Electronic Supplemental Material Accreditation and Quality Assurance vol. 12, 2007 Springer Verlag

1. Electronic Supplemental Material Accreditation and Quality Assurance vol. 12, 2007 Springer Verlag Metrology, essential to Trade, Industry and Society Robert Kaarls Secretary CIPM, President CCQM Klaverwydenstraat 13 2381 VX Zoeterwoude, The Netherlands Tel +31 71 580 22 31 Fax +31 71 580 47 77 Presented at the 3rd International Conference on Metrology, November 2006, Tel Aviv, Israel

2. Need for global metrological infrastructure • Global trade, globalized industry, world wide travelling of people, health care, food safety and pollution control and possible climate change require reliable, traceable and comparable measurements • Of high economic and societal interest • Taking away Technical Barriers to Trade • Securing good quality of life • In compliance with WTO TBT and SPS Agreements and other regional and national regulations

3. Need for global metrological infrastructure • Non-reliable and non-comparable measurement and test results means non-acceptance by the consignee • A not internationally recognized national measurement system leads to technical barriers to trade by non-compliance with technical and sanitary/phytosanitary requirements • Sectors affected by the lack of a reliable measurement system are many, like: food, health care, environment, electronics and optical, transport, navigation, air and space, energy, ionizing radiation, information technology and telecommunications sector

4. Why Metrology ? • Aiming global comparability of measurement and test results • Measurement results traceable to the same long term stable references, the SI • Globally credible, recognised and accepted measurement results with stated measurement uncertainty, fit for purpose • Once measured/tested, everywhere accepted

5. The expanding need on Metrology • Industrial production (components and parts produced at another time somewhere else on the globe must fit together) • Worldwide services (e.g. banking, maintenance) • Innovation • Trade (fair trade, internal markets) • Trade agreements (WTO Technical Barriers to Trade and Sanitary and Phyto-Sanitary measures) • Accreditation agreements • Metrological agreements • Once measured/tested, everywhere accepted

6. The expanding need on Metrology • Society - environment, pollution control and climate change - health care and protection - food (safety and nutritional value) - drugs and pharmaceutics - anti-doping - biological activity, micro-biology - “soft/perceptive” metrology (smell, taste, blends, color, glance, form, etc.) • Regulators • Forensics • Security • One measurement system, less errors

7. Sustainable competitiveness and innovation • Growing metrological demands • Global trade (in commodities >12 trillon US$ of which 80% affected by standards and regulation; compliance costs ~10% of production costs) • Globally spread industrial and service activities • Men travelling all around the globe • New sources of energy (bio, hydrogen, nuclear) • Nano technology, bio technology, advanced materials • Information and communications technology

8. Demanding Metrological Traceability Several (regulatory) driving forces • Trade requirements WTO TBT and WTO SPS • Compliance with regulations (a.o. in-vitro diagnostics, food safety, pollution control) • Labeling (vitamins, amino and sorbic acids, fat, GMO’s, caffeine, additives, pigments) • Tariff classification/customs (butter fat, sugars, caffeine, fat in milk, protein in meat) • EU TRACE project (origin of food products) • EU REACH legislation • Accreditation and certification • Avoidance of market distortions in a single market • International trade agreements (WTO and bilateral)

9. Health Care • Clinical chemistry and laboratory medicine - In Vitro Diagnostic measurements (IVD Directive driven JCTLM: higher order CRMs and methods, PT schemes and reference laboratories) - therapeutic measurements (WHO standards and units) - global market >25 billion US$ • Pharmaceuticals (US Pharmacopeia, European Council - European Directorate for the Quality of Medicines, a.o.) - global market >250 billion US$

10. In vitro diagnostic measurements and its economic and social Impact • Mayo Clinic and NIST studies show that 3% measurement error in cholesterol measurements lead to 5% false diagnoses, leading to unnecessary treatment or dramatic non-treatment • Same applies for measurement errors in Cardiac Troponin-I analysis, a heart attack marker • Avoiding unnecessary measurements could potentially save the US 10 to 30 billion US$ p.a. • In Germany savings would be > 1.5 billion € • Source: NIST/Mayo Clinic and EU study report

11. Demanding Metrological Traceability Sanitary and Phyto-Sanitary measures Quality and product safety with respect to food safety, animal and plant health • FAO/WHO Codex Alimentarius Commission (food safety) • Office International des Epizooties – OIE (animal health) • FAO International Plant Protection Convention - IPPC (plant health) • Food producing companies (suppliers declaration of conformity, e.g. based on Hazard Analysis and Critical Control Points – HACCP, ISO 9001, ISO 14001)

12. Food safety measurements • Regular reports of food exports refused by importing countries due to not acceptance of test reports or due to differences in test results - honey and beef from Argentine - wine and fish from Chile - fish from Kenya, Tanzania, Uganda, Norway - medicines, dietary supplements from China - GMO modified products: soya, rice from USA - chicken from Thailand - etc. The CIPM MRA is essential, assuring reliable comparability and traceability

13. 12 IMEP- 16: Pb in wine -1 Certified value : 27.18 ± 0.25 µg·L [ U = k · u ( k =2)] c 40.8 50 28 values Pb amount content above 50% 38.1 40 35.3 30 32.6 20 OIVV 29.9 10 members 27.2 0 24.5 -10 21.7 -20 19.0 -30 16.3 -40 11 values below -50% 5 'less than' values 13.6 -50 Results from all participants with indication of the results of the OIVV members Assessing the quality of results of measurements : IMEP-16

14. 13 ±50% BIPM-CCQM pilot study 12

15. 14 0.198 50 40 0.176 30 20 0.154 10 0.132 0 -10 0.110 -20 -30 0.088 -40 CCQM-P12 0.066 -50 IMEP-16 OIV using a reference value, demonstrated to be equivalent at global level

16. Developing countries dependence on metrology • Technical Barriers to Trade by doubts and non-compliance with legislations, specifications and Sanitary and Phyto-Sanitary measures (e.g. HACCP) • Lack of internationally recognized metrological and accreditation infrastructure • Refusal of exported products (food, medicins, etc.) • 40% of GDP export of fish and agricultural products • 40% of GDP export raw materials (oil, metals, etc.) • Vulnerability for bad imported products

17. Climate change, environmental and pollution control - ozone and greenhouse gases (WMO GAW) - Volatile Organic Components (WMO GAW) - Radiation (WMO World Radiation Centre) - ocean temperature and salinity measurements (UNESCO) - river and coastel waters (where all our waste, including medicines and personal care products, ends up in living organisms, like whale, dolphin, fish, oysters, shrimp etc. showing changes in genes and proteins) - air quality (transport, industrial production, heating) - soil and sediments (industry, agriculture, etc)

18. Other sector specific metrology needs • Energy sector - oil, bio diesel - hydrogen fuel cells • - nuclear fission • Forensics (International Association of Forensic Sciences, European Network of Forensic Science Institutes) • - DNA, RNA • - drugs, poisons, explosives, chemical and biological traces, finger printing, shell bursts by bullets, etc

19. Other sector specific metrology needs • Security - bio-metric data, like iris and other facial scans, finger prints - airport screening techniques based on ionizing radiation, electromagnetic radiation, heat radiation, optical and acoustical measurements, whole body scanning and imaging - luggage and container screening based on ionizing and other electromagnetic radiation techniques, disease and drugs testers and chemical traces detection

20. Nano metrology, an interdisciplinary area • Micro/nano scale manufacturing (nanolithography) • Nano structures materials (carbon nano tubes) • New composite materials (nanoscale particles) • Nano-electronics, -photonics, -magnetics • Energy conversion (nanorod polymer solar cells) • Nano scale instrumentation (chip based and single electron) • Health care, therapeutics and diagnostics (peptide nanotubes, puncturing cell walls, DNA/RNA strands) • Nano scale processes (e.g. nano particle water filtration) Already an 1x1012 US$ per year market

21. Nano particles, challenges and dangers • Measurement of protein “signatures”, indicators of diseases • Therapeutic possibilities • Infiltrating very easily in other structures, including the human body • Causing impurities and damages • Immediate study of detection and measurement methods and of the toxicity needed

22. Material properties • Electromagnetic properties (magnetic and dielectric) • Thermo-electric properties • Thermodynamic/thermophysical properties (conductivity, heat transfer, phase analysis, expansion, heat capacity, emissivity, diffusivity) • Optical properties (reflectivity, whiteness, glance) • Acoustic properties

23. Material properties • Mechanical properties (hardness, modulus, strength, toughness, fatigue, creep, friction, corrosion, lubrication) • Properties of fluids and gases (viscosity, density, caloric value) • Structural properties (composites, aerosols, gels, grain and particle size, particle size distribution, porosity, defects, shape) CIPM Ad Hoc Working Group on (engineering) Materials Metrology (VAMAS and ANMET) reporting in October 2007

24. Metrological issues to be solved • Clear definition of measurands, e.g. defined molecules in a defined matrix environment • Clear understanding of method dependent results • Understanding the complete measurement equation • Validation of methods, performance criteria based • Measurement uncertainty • Uncertainty sample preparation often substantial

25. Metrological issues to be solved • Understanding of the potency of available methods (answer to the question: how far and how long does the light shine?) • Development of new measurement technologies • Commutability of CRM’s • Availability of sufficient and right CRMs • Linking PT schemes to the CCQM comparisons • Desirable deliverables by the NMIs and other designated institutes

26. Chemical measurements • Bio technology and micro biology (genomics, proteomics, metabolomics, etc.) -DNA and RNA -proteins -cells -GMOs • Certified Reference Materials (enormous lack of) • NMIs to develop more “chemical calibration capabilities” for assigning values to natural samples from customers (industries, PT providers, testing laboratories)

27. Chemical measurements • Further issues to be addressed: - very low concentration levels - development of new (primary and other higher order) techniques and methods needed - lab-on-a-chip, on-the-spot and point-of-care measurements - high purity reference materials needed, purity analysis - sample preparation often largest source of measurement uncertainty

28. Information technology • Directly after analogue sensor follows microprocessor, signal processing, data transfer, computation and display • Remote monitoring and calibrations • “intelligent, self learning devices”, applying corrections • Reliability of hardware and software difficult to understand and to verify (unsatisfactory “black” box testing) • Multi point network, steering completely automated large manufacturing plants; multi point access for measurements • Controlling human well being (health status, climate predictions) • Now computer aided software for testing whole system

29. Establishing worldwide comparability through traceability • Inter-Governmental Treaty of the “Metre Convention”, established in 1875 • Member States (51) and Associate countries and economies (31) (October 2006) • 10 Consultative Committees • International Bureau (BIPM) in Sèvres,France • Coordinating and representing the National Metrology Institutes (NMI’s) globally

31. METROLOGYand REGULATIONS New regulations addressing traceability and measurement uncertainty • Air flight safety regulations • Transmission frequencies and maximum permissible levels of electromagnetic radiation • Regulations requiring traceability in clinical measurements • Regulations concerning food safety, nutrional content and labeling • Regulations dealing with maximum permissible levels of pollution and requirements for water and air quality • Regulations concerning registration and transport of chemicals • -Legal metrology (fair trade, consumer protection, public safety)

32. METROLOGY and ACCREDITATION • BIPM – OIML – ILAC Common Statement and Declaration on the Relevance of their International Agreements on Metrology to Trade, Legislation and Standardisation • CIPM – ILAC Statement by the CIPM and the ILAC on the Roles and Responsibilities of NMIs and NABs • Accreditation of laboratories, CRM producers, PT providers, inspection and certification bodies • CIPM MRA and ILAC Arrangement fully complementary

33. METROLOGY and STANDARDISATION • ISO REMCO (Certified Reference Materials) • ISO CASCO (conformity assessment, laboratory accreditation) • ISO TC 212 (clinical chemistry and laboratory medicine) • Many other ISO and IEC committees • Cooperation in the Joint Committee on coordination of assistance to Developing Countries in Metrology, Accreditation and Standardisation (JCDCMAS) together with BIPM, OIML, ILAC, IAF, IEC, ISO, ITU-T, UNIDO and observers from International Trade Centre (ITC of UNCTAD/WTO) and IMEKO

34. Inter-governmental/international organisations Organisations with clear interest in metrology • MoU with WHO, WMO, ILAC, JCTLM (IFCC and ILAC) • IAEA, Codex Alimentarius Commission/IAM, CIE, IAU, ITU, ICRU, IUGG, IUPAC, IUPAP, WADA, Pharmacopeia, IAFSI/ENFSI, a.o. • Approaches to WTO (Technical Barriers to Trade Committee) and World Customs Organisation (WCO) • CIPM Consultative Committees open for observership from andcooperation with these inter-governmental and international organisations

35. The CIPM Mutual Recognition Arrangement • Mutual recognition of national measurement standards and of calibration and measurement certificates issued by NMI’s (and other designated institutes) • Now signed by a large and increasing number of NMI’s and other designated institutes (some 180), acting as NMI’s for certain quantities and measurement ranges, of about 75 (September 2006) Member States and Associate Economies and 2 international organizations (IAEA and EU – JRC IRMM and JRC Ispra) (See Appendix A) (soon also to be signed by the WMO)

36. The CIPM Mutual Recognition Arrangement • Based on results of key-, supplementary- and bilateral comparisons (Appendix B) • Quality system in place in conformity with ISO/IEC 17025 and ISO Guide 34 • Quality system assessment by international RMO review, accreditation and/or on-site peer review • Regional and inter-regional review of claimed calibration and measurement capabilities

37. Appendix C of the CIPM MRA • Published are the calibration and measurement services of the (designated) NMI’s and other institutes, which are normally delivered to the customers * Analysing/measurement/calibration capabilities and/or * CRM’s delivered/sold to customers (Appendix C) • Key Comparison Data Base – KCDB onwww.bipm.org/kcdb

38. A MAJOR USER “The use of NMIs is formally recognized in the top Boeing Commercial procedure for calibration. It specifically identifies the CIPM MRA...and so the KCDB serves the function of the accreditation scopes in the process for approved suppliers (in this case NMIs).One access to the KCDB at Boeing is on the metrology sites page which is referenced across Boeing in various pages and a search for BIPM internal to Boeing will bring back the KCDB newsletter.” Source: Derek Porter, Technical Principal, Puget Sound Metrology, Boeing Commercial Group

39. EU IVD Directive requires traceability • Implementation of EU-IVD Directive (98/79/EC) • EC-IVD Directive, Annex I, Essential requirements A.3 • '...The traceability of values assigned to calibratorsand/or control materials must be assured throughavailable reference measurement procedures and/oravailable reference materials of a higher order.'

40. Joint Committee on Traceability in Laboratory Medicine - JCTLM Principal promotors • CIPM/BIPM • IFCC • ILAC Supported by • WHO • Other stakeholders

41. Relevant ISO Standards • ISO 17511In vitro diagnostic medical devices - Measurement of quantities in biological samples - Metrological traceability of values assigned to calibrators and control materials • ISO 15193 Presentation of reference measurement procedures • ISO 15194 Description of reference materials • ISO 15195 Reference Measurement Laboratories • ISO 18153Metrological traceability of values for catalytic concentration of enzymes assigned to calibrators and control materials

42. The JCTLM and its database as a result of the CIPM MRA www.bipm.org/en/committees/jc/jctlm/jctlm-db/ • Publishing lists of reliable “higher order” reference materials and measurement procedures under the aegis of the Metre Convention and its CIPM MRA • Traceable to the SI (list I) and, if not (yet) SI traceable, e.g. WHO International Standards and International Units (list II) • List of reliable measurement services, deliverable by potential reference laboratories (based on ISO 15195 accreditation, or other comparable schemes, and regularly good results in inter-laboratory comparisons)

43. CCQM support to the Food sector • Pesticide residues in fruit products (juices) • Butyric acid in milk (marker for milk fat content; customs tariff issue) • Growth hormones in meat • Antibiotics and trace contaminants in fish • Vitamins and Minerals (A, E, Folates in baby food and dietary supplements) • Proximates in milk products (product standards) (still under consideration) • Dietary supplements (green tea) • Nitrates, nitrites (Inorganic Analysis) • Humidity and micro-biological issues, etc.

44. 350 300 IDMS reference value 250 200 Mean result 150 Sn ug/g 100 50 0 0 10 20 30 40 50 ascending results FAPAS Round 0738: Sn in tomato puree

45. Change in Sn performance using reference instead of consensus value

46. PT schemes More than 800 PT schemes in 19 countries (source : EPTIS) In some emerging fields, the number of parameters and matrices covered by PT schemes is much higher than the number of parameters and matrices covered by CRMs Example : Water analysis PT schemes Parameters : 250 (pesticides : 40%) CRMs Parameters : 40 (metals : 65%) PT schemes and CRMs are complementary but the traceability of PT schemes values is questionable Source: C. Rivier, LNE, France, CCQM IAWG workshop Berlin, 2005

47. Establishing a national network of credible, reliable, recognized dissemination of traceability • Top level cooperating under the Metre Convention - NMI’s and other designated institutes • Second level of accredited calibration laboratories and CRM producers under the ILAC Arrangement - traceable to NMI’s and other designated institutes under the CIPM MRA - able to assign values to “in-house” reference materials - delivering Certified Reference Materials • Third level of “field” laboratories

48. ILAC Arrangement • International recognition of calibration, measurement and test results • Accreditation of second level calibration and reference laboratories (ISO/IEC 17025 or ISO 15195) • Accreditation of CRM producers (ISO/IEC 17025 and ISO Guide 34) • Accreditation of Proficiency Testing providers (G 13) • Accreditation of “field” laboratories (ISO/IEC 17025 or ISO 15189) • CIPM MRA and ILAC Arrangement fully complementary • CIPM MRA CMC = ILAC Arrangement BMC