Development of Stability-Indicating HPLC Methods

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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. To fulfill this requirement, a stability-indicating method (SIM) must be developed and validated to ensure that separate and quantify both the active pharmaceutical ingredient (API) and its related compounds (process impurities and degradation products)

Upon completion of this course, delegates will have learned what is necessary to develop and validate methods for drug substance and drug product to comply with international regulatory guidelines.

Who Should Attend?

Scientists working with HPLC who need to further their understanding of the technique in order to develop better methods faster. Scientists who have to validate HPLC methods in accordance with current internationally-accepted guidance. HPLC technicians working in R&D laboratories, quality control laboratories and stability testing laboratories. Managers with a responsibility for generating regulatory submissions

Course Programme

Day One

Overview of developing a stability-indicating method

  • Regulatory framework
  • What can go wrong on storage
  • Real-time, accelerated and forced degradation
  • Chemical and photochemical decomposition
  • Requirements for a stability-indicating analytical method
  • Anticipation of likely degradation products
  • Are degradation products likely to be isomers, enantiomers or diastereoisomers"

Workshop: Anticipation of likely degradation products

  • Forced degradation (stress testing) of drug substance, as per ICH guidance * Note findings of stress-testing industry comparison

Selection of the HPLC method

  • Overview of HPLC separation modes (reversed-phase, normal-phase etc.)
  • Overview of instrumentation including detectors
  • Deciding the ideal chromatographic mode (e.g. reversed-phase, normal phase etc)
  • Ensuring that the HPLC method adequately determines the degradants
  • Calculation of mass balance and its significance

Workshop: Selecting the separation mode for stability methods

End of Day One: Group discussion

Day Two

Optimising the Stability-Indicating HPLC Method

  • Selecting the column for analysis
  • Scouting runs as a guide to optimum conditions
  • Using chromatographic parameters to decide quality of chromatography
  • Gradient/isocratic operation appropriate"
  • Selecting and optimising the mobile phase
  • The effect of pH, considering pKa of the analyte

Workshop: Developing methods to determine degradants

Validation of Stability-Indicating HPLC Methods, part 1

  • Introduction to ICH guidelines: ICH Q2(R1)
  • Types of analytical procedure to be validated: * Quantitative test (impuritiescontent) * Quantitative test of active moiety(assay vs. external standard)
  • 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

Workshop: Validating a typical HPLC method

Validation of Stability-Indicating HPLC Methods, part 2

  • Acceptance criteria
  • Validation procedures and protocols
  • Dealing with validation failures

End of Day Two: Group discussion and close

The course will include interactive workshops

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