Consistency testing of diphtheria and tetanus to replace potency testing for lot release.

ABSTRACT

Diphtheria and tetanus vaccines are among the most effective and safe vaccines in the EPI programme. Their mechanism of toxicity and clinical protection is well documented and toxin neutralising antibodies induced by the vaccines are generally accepted as correlates of protection. Despite these positive aspects there are still no generally accepted methods to estimate their potency for routine lot release. Some of these tests use large numbers of animals and rely on lethal challenge tests. Consequently there are ethical and financial barriers to perform these tests. Test results expressed in IU, depend on the animal species or strain used and there is limited information about their predictive value for clinical protection. WHO, supported by the ECBS, has made a proposal to harmonise the current methods into simplified consistency tests, after clinical safety and efficacy, as well as consistency in manufacturing has been established to the satisfaction of the National Regulatory Authority. In principle these tests aim for a proof of consistency in biochemical and immunological characteristics in comparison with the lots shown to be clinically safe and effective. Given that many manufacturers have recently made, or are planning to make clinical trials with new combination vaccines in the near future, recent clinical data are already available, or will be soon, on the clinical safety and efficacy of the D and T components present in these combination vaccines. This will create a unique opportunity to compare the biochemical and immunological characteristics of routinely produced vaccine lots with the clinical lots and to use the consistency approach as suggested by WHO for lot release purpose. Background information and an update will be given about the proposed consistency approach of WHO for routine lot release of the D and T components in vaccines.