Module 3 Presentations

07/05/2024

Drug Substance Assay Range

• “The interval between the upper and lower concentration (amounts) of analyte in the sample (including these concentrations) for which it has been demonstrated that the method has a suitable level of precision, accuracy and linearity • Normally derived from linearity study and application of the method • Minimum 80 – 120% of nominal theoretical value • Should cover the range of expected results

The Organisation for Professionals in Regulatory Affairs

17

Drug Substance Assay Robustness

• “measure of its capacity to remain unaffected by small, but deliberate variations in method parameters and provides an indication of reliability during normal usage” • e.g. for chromatographic methods: pH, temperature, columns and supplier, mobile phase composition • Univariate or multivariate approach. • Univariate approach is conceptually simple and often quicker – has been acceptable by regulators historically. • Multivariate – should provide more information. Perception that this may be slower but correct design can lead to understanding of interactions between parameters. Commercial software readily available to help guide design. • Both methods useful for estimating reliability (and transferability) and also for assessing system suitability parameters (in conjunction with data through routine use).

The Organisation for Professionals in Regulatory Affairs

18

9