USP GENERAL CHAPTER<1210> STATISTICAL TOOLS FOR PROCEDURE VALIDATION


Procedure validation is a cornerstone in the process of establishing an analytical procedure. The aim of procedure validation is to demonstrate that the procedure, when run under standard conditions, will satisfy the requirement of being fit for use.


Analytical Procedure Validation Terminology:

  • Laboratory sample: The material received by the laboratory.
  • Analytical sample: Material created by any physical manipulation of the laboratory sample, such as crushing or grinding.
  • Test portion: The quantity (aliquot) of material taken from the analytical sample for testing.
  • Test solution: The solution resulting from chemical manipulation of the test portion such as chemical derivatization of the analyte in the test portion or dissolution of the test portion.
  • Individual determination (ID): The measured numerical value from a single unit of test solution.
  • Reportable value: Average value of readings from one or more units of a test solution.


Questions considered prior to validation may include the following:

  • What are the allowable ranges for operational parameters, such as temperature and time,that impact the performance of the analytical procedure?
  • What are the ruggedness factors that impact precision?
  • Are statistical assumptions r during pre-validation or based on a risk regarding data analysis assessment reasonably satisfied?
  • What is the required range for the procedure?
  • Do accepted reference values or results from an established procedure exist for validation of accuracy?
  • How many individual determinations will compose the reportable value, and how will they be aggregated?
  • What are appropriate validation acceptance criteria?
  • How large a validation experiment is necessary?


Major parameters to be validated:

  • Accuracy 
  • Precision
  • Limits of Detection (LOD)
  • Limits of Quantitation (LOQ)


Read also: Dissolution Method Development and Validation