Assessing the reproducibility of an analytical method.

The reproducibility of a validated analytical method may require reassessment because of various reasons, such as the transfer between laboratories or companies, changes in the instruments or software platforms (or both), or changes in critical reagents, among others. This paper is a demonstration of an assay bridging study in evaluating reproducibility. The approach is simple but very informative and offers many advantages over existing approaches.

Assessing parallelism prior to determining relative potency.

In the course of preparing a revision to Chapter (111) of the U.S. Pharmacopeia, the revision committee came to a unanimous agreement that the method for assessing parallelism that is currently presented in (111) and in the European Pharmacopeia's Chapter 5.3 is flawed and should be replaced. The symptoms are that perfectly acceptable assay results may fail due to good precision and that obviously faulty assay results may pass due to poor precision. The flaw is that the wrong statistical technique has been used. We propose an alternative approach based on the equivalence testing paradigm that does not have these shortcomings. Equivalence testing requires the establishment of equivalence limits. Specific approaches for establishing equivalence limits are discussed.

Assessing similarity in bioanalytical methods.

Due to the comparative nature of a bioassay, the relative potency is usually used to describe the potency of a sample. Only when the two samples are similar can a valid and meaningful estimate of relative potency be obtained. Thus, assessing similarity is a crucial part in developing a bioanalytical method. The current commonly used approach for assessing similarity focuses on the response parameters, such as the slope in the linear case, using either a significance test or an equivalence test. The current direct evaluation of the response parameters ignores the information about the shape of the curve and the possible variance heterogeneity. To overcome this, we propose a method based on the idea of equivalence testing that compares the shapes of the curves directly. The new method first measures the difference of the response between the standard sample and the test sample at each of the concentration (dilution) levels and then determines whether the differences are consistent by comparing them to the equivalence limits. The benefits of the new method are investigated by a simulation study. LAY ABSTRACT: Due to the comparative nature of a bioassay, the relative potency is usually used to describe the potency of a sample. Only when the two samples are similar can a valid and meaningful estimate of relative potency be obtained. Thus, assessing similarity is a crucial part in developing a bioanalytical method. The current commonly used approach for assessing similarity focuses on the response parameters, such as the slope in the linear case, which have many drawbacks To overcome this, we propose a method based on the idea of equivalence test but comparing the shape of curve directly. The new method first measures the difference of the response between the standard sample and the test sample at each of the concentration (dilution) levels and then determines whether the differences are consistent by comparing them to the equivalence limit.