Validation

• • Aids in international pharmacopoeial harmonization, especially in impurities determination and limits
  • Helps in taking appropriate action in case of non-compliance
• Purposes for Validation:

  • Enables scientists to communicate effectively on technical matters
  • Sets standards for evaluation procedures and compliance checking
  • Economic benefits: Reduces costs associated with process sampling and testing
  • Ensures the quality of the product by providing adequacy and reliability of a system or procedure to meet pre-determined criteria
  • Retrospective validation is useful for trend comparison of results compliance to CGMP/CGLP
  • Allows closer interaction with pharmacopeial forum to address analytical problems
• Selection of Analytical Method:

  • Should be as simple as possible
  • Should be the most specific
  • Should be productive, economical, and convenient
  • Should be as accurate and precise as required
  • Avoid multiple sources of key components (reagents, columns, TLC plates)
  • Must be fully optimized before transfer for validation
• Analytical Parameters to be Validated:

  • Accuracy
  • Precision
  • Selectivity (Specificity)
  • Linearity
  • Range
  • Sensitivity
  • Limit of Detection (LOD)
  • Limit of Quantitation (LQD)
  • Ruggedness
  • Robustness
• Accuracy:

  • Relates to the closeness of test results to the true value
  • Expressed as % recovery by the assay of known/added amount of analyte in the linearity range
  • Can be determined by comparing results with those obtained using an alternative validated method
• Precision:

  • Degree of agreement among individual test results
  • Usually expressed as SD/RSD
  • Measure of repeatability or reproducibility under normal conditions
  • Includes:
  • Repeatability (under the same conditions)
  • Reproducibility (under different conditions)
  • Intermediate Precision
• Selectivity/Specificity:

  • Ability of the method to measure accurately and specifically the analyte of interest in the presence of matrix and other components
  • Ensures accurate measurement in the presence of impurities and related substances
• Linearity:

  • Ability of the method to elicit test results directly proportional to the concentration of analyte
• Range:

  • Lowest and highest level of analyte that the method can determine with reasonable accuracy and precision
  • In the range of 80/100/120% of the claim
• Limit of Detection (LOD):

  • Lowest concentration of analyte in the sample that the method can detect but not necessarily quantify
  • Prescribed as a percentage or parts per million (ppm - mcg/mL)
• Ruggedness:

  • Degree of reproducibility of test results obtained under a variety of normal test conditions
• Robustness:

  • Measure of the capacity of the analytical method to remain unaffected by small deliberate variations in procedure
• Sensitivity:

  • Capacity of the test procedure to record small variations in concentrations
• Steps for Validation Procedures:

  • Establish validation of proposed protocols
  • Perform experimental studies
  • Evaluate analytical results
  • Carry out statistical evaluation
  • Prepare a report documenting all results