Control Strategies for Elemental Impurities in final dosage forms – Case studies
- Utilisation of Data as part of an Integrated EI Risk Assessment Process
- Potential Sources of Elemental Impurities in the Finished Product
- API
- Equipment
- Container-closure System
- Excipients
- Conclusions
Analytical methods to determine elemental impurities
- Principles and characteristics of the most common spectrometric techniques AAS, ICP-OES, ICP-MS
- Compound methods (sample preparation plus spectrometric detection and quantification)
- Special considerations for trace-elemental analysis
- Application-based approach for choice of methodology
- Analytical process (method development, validation strategy, routine testing)
Mutagenic Impurities: how to develop suitable analytical methods for detection
- Challenges associated with MI analytical method development
- Class based methods vs individually designed messages
- Technologies
- GC-vs LC
- Chromatography vs NMR
- Validation requirements
Workshop: Conducting a risk assessment
In this Workshop the participants will work on several case studies and perform a risk assessment for different scenarios taking into account e.g. manufacturing equipment, dosage form of the drug product etc.
Mutagenic Impurities – requirements, authorities expectations and case studies
- General documents and Guidelines for the assessment of mutagenic impurities
- The assessor’s approach: principles of toxicological assessment
- The TTC concept
- Structural alerts
- Limits and Permitted Daily Exposure
- The ALARP principle
- Applicability of the EU “Guideline on the Limits of Genotoxic Impurities”
- Examples of low daily dose drug substances
- Impurities derived from alkylating agents (mesilate, besilate, tosilate, diisothionate); examples
- Nitrosamines – the Valsartan case
- Potential mutagenicc residual solvents
- Impurities derived from metal catalysts