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.

Costs

ECA-Member*: EUR 2070,--
Non ECA Member*: EUR 2270,--
EU/GMP Inspectorates*: EUR 1135,--
APIC Member Discount*: EUR 2170,--

(All prices excl. VAT)

* also payable by credit card American Express Visa Mastercard

If you have any questions, please contact us:
Tel.: +49 (0)6221 / 84 44 0 E-Mail: info@gmp-compliance.org

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

Technical Requirements

We use WebEx Events for our live online training courses and webinars. At https://www.gmp-compliance.org/training/online-training-technical-information you will find all the information you need to participate in our trainings and you can check if your system meets the necessary requirements to participate. If the installation of browser extensions is not possible due to your rights in the IT system, please contact your IT department. WebEx is a standard nowadays and the necessary installation is fast and easy.

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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