The COMET Project : Manufacturing commutable calibrators and quality control materials for standardisation and post-market surveillance of IVD tests

Abstract

According to the in vitro diagnostic regulation (IVDR) EU/2017/746, the metrological traceability of values assigned to calibrators and/or control materials shall be assured through suitable reference measurement procedures (RMPs) and/or suitable Certified Reference Materials (CRMs) of a higher metrological order. Due to a lack of biological CRMs and RMPs, IVD manufacturers are often unable to fully comply with regulation. The lack of higher order RMPs to assign target values to calibrators or quality control materials is mostly due to i) the time needed to validate high accuracy methods with fit for purpose measurement uncertainties, ii) the cost to operate such labour-intensive methods and iii) the lack of primary calibrators of well-characterised purity. In addition to the lack of RMPs, the lack of secondary CRMs largely originates from the difficulty and cost to properly assess materials’ commutability, which is a property describing their ability to properly mimic the behaviour of patient samples. The paramount importance of commutability has only been recognised recently and to date, causes for materials non-commutability remain largely unknown. Addressing these needs requires a coordinated metrological response involving all stakeholders: IVD manufacturers, EQA providers, RM producers, international organisations promoting standardisation. The objectives of the COMET project are: 1. To improve the availability of fit for purpose calibrators and quality control materials that can be used by in vitro diagnostic (IVD) manufacturers and External Quality Assessment (EQA) providers for establishing and verifying metrological traceability of clinical measurements for various measurands : neonatal bilirubin, immunosuppressants, Parathyroid Hormone (PTH), Human Cytomegalovirus (hCMV), Point of Care Tests for glucose and a panel of clinically relevant biomarkers (glucose, testosterone, calcium, total cholesterol, HDL-cholesterol, triglycerides, total protein, ALT and CK). 2. To improve the understanding of key common causes of affecting materials commutability. To achieve this, commutability of various secondary CRMs and EQA materials consisting of different matrices and sample formats will be evaluated and compared. 3. To develop more efficient and cost-effective ways of conducting commutability studies. In order to make commutability assessment more straightforward, new approaches will be developped, including abbreviated commutability studies, multiparameter commutability studies, the use of commutability panels, the use of high throughput RMPs, automated data analysis and mutualising the resources of a network of calibration laboratories. 4. To support post-market surveillance of IVD tests by working in close cooperation with EQA providers and IVD manufacturers. Reference method target values will retrospectively be assigned to EQA materials which commutability has been evaluated and deemed adequate. A large scale accuracy-based program will be organized in which commutable EQA materials with reference method target values will be distribued across different countries. The EQA data will be aggreagated in order to evaluate harmonisation and accuracy of measurement results on an international basis.