Around the Globe

Emergency Regulatory Approval System in Japan
Kaneko Miyuki
Pfizer R&D Japan G.K.

s of May 2022, a new emergency approval system has been established in Japan through partial revision of the Pharmaceutical and Medical Device Act. The purpose of this revision is to “establish a mechanism for promptly approving new pharmaceutical products, medical devices, and regenerative medical products (hereinafter referred to as ‘pharmaceutical products, etc.’) in an emergency to prevent the spread of health hazards in situations such as the spread of diseases that may seriously affect the lives and health of citizens.”

Before this revision, a special approval system which relied on approval/authorization from major Western countries was used in such emergency situations (e.g., vaccines and treatments for COVID-19 and new H1N1 influenza vaccines).

The major advantage of this new system is that a product sponsor can file for this emergency approval in Japan without any pre-existing approval or emergency authorization in a Western country (e.g., emergency use authorization in US) or conditional marketing authorization in the EU, and even if all required data are not yet available. In addition, document compliance review and GCP and GMP inspections can be waived at the time of emergency approval, allowing for a quicker regulatory review response.

Although all data and inspection requirements will be imposed after the emergency approval in this revised framework, it still offers significant promise that therapeutic drugs and vaccines will be delivered to the Japanese people at the same time as in Western countries in future pandemics or other emergencies.

Efficacy and Safety Requirements

Data requirements pertaining to safety under the revised emergency approval system are the same as regular regulatory review and approval, but efficacy data is more flexible in this revised approval system.

  • Efficacy standard for therapeutic drugs: “Clinical trials at the level of late phase 2 trials fall under this category, and Japanese data may not be required depending on the target drug.”
  • Efficacy standard for vaccines: “If significant results have been obtained in a confirmatory large-scale clinical trial conducted outside Japan, clinical trial results on Japanese subjects in Japan may not be necessary.”

Regarding the confirmatory clinical trial data that must be submitted after the emergency approval: “If it is reasonably considered difficult to complete confirmatory clinical trials after the emergency approval, methods to confirm efficacy using real-world data such as post marketing surveys and/ or patient registries etc. may be considered.” Accepting these alternate data sources, even under the limited circumstances of emergency approval, represents a step forward from only accepting data generated through traditional clinical trial methods.

In June 2022, the Committee on Drugs II met to discuss the first drug expected for approval under this revised emergency system, and a joint meeting of the Committee on Drugs II and the Pharmaceutical Affairs Committee held in July 2022 did not reach a conclusion on this drug. After jointly determining that the submitted clinical trial data does not presently meet the “estimation of efficacy” criteria requirement for the emergency approval, the Committee on Drugs II will continue these discussions after obtaining and reviewing results of the phase 3 part of the ongoing phase 2/3 multiregional clinical trial (T1221 study).

Emergency Approval Time Limit

This emergency approval cannot exceed two years but can subsequently be extended for a period not to exceed one additional year. Sponsors applying for extended approval within the time limit must present all necessary data required for regular approval.

Closing Reflections

Assessing whether the pre-specified objectives have been achieved is important in evaluating the results of a clinical trial. In this revised system, estimation of efficacy may be a critical issue unless the basis for determining the estimation is clearly agreed upon with the regulatory authorities at the trial planning stage, and it will be interesting to continue to watch discussions around the first few products approved for emergency use through this new system. Above all, we all hope for the return of normalcy in which emergency approvals or authorizations are not required. It is most important that we remember our COVID-19 experience and that industry, government, and academia work together to ensure that we are all better prepared for the next pandemic.