National Toxicology Program

National Toxicology Program
https://ntp.niehs.nih.gov/go/iccvam-biologics

Alternative Methods for Biologics and Vaccine Testing


Accepted Alternative Methods for Biologics and Vaccine Testing

Vaccines improve human and animal health and welfare by preventing the spread of infectious diseases. Testing to ensure effectiveness and safety of vaccines and other biologics often requires the use of large numbers of animals, many of which experience significant pain and distress during testing. Therefore, identification of methods that would reduce or eliminate the need for animal testing for vaccines is a high priority for NICEATM and ICCVAM.

International Workshop on Alternatives to the Murine Histamine Sensitization Test (HIST) for Acellular Pertussis Vaccines

Vaccination has greatly reduced the incidence of pertussis, once one of the most common childhood diseases in the United States. Prior to marketing these vaccines, manufacturers must confirm the absence of residual pertussis toxin by using the rodent-reliant murine histamine sensitization test, or HIST. There is widespread interest among vaccine manufacturers and animal welfare advocates in finding a non-animal alternative to the HIST: the test is technically challenging, each test requires up to 60 animals, and the animals experience significant unrelieved pain and distress.

NICEATM and international collaborators conducted a series of workshops to discuss and review in vitro protocols and available data from an ongoing international study of a non-animal alternative to the HIST. The study used a Chinese hamster ovary cell line assay to measure pertussis toxin in vaccine samples containing reference preparations, or specific quantities of added toxin. Experts at the final workshop in March 2015 concluded that the assay worked adequately, and they recommended that vaccine manufacturers begin using the assay alongside current HIST testing to demonstrate its validity for their specific products.

International Workshop on Alternative Methods for Leptospira Vaccine Potency Testing (2012)

Leptospirosis is a serious and often fatal disease in humans and animals. NICEATM and the U.S. Department of Agriculture (USDA) organized a workshop that brought together over 80 international scientific experts from government, industry, and academia to review recent advances in the science and technology of Leptospira vaccine potency testing and available alternative test method approaches. The proceedings of the workshop were published in 2013 in a special issue of the journal Biologicals.

In response to the workshop recommendations, the USDA Center for Veterinary Biologics (CVB) issued guidance for vaccine manufacturers on obtaining an exemption that allows use of a non-animal test for Leptospira vaccine potency testing. The USDA will monitor trends in animal use to assess the impact of this test and report the findings annually to ICCVAM.

International Workshop on Alternative Methods for Human and Veterinary Rabies Vaccine Testing (2011)

Rabies vaccination has significantly reduced human and animal deaths from rabies infections worldwide. There is interest in identifying new methods and approaches for determining the safety and effectiveness of rabies vaccines that are more humane, use fewer or no animals, are more efficient and accurate, and are safer for laboratory workers. Over 70 international scientific experts from government, industry, and academia attended a NICEATM-organized workshop to review alternative methods for rabies vaccine testing and to define the efforts necessary to achieve global acceptance and implementation. A workshop report was published in 2012 in the journal Biologicals.

The CVB subsequently issued policies reflecting the recommendations and goals of the workshop. CVB Notice No. 12-12 (2012) contains specific guidance on implementing humane endpoints during the rabies challenge test and other biologics testing. CVB Notice No. 13-10 (2013) revises validity requirements for the rabies vaccine potency test to eliminate unnecessary testing.

Workshop on Alternative Methods for Vaccine Potency and Safety Testing (2010)

NICEATM and ICCVAM organized a workshop that brought together scientific experts from relevant stakeholder organizations to review the current status and use of alternative test methods for human and veterinary vaccines. Several subsequent NICEATM and ICCVAM activities related to vaccine testing (described above) resulted from recommendations from this workshop. Proceedings of the 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 (2006)

Botulinum neurotoxin (BoNT) is used in a number of therapeutic and cosmetic applications. An animal method used to assess potency of BoNT preparations caused concern because of the pain and distress experienced by the animals and the method’s level of reliability. In collaboration with international partners, NICEATM and ICCVAM sponsored a workshop to review the state of the science and current knowledge of alternative test methods proposed to replace, reduce, and refine the use of mice for BoNT testing. The workshop also identified priorities for research, development, and validation efforts needed to advance the use of alternative methods. A report of the workshop was published in 2008. 

A cell-based assay method discussed at the workshop was later accepted by the FDA (2011) for stability and potency testing of BoNT type A products.

NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.