PMDA’s Efforts in Medicinal Area- Cultivate Human Resources &Cultivate Human Resources & Science Board -

Hideo Utsumi, Ph.D.Executive Director, andDirector General of the Office of Review Innovation

25th AnnualDirector General of the Office of Review Innovation Pharmaceuticals and Medical Devices Agency (PMDA)

EuroMeeting4-6 March 2013RAI, Amsterdam

Netherlands

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Today’s Presentation

1. Council for Science and Technology Policy, Cabinet Officey,

2. Establishment of the Science Board3. Current Status of Pharmaceutical Affairs

Consultation on R&D StrategyConsultation on R&D Strategy4. Advancing Regulatory Science and

CCollaboration with Academia

3

Innovation 25 (2006) ← Liberal Democratic PartySeptember 2006 Abe CabinetOctober 2006 Establishment of Committee for the Investigation of Innovation Promotion, Science

Council of JapanIt is said that the word "Innovation" is derived from the Latin "Innovare" (renew) （＝ "in" (within) + "novare" (change) ） In Japanese the word is rephrased to mean technological renovation andnovare (change) ）. In Japanese, the word is rephrased to mean technological renovation and management reorganization or simply renovation or renewal, but innovation also means using new technology and ways of thinking in existing materials and structures to create new value and to make significant changes in society. “Innovation 25” is a long-term strategy initiative for the creation g g y g gyof innovation contributing to the growth with an eye on the year 2025.

（Preventive medicine for individual, Cell & Tissue Products-related technology, advanced nurse-robot, magic bullet for dementia）nurse robot, magic bullet for dementia）

Medical Innovation（November 2010） ← Democratic PartyJapanese Government established a multi-disciplinary group tasked with setting the agendas for medical innovation and research in the country for a ten to twenty-year period, and follow up them up to 50 years.Offi f M di l I ti (Fi t G l Y k N k P t Y i hi M t t ）

4

Office of Medical Innovation (First General；Yusuke Nakamura, Present；Yoichiro Matumoto）

Science & Technology Basic Plan- Aiming at a Nation that is CreativeAiming at a Nation that is Creative

in Science & Technology -

Basic Plan 4th Stage （FY2011 - 2015）

Basic Plan 2nd Stage

Basic Plan 3rd Stage（FY2006 - 2010）

• 25 Trillion Yen

・ 25 Trillion Yen・Promotion of the

Two Major Inno ations as aBasic Plan 2nd Stage

(FY2001 - 2005）• 24 Trillion Yen・Policy Strategically

• Making Promotion Strategy by the filed, Screening Strategic Science Technologies

Innovations as a Pillar of Growth:

Green Innovation & Life Innovation

Basic Plan 1st Stage(FY1996 - 2000）

・17 Trillion Yen

・Policy Strategically focusing on Science Technology

・ Science T h l S t

Science Technologies &National Key Technologies

• Human ResourcesI i R

・Building New R&D System

Technology System Innovation

• Increasing Resources for Competent Researches

Establishment of PMDA

Innovative Medicinal seeds from Academia in Japan

ACTEMRA® Injection (Tocilizumab (r-INN))

p

●Target Identification / Target Validation

f (O ) f

Approved in JAPAN; April 2005(First marketing authorization)

Professor Tadamitsu Kishimoto (Osaka University, Japan) identified IL-6 related to Castleman’s disease (Blood 1989; 74:1360-1367)

●Extensive research & Development

ACTEMRA® (Tocilizumab) is a humanized monoclonal antibody targeting IL-6 receptor developed by Osaka University and Chugai Pharmaceutical Co., Ltd.

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Innovative Medicinal seeds from Academia in Japan

XALKORI® capsules (Crizotinib(INN))

p

Approved in JAPAN; May 2012

●Target Identification / Target Validation

Approved in JAPAN; May 2012(International Birth Date: Aug. 2011)

Professor Hiroyuki Mano (Jichi Medical University, Japan) identified EML4-ALK fusion gene in non-small-cell-lung cancer (Nature 2007; 448:561-6 etc.,)

●Extensive research & Development●Extensive research & Development

XALKORI ® (Crizotinib) is the ATP competitive inhibitor of tyrosine kinase of the Hepatocyte growth factor receptor developed by Pfizer Inc. NH2

H ClN

CH3H

Cl

ClFN

N

7

Cl

HNCrizotinib

Innovative Medicinal seeds from Academia in Japanp

1950 201X

"HAL" (Hybrid Assistive Limb®)

University of TsukubaUniversity of Tokyo

OLYMPUS GASTROCAMERA GT-IHAL (Hybrid Assistive Limb®)

Copyright: The Japan Society of Mechanical Engineers.

8Copyright: CYBERDYNE INC

Today’s Presentation

1. Council for Science and Technology Policy, Cabinet Officey,

2. Establishment of the Science Board3. Current Status of Pharmaceutical Affairs

Consultation on R&D StrategyConsultation on R&D Strategy4. Advancing Regulatory Science and

CCollaboration with Academia

9

Environments surrounding PMDAWhat should PMDA do next in the course of achievement of acceleration?What should PMDA do next in the course of achievement of acceleration?

＜Fiscal Year 2011 Plan＞

品目Total Review Period

Regulatory Review Period

Applicants' time

New Drug

＜Fiscal Year 2011 Plan＞

New Drug（Priority） 9month 6month 3month

New Drug（Standard） 12month 9month 3month

Apr 1st Apr 1st

Increasing Number of Executives and Regular Employees

FY 2007 FY 2011

【Total Review Period New Drug(Priority)】(median)

＜Record＞Apr 12012

Apr 12012

Total 256 678Total 12.3mths 6.5mths(9.2mths)

Regulatory 4.9mths 4.2mths (4.1mths)Applicant 6.5mhs 2.0mths(5.0mths)Number 20 50(18)

Review Department

Safety

154

29

438

136Number 20 50(18)

FY 2007 FY 2011Total 20.7mths 11.5mths

【Total Review Period New Drug(Standard)】(median)

Safety Department 29 136

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Regulatory 12.9mths 6.3mthsApplicant 7.9mths 5.1mthsNumber 53件 80件

Issues of PMDA

① Being required to conduct review and consultation understanding of the research activities in stat-of-the-artunderstanding of the research activities in stat-of-the-art technologies such as antibody drug, Companion diagnostics, artificial heart, cellular & tissue-based products, medicine, , p , ,cancer vaccine etc.,.

② Being required to adequately conduct review and consultation ② e g equ ed to adequate y co duct e e a d co su tat oin the state of the art technologies from early stage of development for prompt supplying of products among the medical work front,.

③ Requiring a cooperation with academia, to continuously train for reviewers to catch up accelerating innovative technologies and contribute practical use of state of the art technologies.

11Science Board

For PMDA To Be More Science-BasedBasic

Research

Seeds of

Non‐clinical tests

CTQuality Tests

Practical use

Innovative Review Approve

Post Marketing

Pharmaceutical consultation on R&D Strategy

Seeds of new

drug / medical

medical productsClinical Trial

Consultation Review Post Marketing Safety MeasureR&D Strategymedical

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

y

E t bli h t f th S i B d

Office of Review Innovation

Establishment of the Science BoardThe Science Board was established in May 2012 to discuss how PMDA can better cope with products with advanced science & technology, in 

h d l l h b i h d l

B d b

each developmental stage such as basic research, development support, product review, and post market safety measures. 

AcademiaBoard members

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Science Board and Office of Review InnovationOffice of Review Innovation

Office of Review Innovation

Director G l

Science Board

・Committee members: External experts from AcademiaGeneral

Associate Secretariat

p

・Declare Conflicts of Interest

・Not involved in the Review Process of individual products

Committee

Recommendation on PMDA tasks

Director General

Secretariat Director

MissionImprovements in the scientific aspects of review

Subcommittee

Reform PMDA reviews and related services based on science with consideration for actual medical practices Subcommittee

Deliberation on problems in each fieldCollaboration with PMDA working team (RS research, guideline development, etc.)

ac ua ed ca p ac ces

PMDA Office g p )

PharmaceuticalsMedical Devices

Bio-based Products

Cell & Tissues-Based products

Projects Across Multi-Offices in PMDAReview/Audit/

Inspection

RS

PMDA Office

Safety

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Inspection SGD

RS: Office of Regulatory ScienceSGD: Office of Standards and Guidelines Development

Rotating Science Board memberOutstanding researchers who have knowledge and experience concerning scientific evaluation on Pharmaceuticalsscientific evaluation on Pharmaceuticals and Medical Devices

Science B dBoard2years/person

Discuss how PMDA can better cope with products with advanced science & technologyLeading development for

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advanced science & technologyLeading development for innovative technology

Strengthen Review System in PMDA

Set up Office of Review Innovation (April 2012) and the Science Board  (May 2012)

‐ Enhance partnership with academia ‐

Science Board

Subcommittee（Drug）

Subcommittee（Medical Device）

Concerned with

Associate director GeneralDirector General, ffi f i

Subcommittee（biologics）

Subcommittee（cell-and tissue-based products）

Concerned with Academia

Executive Director Center for product evaluation

Secretariat Director

Deputy Associate director GeneralOffice of Review

Innovation

Chief

Executive Director

(Review・Research）

Director Center for product evaluation

Deputy Center Director for medical Devices

S i E i

Review Section

Deputy Center Director for Cellular-and Tissue-based products

Executive

Relief Section

Safety Section

Senior Executive Director

（Technology Management）

Executive

Special Assistant

Tissue based products

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Administration Section

Executive Director

（General Coordination）

Main Roles of Science BoardE t ti I

Committee Thrashing out Science & Technology potentially applied to innovative

Extracting Issue

products(Drug/Medical Device) in the near future among the Cutting-edge of Exploratory Research,

On the advanced scientific technology, Requesting the subcommittee to discuss further for providing review and consultation services appropriatelydiscuss further for providing review and consultation services appropriately in PMDA.

Subcommittee On the subject of advanced scientific technology profound

Request

Review Offices On the subject of advanced scientific technology, profound researchers and the PMDA reviewers deliberate assessment tools in order to provide review and consultation services appropriately.

Review OfficesStudy meetings with profound researchers

Exchange Opinions

Committee Review OfficesProblem consciousnesses in PMDADiscussion on the proposed subjects

Coach for issues

Problem consciousnesses in PMDAAnxious to exchange views on

subjects with the Science Committee.

Discussion on the proposed subjectsRequesting adequate subcommittee

to discuss further for the issues.Propose

Request

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SubcommitteeProfound researchers and the PMDA reviewers deliberate the referred issues from the Science Committee.

Exchange Opinions

Request

1st Fiscal Year Activities

Jun NovOctSepAugJuly Dec Jan Feb Mar

2012 2013

Committee

Subcommittees

Pharmaceuticals

Medical DevicesMedical Devices

Bio-based Products

Cell & Tissues-Based products

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Possible Issues on Science Board

Under Discussion

Pharmaceuticals & Bio products• Discussion about personalized medicine

N li i l Ph l t di ti h ti l• Nonclinical Pharmacology studies on anticancer pharmaceuticals

Medical Devices• Discussion about

• Registry for Medical Device• Category of application for Generic Medical Device• Category of application for Generic Medical Device• Development for combination product

Cell- & tissue- Based productsCell & tissue Based products• Discussion about

• Tumorigenicity

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• Requirement for CPC

Today’s Presentation

1. Council for Science and Technology Policy, Cabinet Officey,

2. Establishment of the Science Board3. Current Status of Pharmaceutical Affairs

Consultation on R&D StrategyConsultation on R&D Strategy4. Advancing Regulatory Science and

CCollaboration with Academia

19

Pharmaceutical Affairs Consultation on R&D Strategygy

Valley of Death -Short of funds, Knowledge on Regulation and development strategy, g g p gy

Strategic ConsultationPractical

Use

Basic Research

Pharmaceutical and

Strategic Consultation 

Innovative Products

Pharmaceutical and Medical Devices

candidatesNon-

Clinical Study

Quality Study

Clinical Trial

Up to the levelf POC diStudy of POC studies

* Further studies are handled by the Regular

Consultation on quality or toxicity study of biologics,

Consultation on endpoints or sample size

Consultation

20

y y gcell-and tissue-based products

p pof early clinical trial

Flow of R&D Strategy Consultation

Regulation Data Package Discussion

I t d tPre- Face-to-Face

Introductory Consultation(No Charge)

Consultation(No Charge)

Consultation (charged)

Binding(No Charge) - Not binding- 30 minutes

- Binding- Written record to Applicant- 2 hours

331 54370

331Consultations

54Consultations

Consultations

(7/1/2011 – 12/28/2012)21

Today’s Presentation

1. Council for Science and Technology Policy, Cabinet Officey,

2. Establishment of the Science Board3. Current Status of Pharmaceutical Affairs

Consultation on R&D StrategyConsultation on R&D Strategy4. Advancing Regulatory Science and

CCollaboration with Academia

22

Program of Collaborative Graduate Schools（MEXT）Graduate Schools（MEXT）

１．SummaryIt i f th d ti l d h th d f thIt is one of the educational and research method for the education in graduate schools to take advantage of utilities and/or human resources of extramural National Institutes and/orand/or human resources of extramural National Institutes and/or private laboratories which conduct higher level research.

２．Position of the systemA graduate school may, when deeming it to be effective from an d ti l t d i t d t h l t d t ll t t keducational standpoint, graduate school students allow to take

the necessary research guidance in extramural laboratory etc., (Article 13 in the requirements for establishing graduate schools)(Article 13 in the requirements for establishing graduate schools). The Program of collaborative graduate schools is systematically implement in this system.

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Program of Collaborative Graduate SchoolsGraduate Schools

ＰＭＤＡGraduate

Collaboration

ＰＭＤＡ schoolConclusion of

•• PMDA StaffsPMDA Staffs–– Engaging on education/research in the university asEngaging on education/research in the university as

Conclusion of agreement

Engaging on education/research in the university as Engaging on education/research in the university as visiting professor etc.visiting professor etc.

–– Conducting the research and pursuing Ph.D. as graduate Conducting the research and pursuing Ph.D. as graduate g p g gg p g gstudentstudent

•• Graduate school studentsGraduate school students–– Accepted graduate students from university are provided Accepted graduate students from university are provided

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p g y pp g y pfor research guidance learning about PMDA’s operation for research guidance learning about PMDA’s operation and pursing Ph.D.and pursing Ph.D.

Program of Collaborative Graduate SchoolsGraduate SchoolsAgreement with 15 Universities (as of November, 2012)

Yamagata University

M hi U i it University of Tsukuba

C

Musashino University

Kyoto Pharmaceutical University Chiba University

Teikyo University

UniversityOkayama University

Yokohama City University

Shujitsu University

K b U i it Shi k P f t lGifu Pharmaceutical

University

Kobe University Shizuoka Prefectural University

Osaka University Nagoya University

25

UniversityGifu University

Osaka University Nagoya University

医療イノベーションプロジェクト厚生労働省Enhancement on approval review / safety measures in response to the progress of technology (MHLW New Budget FY 2012：2.1 billion yen)

Promoting practical use of innovative drug, medical device, Cell- & Tissue-based product

（１）Enhancement on Approval Review/ Safety Measure in Response to the Progress of Technology 【1.2 billion yen】

○ Develop draft guideline/guidance based on Regulatory Science ○ Promote human resource exchange between PMDA & research institutes

（２）Developing guideline/guidance for innovative drug/medical device/biologics to streamline regulatory review based on Regulatory Science 【366 million yen】

Research I tit ti P l

Develop Guidelines

streamline regulatory review based on Regulatory Science 【366 million yen】

NIH

Establishment on approval review/safety measures

Institutions Personal Exchange

SupportCultivate Human Resource

MHLW

（３）Strengthen measure for the safety of unknown risk for innovative technology 【0.35 billion yen】

Resource

（４）Dealing with globalization of production and distribution of Drug, Medical Device, Cell- &Tissue-based product 【0.18 billion yen】

Promoting of personal exchangeDrug

・Cancer / Alzheimer Disease / Pediatric

北海道大学大学院薬学研究院

京都大学大学院医学研究科

北海道大学大学院医学研究科

・Biomarker・Gene therapy/Nucleic acid medicine / nanotechnology

東北大学大学院薬学研究科

大阪大学大学院薬学研究科

東北大学大学院医工学研究科

大阪大学大学院

京都大学ｉＰＳ細胞研究所

Medical Devices・Innovative Therapeutic apparatus・Combination productQuantitative non clinical Evaluation

筑波大学医学医療系

国立循環器病研究センター 国立がん研究セ

大阪大学大学院医学系研究科

国立がん研究センター中央病院

Cell & Tissues

・Quantitative non-clinical Evaluation・Endoscope

東京大学医学部附属病院

研究センタンター東病院

千葉大学大学院医学研究院

早稲田大学（先端生

九州大学大学院医学研究院

・iPS / ES cells・Stroke / Spinal Cord injury・Clinical Path Initiative・Establish on Reflection Paper for

附属病院

名古屋市立大学大

東京大学大学院工学系研究科

先端医療振興財団

命医科学センター）

国立成育医療研究センター・病院

国立成育医療研究

Exchanging program in FY2012 Planning employment for 18 researchers from university, Research

Establish on Reflection Paper for evaluation

名古屋市立大学大学院薬学研究科 国立成育医療研究

センター

27

g p y y,Institute etc., as accepted graduate students

Planning temporary transfer from 28 PMDA staffs (including non-regular staff)to University, Research Institute etc..

Summaryy

• Science Board was established to be more science based review / consultation in PMDA.

• Pharmaceutical Affairs Consultation on R&D Strategyffis offering consultation to innovative products

developed by academia/venture businesses.

• Exchanging program between Academia and PMDA ill lti t h d l d l d ftwill cultivate human resources, and also develop draft

guideline/guidance.

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Thank you for your y yattention !

http://www.pmda.go.jp/29