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Biologicals. 2014 Mar;42(2):114-22. doi: 10.1016/j.biologicals.2013.11.011. Epub 2014 Jan 4.

Report on the international workshop on alternatives to the murine histamine sensitization test (HIST) for acellular pertussis vaccines: state of the science and the path forward.

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Health Canada, Biologics and Genetic Therapies Directorate, 100 Eglantine Drive, Ottawa, Ontario K1A 0K9, Canada. Electronic address:
United States Food and Drug Administration Center for Biologics Evaluation and Research, 1401 Rockville Pike, Rockville, MD 20852, USA.
Sanofi Pasteur, Lyon, France.
Division of Bacteriology, National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Hertfordshire EN6 3QG, UK.
Paul-Ehrlich-Institut, Paul-Ehrlich-Strasse 51-59, 63225 Langen, Germany.
Sanofi Pasteur, Toronto, Ontario, Canada.
European Directorate for the Quality of Medicines and Healthcare, Strasbourg, France.
Netherlands Vaccine Institute, Antonie van Leeuwenhoeklaan 9-11, 3721MA Bilthoven, The Netherlands.
GlaxoSmithKline, Rue de l'Institut 89, 1330 Rixensart, Belgium.
European Commission Joint Research Centre, Institute for Health and Consumer Protection, The European Union Reference Laboratory for Alternatives to Animal Testing, Via E. Fermi 2749, TP 580, 21027 Ispra, Varese, Italy.
National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, P.O. Box 12233, MD: K2-16, Research Triangle Park, NC 27709, USA.
Integrated Laboratory Systems Inc., 630 Davis Drive, Suite 160, Morrisville, NC 27560, USA.


Regulatory authorities require safety and potency testing prior to the release of each production lot of acellular pertussis (aP)-containing vaccines. Currently, the murine histamine sensitization test (HIST) is used to evaluate the presence of residual pertussis toxin in aP containing vaccines. However, the testing requires the use of a significant number of mice and results in unrelieved pain and distress. NICEATM, ICCVAM, their partners in the International Cooperation on Alternative Test Methods, and the International Working Group for Alternatives to HIST organized a workshop to discuss recent developments in alternative assays to the HIST, review data from an international collaborative study on non-animal alternative tests that might replace the HIST, and address the path toward global acceptance of this type of method. Currently, there are three potential alternative methods to HIST. Participants agreed that no single in vitro method was sufficiently developed for harmonized validation studies at this time. It is unlikely that any single in vitro method would be applicable to all aP vaccines without modification, due to differences between vaccines. Workshop participants recommended further optimization of cell-based assays under development. Participants agreed that the next international collaborative studies should commence in 2013 based on discussions during this workshop.


Acellular pertussis vaccines; Alternative methods; Biochemical assays; Cell-based assays; Pertussis toxin; Safety

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