Host: The Japanese Society of Toxicology
Vaccines for the prevention of infectious diseases are characterized by the fact that they exert their efficacy through the induction of an immune response, and therefore, non-clinical study guidelines for ordinary drugs are not always applicable. In Japan, the concept was presented in 2010 by the "Guidelines for Non-clinical Studies of Vaccines for the Prevention of Infectious Diseases" (May 27, 2010), but the development environment for vaccines has changed in recent years, and the need for revision of guidelines was recognized.
In a questionnaire survey of companies on difficulties in vaccine development, it was pointed out that the necessity of a systemic exposure toxicity study when adding a new route of administration and criteria for determining whether a safety pharmacology study is necessary in terms of non-clinical studies. To address these issues, we surveyed the status of developed products by review reports and compared domestic and overseas guidelines.
With regard to the additional routes of administration, for the seven products that could be administered both intramuscularly and subcutaneously, repeated-dose toxicity studies were conducted for only one route of administration, while local irritation studies were conducted for both routes. The WHO guidelines also provided specific points to keep in mind when developing alternative routes, such as the effects of intranasal administration on the brain and nervous system.
With regard to safety pharmacology studies, the domestic guidelines required that safety pharmacology endpoints could be assessed in advance by other toxicity studies, whereas the WHO guidelines stated that such studies should be conducted when there was concern about effects on physiological functions in other studies. Reflecting this difference, the rate of safety pharmacology studies was higher for vaccines developed only in Japan than for vaccines also developed overseas.
Based on these results, we proposed that a systemic exposure toxicity study is not necessarily required for all routes of administration, and that safety pharmacology studies can be evaluated in other non-clinical safety studies. With regard to vaccines, it is important that new vaccines are introduced in Japan without delay. In order to prevent non-clinical trials from being redone due to differences in guidelines, we proposed revisions based on international consistency of requirements.
