1.INTRODUCTION The aim of this validation study has been to demonstrate that the method AD-TM-R165335-F051-POW-LD-000959-v2 is suitable for determination of the particle size distribution of R165335 – F051 by means of laser diffraction. T... 1.INTRODUCTION
The aim of this validation study has been to demonstrate that the method AD-TM-R165335-F051-POW-LD-000959-v2 is suitable for determination of the particle size distribution of R165335 – F051 by means of laser diffraction. The following compounds have been used in the validation.
2. METHOD VALIDATION
2.1. Precision
2.1.1. Analysis Repeatability – test results and acceptance
criteria
Analysis repeatability expresses the precision of the analytical method under the same operating conditions over a short interval of time. The repeatability of the method has been determined by the 6-fold analysis of 1 sample of the drug product batch by 1 analyst on 1 day， using 1 instrument. Based on the
volume distribution， for each analysis the dV10， dV50 and dV90 cumulative undersizes are reported. In addition， for each series of particle size data the averages， standard deviations， relative standard deviations (RSD)， and 95% confidence intervals are reported. For evaluation purposes， the RSD values are compared with the acceptance criteria.
2.1.2. Intermediate Precision – test results and acceptance
criteria
Intermediate precision expresses the within laboratory variations， e.g.different days， different analysts， etc. For this purpose， the intermediate precision of the method has been determined by 2 analysts， each analysing the product in 6-fold. The analyses have been done using 1 instrument，whereas analyst 1 performed a 6-fold analysis on day 1， and analyst 2 performed a 6-fold analysis on day 2. The validation data as obtained for the
analysis repeatability testing will be used as the analyst 1 data set. Based on the volume distribution， for each analysis the dV10， dV50 and dV90 cumulative undersizes are reported. In addition， for each series of particle size data the averages， standard deviations， relative standard deviations (RSD)， and 95% confidence intervals are reported. For evaluation purposes，the RSD values are compared with the acceptance criteria.
Participating Analysts:
? Analyst 1: Global Analytical Development， Method Development， Beers (Belgium)
? Analyst 2: Global Analytical Development， Stability Evaluation and Release， Beers (Belgium)
2.1.3. Conclusions
The particle size method AD-TM-R165335-F051-POW-LD-000959-v2 has
been demonstrated to show an adequate analysis repeatability and
intermediate precision.
2.2. Robustness
The robustness of the analytical method has been tested during the method development and is a measure of its capacity to remain unaffected by small but deliberate variations in method parameters. The capability of method AD-TM-R165335-F051-LD-000959-v2 to remain unaffected has been tested by varying the following parameter:
1. Slid Width (and thereby the mass flow of the product in the instrument)
2.2.1. Conclusions
The robustness of the method has been demonstrated by showing the validity of the method after small deliberate changes to the slid width. 展開
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