Clinical and Laboratory Standards Institute guideline EP25—Evaluation of Stability of In Vitro Medical Laboratory Test Reagents provides recommendations and regression‑based procedures for establishing and subsequently confirming stability‑related claims of in vitro medical laboratory reagents such as reagent kits, calibrators, control products, and sample diluents. This guideline was written primarily for manufacturers and regulatory agencies but will also be of interest to medical laboratories and developers of laboratory‑developed test methods. It provides information on the design, implementation, data analysis, and documentation needs for studies to establish and confirm shelf life and in‑use life of in vitro diagnostic products. Additional topics cover the assessment of product transport conditions on stability, use of mean kinetic temperature to reflect product exposure to temperature changes during distribution and storage, and accelerated stability testing.

This guideline replaces the previous edition of the approved guideline, EP25-A, published in 2009. Several changes were made in this edition, including: 

• Revising the approach to statistical power analysis for planning studies to assume there will be some drift in reagent performance 

• Designing a testing plan to demonstrate the drift is within the allowable drift limit 

• Eliminating the custom of using the t-test of regression slope results (P>0.05) as a rationale for passing a stability assessment. This practice tends to reward the manufacturer for designing underpowered stability studies. 

• Eliminating the requirement for a confidence interval within the acceptance criteria as a basis for stating claims 

• Revising the regression analysis approach that now requires point data at the claimed time and beyond the claimed time 

• Expanding the practices for transport simulation stability testing 

• Adding a discussion about the use of mean kinetic temperature as an integrated measure of temperature changes experienced by a product during distribution and storage 

• Expanding the use and practices for accelerated stability testing

This guideline provides information for establishing and verifying (confirming) shelf-life and in-use stability claims for quantitative in vitro diagnostic (IVD) medical laboratory reagents or products. The information also applies to qualitative IVD products, provided that an underlying continuous response or signal responsible for the qualitative result(s) is available to the investigator. This guideline also includes background information and typical content for creating a stability testing plan, determining the logistics for performing the studies, conducting recommended data analyses, and documenting stability claims for a product. Additional topics include assessment of product distribution conditions on stability claims (transport simulation), verification of stability claims, appropriate uses of accelerated testing, and considerations for testing with difficult samples. 

The intended users of this guideline are primarily product manufacturers and regulatory agencies. Medical laboratorians may find this information useful for interpreting and confirming commercial product stability claims (eg, in-use life of QC materials), as well as for establishing stability attributes for laboratory-developed test methods. For this guideline, “products” is understood to encompass reagents, calibrators, controls, diluents, and similar materials that are used as IVD medical devices to conduct a measurement procedure for a measurand of medical interest. 

This guideline does not cover instrument systems, laboratory equipment, software, or patient specimens. Stability testing of raw materials or components of reagent kits or consumables is not covered explicitly; however, the principles described in this guideline can be adapted by manufacturers for that purpose.