B-143 Defining Proximity Limits for Semi-Annual Analytical Measurement Range Verification Studies

Background Regulatory requirements by College of American Pathologists (CAP) require a semi-annual analytical measurement range (AMR) verification for analytes with less than 3-point calibrations. Proximity limits define the closeness of standards/linearity material to the lower limit of quantitation (LLoQ) and upper limit of quantitation (ULoQ) for a given analyte. These limits may be expressed in concentration units or percentages. Clinical Laboratory Standards Institute (CLSI) EP06-ED2 suggests method-specific proximity limits based on the analytical imprecision at the LLoQ and ULoQ. CAP recommends 10-15% at ULoQ and “reasonably close” to the LLoQ. Clearly, this requirement is subject to the Medical Director*s discretion. The aim of this study is to establish and standardize proximity limits based on workgroup consensus at a large rural health network. Methods A workgroup was formed to standardize the semi-annual AMR verification practices with key representatives from over 40 laboratories. Majority of the health system utilizes Abbott Alinity or Architect instruments for chemistry and immunoassay tests. Linearity material from third-party vendors like Maine Standards or AUDIT is used to assess the acceptability of established proximity limits. Analytical imprecision of the low level quality control material is taken into consideration for establishing low proximity limits. Results Proximity limits were established for 115 analytes spanning key testing areas such as chemistry, endocrinology, immunology, tumor markers and toxicology. Multiples of LLoQ or analytical imprecision at the lower end and 20% of the ULoQ at the upper end was reviewed for acceptability using linearity material. An exemplary proximity limit criteria for comprehensive metabolic panel is shown in Table 1. Importantly, these consensus based proximity limits considered crucial factors like analytical imprecision, clinical impact of error and the availability of test material near the limits. In addition to total allowable error, proximity limits could be utilized as acceptance criteria in the EP evaluator linearity and calibration verification module for semi-annual AMR verification studies. Conclusion Defining proximity limits in semi-annual AMR studies are crucial for evaluating the accuracy of quantitative measurement procedure and for regulatory compliance. Due to practical challenges, current regulations do not provide a formulary of proximity limits. Here we provide recommendations for method-specific proximity limits.