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Abstract Background It is necessary that each step of in vitro diagnostic assay development and manufacturing processes be documented and executed in alignment with established quality management systems. Here, we describe how Siemens Healthineers (SHS) maintains assay traceability and focus on continuous improvement using the Atellica® CH A-LYTE® Integrated Multisensor Technology (IMT) assays measuring electrolytes sodium (Na), potassium (K), and chloride (Cl) as a prime example. Methods Establishing an unbroken chain of comparison from the National Institute of Standards and Technology (NIST) higher standard references to the product calibrators ensures accurate value assignment within stated measurement uncertainties. Traceability and standardization are achieved by creating a panel of 10 serum anchor pools spanning the analytical measuring interval for each electrolyte: Na, K, and Cl. The concentrations of the anchor pools are determined at a reference laboratory using methods calibrated with standard solutions derived from NIST reference material. These serum anchor pools are used by SHS, assigning values to product calibrator material which maintains the chain of traceability to the primary reference methods. In addition to traceability, onboard stability for the A-LYTE® IMT multisensor is continuously monitored and evaluated against allowable drift limits for each electrolyte. Although observed drift was within allowable limits, a design change was implemented to improve recovery drift over the use life of the sensor. Results To ensure consistent, robust, and accurate performance of the A-LYTE IMT, a strict set of testing procedures are used to verify the accuracy of value assignments for each manufactured lot of master standards. The recovery of the NIST standard reference material must fall within manufacturer established acceptable bias limits. Consistency over nine master lots is shown with bias ranging from -0.9% to +1.9%, -2.4% to +1.8% and -1.8 to +0.5%, for Na, K and Cl, respectively. By further optimizing the amount of Na ionophore and the polymer matrix of the Na sensor, drift over the use life was minimized and onboard stability improved. Prior to making the sensor change, customer Na QC data at 116 mmol/L showed an SD of 1.1 mmol/L (n=585), whereas the precision improved to an SD of 0.6 mmol/L (n=470) post-optimization. As Manufacturers optimize assay performance, it may become necessary for laboratories to re-evaluate reference intervals for their patient populations. For example, one large integrated delivery network established a new reference interval for patient anion gap (AG). A re-evaluation of the historical AG reference interval which was 5-15 mmol/L identified the need for an update. AG values were calculated from 16,948 healthy patients and used to establish a new reference interval of 2-10 mmol/L. Conclusions Accurate clinical laboratory measurements are critical for diagnosing, monitoring, and treating diseases. A-LYTE assays have an unbroken chain of traceability to NIST reference material and minimal drift over the life of the multisensor. Continuous monitoring to identify improvement projects and rigorous control systems ensure sensor performance over time. This provides confidence that the patient results produced by the laboratory are accurate and consistent over time and across different laboratory locations.
Lewisch et al. (Tue,) studied this question.