Experience of Japanese RegulatorExperience of Japanese RegulatorExperience of Japanese RegulatorExperience of Japanese RegulatorWWWWorkshop2: Regulating medical devicesorkshop2: Regulating medical devicesorkshop2: Regulating medical devicesorkshop2: Regulating medical devices

–––– the involvement of stakeholdersthe involvement of stakeholdersthe involvement of stakeholdersthe involvement of stakeholders

Madoka Murakami, PhD

Pharmaceuticals and Medical Devices Agency (PMDA)

Japan

Agenda

• Introduction

• Systems for communication among stakeholders in Japan

• Science board

• Pharmaceutical Affairs Consultation on R&D Strategy

• Collaboration plan for Acceleration of Medical Device Review

• HBD: unique platform for communication and activity among stakeholders in US and Japan

3

3

Kansai Branch

Date of Establishment : April 2004

� Scientific Review for Drugs & Medical Devices

� GCP, GMP Inspection

� Consultation on Clinical Trials

� Safety Measures

� Relief Services

Major Services

Unique Three-pillar System Securing Nation’s Safety

Safety

Review

Relief

Japanese

citizens

Pharmaceuticals and Medical Devices AgencyIncorporated administrative agency

Regulatory Authorities in JAPAN

� Scientific Review for Drugs & Medical Devices

� GCP, GMP Inspection

� Consultation on Clinical Trials etc.

� Final Authorization of

applications

� Publishing Guidelines

� Advisory committee

� Supervising PMDA Activities

PMDAMHLWPharmaceuticals and Food Safety Bureau, MHLW Pharmaceuticals and Medical Devices Agency

5

5

To Improve Public Health

Review Safety Relief

Agenda

• Introduction

• Systems for communication among stakeholders in Japan

• Science board

• Pharmaceutical Affairs Consultation on R&D Strategy

• Collaboration plan for Acceleration of Medical Device Review

• HBD: unique platform for communication and activity among stakeholders in US and Japan

Establishment of the Science Board

The Science Board was established in May 2012 to discuss how PMDA

can better cope with products with advanced science & technology,

in each developmental stage such as basic research, development

support, product review, and post market safety measures.

Office of Review

Innovation

Pharmaceutical

consultation on R&D

Strategy

Basic

Research

Seeds of

new

drug /

medical

devices

Non-clinical

tests

Clinical

TrialQuality Tests

Practical use

Innovative

medical

products

Offices of Review (Drugs & Medical Devices), Office of Safety

Clinical Trial

ConsultationReview

Review ApprovePost

Marketing

Post Marketing

Safety Measure

Board members

Academia (Knowledge of the Latest Innovative Technologies)

Communication with Academia

- The Science Board -

7

8

Work of the Science Board

The First Term (2012- 2014 March) Subcommittees’ report

1. Current Perspective on Evaluation of Tumorigenicity of Cellular and Tissue-

based Products Derived from iPSCs and iPSCs as Their Starting Materials

(Aug. 21, 2013)

2. Summary of Discussion on Non-clinical Pharmacology Studies of

Anticancer Drugs (Dec. 10, 2013)

3. Summary of the discussion on assessment of the current status of

personalized medicine relating to drug development and review (Mar. 11,

2014)

The Second Term (2014 April - ) Subcommittees1. Placebo-controlled trials

2. Utilization of non-clinical testing

3. Application of numerical analysis for non-clinical testing

4. Evaluation of medical devices for pediatric use

5. CPC (Cell Processing Center)

9

Communication with developer

Pharmaceutical Affairs Consultation on R&D Strategy

Practical Use

Innovative

Products

Basic Research

Pharmaceuticals and

Medical Devices

candidates

Non-Clinical

Study

Quality

StudyClinical Trial

Valley of Death -Shortage of funds, Knowledge on Regulation and developmental strategy

（Up to POC studies）

* Further studies are handled by the Regular Consultation

Consultation on quality and

battery of pre-clinical,

including examining

tumorigenicity,

biological ingredient safety

Consultation on

endpoints or sample

size of early clinical trial

Strategic Consultation

Communication with Manufactures

Action Program for Acceleration of Medical Device Reviews

(FY2009 – FY2013)

Collaboration Plan for Acceleration of Medical Device Review

(FY2014 – FY2018)

Increase staff 35 → 104 (FY2013)

Formulate Approval standards/ Good Review Guideline

3-track Review System

Transit by FY2011

Government & Industry Dialogue 2/year （（（（from FY2009））））

Action program for Acceleration of Medical Device Reviews

•New Medical Devices (Standard 14 mos. Priority 10 mos.)

•Improved MD with clinical data: 10 mos.

w/o clinical data: 6 mos.

•Generic MD 4 mos. (FY2013)

90% Tile Review Times for Medical Devices(Total time in submission cohort)

Category FY 2009 2010 2011 2012 2013

New 100% 92.0% 95.2% 96.3% 46.9%

Improved (w clinical data) 100% 96.1% 96.0% 100% 75.0%

Improved (w/o clinical data) 100% 95.7% 94.2% 88.9% 44.8%

Generic 98.4% 96.2% 97.2% 95.6% 63.9%

Completion rate

26.8

19.418.4

14.8

3.7

29.332.1

23.8

17.4

10.5

29.226.1

19.8

13.6

8.7

20.4

22

14.6

10.57.1

0

5

10

15

20

25

30

35

2009 2010 2011 2013 2013FY

Agenda

• Introduction

• Systems for communication among stakeholders in Japan

• Science board

• Pharmaceutical Affairs Consultation on R&D Strategy

• Collaboration plan for Acceleration of Medical Device Review

• HBD: unique platform for communication and activity among stakeholders in US and Japan

Harmonization By Doing (HBD)

•HBD Think Tank West 2014 (September 19, Washington DC, US)

•HBD Think Tank East 2015 (September 18, Kyoto, Japan)

•HBD Think Tank West 2016 (October 30, DC, US)

Steering

Committee

Working

Groups

�WG1:Global Cardiovascular Device Trials

�WG2: Study on Post-market Registry

�WG3:Clinical Trials Infrastructure and Methodology

�WG4: Regulatory Convergence and Communication

Report, RequestGuidance/Suggestion

FDA MHLW/PMDA DCRI JAG AdvaMed JFMDA

Activity between Japan and USA to develop global clinical trials and

address regulatory barriers that may be impediments to timely device

approvals. (since 2003)

15

Regulatory

Decision

Regulation,

Procedures

Technical

Requirements

Regulatory

Technical

HBD

Theoretical

General

Practical

Specific

Concept of HBD

Prod

uct

Cate

gory

Applica

tion in

JP

Approv

al in JP

Applica

tion in

US

Approval in

US

Device Lag

(Mo.)

Application

Lag (Mo.)

Clinical data

submitted to

PMDA**

A CA,

DES

2005.12

.22

2007.03.

30

2003.06.

19

2004.03.04 36 30 US study + small

Japanese study

B CA,

BMS

2007.03

.29

2008.07.

04

2004.04.

12

2004.09.10 46 35 Foreign*** study

C CA,

DES

2008.03

.31

2009.01.

28

2006.03.

08

2008.10.10 3 24 Foreign study

D CA,

DES

2007.05

.09

2009.03.

24

2006.11.

20

2008.02.01 13 6 Foreign study + small

Japanese study

E CA,

DES

2008.05

.29

2010.01.

08

2007.06.

01

2008.07.02 18 11 US study + Japanese

study

F CA,

DES

2010.07

.14

2011.09.

05

2010.06.

17

2011.04.22 5 1 Foreign study

G SFA,

DES

2010.07

.30

2012.01.

24

2010.06.

04

2012.11.14 -10 1 MRCT (US, Japan,

Germany)

H CA,

DES

2011.03

.15

2012.02.

08

2011.03.

28

2011.11.22 3 0 MRCT

I CA,

DES

2011.08

.18

2012.09.

06

2011.12.

05

2012.06.01 3 -4 MRCT +Japanese

study

J SFA,

BMS

2013.12

.06

2015.01.

14

2014.03.

11

2015.05.22 -4 -3 MRCT (US, Japan) +

Japanese study

Major vascular stents approved in US & Japan (2007-12)

HBD related product

Outcome from HBD WG4: Study

of comparison between

• US GCP,

• JGCP and

• ISO 14155:2011

Available to access: JFMDA

News. 81:2013(April)

P46-56

(in Japanese).

17

© January 2013 by the Regulatory Affairs Professionals Society

(RAPS)

Building Trust

Patient

Industry

Regulatory

Authorities

Academia

???

Any questions?

Thank you!Thank you!Thank you!Thank you!

Madoka Murakami, Ph D

murakami-madoka@pmda.go.jp

https://www.pmda.go.jp/english/index.html

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