Metrological assistance of medical measurement devices using certified reference materials of physicochemical properties

This article reviews some issues of metrological support of medical measurement devices using certified reference materials of physicochemical properties. The extensive application of modern automatic analyzers of new generation helps clinicians in diagnostics and therapy. Comparability of analyzer readings is possible only if metrological approaches to measurements are used.

The modern development of the medical industry and the shift in the focus of healthcare from medical care to disease prevention raises the higher level of the problem of medical diagnostics results reliability.
A wide range of new-generation automatic bioanalyzers helps medical doctors, optimizing the testing process and minimizing time and efforts to perform analyses. There are various types of laboratory analyzers depending on the specialization of the laboratory and the purpose of the research, such as: hematological, acid-base status analyzers, biochemical, blood gas analyzers, immunoassay, chemiluminescence, coagulometers, urine analyzers, PCR analyzers, etc. Unfortunately, metrological support of this type of equipment does not keep pace with technological progress. At present more than 400 analyzers of the approved type, widely used in bioanalytical and medical measurements, are entered in the Federal Information Fund on Ensuring Uniformity of Measurements.
Dozens of analytical technologies are currently available in laboratory analyzers to measure a wide variety of human biomaterial components (Table 1), whose deviations from reference ranges provide important information for clinical decision-making. Relevant information on laboratory tests can be found in the "Federal Laboratory Test Handbook. Handbook of Laboratory Tests" [1], developed by the Regulatory and Reference Information Service (RRIS) of the Russian Ministry of Public Health, developed at the Central Research Institute for Health Organization and Informatization. Comparability of analyzer indications is possible only with the use of metrological approaches and can be ensured by close interaction of analyzer developers (manufacturers) and clinicians with metrologists. At the international level, the activity of JCTML (Joint Committee for Traceability in Laboratory Medicine) is an example of such interaction. There is no such committee in the Russian Federation yet, but collaboration in certain areas is underway. The solution of the problem of assuring the uniformity of measurements performed in laboratory medicine can be found in the context of complex interdisciplinary concept of assuring the uniformity of measurements in laboratory diagnostics, proposed by V.L. Emanuel [2]. The Russian Federation legislation provides as the highest level of traceability either to the State Primary Measurement Standards (GET) of units or, in their absence, to the National Primary Measurement Standards of the corresponding units of foreign countries. At the same time, ISO 17511:2020 [3] proposes six possible calibration hierarchies in laboratory medicine, supported with available reference measurement procedures (RMPs) and primary reference materials (RMs) with full metrological traceability to SI, RMP in the absence of RM for the quantity, RMP calibrated with a particular primary calibrator traceable to SI, an international conventional calibrator or a certified reference material with a consensus-based protocol for value assignment, international protocols for harmonization of in vitro diagnostic test systems, and also manufacturer arbitrary selected RMs.
All analytical systems used in clinical diagnostic laboratories reproduce physical and chemical methods of determining these or those analyte quantities, but the specificity of biological material implies matrix-dependent methods of determining the quantitative composition of the sample under study [4]. Hence, there is also a need to ensure traceability using certified reference materials and the elaboration of reference methods.
Most modern biochemical, hematological and immunological analyzers are closed analytical systems with following metrologically important parts: photometric system, potentiometric system, conductometric system, sample and reagent dosing system, dilution system, incubation system, reaction time reference system, rotational and vibratory mixing system, washing system and others. The reagents, most importantly the calibrators used in the operation and setup of the analyzers, have a significant influence on the measurement results in the biological sample of the analyte. Calibrators included in test systems are a key element of metrological reliability of measurement results in laboratory medicine, allowing the calibration of analytical systems and metrological traceability [5]. Hence, all the above mentioned influences the reliability of analytical results obtained with the help of modern analytical systems universally used in medical clinical-diagnostic laboratories. It is to be noted that the accuracy of reproduction and reliability of obtaining a unit concentration of a particular component (analyte) of biological material directly affects the decision-making process when making a diagnosis of the patient.
More than 15 years ago the D.I. Mendeleyev Institute for Metrology (VNIIM) identified the need for certified reference materials (CRMs) for metrological supporting of human biomaterials components (analytes) measurements. The work on the development and production of CRMs in this area was started. As of today, ten approved types of reference materials (GSO) of different components (analytes) developed in VNIIM have been registered in the Federal Information Fund on Ensuring Uniformity of Measurements: The international agreement "Agreement on cooperation in the creation and application of standard samples of composition and properties of substances and materials" was adopted in October 2019 and came into force in August 2020. The main target of signing this Agreement is to meet the needs of the states-participants of this agreement in standard samples of substances and materials and especially in the field of medicine and microbiology.