Clinical and Laboratory Standards Institute guideline EP26—User Evaluation of Acceptability of a Reagent Lot Change provides recommendations for laboratories on evaluating a new reagent lot, based on a protocol that uses patient samples to detect clinically important changes from the current lot. It provides guidance on determining whether lot-to-lot differences are significant and whether an observed difference is acceptable based on the established criteria. The protocol attempts to balance the need to detect changes in reagent performance that may adversely affect patient results with the fact that reagent lot verification is a relatively frequent task that places demands on the laboratory’s limited resources. The more extensive initial setup of the protocol at the individual site is a one-time task performed in advance, making the subsequent testing of new reagent lots a straightforward procedure.

This guideline replaces the previous edition of the approved guideline, EP26-A, published in 2013. Several changes were made in this edition, including: 

• More clearly delineating the two stages of the protocol to clarify that the setup stage is performed only once, before any new reagent lot evaluations 

• Providing additional detail about the statistical techniques used, so that the included tables can be extended as needed 

• Revising discussion of allowable total analytical error (TEa) as a basis for determining critical difference (CD) to align with current recommendations and to improve clarity regarding the relationship between the CD and TEa 

• Expanding the examples of reagent lot change evaluation to provide more detail on determining the CD and other critical parameters 

This guideline describes a practical approach for screening new reagent lots for clinically significant performance changes with patient samples. This protocol is designed to use a small number of samples. Thus, lots can be screened quickly with limited resources. The protocol consists of two stages: 

• Stage 1 sets up the protocol for each analyte. This stage involves making decisions about the medically acceptable differences caused by reagent lot change and the acceptable risks associated with incorrect inferences. However, this stage can be performed before any reagent lots are evaluated. 

• Stage 2 is the evaluation of a new reagent lot, using the protocol developed in stage 1. This stage is simple and rapid and is performed for every new reagent lot. 

Additionally, the process described enables the laboratory to determine the effectiveness of the protocol used, including the expected probability of detecting a significant lot-to-lot difference and the probability of falsely rejecting an acceptable lot. The process also shows how factors such as measurement procedure imprecision and choice of CD affect the effectiveness and practicality of the chosen protocol. No single fixed protocol is appropriate for all measurement procedures. Therefore, this guideline provides recommendations on developing specific protocols.

This guideline describes a statistically sound protocol for evaluating the consistency of patient sample results when a new analytical reagent lot replaces a reagent lot currently in use. It is designed for use with quantitative measurement procedures, and more generally for measurement procedures that report on a continuous scale. The same principles can be applied to measurement procedures that convert results from a continuous scale to a qualitative report based on a cutoff value. This guideline is intended for use in the medical laboratory and is designed to work within the practical limitations of that environment. 

This guideline is not intended for use with measurement procedures that provide only qualitative or semiquantitative results. It is also not intended for measurement procedures for which a shift in patient results is expected with new reagent lots. For some measurement procedures, a shift in patient results with a new reagent lot is usual and expected, because the reagents are biological materials that may have lot-to-lot differences. Such measurement procedures include prothrombin time and activated partial thromboplastin time. The usual processes for clinical use of these measurement procedures account for this expected difference, and new lot evaluation as described in this guideline is not necessary or useful. Guidance for these measurement procedures provides detail on handling reagent lot changes. See CLSI documents H47 and H54. 

Additionally, this guideline is not intended to describe procedures for reagent manufacturers. The requirements of reagent lot-to-lot testing by manufacturers, as well as the resources available, are different from those of the medical laboratory. However, reagent manufacturers may use this guideline to understand the types of verification studies that may be performed in their customers’ laboratories.