Global Cooperation

by Regulatory Authorities

and Japan’s Activities

Kazuhiko Mori, MSc

Councilor for Pharmaceutical Affairs,

Ministry of Health, Labour and Welfare (MHLW)

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温故知新

Learning from the past

to prepare for the future

12th Summit & ICMRA in Kyoto

~Key Concept~

Right: Dopaminergic neurons derived hrom human iPS cell

Asuka Morizane, Center for iPS Cell Research and Application, Kyoto University 2

1. History of Global Regulatory

Cooperation

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ICDRA: International Conference of

Drug Regulatory Authorities

WHO convened conference in 1980 to promote

exchange of information and collaborative

approaches by regulatory authorities

More than 100 countries, 300 people

Every 2-3 years: 1st meeting in US (1980), …, 4th in

Japan (1986), ..., 17th in South Africa (2016), 18th in

Ireland (2018)

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ICH International Council for Harmonisation

of Technical Requirements

for Pharmaceuticals for Human Use

• Founded in 1990 by US, EU and Japan

• Harmonisation initiative for new drugs by

regulators and pharmaceutical industry

• Reformed to be a global organization in 2015

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ICH Successes (1) 1996GCP (Good Clinical Practice)

Clinical trials conducted in one ICH region can be utilisedin other ICH regions by setting the common standards on science and ethics.

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ICH Successes (2) 2000/2002CTD/eCTD (Common Technical Document)

CTD

eCTDReview

ICH

Guidelines

CTD brings together all Quality, Safety and Efficacy information in a common, harmonised format, accepted by regulators in all ICH regions. It has revolutionised regulatory review processes for regulators and industry.

Review

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Expansion of ICH Members

Founding Members

JapanMHLW/PMDAJPMA

USFDAPhRMA

EUEC/EMAEFPIA

Swissmedic Health Canada

＋Observers

1990~

2014~

2016/17~

ANVISA

MFDS

CFDA

BIO

WSMI

IGBA

Standing Members

Members

ICH Reform: 2015

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Enhanced ICH Activities

Original Concept: To prevent unnecessary duplication of animal

testing and clinical trials in humans To reduce cost of development and speed up

marketing approval process

The world’s leading forum of drug regulation: Developing guideline on MRCTs GCP Renovation for various study design and data

source Innovation in manufacturing techniques

27 years

Establishments of various specific initiatives

GHTF (1992-)/ IMRDF (2012-) for

harmonizing medical device regulations

PIC/S (1995-) for harmonizing inspection

procedures and facilitating communication

IPRF (2008-) for exchange of information and

regulatory cooperation for pharmaceuticals

IGDRP (2011-) for promoting collaboration and

convergence in generic drug regulations

APEC-LSIF-RHSC (2009-) for regulatory

convergence by promoting ICH and other

international guidelines in the APEC region

… and there are several others.10

Still remaining global public health issues

There are many issues unaddressed yet:

Innovative technologies

AMR

Counterfeit drugs

Emergency situation e.g., infectious diseases, disasters

Regulatory System Strengthening

Soaring cost of R&D, Price, and Access

etc…

Recognition of the need of top-level,

comprehensive initiative to effectively address

various issues and complement existing initiatives11

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Summit: started in 2006; consists of the heads of 23 regulatory

agencies; chaired by a host country; and discusses timely global

public health issues; closed discussion

ICMRA: started in 2012; overlapped members with Summit;

chaired by MHRA (UK) at present; and addresses strategically

important topics; publishes outcomes

Closely linked

Establishments of Summit and ICMRA

Joint actions in public health emergencies

ICMRA took joint actions

against Ebola/Zika virus outbreaks.

Consolidated Joint ICMRA

statement Ebola

- Sep. 4, 2014

ZikaVirus Disease Press

Release - Feb. 9, 2016

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12th Summit & ICMRA 2017 Outcomes

Merger of Summit and ICMRA

12th Summit

・Regenerative Medicine Products: Promote discussion

for international regulatory convergence

・Real World Data: Promote information exchange on the

use of RWD such as through international symposium

・AMR: Regulators’ roles including clinical evaluation guideline

・Counterfeit drugs: More collaborated network by

Regulators and WHO

ICMRA

・Innovation: Project launched, e.g., Horizon Scanning

・Supply Chain Integrity: Report on Track & Trace Systems

・Pharmacovigilance: Report on the use of Big Data

・Emergency: Network by Regulators and WHO 14

Future Prospective of Global Cooperation

“Patient Access” is the fundamental goal – a shared view.

Speed and Reasonability are both important factors for access.

Access is increasingly important in global aging society.

Regulation necessarily has cost implication.

Regulation should not be a barrier to access. It should be transparent and predictable.

Global regulatory cooperation will aim to address the access issue.

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2. Japan’s Activities

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Chronology of Japan’s International Activities ~ Together with Global Cooperation ~

Multilateral initiatives:

ICDRA:1980-, the host in 1986

ICH:1990-, GHTF: 1992- and other initiatives

Summit:2006- & ICMRA: 2012-, the host in 2017

Bilateral cooperation:

• Confidential Arrangements: 2004-

• Memorandum of Cooperation: 2009-

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“Drug Lag” – Societal demand to resolve

1,417 days（＝approx. 4 years）

915days

757days

620 days 583 days538 days 512 days 505 days

Japan France Denmark Germany Sweden Switzer-land

UK US

In 2006, new drug marketing in Japan lagged on average 4 years behind the

initial global launch, a gap of around 2.5 years over the US, the country with

the smallest lag.

2.5 years lag

PMDA was required to implement full-organizational

reform and enhancement of its performance.

History of Acceptance of Foreign Clinical Data

1. Until Early 1990s

Limited use of foreign clinical data.

2. Late 1990-Early 2000

Extrapolating foreign clinical data and bridging study based ICH E5: Ethnic Factors in the Acceptability of Foreign Clinical Data

3. Later 2000s-Japanese guidelines on Multi-Regional Clinical Trials

(MRCTs) in 2007, 2012, 2014

4. Current (2017)Developing ICH E17 Guideline: General principles on

planning/design of Multi-Regional Clinical Trials

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SAKIGAKE Designation System

1st round pilot designation (Oct., 2015)

6 Pharmaceuticals, 2 Medical Devices, 3 Regenerative Products

2nd round pilot designation (Feb. & Apr., 2017)

5 Pharmaceuticals, 3 Medical Devices, 1 In-Vitro Diagnostic, 3 Regenerative

Products

3rd round pilot: Currently open to application (Oct. 5 ~ Nov. 22, 2017) 20

Exploratory clinical trials

ADR reportsPost-market Surveillance

Confirmatory

clinical trials

Exploratory clinical trials

ADR reportsPost-market Surveillance

Approval Conditions・Post-market reconfirmation of

safety and efficacy (including by use of Real World Data)

・Limitation on institutions for appropriate clinical use

Approval

Review

Ap

pro

val

To realize early access to innovative treatments that are: For severe diseases with limited choice of treatments Difficult to conduct confirmatory clinical trials due to small number of

patients or prolonged follow-up period

Standard Approval Review

Approval

Review

Ap

pro

val

Conditional Early Approval System

・Early application based on the results of exploratory clinical trials and other data

・Priority Review

Conditional Early Approval System for Pharmaceuticals<Implemented on Oct. 20, 2017>

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Market - Use

Conditional Early Approval System for Medical Devices

Accelerate approval of MDs in high clinical needs by balancing the pre- and post-market requirements, based on the lifecycle management of the MDs.

Market - Use

Collection of clinical

data

Long period

Collection of clinical data

Partial change application (e.g.

expanded indication, etc.)

- Implementation of Post-market Risk Management Measures- Data collection to confirm use results, long-term performance

Review

Post-market Risk

Management Plan (draft)

Planning Post-market

Risk Management

Conditional Early Approval for Innovative MDs

Cooperation with academia

Present

Review

Cooperation with academia

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Approval

Approval

<Implemented on July 31, 2017>

Tohoku Univ.

NTT hospital groupTokushukai group

7 hospitals

3 hospital

groups(incl. 16

hospitals)Kyushu Univ.

Saga Univ.

Kagawa Univ.

Univ. of Tokyo

Chiba Univ.

Hamamatsu Univ.Kitasato Univ.

MID-NET (Medical

Information Database

Network) is a project to establish

the DB network for MIHARI Project

to utilize electronic healthcare data

for drug safety.

On-going projects for

the use of Real World Data

CIN (Clinical Innovation

Network) is an infrastructure

to support conducts of efficient

clinical trials using patient’s

registered information.

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・ Plan, design and coordinate training for Regulatory Authority

staffs (established in April 2016)

・ Provide training opportunities including on-site training

・ Help raise the level of Regulations in Asia and the world.

・ In FY2016, 161 regulators from 27 countries/regions participated.

Asia Training Center for Pharmaceuticals and

Medical Devices Regulatory Affairs

Lectures, case studies,

and on-site training

Outside Japan

Establishing a centralizedtraining center for multi-regional clinical trials

APEC regions

Training seminar seminars to Regulatory

Authority members by PMDA

PMDA Office

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Conclusion

Global regulatory cooperation has nearly 40 years

history originating from ICDRA. Various specific initiatives

followed and succeeded. (e.g., ICH)

Still remaining public health issues necessitated a top-level

initiative by the regulatory authorities. Summit & ICMRA,

with the merger, aims to address global public health

issues. (e.g., Innovation, AMR and Counterfeit drugs)

Japan has been together with the history of global

cooperation, which facilitated the improvement of

regulatory performance.

All the players in good

harmony

Thank you for your attention

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