International Workshop on Alternative Methods to Reduce, Refine, and Replace the Use of Animals in Vaccine Potency and Safety Testing: State of the Science and Future Directions

Veterinary vaccines contribute to improved human and animal health and welfare by preventing diseases and deaths caused by a wide range of infectious agents. However, testing necessary to ensure vaccine effectiveness and safety can involve large numbers of animals and significant pain and distress. NICEATM and ICCVAM convened an international workshop to review the state of the science of human and veterinary vaccine potency and safety testing methods and to identify opportunities to advance new and improved methods that can further reduce, refine, and replace animal use. This workshop report is the fourth in a series of six, and addresses methods and strategies for veterinary vaccine potency testing that can avoid or lessen pain and distress, improve animal welfare, and reduce animal use. Vaccine potency tests considered to have the highest priority for further reduction and refinement were those that require an infectious agent challenge test or an in vivo toxin neutralization test, those that require large numbers of animals, and those that require the use of infectious agents hazardous to laboratory workers and/or animals. Vaccines identified as high priorities for improved alternative test methods were rabies, Clostridium spp., Leptospira spp., foreign animal diseases (e.g., foot and mouth disease), and poultry and fish vaccines. The workshop recommended priority research, development, and validation activities to address critical knowledge and data gaps, including opportunities to apply new science # The National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods and the Interagency Coordinating Committee on the Validation of Alternative Methods * Corresponding author e-mail address: stokes@niehs.nih.gov This article may be the work product of an employee or group of employees of the National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), or European Commission, however, the statements, opinions or conclusions contained therein do not necessarily represent the statements, opinions or conclusions of NIEHS, NIH, the United States government, the European Commission, or other organizations. 1877-282X © 2011 Published by Elsevier Ltd. Selection and/or peer-review under responsibility of the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM). Open access under CC BY-NC-ND license. 85 William S Stokes et al. / Procedia in Vaccinology 5 (2011) 84 – 105 85 William S Stokes et al. / Procedia in Vaccinology 5 ( 2011 ) 84 – 105 and technology. Recommendations to support more humane animal use included development and use of humane endpoints for all challenge tests, development of serologic assays to replace challenge tests, and development of in vitro toxin neutralization tests to replace in vivo TNTs. Workshop participants recommended approaches to reduce the number of animals required for potency testing, and recommended enhanced international harmonization and cooperation, and closer collaborations between human and veterinary researchers to expedite progress in the development and application of alternative methods. Implementation of the workshop recommendations is expected to advance new methods for veterinary vaccine potency testing that will benefit animal welfare and reduce animal use while ensuring continued protection of human and animal health. © 2011 Published by Elsevier Ltd. Selection and/or peer-review under responsibility of the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM)