Scientific Publications by FDA Staff

Biologicals 2014 Mar;42(2):114-22

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.

Isbrucker R, Arciniega J, McFarland R, Chapsal JM, Xing D, Bache C, Nelson S, Costanzo A, Hoonakker M, Castiaux A, Halder M, Casey W, Johnson N, Jones B, Doelling V, Sprankle C, Rinckel L, Stokes W

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.