hat can we do to promote Rational Medicine? In Japan, our universal National Health Insurance (NHI) system has supported Japanese citizens’ healthcare for close to sixty years. The NHI system gives every Japanese citizen the opportunity to pursue the most high-quality and advanced medical care in the world, anywhere and anytime. But when we think about further development of care, we need to resolve various problems in and surrounding the healthcare system in a rational way. Rational Medicine will only be realized when various technologies—including medicine, ethics, regulations, etc.—are applied to rationally work in harmony.

Patients should be placed at the center of promoting Rational Medicine. This ideal will create benefits and trust for future patients (including ourselves) that we could only imagine before now, as we gather all our wisdom in science and ethics in a collaborative movement toward this valued healthcare environment in Japan. No discussion of the unprecedented change that the global clinical trial and drug development industry has undergone over the past decade would be complete without accounting for the regulatory innovation that has correspondingly emerged and spread worldwide.

As Program Chair and former Chief Executive of the Pharmaceuticals & Medical Devices Agency (PMDA), Japan, I captured the essence of current and future challenges in my 16th DIA Japan Annual Meeting 2019 keynote speech.

After being appointed as Chief Executive of PMDA in 2008, I enthusiastically collaborated with many stakeholders to promote regulatory innovation by focusing on eliminating the “drug lag” in Japan and advancing medicine development from the regulatory science perspective, which also helped to build trust in the Agency.

Through the collective wisdom of many colleagues and experts, various initiatives were implemented: Establishing an early approval process for regenerative medicine products; building the SAKIGAKE designation accelerated review system; promoting pre-NDA consultation and shortening NDA review time; implementing personnel exchange programs with academic institutions; establishing the Regulatory Science Center within PMDA; founding drug safety measures utilizing medical data; implementing CDISC standards; establishing the Asia Training Center; and promoting international collaboration with foreign regulatory agencies such as ICMRA, the International Coalition of Medicines Regulatory Authorities.

Importance of Supporting Drug Discovery Ventures

Since the year 2000, the number of Nobel prize winners from Japan in the natural sciences (Medicine/Physiology, Chemistry, and Physics) has been second in the world, behind only the US. In 2016, Japan also ranked second in the world among the originators of the top 100 best-selling pharmaceutical products, again behind only the US.

Although we can often find seeds of innovation in Japan, it has been far less common to see world-class bio-ventures originating from Japan. Discussions at this DIA Japan Annual Meeting addressed the lack of such bio-ventures from the viewpoint of talent development and the environment for financial investment.

The Entrepreneurial Activity Index of Japan is the lowest among the world’s five most developed countries; curiously, the rate of “Fear of Failure” in Japan is the highest in this same group. The size of the industry segment with a spirit that welcomes challenges seems to be small in Japan. Similarly, institutional investors in Japan are fewer compared to Western countries; in fact, total amount of annual investment is about 50 times higher in the US than in Japan. Even if a Japanese bio-venture company lists on the stock market to raise funding, it is sometimes difficult to maintain economic viability because bio-venture business models are based on long-term capital recovery.

Artificial Intelligence (AI) and Related Topics

Japan boasts an academic-initiated AI consortium in which more than 100 members, including pharmaceutical companies, information technology firms, and academia participate. More than 30 AI-related projects broadly cover the entire pharmaceutical R&D chain from molecular discovery platforms to post-marketing safety measures. Many considered building an industry-academia-government collaboration in the pharmaceutical segment to be too difficult, but Japan Annual Meeting sessions shared several examples as a promising model for the future.

AI is a tool which could enable greater efficiency by improving, empowering, and modifying the current labor-intensive R&D chain model. To bring about such efficiency, many pharmaceutical companies are accelerating their introduction of Robotic Process Automation (RPA). From the research field, AI-empowered multi-omics approaches using enormous databases (from the gene to the protein level) conduct comprehensive analyses to identify potential biomarkers for disease diagnosis/prognosis. While we can find these and other excellent examples of AI expertise, talent development in this area is becoming a new challenge as we work to propose how and where AI technologies could improve current R&D working models.

Medical Database Utilization

Utilization of medical databases (“big data”) has come into the world’s focus for its potential to serve as the source for new clinical evidence. In Japan, a new drug safety database system called MID-NET (owned by the PMDA Regulatory Science Center) has launched services to support pharmaceutical companies’ post-marketing safety obligations. A new ICH guideline (E6R2) has positioned real world data (RWD) as an important tool in promoting new drug development and in constructing historical data as a virtual external comparator. Properly validated medical data collected by a system with appropriate quality controls can provide this type of high precision historical data. Discussion around the necessity (or lack thereof) of a placebo group in clinical trials was another popular topic at the DIA Japan Annual Meeting 2019.

Conclusions

Many sessions featured impressive discussions about patient centricity, a topic that was not even addressed by the Japan Annual Meeting just a few years ago. As was clearly seen in the Keynote Address and DIAmond session, patient and public involvement (PPI) is increasingly gaining attention in drug development, and speakers from a patient advocacy group, regulatory agencies from Japan and the EU, the pharmaceutical industry, and academia, exchanged thoughts from their own perspectives. Continued development of “Japanese PPI,” which should include unique aspects of patients in Japan based on their specific local culture, social systems, regulations, and environment, is greatly anticipated.

Brand-new technologies and concepts–such as digital technology, AI, medical care database or health technology assessment– are rapidly paving a new path from labor-intensive R&D to a more efficient model based on new technologies. “Soft skills” such as human creativity and “hard skills” such as regulatory science and organizational productivity or processes-oriented quality control must work together rationally.

It is important to note that the younger generation is adding its power to the drug development field as well as to DIA in Japan. This generation is increasingly important because of their role in creating new ideas for utilizing these new technologies, and for new concepts/models that will reach far beyond current organizations and positions. Working across generations in Japan will increase DIA’s essential importance as “a forum for discussion to create Rational Medicine with collaboration among government, industry, academia and patients.” To realize Rational Medicine for patients, we must diligently seek “medical excellence” and implement it with stakeholders all over the world.

The author extends appreciation and thanks to Takashi Sato (Kyowa Kirin Co., Ltd.) for his editorial contributions to this report.

The author delivering his DIA Japan Annual Meeting 2019 keynote speech.