PREMIER partners publish new scientific paper: Minimizing Experimental Testing on Fish for Legacy Pharmaceuticals

This is the third scientific publication in PREMIER and represents a clear example of the success of this public-private partnership. The work has been published in Environmental Science & Technology and it was authored by scientists working at PREMIER’s public partners ECT Oekotoxikologie and the University of Exeter and at PREMIER’s industry partners AstraZeneca and Eli Lilly.

Since 2006, assessing the environmental risks of new human medicines has been mandatory in the European Union. Yet, many active pharmaceutical ingredients used in human medicines were on the market before 2006 (so-called ‘legacy pharmaceuticals’), and therefore lack data that are necessary to assess their environmental risks. Much research effort is now in place to generate these missing data and the Innovative Medicines Initiative (IMI)-funded project PREMIER is among the most recent projects to support this endeavour.

 The regulatory data requirements for an environmental risk assessment of new medicines include toxicity tests with vertebrate animals, namely fish. Motivated by animal welfare considerations, we have developed a structured decision tree to help minimise fish testing for legacy pharmaceuticals as much as possible, whilst ensuring a high level of environmental protection. The decision tree uses a combination of experimental laboratory tests with non-vertebrate organisms and a fish-specific in silico model to characterize the potential environmental impact by ‘risk quotients’. These quotients are then compared to a conservative threshold value. The decision tree only advises fish testing of a given legacy pharmaceutical if either the threshold value is exceeded or other information indicates highly specific toxicity to fish.  

 We have run approximately 100 pharmaceuticals that have high-quality data through the decision tree and show that its use could potentially reduce fish testing by around 35%, without lowering the level of environmental protection. Future work includes further verification of the decision tree with new experimental data as they are generated in PREMIER and incorporation of new animal-free methods into the decision tree. 

Read the full publication here.