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Biological Evaluation of Medical Devices - European standards

This article, the first of a regular feature an European (CEN) and international (ISO) standards for biological evaluation of medical devices, represents an overview of the current European situation. Future articles will address the US approach, international harmonisation, and the key issues of specific standards of interest to TRAN participants.

European legislation for medical devices, laid down in the Active Implantable Medical Devices (90/385/EEC) and Medical Devices (93/42/EEC) Directives, is restricted to basic safety requirements. It is the European standardisation process (CEN) which, through a range of its Standards, allows checking for product compliance with the legislative safety (*essential*) requirements.

The European Standards addressing the biological evaluation of medical devices are the EN30993 (horizontal) series; consensus with international standardisation means many CEN standards are adopted from ISO. To data there are 12 parts of the series, which have been finalised, and a further 5 parts which are in preparation (see Table below).

Table - ISO10993

Part 1 - Guidance on selection of tests

Part 2 - Animal welfare requirements

Part 3 - Tests for genotoxicity, carcinoqenicity and reproductive toxicity

Part 4 - Selection of tests for interaction with blood

Part 5 - Tests for cytotoxicity in vitro methods

Part 6 - Teats for local effects after implantation

Part 7 - Ethylene oxide sterilisation residues

Part 8 - Clinical investigation (not part of EN30993)

Part 9 - Degradation materials related to biological testing

Part 10 - Tests for irritation and sensitisation

Part 11 - Tests for systemic toxicity

Part 12 - Sample preparation and Reference Materials (In preparation)

Part 13 - Identification and quantification of degradation products from polymers

Part 14 - Identification and quantification of degradation products from ceramics

Part 15 - Identification and quantification of degradation products from metals and alloys

Part 16 - 'Toxicokinetic study design for degradation product and leachables

Part 17 - Materials characterisation.

Part 1 specifies the minimum requirements and rationale for a systematic approach to the biological evaluation of any medical device. It does not prescribe specific tests or acceptance criteria for or between tests. It is solely for guidance and considers:

the basic principles of biological evaluation within safety assessment
the procedure for identification and characterising products potential biological hazards
the procedure for evaluating real exposure and asssessing the resulting affect(s).

In many ways therefore, it is the most important part of the series the, remaining parts providing evaluation. of the different important aspects of behaviour observed between both the implant material and surrounding tissue, and the tissue and the material.

Nonetheless despite these Standards, medical device evaluation remains complex. This may, in part, be due to the general nature of horizontal standards which restricts the use of acceptance criteria and introduces uncertainty into the evaluation process. This is borne out by experience gained from the marketplace which shows that Standard-based conformity data and its subsequent safety assessment cannot consistently guarantee safe and weal-performing products, although the uncertainty is currently being addressed by means of risk analysis, a draft Standard, prEN1441, for which is under development. Thus there is a clear requirement for the future development of specific test methods focused on end-use application and performance criteria.