Japan changed important parts of its clinical development system in December 2023, when the Ministry of Health, Labour and Welfare, MHLW, introduced new principles governing the need for Japanese Phase I studies before participation in multi-regional clinical trials.
That was the beginning, not the end
Since then, Japan has introduced further changes aimed at reducing drug lag and drug loss, making participation in global development easier, improving access for overseas biotech companies and removing some of the operational friction around Japanese clinical trials.
In October 2024, MHLW clarified circumstances in which certain rare-disease drugs may be submitted for approval without clinical trial results in Japanese patients. In June 2025, the government published a broader clinical-trial reform programme. In February 2026, Japan introduced closer coordination between its international clinical-trial one-stop service and PMDA. In June 2026, guidance moved Japan further towards Single IRB review, while PMDA continued work on domestic implementation of the new ICH E6(R3) framework.
This question has passed its expiry date:
“Do we need a Japanese Phase I trial?”
You need to ask yourself:
“How early should Japan enter our global development programme, what Japanese evidence will we need, and can we design the programme so that Japan does not become a separate development track?”
December 2023: the Japanese Phase I position changed
On 25 December 2023, MHLW issued new principles concerning Japanese Phase I studies before participation in multi-regional clinical trials, MRCTs, when early clinical development had already started outside Japan. The practical change was significant. A separate Phase I study in Japanese subjects is not automatically required before Japan joins an MRCT. PMDA and the sponsor can assess the available evidence and determine if Japanese participants can safely enter the global study without such a study. Relevant considerations include PK/PD, safety, dose, ethnic sensitivity and available information from related compounds.
For medicines addressing high unmet medical need, including rare diseases, serious refractory diseases and paediatric indications, the guidance provides additional flexibility where participation in an MRCT is considered desirable for Japanese development.
This does not mean that Japanese Phase I studies have been abolished.
PMDA can still conclude that Japanese Phase I data or additional safety measures are needed for a particular product. The decision remains product-specific. MHLW also states that early Japanese participation in global development remains desirable because intrinsic and extrinsic ethnic factors are easier to understand when Japan is included early. I like to think of it as Japan has (finally) removed some unnecessary sequencing. Clinical trials in Japan is changing.
October 2024: another important barrier for clinical trials in Japan was reduced
The next important change arrived on 23 October 2024. MHLW published principles covering certain rare diseases and similar situations where pivotal or confirmatory trials had already been conducted overseas. The guidance recognises that requiring another Japanese clinical trial can delay access and, in some cases, can cause companies to abandon Japanese development altogether. Under defined circumstances, an approval application may therefore proceed without clinical trial results in Japanese patients.
The considerations include whether the pivotal overseas study has already been appropriately conducted, whether an additional Japanese trial is impracticable because of very small patient numbers or other factors, and whether the expected benefit for Japanese patients outweighs the risks based on the available efficacy and safety evidence.
Again, this is not a general exemption from Japanese evidence.
If there are clinically meaningful ethnic differences, or uncertainty around safety or appropriate dosing, additional Japanese information can still be required. MHLW also encourages collection of Japanese experience through clinical studies, compassionate use, post-marketing surveillance, registries or medical databases where appropriate.
This is commercially important, especially if you’re developing orphan products.
The old assumption that an overseas programme may have to be partly repeated in Japan is no longer a general truth.
Drug lag has become drug loss
Japan’s problem is no longer simply that medicines reach the country later. MHLW reported in May 2025 that 143 medicines approved in Europe or the United States were unapproved in Japan. For 86 of those, Japanese development had not even started and they are considered drug loss. Venture-originated medicines, orphan products and paediatric medicines are disproportionately represented on that dark list.
Drug lag means development reaches Japan with a delay.
Drug loss means Japan is absent from the company’s development strategy.
This put heavy pressure on the policy makers as they are the ones with the most responsibility for this situation even existing. If an innovative medicine is controlled by a biotech company with no Japanese subsidiary, limited management capacity and no experience with PMDA, simply accelerating an existing Japanese review process does not solve the problem. Japan first has to persuade the company to develop the drug here.
June 2025: Japan sets out a wider clinical-trial reform programme
On 30 June 2025, MHLW published its new policy direction for clinical trials and clinical research. The agenda goes well beyond Phase I requirements. It includes stronger capacity for international trials, a one-stop consultation system, better patient recruitment, greater use of registries and real-world data, wider use of decentralised clinical trials, Single IRB review, greater standardisation of trial documents, improved cost transparency and preparation for ICH E6(R3).
The policy also addresses something overseas sponsors notice quickly in Japan: operational competitiveness. Japan has world-class investigators and hospitals. Yet an excellent institution can still be commercially unattractive for a global study if contracts, IRB procedures, start-up times, documentation and site costs are difficult to predict. This new MHLW strategy has explicitly recognised these issues.
February 2026: a more direct route for overseas companies
One of the 2025 proposals became more concrete on 10 February 2026. MHLW established formal coordination between the International Joint Clinical Trial One-Stop Service and PMDA. The service is particularly relevant to overseas pharmaceuticals without an established Japanese development base. It can support discussions about conducting clinical trials in Japan and the identification of suitable Japanese medical institutions.
For qualifying products with high medical need, the mechanism can provide priority access to PMDA face-to-face consultation. There is another detail that deserves the attention of smaller companies.
For certain emerging biopharmaceutical companies without a Japanese entity, the one-stop service and PMDA can agree to permit submission of PMDA consultation materials in English. The notification gives an indicative definition of emerging biopharma as companies with global annual sales below USD 500 million and annual R&D expenditure below USD 200 million.
It sounds administrative, but it’s commercially rather interesting. Japan continues to reduce the friction faced by precisely the companies responsible for many medicines caught in the drug-loss problem.
April 2026: drug loss remains very real
Japan has not solved the problem yet. MHLW published another drug-loss assessment in April 2026. It examined medicines approved in Europe or the United States between January 2021 and March 2023 and found 28 products for which Japanese development had still not started as of 31 March 2025. Five were classified as having particularly high development need, with another product classified as having high need.
MHLW has said that drug-loss surveys will continue periodically. So the trend is positive, but overseas sponsors should not confuse policy activity with a finished reform programme. Japan is actively competing to be included earlier. Companies still have to decide that Japan deserves their investment. Or not (yet?).
June 2026: Single IRB becomes much more concrete
Japan has traditionally been criticised for fragmented IRB procedures across multi-site trials. A significant operational step came on 22 June 2026, when Japanese ministries issued guidance encouraging institutions participating in multi-centre clinical trials to use a single IRB for review instead of automatically relying on separate institutional IRBs. Institutions whose internal rules require their own IRB are encouraged to review those rules.
This matters because site start-up time is part of the international competition for trials. A Japanese site may have excellent investigators, patients and clinical capability. That advantage becomes less valuable if the administrative route is substantially slower than in competing countries. Single IRB will not remove every local process overnight. It does, however, clearly show where the Japanese system is headed.
ICH E6(R3) is also changing the operating model
Clinical-trial reform in Japan is now connected to a wider international change. ICH E6(R3) Annex 1 reached Step 4 in January 2025. Annex 2 reached Step 4 in June 2026, with the consolidated E6(R3) document adopted on 16 June 2026. The revised framework places greater emphasis on proportionality, Quality by Design, Critical to Quality factors and risk-based approaches to trial conduct.
As of August 2026, Japan is working on the associated domestic GCP changes and operational implementation. PMDA’s June 2026 materials describe reform work around Single IRB, decentralised trials, risk-based approaches, trial documentation and other procedural issues. Some elements are already moving into practice, while wider GCP reform remains a work in progress. Japan has not yet managed to complete its GCP reform. Hopefully JApan is geting there before too long. More change is coming.
Ethnic factors still matter
None of these reforms eliminates the scientific question of how foreign clinical data apply to Japanese patients. Intrinsic factors can include genetics, metabolism, body weight, organ function and pharmacokinetics. Extrinsic factors can include medical practice, concomitant medicines, diagnostic criteria and standards of care.The regulatory question has become more sophisticated.
Instead of assuming that a separate Japanese study is required because the patients are Japanese, sponsors should establish which differences could materially affect efficacy, safety, exposure or dose, and what evidence is needed to address them.
For some products, existing global evidence may be sufficient. For others, Japanese data will remain essential. Early PMDA discussion therefore becomes more valuable, not less.
Site feasibility remains brutally practical
Regulatory flexibility does not recruit a single patient. You still need the right investigators, hospitals and patient population. Before adding Japan to a global programme, your team needs credible answers on patient numbers, referral pathways, competing studies, investigator interest, standard of care, protocol fit, start-up timing and recruitment capacity.
A famous Japanese hospital is not automatically a good clinical-trial site for your study. A good Japanese KOL is not automatically a high recruiter. And a regulatory route that works beautifully on PowerPoint does not rescue weak site feasibility.
What should an overseas sponsor do in 2026?
This is clear: Japan should now be assessed before the global programme becomes difficult to modify.
I would ask five questions:
- Does Japan matter commercially and medically?
Consider patient numbers, unmet need, competitive environment, pricing potential and strategic importance. - Can Japan join the existing global programme?
Examine the available PK, safety, dose and ethnic-sensitivity evidence before automatically designing a Japanese Phase I study. - Can the programme recruit in Japan?
Test real site and patient feasibility, not theoretical epidemiology. - Which Japanese regulatory and operating route fits the product?
The answer may be different for a common-disease product, an orphan drug, a paediatric medicine or a product whose confirmatory development has already finished overseas. - Who will own Japan inside your organisation?
PMDA strategy, CRO management, site development, commercial planning and eventual market access need internal ownership. A distributor or CRO cannot replace the sponsor’s strategic responsibility.
Where Biosector can help
Biosector helps overseas companies targeting Japan’s pharma and biopharma industries. We understand the commercial implications of developing in Japan. We can help assess the Japanese opportunity, map relevant pharmaceutical companies, CROs, investigators and other potential partners, identify suitable organisations, open senior-level discussions and support commercial planning around the development programme. And we can also make sure that you get commercial traction here. We will hunt for you.
We do not perform regulatory submissions, clinical-trial management or CRO services. Where these capabilities are required, we can help identify suitable specialist partners.
If Japan is beginning to appear on your global development roadmap, book a meeting with Biosector.
Or drop us an email info@biosector.jp
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