The Bodies in Charge of Animal Welfare: What They Do and What They Could Do?

The coming into force of the 2010/63/EU (Directive of the European Parliament and of the Council of 22 September 2010) Standard, regarding the protection of animals used for scientific purposes, has made it mandatory for all establishments breeding, supplying, and using said animals to have an Animal Welfare Body (AWB). The establishment of a body such as the AWB represents a strong innovation compared to previous regulations (Dir. 86/609/CEE). Building from the key concept of the 3 Rs, European Community legislators acknowledged that the effective safeguard of animal welfare depends in large part on the professional skills of personnel in charge of their care and use. The European Community legislators therefore identify a body inside the institution that houses the animals and entrust it with the task to stimulate and support the practical implementation of the 3 Rs, by informing on technical and scientific developments on the application of said principle and the subsequent training and follow-up training of personnel. The functions assigned by the Standard to the AWB therefore focus on technical-scientific support: to supply advice to personnel in charge of animals concerning their welfare, matters relating to their acquisition, housing, care, and use, and to their integration/adoption (rehoming) at the end of their use. This approach is also emphasized by vesting the AWB with the responsibility to define and review internal monitoring and communication procedures pertaining to the welfare of the animals housed in the establishment, and to follow their development and the outcome of research projects concerning the effects produced on the animals used, supplying advice on activities that could result in possible improvements. Aware of the complexity and sensitivity of the role assigned to the AWB, and of the difficulty to put into practice the directions subject matter of the Standard, The European Commission, in the years following the issue of the Directive, appointed groups of experts with the task to formulate guidelines which would be beneficial both to the establishments and to control authorities of the various Member States and guarantee the implementation of effective and to control authorities of the various Member States and guarantee the implementation of effective and harmonized solutions. (National Competent Authorities for the implementation of Directive 2010/63/EU, http://ec.europa.eu/environment/chemicals/lab_animals/pubs_guidance_en.htm).

Brain penetration assessment in vivo: a reliable and simple method in anesthetized rats at steady state.

BACKGROUND: For CNS drugs, brain disposition is of critical importance during drug discovery. In vitro methods are used early followed by more predictive in vivo methods later on in the drug discovery process. Current in vivo methods are costly, have long turnover times or do not measure brain disposition at steady state. NEW METHOD: A new method to evaluate drug brain disposition in vivo was developed in anaesthetized rats. Seven reference compounds were administered as an initial IV bolus (loading dose) followed by IV infusion for 4.5 h in order to obtain a steady state plasma concentration before brain sampling. The loading dose was estimated from a preliminary single dose IV pharmacokinetic study and was found to successfully bring plasma concentrations to steady state for compounds exhibiting either mono- or bi-compartmental pharmacokinetics. RESULTS: Using this method, a steady state lasting at least 2h was obtained, thus making the in vivo method robust with respect to differences in the pharmacokinetics and/or blood-to-brain equilibration rate of the compounds tested. The method produced highly reproducible results, with substantial advantages in terms of cost, turnaround time and animal welfare. COMPARISON WITH EXISTING METHODS: The results agreed with those reported in other, more elaborate preclinical models and in humans, enabling brain disposition to be assessed in a simple, efficient and robust in vivo model for new chemical entities. CONCLUSIONS: Introducing the presented method in drug discovery allows brain disposition to be assessed earlier in the drug discovery pipeline and thus facilitate the selection of potent and penetrant CNS drugs.