[Federal Register Volume 63, Number 105 (Tuesday, June 2, 1998)]
[Notices]
[Pages 30002-30005]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-14462]
[[Page 30002]]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
Memorandum of Understanding Between the Food and Drug
Administration and the National Institutes of Health's National
Institute of Dental Research
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
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SUMMARY: The Food and Drug Administration (FDA) is providing notice of
a memorandum of understanding (MOU) between the National Institutes of
Health's National Institute of Dental Research (NIDR) and three of
FDA's line organizations: the Center for Devices and Radiological
Health, the Center for Drug Evaluation and Research, and the Center for
Biologics Evaluation and Research. The purpose of the MOU is to
facilitate interactions between NIDR and FDA regarding improvements in
the quality and relevance of preclinical and clinical research, which
is directed to the development of products for use in oral healthcare.
DATES: The agreement became effective August 10, 1997.
FOR FURTHER INFORMATION CONTACT:
Susan Runner, Center for Devices and Radiological Health (HFZ-410),
9200 Corporate Blvd., Rockville, MD 20850, 301-443-8879, or
Norman S. Braveman, National Institute of Dental Research, National
Institutes of Health, 45 Center Dr., MSC 6400, Bldg. 45, rm. 4AN-24,
Bethesda, MD 20892-6400, 301-594-2089.
SUPPLEMENTARY INFORMATION: In accordance with 21 CFR 20.108(c), which
states that all written agreements and MOU's between FDA and others
shall be published in the Federal Register, the agency is publishing
notice of this MOU.
Dated: May 21, 1998.
William K. Hubbard,
Associate Commissioner for Policy Coordination.
225-97-6000
Memorandum of Understanding Between the National Institutes of Health,
National Institute of Dental Research and the Food and Drug
Administration, Center for Devices and Radiological Health, Center for
Drug Evaluation and Research, Center for Biologics Evaluation and
Research
I. Purpose
This Memorandum of Understanding hereby establishes a formal
collaborative arrangement between the National Institutes of
Health's National Institute of Dental Research (NIDR) and three of
the Food and Drug Administration's (FDA) line organizations: Center
for Devices and Radiological Health (CDRH), Center for Drug
Evaluation and Research (CDER), and Center for Biologics Evaluation
and Research (CBER).
This agreement has been developed to facilitate interactions
between the NIDR and the FDA regarding improvements in the quality
and relevance of pre-clinical and clinical research which is
directed to the development of products for use in oral health care.
The principal goal of this agreement is to reduce the time between
the research and development phase of a product's life cycle and its
commercial availability. This goal will be attained by enhancing the
quality of product-related research and thus facilitate and improve
premarket evaluations.
This agreement also sets forth certain working arrangements
between both parties that will enable each to fulfill its respective
mission more efficiently and effectively.
II. Background
It is widely accepted that the United States has a world-class
health care system. This status is due in part to entrepreneurship
and capital investment in the private sector. It is also the result
of our nation's longstanding commitment to Federally-funded research
into health promotion, disease prevention, diagnosis, etiology and
pathogenesis, as well as cost-effective therapeutic approaches for
varied and complex health conditions. A third contributing factor is
the existence of a vigilant national regulatory system that ensures
health professionals and consumers are provided with safe, high
quality and clinically viable medical products. Despite the
reputation of the U.S. system, however, government agencies with
responsibility for the development, promotion and regulatory
oversight of new medical products are today, as always, striving to
eliminate operational inefficiencies that can act as barriers to the
development of new technologies and therapeutics and their timely
introduction into the marketplace. Leaders throughout the government
sector have intensified efforts to sharpen current modes of business
as a means to economize, to insure the expenditure of public funds
will yield commensurate public benefits, and to enable the Federal
government to better serve the contemporary needs of its
constituencies.
Increasingly in recent years, NIDR and FDA component
organizations have harnessed their interdisciplinary skills and
professional expertise in a number of areas affecting the public
health. Although complementary and beneficial, these interactions
have largely been ad hoc and informal. Leaders of both agencies have
recognized the added benefits that can accrue from a broader, more
formal working arrangement. To this end, this agreement establishes
a generalized, cooperative framework with end-goals and categories
of activities that, taken together, provide the foundation for a
working relationship that is better focused and takes fuller
advantage of each organization's strengths and experience.
III. Substance of Agreement
As noted above, this agreement charts a general course of
interaction between the NIDR and three of FDA's product centers that
encompasses the following areas:
(A) information exchange;
(B) state-of-the-science workshops and conferences;
(C) staff development;
(D) fellowship sponsorship;
(E) policy development;
(F) research; and
(G) advisory committee and study section review and
appointments.
The ``Implementation Work Plan'' attached to this agreement
identifies the range of specific projects and activities that fall
within each of the seven categories. The Work Plan also provides a
narrative description of the commitments made by each of the
signatory agencies and specifies relative priorities and projected
implementation timeframes, which are subject to change during the
period when this agreement is in effect.
Both parties envisage this agreement and its components to be
implemented on an evolutionary and incremental basis in accordance
with available organizational resources and mutual determination of
the feasibility and anticipated benefit(s) of individual activities.
Moreover, both parties have agreed that whenever appropriate and
possible, interagency activities--either on a categorical or
individual basis--should be periodically evaluated to confirm that
the putative benefits in relation to administrative costs and other
considerations justify continuation or expansion of the activities
specified in this agreement. Evaluation of this pioneering agreement
may also serve to establish the basis for similar collaborative
arrangements between other NIH Institutes and FDA in the future.
IV. Name and Address of Participating Parties
(1) National Institute of Dental Research, National Institutes of
Health, 31 Center Drive, MSC 2290, Building 31, 2C39 Bethesda, MD
20892-2290, Telephone: 301-496-3571, FAX: 301-402-2185.
(2) Food and Drug Administration (HF-1), 5600 Fishers Lane,
Rockville, MD 20857, Telephone: 301-827-3310, FAX: 301-443-3100.
(a) Center for Devices and Radiological Health (HFZ-1), 9200
Corporate Boulevard, Rockville, MD 20850, Telephone: 301-443-4690,
FAX: 301-594-1320.
(b) Center for Drug Evaluation and Research (HFD-1), 5600
Fishers Lane, Rockville, MD 20857, Telephone: 301-594-6740, FAX:
301-594-6197.
(c) Center for Biologics Evaluation and Research (HFM-1), 8800
Rockville Pike, Bethesda, MD 20892-001, Telephone: 301-827-0548,
FAX: 301-827-0440.
V. Liaison Officers
For the National Institute of Dental Research:
Dushanka V. Kleinman, D.D.S., M.Sc.D., Deputy Director, National
Institute of Dental Research, National Institutes of Health, 31
Center Drive, MSC 2290
[[Page 30003]]
Building 31, Room 2C39, Bethesda, MD 20892-2290, Telephone: 301-496-
9469, FAX: 301-402-2185, E-mail: [email protected]
Lois K. Cohen, Ph.D., Alternate Director, Division of Extramural
Research, National Institute of Dental Research, National Institutes
of Health, 45 Center Drive, MSC 6400, Building 45, Room 4AN-18,
Bethesda, MD 20892-6400, Telephone: 301-594-7710, FAX: 301-480-8319,
E-mail: [email protected]
For the Food and Drug Administration:
Bernard A. Schwetz, D.V.M., Ph.D., Interim Chief Scientist,
Office of the Commissioner (HF-32), Food and Drug Administration,
5600 Fishers Lane, Room 17-35, Rockville, MD 20857, Telephone: 301-
827-3340, FAX: 301-827-3042, E-mail: [email protected]
Elizabeth D. Jacobson, Ph.D., Alternate Deputy Director for
Science, Center for Devices and Radiological Health (HFZ-2), 9200
Corporate Boulevard, Room 100G, Rockville, MD 20850, Telephone: 301-
443-4690, FAX: 301-594-1320, E-mail: [email protected]
VI. Interagency Steering Committee
To assist the Liaison Officers in the management, coordination
and oversight of this agreement and the concomitant Implementation
Work Plan, an interagency steering committee shall be established.
The Committee will be comprised of an equal number of member
representatives from the NIDR and FDA, including the Liaison
Officers who shall serve as co-chairs of the Committee. Member
appointments shall be authorized by the signatories to this
agreement and shall last for a period of one (1) year, unless
renewed by the agreement signatories upon recommendation from the
Liaison Officers. The Committee shall meet at least once every six
months for the first year of this agreement and then at least once
annually thereafter to review the progress of this agreement,
resolve any issues and disputes that may arise, re-direct specific
activities set forth in the Work Plan, and oversee necessary
modifications to the agreement.
As of the date this agreement is approved and accepted, the
following persons are designated to serve on the Committee for the
initial one-year term.
For the National Institute of Dental Research:
Dushanka V. Kleinman, D.D.S., M.Sc.D., Co-Chair
Lois K. Cohen, Ph.D., Alternate
Norman S. Braveman, Ph.D., Chief, Program Development Branch,
Division of Extramural Research, National Institute of Dental
Research, National Institutes of Health, 45 Center Drive, MSC 6400,
Building 45, Room 4AN-24, Bethesda, MD 20892-6400, Telephone: 301-
594-2089, FAX: 301-480-8318, E-mail: [email protected]
Henning Birkedal-Hansen, D.D.S., Ph.D., Scientific Director,
Division of Intramural Research, National Institute of Dental
Research, National Institutes of Health, 30 Convent Drive, MSC 4326,
Building 30, Room 132, Bethesda, MD 20892-4326, Telephone: 301-496-
1483, FAX: 301-402-8318, E-mail: [email protected]
For the Food and Drug Administration:
Bernard A. Schwetz, D.V.M., Ph.D., Co-Chair
Elizabeth D. Jacobson, Ph.D., Alternate
Michael Weintraub, M.D., Director, Office of Drug Evaluation V
(HFD-105), Center for Drug Evaluation and Research, 9201 Corporate
Boulevard, Room S219, Rockville, MD 20850, Telephone: 301-827-2250,
FAX: 301-827-2317, E-mail: [email protected]
Philip D. Noguchi, M.D., Director, Division of Cellular and Gene
Therapies (HFM-515), Office of Vaccines Research and Review, Center
for Biologics Evaluation and Research, 8800 Rockville Pike, Building
N29B, Room 2NN20, Bethesda, MD 20892-001, Telephone: 301-827-0680,
FAX: 301-827-0449, E-mail: [email protected]
VII. Period of Agreement
Upon acceptance by both parties, this agreement will become
effective immediately and remain in effect for a period of three (3)
years from the date of signature by authorized officials from both
agencies unless extended by the parties. The terms of this agreement
may be modified upon mutual written consent, or terminated by either
party with a minimum 30-day advance written notice to the other
party. Evaluation of the terms and success of this agreement will be
made periodically throughout the existence of the interagency
arrangement. Within ninety (90) days prior to expiration of this
agreement, a formal written evaluation shall be prepared by both
parties and submitted to appropriate officials of both agencies with
recommendations regarding the furtherance or discontinuation of the
agreement.
VIII. Funding
No funding will be provided or exchanged by either party as part
of this agreement. NIDR and FDA personnel will collaborate on
projects of mutual interest. Facilities and equipment of each party
will be made available to the other on an as needed basis in
accordance with the individual project and activity plans and
arrangements.
IX. Reporting Requirements
In addition to the evaluation report(s) referenced in section
VII. above, reporting responsibilities will be determined on a case-
by-case basis and as required by individual projects and activities.
Reports will be provided to all Liaison Officers named in this
agreement.
X. Schedules and Milestones
Schedules and milestones for all collaborative projects and
activities authorized by this agreement will be developed by mutual
agreement on a case-by-case basis. Schedules and milestones may be
set by interagency working groups established and tasked to
implement the specific projects and activities outlined in the
Implementation Work Plan appended to this agreement.
XI. Disposition of Data
The plan for each project and activity set forth in the
Implementation Work Plan as appended to this agreement will specify
the disposition of data and other information that may result from
or be used during the course of a project or activity. Publication
or public dissemination of data and information exempt from public
disclosure under applicable law shall not occur without prior
notification and concurrence of the Liaison Officers of both
parties.
XII. Sharing Data and Information
Both parties agree that a free exchange of data and information
is vital to the successful execution of this agreement. Therefore,
to the extent allowed under 21 U.S.C. 331(j), 21 U.S.C. 360j(c), 42
U.S.C. 353g(d), 42 U.S.C. 263i(e), 21 CFR Part 20, or other
applicable law, the parties agree to share data and information as
necessary. No exchange of non-public information will occur unless
appropriate safeguards are established and set forth in individual
work plans and first approved by the agencies' Liaison Officers.
XIII. Disclosure of Data and Information in Response to Requests
If disclosure of data or information received by a party under
this agreement is requested under the Freedom of Information Act, a
Congressional inquiry or pursuant to other duties and
responsibilities of either party to this agreement, the agency that
receives the request shall notify the agency that provided the
information. The notified agency will be responsible for making any
requisite contact with the submitter of the protected information
and will accept full responsibility for evaluating the submitter's
comments prior to rendering a disclosure determination.
To preserve maximum control over actual disclosure of their
respective records, each party to this agreement shall retain legal
authority and the concomitant responsibility regarding disclosure of
documents provided to the other agency.
XIV. Government Property/Facilities/Personnel
Both parties to this agreement will make available personnel and
facilities as required by individual projects and activities as set
forth in the mutually developed work plans. NIDR personnel enlisted
to serve as Federal consultants or liaisons on FDA advisory
committees and panels will be subject to the same rights,
privileges, obligations and restrictions as all other special
government employees who serve on the agency's advisory bodies.
Similarly, all FDA employees selected to serve in a consultative
capacity on NIDR research study sections and advisory bodies will be
bound by the same rules and allowances that apply to all other
consultants appointed by NIDR.
Approved and Accepted for the National Institute of Dental
Research:
By: Harold C. Slavkin, D.D.S.
Title: Director, National Institutes of Dental Research, NIH
National Institutes of Health
[[Page 30004]]
Date: August 1, 1997
Approved and Accepted for the Food and Drug Administration:
By: Michael A. Friedman, M.D.
Title: Lead Deputy Commissioner
Food and Drug Administration
Date: August 10, 1997
Appendix: Implementation Work Plan
Appendix
Implementation Work Plan for Memorandum of Understanding Between the
National Institute of Dental Research and the Food and Drug
Administration
Introduction
The National Institute of Dental Research (NIDR) and the Food
and Drug Administration (FDA) have embarked upon a formal
collaborative arrangement whose dual aims are to: (1) facilitate the
development and market introduction of newly-emerging, safe and
effective health care products to enable oral health professionals
and auxiliaries to provide higher quality services and equip
consumers with the tools necessary to improve and sustain their own
oral, dental and cranio-facial health; and (2) provide complementary
support and expertise to enable each agency to better fulfill its
public health mission.
This Implementation Work Plan describes the specific projects
and activities that initially constitute the substance of the
collaborative arrangement between the two agencies. The information
that follows is intended to serve as an overall work plan or
framework for NIDR and FDA personnel assigned individual projects
and activities. The specific outcomes, completion timeframes,
interaction mechanisms, etc. associated with each project and
activity will be defined by those persons designated by each agency
to serve on interagency working groups. The relative priority of
each project/activity is identified by the use of the letters ``I''
(immediate-- within 3 mos.), ``S'' (short-term--within 6-12 mos.),
and ``L'' (long-term--beyond 12 mos.).
A. Information Exchange
In this area of collaboration, NIDR and FDA agree to pursue the
following activities:
Initiation of an ongoing series of introductory
meetings and orientation briefings to acquaint NIDR and FDA
personnel with each other's statutory obligations, programs,
operational capacities, policies, processes, etc. that are relevant
to this agreement. [I]
Identification of key contact persons at each agency
and preparation of a contact/referral directory to facilitate
interagency communication and information exchange. [I]
Establishment of a hyperlink between existing FDA and
NIDR Internet websites to permit continual and instantaneous access
to routine and late-breaking information of mutual interest. [I]
Establishment of an internal exchange forum to enable a
periodic two-way sharing of information related to new research
initiatives by both agencies, market applications for important new
products pending with FDA, emerging public health issues and
emergencies and policy development. Biomimetics is a case in point
and could be used as a case study to identify optimal methods for
both parties to monitor an issue from the conceptual stage through
research and development. [S]
Creation of a ``Oral, Dental and Cranio-Facial Forum''
in which NIDR and FDA can interact periodically with leading
representatives of the regulated industry, academia, the research
community and others on issues relating to technology development
and transfer (including regulatory processes for acquiring market
clearance), product utilization and treatment outcomes, adverse
event reporting, etc. [S]
Assessment of the viability of NIDR and/or FDA experts
serving as Federal ``ombudsmen'' to oversee state-of-the-art
advances in oral, dental and cranio-facial technologies and
therapeutics through direct, ``in the field'' interactions with
clinical investigators, product developers, scientific researchers,
etc. The ombudsmen would act as conduits through which regulatory
process and research funding information could be funneled to the
industrial and research sectors. Information on emerging products,
in both the concept and development stage, could in turn be fed back
to NIDR and FDA with the end goal of accelerating the flow of new
products that are safe and effective from the R&D arena to the
clinical environment. [L]
This feasibility assessment could also encompass the concept of
an ombudsman or independent, non-government expert(s) conducting an
evaluation of a sampling of dental products whose basic research
costs are underwritten by NIDR that traces the developmental
histories through patent acquisitions and FDA market clearances. The
purpose of such evaluations would be to augment the existing patient
evaluation study by providing documentation of selected impact(s) of
NIDR-funded research on public health and the ``bench-to-chairside''
delivery of important new oral care products. [L]
B. Science Transfer & State-of Science Workshops/Conferences
Participation by FDA regulatory policy-makers and
program officials in various conferences in 1997-98 sponsored by
NIDR or in which NIDR has a planning/participant role. FDA
involvement could entail formal workshops (e.g., FY99 meeting of
AADR/AADS meeting), individual presentations, use of existing
videotaped FDA teleconferences on selected regulatory policy and
process issues, technology transfer, etc. In addition, NIDR staff
will participate in FDA-sponsored workshops and conferences with
relevance to oral and dental health care products and services.
Collaborative discussions and planning between NIDR and FDA could
serve to focus the form and content of information conducive to each
presentation setting and ensure proper coverage by both agencies at
key outside conferences and meetings. [I/S]
Development and joint sponsorship of conferences,
symposia and workshops whose foci and outputs will mutually benefit
NIDR and FDA, e.g., in the area of technology transfer. [S/L]
Review of the feasibility and utility of live, jointly-
produced videoteleconferences using FDA/CDRH and/or NIDR facilities
to communicate to each agency's constituencies on topical areas of
interest, fast-moving events, new research and regulatory
initiatives, etc. [S]
Development, pilot testing and nationwide dissemination
of a regulatory training module for U.S. dental school instructors,
dental students, clinical trial sponsors and investigators to
broaden their understanding of FDA's market clearance requirements
and product evaluation processes. [L]
C. Staff Development and Collaborations
Arrange for the temporary exchanges of NIDR and FDA
specialists for pre-set periods of time (e.g., 6-12 months). These
cross-appointments, which could include rotation of FDA scientists
and clinicians through the NIH Clinical Center where research is
performed, could enhance the understanding of each party to the
policies and procedures of the other. This cross-fertilization of
knowledge and experience could subsequently be shared with in-house
colleagues and outside constituent groups in ways that could
expedite technology transfer. [S]
Provide for FDA scientists and regulatory process
experts to participate in NIDR reviews of research applications
(e.g., SBIR/STTR) as a means of gaining insights into future
research and product development directions, which in turn would
enable FDA product reviewers to better anticipate and prepare for
scientific and clinical issues associated with future product
applications. [S]
Provide for NIDR experts to directly participate in
premarket evaluations of selected new dental products whose
scientific and clinical aspects may be complex or controversial, in
addition to submissions seeking FDA authorization to conduct
clinical studies involving experimental products. [S]
Involvement of NIDR experts in a ground-breaking
initiative relating to FDA's review process for medical devices,
specifically the Product Development Protocol, a mechanism
authorized by Federal law by which FDA and device producers can
reach agreement at the front end of the premarket review process on
test endpoints that, once satisfied, provide for a higher degree of
assurance (but no guarantee) of market clearance. Resident
scientific and clinical expertise at NIDR could be relied upon as
this mechanism is pilot tested and in actual ``negotiations'' with
product manufacturers and study sponsors. [S]
Development of reference documents describing FDA
investigational product and market approval processes for use by
NIDR reviewers in conferring with prospective research grantees and
contractors to better assure their clinical studies conform to FDA
marketing requirements, which will help spur the clinical
availability of valuable new products. Such documents could be
adaptations of the regulatory training module discussed in Section
B. of this document. [S]
Evaluation of the feasibility of NIDR requiring
prospective research contractors
[[Page 30005]]
and grantees, as a condition for a funding award, to submit review
protocols or criteria that FDA can use in performing premarket
reviews of breakthrough products used in the prevention, diagnosis
and treatment of oral, dental and cranio-facial diseases and
conditions. [S]
Investigation into methods by which NIDR and FDA can
jointly and individually promote the availability and use of FDA's
adverse incident reporting systems (e.g., MedWatch) among oral
health professionals and other health and dental product user
groups. [S]
Enlistment of NIDR technical, statistical and clinical
experts to assist FDA in the design and content development of
guidance documents that FDA product reviewers can use to assess
product safety and effectiveness. [L]
D. Fellowship Sponsorship
Investigation into the merits and legal aspects of
establishing non-Federal fellowships in which interested parties
from the private sector would subsidize individuals with an interest
in FDA regulatory processes for one-year residency periods. Under
such an arrangement, NIDR could serve as fiduciary in order to
prevent appearances of conflict-of-interest. Fellowship assignments
would entail generalized exposure to and experience with FDA
regulatory procedures so as to also avoid access to protected,
product-specific information that could be used for competitive
advantage. Fellows would also be subjected to the controls, rights,
privileges and restrictions to which all other FDA-recruited special
government employees are subjected. [L]
E. Policy Development
Continuation of current interchanges and expert
consultations on selected policy issues that engender wide-scale
interest among consumers and/or oral health professionals, involve
products or therapies that pose a known or potential health risk to
the general public, relate to research and regulatory processes
affecting the pace of technology transfer, etc. This activity should
extend to other matters of major import such as the Surgeon
General's report on oral health which NIDR has been charged to
produce and to which FDA can substantively contribute. [I]
F. Research
Continuation of ongoing research collaborations, such
as those between CBER and NIDR's Division of Intramural Research.
Coordination of NIDR's biological and clinical
resources and the CDRH's engineering and life sciences expertise to
address a number of diverse issues relating to cleaning, infection
and sensitivity reactions to new biomaterials. [S]
Establishment of one or more patient registries for
purposes of monitoring adverse incidents linked to particular dental
products in addition to product-specific performance trends. Such an
activity could be jointly undertaken by FDA and NIDR, as well as in
conjunction with involvement by other organizations such as USP and
various dental professional and product user organizations. [L]
Initiation of collaborative research aimed at
developing fundamental data and methods needed to assess long-term
performance of dental devices and systems. Such research could
include the joint development of physical, animal and computer-based
models to adequately evaluate long-term clinical performance of
marketed and evolving dental devices (e.g., osseous integration of
dental implants, fatigue performance of ceramic porcelains, etc.).
[L]
G. Advisory Committee & Study Section Review/Appointments
Provision of ad hoc or liaison status to FDA officials
on the NIDR National Advisory Dental Research Council (including
access to closed sessions of the Council on a case-by-case, need-to-
know basis), in addition to DRG and other study sections/review
groups for the purpose of assisting NIDR in its review of extramural
research submissions. [S]
Expansion of current NIDR participation as consultants
and/or Federal liaisons on dental-related advisory committees and
panels managed by FDA (including access to closed sessions on a
case-by-case, need-to-know basis) for the purpose of augmenting the
scientific and clinical expertise that is brought to bear on product
applications and proposed policies on which outside advice is sought
by the agency. [S]
Formal solicitation of advice by each party from the
other on candidate nominations for appointment to NIDR and FDA
review and advisory bodies. [S]
[FR Doc. 98-14462 Filed 6-1-98; 8:45 am]
BILLING CODE 4160-01-F