What does the ZLG Aide mémoire 07123101 "Inspection of analytical validation and method transfer" actually tell us?
Do you manage a QC laboratory in the pharmaceutical industry or a contract laboratory in Germany and are you due for the next inspection by the regional council? Then it may also be worth looking at the Aide mémoire AiM 07123101 "Inspection of analytical validation and method transfer", which was published by the Central Authority of the Federal States (“Länder”) for Health Protection with regard to Medicinal Products and Medical Devices (German: Zentralstelle der Länder für Gesundheitsschutz bei Arzneimitteln und Medizinprodukten, ZLG) in 2017.
In this blog article, we’d like to give a brief outline of what this ZLG inspection guideline tells us to do in terms of method validation and method transfer.
Information about method validation
It is expected that the appropriate regulatory guidance documents such as the relevant sections of the EU GMP Guidelines and its corresponding annexes, the ICH Q2(1) as well as the ICH Guidelines on Stability Studies and Impurities, Chapter 1.1. of the European Pharmacopoeia (Ph. Eur.) and, if applicable, Annex 7 of TRS 961 published by WHO will be considered during method validations or method transfers.
In addition to general requirements with information on the verification of compendial methods, the scope, special aspects of microbiological methods, method changes and change control as well as system suitability tests of chromatographic methods, special attention is also paid to batch sampling and sample preparation, especially if this takes place in third countries. Detailed information is given on the contents of a work instruction for batch sampling, so that it can certainly be expected that such a work instruction will be looked at more closely during an inspection...
The section on the extent of validation deals with the necessary analytical validation parameters of method validations. This section is strongly based on the specifications of ICH Q2(R1) and thus certainly represents an additional, simplified guide for one or the other German-speaking analyst. Interesting in this context is also the information that is not included in the ICH Q2(R1), such as the information on the relative standard deviation (RSD) for the precision of chromatographic methods with corresponding source, expected recovery rates or the specification on the statistical test to evaluate trueness using a second independent test method. The definitions of the analytical parameters, which are explained in a separate appendix, are certainly also very helpful for basic understanding in method validation.
Detailed are also the specifications, which contents a method validation plan and report should contain. These are certainly points that might be checked during an inspection...
Method transfer information
Regarding method transfers, the Aide mémoire AiM 07123101 states that necessary validation activities should be evaluated on a risk basis, considering, among other things, the robustness of the analytical method, the qualification of the analysts at the new site, or the existence of comparable quality management systems. A detailed section is about the documents required for a method transfer, such as the test method and its validation as described in the submission documents, the corresponding test instructions, and also a method transfer SOP with concrete details. These concrete, easy-to-understand specifications are certainly an advantage for all those who are currently creating a method transfer SOP... The last section also deals with the documentation to be prepared as part of the method transfer, such as the transfer plan and report, the corresponding risk analyses, any qualification and validation plans and reports, and any change requests that may be required.
In summary, I’d like to say that I personally was pleasantly surprised by the level of detail and comprehensibility of the specifications provided and look forward to seeing how the next version of this aide mémoire will concretise the new ICH Q2(R2) method validation guideline...