European Business Council (EBC) Medical Devices and IVD Committee

Meeting of Representatives
Report of the Pharmaceutical Affairs
Subcommittee of PMDA
December 10, 2020

Committee Vice-Chairperson in Charge: Takeshi Fujiwara
Subcommittee Chairperson: Miyo Nishimuta

Page 1

Basic Action Plan of Pharmaceutical Affairs Subcommittee

In 2020 and 2021
Through meetings with the government and pharmaceutical affairs related
activities of the EBC, we propose optimization of the medical devices review
and the related legal system.

Page 2

Report of the Pharmaceutical Affairs Subcommittee

Agenda• Report of the activities of the Pharmaceutical Affairs
Subcommittee from January to December 2020
• Topics in 2020

Page 3

Report of the activities of the Pharmaceutical Affairs
Subcommittee from January to December 2020
▪ Legislation Committee(5 times)
Review Related Subcommittee (6 times)
WG to Improvement of review operations:notifications (1 time)
WG on Interpretation of Fair Advertising Standards(3 times)
WG on the Revision of the Law (1 time)▪ QMS Committee (5 times)▪ PMS Committee (5 times)
Defect Terminology WG (12 times)
WG to study improvement of package insert
use (3 times)▪ Small Bore Standards Review WG (2 times)▪ WG on Medical Device Cyber Security (4 times)▪ MDSAP Opinion Exchange Meeting (2 times)▪ Clinical Evaluation Committee (4 times)▪ Health and Labour Sciences Research: QMS(3 times)▪ Health and Labour Sciences Research :Watanabe Group (1 time)▪ WG for Consideration of New Approval System(8 times)▪ Plan on Collaboration for Optimizing Medical Device Regulations and Review (January 22)▪ Regular meetings to exchange opinions on approval reviews and safety measures for medical
devices and in-vitro diagnostics (August 28)▪ Public-Private Dialogue for the Creation of Innovative Pharmaceuticals, Medical Devices, andRegenerative Medicine Products (November 16)

Thank you all for taking time out of your busy schedule.
Page 4Based on the progress table of the collaboration plan, various factors in the approval review will be extracted, shared within theindustry, and presented to the administration as input.
PIC

Mr. Murakami [Novocure Co., Ltd.]
Ms. Makishima [B. Braun AESCULAP, Ltd.]
Ms. Nishimuta [Biotronik Japan, Inc.]

In order to implement the new approval system and realize smooth approval reviews, we will, when appropriate, cooperate withthe government to address issues and promote action on each issue to be resolved.
•

Improve review quality and efficiency:
Enhancement of training, minimization of mandatory Japanese-language attachments, improvement of the operation of thecertification system, response to ISO 10993-1 revisions, efficient response to changes, review of new approval systems,
streamlining and computerization of procedures, assurance of data reliability and reduction of burden•

Clinical related: How best to evaluate, use of RWD, international harmonization•

QMS related: certificate of conformity, operation of MDSAP•

Safety related: Legislation on digitization of package inserts and UDI•

Utilization of international standards for medical devices

Page 5*Activity report from WG is available for items in gray

Development of standards, clear guidelines, and Q&A for medical device advertising.
Revision of guidelines for advertising-related display of unapproved medical devices.

PIC

Mr. Mizumachi [LivaNova Co., Ltd.]Starting on 9/24, a WG meeting was held once a month (3 times by November), and the following were discussed.
(1) Consideration of Q&A for concerns regarding viewing of advertisements by public (2nd installment)→ This will not be published as a Q&A, but will be published on the JFMDA website as an industry guideline.
(2) Revision of the Detailed Rules for Guidelines on the Display of Unapproved Medical Devices→ The current "Detailed Rules for Guidelines on the Display of Unapproved Medical Devices" has a part referring to"Import Inspection Procedure for Drugs and Deleterious Substances" but as of August 31, 2020 it was changed to"Main points of import confirmation of drugs", so the content will be changed accordingly. This will also be publishedon the JFMDA site after revision.
(3) Revised Q&A on Medical Device Advertising→ As the content of "Q&A on Medical Device Advertising" issued on January 27, 2011 has become outdated, we decided
to review it together with the other matters. (now in progress)
Page 6

Full-scale implementation of MDSAPPIC

Mr. Takeda [Radiometer K.K.]

Mainly the following activities were carried out• The following items were examined for full-scale introduction of MDSAP.
• MDSAP Expenses• Timing of full-scale implementation of MDSAP• Consideration of notifications that need to be revised for full implementation of MDSAPThe following results were obtained from the above activities.
• MDSAP costs 200,000 yen per facility. However, there is no need to pay this fee if MDSAP is not used. (selective system)• The timing of full-scale implementation of MDSAP will be around April 2022. The current pilot operation will be maintained in
2021. (It will involve no expenses)• Notifications that need to be revised include notices of extension of pilot operations and notices of inspection procedures. We
will continue to review the affected notifications.

Page 7

Move from ISO 594-1 to ISO 80369 series

PIC

Mr. Araki [Philips Japan Co., Ltd.]Mr. Takeda [Radiometer K.K.]

Mainly the following activities were carried out• Changes in field of neuroanesthesia (ISO 80369-6)• Changes in field of enteral nutrition (ISO 80369-3)
The following results were obtained.
• Changes in the field of neuroanesthesia have almost been completed.
• In the field of enteral nutrition, progress on making changes has been slow. Therefore, government and academic societies
are collaborating to promote change.

Page 8

Objective: To examine legal and regulatory issues related to clinical trials and clinical research and make proposals

PIC

JFMDA Clinical Evaluation Committee
Mr. Ohta [Biotronik Japan, Inc.]
Mr. Mori [Medical U&A Co., Ltd.]

Activities:
Reviewed “clinical trial related” notifications issued pursuant to the revision of the Drugs and Medical Devices Law on 9/1 andexchanged opinions with MHLW regarding the definition and applicability of the term "devices used in clinical trials" that is to be
used from this time onward.
Outcome:
It was confirmed that the purpose of the revision was to unify the reporting of adverse reactions and adverse events in order toprotect trial subjects.
It was also confirmed that the transitional measures for "Clinical trial notifications and reports of defects" could be made using
the same format as before for 2 years, until September 2022.
The explanation of specific cases was completed at the 2020 briefing session on clinical trials and clinical evaluations of
medical devices (November 20).
In the future:
The basic line of thinking on the devices used in clinical trials (especially in combination with other devices) that are specified in
the protocol will be discussed continuously and issued as a Q&A.
Page 9Objective: To study the effective use of the "clinical evaluation report"

PIC

JFMDA Clinical Evaluation Committee
Mr. Ohta [Biotronik Japan, Inc.]
Mr. Mori [Medical U&A Co., Ltd.]

Activities:
Revision of the “Guidelines for Preparation of Clinical Evaluation Reports ”: After repeated discussions with PMDA, this WG
prepared revisions, which were confirmed and finalized by PMDA.
The Guidelines are intended to be used as a manual for the preparation of the “clinical evaluation report” that is prepared asmaterial for use in consultations or for attachment to the approval application when a literature-based clinical evaluation is
acceptable for an item that must go through clinical trials.
Outcome:Completed revision of the “Manual for Preparation of Clinical Evaluation Reports and Materials for use in Consultations on
Clinical Evaluation, Part 1: Preparation Procedures” (November 1)
An explanation was provided at the 2020 briefing session on clinical trials and clinical evaluations of medical devices(November 20), and the Manual has been posted on the JFMDA website.
A link will be posted on the PMDA website in the near future.
In the future, we plan to discuss the "basic line of thinking" (part 2) in relation to cases described in clinical evaluation reports
and their acceptability.
Page 10

Consider what medical devices are particularly necessary in medical care and examine the related approval processes in orderto ensure quick access to innovative medical devices introduced after the revision of the PMD Act, and to enhance safetymeasures
PIC

Ms. Makishima [B. Braun AESCULAP, Ltd.]Mr. Toyofuku [Siemens Healthcare Co., Ltd.]
Ms. Nishimuta [Biotronik Japan, Inc.]

Examined laws, ordinances, and draft notifications, etc. with an eye to implementing mainly the following two new approvalsystems
1. Conditional early approval system (PHOENIX: PHysical OpEratioN of Items’ eXtrapolative and inclusive approval)
This system pertains to devices whose functions have potential application to other fields. Its purpose is to expedite addition of
application to other organs and parts by limiting the number of facilities and operators that can use the device and enhancing
post-marketing safety measures.
 Relevant major notifications have been issued
2. Procedure for expansion of indication, etc. using change plan (IDATEN: Improvement Design within Approval for Timely
Evaluation and Notice)This system pertains to medical devices that are expected to be modified or improved immediately after approval. Its purpose isto realize an approval review pathway that enables continuous improvement and refinement by confirming the change plan
during the review process and accepting partial changes that are made rapidly within the planned scope.
 Issues to be considered in the future• Examine the process from the standpoint of ensuring smooth insurance coverage after final notification of change to which
IDATEN applies• Preparation of operational Q&A
Page 11

Collection and dissemination of opinions on QMS from industry associations and issuing requests to government

PIC

Mr. Suga [Radiometer K.K.]
Mr. Hatoyama [B. Braun AESCULAP, Ltd.]Mr. Takeda [Radiometer K.K.]

Mainly the following activities and requests were carried out• Request for revision of the QMS Ministerial Ordinance (Consistency with ISO 13485: 2016)• Request for expanded application of certificate of conformity (A wide range of certificates also proves a small range)
The following results were obtained.

• Publication of public comments on the revised QMS Ordinance in 2020, scheduled to take effect in March 2021
• The application of the certificate of conformity was expanded by amendment of the law last year, and the expansion was
enforced as of September, 2020.

Page 12

Promote more rational use of QMS certificates

PIC

Mr. Takeda [Radiometer K.K.]

Considered systems by which multi-sheet certificates could be converted a single page in order to facilitate the management ofcertificates of conformity.
• It was discovered that making certificates a single page does not necessarily make management easier.
• The opinion was expressed that we should take future amendments of the law into account when considering the ideal form
for the certificate of conformity, and we intend to look into this in the future.

Page 13

Revision of the Defect Reporting Handbook and change in method for submitting applications electronically

PIC

Mr. Tanita [Nippon Lifeline Co., Ltd.]

1. WG for Revision of Defect Reporting Handbook
In response to related notifications issued after the 7th edition, the handbook was revised to accommodate the newdefect report form to which all reporters must switch by April 2021, with the addition of an explanation on selection ofterminology for describing defects. The 8th edition of the handbook was published in October.
2. System Improvement WG
The XML tool is being modified to comply with the 4th edition of the Glossary of Defect Terminology, which isscheduled to be published at the end of December 2020.

Page 14

Update Glossary of Defect Terminology and Import IMDRF Glossary

PIC

Mr. Tanita [Nippon Lifeline Co., Ltd.]

1. Update of defect reports collection
The 3rd edition of the glossary was published in March, which incorporates change requests by various groups and
IMDRF survey result terminology. The 4th edition of the glossary is currently being created in accordance with theupdated IMDRF glossary.

2. Incorporating IMDRF Glossary
The 4th edition that is currently being created will include a translated version of the IMDRF Glossary as a common
glossary in the glossary for Japan.

Page 15

Improvement of the use of package inserts and consideration of electronic methods of use

PIC

PMS Committee
Mr. Araki [Philips Japan Co., Ltd.]

Summary of Activities
In order to improve use on the basis of the provisions of Article 68-2-2, it was divided into TF 1–3 as of September 2020, and a
Q&A notification was prepared.
1) The paper version is to be provided at the time of the initial delivery of pharmaceuticals, medical devices, etc., with thecooperation of wholesalers as necessary.
2) In addition, it is necessary to establish a system to display information on the outer packaging of the product that enables
access to the latest package insert information, and to reliably deliver the information to medical institutions, pharmacies, etc.
via paper media, etc. when the information is revised.
3) For medical devices, etc., attention should be paid to the methods of providing information as befits the characteristics ofproducts such as programmable medical devices and specially controlled medical devices requiring expert installation.

Page 16

Conduct research on international harmonization of QMS

PIC

Mr. Takeda [Radiometer K.K.]

Mainly the following activities were carried out• Preparation of QMS ministerial ordinance and detailed explanation in accordance with ISO 13485: 2016
• Preparation and dissemination of guidance on the management of electromagnetic documents and records
The following results were obtained for these activities.
• Publication of comments on the QMS Ministerial Ordinance and preparation of a draft of an article-by-article
explanation (currently in final proofreading).
• Prepared guidance on the management of electromagnetic documents and records and posted it on the PMDA
website.

Page 17

Research on guidance on appropriate implementation of hazard prevention measures for medical devices

PIC

Mr. Tanita [Nippon Lifeline Co., Ltd.]

1. Fact-finding survey on implementation of safety management practices by MAHs
The objective is to conduct a questionnaire survey of marketing authorization holders to provide guidance on
effective safety management practices and balance with QMS.

We are currently reviewing the contents of thequestionnaire.
2. Investigation and analysis of recall (repair) cases
The objective is to survey and analyze occurrence by type over the past 3 years and use the data for early discovery
of devices that need to be recalled. We are currently surveying and analyzing cases.

Page 18

Plan for Collaboration on Optimizing Medical Device Regulations and Review (5-year plan starting in FY 2019 (first fiscal year of
the Reiwa era))
PIC

Ms. Makishima [B. Braun AESCULAP, Ltd.]Mr. Murakami [Novocure Co., Ltd.]
Ms. Nishimuta [Biotronik Japan, Inc.]

In order to optimize the medical device development process and the related regulations, the plan will promote the following:
eliminating development lag to reduce the time until companies submit applications, firmly maintaining the review period at theworld’s fastest level, improving the quality of reviews and applications, making operations more streamlined and efficient, andinternational harmonization of various regulations.
1. Efforts to streamline applications and the approval process
while also improving their quality

Action Program to
Speed up Review(2009-2013)

Plan for Collaboration to
Speed up Review(2014-2018)

2. Efforts to enhance safety measures based on thecharacteristics of medical devices
3. Other efforts to improve access to medical devices,
streamline and optimize application procedures, andpromote international harmonization
4. Establishment of a Standard Business Processing Period
5. Continued implementation of time clock surveys (industry)
Page 19[Challenges]✓ Expansion andimprovement of thereview system✓ Eliminating device lag✓ Improving the quality ofreviews and applications✓ Further shortening of thereview period andstandardization of the review
periodPlan for Collaboration
on Optimizing
Regulations and Review(2019-2023)✓ Improving the quality of reviews
and applications✓ Maintenance of the review period✓ Streamlining and optimizing
operations✓ Elimination of pre-development
lag(Promotion of simultaneousdevelopment with overseas)✓ Promotion of internationalizationand international harmonization✓ Enhancement of safetymeasuresOverall Review Period for Medical Devices (application cohort) (plan for collaboration)
Standard review period

Standard review period

9 months

12 months

9 months

Overall Review Period (80th percentile value) (month)Standard review period

FY 2013

FY 2014

FY 2015

FY 2016

FY 2017

FY 2018

Standard review period

Standard review period

Standard review period

7 months

5 months

4 months

Processing rate(%)
Number of
approvals

New medical device(Priority)

New medical device(Ordinary)

Improved medical device Improved medical device(Without clinical data)(With clinical data)

Generic medical device Generic medical device(Partial change)(New)* Calculated in accordance with "Plan for Collaboration to Speed up Review" and Item 2 of the Agreement of Implementers For each fiscal year’s application items, the overall review period for approved items
as of the end of September of the following year.
* The processing rate is calculated by dividing the number of approvals by (number of approvals + number under review) × 100.
* For generic medical devices, the start date is the date on which compliance with the checklist is confirmed. There is no data for FY 2013 because that was before the checklist came into use.

Page 201. Change in documents to be submitted and submission methods
before and after introduction of online submissions
Types of applications andnotifications

How to prepare and submit application forms
FD application software

All notifications
Prepare notification

FD application software

All applications
Prepare application

Print out & affix seal
Mail or bring to counter

Print out & affix seal
Mail or bring to counter(Physical) documents
to be submitted
Notification dossier

Application dossier
Revenue stamp/
certificate stamp, original
documents, and actual
articles for confirmation

Prefectural
reception
counterPMDA
reception
counterWith online submission

All notifications

FD application software
Prepare notificationAllapplications*1*2

FD application software
Prepare application

PDF files
Application electronic
data system(Gateway)

None
(* 1)

None
(* 2)

Plan to accept online submission of notifications and applications created with DWAP as well (for notification: starting in April 2022; for applications: concurrently with FDapplication software in FY 2022).
When the application fee is paid to the national or prefectural government not by a revenue stamp or certificate stamp but by electronic payment, transfer, etc. The
application fee to the government will be processed by Pay-easy. Application fees to prefectures should be paid according to the respective prefecture’s payment method.

Page 21

Prefectural
reception
counterPMDA
reception
counter

Topics in 2020
• Response to COVID-19• Response to new types of medical devices• Recent movement toward enforcement of the revised PMD Act

Page 22

Status of approval and certification of medical devices targeting
COVID-19 and related symptoms(Last Updated: August 5, 2020)

No.

Product Name

Company Name

Category

Approval Date
(Certification Date)NIPPON KODEN KOGYO CO.,LTD.

Ventilator

April 24, 2020

1

NKV-550 Series Ventilator

2

E30 System

Philips Japan Co., Ltd.

Ventilator

May 1, 2020

3

Trilogy Evo Series

Philips Japan Co., Ltd.

Ventilator

May 12, 2020

Omron Healthcare Co., Ltd.

Noncontact far infrared
thermometer(May 26, 2020)

CES Descartes Co., Ltd.

Image detection
support program

June 3, 2020

4
5

OMRON Infrared Forehead
Thermometer MC-720
Pulmonary Image Analysis
Program InferRead CT
Pneumonia

6

Puritan Bennett 560

Covidien Japan Co., Ltd.

Ventilator

June 12, 2020

7

MEDIGRIP Surgical Gloves, No
PowderToray Medical Co., Ltd.

Surgical gloves(June 12, 2020)8

Acoma Ventilator ART-21 EX

ACOMA Medical Industry Co.,
Ltd.

Ventilator

June 19, 2020

9NSH Heparinized Cannula

Senko Medical Instrument Mfg.
Co., Ltd.

Cannula for
extracorporeal
circulation

June 25, 2020

10

COVID-19 Pneumonia Image
Analysis Support Program Ali-M3

MIC Medical Co., Ltd.

Image detection
support program

June 29, 2020

11

Heart-lung machine S5

LivaNova Co., Ltd.

Heart-lung machine
systemJuly 13, 2020

12

Biometric Monitor InteliVue
MX850/750

Philips Japan Co., Ltd.

Multi-item monitor with
important parameters

July 31, 2020

Page 23*Only those with approval conditions are listed.

Materials submitted to Ministry of Health, Labour and Welfare at the 18th Regular Meeting for the Exchange of Opinions on Approval Reviews and Safety Measures for Medical Devices and In-Vitro Diagnostics https://www.mhlw.go.jp/content/11124500/000681361.pdf

Program for the Promotion of Research and Development in the
Medical Field
March 27, 2020 decision by the Health and Medical Strategy Promotion Headquarters
Medical Devices and Healthcare ProjectThis project uses AI and IoT technologies, measurement technologies, and robotics
technologies in an integrated manner to research and develop the following: systems that use
medical devices and medical device programs (treatment apps, etc.) to provide moreadvanced diagnosis and treatment, medical devices for which there is a great need in medical
settings, and medical devices and healthcare that contribute to prevention and improvementof QOL for the elderly.
Patient app
Delivers messages and videos promoting understandingof nicotine dependence and the establishment of
behavioral changes related to smoking cessation
CO Checker

Measures exhaled CO concentration and sends topatient app

Doctor's screen

Doctor’s app
Doctor’s app

Support for medical care such as checking progress on
the patient application

Excerpt from Chuikyo General-1-1

Page 24

2.11.11https://www.mhlw.go.jp/content/12404000/000693018.pdf

Amended PMD Act
Act for Partial Revision of the Measures to Ensure Quality, Efficacy and Safety of Pharmaceuticals, Medical Devices, etc.

Promulgation Date: December 4, 2019
[Enforcement in the first year](Approval system tailored to the characteristics ofinnovative medical devices, medical devices with specific applications, and othermedical devices, etc.)• June 4 - July 3, 2020 Public Comment• Cabinet Order promulgated on July 28, 2020
• Promulgation of Ministerial Ordinance at the end of August 2020 and issuance of various
notices• Enforced September 1, 2020
[Second year of implementation] (Digitization of package inserts, legal compliancesystem, surcharge system, etc.)• To be enforced August 1, 2021
[Enforcement in the third year] (Bar code displays, etc.)• To be enforced December 1, 2022
Page 25

Current system and issues related to package inserts
Existing system

Presently, dosage and administration, and other precautions for use and handling of drugs, etc. are to be described in"package inserts or on containers or wrappers". (PMD Act Article 52, etc.)

For prescription drugs, OTC drugs requiring a pharmacy consultation, and specially controlled medical devices, notification is
given on content of package insert, and the package inserts are published on the PMDA website. (PMD Act Article 52-2)

Information may be outdated

Package inserts: packaged with product to provide information

Medical institution

Marketing authorization holder
Waste of paper
resources
Notification of content of package insert, etc.

Publication via PMDA website

Challenges
For discussion at Council meeting (November 8, 2018; The 8th meeting of the Pharmaceutical and Medical Devices System
Subcommittee of the MHLW Health Science Council)
 Package inserts are frequently revised, and the one packaged with the product may not be up-to-date.
 Each time the same drug, etc. is delivered to a medical institution or pharmacy, a large number of package inserts accumulate
in one facility, leading to waste of paper resources.

Page 26https://www.mhlw.go.jp/content/11121000/000682481.pdf

Enforcement in
the second year
R3.8.1

System after legal revision (Effective August 1, 2021)
 Discontinue packaging of package insert with products and basically adopt provision of information electronically.
 In addition to electronic methods of providing information, the information must also be provided in paper form at the time of
the initial delivery of the pharmaceutical or medical device, with the cooperation of the wholesale distributor when necessary,at the responsibility of the marketing authorization holder. In addition, makers must display information on the outer packagingof the product that enables access to the latest package insert information and build a mechanism whereby information can bereliably delivered in paper form, etc. to medical institutions, pharmacies, etc. when the information is revised.
 For OTC drugs and other products that are purchased directly by consumers, it is necessary to ensure that the contents ofpackage inserts can be immediately confirmed at the time of use, so package inserts should continue to be enclosed in the
package in paper form.

Providing information electronicallyMarketing authorization holder:• Outer box displays a code that enables
access to package insert information• Also provide information in paper form
(No need to include package inserts inboxes)

Marketing authorization holder

Prescription drugs

Marketing authorization holder:
Prepare a website with thelatest package insert
information○○○○ Tablets 10 mg

MAH (with cooperation of wholesale distributors as needed):
1) Provides package inserts in paper form when visiting medical institutions
and pharmacies for the initial delivery2) At the time of revision, promptly provides medical institutions andpharmacies with revised information in paper form, etc.

Medical institutions and pharmacies:
Obtain the latest package insert
information through the code○○○○ Tablets 10 mg
Notice of Revision ofPrecautions

Medical institutions and pharmacies○○○○ Tablets 10 mg

Also provides information in paper form
MRs, etc.

Page 27https://www.mhlw.go.jp/content/11121000/000682481.pdf

Schedule, etc.
December 1, 2022

August 1, 2021

March 31, 2021

August 1, 2023

Transitional period

Digitization of
information on
precautions, etc.

Post package insert on
PMDA website

Indicate the code on the container orwrapper of the product (transitional period)

Accommodations
for digitization of
information on
precautions, etc.

Improvement oftraceabilityPage 28

Completion ofmodification of
PMDA's website(Within the fiscal
year)

Start of app
service

Package inserts in paper form can be packaged with the product
Early trial use
of app

Provided
electronically ** Package insert in paper form willcontinue to be packaged with products
purchased directly by consumers

Full-scale use of app

Dissemination to healthcare professionals by industry andgovernment, app DL announcement, etc.

Indicate the code on the container orwrapper of the productPrint code according to PMD Act** The contents accessed through the code will be the sameas in the notification

Related systems are being developed to enable access to information on precautions, etc. published by PMDA
by reading codes.
In order to ensure a smooth transition, information will be provided to marketing authorization holders andmedical and pharmaceutical providers through seminars, etc.

https://www.mhlw.go.jp/content/11121000/000682481.pdf

Thank you very much.

Page 29