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

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

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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-

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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 http://www.nih.gov/grants/funding/phs398/

forms__toc.html). 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