Overview
Read the 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
November 2006 workshop entitled Scientific Workshop on Alternative Methods to Refine,
Reduce, and Replace the Mouse LD50 Assay for Botulinum Toxin Testing. The goals of the workshop were:
- 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;
- To identify priorities for research, development, and validation
efforts needed to advance the use of alternative methods.
Specific objectives of the workshop included:
- Review the public health needs for botulinum toxin testing,
including the necessity to determine the safety and efficacy of products
containing botulinum toxin;
- Review the current state-of-the-science and identify knowledge
gaps regarding botulinum toxin structural aspects, mechanisms, and
modes of action that are important to the development of alternative
methods for in vivo botulinum toxin tests, and prioritize future
research initiatives that would address these knowledge gaps;
- Review current development and/or validation status of alternative
test methods for in vivo botulinum toxin tests and their potential to reduce,
refine (less pain and distress), or replace the use of the mouse LD50 assay;
- Identify alternative methods that should have the highest
priority for future development and validation studies to assess
potency/toxicity of botulinum toxin.
Workshop Outcomes
In general, the panel's consensus was that the reviewed methods could be used,
in specific circumstances or in a tiered-testing strategy, to reduce or refine the use of mice in
the current botulinum toxin test method. However, none of the reviewed methods could currently be used as
a complete replacement for the current botulinum toxin test method. The panel noted that with
additional development and validation efforts, one or more of the reviewed methods might be useful
as a replacement for the current botulinum toxin test methods in the future. It was noted that
additional validation studies were needed for most methods (e.g., comparison of results to in vivo
outcomes, validation of methods for the specific applications). Finally, some best practices discussed
to decrease the number of animals tested for studies included (a) use of reference standards to minimize
the number of replicate animals needed, (b) use of standardized methodology, and (c) reduction in the
number of doses tested for assays where confirmation of potency is being evaluated.
Nomination
USDA Policy Concerning the Use of Humane Endpoints in Biologics Testing
The USDA Center for Veterinary Biologics (CVB) issued a notice (April 1, 2004) clarifying policy on the use
of humane endpoints for animal challenge potency tests on biologics. The notice covers potency tests that
involve administration of viable virus, bacteria, or bacterial toxin to animals in doses expected to be
lethal.
View CVB notice (April 1, 2004) [PDF]
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