“Japan has the second biggest market for branded drugs and is the third largest market for pharmaceuticals overall,” says Kento Nakamura, strategy and corporate development at the CMIC Group, thereby presenting a fertile ground for clinical trial operations.
Nakamura, who works for the contract research organisation (CRO) and site management organisation (SMO) CMIC, introduced the country as an attractive opportunity for clinical trials during a presentation at the 12th Annual Outsourcing in Clinical Trials (OCT) UK and Ireland, which took place from 10 to 11 June in London.
With approximately double the population of the UK (123.2 million), the same percentage of GDP spent on healthcare expenditure (nearly 11%), Japan has almost eight times more hospitals than the UK, and thus a high number of potential trial sites, said Nakamura.
According to the speaker, there are also advantages to Japan has a fast pricing and reimbursement process, with price negotiations running in parallel with new drug application (NDA) reviews. In the EU, even after receiving European Medicines Agency (EMA) approval, companies still need to go through a separate Health Technology Assessment (HTA) process in each country to launch a drug.
In contrast, Japan conducts its pricing and reimbursement process under Ministry of Healthy, Labor, and Welfare (MHLW), in parallel with the marketing authorisation review, and once marketing approval is granted, the drug typically gets listed with a price and is covered by insurance within 60 to 90 days Additionally, Japan is considered a strategic entry point into other Asian markets.
Nakamura mentioned that drug approvals in Japan can potentially act as a gateway to other Asian markets, such as Taiwan, Malaysia, Singapore and the Philippines, which might accept Japan’s approval package, since Japanese regulators have high credibility.
Clinical trial environment and services offered in Japan
Regarding clinical trials, Japan has a well-established environment, with significant experience in conducting clinical trials and well-trained investigators, he said. In 2023, Japan had a median approval time for marketing authorisation applications of 332 days, closely aligned with the US at 333 days and faster than Europe, which was significantly longer at 453 days, said Nakamura.
He added that, in terms of quality, inspections by the US Food and Drug Administration (FDA) between 2009 and 2023 indicate high quality and strong regulatory compliance on par with or better than Western countries.
While many are familiar with CROs, SMOs are a unique aspect of Japan’s clinical trial infrastructure, with approximately 70% of trial sites in Japan comprising SMOs. Nakamura explained that SMOs are commercial entities that dispatch staff such as clinical research coordinators and site management associates—the rough equivalent of clinical trial coordinators—to clinical trial sites, hospitals, and clinics, which may lack the resources to run trials effectively.
He added that SMOs assist with document preparation and coordination for ethics committee approvals, budget negotiations, site staff training with protocol-specific training, patient recruitment, engagement and visit coordination strategies. SMOs can also reduce the administrative burden placed on physicians and investigators and accelerate trials due to staffing shortages at study sites.
A shift of research focus from primary care diseases to oncology and rare diseases in the past two decades has increased the number of clinical trials conducted at large hospitals, Nakamura claimed. This rising stress on large hospitals increased the need for SMOs at these large sites, he added. An analysis from the Japan Pharmaceutical Manufacturers Association (JPMA) has shown that the time from study initiation to first patient enrollment can be an average of 110 days with SMO involvement as opposed to 130 days without SMO involvement. Moreover, with SMO involvement, data showed that on average, 117 days passed from first patient-in to last patient-in in trials, compared to 145 days without SMO involvement.
Regulatory landscape challenges and changes
While progress has been made in recent years, there are some unique regulatory challenges in Japan. The country is shifting from fragmented ethics committees/ institutional review boards (IRBs) to a more centralised IRB, with one ethics approval to go across sites in Japan, said Nakamura.
To combat drug loss—the approval of a drug in other locations but not Japan—the PMDA introduced some regulatory changes in the past few years, one of which relaxed Phase I bridging study requirements, in late 2023. Previously, regulation in Japan strictly required a drug to be studied in the population for safety, before national patients could be introduced in the global Phase III studies.
According to Nakamura, the PMDA has relaxed this regulation slightly: “It is not that you do not have to do the Phase I bridging study, but [it depends] on a case by case basis, and if you can provide good scientific rationale that there are no ethnic differences with your drug, then sponsors are more likely to be able to Japan included in their global phase III studies without a phase I bridging study.
“There is a chance you may have to do a safety run-in with Japanese patients for your Phase III study, but this will be less taxing than a Phase I bridging study.”
In September 2024, the PMDA also started allowing common technical documents (CTD) modules one and two to be in English, for sponsors that do not have a Japanese presence. Nakamura added that last month, the conditional approval process was made more clear.
He commented that, regardless, clinical trial costs in Japan are sometimes perceived as costly or lacking transparency, but the government is making strides to make the country more price-competitive for sponsors.
