Abstract

Safety testing of veterinary vaccines requires the use of a large number of animals to investigate possible local and systemic reactions. This includes amongst others the pathological examination of the injection site in frequent intervals. For this a selected killing of animals in frequent intervals is inevitable. To reduce the number of animals needed for this kind of safety testing, magnetic resonance imaging (MRI) was used to detect and quantify possible inflammatory reactions after vaccination in vivo. Sixty four pigs were subdivided into 4 experimental groups (n=16); two groups consisting of 12 weeks old pigs and 2 of 6 month old pigs at vaccination day. The pigs were vaccinated with four licensed products (each group receiving one vaccine) and examined up to 6 times using MRI during a period of 5 weeks. The MRI images were evaluated semi-automatically comparing the volumes of altered signal intensities at the vaccination side (VS) with the volumes of the signal intensities at the control side (CS). A paired t-Test was used to identify significant differences (p<0.05) between VS and CS. The results show that MRI allows a 3D-quantification of the extent of local reactions in vivo, scanning the same animals at several points of time after vaccination. MRI is a suitable alternative method for non-invasive safety testing of injectable medicines and can therefore be used as an alternative method to reduce animal numbers for safety testing purposes.

Highlights

  • Safety testing in animals is an important part of the licensing procedure for veterinary vaccines required by the European Pharmacopoeia and other legal regulations, such as Directive 2001/82/EC (EDQM, 2008; EC, 2001)

  • Some animals have to be euthanized in frequent intervals after vaccination in order to perform a pathologic examination of the vaccination site (EC, 2001)

  • This study was conducted in order to minimize the number of animals used in safety testing of veterinary vaccines according to the 3R principle

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Summary

Introduction

Safety testing in animals is an important part of the licensing procedure for veterinary vaccines required by the European Pharmacopoeia and other legal regulations, such as Directive 2001/82/EC (EDQM, 2008; EC, 2001). For these regulatory tests a large number of animals is needed, because every target animal species and category, for which the use of a medicinal product is intended, has to be tested. This study was conducted in order to minimize the number of animals used in safety testing of veterinary vaccines according to the 3R principle.

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