[Federal Register Volume 66, Number 86 (Thursday, May 3, 2001)]
[Notices]
[Pages 22236-22240]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-11159]


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration


Single Source Cooperative Agreement to Support the National 
Center for Natural Products Research (NCNPR), University of Mississippi

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA) is announcing its 
intention to accept and consider a single source application for the 
award of a cooperative agreement to the University of Mississippi (UM) 
to support the National Center for Natural Products Research (NCNPR), 
which is located on UM's Campus at Oxford, MS. FDA anticipates 
providing up to $1 million in fiscal year 2001 (direct and indirect 
costs) for this project, with an additional 4 years of funding up to $1 
million per year predicated upon acceptable performance and the 
availability of future fiscal year funding. These collaborations will 
support and benefit the public health by promoting more efficient 
development and dissemination of natural products research and science 
and will complement the diverse activities of both the public and 
private sector that may become collaborators.

DATES: Submit applications by June 18, 2001.

ADDRESSES: An application is available from, and should be submitted to 
Rosemary Springer, Grants Management Specialist, Division of Contracts 
and Procurement Management (HFA-520), Food and Drug Administration, 
5600 Fishers Lane, Rockville, MD 20857, 301-827-7182, e-mail: 
[email protected]. Applications hand-carried or commercially 
delivered should be addressed to rm. 2129, 5630 Fishers Lane, 
Rockville, MD 20857. Application forms can also be found at http://
www.nih.gov/grants/funding/phs398/forms__toc.html.

FOR FURTHER INFORMATION CONTACT:   
    Regarding the administrative and financial management aspects of 
this notice: Rosemary Springer (address above).
    Regarding the programmatic aspects: Jeanne I. Rader, Center for 
Food Safety and Applied Nutrition (HFS-840), Food and Drug 
Administration, 200 C St. SW., Washington, DC 20204, 202-205-5375, e-
mail: [email protected].

SUPPLEMENTARY INFORMATION: FDA is announcing its intention to accept 
and consider a single source application from UM for a cooperative 
agreement to support NCNPR. FDA's authority to enter into grants and 
cooperative agreements is detailed 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 at 93.103. Before 
entering into cooperative agreements, FDA carefully considers the 
benefits such agreements will provide to the public.
    The Public Health Service (PHS) strongly encourages all award 
recipients to provide a smoke-free work place 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 Healthy People 2010 objectives, 
volumes I and II,

[[Page 22237]]

conference edition (B0074) for $22 per set, by writing to the Office of 
Disease Prevention and Health Promotion (ODPHP) Communication Support 
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 to the ODPHP Center on 301-468-5690. The ODPHP 
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/. Web site viewers should proceed to 
``Publications.''

I. Background

    Congress amended the Federal Food, Drug, and Cosmetic Act (the act) 
with the passage of the Dietary Supplement Health and Education Act of 
1994, to create a regulatory framework for dietary supplements under 
food provisions of the act. FDA has primary responsibility for ensuring 
that appropriate regulatory actions are taken against marketed products 
that: (a) Present an unreasonable or significant risk of illness or 
injury when used according to label directions or under ordinary 
conditions of use, or (b) bear labeling that is false or misleading.
    The ability to identify and analyze specific components in 
ingredients, including botanical ingredients, and in finished products 
is an essential component of research and regulatory programs directed 
at ensuring that dietary supplements are safe and that their labeling 
is truthful and not misleading. The availability of authenticated 
reference materials is an essential prerequisite to the accurate 
identification and quantitative analysis of ingredients or finished 
products. For many botanical ingredients currently used in marketed 
dietary supplement products, however, appropriate reference materials 
are not readily available, their authenticity is not well documented, 
and their compositional characteristics are not adequately defined and 
evaluated for biological effects.
    The use of botanical products in dietary supplements in the U.S. 
has increased significantly in recent years. The newness of the 
regulatory approaches and marketed uses of these products has created a 
critical need for bringing sound science to a number of issues that are 
necessary to ensure that marketed products are safe and their labeling 
is truthful and not misleading. Therefore, it is essential that general 
principles and criteria for ensuring scientific validity in 
manufacturing of botanical products and the use of botanical 
ingredients in dietary supplements be developed through scientific 
discussion and consensus-building. Such general principles and criteria 
will be applicable not only to FDA regulatory and research activities, 
but will also promote consistency and scientific rigor with respect to 
research and standard-setting activities performed by other 
organizations and agencies, and will assist in the development of 
quality control practices by industry.

II. Goals and Objectives

A. Concept

    FDA believes that cooperative research with the UM-NCNPR will 
provide opportunities to address important national and international 
problems in natural products research in a timely manner. However, only 
FDA employees will perform any official regulatory activities. Further, 
FDA believes that cooperative research through UM will promote the 
efficient use of the complementary resources of both parties.
    The applicant would propose to design, implement, and evaluate a 
comprehensive, multidisciplinary array of scientific activities in the 
broad area of natural products' ingredients. The applicant's proposal 
must be designed to meet the objectives of the request for applications 
(RFA). The applicant's proposal should identify and assess innovative 
approaches to address the RFA objectives relative to the broad area of 
natural product identification and safety.
    The purpose of this cooperative agreement would be to:
     Coordinate scientific workshops and conferences on 
relevant topics of public interest to address high priority science and 
research needs;
     Obtain and characterize authenticated reference materials 
for botanicals;
     Develop literature reviews on relevant topics; and
     Share technical information and scientific concepts.

B. Project Emphasis

    The purpose is to augment and enhance research and scientific 
expertise in natural products research. There is a critical need to 
address the increasingly complex problems in such areas as acquisition, 
validation, and characterization of botanical reference materials, 
related research and literature reviews to ensure the safety or 
effectiveness of marketed products, and the development of sound 
scientific principles and consensus-building for dealing with these 
ingredients and products. Since there is increased concern regarding 
the safety of dietary supplements, the need to find other ways of 
expanding the current science base is essential.
    The sharing of complementary resources will create opportunities 
for important national and international issues in natural products 
research to be addressed in a timely and scientifically sound manner. 
Many of these issues (e.g., development and characterization of 
authenticated botanical reference standards, and scientific review and 
consensus-building) can only be addressed with close cooperation of the 
public and private sectors. UM's expertise and facilities for obtaining 
and characterizing authenticated botanical reference materials are 
needed to conduct investigations at the forefront of natural products 
research. Additionally, UM's experimental field plots, vast repository 
containing thousands of natural products extracts for testing in a 
variety of biological assays, and their expertise and long history of 
active scientific investigations are well known in these areas. 
University personnel will provide enhanced scientific expertise in 
advanced techniques for the characterization of natural products as 
well as expand the current capabilities in research to support 
regulatory actions and respond to emergency situations.

C. Summary

    FDA believes that research conducted at the UM is a sound 
investment in the future public health of American consumers. It 
provides an opportunity for extensive cooperation with university 
scientists; and it will stimulate collaborative efforts to ensure a 
safe food supply contributing significantly to the implementation of 
the goals for government, academia, industry, and consumers to work 
together to improve the safety of natural products. The UM scientists 
would bring a special perspective to advancing the knowledge of natural 
products germane to the public interest. Interaction among those 
scientists will stimulate creativity and innovation. FDA's 
participation in this venture will promote a greater awareness and 
understanding of regulatory science and practice among academic 
scientists, thereby providing economic and program benefits to both. In 
summary, collaboration between the public and the private sector 
provides an efficient means of remaining current with scientific and 
technical accomplishments in the areas of natural products research.

[[Page 22238]]

III. Mechanism of Support

A. Award Instrument

    Support for this program, if awarded, will be in the form of a 
cooperative agreement. The award 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, 45 CFR parts 74 and 92, and 
PHS's grants policy statement. The regulations issued under Executive 
Order 12372 do not apply.

B. Length of Support

    The length of support will be for 1 year with the possibility of an 
additional 4 years of noncompetitive support. Continuation, beyond the 
first year, will be based upon performance during the preceding year 
and the availability of Federal fiscal year appropriations. The 
National Institutes of Health (NIH) modular grant program does not 
apply to this FDA program.

IV. Reasons for Single Source Selection

    Competition is limited to UM because: (1) FDA's appropriations 
language has included funds for collaborative research on dietary 
supplements between UM-NCNPR and FDA; and (2) UM has been determined to 
be the only institution with the unique capability of providing a broad 
range of highly relevant scientific expertise and facilities that are 
physically co-located and singularly dedicated to natural products 
research.
    FDA believes that there is compelling evidence that UM is uniquely 
qualified to fulfill the objectives of the proposed cooperative 
agreement. UM is a comprehensive research institution with numerous 
academic programs relevant to natural products which can help to ensure 
that market products are safe for the American public. The UM School of 
Pharmacy has been in existence for 90 years and has an outstanding 30-
year track record for isolating and developing prospective new 
pharmaceuticals from plants and microorganisms.
    NCNPR, which opened in July 1999, is a division of the Research 
Institute of Pharmaceutical Sciences of the UM's School of Pharmacy. 
NCNPR was created to bring together an alliance of academia, 
government, and the pharmaceutical and agrochemical industries to 
integrate research, development, and commercialization of potentially 
useful natural products. The facility is the nation's only university-
affiliated research center devoted to improving human health and 
agricultural productivity through the discovery, development, and 
commercialization of pharmaceuticals and agrochemicals derived from 
natural products. The goal of NCNPR in botanical dietary supplements is 
to enable safe, effective, and proper use of high quality botanical 
products by informed professionals and consumers. NCNPR conducts basic 
and applied multidisciplinary research to discover and develop natural 
products for use as pharmaceuticals, dietary supplements and 
agrochemicals. NCNPR also maintains a repository of several thousand 
natural product extracts that are available for screening by 
collaborators working in other areas.
    NCNPR has substantial expertise to carry forward specific 
discoveries, products, and technologies. Most of the projects to 
develop promising high priority products or technology are conducted in 
collaboration with industrial partners or through externally funded 
grants and contract. NCNPR is staffed with a highly synergistic mix of 
full-time research faculty and support staff and employs a number of 
undergraduate and graduate students and postdoctoral scientists. 
Additionally, the USDA's National Products Utilization Research Unit is 
co-housed and programmatically integrated with the NCNPR thus expanding 
the available expertise and facilities. Together, the faculty, 
scientists, staff, students, USDA scientists, and external 
collaborators, provide the human resources required to accomplish the 
research and development goals of the RFA.
    Additionally, FDA's appropriations language includes funds for 
collaborative research on dietary supplements between NCNPR and FDA. 
NCNPR has the unique capability to bring together diverse scientific 
expertise on bioactive natural products research from: (a) The UM 
faculty in the School of Pharmacy involving researchers in the 
Departments of Pharmacognosy, Medicinal Chemistry, Pharmaceutics, 
Pharmacology, and the Research Institute of Pharmaceutical Sciences; 
(b) research scientists in the U.S. Department of Agriculture/
Agricultural Research Service's (USDA/ARS) National Products 
Utilization Research Unit who are physically co-housed and 
programmatically integrated in the NCNPR; and (c) its close academic 
links and historical collaborations with agricultural and botanical 
programs and facilities at the UM system. UM-NCNPR's ability to 
successfully and uniquely collaborate with FDA is also enhanced by its 
a repository of several thousand natural product extracts; and its long 
history of successful basic and applied multidisciplinary research to 
discover and develop natural products for use as bioactive ingredients 
in dietary supplements and pharmaceuticals, and for improving the 
quality and safety of dietary supplements. Finally, the large number of 
established collaborations among NCNPR scientists and other government 
agencies, academic organizations, and research institutions will also 
be useful in enhancing the collaborative efforts with FDA. These 
collaborations will support and benefit the public health by promoting 
more efficient development and dissemination of natural products 
research and science and will complement the diverse activities of both 
the public and private sector that may become collaborators.
    Research in NCNPR is focused on using state-of-the-art knowledge 
and technology to discover bioactive natural products, develop novel 
technologies or processes that facilitate the discovery of bioactive 
natural products, and provide research-based information on plant 
derived products with health applications. These programs, facilities, 
and expertise are essential for supporting the needs to ensure that 
sound science is available for ensuring the safety and truthfulness of 
labeling of marketed dietary supplement products.
    Collaboration between the public and private sector is an efficient 
means for both FDA and UM to remain current with scientific and 
technical accomplishments from a natural products research perspective. 
Harmonizing regulatory activities is but one example of the need for 
and use of this natural products research knowledge and expertise. The 
partnership between FDA and UM will provide both the technical and 
educational expertise necessary for effective mechanisms that will 
facilitate the movement of new technology and provide direct usefulness 
to the public health.

V. Reporting Requirements

    An annual financial status report (FSR) (SF-269) is required. The 
original and two copies of this report must be submitted to FDA's 
Grants Management Officer within 90 days of the budget expiration date 
of the grant. Failure to file the FSR in a timely fashion will be 
grounds for suspension or termination of the grant.
    An annual program progress report is also required. The 
noncompeting continuation application (PHS 2590) will be considered the 
annual program progress report. The progress report must include a 
description of the progress and accomplishments for each objective 
stated in the RFA.

[[Page 22239]]

    A final program progress report, FSR (SF-269), and invention 
statement must be submitted within 90 days after the expiration of the 
project period as noted on the notice of grant award.

VI. Delineation of Substantive Involvement

    Substantive involvement by the awarding agency is inherent in the 
cooperative agreement award. Accordingly, FDA will have substantial 
involvement in the program activities of the project funded by the 
cooperative agreement. Substantive involvement includes, but is not 
limited to, the following:
    1. FDA will work closely with the grantee and have final approval 
on all project activities. This could include management structure for 
the program, development of plans and strategies for key scientific 
approaches and projects, and for identifying and carrying out the 
research.
    2. FDA will participate in all functions directly related to the 
guidance and development of the program.
    3. FDA will provide technical monitoring and/or direction of the 
work, including monitoring of data analysis, interpretation of 
analytical findings and their significance.
    4. FDA will assist and approve (as deemed appropriate) the 
substance of publications, co-authorship of publications and data 
release.
    5. FDA will have final approval on any re-directions proposed 
during the course of the project.

VII. Review Procedures

A. Review Method

    The application submitted in response to this RFA will first be 
reviewed by grants management and program staff for responsiveness. The 
application will be considered nonresponsive if it is not in compliance 
with this document. If an application is found to be nonresponsive it 
will be returned to the applicant without further consideration. An 
application is considered nonresponsive for the following reasons: (1) 
The applicant organization is ineligible; (2) it is received after the 
specified receipt date; (3) it is incomplete; (4) it is illegible; (5) 
it is not responsive to the RFA; (6) the material presented is 
insufficient to permit an adequate review; and/or (7) it exceeds the 
recommended threshold amount reflected in the RFA.
    A responsive application will be reviewed and evaluated for 
scientific and technical merit by an ad hoc panel of experts in the 
subject field. A responsive application 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. The 
Commissioner of FDA or his/her designee will make final funding 
decisions.

B. Review Criteria

1. Responsiveness to RFA
    The application must demonstrate that the objectives and goals of 
the RFA are understood and the applicant shall offer a logical program 
to meet the objectives of the RFA.
2. Adequacy of Plan
    The applicant must provide a detailed plan to establish a 
collaborative natural products research program as a multidisciplinary 
effort (i.e., FDA and academia). The application will be evaluated on 
the thoroughness of the plan, the reasonableness of the approach, and 
adherence to the concept and its objectives, as stated in the RFA. The 
detailed plan must form the basis of a balanced natural products 
research program directed toward development of skills and expertise in 
aspects of natural products research, as stated in the RFA. Included 
will be development of: Scientific expertise in natural products 
research involving researchers in pharmacognosy, medicinal chemistry, 
pharmacology, and pharmaceutical sciences; state of the art knowledge 
and technology to discover bioactive natural products; novel 
technologies or processes that facilitate the discovery of bioactive 
natural products; and research-based information on potential health 
applications of plant derived products. The plan must also include a 
schedule for accomplishing the objectives outlined above.
3. Timeliness of Program Implementation
    The application will be evaluated for the applicant's ability to 
establish natural products research in an expeditious manner.
4. Adequacy and availability of research facilities
    The application must demonstrate that the applicant has adequate 
research facilities in the areas of: Pharmacognosy, medicinal 
chemistry, pharmacology, and pharmaceutical sciences, as stated in the 
RFA.
5. Ability to Conduct Proprietary Research
    The application shall demonstrate the applicant's ability to 
conduct proprietary research and to protect confidentiality of data, 
procedures, etc.
6. Staff Experience and Capabilities
    The application must demonstrate the availability of core staff 
with the experience and capability to conduct research as described in 
the detailed plan presented in item 2 above. The staff must have the 
capability to deal with natural products research as well as plan long-
range research to assess future needs. The availability of sufficient 
administrative and support personnel to meet the RFA objectives must 
also be demonstrated.
7. Reasonableness of proposed budget
    The application is evaluated on the bases of the reasonableness of 
costs.

VIII. Submission Requirements

    The original and two copies of the completed grant application form 
PHS 398 (Rev. 4/98), with appendices for each of the copies, should be 
delivered to Rosemary Springer (address above). The application receipt 
date is June 18, 2001. 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-2001-2.''

IX. Method of Application

A. Submission Instructions

    Applications will be accepted during normal business hours, 8 a.m. 
to 4:30 pm., 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 nonresponsive and returned to the applicant. 
Applications must be submitted via mail delivery as stated above. FDA 
is unable to receive applications electronically. Instructions for 
completing the application form can

[[Page 22240]]

be found on the following Web site: 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. 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.

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 mailing label address. The face page 
of the application should reflect the request for applications number 
RFA-FDA-CFSAN-2001-2.
    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: April 30, 2001.
William K. Hubbard,
Senior Associate Commissioner for Policy, Planning, and Legislation.
[FR Doc. 01-11159 Filed 5-2-01; 8:45 am]
BILLING CODE 4160-01-S