USP-NF Stimuli Article on Linearity of Measurement Methods

Recommendation

24/25 April 2024

QC Compliance Manager - Live Online Training

In the Pharmacopeial Forum, PF 48(5), a stimuli article entitled "Linearity of Measurement Methods" was published.

According to the authors, Edwin van den Heuvel, Brent Harrington, and Timothy Schofield, the "article provides a very generic definition of linearity that is useful to support both method calibration and accuracy studies, making it possible to discuss linearity for quantal bioassays, and support the life cycle of the method."

The article starts with an Introduction, in which general concepts are referenced, as they are, for example, outlined in ICH Q2(R1), ICH Q2(R2) as well as the USP chapters <1220> Analytical Procedure Life Cycle, <1225> Validation of Compendial Procedures, <1210> Statistical Tools for Procedure Validation, and <1030> Biological Assay Chapters—Overview and Glossary.

It continues with a brief overview of the Accuracy Experiment to investigate accuracy as proposed in validation guidelines like USP <1225> and ICH Q2(R1). After that, in the subchapter on Linearity Enhances Accuracy Understanding, the concepts of proportional and absolute bias are discussed in the context of analytical linearity.

In the following subchapter (General Definition of Linearity), a generic mathematical definition of linearity is provided, followed by sections providing discussions on Estimation of Linearity, Sources of Linearity Violation, and Evaluating Linearity and Proportionality.

The subsequent section provides three Examples:

• 1. An analytical method, where the authors develop the calibration model and investigate the accuracy of the calibration model;
• 2. An investigation of the linearity of a microbiological method;
• 3. An investigation of linearity for the true relative potency around the target value.

The document ends with a final Discussion and references to Additional Information.

The article is available on PF Online via the USP Website Access Point. The deadline for submitting comments is November 30, 2022.