Use of Reference Materials in Medical Testing

SLAB 10th Anniversary CelebrationsAccreditation Conference

10th November 2015Dr Deepani Siriwardhana

Senior Lecturer in PathologyFaculty of Medicine

University of RuhunaGalle

Overview

• What are customer expectations in medical laboratory testing?

• How do we conform to customer expectations?

• What are the requirements regarding accuracy in the ISO 15189 standard?

• What are medical reference materials?• Are there analytes without reference

materials?

Does the ISO 15189 standard address accuracy of test results?

• 5.3.1 Equipment• 5.3.1.4 Calibration and metrological

traceability• Metrological traceability shall be to a reference

material or reference procedure of higher metrological order available.”

• “documentation of calibration traceability to a higher order reference material or reference procedure may be provided by an examination system manufacturer.”

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Metrology

• Definition – science of measurement• Measurements are comparisons against

known standards

Metrological Traceability

• Metrological Traceability “ property of a measurement result whereby the result can be related to a stated reference, through a documented unbroken chain of calibrations (comparisons),each contributing to the measurement uncertainty.”

International Vocabulary of Basic and General Terms in Metrology (VIM)

Metrological Traceability

• Key Features– It is a property of a measurement result– The results are obtained through a series of

comparisons to a reference standard– All comparison steps documented– Measurement uncertainty (MU)stated for each

comparison step– Preferably results traceable to an SI unit

Metrological Traceability for Kg

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What is the significance of traceability?• Link measurement results of a patient sample

to a commonly accepted reference (certified reference material or reference measurement procedure)

• Renders measurement results comparable across different – methods and systems– locations– times

What is the definition for RM?

• Material, sufficiently homogeneous and stable with respect to one or more specified properties, which has been established to be fit for its intended use in a measurement process

http://www.nist.gov/srm/definitions.cfm

What are the uses of reference materials?

•Uses – calibration of a measurement system– assessment of a measurement procedure– assigning values to other materials – for quality control purposes

•What it cannot be used for?– Same RM for both calibration and validation of the

same analytical method

What are different categories of Reference Materials?

Traceability Chain for Serum Calcium

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Do all analytes have primary and secondary Calibrators?

• No• Reason: most analytes are yet inadequately

defined for– Physico-chemical characteristics– Molecular weights

• What are the alternatives for such analytes?

Calibration Hierarchies

Measurement of Total Haemoglobin

• International conventional reference measurement procedure with an international conventional calibrator

• ICSH-endorsed absorptionspectrometry method for measuring haemiglobinocyanide

• international conventional calibrator (IRMM BCR 522)

• Bovine blood lysate containing haemiglobinocyanide – certified value &– uncertainty assigned using calibrated spectrophotometers

International Conventional Reference Measurement Procedures

• Catalytic activities of enzymes• IFCC reference measurement procedure for– Alanine transaminase

International Conventional Calibrators

• C-reactive protein • FSH• TSH• Produced by WHO

Lowest Order Metrological Traceability

• No international reference measurement procedure or calibrator

• Only a manufacturer’s method and calibrators• Eg. Tumour markers like CA 19-9

Information about Reference Materials

• Joint Committee for Traceability in Laboratory Medicine (JCTLM)

• National Institute of Science and Technology (NIST)• Institute for Reference Materials and Measurements

(IRMM)• WHO Expert Committee on Biological Standardization

(WHO-ECBS)• International Federation for Clinical Chemistry and

Laboratory Medicine (IFCC)• International Council for Standardization in

Haematology (ICSH)

SRM for Clinical Diagnostics by NIST

Take Home Message

• Request for traceability information from manufacturers.

• Use methods which are traceable to reference materials/reference methods.

• Awareness needed regarding analytes lacking highest order metrological traceability.

References

• White G. Metrological Traceability in Clinical Biochemistry. Annals of Clin Biochem 2011; 48: 393-409

• Vesper HW, Thienpont LM. Traceability in Laboratory Medicine. Clin Chem 2009; 55: 1067-1075