Method development will be conducted in order to evaluate the ability to measure compounds of interest in final solution of interest under actual use. Prior to any quantitative leachables assessment in the medicinal product, specific analytical methods need to be developed and validated. Although deviations (e.g. reduced validation levels for certain applications) are possible, the basis for the MD&V is the ICH Q2(R1) guideline on method validations. These validations may include the parameters specificity, linearity, method range, accuracy, precision, LOD/LOQ, and robustness.
Method validation is recommended prior to performing any analytical study. The fundamental parameters for method validation are linear, accurate, precise, recovery and selective for the analyte(s) of interest. According to FDA it is recommended that methods are developed and validated in each solution of interest. This allows for more complete evaluation of potential matrix interferences from the test matrix. Should validation not be performed in all matrices, it is recommended that at a minimum spike and recovery analysis of the target analyte is conducted to evaluate potential interference for the target compound.
The linearity of the method describes the ability to measure the instrument’s analytical response in relation to the concentration of the analyte of interest. Linearity is assessed using a minimum of three different concentrations.
Accuracy of an analytical method describes the closeness of mean test results obtained by the method to the true value (concentration) of the analyte.
Precision of analytical method describes the closeness of individual measures of an analyte when the procedure is applied repeatedly to multiple aliquots of a single homogenous matrix.
Intermediate precision of analytical method describes the closeness of individual measures of an analyte when the procedure is applied repeatedly to multiple aliquots of a single homogenous matrix. Analysis is conducted on a different day and/or by a different operator then the precision analysis.
The recovery of an analyte in an assay is the detector response obtained from an amount of analyte added to and extracted from the matrix, compared to the detector response obtained from the true concentration of the pure standard.
Selectivity is the ability of an analytical method to differentiate and quantify the analyte in the presence of other components in the samples.