“Validation of Analytical Procedures: Text and Methodology (ICH Q2(R1))” published by the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human (ICH) is a tripartite harmonized guideline that identifies validation parameters needed for variety of laboratory methods to analyze drugs. The three parties involved in this harmonization are the US, EU and Japan. There are quite a lot of other ICH guidelines, which are categorized into 4 major groups:
- Quality Guidelines (e.g. GMP, Pharmaceutical development, Analytical validation etc.)
- Safety Guidelines (e.g. Toxicity studies)
- Efficacy Guidelines (e.g. Pharmacovigilance, Clinical trial reports, GCP etc.)
- Multidisciplinary Guidelines (e.g. Electronic standards, Gene therapy etc.).
Here again we meet the basic pharmaceutical terms of the German Medicinal Products Act (Arzneimittelgesetz – AMG): quality, safety and efficacy (AMG §1).
These guidelines are formed to bridge any differences that may occur and may affect the quality of the overall drug product, while applying for market authorization by any of the corresponding authorities. They should ensure the same quality of the drug irrespective of the country to be released on. Additionally, they should help the authorities getting the same documents in the application in a good quality facilitating approval as all information required are known to the applicants. Although, the US is part of the ICH tripartite, there are additional guidelines published by its own regulatory body, the US Food and Drug Administration (FDA), which also need to be respected in case of marketing drugs in the USA.
As mentioned earlier, the ICH Q2(R1) is a part of the ICH quality guidelines and is responsible for the validation of analytical methods. This guideline is directed towards three main categories of analytical tests:
- Identification tests
- Quantitative tests for impurities' content and Limit tests for the control of impurities;
- Quantitative tests of the active moiety in samples of drug substance or drug product or other selected component(s) in the drug product and assays for efficacy.
Apart from compendial test methods, which need to be verified, these test categories are to ensure the quality (e.g. by identification of the active ingredient), safety (by demonstrating impurities being below acceptable limits) and efficacy (by showing the drug possess the right amount of active ingredient and its potency). For each analytical method, it is required to prove the method’s suitability to analyze a specific drug substance and / or drug product. The parameters required for validation according to the ICH Q2(R1) are Specificity, Linearity, Trueness, Precision, Limit of detection (LOD) as well Limit of quantification (LOQ), Range, and Robustness. Not all parameters are required for each method category, thus it is very important to identify the type of analytical method to be able to prove its intended use by the validation respecting the correct parameters.
The ICH Q2(R1) method validation guideline allows an understanding to the application and limitations of the test method. During method development no validation is yet needed but the principles noted in the ICH guideline applying to validation should already be kept in mind as after final method development the method needs to be validated. If the method validation has not been performed or has been performed in an inadequate manner, the method is not considered to provide reliable data and will not be accepted by the authorities for the upcoming drug product batch release and stability testing.
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