CCQM, October 2003 1

Consultative Committee for Amount of Substance -

Metrology in Chemistry

President: Robert Kaarls

CGPM, 13-17 October 2003

CCQM, October 2003 2

Contents

•Ten years CCQM•CCQM and CCQM Working Groups•CCQM activities•Certified Reference Materials•Cooperation with other intergovernmental and international organizations•Joint Committee for Traceability in Laboratory Medicine•Material properties•Designated institutes•BIPM programme

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Ten years CCQM

•Established by the CIPM in 1993•Hypothesis: Traceability of measurement results in chemistry is feasible•Many chemists were at least rather sceptical•Clear need for comparable measurements in trade, industry and society, traceable to common, long-term stable, references•However, already implicitly traceability was claimed to SI, but mostly not justified and•lack of measurement uncertainty statement

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Ten years CCQM

•Now, after 10 years, we can state: comparability and traceability can be realized with uncertainties sufficient for intended purpose •Enormous amount of work still to be done•Still developments considerably behind compared to the development of “classical” physical metrology•Need for setting priorities•And in cooperation with many other organizations, like WMO, WHO, IAEA, IFCC, IUPAC, ISO REMCO, ILAC and CITAC

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CCQM and its Working Groups

•CCQM (~60 persons, 25 countries)•CCQM WGs (~140 persons, many institutes)

•Organic analysis NIST, USA•Inorganic analysis LGC, UK•Gas analysis NMi-VSL, Netherl.•Electrochemical analysis SMU, Slovakia•Bio-analysis LGC/NIST, UK/USA•Surface analysis NPL, UK•Key Comparisons and CMC Quality NRC, Canada

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CCQM and its Working Groups

Areas covered:•Health•Food•Environment•Advanced materials•Commodities•Forensics•Pharmaceuticals•Bio-technology•Surface analysis•General analytical applications

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CCQM activities

•Studies (~60 studies on development, try-outs, etc.)•Key Comparisons (~50 Key Comparisons)•Underpinning claimed Calibration and Measurement Capabilities – CMCs of the NMIs and other designated institutes•Harmonization (methods, measurement uncertainty)•Certified Reference Materials•Know-how transfer

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CCQM WG on Organic Analysis

•Cholesterol, glucose, and creatinine in serum•Organic contaminants in tissue•pp´-DDE in corn oil and fish oil•PCB’s in sediment•Ethanol in aqueous water•LSD in urine•Drugs of abuse in urine•Purity studies•NMR studies•Organic solutions of PAHs, PCBs and pesticides

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CCQM WG on Inorganic Analysis

•Calcium in serum•Arsenic in shellfish•Lead, copper, cadmium, zinc in wine•Cadmium and zinc in rice•Metals in synthetic food digest•Lead and cadmium in natural water and sediments•Minor elements in steel•Constituents in aluminium alloy•Di- and tributyltin in sediment•Sulphur in fuels•Elemental solutions

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CCQM WG on Gas Analysis

•CO, CO2, NO, SO2 in nitrogen•Natural gas•Propane, benzene, toluene, xylene in nitrogen and air•VOCs in air•Greenhouse gases at ambient levels•Ozone at ambient levels•Ethanol in air•Reactive gases at ambient levels•SF6 and CFCs in nitrogen•Measurement uncertainty < 1%, approaching 0.001%

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CCQM WG on Bio-Analysis

•Addressing metrological issues in biotechnology and molecular biology•Work distinguishes between nucleic acid/gene, protein and cell measurements• Quantitative DNA analysis important in food testing, clinical and therapeutic measurements and forensics (DNA fingerprinting)•Instrument manufacturers and users require traceability and calibration•Internationally comparable and traceable measurements required by EU IVD directive

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CCQM WG on Bio-Analysis

•DNA profiling•DNA primary quantification•Peptide/protein quantification in proteomics•PCR quantitation study•Fluorescent dyes spectral correction studies•Bio-molecular gene, protein and cell measurements

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CCQM WG on Surface Analysis

•Developments in nanotechnology, semiconductor industry and industries producing and working with thin layer technologies are highly dependent on proper surface measurements•These industries include polymers, coatings and paint, and measurements dealing with corrosion for aerospace, protein adhesion and toxicity for body implants•The industries have asked NMIs to address the metrological problems in surface analysis

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CCQM WG on Surface Analysis

•Dopant distribution in silicium•Fe-Ni and Co-Pt alloy thin-film composition•Coatings•Surface layers, contaminants•Polymer surfaces•Thin-film multilayer systems

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CCQM WG on Key Comparisons and CMC Quality

•Composed of representatives/experts of the Regional Metrology Organizations (RMOs) and of experts from all CCQM Working Groups•Coordination of Key Comparisons•Defining gaps between the CMCs of the NMIs, as claimed under the CIPM MRA, and the demonstration of competence and capability by the results of Key Comparisons and Studies•Discussion on unsolved questions concerning CMCs•Defining criteria for claimed CRMs

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CCQM and Certified Reference Materials

• NMI’s deliver traceability to customers through their calibration/chemical analysis facilities and through sales of Certified Reference Materials CRMs•Appendix C of the CIPM MRA lists these possibilities•CRM’s are widely used by customers for calibration and method validation•Quality of claimed CRMs to be based on NMI’s own competence and capabilities to characterize (stability, homogeneity, etc.) and to assign a value to the CRM in compliance with ISO Guide 34

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CCQM and Certified Reference Materials

•Need for special CRMs, in particular matrix materials, is almost infinite•NMI’s to develop calibration/chemical analysis capabilities •NMI’s to certify and deliver very pure materials•Commercially available CRMs often lack traceability and measurement uncertainty statement•Great difficulties for laboratories seeking accreditation according to ISO 17025 or ISO 15189 in the field of clinical laboratories•Cooperation with ISO REMCO

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Cooperation with other inter-governmental and international organizations

•Accurate measurements traceable to SI, being long-term stable, fixed anchor points are essential for several fields•WMO programmes require highest achievable levels•Comparability and traceability high on the agenda of the clinical and in-vitro diagnostics community•If traceability to SI is not (yet) possible, then traceability to other internationally agreed references (for example WHO units for biological activity)

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Cooperation with other inter-governmental and international organizations

CCQM has established cooperation with:•WMO World Meteorological Organization•WHO World Health Organization•IFCC International Federation of Clinical Chemistry•IAEA International Atomic Energy Agency•IRMM EU Institute for Reference Materials & Meas.•ISO REMCO ISO Reference Materials Committee•CITAC Internatl.Coop. on Traceability A. Chemistry •IUPAC Internatl. Union Pure and Applied Chemistry

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Joint Committee on Traceability in Laboratory Medicine - JCTLM

•Established by BIPM, IFCC and ILAC•In cooperation with all stakeholders•Regulators, industry associations, quality assurance and proficiency testing providers, documentary standards organizations, WHO and WHO laboratories•Aim of JCTLM is to realize and support worldwide reliable comparability and traceability of measurement results in laboratory medicine

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Joint Committee on Traceability in Laboratory Medicine - JCTLM

•EU Directive on In Vitro Diagnostic measurements requires traceability to standards of “higher order”•Traceability to SI, but if not (yet) possible to other internationally agreed references (e.g. WHO units for biological activity)•World market for IVD products ~20 billion € p.a.•Potential savings in health care > 20 billion US $ p.a.

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Joint Committee for Traceability in Laboratory Medicine - JCTLM

•JCTLM Working Group 1 on Reference Materials and Methods is reviewing reference materials and methods nominated as being of “higher order”•JCTLM Working Group 2 on Reference Laboratories and Methods is developing criteria for reference measurement laboratories•JCTLM WG 1 will work in close cooperation with the CCQM

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JCTLM Working Group 1

JCTLM Working Group 1 has eight sub-groups:•Electrolytes (calcium, chloride, potassium, etc.)•Enzymes (AST, amylase, CK, GGT, etc.)•Metabolites, substrates (cholesterol, urea, etc.)•Proteins (albumin, troponin-1, PSA)•Nucleic acids (DNA, RNA)•Drugs (digoxin, lithium, etc.)•Hormones (cortisol, estriol, testosterone, etc.)•Coagulation factors

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JCTLM Working Group 1

JCTLM Working Group 1 new sub-groups:•Blood grouping and typing•Blood gases•Infectious diseases•Non-electrolyte metals•Vitamins

A database of reference materials of higher order will be published by the BIPM and the IFCC

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New networks

CCQM will liaise also with:•Codex Alimentarius Commission of the FAO and the WHO•World Anti-Doping Agency – WADA•Pharmacopeia •And others where relevant

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Material properties

Good knowledge of material properties is indispensable in to-day’s industry and society•CRM’s•Optical filters•Heat transfer coefficients•Viscosity

Ad Hoc Working Group on Viscosity has carried out comparison, organized by PTB and Cannon Instrument Company, demonstrating good agreement within 1% to 0.1% uncertainty

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CCQM General issues

•Joint CCQM working group meetings contribute to cross-fertilization, know-how transfer, harmonization, avoiding duplication, right experts doing the right things•CCQM workshops and thinkshops have been and will be held on:

•Primary methods and on “how far does the light shine?”•Measurement uncertainty•Traceability in general and special fields (clinical)•Traceability in food analysis (November 2003)

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Designated institutes

•Many NMIs do currently not have broad expertise in metrology in chemistry•Trade, industry and society need to be served in an effective and efficient at short notice•Designate other national institutes and laboratories with special expertise as an NMI for certain quantities and measurement ranges, so they can participate in the CIPM MRA

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Designated institutes

•Guarantee a level economic playing field and treat customers on an equal footing in the case that a commercial organization is being designated to act as an NMI in a certain field•Most NMIs do not have expensive facilities like a reactor for instrumental neutron activation analysis (INAA)•If INAA is needed it is recommended to make use of available reactors in the country concerned

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BIPM programme of metrology in chemistry

•CCQM expressed at the 21st CGPM its opinion that it is essential for the BIPM to build up own knowledge in the wide field of metrology in chemistry in order to be able to act as a competent partner in the international community of chemists, assisting in the development of traceability and comparability in the field of measurements in chemistry

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BIPM programme of metrology in chemistry

•CCQM advised the CIPM and the BIPM on its programme of work•In 2003 the CCQM advised unanimously that the chemistry section of the BIPM should add a small activity on purity analysis in the field of organic and clinical chemistry•This programme has been and will be tuned with the IFCC and the NMIs

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Conclusions

Good progress has been made; still several issues have to be addressed:•Education on metrology in chemistry, including the understanding of traceability and meas. uncertainty•Definition of the right measurand•Method-dependent measurements•Matrix problems•Commutability in clinical and therapeutic measurements•Non-SI traceable measurements•Traceability chain via CRMs