General considerations for the analytical method validation process

PQE Group

The development and production of drugs within the pharmaceutical industry requires manufacturers to quantify their components, and this entails the use of an analytical method that must first be validated in order to be implemented. Validation refers to documented evidence that a process is suitable for the intended method and can replicate consistent results, which establishes scientific evidence that the process is capable of consistently producing a quality product. The parameters evaluated during the validation of an analytical method are specificity, linearity, limits of detection, limits of quantification, range, accuracy and precision. 

To carry out the validation process, it is recommended a team is formed that includes experts from different areas who can contribute knowledge from different perspectives. Another important point is to plan and carry out the validation process following scientific principles. In addition, in the validation life cycle of a process or analytical method, a risk analysis of the parameters and everything that could have an impact on the product or the material in process should be used to establish appropriate controls over everything that represents a risk; these risks should be reevaluated each time new information is issued. Finally, validation should ensure that the process is reasonably protected against anything that could represent a source of variability. 

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According to the FDA, the validation process consists of three stages which consist of the following: 


Stage 1 - Process Design  

The objective of this stage is to design a process that can release a product that consistently meets the quality attributes. The design should be carried out following scientific principles and methods. During this stage the design of the experiment is carried out, which should consider the possible variables detected in the risk analysis to obtain as much information and knowledge that can be used for the commercial process. Therefore, it is necessary to document the information appropriately, to support the decisions that were taken during this phase. 


Stage 2 - Process Qualification

During this stage the process design is evaluated in order to determine if it is capable of reproducible commercial manufacturing. This stage consists of two elements:  

  1. Facility design and utility and equipment qualifications: Facility design must be performed following the relevant regulations, and equipment qualification refers to activities that demonstrate that the equipment is suitable for its intended use and can perform properly.

  2. Performance qualification process: This stage evaluates the performance of the process by combining all the elements involved in the production of commercial batches. Successful performance qualification demonstrates that the process design is adequate. As part of the validation, it is necessary to document this stage, so a protocol is written specifying the manufacturing conditions, controls, tests and expected results. 

Stage 3 - Continuous verification of the process

The objective of this stage is to ensure that the process remains in a controlled or validated state during commercial manufacturing. Therefore, it is essential to have a system or systems in place to detect unplanned results or outputs of the process.

In conclusion

Analytical method validation is a requirement, which is why regulatory agencies have created informative guidelines or general recommendations to perform it, however any alternative approach is appropriate as long as it satisfies the requirements of the applicable regulations. 

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