Analytical Method Development and Validation

Outline of course

• Requirements for a stability-indicating analytical method
  • Anticipation of likely degradation products
    • From experience with compound
    • From forced degradation (stress testing) of drug substance, as per ICH guidance
    • What problems may be anticipated with likely degradation products?
    • Are degradation products likely to be enantiomers or diastereoisomers?
• Analytical method development
  • Specificity: peak purity determination (Diode array and MS detectors)
  • Reminder of the importance of resolution, separation factor (selectivity), capacity factor and column efficiency).
  • Selecting the column for analysis
  • Selecting the mobile phase (optimise pH etc)
  • Gradient/isocratic operation appropriate?
  • Calculation of mass balance and its significance
  • Avoiding false identification, particularly in drug product analysis
  • Consideration of ICH Q3A/B (identification of deg prods > identification threshold)
  • Other attributes to be monitored during the stability study?
• Validation of stability-indicating analytical method
  • To ICH Q2(R1)
  • Intro/reminder of parameters to be validated
  • Extent of validation
  • Acceptance criteria
  • Validation procedures and protocols
  • Dealing with validation failures

• Transfer of stability-indicating analytical method
  • In-house or external transfer
  • Which parameters should be compared between originator and second lab?
  • Comparative testing or re-validation?
  • Reference standards and samples
  • The process and communication
  • Transfer protocols and acceptance criteria
  • Typical pitfalls in method transfer
  • What if the acceptance criteria are not met?
• Stability study documentation
  • Designing the ideal stability study
  • The stability protocol
  • The stability report