Purity determinations are applied as part of the quality control of pharmaceuticals, their active pharmaceutical ingredients (and, if applicable, their excipients in case they are not yet obtained in compendial quality). This includes quantitative determinations, resulting in a definite statement of the quantity or concentration, as well as qualitative / semi-quantitative determinations with results allowing only conclusions to be drawn as to whether the impurity is present or not or whether it is below a certain limit value. Such determinations are also known as "limit tests". Some people will think back to a laboratory practical training in drug analysis during their studies with more or less enthusiasm when they hear the word "limit test"...
To make work easier, I’d like to continue with our already started template series and today I’d like to post a template that can be used during method validations to evaluate the validation parameter precision (including repeatability, instrumental precision, and two versions for intermediate precision).
A wide variety of analysis methods are used in the pharmaceutical quality control laboratory. In addition to methods to proof the identity of the active pharmaceutical ingredient and qualitative tests, quantitative determinations are also included. A (calibration) standard of different concentrations is run in parallel within each analysis and the intensity of the measurement signal (detector response) is then plotted against the concentration.
If you are just approaching the topic of method validation, you may be faced with the question which analytical methods are actually affected by method validation.
To answer this question, we have to clarify which methods are used when and for what purpose.
During method validations in pharmaceutical QC laboratories or commissioned contract laboratories, different validation parameters have to be checked. For quantitative impurity determinations and assays, such as content determinations of the active pharmaceutical ingredient or potency tests, studies of the linearity are required according to the method validation guideline ICH Q2(R1).
When evaluating quantitative analytical quality control methods regarding their fitness for purpose during method validation, the validation parameter “intermediate precision” must also be considered. The term “intermediate precision” might also appear under the following names:
- within-laboratory reproducibility or intralaboratory reproducibility
- within-lab(oratory) / within-device precision
- inter-assay precision / between-run precision
We recently spend time on the topic of "Trueness, accuracy and precision".
In today's small article, I would like to briefly illustrate the relationships between these three terms and the underlying types of errors with the help of a beautiful picture.
Templates make life easier. This is true in every field of life. Since this blog is about topics in pharmaceutical laboratories, especially method validation, method verification and method transfer, we have started to provide templates for the validation of analytical methods according to ICH Q2(R1) considering their method type (identification method, impurity test or assay).