Method Validation

Validation Process

The process starts from method definition and development up to reporting of test results. The typical process is as follows:

  • Define the application, purpose and scope of the method
  • Ensure method development, pre-validation and fine-tuning
  • Freeze the method to be validated, develop a validation protocol (specifying validation experiments, acceptance criteria, etc.)
  • Execute the validation experiments according to protocol, check that the acceptance criteria were met
  • Document the validation results in a validation report
  • Approve the method for routine use
  • If any changes are needed that go beyond the original validation, ensure additional validation or re-validation

Parameters

Most guidelines require evaluation of the following method validation parameters:

  • Precision (Repeatability, Intermediate Precision)
  • Accuracy
  • Specificity
  • Limit of Detection
  • Limit of Quantitation
  • Linearity and Range
  • Robustness (Ruggedness)
  • Sensitivity

For more information about the method validation module, see a case study: GC headspace determination of residual solvents in a drug substance, or view software screenshots here.


Related documents

ISO 17025:2005, chapter 5.4.5

ICH Q2(R1)

U.S. FDA, Title 21 of the U.S. CFR: 21 CFR 211—cGMP for finished pharmaceuticals

U.S. FDA – Guidance for Industry (draft) Analytical Procedures and Methods Validation: Chemistry, Manufacturing, and Controls and Documentation, 2000

EPA – Method Validation of U.S. Environmental Protection Agency, Microbiological Methods of Analysis

Eurachem – The Fitness for Purpose of Analytical Methods, A Laboratory Guide to Method Validation and Related Topics, 1998 

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