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Ph. Eur. to replace Histamine Sensitisation Test (HIST) for residual pertussis toxin testing

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European Pharmacopoeia
Ph. Eur. Commission
News
14 January 2019
Strasbourg, France

The European Pharmacopoeia (Ph. Eur.) Commission has decided to replace the Histamine Sensitisation Test “HIST” (test in mice) with a standardised CHO cell clustering assay (in vitro cell-based test) for residual pertussis toxin testing in acellular pertussis vaccines, as of next year. The introduction of a standardised CHO cell-clustering assay for residual pertussis toxin testing is based on the results of two collaborative studies1 run under the auspices of the EDQM’s Biological Standardisation Programme.

The replacement impacts general chapter 2.6.33 Residual pertussis toxin and ten individual monographs on vaccines containing acellular pertussis components. The decision to replace the HIST was approved during the 162nd session of the European Pharmacopoeia (Ph. Eur.) Commission, held in Strasbourg on 20-21 November 2018, and the revised texts will become effective on 1 January 2020.

As part of the same revision exercise, the test for irreversibility of pertussis toxoid has been deleted from monographs on acellular pertussis vaccines. This decision is based on the history of safe use as well as on data confirming that the pertussis toxoid is stable for marketed acellular pertussis vaccines. However, the revised monographs emphasise the need to validate the detoxification process to demonstrate that the toxoid is immunogenic and stably detoxified.

In addition, the requirement to test the final lot for residual pertussis toxin has been removed. Using a CHO cell assay, testing of the pre-adsorbed bulk (a stage where the antigens are highly concentrated and therefore detection of pertussis toxin is easier) is considered to be the most effective and robust approach.

The decision to replace the HIST is in line with the Ph. Eur. Commission’s commitment to phasing out the use of animal tests by continuously reviewing the in vivo tests described in Ph. Eur. texts and applying whenever possible the “3Rs” (Replacement, Reduction, Refinement) set out in the European Convention for the Protection of Vertebrate Animals used for experimental and other scientific purposes.

1 Isbrucker R, Daas A, Wagner L et al. Transferability study of CHO cell clustering assays for monitoring of pertussis toxin activity in acellular pertussis vaccines, Pharmeur Bio Sci Notes 2016:97-114.

Markey K et al. Calibration of pertussis toxin BRP batch 1 in a standardised CHO cell-based clustering assay. Pharmeur Bio Sci Notes 2018 (1):112-123

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