National Toxicology Program

Alternative Methods for Vaccine Testing

Vaccines contribute to improved human and animal health and welfare by preventing the spread of infectious diseases. However, testing necessary to ensure vaccine effectiveness and safety uses large numbers of animals. Many of these animals may also experience significant pain and distress during testing. Therefore, identification of methods that would reduce or eliminate the need for animal testing for biologics is a high priority for NICEATM and ICCVAM.

NICEATM and ICCVAM have convened several workshops to review recent advances and innovations in science and technology that can be applied to new methods and approaches for vaccine testing. The links below lead to pages on the NICEATM–ICCVAM website with more information about these workshops. U.S. regulatory agencies have issued guidances on use of currently available alternative methods that reduce, refine (enhance animal well-being and lessen or eliminate pain and distress) and replace animal use for vaccine testing. See details and links to further information.

International Workshop on Alternative Methods for Human and Veterinary Rabies Vaccine Testing

Rabies vaccines have had a significant impact in reducing human and animal deaths from rabies infections worldwide. 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.

This October 2011 workshop brought together over 70 international scientific experts from government, industry, and academia to review these methods and to define efforts necessary to achieve global acceptance and implementation. A workshop summary, presentations, and other materials are available on the main workshop webpage. A report of the workshop will be published in 2012 in the journal Biologicals.

Workshop on Alternative Methods for Vaccine Potency and Safety Testing

Vaccines represent a vital and cost-effective tool in the prevention of numerous infectious diseases. Before new vaccines are approved for use in humans and animals, the law requires that they be shown to be safe and effective. Individual lots of approved vaccines must also be tested to demonstrate safety and potency prior to marketing. Laboratory animals may be used during this testing, but in recent years, efforts have increased to develop alternative methods that reduce, refine (decrease or eliminate pain and distress), and replace the use of animals for these purposes.

In accordance with the ICCVAM Five-Year Plan, a workshop was organized by NICEATM and ICCVAM September 2010 to bring together an international group of scientific experts from relevant stakeholder organizations to review the current status and use of such alternatives. The experts at the workshop identified future research, development, and validation activities needed to further advance the use of alternative methods for vaccine potency and safety testing. Discussions at the workshop also reviewed the public health needs for both human and veterinary vaccines, considered how to promote the collection and sharing of data, and discussed ways to promote international harmonization and/or acceptance of alternative methods for vaccine potency and safety testing.

The report from the September 2010 workshop was published in December 2011 as a dedicated issue of Procedia in Vaccinology .

Workshop on Alternatives to the Mouse LD₅₀ Assay for Botulinum Toxin Testing

Botulinum neurotoxins (BoNTs) produced by the bacterium Clostridium botulinum are used in over 50 therapeutic and cosmetic applications. Individual lots of BoNT must be tested to demonstrate safety and potency prior to marketing. The current approved test method for this purpose uses animals, and concerns have been raised both about both the reproducibility of the test and the pain and distress experienced by the laboratory animals.

In response to a nomination by the Humane Society of the United States, NICEATM and ICCVAM, in collaboration with the European Centre for the Validation of Alternative Methods, sponsored a November 2006 workshop to review the state of the science and current knowledge of alternatives that may reduce, replace, and refine (decrease or eliminate pain and distress) the use of mice for botulinum toxin testing. The workshop also identified priorities for research, development, and validation efforts needed to advance the use of alternative methods.

The workshop participants concluded that some of the methods considered during this workshop could be used, in specific circumstances or in a tiered-testing strategy, to reduce or refine the use of mice in current in vivo BoNT testing protocols. However, at the present time, none of the reviewed methods can serve as a complete replacement for the mouse LD₅₀ assay, either for detection of BoNT or for potency determination.

Read the workshop report [PDF]

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. It states that animals being used in these tests that are moribund (specifically, exhibiting clinical signs consistent with the expected disease pathogenesis and unable to rise or move under their own power) may be humanely euthanized and considered as deaths as outlined in 9 CFR 117.4.