Extractables & Leachables (10689)

Over the last years, the requirements for the assessment of substances that could leach into the drug substance and drug product in the course of its life cycle have increased considerably.

The specific kinds of extractables/leachables can vary from organic oligomers and catalyst residues to heavy metals – to name only a few. Due to the resulting complexity, it is very important to consider the potential risk factors associated with leaching substances already at a very early stage in process development. Therefore, the ICH is currently working on a new ICH Q3E Guideline for Extractables and Leachables (E&L) to “assist both applicants and regulators by providing focus on critical aspects, and improving transparency in requirements for medicinal products including drug delivery device components”.

Packaging materials have been in the focus of such investigations for a long time as the contact time between drug substance or drug product and packaging material is rather long. But, in addition, other possible sources of contamination also have to be considered. Recently, particular attention has been paid to devices and equipment used in the production process itself, e.g. filters, bags and tubes. The trend towards single-use equipment might relieve the pressure on cleaning validation and the need to introduce control strategies along the supply chain to avoid unintentional added impurities in materials. At the same time leachables/extractables testing will become a topic of major concern.

This webinar will present the latest developments and the current status of regulatory compliant E&L assessments and cover the following aspects: 

Part 1:

08.05.2024 | 10:00 - 12:00 am

• Introduction to extractables and leachables - regulatory and scientific perspectives
• Regulatory guidance and best practice guides (EU/US/ PQRI, PDA, ANVISA and others)
  • ICH Q3E – where are we?  
  • PQRI Guidance Documents and White Papers
  • ISO 10993 Regulation for medical devices and the impact on experimental E&L study design
  • Ph. Eur 2.4.35
  • USP <665>
  • USP <1663>, <1664> and <1665>
• Root causes to be considered in an E&L risk assessment
  • Extractables and leachables from primary packing
  • Extractables and leachables from processing equipment
  • Extractables and leachables OINDP  
  • Extractables and leachables elemental impurities
• Leachables during manufacturing
  • Single-use process equipment (e.g. filters, bags) 
  • Risk-based evaluation and testing strategies under consideration of critical success factors for the pharma/biotech industry, such as cost efficiency, time-to-market and regulatory compliance
• Interference of leachables with biopharmaceuticals during manufacturing, storage and administration
  • Influence of leachables on biopharmaceutical process performance
  • Influence of leachables on the stability of biopharmaceuticals
  • Influence of leachables on the analytics of biopharmaceuticals   
• Extractables from glass and container closure systems 
  • Glass composition
  • Types of extractables from glass 
  • Risk evaluation of glass extractables
  • Concepts to avoid extractables from glass
  • Rubber composition
  • Coated rubbers
  • E&L study design for rubber and other container closure material 

Part 2:

12.06.2024 | 10:00 - 12:00 am

• Designing extractable studies
  • Extractable study designs as part of material qualification and selection
  • Selection of extraction conditions and methods
  • Identification categories, trustable identification
  • Semi-quantitation, analytical uncertainty
  • Analytical methods, target analysis or screening or both
  • Analytical sensitivity adjustment, correlation with analytical evaluation threshold
  • Impacts of sterilisation methods on the chemical composition of materials
• Analytical techniques to be used
  • Analytical method requirements, validation of analytical methods for leachables
  • Method development for leachables and validation 
  • Analytical evaluation threshold (AET)
• Safety assessments/toxicological thresholds
  • Control strategy options
  • PQRI recommendations and ICH Guidelines: Safety Thresholds and Permitted Daily Exposure
  • Available data bases and other scientific sources
  • Development of strategies for leachables based on extractable profile and toxicological report
  • How to deal with trustable and poorly characterised chemical profiles
  • How to establish the “chemical link” between extractables & leachables
  • Explanation of differences in the toxicological evaluation of substances for medicinal products and other regulatory fields like medical devices  
• Interpretation and use of extractables data; from extractables data to potential exposure estimations
  • Physico-chemical principles of extraction versus extractables protocols
  • Use of extractables data in scaling and combination exercises
  • Use of extractables data in exposure estimations
  • Differences in data interpretation for CCS and SUS
  • Quantitative mitigation concepts for the assessment of SUS

Duration: approx. 120 minutes per modul
Language: English | Handout: English

...more from your speaker Dr. Helmut Buschmann...
...more from your speaker Dr. Norbert Handler...

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