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ISO/CD 10993-18 "Biological evaluation of medical devices - Part 18:
Chracterization of materials" のＣＤ投票が行われる。
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コメント先：中村晃忠（国立医薬品食品衛生研究所）
　　　　　　FAX: 03 3707 6950   E-mail:nakamura@nihs.go.jp

Characterisation of Materials

Contents
Introduction
Specification
1 Scope
2 Normative references
3 Definitions
4 General principles
5 Categories of materials
6 Determination of compositional information
7 Extraction of materials
8 Testing of extracts
9 Reporting of data obtained
Annexes
A (informative) Flowchart for the generation and use of data
B (informative) Guidance on material characterisation
C (informative) Bibliography of international and national standards and regulations

Introduction

ISO 10993-1: 1996 Biological evaluation of medical devices PartI: Evaluation and testing provides a framework for a structured programme of assessment for the evaluation of biological safety.
In Section 3 General principles applying to the biological evaluation of materials and devices it is stated that in the selection of materials to be used for device manufacture the first consideration should be fitness for purpose. This should have regard to the characteristics and properties of the material which include chemical, toxicological, physical, electrical, morphological and mechanical properties. This information is necessary prior to any biological evaluation, Also prEN 1441 : 1995, Medical devices - Risk analysis points out that a toxicological risk analysis should take account of the chemical nature of the materials.
The requirements specified in this document are intended to yield the following information :

(a) The chemical composition of the materials used in the manufacturing process and also processing additives and residues. The physico-chemical, mechanical and morphological and predictable

(b) The materials of construction of the medical device.
(c) The potential of materials to release leachable substances when used in the manufacture of a medical device.

Note: This does not cover industrial hygiene aspects which are covered by other regulations.

The compositional characteristics of the materials of manufacture are mainly under the control of the suppliers of these materials. However other characteristics are chiefly influenced by the requirements to be met by the finished medical device as well as the processes used by the medical device manufacturer

Characterisation or materials

1 Scope

This document specifies a framework for the identification and characterisation of materials used in medical devices to provide information relevant to a biological safety assessment.
The procedure comprises the identification of chemicals present in materials and the determination of their potential biological exposure. The determination of relevant physico-chemical mechanical and morphological characteristics is also covered.
The standard does not cover characterisation issues associated with pertormance criteria but is restricted to biological safety evaluation. It also does not cover the identification or quantification of any degradation products.
This standard is intended for use by suppliers of materials, manufacturers of medical devices and those carrying out a biological safety assessment.

2 Normative references

The following standards contain provisions which, through reference in this text, constitute provisions of this International Standard. At the time of publicatiort, the editions indicated were valid. All standards are subject to revision and parties to agreements based on this International Standard are encouraged to investigate the possibility of applying the most recent editions of the standards indicated below. Members of IEC and ISO maintain registers of currently valid International Standards,

ISO 10993-1 Biological evaluation of medical devices - Part 1: Evaluation and testing.

ISO 10993-12 Biological evaluation of medical devices - Part 12: Sample preparation and reference materials.

3 Definitions

For the purposes of this standard the definitions given in ISO 10993 Part 1 and the following additional definitions apply.

3.1 supplier: The person who manufactures and/or supplies the basic starting materials to be used in the manufacture of a medical device

3.2 manufacturer: The natural or legal person with responsibility for the design, manufacture, packaging and labelling of a device before it is placed on the market under his own name, regardless of whether these operations are carried out by that person himself or on his behalf by a third party.

3.3 component: An item which is manufactured from a basic starting material but is not itself a medi cal dcvice. si nce it forms only one part of a medical device.

3.4 convertor: A person who converts a hasic raw material into a semi-finished product, for
example: lengths of rod, tubing or lay-flat film.

4 General principles

Consideration of the characterisation of the materials from which a medical device is made is a necessary first step in assessing the biological safety of the device. An overview of the procedure outlined in this document is given in Annex A.

4.1 Chemical characterisatlon

Qualitative data shall be obtained to describe The chemical composition of a material. When relevant to biological safety quantitative data shall also be obtained. Further guidance is given in Annex B.

4.2 Pliysico-chemical characterisation

Pliysico-chemical characteri stics of a material which should be considered for their influence on biological safety include the following:

the form of the material i e. solid. liquid or gas; adsorption of chemicals or blood components at the sur face, absorption of fluid:
expansion at body temperature or in contact with body fluids;
change in physical for rim at body tcmperature or in contact with body fluids, e.g. gel to fluid, fluid to thixotropic paste;
adhesive properties;
effect of sterilisation processes;
electrochemcal properties.

4.3 Mechanical characterisation

Mechanical properties of a material which should be considered as important for biological safety include the following:

flexibility tinder strain. surface hardness, elasticity;
dynamic wear characteristics against other substances; plasticity (mouldability);
mechanical stability with times
effect of sterilisation processes,

4.4 Morphological characterisation

Morphological characteristics which should be considered for their effect on the biological response of materials include:

cellular interaction with porous or smooth surfaces; fluid flow on different types of surface;

adsorption of proteins by different types of surface;
adsorption of blood components by different types of surface; surface finish;
wear characteristics;
surface area and adsorption properties.

Note: The lists in 4.2, 4.3 and 4.4 are aides-memoire and are not exhaustive

5 Categories of materials
The first consideration should be the physical form of the material i.e solid, liquid or gas. For the purpose of this standard the materials encompassed by the definition may be conveniently divided into two categories. This division is related to the complexity of the chemical composition of the material.

5.1 Polymers, natural and synthetic
Synthetic polymers will usually contain a larger number of components such as unreacted monomer residue, catalyst and solvent residues, oligomers, production aids and modifying additives including pigments. Many of these will be present at very low levels.
Natural polymers may vary significantly dependant on the biological source and may contain impurities and residues resulting from that source. This standard does not cover risks of infection associated with the biological source. Draft European Standards which address these issues should be consulted (prEN 12442, Pans 1-3).

5.2 Ceramics, metals and alloys
These materials are normally less complex in terms of the number of chemical constituents and these will be present in significant proportions.

It should be noted that during manufacture and assembly of medical devices from materials in both categories 5.1 and 5.2 additional chemical components rnay be acquired due to the use of processing aids such as lubricants or mould release agents. As well as the chemical components of the staning material and the manufacturing process aids, adhesive/solvent residues from assembly and also sterilant residues or reaction products resulting from the sterilisation process may also be present in a finished product.

6 Determination of compositional information

Full qualitative data for chemical constituents of the material shall be established. Where relevant to biological safety, quantitative data shall also be obtained. When quantitative data is not obtained the rationale shall be documented and justified.

6.1 From existing data sources

Medical device manufacturers should preferably obtain qualitative and quantitative compositional information from the supplier of the starting material. For polymers this often requires access ro proprietary information and appropriate formalities may be necessary for transfer and use of such confidential information.
Qualitative information about any additional processing additives (for example, mould release agents) should also be obtained from appropriate members of the manufacturing chain, including convertors and component manufacturers.
The composition of ceramics, metals and alloys is likely to be in accordance with ISO materials standards and/or may be specified by the user. However in order to obtain full qualitative and quantitative compositional details it rnay be necessary to request these from the supplier or manufacturer of the starting material and also from component manufacturers to ensure processing aids are also identified. Material master files held by regulatory authorities are another source of data where they are accessible

6.2 By analysis

When compositional details are unavailable or only qualitative information is available it may be necessary to undertake analysis of a material
Analytical methods appropriate for the material under investigation shall be used. All analytical techniques shall be justified and reported.
In the absence of any initial compositional data a literature study to establish the likely nature of the starting material and any additives is recommended to assist in the selection of the most appropriate methods of analysis for the material concerned.

7 Extraction of materials

Use extraction conditions as specified in ISO 10993-12 unless a particular vertical standard is more appropriate. The specific extraction conditions used must be documented and justified.

Note: Suitable extraction conditions should be used to ensure that any constituent that could be released during normal use of the finished product will be released into the extraction media.

Wherever possible extraction tests should be made using representative samples taken from the finished product in its ready to use state in order to take account of residual chemicals arising from all pans of the manufacturing process including sterilisation.

8 Testing of extracts

Extracrant solutions shall be submitted for chemical analysis using appropriate methods for the materials/chemicals concerned
Blank solutions shall be used for comparison to confirm that chemical species detected in the test solution originate from the test sample itself
Analytical methods used shall be documented and justified.

9 Reporting of data obtained

Test reports shall include the following :

9.1 Compositional information

a) Test material description, batch or lot number, and sample dimensions or weight.
b) Description of origin of compositional data, for example : supplied by material/finished product manufacturer, or by analysis.
c) Sample pretreatment (e.g. sterilisation).
d) Detailed description of analytical methods used including specificity, sensitivity, limits of detection and limits of quantification; also standards and reference materials where used.
e) List of all chemical components identified including quantitative data where possible.

9.2 Extraction information

a) Test material description, batch or lot number, and sample dimensions or weight.
b) Sample pretreatment (e.g. sterilisation).
c) Extractant solution details including chemical identity and volume used. Justification shall be provided for the choice of extractant
d) Duration and temperature of extraction including justification for their selection.
e) Detailed description of analytical methods used including specificity, sensitivity, lirnits of detection and limits of quantification, also standards and reference materials where used.
f) List of all chemical components identified including quantitative data where possible.

Note: Quantitative data must permit calculation of human exposure

9.3 Physico-chemical, mechanical and morphological characteristics

a) All the characteristics relevant to the biological safety of the medical device under consideration shall be listed.
b) For each item listed in 9.3.a) an indication shall be given of the possible biological safety hazard(s).

Annex A (informative)

Characterisation of materials
Flowchart for the generation and use of data