Memorandum of Understanding Between the Food and Drug Administration and the National Institutes of Health's National Institute of Dental Research

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