Analytical Method Validation

Analytical Method Validation is defined as ‘‘Establishing a documented proof, which provides a high degree of assurance that a specific process will consistently produce a desired result at its prearranged specifications and quality characteristics,” as per ICH Q2 (R1).  

To put simple, it refers to the process of demonstrating that all the analytical procedures chosen are suitable for their intended use and outcome. It also indicates the identity, quality, purity, and potency of drug substances and drug products.  

Every regulatory authority including FDA, USP, ICH and EU have slightly varying guidelines around the methods used for Analytical Method Validation.  

According to USP guidelines: “The analytical parameters that need to be validated are accuracy, precision, specificity, detection of limit, quantitation limit, linearity, range, ruggedness and robustness.”  

According to ICH guidelines: “The analytical parameters that need to be validated are accuracy, precision, specificity, detection of limit, quantitation limit, linearity, range, system suitability and robustness.”  

According to FDA: ”The analytical parameters that need to be validated are accuracy, precision, specificity/selectivity, detection of limit, quantitation limit, linearity, range, system suitability, reproducibility, sample solution stability and robustness.”  

According to European guidelines: ”The analytical parameters that need to be validated are accuracy, precision, specificity, detection of limit, quantitation limit, linearity and range.”  

What are the steps included in Analytical Method Validation?  

Here are the typical steps involved in the process of validation:  

• Develop a validation protocol or operating procedure for the validation.  

• Define the application, purpose and scope of the method.  

• Define the performance parameters.  

• Define the experiments to perform for validation.  

• Verify relevant performance characteristics of equipment.  

• Qualify materials, e.g. standards and reagents.  

• Perform pre-validation experiments.  

• Adjust method parameters if necessary.  

• Develop SOPs for executing the method routinely.  

• Define revalidation criteria to standardize the process.  

• Define routine analytical quality control checks.  

• Keep validation report furnished with validation experiments and results.  

What are the key parameters against which you can perform analytical method validation?  

The key parameters include: 

• Accuracy  

• Precision  

• Repeatability and Reproducibility  

• Intermediate precision  

• Specificity/Selectivity  

• Limit of Detection (LOD)  

• Limit of Quantitation (LOQ)  

• Linearity  

• Range  

• Robustness  

• Ruggedness  

• System suitability testing  

What are the types of tests that are generally under the radar of Analytical  Method Validation?  

There are mainly three types of analytical procedures that need to be validated, including:  

• Identification Tests (How a product will behave)  

• Quantitative Tests/ Limit Tests (To keep a control on impurities)  

• Quantitative Test for Active Moiety (Measure the analyte present in the drug sample)  

Lastly, when should Analytical Method Validation be performed?  

It should be performed;  

• Before the drug’s initial use in routine testing  

• When you transfer drug to another laboratory  

• Whenever the conditions or method parameters change