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Japan’s slow coronavirus vaccine rollout has again shed light on the cautious process in place for vaccine approval in the country, reigniting the question of how to balance drug safety with the need to combat a public health crisis in a speedy manner.

This challenge seemed to be on the mind of Prime Minister Yoshihide Suga when he acknowledged criticism of the nation’s inoculation program during a news conference last month.

“Most countries overseas don’t need to conduct domestic clinical trials for vaccines, but Japan does,” Suga told reporters. “I strongly feel that we need to revise laws to better respond to this kind of emergency situation.”

In emulation of the framework in the United States, the government is now reportedly eyeing the creation of a system that would enable domestically unapproved drugs to be temporarily used in times of emergency before the completion of clinical trials at home — provided that they have a proven track record overseas.

Approval process

In Japan, drugs tested in clinical trials for their efficacy and safety typically enter the approval process by first being scrutinized by the Pharmaceuticals and Medical Devices Agency (PMDA) and then a panel of experts set up under the health ministry.

In some cases, the approval process can be fast-tracked, as was the case with the COVID-19 vaccine developed by U.S. drugmaker Pfizer Inc. and its German partner BioNTech SE.

At the moment, only the Pfizer vaccine has been formally approved in Japan. The pharmaceutical giant originally filed for fast-track approval in December and the shot was given the green light in February.

Two other companies, Britain’s AstraZeneca PLC and U.S.-based Moderna Inc., had their applications filed with the health ministry in early February and early March, respectively, and are still awaiting approval, reportedly slated for as early as May 20.

The fast-track system used for the Pfizer shot led to the whole approval process being shortened to just two months, compared with the year or two that it usually takes for vaccines to get the green light.

To achieve greater efficiency and flexibility, some have argued that Japan should institute its own version of the emergency use authorization framework that countries such as the U.S. have taken advantage of to swiftly give the public access to COVID-19 vaccines. | RYUSEI TAKAHASHI
To achieve greater efficiency and flexibility, some have argued that Japan should institute its own version of the emergency use authorization framework that countries such as the U.S. have taken advantage of to swiftly give the public access to COVID-19 vaccines. | RYUSEI TAKAHASHI

Certain conditions need to be met in order for this special process to be initiated, such as that no alternative drugs are available. The medicine’s use also needs to be deemed essential to containing a serious public health crisis.

Additionally, the shortcut can only be applied to a drug that has already been authorized for use by countries considered equivalent to Japan in terms of their abilities to “secure the quality, efficacy and safety” of drugs — namely the U.S., the U.K., Canada, Germany and France.

These conditions point to the limitations of the fast-track framework. The fact that it is contingent on drugs having been approved abroad means it cannot be applied to domestically produced vaccines.

And as Suga said, even this simplified process for approval cannot go on without clinical trials being conducted at home first, a rigid requirement that some say has contributed to the sluggishness of Japan’s vaccine rollout.

The PMDA, a government body in charge of the screening process, issued a guideline in September last year clarifying its position that domestic clinical trials are needed to assess the safety of foreign-produced COVID-19 vaccines and in particular the effect they could have on Japanese people.

Emergency use authorization

To achieve greater efficiency and flexibility, some have argued that Japan should institute its own version of the emergency use authorization (EUA) framework that countries such as the U.S. have taken advantage of to swiftly give the public access to COVID-19 vaccines.

Described by the Food and Drug Administration (FDA) as a mechanism to effectively deal with public health emergencies, an EUA allows for the temporary use of unapproved medical products, based on the premise that the benefits of doing so will significantly outweigh the risks. Under the latest EUA, it took the U.S. only about three weeks — compared with the usual 12 months or so — to pave the way for the emergency use of shots by Pfizer, Moderna and Johnson & Johnson.

Despite having undergone clinical trials, vaccines made available under an EUA have not been scrutinized by the “the same type of review as an FDA-approved or cleared product,” the FDA says.

The legal basis for their use expires once a designated emergency period ends. Under an EUA, vaccine manufacturers are also granted immunity from liability.

“The EUA system comes in handy in those situations where drugs or vaccines need to be delivered to the public quickly despite there being not enough time to collect a complete set of data,” said Yasuhiro Suzuki, vice president of the International University of Health and Welfare.

The Pharmaceuticals and Medical Devices Agency, a government body in charge of the vaccine screening process, says domestic clinical trials are needed to assess the safety of foreign-produced COVID-19 vaccines and in particular the effect they could have on Japanese people. | KYODO
The Pharmaceuticals and Medical Devices Agency, a government body in charge of the vaccine screening process, says domestic clinical trials are needed to assess the safety of foreign-produced COVID-19 vaccines and in particular the effect they could have on Japanese people. | KYODO

Japan’s hesitancy

Deep-seated vaccine hesitancy and an emphasis on safety — built on a bitter history of lawsuits prompted by side-effects — have made both the government and pharmaceutical companies reluctant to speed up the approval process.

Separately, in the guideline issued last year, the PMDA also said it is “possible that ethnic differences will affect the efficacy and safety of vaccines for SARS-CoV-2,” the full name for the disease caused by the coronavirus.

Suzuki, who until August last year served as the chief medical and global health officer at the health ministry, agrees, saying results of clinical trials conducted in Europe where only white study participants were involved, for example, shouldn’t automatically be applied to Japanese people.

“Think how Japanese people often get red faces when drunk,” Suzuki said, referring to a condition dubbed the “Asian flush,” which stems from reactions to a toxic product of alcohol metabolism.

Likewise, ethnic differences in drug-metabolizing capacity may cause a situation where “even the consumption of the same dosage leads to lopsided side-effect rates between Japanese and European people,” Suzuki said.

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