ASOURCE Navi

Domestic development of the new coronavirus vaccine, which is expected to be put into practical use, faces new problems. This is because vaccinations from overseas have become widespread, making it difficult to conduct clinical trials, and the problem of the drug approval system in an emergency is a barrier. There is an urgent need to review clinical trial methods and approval processes.

Domestic development and production of vaccines, which are considered to be the key to the end of the epidemic of new coronavirus infection, are significantly delayed compared to overseas. Currently, there are four pharmaceutical companies in Japan that are conducting clinical trials for the new coronavirus vaccine. AnGes is in Phase II / III trials in developing a DNA vaccine. Shionogi is developing a recombinant protein vaccine, Daiichi Sankyo is developing an mRNA vaccine, and KM Biologics is developing an inactivated vaccine, each of which is undergoing Phase I / II trials.

From the materials of the 5th Drug Development Council of the Ministry of Health, Labor and Welfare (May 25, 2021)

Vaccines are targeted at healthy people, unlike therapeutics, so for latecomer vaccine developers, they are in the final stage of a large phase III trial for regulatory approval while the original vaccine is already in use. It has been pointed out that it is difficult to secure tens of thousands of subjects for a double-blind study, and that the high cost of clinical trials also hinders development. In addition, the new coronavirus infection has a risk of death, and there are already highly effective vaccines, which poses ethical problems with the administration of placebo. For these reasons, it is also being considered to confirm the effect of the vaccine by a method other than the onset prevention test, such as comparing it with the neutralization activity data of the vaccine whose effect has already been confirmed.

Regarding the new coronavirus vaccine, it has been pointed out that not only the clinical trial method but also the approval process needs to be reviewed. In overseas countries, we have a system in place to promptly recommend the approval of new drugs, unlike the usual times, in the event of an emergency such as the outbreak of the new coronavirus. In the United States, the Emergency Use Authorization (EUA) system allows the US Food and Drug Administration (FDA) to expedite vaccine production and approval in an emergency. In other words, only in an emergency, even if it is not approved, it will be temporarily approved with the condition that the epidemic of the new coronavirus infection is settled. Phase III trials are required, but you can also apply for interim data from a shorter follow-up period than usual. The FDA has issued an EUA less than a month after applying for the new coronavirus vaccine.

From the materials of the 4th Drug Development Council of the Ministry of Health, Labor and Welfare (April 16, 2021)

In Japan, there is currently no provision to allow temporary use of unapproved vaccines or therapeutic agents, even in emergencies. Normally, it takes about one year from application for approval to approval, but vaccines made by Pfizer, Moderna, AstraZeneca, etc. are subject to the "special approval" stipulated in Article 14 of the Pharmaceutical Machinery Law. There is no appropriate method other than using the vaccine in an emergency, and it is a rule that simplifies the procedure if conditions such as having a track record overseas are met. Since the use of these vaccines has begun overseas, priority was given to review and approval for use. However, even with this special approval, domestic clinical trial procedures cannot be omitted.

For this reason, as an emergency measure, proposals have been made to expand the application of "conditional early approval" to vaccines, which is institutionalized in consideration of drugs for rare diseases that are difficult to conduct clinical trials due to the small number of patients. In other words, after confirming a certain level of safety and efficacy, it is approved before Phase III and confirmed by follow-up after marketing.

The government has positioned the new coronavirus vaccine as "the cornerstone of security that protects the lives of the people," and intends to support the development and production of domestic vaccines as a national strategy. To this end, we are currently studying the ideal form of large-scale clinical trials and simplification of regulatory approval procedures.