As Japan’s regulatory agency for pharmaceuticals and medical devices, the PMDA is transforming how medical products are approved with its emphasis on regulatory science as an industry framework. Through the use of this methodology, the agency has been able to expedite pharmaceutical approval processes by creating efficiencies like conditional approvals, which couple a robust scientific approach to product review with Japan’s unique offering of relief services to patients who experience adverse drug reactions. As a result, Japan has advanced a variety of key innovations, the new product reviews conducted by the PMDA are now among the world’s fastest and the concept of regulatory science has been popularized around the globe.
With Japan’s ageing population and the massive global demand for innovative medical products, the PMDA has noted growing expectations regarding its activities in recent years, both domestically and internationally. As one of the world’s most important regulatory agencies, all eyes are on the PMDA as a global role model for balancing speed, innovation, efficiency and safety throughout the approval process. Likewise, it is playing a strong role at the international level as an advocate for greater harmonization of regulation beyond national borders. PMDA’s Dr. Tatsuya Kondo, who has been the chief executive since 2008, has played a fundamental role in the agency’s increased efficiency and international influence. Previously, he spent most of his career as a neurosurgeon and also serves as an advisor on health and medical strategy for the Japanese government.
After a decade at the helm of PMDA, what have been your biggest milestones and accomplishments at the agency so far?
There are three that come to mind. The first is that I made an effort to clarify our mission statement and really make sure that our three main lines of work were working together in unison and that they were able to produce the results that we intended. I had thought that for our organization to operate in the most effective manner and produce the most effective results, it was important to clarify our purpose and direction and be clear about what results we would actually produce. I thought this clarification would unite us as an organization, and that is exactly what happened.
The second point that I feel proud of is the fact that we have been able to root ourselves in the concept and methodology of regulatory science. This has been at the base of all of our efforts and is something that is now known worldwide within the field. I was really happy to know that this concept of basing our actions on scientific methodologies was recognized as a sound methodology not only here in Japan but also in the U.S. and Europe.
The third point is that I have emphasized the idea that pharmaceuticals and medical devices do not belong to any single nation, they belong to the world. Therefore, medical regulatory agencies around the world must work together, and there must be harmonization across the world’s medical regulatory agencies.
Trust amongst the various stakeholders is critical for this type of agency. In what ways have you, as chief executive, built this trust with all of your stakeholders?
We have made a point to follow through with our promises and not make promises we cannot meet. We have steadily accomplished the goals that we’ve set for ourselves, and our shareholders have been able to recognize that we follow through. That has helped build trust over the years.
You have been public about your goals for regulatory harmonization at the international level. What are Japan’s specific proposals in this regard?
There is definitely a need for the agencies to harmonize and obviously, there are different circumstances in each country, but we should share what we can with each other. It is not about mere negotiations but to have scientific decisions drive forward policies in each country and use regulatory science as a common language in order to do that. One of the things we have proposed is to hold summits between the regulatory agencies, and particularly with participation from the heads of regulatory agencies around the world. One such summit that took place was the Kyoto Summit where we decided that the heads of these regulatory agencies would not just talk but really define the objectives so that they could lead to concrete results for the future.
A specific proposal that we have brought up regards the analysis method for horizon scanning. We proposed it because we think it is important for people to better understand regulatory science. There are two aspects of regulatory science that are important. The first is the concept of science for the purpose of evaluation. For example, science for the purpose of evaluation would include the need to conduct evaluations to assess the positives and negatives of each pharmaceutical/device product. This science involves evaluation not only from a microscopic view but looking at the holistic macro perspective to make sure that the benefits are really evaluated. By doing so, we can better control the risks and minimize them, while maximizing the benefits. Once these products are evaluated based on science, then you can move into the next arena of making sure they become consumer products. Then, when we move into the technical arena and ask the questions about how we should market the product, what regulations are necessary, who the consumer market is, and who should prescribe the medication. In a nutshell, the first point is establishing an evaluation method for cutting-edge technology.
The second important aspect of regulatory science is that when policy-making is shaped by this methodology, it can truly benefit the public. The public will feel they can trust the policymakers and understand what is being marketed to them. They understand that what the products do is based on scientific reasoning rather than simply the whim of the politicians in charge.
From your perspective, what are the similarities and differences between the U.S. Food and Drug Administration (FDA) and Japan’s PMDA?
When we first approached the FDA, the FDA told us they are operating based on regulatory science too. According to the FDA, they consider regulatory science equivalent to translational research; if they deem something to be beneficial they run tests in the laboratory to determine how to turn it into a consumer good. The point between the lab and when it hits the trial in humans is this method of translational research. So, we discovered that there was a discrepancy in our way of thinking and how we define regulatory science. However, we’ve continued to promote our definition of what we believe regulatory science really means. One aspect of this kind of science is the science of discernment, to judge whether a particular product can be beneficial to humans moving forward and employing all the facets of science to one’s disposal to make that determination.
What has been your strategy to speed up the drug and medical device approval process in Japan?
We were aware that the approval of drugs was very slow in Japan compared to America, so we actually inquired with the FDA and asked them directly why that was the case. Interestingly, we followed the U.S. model in the sense that how the FDA goes about drug approval is they consult with the drug companies and clarify which aspects of the drug need to be tested before the application. This way, when the drug is applied for, the period between application and approval is cut down. Before we spoke with the FDA, we received an application for a new drug and then begin our discussions with the drug company in our face-to-face consultation, which really lengthened the time it took to pass the drug. Making this process change was our first step to speeding up our process.
The second step that we took was to organize strategy consultations with the various developers, such as investigators at academic organizations and SMEs, in which we weighed all the risks and benefits of a product. We created a consultation system where our services could be provided across the board to anybody involved at a low cost, which allowed us to offer transparency and ensure we are not favoring one group that would be able to pay more for our services. In the past five years, we’ve held some 4,000 consultations.
The third step is we’ve put a lot of emphasis on regenerative medicine. We’ve really made an effort to make this more understandable and accessible to the wider public. We did so by separating this line of work from the pharmaceuticals and medical devices and created a system called the conditional time-limited approval of regenerative medical products. Usually, when it comes to the approval process of drugs, you need to go through clinical trials in phases I, II, and III. However, we were able to cut out phase III altogether and do the approval at phase II, if certain clinical results are obtained. Before you would go through the phases and at phase III you’d spend up to seven years testing to determine whether that product was really effective. Instead of phase III, at phase II we instated a conditional time-limited approval, where we would authorize and pass that product, but it would be conditional and during that time of maximum seven years it would be tested before being fully approved.
PMDA has three main lines of work we focus on: review, safety measures, and providing relief services. This idea of providing relief services is very unique to Japan. It was introduced in Japan 35 years ago when patients were suffering from the side effects of drugs. The reason we were able to cut out phase III was because we were able to introduce these important relief services. We feel that providing relief services for adverse health effects is really important in the approval of new regenerative medical products. This process is the underlying philosophy and method of regulatory science.
Japan’s is experiencing an important demographic shift in which people are living longer and having fewer children. What does this mean for the PMDA?
There are actually merits to an aging population. Those who are aged can really contribute to society, contributing value in ways that utilize the rich wisdom that they’ve accumulated. We could include in society various mechanisms by which the elderly can contribute and play a significant role. There are many opportunities presented for the elderly to rediscover their social value, and medicine and food play an important role – I can’t rule out the possibility of new medical products that would be able to sustain a culture of longevity. My background is as a brain surgeon. My perspective on illnesses as a whole is that many illnesses often stem as a result of aging or nutritional deficiencies. Often times the root of the problem has to do with the weakening of the immune system. Brain strokes, cardiac arrest, cancer, all of these come from a weakening of the immune system. Moving forward, especially in an aging society, what is important is strengthening the immune system. The three ways to do that: nutrition, rest, and how we use our brain. The brain expends an extraordinary amount of energy when it is stressed or worried. At PMDA, we are looking to longevity and strive to be an honest and open agency that fosters employees with healthy lifestyles and therefore healthy brains.
As a surgeon, you had a direct impact on saving lives. What sense of reward do you get from your work at PMDA?
I view the reward as very similar to being a surgeon. PMDA was an agency that was unwell and my goal was to strengthen its immune system and make it well. We really consider everyone as patients. I believe that this idea of applying rational methodologies to medical decision-making can be applied to different facets of society, including the management of government agencies.