In search of acceptable alternatives to the murine histamine sensitisation test (HIST): what is possible and practical?

Pharmeur Bio Sci Notes. 2016:2016:151-170.

Abstract

The 'International Workshop on Alternatives to the Murine Histamine Sensitization Test for Acellular Pertussis Vaccines: In Search of Acceptable Alternatives to the Murine Histamine Sensitization Test (HIST): What is Possible and Practical?' was held on 4 and 5 March 2015 in London, United Kingdom. Participants discussed the results of the data generated from an international collaborative study (BSP114 Phase 2) sponsored by the European Directorate for the Quality of Medicines & Health Care (EDQM) to determine if a modified Chinese hamster ovary (CHO) cell-based clustering assay is a suitable alternative to replace HIST. Workshop participants agreed that protocol transferability demonstrated in the collaborative study indicates that a standardised CHO cell assay is adequate for measuring pure PTx in reference preparations. However, vaccine manufacturers would still need to demonstrate that the method is valid to detect or measure residual PTx in their specific adjuvanted products. The 2 modified CHO cell protocols included in the study (the Direct and the Indirect Methods) deserve further consideration as alternatives to HIST. Using the CHO cell assay, an in vitro alternative, for acellular pertussis (aP) vaccine batch release testing would reduce the number of animals used for aP vaccine safety testing. A strategic, stepwise adoption plan was proposed, in which the alternative test would be used for release purposes first, and then, once sufficient confidence in its suitable performance has been gained, its use would be extended to stability testing.

Keywords: histamine sensitisation test; pertussis vaccines; replacement alternative.

MeSH terms

  • Animal Testing Alternatives / methods
  • Animal Testing Alternatives / standards*
  • Animals
  • CHO Cells
  • Chemistry, Pharmaceutical / methods
  • Chemistry, Pharmaceutical / standards*
  • Cricetinae
  • Cricetulus
  • Education
  • Histamine / analysis*
  • London
  • Mice
  • Pertussis Toxin / analysis*
  • Pertussis Toxin / therapeutic use
  • Pertussis Vaccine / standards
  • Pertussis Vaccine / therapeutic use
  • Whooping Cough / prevention & control

Substances

  • Pertussis Vaccine
  • Histamine
  • Pertussis Toxin