ISSN0535-1405

No. 508

November 30, 2021
Published by International Medical Society of Japan,
Chairman, Board of Directors: Kenichi Ishibashi, MD, PhD
Editors: K. Ito, MD, PhD, T. Kondo, MD, PhD,
K. Ichihashi, MD, PhD, T. Murakami, PhD, R.Nagai, MD, PhD,
I. Taniguchi, MD, PhD, and T. Yamazaki, MD, PhD
3F MK Sangenjaya Building, 1-15-3 Kamiuma, Setagaya-ku,Tokyo154-0011,Japan.
TEL 03(5486)0601 FAX 03(5486)0599 E-mail: imsj@imsj.or.jp https://www.imsj.or.jp/

The 451st International Symposium on Therapy
The 451st International Symposium on Therapy washeld by the Zoom Webinar on September 16, 2021.
Dr. Takahisa Murakami, Director of the International
Medical Society of Japan (IMSJ), presided over the
meeting.

Trends in pharmaceutical regulations in
the development of pharmaceuticals andmedical devices- The Roles of Pharmaceuticals andthe Medical Devices Agency (PMDA) -Introductory Message from the Chair

Takahisa Murakami, PhD
Director, IMSJ

Needless to say, drugs and medical devices areimportant tools in medical treatment, and safe,
highly efficient drugs and medical devices arealways expected. In a situation like the spreadof COVID-19 infections that occurred recently,
the expectations society has are even greater.
However, increasing social interest may cause
the dissemination of unconfirmed information that
results in confusion.
In addition, the first two COVID-19 vaccines
approved in Japan were RNA vaccines thathave a different development concept fromconventional vaccines. In order to accurately
evaluate such new technology, the people who
evaluate it must be highly capable.
Therefore, a specialized institution that conducts
neutral, scientific evaluations is indispensable.
Today, we are welcoming the chairman of theboard, Dr. Yasuhiro Fujiwara (MD, PhD, Chief
Executive), and the medical management

supervisor, Dr. Haruko Yamamoto (MD, PhD) fromthe Pharmaceuticals and Medical Devices Agency(PMDA), which is an organization that examines
pharmaceuticals and medical devices in Japan.
They will talk about the PMDA's initiatives for the
recent development of new drugs and medical
devices.
We would like to take this opportunity to reaffirm
the importance of the PMDA's activities.

LectureⅠ
PMDA’s efforts to promote medical
innovation in the COVID-19
Yasuhiro Fujiwara, MD, PhD
Chief Executive
Pharmaceuticals and Medical Devices Agency (PMDA)
The Pharmaceuticals and Medical Devices
Agency (PMDA) plays three key roles—relief
services for persons injured by adverse reactions,product reviews, and safety measures. In recent
decades, the progress of medical science andhealth care in the world has been rapid, andpeople’s expectations of medical treatment
have risen accordingly. We aimed to speed up
review and safety assurance measures, in order
to introduce new drugs and medical devices in atimely manner from a social welfare point of view,
while at the same time enabling continuous andrapid monitoring of safety. To provide patientsand healthcare professionals with timely access tosafer, more effective medical products, the PMDA
is engaged in ensuring quality, efficacy, and safety
from development to post-market stages.

Page 7Since its inception in 2004, the PMDA has steadily
attained progress. In April 2008, the number ofPMDA staff was less than 450, but the total has
now reached nearly 1,000. After having overcome
the issues of drug-lag and device-lag, PDMA has
introduced other measures, PMDA has improved
its standing in the global positioning of regulatory
authorities by building up its scientific capabilities tospeed up new drug review and safety measures, as
exemplified by achieving the world's fastest review
speed for new drugs with new active ingredients.
With the emergence of innovative products, thequality of our work has to be further improved
enough to be capable of making first decision in
the world on those products.
As a part of this work, it is important to harmonize
international scientific norms and evaluation
methods. We believe such an approach will
enhance the social implementation of new
outcomes of science and technology for the
benefit of patients in the human society.
Further, based on regulatory science implementation,
we were able to propose and introduce the world's
first regulatory category for regenerative medical
products (cell, tissue and gene therapies), as
well as to introduce a new system of conditional
early approval for medicines. In the Center for
Regulatory Science which PMDA established in2018, we also organized the Science Board to bring
together researchers who are directly involved inadvanced studies leading to the developmentof innovative medicines. The board summarizes
evaluation reports on advances in medical
science and technology, including iPS, providing
the foundation for horizon scanning of potential
medical advances.
The need for such measures has been clearly
illustrated by the recent work to develop, test
and approve coronavirus vaccines. Furthermore,with the worldwide spread of novel coronavirus
infections these days, PMDA has been able
to facilitate developing coronavirus related
products smoothly, by providing consultations
and responding to requests from the early stagesof development of drugs and medical devices
related to the corona virus infectious disease. Oncean application for approval has been submitted,
we work on to proceed review process as fast as
possible. In addition, as large-scale vaccination
program against novel coronavirus infections
has started in Japan, number of Adverse Events
Following Immunization (AEFI) have been reported
more than before. We have been working hard,even day and night, to sort out and to makeanalysis on suspected AEFI associated with thenovel coronavirus vaccines.
The modality of products such as pharmaceuticals
has also been diversified, and the expected effects
and evaluation methods of these products vary,depending on different natures of origin such as

International Medical News

small molecules, macromolecules, cells, genes,
etc. In this lecture, I would like to introduce PMDA’s
activities for faster access to safer and more
effective medical products, even in response to the
products emerging new modalities of medicine.

LectureⅡ
Recent trends of clinical developmentof medical devices and new regulatory
frameworks in Japan
Haruko Yamamoto, MD, PhD
Chief Medical Officer
Pharmaceuticals and Medical Devices Agency (PMDA)
With recent advances in science and technology,
the speed at which innovative technologies will
be adapted and applied to medical devices
continues to increase. On the other hand, thefact remains that there are some medical devices
whose development is challenging to promotebecause of small market size, despite their highdegree of medical necessity.
In 2014, the Pharmaceutical Affairs Law, theessential legislation for regulation of medical
products, was largely revised and renamed. In
the revised law named the “Act on Securing
Quality, Efficacy, and Safety of Products Including
Pharmaceuticals and Medical Devices” (in short,Pharmaceuticals and Medical Devices Act; PMDAct), the independent chapters for medical
devices and regenerative medical products were
newly installed, while medical devices were putin the same chapters for drugs and no description
for regenerative medical products before revision.
This revision enabled to develop more effective
regulatory frameworks for medical devices forJapanese regulatory authority, apart from othercategories of medical products. The Revision of
PMD Act in 2019 gave legal basis of several new
frameworks for approval of medical devices
including the SAKIGAKE designation system”, the“conditional early approval system”, the “PHOENIX(physical operation items’ extrapolative andinclusive approval)”, the “IDATEN (improvement
design within approval for timely evaluationand notice)”, and the “IDATEN for AI”. The
Pharmaceutical and Medical Device Agency(PMDA), Japanese regulatory agency, plays animportant role, in close cooperation with the
Ministry of Health, Labour and Welfare (MHLW), in
these frameworks.
To accelerate emerging global trends ofdeveloping Software as a Medical Device (SaMD),
MHLW has started “DASH for SaMD (Degitaltransformation action strategies in healthcare forPage 8International Medical News

SaMD)” since 2021. PMDA, in collaboration with
MHLW, set up a new review office that specializes
in SaMD in April 2021.
Many medical device industries hesitate to pay
the cost before obtaining market clearance andinsurance coverage because of lack of intensives
in small patient population. Several regulatory
agencies including PMDA has started considering
the use of Real World Data (RWD) such as registrydata on regulatory decision making. PMDA has
developed and finalized several guidelines topromote RWD utilization, and started a series ofconsultation services for registry owners, databaseproviders and developers of medical products
in 2019, in order to provide scientific advice on
feasibility of registry utilization and on registry datareliability.
PMDA will continue to make efforts to expedite
patient access to more effective and safe
medical devices by collaborating with the
manufactures and academia, and by introducing
less burdensome and user-friendly regulatory
frameworks.

Discourse
Introduction of the speaker of discourse
Takahisa Murakami, PhD
Director, IMSJ
Today we have invited Mr. Mikio Kawa, thePresident of the Social Welfare Corporation of
the Japan Association of Physically and Mentally
Challenged Children (Shimada Ryoiku Medical
Center for Challenged Children), who has been
active in the field of social welfare since joining
the Ministry of Health and Welfare (as it was knownat that time) in 1975. He possessed a high levelof insight into the welfare of people with disabilities
before entering the ministry. After entering theministry, he served as chief of the Planning Divisionof the Social Assistance Bureau, counselor in
charge of social security, and Councillor, cabinet
secretariat. After retiring in 2007, he becamea professor at Kanagawa University of Human
Services, and has been in his current position since2017. He will talk about the key points of social
welfare.

Discourse: The social security systemand human services
Mikio Kawa
President
Social Welfare Corporation, Japan Association of Physicallyand Mentally Challenged Children
Shimada Ryoiku Medical Center for Challenged Children[Two types of benefits of social security]
According to statistics on the costs of social security
in 2019 released by National Institute of Populationand Social Security Research at the end of August,Japan's "social security benefits cost" in 2019 was
124 trillion yen (23% of the gross domestic product).
When considering social security, it is customary
to classify them into pensions, medical care, andwelfare according to their purposes, and thendiscuss their ratio and composition. However, it isimportant to pay attention to the nature of thebenefits, and to consider them separately as either"cash benefits" (e.g. pension benefits, etc.) or"service benefits" (e.g. medical service fees, nursing
care fees, etc.).
When talking about social security in developed
countries, in the field of media and politics, andin the subject of economics, many experts discuss
only the "cash benefits", such as pensions andbenefits that protect people's livelihoods.
However, there are also social security systems
such as medical insurance and long-term careinsurance which are there to supply human service
benefits continuously and stably. Medical services
and long-term care services are provided to facility
users in the form of human services at hospitals
and social welfare facilities. In these systems, thecosts of those using the facilities are covered by
the general public's payments such as throughtaxes and insurance premiums, and people canuse these human services if they bear a part of thecost.
Since the benefits themselves are human services,
they should be called "service benefits" (including
drug costs) systems. In these "service benefits"systems, the general public's share of the expenses
is actually paid to hospitals and social welfare
facilities in the form of "remuneration", where mostof the amount will be spent on personnel expenses
for staff members.
Hence, "money" is replaced with "service benefits".
[A review of service benefits]
Ten years ago, when I analyzed and calculated
100 trillion yen of social security benefits costs

Page 9(FY2009), I found that "cash benefits" accounted
for 60 trillion yen (60%) and "service benefits"
accounted for 40 trillion yen (40%). Breaking down
the financial resources, tax financial resources were40% and insurance premium financial resourceswere 60%. As much as 40% of social security
benefits costs were "service benefits".
According to recent materials, social security
benefits costs (FY2019) were 124 trillion yen,"cash benefits" were 62 trillion yen (50%), and"service benefits" were 62 trillion yen (50%). Service
benefits actually accounted for 50% of the costs.
(Regarding financial resources, tax financial
resources were 40% and insurance premium
financial resources were 60%)
Here are three reasons for discussing the twocategories, which are cash benefits and service
benefits.
(1) Cash benefits are derived from a standpoint of"human rights", and service benefits are derived
from a standpoint of "necessity".
(2) Cash benefits are paid mechanically, andservice benefits are paid "face-to-face".
(3) Cash benefits are described in terms of"how much they cost" and service benefits areevaluated in terms of their "quality".
[Service benefits supply system theory]
In order that the social security "service benefits"
are properly and fairly practiced nationwide, there
should be a service supply system nationwide inwhich there are some people who live there andwho can provide human services with a certain
level of quality. In order that these human services
may be provided stably and continuously, it isnecessary that qualified people are engaged
in performing these service benefits as theirprofession, and that they are present [living] in thevicinity of the users.
Moreover, as long as people are required to bear
the costs of "service benefits", "publicness" is arequisite for these human services. The humanservices themselves are "private" things that protect
and support the lives of users; however, they havea public nature because they provide safety andsecurity to everyone in local communities. In thatsense, the system of providing human service
benefits itself should be considered a public asset.
No matter how much money is allocated,
providing human services beyond the qualities
of service providers or beyond the capabilities ofservice institutions is impossible.
Great human services cannot be created fromInternational Medical News

enormous or excessive workloads. Although thisservice provision system theory might seem to bea function of "money", ultimately it is a matter ofthe "existence of professionals". Thus, we haveto promote such awareness until it is a common
understanding in society.