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Do not let an opportunity slip

In a way, a pandemic like this is a business opportunity for healthcare innovation. Since it could end in a relatively short period of time, you may say do not miss it. Since innovation means creating some new value in society, even for existing medical products that are used for COVID-19, it can be considered as a kind of innovation. In other words, there are two types of healthcare innovations for COVID-19; one is something completely new and the other is the creative use of existing products. Apparently, a definition of innovation is that something new was actually implemented in society. Therefore, successfully introduced and well-used is necessary behind the word not to miss the season is to produce results.

Everyone thinks the same

Various items such as toilet paper, face masks, rubbing alcohol, etc. were lacking in this new Corona pandemic . Of course, there was speculation that there would be a significant shortage of ventilators that are directly linked to life. Nonetheless, no one would think of starting a new toilet paper manufacturer because the toilet paper has disappeared from the store. This is because it is a temporary shortage due to a temporary stockpile and a distribution gap due to a decrease in the amount used outside the home, and it is intuitively thought that it is not an absolute number shortage.

Well, now almost everyone wears a mask, even in Europe and America, where there was no custom of wearing masks. The demand is overwhelming. Moreover, the habit of wearing masks has spread to Europe and the United States, and a certain global demand for masks may occur in the future like when the winter flu epidemic occurs. If so, it may be an opportunity to enter the mask business. In fact, a large-scale supply system was created in the short term, including products made in China, and masks are already spreading around the world. Some start-up companies may have made a profit in this process. On the other hand, there is no doubt that major companies such as 3M have increased their production considerably. At this time, is 3M investing capital in the increase in production lines in anticipation of future global demand? If the number of production lines has increased and the emerging companies that have arisen during this time have greatly increased their manufacturing capacities, there is a risk of competing for share and a potential collapse, even if there is a certain increase in demand.

How about a ventilator? In fact, even when SARS became a problem, there was a growing concern that there would be a shortage of ventilators in Japan. There were few ventilators made in Japan at that time, and most relied on imports, so if there was a global emergency, it was rumored that the number of ventilators coming to Japan would be insufficient. Then, the Japanese government urgently asked the private sector to manufacture domestically-produced ventilators in a panic.　　As a result, SARS was not so harsh in Japan. However, since the manufacturing and approval of the ventilator could not be done overnight, for the first time ever, society recognized that relying on importing medical products related to pandemic is a national security issue at this time. Today, there are several domestic manufacturers that started manufacturing and selling ventilators because of the SARS problem. Here, there is a question if these lessons resulted in a sufficient domestic respiratory reserve and supply system for a pandemic between the SARS problem in 2003 and this COVID-19 problem in 2020? As a matter of fact, as I described above, some specialists estimated that there would be a shortage of ventilators when an infection explosion occurred in Japan. In many ways, no one exactly knows how many ventilators are necessary exactly at the time of a pandemic. As such, a pandemic is a business whose market is unknown.

The speculation that there will be a shortage of personal protective equipment (PPE) products such as face shields, surgical masks, specific gowns and medical devices; such as mechanical ventilators, quickly spread around the world given the current internet-connected society. As a result, groups such as Open Source COVID19 Medical Supplies was created on Facebook, and many prototypes of homemade PPE and ventilators were made by using 3D printers or simple engineering were posted. As of May 9, Open Source COVID19 Medical Supplies has more than 70,000 members. There is also an original ventilator that works without electricity, which is interesting because it may be useful in the event of other natural disasters. But in this society, where everyone thinks the same thing and everyone can send the same message/information through internet, it is extremely difficult to select the most appropriate information and quickly make a decision to identify which one is the best. For this reason, it is difficult as individuals and start-ups to immediately embody good ideas during a pandemic like this one.

Large company strategy, national strategy

In the beginning of April 2020, when the situation became suddenly serious in Japan after the nationwide declaration of an emergency, the number of infected and dead people in Europe and the United States had already become a big problem. In the meantime, the crisis situation became very critical in the Middle East. At that moment, Saudi Arabia was working nationwide to urgently set up a system for PCR diagnostic testing for COVID-19, leading to a contact coming to JOMDD as to whether a Japanese company could help. Although there are several PCR diagnostic devices in Saudi, the problem is that the supply of consumables is not sufficient. The Saudi government had allocated a considerable amount of money, so that a Japanese company could provide comprehensive support. Immediately, JOMDD consulted with several large companies potentially able to deal with this situation.

In order to collect more detailed information, such as the scale of the project, so that the individuals in charge at Japanese companies could make internal adjustments, JOMDD’s liaison communicated with the Saudi counterpart, a Saudi medical device manufacturer representing the Saudi government. At the time two weeks past for such communications, the Saudi side regretted that a Chinese company would take over the role. A few days later, the news was posted online that a company called BGI in China had signed the contract¹. The contract values US $ 265 million (approx. ¥ 29 billion). In addition to supplying equipment and consumables, about 500 support staff including technicians and engineers were dispatched to the Saudi Arabia. Large labs were to be set up at six location for 10,000 tests a day using newly built mobile inspection stations. The person in charge, from a large domestic company, who had been communicating with JOMDD until then, said with a big surprise, “No way, this could not have done by my company…”

Likely that the demand for PCR tests will grow rapidly in Japan under this circumstance, and therefore, there may not be enough resource for these Japanese companies to respond to the request from Sandi Arabia. The reality was that the project needed to dispatch 500 staff and this may be beyond the capabilities of the Japanese companies. Although it is a large deal of approximately 30 billion Japanese yen, many people think that it is probably not realistic to prepare the surplus for this type of emergencies. In fact, the most recent pandemic before COVID-19 was the Spanish flu that happened 100 years ago, and no one can predict when the next pandemic will come. Similar to the demand for the scenario of increasing demand of masks and capital investment mentioned above, it is very difficult for large companies to decide how much they can expand their existing capacity of manufacturing for pandemic related products in an emergency, there is no correct answer.

On the other hand, Japan should not ignore the fact that a Chinese company actually made this happened. It seems that this Chinese company was also backed by the Chinese government. The Japan’s Abenomics is supposed to seek for more export of Japan’s medical innovations, but here it ended behind China. In the meantime, Saudi Arabia recognized the danger of relying on overseas virus diagnostic kits necessary for pandemics in this case. This time, they changed their perspective from simply importing medical products in a pandemic to developing infrastructure of R&D that could respond swiftly to the next pandemic. There may be countries other than Saudi Arabia who are thinking in a similar way. From the perspective of the nation, there is a possibility that many countries, who are heavily relying on other countries for leading pharmaceutical or medical device innovations, will wonder if this situation is a real danger, in terms of national security, and encourage domestic innovation to cover its own country for pandemic crisis.

Innovations do not breakthrough by themselves

Even if one’s foresight and decision to read time are correct, medical products cannot always be introduced to the market in a timely manner during a pandemic.
An antiviral drug, Remdesivir from Gilead, Inc. of the United States, was approved earlier than the domestic antiviral drug, Favipiravir in Japan. Why was not the domestic Favipiravir, that had been stockpiling for 2 million people in Japan for a flu pandemic before the COVID-19 disaster, approved earlier than Remdesivir? It would be understanding if there were apparent significant differences in effectiveness through past studies between these studies. However, with such a new virus, it was not clear, especially when one thinks about mechanism of action of these drugs. There is also a large difference in national systems regarding approval of therapeutic agents in emergencies. In the United States, there is a system called Emergency Use Authorization (EUA) ², which allows the U.S. Food and Drug Administration (FDA) to authorize use in the medical field with certain data urgently in emergencies such as a pandemic. On the other hand, as far as I know, there is no emergency drug use permit system in Japan (separate from the special approval path called Tokubetsu Shonin Seido (TSS) described later). A prospective clinical trial for the normal approval review process called a Chiken are probably too time consuming and impractical at this time for COVID-19 in Japan. For this reason, it can be said that drug administration at the discretion of the doctor is practical when medical institutions obtain approval from their own ethical committee under observational studies. In fact, in Japan, medical institutions wishing to use Favipiravir have a way to use this method, and the Ministry of Health, Labor and Welfare (MHLW) has made it known to the public³. Of course, MHLW also knows that such observational studies are not enough as compared to Chiken clinical trials to approve a new drug※. This time, Remdesivir was granted special approval through TSS in Japan following to the FDA’s EUA. For reference, what is the special approval path, TSS⁴? To put it simply, (1) there is no alternative in an urgent situation; (2) the product or drug has already been approved in the United States or equivalent countries and has started or already been in use. TSS is available when these two conditions are met at the same time. In other words, special approval is not granted unless sales are permitted in such foreign countries. Therefore, it may be the shortest way to obtain a special approval, TSS, in Japan after obtaining the U.S. FDA’s EUA, such as Remdesivir, in order to get Favipiravir approval for use earlier in Japan from MHLW.

※ Chiken clinical trials, clinical trials for market approval under certain regulation, are not always required to approve new drugs or new medical devices when there is a sufficient history in foreign countries based on the “Pharmaceuticals and Medical Devices Act” and relevant government ordinances and notifications. The special approval path, TSS, is approved by the Minister of Health, Labor and Welfare with reference to the opinion of the Pharmaceutical Affairs and Food Sanitation Council, which consists of external experts, without going through the review by the Pharmaceuticals and Medical Devices Agency (PMDA) that usually reviews a new drug. In any case, the current system of Japan cannot approve new drugs or new medical devices at the discretion of the Prime Minister or the Mayor of the Municipality, even if an emergency is declared.

Even very innovative new drugs and new medical devices cannot be used without approval in the event of a pandemic or natural disaster. In other words, having the proper knowledge and understanding of regulations is very important to bring out the medical innovation.

Healthcare Innovation after COVID-19

I have touched on how to breakthrough medical innovation during a pandemic above. After all, there are many uncertainties, for example, whether once every 100 years or coming again 10 years from now, how big, how long it is, whether it is influenza or corona, whether the severity is regional, etc. It is not easy to decide whether a “go or no go” for a new program, a product modification or capital investment. It is extremely difficult to discuss the path for innovation against a pandemic using existing products from the viewpoint of anticipating demand. By the way, discussions concerning lifestyle changes after the COVID-19 disaster are becoming more active. Like the matter of September admissions into Japanese schools, in education, and the spread of remote work in the society. National disasters like this are, in a way, an opportunity to boldly change the national system and lifestyle. Rather, it would be unreasonable to compensate for the stay home period of the people and a large economic loss due to COVID-19, if we do not change anything and just try to restore. The changes I would like to propose are the following:

●Introduction of new regulation similar to the U.S. Emergency Use Authorization
 ― Without a system like the EUA in the United States, the MHLW may find it difficult to work during a pandemic. When most Japanese people believe that the government shall take responsibility if something happens to the people, any time for any public matter, this is one of the biggest negative factors when the country tries to introduce a bold new system. However, at least in an emergency like a pandemic, even if people feel a new system/regulation a little too aggressive, such changes will not be implemented unless people stop blaming the government too much.

●Develop a flexible medical system during a pandemic
 ― The hotel whose customers have drastically decreased due to COVID-19 is being used as a place of observation for the patients virus-positive, but not serious. This is a good and flexible public action, I think. The benefits will outweigh disadvantages to maintain this type of flexibility and plan beforehand when and how much additional temporary medical facilities and medical products are needed during a pandemic like this. Obviously, it will also be necessary to stockpile the sufficient PPE at national and local government levels. It is not easy to determine how many special medical devices such as ventilators and extracorporeal membrane oxygenators (ECMO). However, it is necessary to prepare and consider specific treatment methods including pharmaceuticals for symptoms, pneumonia, etc. For now, we are gaining a lot of new valuable knowledge through treatment and clinical research done worldwide. For example, one aspect of disease progression of COVID-19 infection is initiation of a cytokine storm, after viral infection, resulting in acute respiratory distress syndrome (ARDS) and systematic microthrombus among severe patients. Based on this experience, the medical community should sort out what kind of specific treatment is potentially needed during the next pandemic, and the government should prepare for it based on this new knowledge.

●Promote self-medication at home
 ― To some extent, individuals will keep extra toilet paper, masks, alcohol disinfectants, etc. stored at home for another pandemic. This time we learned that toilet paper runs out of stock due to a temporary shift from outside to home use, which is resolved in about two months. Also, both masks and alcohol disinfectants are supplied relatively quickly, and if each household had a little more pandemic preparedness, the shortage would not have been a problem any longer.

 ― Common cold and some other common illnesses could be routinely managed at home. As a matter of fact, people in the United States and some other countries do not go to a medical institution for cold symptoms. These people rely much less on antiviral drugs, unlike Japan. However, it has never become a social problem normally. I think this is an opportunity to use self-medication more positively for colds and the like. As with flu, it is not good for the person to go to a medical institution for a flu symptom, to get a prescription followed by fast diagnostic test with a simple kit, and then go to the pharmacy and wait for the drugs; because the symptom itself pains the patient and the infected person is contagious to others. This makes no sense. Therefore, it would be much better to establish mechanism in which the patient with flu symptoms stay at home and provide saliva to delivery staff that performs diagnostic test using PCR or antigen-antibody reaction kit and let a physician know and pass a prescription to a pharmacy finally delivering a flu drug to the home. This is where the real need for a telemedicine system becomes apparent. If saliva is too low in sensitivity, there is a need for a new innovation. Or nasal swab would be OK, even at home. It can be done at most households at their own risk with a little training. The idea is that the benefits outweigh the risks. If we go further, there may be a need for a small PCR machine for home use as the next innovation. It may be useful to easily carry out PCR tests at home not only for pandemics, but also for infections such as some rash and rubella in children, as well as, some diarrhea, influenza and norovirus. However, a certain number of outpatient facilities are necessary to maintain accessibility, which is one of the biggest advantages of Japan’s medical system. Also, doctors should be responsible for diagnosis and treatment to ensure safety. The spread of self-medication may reduce medical expenses. Then, that money could cover the amount of the medical expenses, which is set lower than in the United States.

Conclusion

It is not easy for healthcare innovators to prepare for a pandemic because a pandemic like COVID-19 has too many unpredictable factors such as arrival time, scale, and regional characteristics. However, there is no doubt that utilizing lessons learned from this COVID-19 crisis will provide valuable tips for healthcare innovation during the next pandemic. Also, because of this disaster, I would like to boldly change some social systems and lifestyle. From these changes, new innovations can be born. In addition, this COVID-19 crisis is an opportunity for countries around the world to reconsider the self-sufficiency status of pharmaceuticals and medical devices, and it seems that this needs to be taken into consideration in the global strategy for post-COVID-19 healthcare innovation.

¹ ITP Media Group , Arabian Business, Saudi Arabia signs ＄265m China deal to ramp　up Covid-19 testing, Sun 26 Apr 2020
https://www.arabianbusiness.com/healthcare/445730-saudi-arabia-signs-265-china-deal-to-ramp-up-covid-19-testing