Food Safety Research: Availability of Cooperative Agreements; Request for Applications

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

Food Safety Research: 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

research funds for fiscal year (FY) 1998 to conduct research to support

the reduction of the incidence of foodborne illness, specifically to

support: The development of sampling methods to enhance the detection,

and more specifically the enumeration, of low levels of pathogens in

foods; the development of intervention strategies for consumers to

improve food safety in the home; and total genome sequence analyses of

the pathogen Escherichia coli O157:H7, towards a molecular definition

of microbial virulence and pathogenicity. Approximately $700,000 will

be available in FY 1998. FDA anticipates making three to five awards at

$100,000 to $200,000 (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, additional years of noncompetitive support are

predicated upon performance and the availability of Federal FY funds.

FDA is mandated by the President's Food Safety Initiatiative (FSI) to

reduce the incidence of foodborne illness to the greatest extent

feasible.

DATES: Submit applications by July 13, 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, Division of

Contracts and Procurement Management (HFA-520), Food and Drug

Administration, 5600 Fishers Lane, Rockville, MD 20857, 301-443-6170.

(Applications hand-carried or commercially delivered should be

addressed to 5630 Fishers Lane, rm. 2129, Rockville, MD 20852.)

FOR FURTHER INFORMATION CONTACT:

Regarding the administrative and financial management aspects of

this notice: Robert L. Robins (address above).

Regarding the programmatic aspects of this notice: Robert L.

Buchanan, Center for Food Safety and Applied Nutrition, Food and Drug

Administration (HFS-500), 200 C St. SW., Washington DC 20204, 202-205-

5053.

SUPPLEMENTARY INFORMATION: FDA will support the research studies

covered by this notice under section 301 of the Public Health Service

Act (the PHS 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. 017-00100474-0)

through the Superintendent of Documents, Government Printing Office,

Washington, DC 20402-9325, 202-512-1800.

[[Page 29017]]

I. Background

FDA is mandated by the President's Food Safety Initiative (FSI) to

reduce the incidence of foodborne illness to the greatest extent

feasible. 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 a year, primarily the

very young and elderly, die as a result. Research in food safety seeks

to reduce the incidence of foodborne illness by improving our ability

to detect and enumerate pathogens in the food supply and to find new

ways to control them. The President's FSI requires that 1998 funds be

used to develop rapid cost effective tests for the presence in foods of

pathogens and to develop technologies for preventing foodborne illness

through the control of pathogens.

FDA has continually sponsored research to improve the detection of

pathogens in foods. One area that may now be addressed is the problem

of detecting sporadically-occuring low-level pathogens in foods. A

caveat to employing existing detection regimens is the need to develop

effective sampling strategies. Therefore, one objective of this funding

initiative is the development of new approaches to sampling that will

allow the use of existing detection regimens for screening larger

sample volumes, thereby increasing the probability of detecting the

presence of low levels of a pathogen. The ideal sampling method would:

(1) Be nondestructive, (2) enhance the detection of multiple target

microorganisms at or below current regulatory limits, (3) provide

quantitative data of the level of the target pathogen to aid microbial

risk assessment, and (4) be capable of being automated.

FDA has continually sponsored research in intervention strategies

to mitigate the risk of foodborne illness. The initiative provides an

opportunity to expand the range of research questions addressed by FDA

in intervention strategies. The development of specific intervention

strategies that may be used by consumers or food service providers is a

priority need. A substantial number of disease outbreaks are associated

with food consumption in the home or food service facilities, and in

many of these incidences faulty food handling practices are identified

as contributing factors. Some of these practices may be addressed by

education. However, even with the strict adherence to recommended food

handling practices, there is a risk of pathogenic microorganisms

entering the home kitchen. Such hazards have traditionally been

controlled by cooking, but this is not an option for many foods (e.g.,

lettuce, fresh fruit). New methods or technologies are needed that can

empower the consumer and food service providers by providing them a

means to actively reduce the incidence and prevalence of pathogens on

foods that are not amenable to cooking. An effective intervention is

one that can consistently reduce the levels of target pathogens (i.e,

Salmonella typhimurium, Listeria monocytogenes, E. coli O157:H7,

Cyclospora cayetenensis, Cryptosporidium parvum) by at least 1,000-fold

under standardized test conditions. The funding initiative seeks to

develop these new methods or technologies.

FDA has continually sponsored research for characterization of

microbial virulence factors and the evolution of microbial survival and

growth, especially as it impacts pathogenesis. The initiative provides

an opportunity to expand the range of research questions addressed by

FDA in the virulence and evolution of E. coli O157:H7. This pathogen is

of special interest because of its virulence and resistance to

traditional methods of food preservation. FDA needs to better

understand the mechanisms of the pathogen's survival, growth, and

evolution, with respect to the factors associated with its

pathogenesis. An important tool for acquiring this information is the

sequence of the genome of the pathogen. It is expected that sequence

information of E. coli O157:H7 will provide unique insights into the

evolution of the pathogen, particularly in comparison with

nonpathogenic E. coli sequences. Further insights are anticipated with

respect to identifying sequences of deoxyribonucleic acid from other

organisms and deducing the mechanism of transfer based upon collateral

sequences. Proposed research should initiate a pathway to the eventual

development of rapid and sensitive methods for detection,

identification, and enumeration of this important pathogen.

II. Research Goals and Objectives

The specific objectives of this program will be: (1) The

development of sampling methods or strategies to facilitate existing

detection methods towards detecting, and more importantly enumerating,

low-level microbial pathogens in food; (2) the development of

intervention strategies for use by consumers in the home and by food

service providers that will reduce the incidence of food borne illness,

particularly that associated with fresh or minimally processed produce;

and (3) the expansion of knowledge of the genome of E. coli O157:H7,

towards a molecular definition of pathogen emergence and resistance to

traditional food processing/preservation practices.

Projects that fulfill any one of the following specific objectives

will be considered for funding. Applications may address only one

project objective; however, applicants may submit more than one

application for any of the following project objectives:

A. Project Objective 1

Project objective 1 is intended to develop sampling and statistical

methods that facilitate existing pathogen detection regimens to allow

the detection, and more importantly enumeration, of low-levels of

pathogens in or on foods, particularly fresh or minimally processed

produce. Projects will be considered that seek to develop new ways of

sampling large volumes of foods in a nondestructive or contaminating

manner and provide quantitative estimates of the level of the pathogen

to aid microbial risk assessment. Proposals may include any of a

variety of potential isolation, recovery, and/or concentration systems,

as long as they are suitable for use in food production, processing, or

preparation facilities. An ideal sampling plan should also consider not

only occurrence of pathogen(s), but also dispersion or distribution of

the pathogen in the food. These pathogen enumeration and distribution

data would aid reconstructing the estimated ingested dose that caused

illness, lending support to development of dose-response models in

microbial risk assessment. A plan for demonstrating the feasibility of

the developed methodology in contaminated foods collected under ``field

conditions'' should be included.

B. Project Objective 2

Project objective 2 is intended to develop intervention methods or

technologies other than cooking that can be used by consumers in the

home or by operators of food service facilities. Proposed approaches

should provide consumers with new tools and methods that can enhance

the microbiological safety of foods, particularly fresh or minimally

processed produce, that is prepared in the home or food service

facilities by decreasing the level of pathogens in or on the food. The

proposed intervention strategy can be at any point between the

consumer's, or food service proprietor's, purchase of a

[[Page 29018]]

food or food ingredient and its consumption. The proposed intervention

strategy must be affordable and easy enough to perform so as to be

adopted by consumers. The estimated performance characteristics of the

proposed strategy, with respect to added safety, must be carefully

detailed in the proposal and validated during the research if the grant

is awarded. Validation will include testing with a variety of fresh

vegetables and fruit with at least two of the five pathogens mentioned

previously.

C. Project Objective 3

Project objective 3 is intended to provide genomic sequence data on

E. coli O157:H7. Preference will be given to applicants demonstrating

documented success of other genomic sequencing projects and well-

developed sequencing plans for areas of the genome that have special

relevance to food safety. Applicants must demonstrate that they can

apply the most recent technology cost-effectively to the production of

sequence data and show that they can adequately and efficiently

accumulate, store, and disseminate those data for future interpretation

and application. A commitment to and a plan for making the sequence

data publicly available by deposition into an accessible sequence data

base (GenBank and GSDB) within 3 months of data acquisition and

annotation, must be included in the project description.

D. Protection of Human Research Subjects

Some activities carried out by a recipient under this announcement

may be governed by Department of Health and Human Services (DHHS)

regulations for the protection of human research subjects (45 CFR 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 46. This assurance to comply is called

an assurance document. It includes the designated Institutional Review

Board (IRB) 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-

approved and applicable assurance, may proceed without approval by OPRR

of an applicable assurance for the recipients. Applicants may wish to

contacting OPRR by facsimile (301-402-0527) to obtain preliminary

guidance on human subjects issues. When contacting 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, and October

31), except that the fourth report 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 exclude fees or profit

from their request for support to receive grant awards. Organizations

described in section 501(c)(4) of the Internal Revenue Code of 1968

that engage in lobbying are not eligible to receive awards.

C. Length of Support

This agreement is planned 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 fiscal year 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 a 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.

3. FDA scientists will collaborate with the recipient and have

final approval on experimental protocols. 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

[[Page 29019]]

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. Review Criteria

The funding priority categories are as follows:

Project Objective 1-first priority

Project Objective 2-second priority

Project Objective 3-third priority

All comments received on these funding priority categories will be

taken into consideration and will receive a written response.

Applicants must clearly state in their applications which of the

previously listed established funding priority categories is relevant

to their proposed project. Applications will be grouped, reviewed, and

ranked within each funding priority category. Funding priority will

start with the highest ranked applications under each of the three

objectives, then the second highest, etc., until available funds have

been exhausted. All applications will be evaluated by program and

grants management staff for responsiveness. 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. (See FOR FURTHER INFORMATION CONTACT caption at the

beginning of this document.) Applications will be reviewed and scored

on the following criteria:

1. Research should be proposed on microbiological sampling or

intervention strategies that is within one of the three objectives

listed in 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 the

RFA;

4. Availability and adequacy of laboratory facilities and

equipment;

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.

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 Form 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

Form PHS 398 in lieu of the Form PHS 5161. The application closing date

is July 13, 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 work day. No supplemental or addendum material will be

accepted after the closing date. The outside of the mailing package and

item 2 of the application face page should be labeled, ``Response to

RFA FDA CFSAN-98-2, Project Objective 1 (2 or 3).''

VIII. Method of Application

A. Submission Instructions

Applications will be accepted during normal working hours, 8 a.m.

to 4:30 p.m., Monday through Friday, on or before the established

closing date. Applications will be considered received on time if sent

or mailed on or before the closing 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), National Institutes of Health (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 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.

Applicants are advised that FDA does not adhere to the page limitations

or the type size and line spacing requirements imposed by NIH on its

applications. Applications must be submitted via mail delivery as

stated previously. FDA is unable to receive applications via the

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 closing dates and the mailing label address. Do not

send applications to the 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 the RFA number RFA-

FDA-CFSAN-98-2, Project Objective 1 (2 or 3).

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 information shall not be used or

disclosed except for evaluation purposes.

Dated: May 18, 1998.

William B. Schultz,

Deputy Commissioner for Policy.

[FR Doc. 98-13918 Filed 5-26-98; 8:45 am]

BILLING CODE 4160-01-F