The Impurities Workshop Part I, II and III - Live Online Training Practical approaches for assessing the risks of Impurities

The Impurities Workshop Part I, II and III - Live Online Training

Course No 20038

This course is part of the GMP Certification Programme "ECA Certified Quality Control Manager". Learn more.

All times mentioned are CEST.

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Speakers

Dr Karl Abele, Solvias AG, Switzerland
Dr Ward D‘Autry, Nelson Labs, Belgium
Dr Gerd Jilge, formerly Boehringer Ingelheim, Germany
Jürgen Martin, Martin-Consulting, Germany
Dr Cornelia Nopitsch-Mai, BfArM, Germany
Dr Ulrich Rose, Formerly EDQM, France
Dr Xaver Schratt, GBA Pharma GmbH, Germany
Dr Andrew Teasdale, Astra Zeneca, UK

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Programme

Part I: General Strategies for Identification and Control of Impurities
 
Analysis and Qualification of Impurities 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
Analytical Method Validation for Impurities
  • Determination at Various Development Stages
  • Quantification 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: Selecting Analytical Procedures and Setting Acceptance Criteria of Impurities during Drug Substances Synthesis
  • Purity analysis by HPLC, impurity profile
  • Residual solvents by GC
  • Inorganic impurities (heavy metals, sulphated ash)
  • For chiral compounds in addition: enantiometric purity and proof of the absolute configuration
In the Workshop the participants will learn which activities are necessary to characterize drug substances taking into account the following aspects:
  • Analytical procedures are necessary for the characterization
  • 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
Unexpected Impurities: Approaches for Investigation and Determination
  • Is there such a thing as ‘unexpected impurities” or is there a lack of process understanding?
  • Valsartan – overview of events
  • Source of contamination
  • Mechanistic understanding
  • Examination of risk within other Sartans – overview of how to conduct a risk assessment and to identify key factors
  • Are there other Mutagenic Impurities related risks?
Part II: Nitrosamine Impurities
 
European Pharmacopoeia Activities (Policy) on Mutagenic Impurities with Focus on Nitrosamines
  • Ph. Eur. General policy on DNA reactive impurities
  • Control of Nitrosamines in Ph. Eur.
  • Changes in individual and general monographs following the Sartan case
  • New general chapter on control of nitrosamines
Root Causes for Nitrosamine Impurities and other Mutagenic Impurities – Practical Approaches to Assess the Risks
  • Development of a systematic risk based approach
  • Key factors and the development of a decision tree
    • API
    • Drug Product
    • Packaging
Analytical Solutions for Monitoring Presence/Formation of N-Nitrosamines within APIs and Drug Products
  • Detection limits requested by in Article 5(3) of Regulation EC (No) 726/2004
  • Techniques used for analysis of non-API related N-Nitrosamines
  • Formation of N-nitrosylated APIs in drug products
  • Analytical methods used for quantification of N-nitrosylated APIs in drug products
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.

Nitrosamines and Other Genotoxic Impurities – Authorities' Expectations and Dossier Requirements
  • The assessor’s approach: principles of toxicological assessment
  • Structural alerts
  • Limits and Permitted Daily Exposure
  • The ALARP principle
  • 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
Part III: Elemental Impurities
 
European Pharmacopoeia Activities (Policy) on Elemental Impurities – an Update
  • Implementation of Q3D in Ph. Eur.
  • Changes in individual and general monographs
  • Harmonisation of general chapter 2.4.20
  • Second phase for revision of excipient monographs
Risk-Based Approach for Elemental Impurities in the Supply Chain
  • APIs, excipients, packaging materials impacting the purity profile
  • Evaluation of supply chain processes
  • Risk analysis as evaluation tool
  • Audits and monitoring programs as important sources
  • Testing strategies
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.

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