Japan takes the lead,
in early Commercialization and early Reimbursement
New regulations accelerating the approval of regenerative therapeutics in Japan took effect Nov. 25, 2014, propelling that nation onto the radar screens of life sciences companies around the world. The main benefit of these new rules is that they enable companies to receive early conditional marketing approval and generate revenue from regenerative products while trials are being conducted.
The acceleration of regenerative medicine development and commercialization is part of the economic revitalization plan – “Abenomics” – launched by Prime Minister Shinzō Abe in 2012. That plan also includes ¥110 ($1 billion) in funding for stem cell research.
Regenerative medicine is a huge issue for Japan. Half the population is over age 50, but regenerative medicines have been limited because of the difficulty getting through Japan’s Pharmaceuticals and Medical Devices Agency (PMDA). Japan’s goal with this new regulation is to increase the number of approved cell therapy products, expand targeted indications, and extend its capabilities from manufacturing to bedside. Interest not only from Japanese pharmaceutical companies, but globally is becoming very strong.
Japan’s new regenerative medicine legislation is subdivided into two separate laws.
- Law No. 84/2013 amends the Pharmaceutical Affairs Act, renamed the Pharmaceutical and Medical Device (PMD) Act, and pertains to the commercial development of regenerative therapeutics.
- Law 85/2013, the Safety of Regenerative Medicine Act, deals with clinical and physician-led research.
The PMD Act defines regenerative medicine as cultured or processed human or animal cells, or transgenic cells, used to reconstruct, repair, or form structures or functions in the human body, or to treat or prevent human diseases.
Gene therapies are also covered by that act, providing they are at least equivalent to cellular and tissue-based products and meet either the FDA definition of gene therapy or the EU definition of advanced-therapy medicinal products.
This law in not only speeding up the time of therapeutics to market by allowing an early conditional marketing authorization, but clearly indicates the understanding that regenerative medicine cannot be regulated with rules of chemicals and biochemical developed in the last century.
As an example; “A 20-person trial that shows safety and is predictive of efficacy is sufficient to get conditional approval for seven years, without needing placebo trials. Efficacy will be determined by the market. The new regulations dramatically change the pathway not only toward revenue but also towards applied science.
During the seven-year conditional approval period, companies are expected to continue filing data. By the end of that period, they must either apply for final marketing approval (the equivalent of a BLA [Biologic License Application]) or withdraw the product.
The companion law, the Safety of Regenerative Medicine Act, governs clinical and physician-sponsored research. It allows cells to be processed outside hospitals for safer and faster manufacturing. Oversight is provided through tier-based, risk-dependent analysis, and through accreditation of cell-processing centers.
It appears that the PMDA with the PMD Act is looking for more than just a Phase 1-type analysis but the application should reflect on safety and some meaningful evidence of therapeutic benefit, while post-commercialization and observational studies are reconfirming the treatment potential. This most likely will increase clinical trial activity in Japan, though the new regulations don’t specify that trials must be conducted in Japan, on the other hand, however, the PMDA is clearly guiding sponsors toward running a clinical trial in Japan.
Policymakers in Japan realized regenerative medicine has tremendous potential to address serious areas of unmet medical need that impact positively their national healthcare system. By providing a new regulatory framework they are encouraging clinical development, which simultaneously is fostering innovation, the creation of more effective healthcare solutions, and economic development.
Some western companies are already envision that they can get much faster approvals in Japan, and then license those products to other especially American and European countries, this makes it a very attractive business model, to involve stem cell activities and technology in Japan because this pathway could reduce time to market by several years with the attractive fast “pre authorisation” followed by post-commercialization and observational studies.
Improvements in regenerative / stem cell regulations to reflect the new science potential are in discussions at American and European regulatory agencies, while Asian, but also Central American countries acted and provided already today an effective regulatory support.
With the Japanese new regulatory process, granting conditional approval, Japan delivers a path to reimbursement while trials are underway, demonstrating a commitment to bringing advanced regenerative allogeneic medicine to patients with unmet medical need in their country, while other non FDA / EMA regulated countries support also the alternative pathway for new medicinal treatment via practice of medicine with autologous stem cells.