Dr J. Susanne Becker, Intertek Switzerland AG
Lothar Fruth, Toxicology Expert Services
Dr Armin Hauk, Sartorius Stedim Biotech GmbH
Desmond G. Hunt, United States Pharmacopoeia (USP)
Michael Jahn, Lonza AG
Petra Motzkau, Sartorius Stedim Biotech GmbH
Dr Andreas Nixdorf, SGS Institut Fresenius GmbH
Gaby Reckzügel, Boehringer Ingelheim Pharma GmbH & Co. KG
Dr Mike Schäfers, West Pharmaceutical Services GmbH & Co. KG
Dr Alicia Sobantka, Octapharma GmbH
Dr Jörg Zürcher, Bayer AG
Over the last years, the requirements on the assessment of substances that could leach into the drug product in the course of its life cycle have increased considerably.
The kind of leachable you would have to look for can vary from organic oligomers and catalyst residues to heavy metals – to name 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
Packaging materials have been in the focus of such investigations for a long time as the contact time between drug product and packaging material is rather long.
But in addition you have also to consider other possible sources of contamination. Recently, particular attention was paid to devices and equipment used in the production process itself, e.g. filters, bags, 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.
Within the scope of this GMP Education Course, all relevant aspects of Pharmacopoeia/GMP-compliant leachables and extractables testing will be addressed ranging from regulatory requirements to routine extractables testing in quality control.
Experienced industry speakers share their in-depth knowledge with you.
The course is designed for personnel of pharmaceutical companies and their suppliers who
- are responsible for qualification of extractables/leachables in quality control.
- perform leachables/extractables testing.
- work in quality control of packaging materials.
- choose and define polymeric, glass and rubber
- materials in process development.
- choose and define Single Use Equipment for manufacturing
- develops materials sourcing strategies.
Introduction to Plastics Construction and related Additives
Regulatory Requirements for Extractables / Leachables Testing for finished Packagings
- Classification of plastics
- Physical and chemical characteristics
- Different types of additives in plastics
Determining the Suitability of Packaging Systems for Therapeutic Products: Compendial Perspective
- Why should Extractables & Leachables be assessed?
- Regulatory requirements of EMA and US-FDA
- Compendial requirements and foodstuff regulations
- PQRI recommendations and ICH Guidelines: Safety Thresholds and Permitted Daily Exposure
- USP <1663>, <1664>: Best Practices for Extractables & Leachables testing
Principal Organisation of E&L Assessments - an Overview; Practical aspects beyond Theory
- Rationale and current thinking around USP’s packaging standards
- How Chemical Characterization is being integrated into USP packaging standards
- Current, and future, changes to USP plastic, glass and elastomeric standards
- Chemical Characterization of component used to manufacture drug products
Extractables and Leachables testing in Packaging Material, Correlation between Extractables & Leachables, Leachables Strategies
- Extractables & Leachables Study organization for finished packaging’s, timely planning
- Extractables 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 sterilization methods on materials chemical composition
- Failure modes
How to establish the “chemical link” between Extractables& Leachables
- Analytical method requirements, validation of Leachables analytical methods
- Development of Leachables strategies based on Extractable profile and toxicological report
- How to deal with trustable and poorly characterized chemical profiles
Leachables observed only in Leachables study but not in the Extractables Study: What to do?
Routine Extractables Testing in Quality Control
- OOS case
- Combination medical devices ISO 10993 vice versa USP
L&E Strategies in Practice
- Batch-to-batch consistency in composition and purity of packaging components
- Acceptance criteria for extractables profiles
- Quality agreements with suppliers
- Change Management
Extractables from Glass
- How to design a reasonable E&L Study for single and multicomponent CCS including printings and adhesives (“to do enough but not too much”)
- The translation of regulatory requirements into analytical lab work
- The evaluation of Extractables data and consequences to Leachables Studies
- Illustrative examples
Extractables from Elastomers – Parenteral Packaging Testing
- Glass composition
- Type of extractables from glass
- Risk evaluation of glass extractables
- Concepts to avoid extractables from glass
Toxicological Assessment of Leachables and Extractables Studies
- Composition of Elastomers used for Pharmaceutical Applications
- Discussion Material Composition and Extractables (Potential Extractable List)
- Approaches to minimize Extractable/ Leachable from Elastomeric Closures
- General Approach to Extractable/ Leachable Studies for Parenterals
- Minimum requirements for a toxicological assessment of E&L substances
- Recommendations for an effective search for toxicological data
- The art of PDE derivation in a nutshell - for non-toxicologists
- How to deal with poorly identified substances or substances without sufficient toxicological information
In the course of this workshop you will develop a strategy for conducting a compliant and reasonable leachables study. The task will be based on an industry example. It will be your challenge to answer the following questions:
A reasonable E&L Design for complex Products
- Which activities are necessary during the development phase?
- How will you deal with quality control during routine production?
- Where will you find useful information about the material you are going to use?
USP strategy for developing Standards for Plastic Components and Systems used on the Manufacturing of a Drug Product
- Summary of the different steps to be addressed for a proper Extractables-Leachables Screening Study
- Illustration of different study designs which may be applied for complex materials consisting of many different parts
- Importance of a Leachables check experiment as part of the formal Extractables screening study
- Case studies/examples of complex materials, such as, nasal spray device, multilayer bag from single use dosage system
Leachables during Manufacturing
- Objective of standard
- Risk-based approach outlined in the standard
- Rationale for solvent chosen for standards
Interference of Leachables with Biopharmaceuticals during Manufacturing, Storage and Administration
- 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
Aspects of a targeting L&E Evaluation from the Point of View of a Biopharmaceutical Manufacturer
- Influence of leachables on biopharmaceutical process performance
- Influence of leachables on the stability of biopharmaceuticals
- Influence of leachables on the analytics of biopharmaceuticals
In this workshop you will handle examples of Leachables studies in the field of Biopharmaceutical manufacturing. These examples will base on industrial and contract lab issues and challenges relating to modern process strategies