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Workshop on Alternative Methods for Rabies Vaccine Testing

 October 11-13, 2011
U.S. Department of Agriculture Center for Veterinary Biologics
National Centers for Animal Health
Ames, Iowa, USA

This workshop brought together over 70 international experts from government, industry, and academia to

  • Review the available methods and approaches that reduce, refine, and replace animals used in human and veterinary rabies vaccine potency testing
  • Develop an implementation strategy to achieve global acceptance and use of these alternatives
Workshop Overview

Printable version of workshop overview

Rabies in humans is a uniformly fatal disease, with infections killing over 70,000 people worldwide each year. Rabies vaccines serve a vital role in preventing further deaths and controlling the disease in certain animal populations. According to the World Health Organization, an estimated 15 million people receive post-exposure vaccine prophylaxis annually due to actual or suspected exposures to the rabies virus. In the U.S. and other developed countries, rabies vaccines have effectively eliminated domestic canine rabies virus strains. However, determining the safety and effectiveness of rabies vaccines requires large numbers of laboratory animals and involves significant pain and distress. New methods and approaches are sought that (1) are more humane and use fewer or no animals, (2) are faster, cheaper, and more accurate, and (3) are safer for laboratory workers.

An international workshop organized by NICEATM, ICCVAM, and its international partners identified rabies vaccines as one of the three highest priorities for future research, development, and validation of alternative test methods that could further refine, reduce, and ultimately replace animal use for potency and safety testing. One of the highest priority implementation activities was organization of an international workshop on alternative methods for rabies vaccine potency testing. Based on recent scientific and technological advances, several alternative approaches have been proposed or are currently available. For example, scientists at the Paul-Ehrlich-Institut recently conducted an international collaborative study for the validation of a serological potency assay for rabies vaccine (inactivated) for veterinary use. A single-dilution assay that significantly reduces the number of mice utilized for the current in vivo NIH test is available for human and veterinary rabies vaccine potency testing. Protective antigen quantification methods that do not require animals or the use of live rabies virus are now available and may be applicable to batch release testing for rabies vaccines. This workshop brought together international scientific experts from government, industry, and academia to review these methods and to define efforts necessary to achieve global acceptance and implementation.

The U.S. Department of Agriculture Center for Veterinary Biologics and the International Alliance for Biological Standardization were sponsors of the workshop.

USDA Issues Policies Incorporating Workshop Recommendations

The U.S. Department of Agriculture (USDA) Center for Veterinary Biologics (CVB) Notice 12-12 (May 2012) provides guidance on the use of humane endpoints and methods in animal testing of biological products, refining animal use for this purpose. Key provisions include:

  • Clarification of the humane endpoint for all animal challenge potency tests codified in 9 CFR 113
  • Guidance on establishing humane endpoints for potency test that do not follow standard requirements
  • Statement encouraging the use of anesthesia for intracranial inoculation of mice

CVB Notice 13-10 (July 2013) eliminates the upper limit LD50 for a valid challenge test as a validity requirement when conducting the rabies virus potency test. Tests in which the challenge LD50 is greater than the upper limit are now acceptable. This is expected to reduce the number of animals used for rabies vaccine testing.

Video on Humane Endpoints to Replace Lethal Parameters in Batch Potency Tests of Rabies Vaccines

This video, discussed at the October 2011 rabies vaccine workshop and the September 2010 ICCVAM vaccine workshop, is available on the Humane Endpoints in Laboratory Animal Experimentation website, which is administered by the Netherlands Center for Alternatives to Animal Use. Please note that the video is on the secured section of the website, which requires the user to register and receive approval for access.

Video credit: Klaus Cussler, Tamara Folz, Joachim Hartinger, Coenraad F.M. Hendriksen, Bjorn V.L. Steen and David A. Morton.  The HELP Group (Humane Endpoints – Lethal Parameters), Bilthoven, The Netherlands, 2001.