Extractables & Leachables Summit 2019

Tentative Schedule:

07:50 Registration and Welcome Coffee

08:20 Opening Address from the Chairman

08:30 USP <665> draft standard: A rational risk-based approach to characterization of polymeric biopharmaceutical manufacturing systems.

USP <665> draft will be the first standard for characterization of specifically single-use systems (SUS) used in manufacturing. In this session we will discuss:

• Risk assessment with respect to patient safety to assign a risk level
• Risk level appropriate testing of components
• Approach for compliance for filters and SUS from a SUS supplier’s perspective

Dr. Lars Albermann,
Head of Pharma and Food Regulatory Subject Matter Experts, Merck KGaA, Frankfurt Am Main, Germany

09:10 Speed Networking

09:50 Strategies for assessment of impurities and E&Ls.

• Definitions of E&L and impurities
• Qualification thresholds
• Use of QSAR
• Role of API in assessment
• Experience with regulators on PQRI proposals

Prof. Dr. Johannes Harleman
Independent Consultant, , Darmstadt, Germany

10:30 Morning coffee and networking break

11:00 Safety assessment of extractables/leachables: Challenges with different administration routes.

• Safety thresholds for extractables/leachables in pharmaceutical products will be introduced
• Applicability of these thresholds to products for different administration routes will be discussed
• Specific safety considerations and approaches for parenteral and ophthalmic products are summarized

Dr. Christian Trendelenburg,
Associate Director, Novartis, Basel, Switzerland

11:40 Toxicological assessment of non-genotoxic E&L.

• Regulatory Guidance
• Searching for toxicological information
• No data available - The Threshold of Toxicological Concern (TTC) approach
• Point of departure available - How to define the Permitted Daily Exposure

Dr. Clemens Günther,
Director Nonclinical Safety Consumer Care, Bayer AG, Berlin, Germany

12:20 Challenges and pitfalls during E&L studies and how to handle them.

For patient safety reasons a precise knowledge about potential drug impurities is essential. With increasing complexity of container closure systems and single use process equipment the risk of leachables being introduced as real drug impurities increases significantly. Authorities are extensively focusing on determination of leachables present in the real drug matrix which increases the analytical effort and complicates data interpretation.

According to general guidelines the E&L studies are commonly divided into different parts:

• Screening of containers and process equipment for extractables
• Screening of the formulation stored under accelerated conditions for potential leachables
• Tox-assessment and definition of the target leachables and their specification
• Leachables method validation
• GMP monitoring of leachables during a stability study in real samples

During this presentation we will focus on the problems which may occur when extractables or leachables above the analytical evaluation threshold are detected during the different steps. Several case studies will be presented. Content:

• Illustration of a suitable study design covering production process, filling line and final container closure system
• Extractables of multi-material-equipment and how to clarify their source
• Temporary leachables detected during stability study
• Unknown leachables and how to identify them

Dr. Tino Otte,
Managing Director, Intertek (Schweiz) AG, Basel-Landschaft, Switzerland

12:45 Business lunch

13:45 Setting up effective E&L Studies.

• Extractable condition selection
• Leachable study design
• Leachable study monitoring and design

Tim Hulme,
Principal Consultant, Smithers Rapra Ltd., Shrewsbury, United Kingdom

14:25 Comparative Extractables Study of Autoclavable Polyethersulfone Filter Cartridges for Sterile Filtration.

Sterile filters are ubiquitous in biopharmaceutical manufacturing processes. They are in direct contact with the process fluid, and the profiling of the extractables is of high importance, especially in process steps “close to patient” such as single-use final fill. The talk will compare and discuss the extractables profiles of sterilizing-grade 0.2 μm polyethersulfone membrane filter cartridges from different vendors. Pure ethanol and purified water were used as extraction media. Several orthogonal analytical techniques such as HS GCMS and GC-MS and LC-HRMS in combination with ICP-MS for single analyte detection and the sum parameters total organic carbon, nonvolatile residue, conductivity, and pH were used to obtain a most comprehensive extractables profile. Various extractables were found such as antioxidants and degradation products thereof, hydrocarbons, and processing aids. The identified compounds can all assigned to the materials of construction, such as plastic parts or membranes. Focus is given also on the challenges one encounters in Extractables screening studies for example in the analysis of hydrophilizing agents. A basic toxicological evaluation for material safety assessment will be presented showing the overall low risk of the extractables toward patient safety.

• Quantitative extractables profile for widely used polyethersulfone membrane filters for sterile filtration
• The relationship between raw material production and membrane manufacturing to the main membrane-related extractables
• Relevance and limits of the TOC reconciliation of screening studies
• Toxicological evaluation for material safety assessment of Extractables results to process conditions

Dr. Roberto Menzel,
Laboratory Supervisor and Manager Extractables, Sartorius Stedim Biotech, Göttingen, Germany

15:05 Afternoon coffee and networking break

15:35 Neat and Ready-to-use Calibrants for Extractables & Leachables Testing Methods

• New Certified Reference Materials for Extractables & Leachables Testing
• Neat products and ready-to-use calibrants for accurate analysis
• Characterization by quantitative NMR (qNMR) spectroscopy, HPLC and GC
• Following ISO/IEC 17025 and ISO 17034 accreditation workflow
• Tested for homogeneity and long-term stability
• Time and cost saving solution for customers

Markus Obkircher,
Director R&D, Head of Reference Materials and Proficiency Testing, Merck, Sankt Gallen, Switzerland

16:15 Risk Based approaches to Extractable and Leachable Study design.

• Factors affecting Dose Form risk of leachables
• A structured approach to assessment of leachable risk
• Linking risk to extractable or leachable studies
• How extractable and /or leachable studies reduce project risk

Jason Creasey,
Managing Director, Maven E&L Ltd, Stevenage, United Kingdom

16:55 Data Integrity.

Rick Reiley,
Principal Scientist, GlaxoSmithKline, London, United Kingdom

17:35 Panel Discussion

18:15 Chairman’s closing remarks and end of day one

19:00 Business dinner