CORDIS Archive

Traceability issues related to the EU directive 98/79/EC (in vitro diagnostic medical devices)e

1. CONFORMITY WITH THE WORK PROGRAMME

This topic is directly related to the activity Support for research infrastructures (Networking), under the Competitive and Sustainable Growth Programme. Specifically it is related to the Objective GROW-2000-7.4 Measurement and Quality Management Infrastructures for which expressions of interest have been called.

2. KEYWORDS

Network, metrology, traceability, EU in vitro diagnostic medical devices directive, knowledge transfer.

3. SUMMARY OF OBJECTIVES AND JUSTIFICATION

The objective of the project is to bring together representatives from National Metrology Institutes (NMIs) and the Joint Research Centre IRMM, professional scientific organisations such as the International Federation of Clinical Chemistry (IFCC), industrial in vitro diagnostic (IVD) medical device manufacturers, organisers of external quality assessment schemes and from regulatory agencies, to increase the understanding about the traceability requirements of the EU in vitro diagnostic medical devices directive (98/79/EC) and to improve the knowledge transfer between the participants about metrological issues such as traceability, comparability, and measurement uncertainty.

The IVD directive requires that for IVD measurement results:

"The traceability of values assigned to calibrators and/or control materials must be assured through available reference measurement procedures and/or available reference materials of a higher order."

This traceability requirement is mandatory for all IVD products to be used in Europe from December 7, 2003 onwards, and is subject to further detail in the CEN Technical Committee TC 140 "In vitro diagnostic medical devices" in parallel with the ISO/TC 212 "Clinical laboratory testing and in vitro diagnostic test systems".

It is important that all parties involved interpret the traceability requirements in an uniform way in an extremely complex working area which varies from the measurement of well defined chemical compounds in complex biological matrices to disease markers with unknown structures and rather ill-defined measurement procedures. Knowledge transfer about metrological aspects in the broadest sense between all parties involved is necessary to reach world wide consensus.

4. BACKGROUND

Reliable measurement results are a key issue in medical health care and should provide patients, users and third parties with a high level of health protection. The European IVD directive contributes to this goal by defining so-called "essential requirements" that devices must meet in order to guarantee their safety and quality.

The traceability requirement in Annex I-A.3 obligates manufacturers to use available reference measurement procedures and/or available reference materials of a higher order. Depending on the type of measurement this requirement varies in complexity. To work out the further details the CEN Technical Committee TC 140, in close collaboration with ISO TC 212, has drawn up a draft international standard prEN ISO 17511 "In vitro diagnostic medical devices – Measurement of quantities in samples of biological origin – Metrological traceability of values assigned to calibrators and control materials". Major problems in the implementation of the traceability requirement are the (un)availability of adequate reference materials and reference procedures, but also the interpretation of traceability and the associated uncertainty in complex measurement areas such as the determination of proteineous disease markers with immunochemical techniques.

Since this directive will apply to all IVDs on the European market, also manufacturers from other continents must comply with the regulation. In fact, about 70% of all IVD products on the European market are produced outside Europe.

A world-wide acceptance of concepts and definitions about metrological traceability in all IVD areas is essential for all parties involved, in order not to introduce trade barriers between countries because of biased interpretations leading to redundant product testing.

The free trade goals have resulted on October 5, 1999 into the signing of "The Implementing Arrangement for Cooperation in the Fields of Metrology and Measurement Standards" between the US National Institute of Standards and Technology and the EC Directorate General Research. The arrangement will lead to a trans-Atlantic system for assessing measurement equivalency. Inclusion of the traceability requirements in the IVD area as a work item in this arrangement, will help to reduce the technical obstacles that may impede the free flow of IVD products between the world’s largest trading partners, including other countries such as Japan.

The network therefore should be open for participants from these parts of the world.

5. ECONOMIC AND SOCIAL BENEFITS

The European production of IVD devices is estimated by the European Diagnostic Manufacturers Association (EDMA) at just over 5 billion Euro, while the world-wide production is estimated at about 20 billion Euro. The IVDs on the European marketplace are produced world-wide since only 30-40% of the IVDs used in Europe are produced in Europe. The major manufacturers outside the EU can be found in the USA and Japan and they export IVDs to the European marketplace. The successful implementation of the IVD directive is therefore an international problem of a world-wide dimension.

The IVD devices are used in analyses in laboratory medicine in support of diagnosis and monitoring of diseases and thereby support healthcare and the whole population. Healthcare without IVDs is unthinkable and the diagnosis and treatment of many diseases such as diabetes, cardiovascular diseases, autoimmune diseases, etc. are impossible without the use of IVDs. The quality of life for many patients depends on the accurate determination of disease markers in body fluids, or even on the availability of self-testing devices such as those for glucose in the case of diabetes.

The testing of the safety and quality of IVDs is a prerequisite for free trade, fair competitiveness, demonstrated quality and ultimately consumer satisfaction. Traceability is one of the key factors that contributes to a sustainable growth for the IVD industry, the formation of a single marketplace in Europe, and improvement of comparability of IVD measurements between countries and continents.

6. SCIENTIFIC AND TECHNOLOGICAL OBJECTIVES

The traceability chain from a measurement result to an available reference material of higher order, is the responsibility of several organisations:

· National Metrology Institutes (NMIs) and the European JRC IRMM, have a responsibility for providing the link to the SI system by primary measurement standards and primary measurement procedures. The major producers of traceable measurement standards in support for the IVD industry are NIST and IRMM. Primary reference methods can be provided by several European organisations and NIST.

· Reference measurement laboratories specialised in the application of primary measurement procedures, will form a link between NMIs and the clinical marketplace, which may include clinical chemical test laboratories and industries. Reference measurement laboratories may demonstrate their quality through external quality assessment leading to accreditation as a calibration laboratory.

· Industrial IVD manufacturers will have to apply measurement standards of a higher order to the calibration of the calibrators of the final IVD products, in order to comply with the IVD directive.

· Professional scientific organisations such as IFCC play a key role in establishing reference measurement procedures and are the platform organisation for all discussions between the clinical chemical working field and other parties.

· Organisations of external quality assessment schemes (EQAS) are indispensable for the improvement of comparability between end-users. The use of survey samples with traceable assigned values by EQAS organisers will improve traceability of the measurement results in the whole working field.

· Other parties are also involved in the maintenance of the traceability chain, such as accreditation organisations, regulatory bodies, standardisation organisations.

The objective of the network is to establish a structured co-operation between all the parties mentioned above. The network should aim to become self-supporting in the longer term and proposers should address how this would be achieved in detail.

The strength of the traceability chain will depend on the measurement uncertainty of all the individual comparisons and the evaluation of this uncertainty is a subject, which needs discussion. The GUM gives general guidelines, but specific examples need to be developed that are illustrative for the whole working field.

Objectives.

Typical examples of objectives of this network are given below. Proposers should detail their specific solutions including the activities, milestones and deliverables:

6.1 Consensus on traceability issues

6.2 Knowledge transfer

7. IMPORTANT ADDITIONAL INFORMATION

Proposed network should be of manageable size. However the structure should be such that all relevant parties that are not part of the proposed contractual network but who wish to be classified can be included.

Proposers should note that submissions must follow the network modality and the allowable cost structure.