Evaluation of each new reagent lot prior to use is extremely vital to ensure that the lot maintains reliable results for patient specimens, which will help to conserve the long-term stability of analytical procedures. In the case of biomarkers, small changes in concentration can give rise to the need for further lab tests and other clinical interventions, and in such situations, ensuring lot-to-lot consistency is especially critical. Lot verification is also a compliance requirement of CLIA (Clinical Laboratory Improvement Amendments), the Joint Commission, and many other regulatory bodies.

Clinical Laboratories

A paper published in the July issue of Clinical Laboratory News discusses the main factors that make reagent lot-to-lot verification a major challenge for manufacturers and medical laboratories. Let’s take a look at the main points made in this paper. According to the author, the factors that can affect performance of a new reagent lot include

  • Changes in a critical reagent material or instability of the reagents
  • Reagent damage during transportation or storage
  • Incorrect calibration
  • The detection agent indicates of immunoassay

New reagent lots affect quality control (QC) material and verifying each lot used will promote consistent patient sample performance.

Problems with Ensuring Lot-to-lot Reagent Consistency

Both reagent manufacturers and clinical laboratories face many issues when it comes to minimizing lot-to-lot differences.

  • Manufacturer Issues

Reagent manufacturers should
– aim to ensure that the assay can measure the analyte correctly based on a known        expected concentration
– minimize lot-to-lot variation when recovering patient samples

Though they have specific procedures to qualify the release of new reagent lots, manufacturers’ processes to ensure lot-to-lot consistency vary greatly. Moreover, patient samples may not be accessible to them and this would limit their ability to see changes that happen after the laboratory tests a sufficient number of samples.

  • Clinical Laboratory Issues

– The main problem is that there is no standard protocol that medical laboratories can rely on to verify lot to lot consistency. Practices differ widely. While some laboratories evaluate just three or four samples, others test up to 20-40 samples.

– There are also issues with regard to the selection of samples. Practices currently in place for lot-to-lot comparison of samples include the use of control materials supplied by the reagent vendors, third-party quality control material, in-house control materials, or patient samples.

– In the case of patient sample comparisons, the type of samples tested vary widely among labs – some labs test samples with low, mid, and high analyte concentrations, some use randomly selected samples, and some test samples with values that span the analytical measurement range of the assays. As there are no standard acceptance or rejection criteria for new reagent lots, labs have to make individual decisions on this based on the past performance of the assay, assay impression, and other relevant considerations.

– Matrix related differences between patient samples and QC material can make it difficult to reach conclusions that the findings of the lot-to-lot comparison procedure apply to actual patient samples. Therefore, laboratories should be cautious when using QC material for lot verification.

Adhering to New CLSI Guideline Can Help

The Clinical and Laboratory Standards Institute (CLSI) publication EP26-A-User Evaluation of Between-Reagent Lot Variation offers clinical laboratories a standardized protocol for reagent lot verification. The document provides guidelines on the evaluation of a new reagent lot including a protocol that uses patient samples to detect significant changes from the current lot.

With their time and resource constraints, laboratories can succeed in managing reagent lot-to-lot verification by planning ahead and adhering to the protocols established by EP26-A.