Novel pyrogen tests based on the human fever reaction - The report and recommendations of ECVAM Workshop 43

This is the report of the forty-third of a series of workshops organised by the European Centre for the Validation of Alternative Methods (ECVAM). ECV AM's main goal, as defined in 1993 by its Scientific Advisory Committee, is to promote the scientific and regulatory acceptance of alternative methods which are of importance to the biosciences, and which reduce, refine or re place the use of laboratory animals. One of the first priorities set by ECV AM was the implementation of procedures which would enable it to become wel l informed about the state of the art of non-animal test development and va lidation, and the potential for the possible incorporation of alternative t ests into regulatory procedures. It was decided that this would best be ach ieved by the organisation of ECVAM workshops onspecific topics, at which sm all groups of invited experts would review the current status of various ty pes of in vitro tests and their potential uses, and make recommendations ab out the best ways forward (1). The workshop on novel pyrogen tests based on the human fever reaction was h eld in Konstanz, Germany, on 16-20 January 2000, under the chairmanship of the local organiser. Thomas Hartung (University of Konstanz). The participa nts came from industry, academia and national control authorities (in Europ e and the United States), and their expertise extended to pharmacology and toxicology, quality control and quality assurance, immunology, biochemistry , microbiology, laboratory animal science, human medicine, and the developm ent of in vitro assays as alternatives to animal testing, including the per tinent regulatory procedures. The objectives of the workshop were: to identify the need for new pyrogen t ests; to review the current status of the development of new pyrogen tests; to evaluate the capabilities of the new pyrogen tests and to give recommen dations for further development; to identify regulatory requirements and to give recommendations for promotion to regulatory acceptance; and to summar ise the EU project "Human(e) Pyrogen Test" (QLRT-1999 00811; see Appendix 1 ). The outcome of the discussions and the recommendations agreed by the worksh op participants as individuals are summarised in this report.