[Federal Register Volume 65, Number 132 (Monday, July 10, 2000)]
[Notices]
[Pages 42382-42386]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-17276]


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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) is announcing the 
availability of research funds for fiscal year (FY) 2000 to support 
research in the following areas of produce safety, egg safety, 
development of extraction procedures of foodborne viruses from foods to 
enhance detection, and food service, transportation, and consumer 
practices. Approximately $600,000 will be available in FY 2000. FDA 
anticipates making three to four 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 fiscal year funds.

DATES: Submit applications by August 24, 2000.

ADDRESSES: Application forms are available from, and completed 
applications should be submitted to: Maura C. Stephanos, Grants 
Management Specialist, Grants Management Office (HFA-520), Division of 
Contracts and Procurement Management, Office of the Director, Food and 
Drug Administration, 5600 Fishers Lane, rm. 2129, Rockville, MD 20857, 
301-827-7183, FAX 301-827-7106, e-mail: [email protected]. 
(Applications hand-carried or commercially delivered should be 
addressed to rm. 2129, 5630 Fishers Lane, Rockville, MD 20852).

FOR FURTHER INFORMATION CONTACT: Regarding the administrative and 
financial management aspects of this notice: Maura C. Stephanos 
(address above).
    Regarding the programmatic aspects of this notice: Marianna D. 
Miliotis, Food Safety Initiative Extramural Research Coordinator, 
Office of Plants, Dairy Foods, and Beverages (HFS-327), Center for Food 
Safety and Applied Nutrition, Food and Drug Administration, 200 C St. 
SW., Washington, DC 20204, 202-205-4824, e-mail: 
[email protected].

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.
    FDA is committed to achieving the health promotion and disease 
prevention objectives of ``Healthy People 2010,'' a national activity 
to reduce morbidity and mortality and to improve the quality of life. 
Applicants may obtain a hard copy of the ``Healthy People 2010'' 
objectives, vols. I and II, conference edition (B0074) for $22 per set, 
by writing to the Office of Disease Prevention and Health Promotion 
(ODPHP) Communication Support Center (Center), P.O. Box 37366, 
Washington, DC 20013-7366. Each of the 28 chapters of ``Healthy People 
2010'' is priced at $2 per copy. Telephone orders can be placed at the 
Center on 301-468-5690. The Center also sells the complete conference 
edition in CD-ROM format (B0071) for $5. This publication is available 
as well on the Internet at www.health.gov/healthypeople. Internet 
viewers should proceed to ``Publications.''

[[Page 42383]]

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. 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. In 
FY 1998, the Center for Food Safety and Applied Nutrition (CFSAN) 
obligated $2 million to support eight multiyear cooperative agreements. 
This extramural program inaugurated a novel collaborative research 
effort between CFSAN and academic scientists, and leveraged expertise, 
not found within FDA, to accelerate ongoing research. Collaborations 
such as these provide information critical to food safety guidance and 
policymaking, and stimulate fruitful interactions between FDA 
scientists and those within the greater research community.
    In continuation of this effort, CFSAN/FSI will provide FY 2000 
funds to be used for research to help ensure produce and egg safety, 
develop extraction methods for viruses in foods, and determine food 
storage practices from processing to consumption.

II. Research Goals and Objectives

    The goals and objectives of this program will be to: (1) Ensure 
produce safety by standardizing inoculation methods for determining the 
efficacy of antimicrobial chemicals or technologies or for validation 
of Hazard Analysis Critical Control Point (HACCP) systems, particularly 
in fresh or minimally processed produce; (2) evaluate surrogate 
microorganisms for use in HACCP validation; (3) ensure egg safety by 
developing improved sampling and detection methods for detection of 
low-levels of and enumeration of Salmonella Enteritidis (S. 
Enteritidis) in eggs; (4) develop extraction and processing methods 
suitable for reverse-transcription polymerase chain reaction (RT-PCR) 
based identification/detection of foodborne viruses; and (5) obtain 
information to support the science behind the U.S. Public Health 
Service Food Code, which provides guidance to the retail and food 
service industry, as well as information to support guidance to the 
consumer.
    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 project objectives. The project objectives 
are listed below in order of priority.

A. Project Objective 1 (Priority #1)

    The first priority is to develop extraction and processing methods 
suitable for RT-PCR based identification/detection of foodborne 
viruses, such as Hepatitis A virus (HAV) and Norwalk virus. Commodities 
of interest include raw or minimally processed foods, such as 
strawberries, raspberries, grapes, tomatoes, and seafood. Extraction 
and sample processing methods must not interfere or inhibit RT-PCR 
based detection of the virus(es) and be applicable for analysis of 
large or bulk quantities of foods. The entire methodology, from 
extraction to detection, must include appropriate and exhaustive 
positive and negative controls to ensure validity of the extraction, 
processing, and detection (RT-PCR based) methods. These controls must 
also include those designed to confirm or exclude the absence of viral 
particle/genome contamination among and/or between food samples and 
reagents.

B. Project Objective 2 (Priority #2)

    The second priority is to determine the effect of different 
inoculation procedures (e.g. dipping, spraying, spotting) on the 
efficacy of disinfectants and intervention technologies to remove or 
inactivate microorganisms, and determine how procedures perform under 
practical conditions. Ensuring produce that is safe for the consumer to 
eat is a major priority. Research needed to address this issue includes 
standard inoculation methods for performing challenge studies. FDA has 
continually sponsored research in intervention strategies to mitigate 
the risk of foodborne illness and reviewed applications for new 
antimicrobial agents and intervention technologies. The initiative 
provides an opportunity to expand the range of research questions 
addressed by FDA in intervention strategies for standardization of 
inoculation procedures for testing efficacy of intervention strategies. 
Currently, challenge inoculation methods tend to allow limited times 
for attachment of cells to food surfaces (and often under unrealistic 
conditions). This makes interpretation of the results difficult. 
Published studies have also demonstrated problems with statistical 
reproducibility when the attachment period is lengthened. An ideal 
inoculation protocol would permit sufficient time for cell attachment 
under conditions simulating those encountered in food growing and 
processing environments, such as low nutrient levels and ambient 
temperatures. The protocol tests must include a comparison of 
application techniques including spot, spray, and dip inoculation 
methods.

C. Project Objective 3 (Priority #3)

    To determine whether consumer and industry practices are sufficient 
to protect the consumer from foodborne illness, research is needed in 
the following areas:
    (1) Examine acceptability of the U.S. Public Health Service Food 
Code's requirements for: (a) Four-hour holding limit for all foods at 
ambient temperature, (b) the appropriateness for cooling foods from 140 
to 41 \1/2\F in 6 hours, and (c) the potential impact for human health 
risks if hot foods are held at 130 \1/2\F.
    (2) Quantitatively describe whether cooking practices used in the 
home are sufficient to inactivate pathogenic bacteria, viruses, or 
parasites that may be present in specific foods.
    (3) Explore consumer practices related to storage of selected food 
products, including when and where it is stored in the refrigerator, 
refrigerator temperatures, length of time refrigerated food is kept, 
and consumer knowledge and beliefs related to food safety and 
refrigeration.

D. Project Objective 4 (Priority #4)

    To ensure that eggs are safe, there is a need to study egg safety, 
specifically sampling and detection methods for S. Enteritidis in eggs 
and layer flocks. Current egg sampling practices may fail to detect low 
levels of S. Enteritidis. Therefore, there is a need to:
    (1) Develop improved sampling and detection methods to detect low-
levels of, and more significantly enumerate, S. Enteritidis in eggs and 
layer flocks. The development of a sampling plan should be based on 
known incidence data to ensure that a negative test result from a 
sample, indicates with a high level of confidence that the organism is 
not present in the entire lot or shipment. The sampling plan should 
consider not only occurrence of S. Enteritidis, but also dispersion or 
distribution of this pathogen among groups of eggs, and should be 
statistically superior to present sampling and detection techniques.
    (2) Develop better on-farm indicators for predicting whether eggs 
are contaminated with S. Enteritidis.

E. Project Objective 5 (Priority #5)

    The fifth priority is to determine which microorganisms are most 
suitable for use as surrogates for foodborne pathogens and are 
appropriate for specific commodities in challenge

[[Page 42384]]

studies to validate microbial hazard reduction technologies. The 
experimental use of pathogenic microorganisms in food establishments or 
pilot plants is generally contraindicated, but it is necessary to 
perform challenge studies to validate microbial hazard reduction 
technologies. In order to overcome this problem, the comparison of 
surrogate microbes to pathogenic counterparts (bacteria, viruses, and 
parasites) is necessary. Surrogates that are appropriate for specific 
commodities should be proposed. They should exhibit similar growth and 
binding characteristics, on a target commodity, of the foodborne 
pathogen represented, and should exhibit equivalent resistance to 
common classes of disinfectants. Successful projects will recommend 
surrogates based on a range of comparative physiological, genetic, and 
kinetics studies.

III. Human Subject Protection and Informed Consent

A. 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 (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 contact 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 Applications (RFA) citation information.
    Applicants are advised that the section on human subjects in the 
application kit entitled ``Section C. Specific Instructions--Forms, 
Item 4, Human Subjects,'' on pages 7 and 8 of the application kit, 
should be carefully reviewed for the certification of IRB approval 
requirements. Documentation of IRB approval for every participating 
center is required to be on file with the Grants Management Officer, 
FDA. The goal should be to include enough information on the protection 
of human subjects in a sufficiently clear fashion so reviewers will 
have adequate material to make a complete review. Those approved 
applicants who do not have a current Multiple Project Assurance with 
OPRR will be required to obtain a Single Project Assurance from OPRR 
prior to award.

B. Informed Consent

    Consent and/or assent forms, and any additional information to be 
given to a subject, should accompany the grant application. Information 
that is given to the subject or the subject's representative must be in 
language that the subject or his or her representative can understand. 
No informed consent, whether oral or written, may include any language 
through which the subject or the subject's representative is made to 
waive any of the subject's legal rights, or by which the subject or 
representative releases or appears to release the investigator, the 
sponsor, or the institution or its agent from liability.
    If a study involves both adults and children, separate consent 
forms should be provided for the adults and the parents or guardians of 
the children.

C. Elements of Informed Consent

    The regulations on informed consent are set forth in 45 CFR 46.116 
and 21 CFR 50.25. The basic elements of informed consent are as 
follows:
1. Basic Elements of Informed Consent
    In seeking informed consent, the following information shall be 
provided to each subject.
     A statement that the study involves research, an 
explanation of the purposes of the research and the expected duration 
of the subject's participation, a description of the procedures to be 
followed, and identification of any procedures which are experimental.
     A description of any reasonably foreseeable risks or 
discomforts to the subject.
     A description of any benefits to the subject or to others 
which may reasonably be expected from the research.
     A disclosure of appropriate alternative procedures or 
courses of treatment, if any, that might be advantageous to the 
subject.
     A statement that describes the extent, if any, to which 
confidentiality of records identifying the subject will be maintained, 
and that notes the possibility that FDA may inspect the records.
     For research involving more than minimal risk, an 
explanation as to whether any compensation and any medical treatments 
are available if injury occurs and, if so, what they consist of or 
where further information may be obtained.
     An explanation of whom to contact for answers to pertinent 
questions about the research and research subject's rights, and whom to 
contact in the event of research-related injury to the subject.
     A statement that participation is voluntary, that refusal 
to participate will involve no penalty or loss of benefits to which the 
subject is otherwise entitled, and that the subject may discontinue 
participation at any time without penalty or loss of benefits to which 
the subject is otherwise entitled.
2. Additional Elements of Informed Consent
    When appropriate, one or more of the following elements of 
information shall also be provided to each subject.
     A statement that the particular treatment or procedure may 
involve risks to the subject (or to the embryo or fetus, if the subject 
is or may become pregnant) which are currently unforeseeable.
     Anticipated circumstances under which the subject's 
participation may be terminated by the investigator without regard to 
the subject's consent.
     Any costs to the subject that may result from 
participation in the research.
     The consequences of a subject's decision to withdraw from 
the research and procedures for orderly termination of participation by 
the subject.
     A statement that significant new findings developed during 
the course of the research that may relate to the subject's willingness 
to continue participation will be provided to the subject.
     The approximate number of subjects involved in the study.
     The informed consent requirements are not intended to 
preempt any

[[Page 42385]]

applicable Federal, State, or local laws which require additional 
information to be disclosed for informed consent to be legally 
effective.
     Nothing in the notice is intended to limit the authority 
of a physician to provide emergency medical care to the extent that a 
physician is permitted to do so under applicable Federal, State, or 
local law.

IV. 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 (address same as given above for Grants 
Management Specialist) 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 fiscal 
year quarter (January 31, April 30, July 30, 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.

V. 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 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

    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.

VI. 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 provide guidance and direction with regard to the 
scientific approach and methodology that may be used by the 
investigator.
    2. FDA will participate with the recipient in determining and 
executing any: (a) Methodological approaches to be used, (b) procedures 
and techniques to be performed, (c) sampling plans proposed, (d) 
interpretation of results, and (e) microorganisms and commodities to be 
used.
    3. FDA will collaborate with the recipient and have final approval 
on the experimental protocols. This collaboration may include protocol 
design, data analysis, interpretation of findings, coauthorship of 
publications and the development and filing of patents.

VII. 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. 
Applications will be considered nonresponsive if they are not in 
compliance with sections VII.B and VIII of this document. If 
applications are found to be nonresponsive to this announcement, 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 FDA 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; Project Objective 4--fourth priority, and 
Project Objective 5--fifth priority.
    Applicants must clearly state in their applications which of the 
above-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 five 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 the Information Contact 
section at the beginning of this document for addresses.) Applications 
will be reviewed and scored on the following criteria:
    1. For Project Objective 3 only--Research should be proposed on 
commercial time/temperature practices, Food Code requirements, home 
cooking practices, or home refrigeration practices, that is within 
Project Objective 3 in Section II. Research Goals and Objectives of 
this document;
    2. For Project Objective 4 only--Research should be proposed on 
sampling and detection of S. Enteritidis in eggs, or on farm indicators 
for predicting whether eggs are contaminated with S. Enteritidis, that 
is within Project Objective 4 in Section II. Research Goals and 
Objectives of this document;
    3. For all Project Objectives--Whether the proposed study is within 
the budget,

[[Page 42386]]

and costs have been adequately justified and fully documented;
    4. For all Project Objectives--Soundness of the rationale for the 
proposed study and appropriateness of the study design to address the 
objectives of the RFA;
    5. For all Project Objectives--Availability and adequacy of 
laboratory facilities and equipment;
    6. For all Project Objectives--Availability and adequacy of support 
services, e.g., biostatistical computer, data bases, etc., and;
    7. For all Project Objectives--Research experience, training, and 
competence of the principal investigator and support staff.

VIII. Submission Requirements

    The original and two copies of the completed Grant Application Form 
PHS 398 (Rev. 4/98) or the original and two copies of PHS 5161 (Rev. 6/
99) for State and local governments, with copies of the appendices for 
each of the copies, should be delivered to Maura C. Stephanos (address 
above). State and local governments may choose to use the PHS 398 
application form in lieu of PHS 5161. The application receipt date is 
August 24, 2000. 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-00, Project Objective 1 (1-5).''

IX. 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 
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 
at http://www.nih.gov.grants/phs398/phs398.html; the forms can be found 
at http://www.nih.gov/grants/phs398/forms--toc.html. However, as noted 
above, 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 above. 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. 4/98). 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.
    The face page of the application should reflect the request for 
applications number RFA-FDA-CFSAN-00, Project Objective 1 (2, 3, 4, or 
5).
    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 (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 the Freedom of Information Act 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 that 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: June 27, 2000.
Margaret M. Dotzel,
Associate Commissioner for Policy.
[FR Doc. 00-17276 Filed 7-7-00; 8:45 am]
BILLING CODE 4160-01-F