GMP News No. 153
13 December 2001
of Analytical Methods:
At seminars on "Validation of analytical methods" the question emerges again and again as to how "INTERMEDIATE PRECISION" - as it is referred to in ICH Guidelines Q2A and Q2B - is to be verified and expressed.
ICH lays down that Intermediate Precision is to cover the various influences within a laboratory, i.e. conducting analyses on two different (or several) days by different laboratory staff members, with different equipment (if available), etc. This is to examine in accordance with ICH Guideline Q2A the effects of random events on the precision of an analytical method. Intermediate Precision therefore gives a first indication already of the future transferability of an analytical method, but it must not be confused with robustness since in the testing of the robustness of an analysis method deliberate changes are made with an assumed influence on the results.
How can we now determine Intermediate Precision?
The easiest option is to summarize or compare without comment the two series of numbers obtained. This procedure might not always be sufficient when applying for marketing authorization.
Furthermore, the two series of numbers (e.g. 6 [or 10] measurements each with a mean and relative standard deviation) can be compared with the aid of statistical tests (F- and t-test). However, argumentation problems often ensue when the test arrives at the result that the two series of measurements differ statistically significantly (particularly frequent and problematical in case of good performance, i.e. little scatter)! In this case it is recommended that the validation SOP used be furnished with an opening clause in case a difference is statistically significant but analytically irrelevant.
In practice the procedure has proved successful of calculating the mean and the relative standard deviation from all results obtained in test for intermediate precision and prescribing an acceptance criterion for the standard deviation (e.g. 3% relative standard deviation for intermediate precision in case of 2% relative standard deviation for the repetition precision).
Furthermore, FDA also expects an extensive validation protocol now already in which methodology and acceptance criteria for the individual validation parameters are defined. The basis of the acceptance criteria for the validation parameters is, of course, always the specification.
Owing to large demand, our Education Course "Validation of Analytical Test Procedures" will be repeated in Vienna on 14-15 May. (Early booking is recommended.) The course will be recognised for the ECA Certification.
Summary compiled after the CONCEPT seminar "Validation of analytical methods" held on September 25/26, 2001 in Ladenburg, Germany.