WHO Mass Jabbing Programs rely on German Innovation in Endotoxin measurement
Paul Ehrlich Institute spends millions of Euros to satisfy WHO and EU 3Rs plan to reduce Rabbit and Horseshoe Crab Death toll involved in Jab Endotoxin tests
Among hundreds of documents I downloaded from the EU after searching on Endotoxin, there are many that detail the key role of German scientists at Paul Ehrlich Institute who coordinate international efforts to replace Animal Testing with other techniques for the critical function of Batch Release of treatments subject to Endotoxin and other Pyrogen contamination as discussed earlier.1234
Paul Ehrlich Institute was using up to 7,000 Rabbits per year to detect Endotoxin by measuring their induced Fever.
Like Australia’s TGA, Paul Ehrlich Institute is also a big customer for Horseshoe Crab Blue Blood Amoebocyte Lysate used in the Lyophilised Amoebocyte Lysate (LAL) Bacterial Endotoxin Test (BET).5
They are moving to revise the European Pharmacopoeia that specifies acceptable test methods including the Human Blood Monocyte Activation Test (MAT), as shown in this 2022 slide6 from a conference organized by European Directorate for the Quality of Medicines and the Council of Europe.
The effort to reduce the possible Horseshoe Crab extinction in certain harvest areas has included development of synthetic Recombinant Factor C (rFC) that can replace the Crab Blood extract. More on that later.
3Rs
At the same 2022 conference, GSK stated they will continue using Animals in their testing while seeking to reduce the numbers killed under the 3R program.7
The 3Rs refer to Replace, Reduce or Refine use of Animals in Endotoxin and Pyrogen testing.
The adoption of 3Rs approaches has been a legal requirement in Europe since 1986 (former Directive 86/609/EEC; current Directive 2010/63/EU).
Since leaving Europe, the UK has continued with its 3Rs effort to follow WHO guidelines for the batch release testing of biologicals.8
Note that GSK tends not actually show the animals they use in Endotoxin testing. Click on the image to see it larger.
Australia’s NHMRC also subscribes to the 3Rs in research.9
WHO removal of “Innocuity Test” does not apply to Endotoxin
In 2020 WHO relaxed its requirements for Innocuity Testing of medicines as part of its 3Rs initiative, but this does not apply to Endotoxin.10 The Innocuity test consisted of injecting the product into Guinea Pigs and/or Mice. A batch passed the test if no animal showed any signs of illness, relevant body weight changes, or Died within 7 days.
Move to detect Non-Endotoxin Pyrogens in Jabs
There is a trend in development of various Pharmacopoeia used in Jab regulation to move almost exclusively to MAT, however this reacts to numerous other toxic contaminants apart from Endotoxin. That is a long story for a future post.
Emmanuelle Charton, Head of DivB, European Pharmacopoeia Department, EDQM, Council of Europe. 2022. New pyrogenicity strategy of the European Pharmacopoeia. in International Conference, 19-21 September 2022. Collaboration, Innovation and Scientific Excellence: the European Pharmacopoeia 11th Edition. Session 5: Supporting microbiological and viral safety
Shahjahan Shaid. 3R & Pyrogen detection in the vaccine industry. GlaxoSmithKline Biologicals SA. International Conference, 19-21 September 2022. Collaboration, Innovation and Scientific Excellence: the European Pharmacopoeia 11th Edition. Session 5: Supporting microbiological and viral safety
Elliot Lilley, Richard Isbrucker, Ian Ragan, Anthony Holmes. 2021. Integrating 3Rs approaches in WHO guidelines for the batch release testing of biologicals. https://www.sciencedirect.com/science/article/pii/S1045105621000841
https://www.nhmrc.gov.au/research-policy/ethics/animal-ethics/3rs
Dianliang Lei, Herbert Schmidt, Ivana Knezevic, Tiequn Zhou, Hye-na Kang, Sabine Kopp. 2020. Removal of the innocuity test from The International Pharmacopoeia and WHO recommendations for vaccines and biological products. https://www.sciencedirect.com/science/article/pii/S1045105620300610