[Federal Register Volume 60, Number 89 (Tuesday, May 9, 1995)]
[Notices]
[Pages 24635-24636]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 95-11415]



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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[FDA 225-94-6001]


Memorandum of Understanding Between the Food and Drug 
Administration and the National Institute of Standards and Technology

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 FDA and the National 
Institute of Standards and Technology (NIST). The purpose of the MOU is 
to collaborate in a program to develop standard reference materials 
(SRM's) for a variety of biomaterials.

DATES: The agreement became effective February 14, 1994.

FOR FURTHER INFORMATION CONTACT: Sandy Cordes, Center for Devices and 
Radiological Health (HFZ-20), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-443-3516.

SUPPLEMENTARY INFORMATION: In accordance with 21 CFR 20.108(c), which 
states that all written agreements and memoranda of understanding 
between FDA and others shall be published in the Federal Register, the 
agency is publishing notice of this memorandum of understanding.

    Dated: May 2, 1995.
William B. Schultz,
Deputy Commissioner for Policy.

Memorandum of Understanding Between the National Institute of Standards 
and Technology and the Food and Drug Administration, November 10, 1993

    This memorandum of understanding (MOU) between the U.S. 
Department of Commerce, National Institiute of Standards and 
Technology (NIST) and the U.S. Department of Health and Human 
Services, Food and Drug Administration (FDA) has been implemented to 
facilitate the development of Standard Reference Materials (SRMs) 
for materials used in medical implant applications. These materials 
are commonly referred to as biomaterials.

Background

    The National Institute of Standards and Technology has, as one 
of its long-standing programs, the development of and marketing of 
standard reference materials required for precision metrology in a 
variety of applications. The Food and Drug Administration is 
responsible for the regulation of medical devices made from 
biomaterials. For many of these biomaterials, it has been determined 
that subtle variations in chemical composition, trace element 
content, crystalline structure or morphology, homogeneity, surface 
topology and chemistry, and other material characteristics can 
significantly alter the response of living tissue (i.e. the body) to 
a material, either as an implant or by external contact. Thus the 
availability of well-characterized reference materials for use in 
generating baseline data on the biological performance of a 
biomaterial, is essential.

Overview

    The parties to this MOU will collaborate in a program to develop 
(SRMs) for a variety of biomaterials. This collaboration will enable 
NIST to enhance its activities in the biomedical area and increase 
the utility of its SRM Program by addressing many critical 
measurement needs in the assessment of biomaterials and medical 
devices. The SRM Program at NIST will gain marketable SRMs for 
biomaterials, an area in which NIST has had no previous products. At 
the same time, [[Page 24636]] FDA will be assuring the availability 
of well-characterized and uniform reference materials for the 
comparative evaluation of new materials and devices. Evaluation of 
biological performance data based on comparison to previously-used 
and successful products will be both facilitated and improved.

Program Description

    1. Selection of Materials--Candidate materials for SRM 
development will be selected by mutual agreement between FDA and 
NIST. The goal is to provide more realistic calibration standards 
for the determination of physical, chemical, electrical, and 
biological characteristics and/or properties of biomaterials. 
Criteria for selection will include magnitude of the current or 
potential utilization of the material in biomedical applications, 
documented or reasonably foreseeable variability in response from 
``off-the-shelf'' materials, criticality of the medical application, 
cost of developing and potential market for the SRM, and others 
mutually agreeable to both parties. At the time of selection, the 
properties and characteristics to be controlled and measured will be 
identified for each candidate SRM, as will be the proposed unit size 
for distribution.
    1.a An initial listing of candidate materials proposed at the 
time of the initial agreement is given in Appendix A. Materials 1 & 
2 were developed as a collaborative research iniative between FDA 
and the American Dental Association (ADA) at both the FDA and NIST 
laboratories. Material 1 has been provided to NIST for consideration 
as an SRM. Material 2 which is currently being synthesized will be 
provided on or about September 1993. No development work has been 
done on materials 3-8.
    2. Production of Materials--SRMs will be developed by any of 
several laboratories, including NIST, FDA, NIH, commercial materials 
suppliers, device manufacturers, academic institutions, and others. 
A Material Safety Data Sheet (MSDS) will be required from the 
supplier of all component materials and precursor/catalyst/ancillary 
materials used in the production of SRMs developed under this MOU.
    3. Certification--NIST will determine and specify what testing 
must be performed and be the sole reviewer of the adequacy of data 
used in the qualification of SRMs developed under this MOU. NIST 
reserves the right to refuse distribution of materials if the data 
are inadequate. All SRMs developed under this program will be 
supplied with NIST certification for the properties/characteristics 
deemed critical to the application.
    4. Packaging--NIST will determine for each SRM the appropriate 
source of packaging, either in-house or contract. Contract packagers 
will seal the entire shipment in appropriate packages for shipment 
to NIST.
    5. Replenishment--NIST agrees to assume the responsibility for 
replenishment of stocks for SRMs for which the market is at a level 
that is financially beneficial to the Standard Reference Materials 
Program.
    6. Program Funding--FDA does not commit to providing any funding 
or equipment to NIST or any selected SRM producer, or to providing 
any laboratory effort in the development, characterization, or 
production of SRMs being developed under this program.

Costs and Pricing

    1. Initially, FDA will provide 900 grams of hydroxyapatite 
(material 1, Appendix A) and 1000 grams of <greek-b>-Tricalcium 
Phosphate (material 2, Appendix A) to NIST for use as an SRM. No 
compensation to FDA is required for this initial supply of material. 
Monies collected from the sale of the SRMs, which is over and above 
the cost to produce, characterize and package the materials will be 
used for additional SRM development.
    2. NIST will have final authority over all matters pertaining to 
pricing policy and for setting the price of individual SRMs.

General

    1. SRMs developed in whole or in part by FDA prior to or under 
this MOU, which remain unsold and are deemed by NIST, to be 
technologically obsolete or otherwise no longer acceptable as SRMs, 
may be removed from the NIST inventory without liability for 
reimbursement to FDA by NIST. If FDA desires such products returned 
to FDA, NIST will do so at FDA's expense after removal of SRM 
certification.
    2. The official representatives of the respective organizations 
will be:
    FDA: Director Division of Mechanics and Materials Science Office 
of Science and Technology Center for Devices and Radiological Health
    NIST: Chief Standard Reference Materials Program Office of 
Measurement Services

Effective Dates

    1. This MOU will become effective 30 days after being signed by 
the appropriate authorities at both NIST and FDA. It will remain in 
effect until terminated.
    2. Either NIST or FDA may unilaterally terminate this MOU by 
providing the other party written notice. It will become ineffective 
60 days after such notice is delivered.

 Approval/Acceptance

    Signed:
D. Bruce Burlington, M.D.
Director, FDA/CDRH
Date: November 19, 1993
    Approved:
Peter L.M. Heydemann, PhD.
Director, NIST/Technology Services
Date: January 14, 1994
    Concur:
Thomas E. Gills
Chief, NIST/SRMP
Date: January 14, 1994

Appendix A

Purpose:

    Development of a series of Calcium-Phosphorous based SRMs for 
use in determining the composition of mixtures of calcium phosphate 
based biomaterials or biomaterial coatings.
    Proposed Calcium Phosphate Reference Biomaterials

1. Ca<INF>3(PO<INF>4)<INF>3OH.........  Hydroxyapatite.........  Ca/P=1.67             
2. Ca<INF>3(PO<INF>4)<INF>2...........  Tricalcium Phosphate     Ca/P=1.50             
                          (<greek-b>).                                  
3. Ca<INF>3(PO<INF>4)<INF>2...........  Tricalcium Phosphate     CA/P=1.50             
                          (amorphous).                                  
4. Ca<INF>4(PO<INF>4)<INF>2O..........  Tetracalcium Phosphate.  CA/P=2.0              
5. Ca<INF>3(PO<INF>4)<INF>2...........  Tricalcium Phosphate     CA/P=1.50             
                          (<greek-a>).                                  
6. Ca<INF>2P<INF>2O<INF>7.............  Calcium Pyrophosphate    CA/P=1.0              
                          (<greek-a> <greek-b>                          
                          <greek-g>).                                   
7. CaO.................  Calcium Oxide..........  NA                    
8. Ca<INF>10 (PO<INF>4) <INF>5F<INF>2......  Fluorapatite...........  CA/P=1.67             

[FR Doc. 95-11415 Filed 5-8-95; 8:45 am]
BILLING CODE 4160-01-F