National Toxicology Program

Workshop Documents

ICCVAM/NICEATM/ECVAM Scientific Workshop on Alternative Methods to Refine, Reduce and Replace the Mouse LD50 Assay For Botulinum Toxin Testing Nov. 13-14, 2006      Silver Spring, MD Workshop Report [PDF]

In response to a test method nomination from the Humane Society of the United States (HSUS), ICCVAM, in collaboration with NICEATM and ECVAM, co-sponsored a Scientific Workshop on Alternative Methods to Refine, Reduce, and Replace the Mouse LD₅₀ Assay for Botulinum Toxin Testing. The 116 attendees from 9 countries included scientists from government and academic institutions, regulatory authorities, and the animal protection community. The workshop goals were: (a) to review the state-of-the-science and current knowledge of alternatives that may reduce, replace, and refine (less pain and distress) the use of mice for botulinum toxin testing and (b) to identify priorities for research, development, and validation efforts needed to advance the use of alternative methods (see the agenda for additional details).

Five workshop sessions covered a variety of topics including:

• An overview of public health needs for botulinum toxin testing and regulatory requirements
• An overview of the current understanding and knowledge gaps for botulinum toxin
• A review of methods as potential replacements or refinements for the current botulinum toxin test
• A review of strategies to reduce the number of animals used for the current botulinum toxin test

During the workshop, panel discussions were held to (a) review and supplement the background information presented during the speakers' presentations, (b) more precisely define the state-of-the-science, knowledge gaps and identify priorities for research, development, and validation efforts needed to advance the use of alternative methods for each area discussed, and (c) develop specific guidance and recommendations to advance the use of alternative methods for each area discussed.

Background

In October 2005, the Humane Society of the United States (HSUS) submitted a test method nomination entitled Alternative Methods to Replace the Mouse LD₅₀ Assay for Botulinum Toxin Potency Testing (view nomination in PDF format). In the nomination, the HSUS proposed a review of the validation status of available in vitro, ex vivo, and non-lethal in vivo test methods as potential replacements for the current botulinum toxin potency test method. The nomination also requested that ICCVAM work with partners and stakeholders to validate one or more of the alternative test methods available.

The HSUS nomination was reviewed by both ICCVAM and SACATM in November to December 2005. Both committees endorsed the sponsorship of a workshop on alternative botulinum toxin test methods with high priority. Accordingly, ICCVAM established a Biologics Working Group to organize the workshop.