ZEBET's activities to promote alternative methods for the ID50 potency test in botulinum neurotoxin product testing

Botulinum neurotoxin (BoNT) products are used for treatment of many medical disorders such as cervical dystonia or blepharospasm. Prior to release, every production lot of BoNT requires characterisation in a mouse LD50 potency test according to the monograph "Botulinum Toxin Type A for Injection" issued in the European Pharmacopoeia (EP) 6.0. Due to the paralysing toxic syndrome of BoNT, the treatment of animals is associated with severe suffering. As part of the German Federal Institute for Risk Assessment (BfR) in Berlin, the Center for Alternative Methods to Animal Experiments (ZEBET ) has recently increased its efforts to promote the implementation of the 3Rs in BoNT potency testing. In April 2009, ZEBET organised an international expert meeting on the issue of alternative methods to replace the LD50 Potency Test for BoNT Testing. As a main result of this meeting a "BoNT Expert Working Group- BoNT EWG" was established dedicated to convene several times per year at BfR to further discuss all aspects of BoNT potency testing. It aims to clarify the regulatory requirements regarding BoNT product testing on an international level, to select the most promising alternative test methods and to pinpoint further steps necessary to succeed with their validation and regulatory acceptance. ZEBET in collaboration with the BfArM (Federal Institute for Drugs and Medical Devices) has taken the chair of the BoNT EWG. Members are representatives of national and international competent authorities, validation organisationsand manufacturers of BoNT products as well as academia