Analytical Method Development and Validation

Overview

Analytical methods must be validated to provide reliable data for regulatory submissions. These methods are essential for a number of purposes, including testing for QC release, testing of stability samples, testing of reference materials and to provide data to support specifications.

This course provides a comprehensive coverage of the method development and validation requirements that are essential to progress a pharmaceutical compound, at each stage of product development.

Outline of Course

Day One
Analytical method development, part 1

• Theory and factors affecting resolution – a reminder of the importance of resolution, separation factor (selectivity), retention factor (capacity factor) and column efficiency).
• Selecting the HPLC separation mode (reversed-phase,
  normal-phase etc.)
• Selecting the most appropriate detector

Workshop: Selecting the separation mode
Analytical method development, part 2

• Gradient/isocratic operation appropriate?
• Selecting the column for analysis
• Selecting and optimising the mobile phase
• The effect of pH, considering pKa of the analyte

Workshop: Selecting the column and mobile phase

End of Day One: Group discussion

Day Two
Developing stability-indicating methods

• 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
  • Note findings of stress-testing industry comparison
  • Are degradation products likely to be enantiomers or diastereoisomers?
• Calculation of mass balance and its significance

Workshop: Developing stability-indicating methods

Validation of chromatographic methods, part 1

• Introduction to ICH guidelines: ICH Q2(R1)
• A detailed discussion on the parameters to be validated:
  • Specificity: peak purity determination (Diode array and MS detectors)
  • Linearity
  • Range
  • Accuracy
  • Precision
  • Detection Limit
  • Quantitation Limit
  • Robustness

Validation of chromatographic methods, part 2

• Extent of validation: how much work at each phase of development?
• Acceptance criteria
• Validation procedures and protocols
• Dealing with validation failures

Workshop: Validation of chromatographic methods
End of Day Two: Group discussion and close

The course will include interactive workshop.