Irreversibility of toxoids. An improved method of testing

Reversion of toxoid to toxin has been described by several authors yet present day regulations of all National Control Authorities have no specific requirements to check for this possibility. Most producers however have included some form of test in their own protocols for release. We have developed a satisfactory test for both diphtheria and tetanus toxoids which involves storing diluted toxoid at 20 degrees C and 34 degrees C for 6 weeks and performing a full toxicity test on the samples. In the case of diphtheria toxoid we have evidence that it may be dangerous to rely on the simpler guinea-pig skin test, since we have shown that several lots, while giving a negative skin reaction, exhibit diphtheria toxicity when given systemically. It is felt that an in vivo conversion to toxin may occur in some lots which would not be detected by the skin test.