State-of-the-art regulation-compliant validation of analytical methods

We validate your analytical methods for the production and testing of active pharmaceutical ingredients (API) or medicinal products, as well as for qualification, validation, and cleaning processes.

Regulatory background

Analytical methods are currently developed and validated according to the guidelines ICH Q14 and Q2(R2), which were transposed into European law by the corresponding regulations EMA/CHMP/ICH/195040/2022 and EMA/CHMP/ICH/82072/2006. These guidelines, which were developed by the International Council for Harmonisation (ICH), provide only a very rough framework that must be adapted by the user according to the current state of science and technology. These guidelines are to be understood as a binding framework for the validation of analytical methods. However, they must be further method-specifically specified and interpreted with regard to validation, based on the type of testing performed (identity, content, purity (impurities)) and the analytical method.

Due to the complexity of various and newly developed methods, a great deal of method-specific expertise on the part of the user and a careful consideration of risk management is necessary for method validation and development. The ICH Q14 guideline describes the harmonized requirements for the development of analytical methods. Particular attention is paid to demonstrating the robustness of the method. Another focus is on the principles for facilitating more efficient, science-based and risk-based post-approval change management. The ICH Q2(R2) guideline, on the other hand, describes the principles of analytical method validation, including validation principles. In particular, the updated version adds requirements for individual analytical methods. Depending on the intended use of the method, the specificity, range, precision and accuracy of the method must be determined, acceptance criteria for the validation must be defined in advance and given limit values must be adhered to.

Both guidelines were adopted and published by the ICH Assembly in November 2023. The requirements began to come into force in March 2024.

Pharmacopeial methods and system suitability

Depending on the planned application, pharmacopeial methods can be used after verification and without prior validation, provided that all pharmacopeial specifications are met. The scope of verification must be determined on the basis of the planned application and the risks arising for both product and method and must partly be supplemented by individual validation tasks. If the method has already been established in another laboratory, the risk-based method transfer applies.

The proof of system suitability is processed as a daily standard and secures the analysis. However, it does not replace the validation of the method. Currently, trend analyses are expected based on the results of the system suitability samples in order to recognize changing conditions as early as possible. In addition, a validation is no longer considered indefinitely valid, so that revalidations or validation reviews must be carried out at risk-based intervals.

Your analytical method, our experience

Valicare offers detailed training as an introduction to this complex topic. We advise and support you in planning, documenting and evaluating verifications and validations as well as in transferring methods and preparing the corresponding risk analysis. Thanks to the expertise and many years of practical experience of our staff in almost all areas of quality control, we can support you in a wide range of analytical methods, from small molecule drugs to advanced therapy medicinal products (ATMPs). Our experts have applied all common chemical and biochemical analysis and coupling techniques as well as cell and molecular biological analysis and functional assays in practice, which enables them to fully support you in preparing of the required documentation, planning the experiments, and interpreting the analytical data.

We offer support for the following analysis and coupling techniques:

• IR, UV/Vis, NIR, Raman, GC, CE, HPLC, MS, MS/MS, ELSD, titration, XRD, NMR, gel electrophoresis
• Microbial contamination (TAMC/TYMC), absence of certain germs, endotoxin concentration determination

We offer support for the following cell and molecular biological analysis and functional assays:

• Gene or protein expression analysis, hematological-immunological flow cytometry, viability, phagocytosis, cell-based functional tests (stimulation, inhibition, toxicity) with different endpoints

Support in developing and establishing GMP-compliant analytical methods and in method validation in the context of manufacturing medical devices round off our range of services.

The following brochure provides a summary of our services in this area. Please do not hesitate to contact us.