
applicant or performance site, without an approved and applicable 
Assurance on file with OPRR, may spend funds on human subject 
activities or accrue subjects. No performance site, even with an OPRR-

[[Page 24555]]

approved and applicable Assurance, may proceed without approval by OPRR 
of an applicable Assurance for the recipients. Applicants may wish to 
contact OPRR by facsimile (301-402-0527) to obtain preliminary guidance 
on human subjects issues. When contact OPRR, applicants should provide 
their institutional affiliation, geographic location, and all available 
request for application (RFA) citation information.

III. Reporting Requirements

    A Program Progress Report and a Financial Status Report (FSR) (SF-
269) are required. An original FSR and two copies shall be submitted to 
FDA's Grants Management Officer within 90 days of the budget expiration 
date of the cooperative agreement. Failure to file the FSR (SF-269) on 
time may be grounds for suspension or termination of the agreement. 
Progress reports will be required quarterly within 30 days following 
each Federal fiscal quarter (January 31, April 30, July 30, October 
31), except that the fourth report which will serve as the annual 
report and will be due 90 days after the budget expiration date. CFSAN 
program staff will advise the recipient of the suggested format for the 
Program Progress Report at the appropriate time. A final FSR (SF-269), 
Program Progress Report and Invention Statement must be submitted 
within 90 days after the expiration of the project period as noted on 
the Notice of Grant Award.
    Program monitoring of recipients will be conducted on an ongoing 
basis and written reports will be reviewed and evaluated at least 
quarterly by the Project Officer and the Project Advisory Group. 
Project monitoring may also be in the form of telephone conversations 
between the Project Officer/Grants Management Specialist and the 
Principal Investigator and/or a site visit with appropriate officials 
of the recipient organization. The results of these monitoring 
activities will be duly recorded in the official file and may be 
available to the recipient upon request.

IV. Mechanism of Support

A. Award Instrument

    Support for this program will be in the form of cooperative 
agreements. These cooperative agreements will be subject to all 
policies and requirements that govern the research grant programs of 
the PHS, including the provisions of 42 CFR part 52 and 45 CFR parts 74 
and 92. The regulations issued under Executive Order 12372 do not apply 
to this program.

B. Eligibility

    These cooperative agreements are available to any public or private 
nonprofit entity (including State and local units of government) and 
any for-profit entity. For-profit entities must commit to excluding 
fees or profit in their request for support to receive awards. 
Organizations described in section 501(c)(4) of the Internal Revenue 
Code of 1968 are not eligible to receive awards.
    Members of the Food Safety Initiative Risk Assessment Consortium 
and/or their collaborators are not eligible to compete for these 
program funds.

C. Length of Support

    The length of support will be for up to 3 years. Funding beyond the 
first year will be noncompetitive and will depend on: (1) Satisfactory 
performance during the preceding year, and/or (2) the availability of 
Federal FY funds.

V. Delineation of Substantive Involvement

    Inherent in the cooperative agreement award is substantive 
involvement by the awarding agency. Accordingly, FDA will have a 
substantive involvement in the programmatic activities of all the 
projects funded under this RFA. Substantive involvement includes but is 
not limited to the following:
    1. FDA will appoint project officers who will actively monitor the 
FDA supported program under each award.
    2. FDA will establish an Project Advisory Group which will provide 
guidance and direction to the project officer with regard to the 
scientific approaches and methodology that may be used by the 
investigator.
    FDA scientists will collaborate with the recipient and have final 
approval on the experimental protocol. This collaboration may include 
protocol design, data analysis, interpretation of findings, co-
authorship of publications, and the development and filing of patents.

VI. Review Procedure and Criteria

A. Review Method

    All applications submitted in response to this RFA will first be 
reviewed by grants management and program staff for responsiveness. If 
applications are found to be nonresponsive, they will be returned to 
the applicant without further consideration.
    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. Responsive applications will 
also be subject to a second level of review by a National Advisory 
Council for concurrence with the recommendations made by the first 
level reviewers. Final funding decisions will be made by the 
Commissioner of Food and Drugs or his designee.

B. Program Priorities and Review Criteria

    Funding priority will be for research proposals that will provide 
data for dose-response models for the following foodborne pathogens: 
Shiga-like toxin-producing Cryptosporidium parvum, pathogenic 
Escherichia coli, Listeria monocytogenes, Norwalk virus, Salmonella 
spp., Shigella spp., Vibrio spp., and Staphyloccocus spp. enterotoxin. 
Other foodborne pathogens will also be considered. As previously 
stated, proposed research must be conducted in collaboration with 
completed, ongoing, or planned human clinical trials.
    All comments received on the funding priority will be taken into 
consideration and will receive a response.
    All applications will be evaluated by program and grants management 
staff for responsiveness. Applications determined not to be within the 
scope of the project objectives will be considered nonresponsive. 
Applications considered nonresponsive will be returned to the 
applicant, without being reviewed. Applicants are strongly encouraged 
to contact FDA to resolve any questions regarding criteria prior to the 
submission of their application. All questions of a technical or 
scientific nature must be directed to the CFSAN program staff and all 
questions of an administrative or financial nature must be directed to 
the grants management staff (address above). Applications will be based 
on the following criteria:
    1. Research should be proposed on dose-response that is within the 
objectives listed in Research Goals and Objectives, section II of this 
document.
    2. Whether the proposed study is within the budget and costs have 
been adequately justified and fully documented;
    3. Soundness of the rationale for the proposed study and 
appropriateness of the study design to address the objectives of RFA;
    4. Availability and adequacy of laboratory and associated animal 
facilities;
    5. Availability and adequacy of support services, e.g., 
biostatistical computer, data bases, etc., and;
    6. Research experience, training, and competence of the principal 
investigator and support staff.

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VII. Submission Requirements

    The original and five copies of the completed Grant Application 
Form PHS 398 (Rev. 5/95) or the original and two copies of the PHS 5161 
(Rev. 7/92) for State and local governments, with copies of the 
appendices for each of the copies, should be delivered to Robert L. 
Robins (address above). State and local governments may choose to use 
the PHS 398 application form in lieu of the PHS 5161. The application 
receipt date is June 18, 1998. If the receipt date falls on a weekend, 
it will be extended to Monday; if the date falls on a holiday, it will 
be extended to the following workday. No supplemental or addendum 
material will be accepted after the receipt date.
    The outside of the mailing package and item 2 of the application 
face page should be labeled ``Response to RFA-FDA-CFSAN-98-1.''

VIII. Method of Application

A. Submission Instructions

    Applications will be accepted during working hours, 8 a.m. to 4:30 
p.m., Monday through Friday, on or before the established receipt date. 
Applications will be considered received on time if sent or mailed on 
or before the receipt date as evidenced by a legible U.S. Postal 
Service dated postmark or a legible date receipt from a commercial 
carrier, unless they arrive too late for orderly processing. Private 
metered postmarks shall not be acceptable as proof of timely mailing. 
Applications not received on time will not be considered for review and 
will be returned to the applicant. Applicants should note that the U.S. 
Postal Service does not uniformly provide dated postmarks. Before 
relying on this method, applicants should check with their local post 
office.
    Do not send applications to the Center for Scientific Research 
(CSR), NIH. Any application that is sent to NIH, that is then forwarded 
to FDA and not received in time for orderly processing, will be deemed 
unresponsive and returned to the applicant. Instructions for completing 
the application forms can be found on the NIH home page on the Internet 
(address: http://www.nih.gov/grants/funding/phs398/phs398.html; the 
forms can be found at <a href="http://www.nih.gov/grants/funding/phs398/
forms__toc.html">http://www.nih.gov/grants/funding/phs398/
forms__toc.html</a>). However, as noted previously, applications are not to 
be mailed to NIH. Applications must be submitted via mail delivery as 
stated previously. FDA is unable to receive applications via Internet.

B. Format for Application

    Submission of the application must be on Grant Application Form PHS 
398 (Rev. 5/95). All ``General Instructions'' and ``Specific 
Instructions'' in the application kit should be followed with the 
exception of the receipt dates and the mailing label address. 
Applicants are also advised that FDA does not adhere to the page 
limitations or the type size and line spacing requirements imposed by 
NIH on its applications. Do not send applications to CSR, NIH. 
Applications from State and local governments may be submitted on Form 
PHS 5161 (Rev. 7/92) or Form PHS 398 (Rev. 5/95).
    The face page of the application should reflect RFA's number RFA-
FDA-CFSAN-98-1.
    Data included in the application, if restricted with the legend 
specified below, may be entitled to confidential treatment as trade 
secret or confidential commercial information within the meaning of the 
Freedom of Information Act (FOIA) (5 U.S.C. 552(b)(4)) and FDA's 
implementing regulations (21 CFR 20.61).
    Information collection requirements requested on Form PHS 398 and 
the instructions have been submitted by PHS to the Office of Management 
and Budget (OMB) and were approved and assigned OMB control number 
0925-0001.

C. Legend

    Unless disclosure is required by FOIA as amended (5 U.S.C. 552), as 
determined by the freedom of information officials of DHHS or by a 
court, data contained in the portions of this application which have 
been specifically identified by page number, paragraph, etc., by the 
applicant as containing restricted and/or proprietary information shall 
not be used or disclosed except for evaluation purposes.

    Dated: April 3, 1998.
 William K. Hubbard,
 Associate Commissioner for Policy Coordination.
[FR Doc. 98-11743 Filed 5-1-98; 8:45 am]
BILLING CODE 4160-01-F