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).
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 (impurities content)
* 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
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 (impurities content)
* 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
