Impurities Forum- Part I and Part II

Programme

Part I:
Impurities analysis and qualification in Drug Substances and Drug Products – general overview

• Impurity profiling in synthetic drug substances
• Qualification of impurities
• Degradation studies
• Identification of chiral impurities, polymorphic phases and new impurities
• Residual solvents
• Impurities in starting materials and intermediates
• Pharmacopoeial tests and acceptance criteria
• Drug product specifications and parametric release
• Inorganic impurities

Control of organic impurities in the European Pharmacopoeia

• Ph. Eur. analytical techniques used for impurity control
• Impurity control in general chapters and monographs: General monograph 2034, General chapter 5.10 - control of impurities, General chapter 2.2.46 - chromatographic separation techniques
• Qualitative and quantitative control: System suitability tests, Methods of quantification, Limit test vs quantitative test
• Response and correction factors

Practical aspects of method validation for impurity determination

• Important ICH and FDA guidelines
• Quantitation of impurities
• How to define an impurity profile (stress tests)
• Reference substances
• Validation of methods at various development stages
• Statistical approaches to method validation (LOD & LOQ)

Presentation and Workshop: Analytical techniques for determination and qualification of impurities in Starting Materials and Intermediates

• Purity analysis by HPLC, impurity profile
• Residual solvents by GC
• Inorganic impurities (heavy metals, sulphated ash)
• For chiral compounds in addition: enantiomeric puritymand proof of the absolute
• configuration

In the Workshop the participants will learn which activities are necessary to characterise drug substances taking into account the following aspects:

• analytical procedures are necessary for the characterisation
• experiments necessary to check the downstream impurities in order to justify acceptance criteria for the respective impurities
• other impurities have to be taken into account
• experiments to be performed in order to get a stability-indicating analytical procedure

Leachables and extractables

• Why should Extractables & Leachables be assessed?
• Regulatory requirements in the EU and US
• Compendial requirements and industry standards
• Safety qualification of Leachables and Extractables

Stress stability testing during development

• Elucidation of impurities of the drug substance
• Identification of possible degradation products
• Check of the degradation pathways
• Typical experiments
• Test parameter
• Storage conditions
• Stress tests of multi-use products
• Impact on excipients and packaging materials

Part II.
EDQM’s implementation strategy of ICH Q3D in the European Pharmacopoeia – an update

• History of heavy metals tests
• Implementation strategy of ICH Q3D in Ph. Eur.
• Modifications of general chapters and general monographs
• Specific metal tests in individual monographs

ICH Q3D on elemental impurities – requirements and implementation status in the USP general chapters and monographs

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)

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

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.