The Japanese stem cell and regenerative medicine oversight system is different than here in the U.S. and in Europe.
Japan has had a more permissive approach to overseeing regenerative medicine.
While most of the attention has focused on fairly legitimate regenerative biotechs and other sponsors in Japan, there are unproven stem cell clinics there. These clinics can take advantage of the system.
Even so, it’s rare to see news of a Japanese stem cell clinic getting hit by regulators. That’s why a new case is interesting.
Japanese stem cell clinic gets in hot water
Here’s the news: Fukuoka clinic issued business improvement order over stem cell treatments, The Japan Times.
This may not sound like much from the headline, but it is a striking case. From the article:
“The health ministry on Wednesday issued a business improvement order to a clinic in Fukuoka, saying a range of stem cell treatments it offers violate the law on the safety of regenerative medicine…Seijikai Fukuoka MSC Clinic, run by Dr. Kenji Fukamatsu, offers various stem cell treatments whose plans have not been submitted to the authorities, according to the ministry. The treatments include bone regeneration, skin care and therapies to combat cancer and preventing arteries from becoming hardened.”
What does it mean when a business like a medical clinic in Japan is issued a business improvement order? It means that authorities have found substantial problems that need fixing.
The marketing claims mentioned above like supposed bone regeneration and cancer therapies raise big red flags.
Seijikai Fukuoka MSC clinic claims
Here’s Google Translate’s translation of this clinic’s statements and claims on its website:
“Fukuoka MSC Medical Clinic is a clinic specialized in regenerative medicine. Regenerative medicine is a medical technology aimed at regenerating and repairing patients’ cells and tissues to restore function. It can treat damaged cells and tissues caused by diseases or injuries, and is expected to provide effective treatment methods for difficult diseases and chronic conditions that traditional treatments cannot address. These technologies contribute to the development of new treatments for various diseases such as diabetes, Parkinson’s disease, spinal cord injuries, and myocardial infarction. Fukuoka MSC Medical Clinic conducts daily research to help everyone achieve a better life through regenerative medicine in both medical and aesthetic aspects.”
More red flags.
There are no stem cell therapies for these conditions. Is the clinic being vague enough to mention it here without implying they actually treat it?
They also separately mention aging therapy and stem cell cosmetics.
American vs. Japanese stem cell systems
This Japanese MSC clinic made claims similar to many MSC clinics here in the U.S.
As is the case with a vast number of U.S. clinics not working with the FDA, Seijikai Fukuoka MSC Clinic reportedly did not work with authorities.
There’s a literature on the regenerative medicine oversight system in Japan. Recent papers suggest the framework is not working to ensure safety and efficacy. For example, check out this Cell Stem Cell paper: Too little, too soon: Japan’s experiment in regenerative medicine deregulation.
There’s also this Regenerative Medicine article: Japan and Australia’s online market for unproven stem cell treatments.
Other systems and looking ahead
This new paper Dark Clouds Looming Over Regenerative Medicine in Japan highlights problems with the standard pathway there and how regenerative products have failed in clinical trials.
Last summer I wrote about how regenerative medicine in Japan is often hyped in the media. Hype on stem cells and related products is not unique to Japan. However, overall due to multiple issues including their soft oversight system, Japan does face unique challenges.
This recent piece in Cell Stem Cell Effective regulatory responses to predatory stem cell markets in Australia and Canada highlights how well oversight systems can work.
Regulators in both the U.S. and Japan need to be more active, more proactive, and use creative approaches to deal with the unproven clinic problem. The U.S. is likely to face more clinic problems with HHS Secretary Kennedy seeming to be a friend of the clinics.
Overall, Japan is a leader in stem cell and regenerative medicine research, but I believe it must change its oversight system to be more rigorous.
The stem cell clinic situation seems worse here in the U.S., but I’m not optimistic about federal regulators helping things over the next four years. They may make things much worse. On the other hand, state attorneys general are having a positive impact.
Paul,
In line with my previous comment, the Japanese Society for Regenerative Medicine has announced on March 20th that “among regenerative medicines that have not been approved by the government, the Society has decided to distinguish between “verification-type medical care” and those that have a mechanism to collect clinical data from patients and verify the safety and efficacy of the treatment, and “unverification-type medical care” and all others. It has also announced its intention to curb unverification-type medical care. It is envisioned that the Society will examine each treatment plan to determine whether it is verification-type or unverification-type, and then make it public in some form so that patients can refer to it. The specific methods will be worked out in the future.”. This announce is refered as the “Yokohama declaration” (https://www.nikkei.com/article/DGXZQOSG17A0Y0X10C25A3000000/).
Well said, Paul. Even if the investigators mean well, there are too many that fall in love with their ideas and are blind to their failures. But there are still more who are either willfully ignorant or deliberately taking advantage of desperate people just to make money. Immorality knows no borders- there are charlatans in every country. Let’s keep trying to do something about it!
In Japan, regenerative medicine is seen as a national treasure and a strategic axis of economic development, and there is no question of jeopardizing it: unlike in the United States, there is a consensus to better control the safety of treatments.
The Japanese regulatory framework (PMD Act) is designed to promote the development of cell therapies, with conditional (= time-limited, 7 years) approval granted on the basis of confirmed safety and likely efficacy (the period of approval is supposed to allow to collect evidence for efficacy).
The system works quite well for class I products (grossly, PSC-derived , allogeneic, or with genetic modification). In contrast there are a number of issues with class II and III, especially MSCs (see https://doi.org/10.1016/j.stemcr.2024.10.006). This problem is the topic of a recent recommendation involving leading figures of regenerative medicine in Japan and the Japanese Society for Regenerative Medicine (https://doi.org/10.1016/j.reth.2025.01.024). In addition, MHLW (Ministry of Health) has recently revised the PMD Act and is implementating increased control measures. In brief, even if the pace may seem slow, the direction seems to be the good one in terms of control/safety. My guess is that we will see more cases such as Seijikai, the development of medical hubs (near Haneda airport for example) is at the price of more stringent controls and confirming the interest of treatment in a number of indications (such as e.g MSC for osteo-arthrithis..).
The Japanese Advanced Cell and Gene Therapy Regulations are by far the best in the world to advance stem cells and cellular therapy to patients.
In the Japanese regulatory framework the company sponsors (pays and conducts) a Phase I Safety clinical trial ($5 Million). If the product is shown to be safe then under the Pharmaceutical and Medical Devices Act (PMD Act) the company can be granted Conditional Approval.
Once the product is granted Conditional Approval, the company continues to conduct Phase II and Phase III efficacy clinical trials but the company can either charge patients to participate or in many studies in Japan national health insurance pays for the cost to finish the clinical trials. Under the Japanese system the company is allowed to charge more than just the cost of manufacturing the cellular product where as in the US under an RMAT, only the cost of manufacturing is eligible for financial reimbursement which doesn’t account for significant overhead to operate the company and manufacturing.
If this system were to be brought to the US and US companies could charge patients a rate that is set by the market to be a participant in the clinical trials, this would bring about a revolution in the cellular field.
An example of this could be a company wants to get an FDA approved stem cell injection for a knee treatment.
The company would raise 5 Million to conduct a Phase I safety trial at MGH or Cedar Sinai or any hospital. This would be easy to raise if the investors knew that the rest of the clinical development would be paid for by volunteer patients. This would create competition and market pressure to keep costs down or what the market bears. This would enable 100s of companies to be doing similar trials.
If the company is able to charge whatever the market bears to fulfill the patients needed for the phase II trial. (100-150 patients). Say it costs 10-15K per patient (What people pay now for unregulated clinics) that would easily be filled with willing patients to get his treatment at a renown US hospital . The study would still be conducted as a clinical trial with rigorous oversight and safety.
The phase III would also be covered by volunteer paying patients. (1000-1500 patients).
After completing the Phase III trial the company and if successful the product would be FDA approved. Once FDA approved it would now be covered by insurance and available to the masses.
Here is more details on how this would work in the US.
https://www.perinatalstemcells.com/our-plan.html
Happy to discuss this idea with anyone in a professional manner. Convince me how this wouldn’t be a huge improvement and bring stem cells and cellular therapy to the masses at affordable rates.
@Kyle,
I see many problems with your proposed plan for the U.S.
Most trials go on to fail even after Phase 1 so in your hypothetical system trial participants would be paying for Phase 2, etc. trial enrollment with (1) little possibility of benefit and (2) still taking on substantial potential risks. Safety is not completely established after Phase 1. No matter what you say to them via consent, you’re still giving them a lot of false hope too.
I believe it is unethical to require people to pay for participation in clinical trials.
Getting back to the Japanese system, to my knowledge it has not been a big success so far. Research has documented problems with that system (e.g., https://www.sciencedirect.com/science/article/pii/S1934590923002163?via%3Dihub) and numerous patient deaths have occurred in Japan in the regenerative space. I don’t see a bunch of innovative new proven therapies emerging there either via that system.
Another issue here is that your system seems to assume that most sponsors of pay-for-play trials would be good citizens, but we’ve seen over the last dozen or so years in the U.S. that in the general regenerative arena including the perinatal space, that’s definitely not true. It might be more the other way around.
For instance, I can think of ongoing “trials” (non-traditional, pay-for-play clinical trials) here in the U.S. that seem to be focused on generating revenue just from “trial” enrollment with little chance of benefit and some participants have said they were harmed. I’m not sure why the FDA has allowed those to continue. The sponsors do not seem to definitely intend to go for final drug-level approval either.
So in your system I can see many sponsors collecting say $20K a pop from 100s of people, with no clear intention of staying in it for the long haul to try to get more data or to go beyond conditional approval. In Japan regulators have not been diligent enough about revoking conditional approval either when problems emerge or data seem discouraging.
That might happen here in the U.S. too. In your system I can imagine many conditionally approved cell “therapies” just sitting out there for years collecting funds (maybe $100s of millions) from vulnerable people without ever amounting to much or getting final approval.
I think it’s highly unlikely that U.S. insurance companies will want anything to do with this system too.