null European Pharmacopoeia on tetanus vaccines – Rationalising toxicity testing requirements

EDQM Strasbourg, France 24/03/2020

At its 165th session (November 2019), the European Pharmacopoeia (Ph. Eur.) Commission adopted 16 revised monographs on tetanus vaccines, following a re-assessment of toxicity testing requirements. The revisions include the suppression of three tests and the harmonisation, as far as possible, of the Ph. Eur.’s toxicity testing requirements for tetanus vaccines for human and veterinary use.

The Test for specific toxicity of tetanus vaccines for human use and the Test for residual toxicity of tetanus vaccines for veterinary use (using guinea pigs), both carried out on the final lot, have been deleted. The tests were considered redundant because a more sensitive test (Test for absence of toxin) is performed routinely at an earlier stage of the process. The revised monographs emphasise the need to validate the detoxification process to demonstrate that the toxoid is stably detoxified.

The Test for irreversibility of tetanus toxoid (using guinea pigs) has also been removed. This decision is based on data on the stability of tetanus toxoid and the fact that tetanus toxin was shown to lose neurotoxic activity under the conditions of the storage test at 37°C. The more sensitive Test for absence of toxin is carried out on non-incubated purified toxoid.

The Ph. Eur. Commission is committed to phasing out the use of animal tests by continuously reviewing in vivo tests described in Ph. Eur. texts and applying, whenever possible, the 3Rs principles set out in the European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes (ETS No. 123). The re-assessment of toxicity testing requirements for tetanus vaccines and the decision to delete three animal tests is an illustration of this commitment.

The revised monographs will be published in Ph. Eur. Supplement 10.3 and become effective on 1 January 2021.

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