title: 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.
abstract: 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.
authors.affiliation: Health Canada, Biologics and Genetic Therapies Directorate, 100 Eglantine Drive, Ottawa, Ontario K1A 0K9, Canada. Electronic address: richard.isbrucker@hc-sc.gc.ca.
authors.forename: Richard
authors.initials: R
authors.lastname: Isbrucker
authors.affiliation: United States Food and Drug Administration Center for Biologics Evaluation and Research, 1401 Rockville Pike, Rockville, MD 20852, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Arciniega
authors.affiliation: United States Food and Drug Administration Center for Biologics Evaluation and Research, 1401 Rockville Pike, Rockville, MD 20852, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: McFarland
authors.affiliation: Sanofi Pasteur, Lyon, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Chapsal
authors.affiliation: Division of Bacteriology, National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Hertfordshire EN6 3QG, UK.
authors.forename: Dorothy
authors.initials: D
authors.lastname: Xing
authors.affiliation: Paul-Ehrlich-Institut, Paul-Ehrlich-Strasse 51-59, 63225 Langen, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Bache
authors.affiliation: Sanofi Pasteur, Toronto, Ontario, Canada.
authors.forename: Sue
authors.initials: S
authors.lastname: Nelson
authors.affiliation: European Directorate for the Quality of Medicines and Healthcare, Strasbourg, France.
authors.forename: Angele
authors.initials: A
authors.lastname: Costanzo
authors.affiliation: Netherlands Vaccine Institute, Antonie van Leeuwenhoeklaan 9-11, 3721MA Bilthoven, The Netherlands.
authors.forename: Marieke
authors.initials: M
authors.lastname: Hoonakker
authors.affiliation: GlaxoSmithKline, Rue de l'Institut 89, 1330 Rixensart, Belgium.
authors.forename: Amélie
authors.initials: A
authors.lastname: Castiaux
authors.affiliation: 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.
authors.forename: Marlies
authors.initials: M
authors.lastname: Halder
authors.affiliation: 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.
authors.forename: Warren
authors.initials: W
authors.lastname: Casey
authors.affiliation: Integrated Laboratory Systems Inc., 630 Davis Drive, Suite 160, Morrisville, NC 27560, USA.
authors.forename: Nelson
authors.initials: N
authors.lastname: Johnson
authors.affiliation: Integrated Laboratory Systems Inc., 630 Davis Drive, Suite 160, Morrisville, NC 27560, USA.
authors.forename: Brett
authors.initials: B
authors.lastname: Jones
authors.affiliation: Integrated Laboratory Systems Inc., 630 Davis Drive, Suite 160, Morrisville, NC 27560, USA.
authors.forename: Vivian
authors.initials: V
authors.lastname: Doelling
authors.affiliation: Integrated Laboratory Systems Inc., 630 Davis Drive, Suite 160, Morrisville, NC 27560, USA.
authors.forename: Cathy
authors.initials: C
authors.lastname: Sprankle
authors.affiliation: Integrated Laboratory Systems Inc., 630 Davis Drive, Suite 160, Morrisville, NC 27560, USA.
authors.forename: Lori
authors.initials: L
authors.lastname: Rinckel
authors.affiliation: 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.
authors.forename: William
authors.initials: W
authors.lastname: Stokes
mesh_terms: D000818:Animals; D006632:Histamine / Q000276:immunology*; D038622:Internationality; D051379:Mice; D010567:Pertussis Vaccine / Q000276:immunology*; D022282:Vaccines, Acellular / Q000276:immunology*
chemical_list: D010567:Pertussis Vaccine; D022282:Vaccines, Acellular; D006632:Histamine
keywords: Acellular pertussis vaccines; Alternative methods; Biochemical assays; Cell-based assays; Pertussis toxin; Safety