28 February - 1 March 2019
Esther Frey, Novartis Pharma AG
Dr Anja Fritsch, Confarma
Stefan Gärtner, Labor LS
Koen Marijt, MAT Research
Dr Ilka Molitor, Novartis Pharma AG
Dr Ruth Röder, Microcoat
Dr Ingo Spreitzer, Paul-Ehrlich-Institut
Dr Sandra Stoppelkamp, University Tübingen and South Westphalia University of Applied Sciences
This unique event is organised to gain practical experience in performing the Monocyte Activation Test. Further, it brings together industry and regulatory representatives in order to discuss the practical experiences in using MAT, the advantages, the pitfalls, the available systems as well as the regulatory experiences. The purpose is to provide the participants with guidance and support and hands on laboratory training for the implementation and use of the MAT.
During recent years manifold advances have taken place to replace both, Rabbit Pyrogen Test (RPT) and in some cases the Limulus Amebocyte Lysate Test (LAL).
Some of the reasons are:
- Animal experiments have to be reduced. Especially with the current EU Regulations.
- Reduction of variance by validatable in-vitro test methods
- Get an alternative test, where the classic LAL shows some gaps, e.g. Contamination of biologicals by non-endotoxin pyrogens not detectable in LAL test is not unlikely.
True In-vitro Pyrogen Tests (IVPT) have been developed in several European countries (United Kingdom, The Netherlands, Switzerland, Germany) in national and international research projects. The tests imitate the central step of human fever reaction, i.e. the activation
of human monocytes by endotoxin as well as non-
endotoxin pyrogens. One result of all these activities is the Monocyte Activation Test (MAT).
Following, with continuous support by the German Pharmacopeia, the EDQM MAT Expert group was re-established and finally the MAT Monograph 2.6.30. was implemented into the European Pharmacopeia in 2010. Meanwhile, the EDQM performed a MAT-survey to improve the MAT monograph and the BET-Guideline 5.1.10. and the Rabbit Pyrogen Test (RPT) monograph, 2.6.8. have been revised to clarify the priorisation of the MAT compared to the RPT (especially in regards to the EU-directive 2010/63). However, there still open questions how MAT can be applied in a routine lab for release testing. The meeting will give guidance for proper use of MAT and strengths and weaknesses will be discussed.
This course is addressed to all persons of
- pharmaceutical manufacturers
- biopharmaceutical companies
- medical device manufacturers
- contract laboratories
- tissue establishments
who are involved in Endotoxin- and Pyrogen Testing in development, IPC or release.
ProgrammePyrogens – Fever inducing agents and the principal of the Monocyte Activation Test
MAT a compendial test method
- What are pyrogens
- Diversity of Pyrogens
- Activation of the human immune system through TLRs Stimulation
- Detection of cytokines using the MAT
Pyrogen Testing - Fever in an animal´s body
- Explanation of European Pharmacopoeia 2.6.30
- International status of MAT
Pyrogen testing from a Pharma QC perspective
- History of the Rabbit Pyrogen Test
- Pharmacopoeial Requirements
- Regulatory Requirements and Animal Welfare
- (EU-Directive 2010/63/EU)
- Field of Application
- Future of Pyrogene Detection
- The Rabbit Pyrogen Test – Pros and Cons for the pharmaceutical industry
- The Monocyte Activation Test – challenges and opportunitie
Case study – Cryo blood and Cell-based MAT
- Performance of cryo blood and cell-based MAT
- Pros and Cons of particular systems
Preparation of Samples (e.g., stimulation of cells)
Multiple read-out of cytokines
Hands-on training in the Lab
- Available multiple read-out platforms
- Case study: Comparison of platforms
Recap of day 1
Measurement of Samples
Case study – PBMC based MAT
Hands-on training in the Lab
MAT on medical devices – suitable alternative test method for pyrogen- and material-induced activation?
- Performance of PBMC-based MAT Pros and Cons of particular system
MAT and its challenges
- How the new ISO 10993-11 guideline affects the testing
- Diversity of the test results with MAT variants
- Possible interpretation of the MAT variant outcomes
- Variability of test systems
- Interpretation of test results
Presentation of results - Plenum
Discussion of results