Anja Cerstiaens, Toxikon
Dr Armin Hauk, Sartorius Stedim Biotech GmbH
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
Ken Wong, Sanofi Pasteur, USA
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 FDA/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,
- develop materials sourcing strategies.
Introduction to Plastics, Classification of plastics
Regulatory Requirements for Extractables/Leachables Testing
- Physical and chemical characteristics
- Different types of additives in plastics
Extractables and Leachables Testing in Packaging Material and SUS
- 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
Routine Extractables Testing in Quality Control
- Why – Regulatory requirements of FDA and EMEA
- Develops materials sourcing strategies
- What – Change in primary and secondary packaging material or labels
- How – Global and tailored approaches
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 multi component 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
BPOG’s E&L recommendations
- 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
Leachables during Manufacturing
- Status on Extractable recommendation and evolutions
- Rationale behind the extractable protocol
- What are the flexibilities on the suggested extractable protocol
- How suppliers engage BPOG team for future studies?
- Status on BPOG Leachable Best Practice guide (publication date)
- E&L Risk Assessment benchmarking results among BPOG members versus BPOG’s proposed model as well as USP<661.3> and USP<1661.2> risk assessment and key considerations
Establishing single extractable standard (BPOG, USP, & ASTM)
- 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
Immunogenicity: the new concern for leachables in bioproduction and for primary packaging of biopharmaceuticals – The link to reactive leachables
- Is it possible to have a single extractable standard?
- Status updates on USP and ASTM progress
- Understand the scope and objective differences among BPOG, USP and ASTM
- Can we perform one set of study to cover all requirements?
Interference of Leachables with Biopharmaceuticals during Manufacturing, Storage and Administration
- Strengths and weaknesses of the BPOG protocol, explained via a Case Study.
- Comparing the Solvent Selection of the BPOG protocol with USP <661.3> solvent selection through a case study.
- Static Versus Dynamic Extraction for Single Use Systems
- Differentiation of E/L-Study Approach for different components in the Bioproduction Process.
- Influence of leachables on biopharmaceutical process performance
- Influence of leachables on the stability of biopharmaceuticals
- Influence of leachables on the analytics of biopharmaceuticals
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:
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?