Conference: Endotoxin and Pyrogen Testing

Background & Objectives

Testing for endotoxins and pyrogens is a critical in-process and final release test for parenteral products. Over the past decades, various approaches have been developed to provide solutions for the wide range of products tested for endotoxins and pyrogens: RPT, LAL, MAT. With the LAL test method as an established, compendial methodology for bacterial endotoxins, including the harmonisation of EP, USP and JP, there is a solid basis for such testing. But the range of products to be tested is becoming broader and more complex as biotechnological and molecular biological techniques advance. Because of the importance of these tests, they are therefore under constant scrutiny by industry and regulators to ensure the effectiveness of the tests and the safe manufacture and release of products onto the market. Novel medicines such as cell and gene therapies and combinations with medical devices, as well as complex biopharmaceutical formulations, pose challenges for testing and require in-depth knowledge and expertise in the field of endotoxins and pyrogens. Furthermore, as the range of solutions offered by endotoxin testing vendors increases (e.g. recombinant factor C, ELISA-based test kits, automated LAL cartridge technology), it is important to gain a data-driven understanding of the benefits and limitations of each approach. Therefore, it is not only the discussions on low endotoxin recovery and endotoxin masking that are important. We should also focus on the need for future innovations within BET that provide solutions to current challenges with modern pharmaceutical and biopharmaceutical products for daily testing. In addition, automated solutions will play an important role, making issues of computer validation and data integrity important.

This conference will inform you about current developments in Endotoxin and Pyrogen testing, implementation of new methods as well as the practical use of established test methods like LAL for Endotoxin testing.

You become informed about

• International regulatory developments
• Feasibility of new and innovative products and methods
• Special issues like masking/LER
• Testing of critical substances
• Application of alternative testing methods – MAT or RFC

 

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Conference Registration

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Target Audience

This conference is addressed to all persons from

• Pharmaceutical manufacturers
• Biopharmaceutical companies
• Contract laboratories
• Tissue establishments
• Authorities

who are involved in Endotoxin- and Pyrogen Testing.

Moderation

Dr Johannes Reich, Member of the ECA Pharmaceutical Microbiology Group, GM at Microcoat Biotechnologie
Dr Sven M. Deutschmann, Roche, Chair of the ECA Pharmaceutical Microbiology Group

Tuesday, 26 November 2024

Key Note on 26 November: The Promise and Challenges of In Vitro and In Silico Models in Drug Development
Dr Julia Schüler, Charles River Laboratories
The presentation will highlight important developments in the drug development technology landscape influenced by the concept of 3R and the evolving legal landscape. General characteristics of the different applications, their translational relevance as well as adoption drivers will be discussed. Case studies from oncology drug development will help to elucidate these trends and their impact on future processes.

Current Pharmacopoeial Developments in the Field of Endotoxin and Pyrogen Detection
Dr Ingo Spreitzer, PEI, German Federal Agency for Vaccines and Biomedicines

Approval of a Monocyte Activation Test as a Replacement of the Rabbit Pyrogen Test
Dr Sven M. Deutschmann, Roche

• Introduction and Problem Statement
• Additional MAT-RPT Equivalency Study

A Comparison of Recombinant Factor C and LAL Based Methods for Bacterial Endotoxin Testing
Hiram Huzeyfe Yakut, Turkish Medicines and Medical Devices Agency

• Four different bacterial endotoxin testing methods were compared
• Six different parenteral products were studied in each method
• Enhancement/inhibiton effects were examined
• The advantages and weaknesses of the methods over each other have been revealed

Good Practice in LER Hold Time Study: the Choice of the Endotoxin
Alessandro Pauletto, bioMérieux

• Look Back on Hold Time Studies- Naturally occurring endotoxin (NOE) or standard endotoxin (CSE/RSE)?
• PDA TR82 and CSE and RSE in low endotoxin recovery (LER) hold time studies
• Possible impact that CSE and RSE may have on the results of a LER hold time study

Addressing Low Endotoxin Recovery During Biological Development - from Early Stage to Submission
Melanie Jänsch und Jessica Stolzenberger, Boehringer

• A strategy to address the issue of low endotoxin recovery (LER) during biological product development
• To avoid underestimation of endotoxins, Boehringer Ingelheim considers individual approaches for early and late stage development in studies for endotoxin recoveries:
  • Exploratory LER
  • Sample hold time
  • Endotoxin removal studies
• A case study will demonstrate proof of concept

The Mitigation Concept - Understanding the Masking Impact on Drug Product Manufacturing of Biologicals
Martina Wespel, Boehringer Ingelheim and Dr Anthea Darius, Microcoat

• The challenge in ensuring accurate in-process control (IPC) testing
• Sample hold time (SHT) is an integral part of Boehringer Ingelheim's low endotoxin recovery (LER) concept
• Effects of downstream process steps such as capture, virus inactivation, filtration, polishing, and ultra-filtration diafiltration on masking, including buffer composition, pH, and conductivity
• Potential impact on the control and removal of endotoxins during the downstream process, leading to masking effects
• Mitigated Masking using multiple approaches, to overcome the masking to guarantee, that no underestimation of endotoxins during IPC measurements occurred - shown by a case study
• Evaluation of SHT data and the findings contribute to enhancing the reliability and accuracy of IPC testing by identifying and mitigating endotoxin masking

Supramolecular Assembly of Micellar Aggregates is the Basis of Low Endotoxin Recovery (LER) in a Drug Formulation that Can be Resolved by a Whole Blood Assay
Prof Klaus Brandenburg, Brandenburg Antiinfektiva c/o Forschungszentrum Borstel

• Sepsis
• Endotoxin supramolecular conformation
• Anti-LPS peptides
• Structural polymorphism

Developing Endotoxin Assays Based on a Novel LPS-binding Peptide
Prof Dirk Linke, University of Oslo

• Preliminary data on our LPS-binding peptide last year
• Updated data on how to build an "ELISA-like" assay using our peptide
• Possible detection limits and industrial-scale feasibility

On the Detection and Quantification of the Endotoxic, or not Endotoxic, Lipopolysaccharides
Dr Flavien Dardelle, LPS-Bioscience

• Lipopolysaccharides are highly diverse at the molecular level
• Comparison of detection and quantification methods (LAL, HEK-blue TLR-4, LC-MS2, and MALDI-MS)
• Structure-activity relationship of lipopolysaccharides
• Not all lipopolysaccharides are toxic

Update on the Status of the USP proposed General Chapter <86> Endotoxin Testing using Recombinant Reagents
Dr Mark Schweitzer, Chair of the USP General Chapters Microbiology Expert Committee

• Overview of the status of the chapter
• Discussion of the rationale for the introduction as a new general chapter
• Next steps in the evolution of the chapter