the future prospects of pmda · the future prospects of pmda international symposium on past,...

The Future Prospects of PMDA

International Symposium on Past, Present and Future of Molecular Pharmacokinetics

Jan 17, 2012

Hideo Utsumi, PhDExecutive Director,

Pharmaceuticals and Medical Devices Agency (PMDA)

(Director, Innovation Center for Medical Redox Navigation of Kyushu University)

Disclaimer

• The views and opinions expressed in the following PowerPoint slides include those of the individual presenter and should not be attributed to PMDA.

2

Today’s Presentation

1. As a Researcher of Kyushu University“Innovation of Bio-Imaging and Medical Redox Navigation”

- Development of Novel Imaging for Pharmaceutical Researches- Establish of Innovation Center for Medical Redox Navigation

2. As a regulator of PMDA“PMDA’s Future Prospect”

- Eliminate the issue of “Drug Lag /Device Lag”- Improve safety measures for ensuring public safety and reassurance- Advance Regulatory Science

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

Basic Plan 1st Stage(FY1996 - 2000）

・17 Trillion Yen・Building New R&D

System

Basic Plan 2nd Stage(FY2001 - 2005）

• 24 Trillion Yen・Policy Strategically

focusing on Science Technology

・ Science Technology System Innovation

Basic Plan 3rd Stage（FY2006 - 2010）

• 25 Trillion Yen• Making Promotion Strategy

by the filed, Screening Strategic Science Technologies &National Key Technologies

• Human Resources• Increasing Resources for

Competent Researches

Basic Plan 4th Stage （FY2011 - 2015）

・ 25 Trillion Yen・Promotion of the Two

Major Innovations as a Pillar of Growth: Green Innovation & Life Innovation

Science & Technology Basic Act (Act No.130,1995)

R&D of Bio-imaging in Kyushu Univ. Regulation in PMDA

Location

Here（Fukuoka city in Kyushu Island)

Innovation Center for medical redox navigationKyushu University

JAPAN

http://www.mext.go.jp/english/�

6Cited from: “FY2010 Report: Japanese Fundamental Technology Research – The Shape of Medical Needs in FY2020” by The Japan Health Sciences Foundation (HS)

Dru

g C

ontri

butio

n

Treatment Satisfaction

Prospective Fields where Creation of Innovative New Drugs is Expected

Correlation between Treatment Satisfaction and Drug Contribution (Survey in 2010)

7

2～3 y 3～5 y 5～10 year

toPMDA

Clinical Evaluation

Pre-clinical

Optimali-zation

DiscoveryComds

Drug-Target

5～10

10,000

1

10,000 ～ 25,000>600,000

compounds

Drug-Discovery is long & hard work

Number of Compounds

Death Valley How do we overcome?

New Strategy is needed

toPatients

8

Pre-clinicalEvaluation

Clinical EvaluationBasic &

Translational Research

2～3 y 3～5 y

5～10 year

toPMDA

Clinical Evaluation

Pre-clinical

Optimi-zation

DiscoveryComds

Drug-Target

5～10

10,000

1

10,0005,000～10,000

Long (10-15 years) and large costs (20 M euro)Probability of success is extremely low

New Innovation for Drug-Discovery

Number of Compounds

Pharma Innovation

GovernmentUniversityIndustry

Innovation Center for Medical Redox Navigation (Redoxnavi Center)

Kyushu University Hospital

Faculty of Medical Sciences

Faculty of Pharmaceutical Sciences

Redoxnavi Center

Faculty of Dental Sciences


10

振興調整費Innovation Center for Medical Redox Navigation

1. Supported by the grant from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) during 2008-2017 (6.5M$/year)

2. Collaboration of 4 Faculties (Pharmaceutical Sciences, Medicine, Engineering, and Agriculture) with 8 Industries (6.5M$/year)

3. New Center (2,000 ㎡) was built close to University Hospital.

6F5F

hospitalInstitute of

Clinical MedicineInnovation Center

Researchers from faculty of Medical, Pharmaceutical, Agriculture, Engineering etc. are studying at the same floor and have desks in the same room.→ It is good environment for collaborative Interdisciplinary research.

Innovation Center for Medical Redox Navigation (Redoxnavi Center)

Collablationstaff room

Staff roomFor company

Meeting room

Common Experimental

laboratory

Translational Research

Collaboration Staff room Meeting

Room

CellCulture

AnimalProbeSynthesis

Animal housing facility

Analytical Room

Metabolic/Profiling Group

DDSGroup

Development of New drugs

RedixNavigation and

Endoscopic

Surgery

Bio-medical Redox

Imaging Group

Medical Redox

ImagingGroup

MedicalNetwork Group

Director) Office

Common Experimental laboratory

6th floor

5th floor

Redoxnavi Center

Animal housing facility Probe Synthesis Animal Experiments Cell Culture

1.5T OMRI0.015T OMRIHypersenceLaboratoryL-band EPR

OMRILC-MS MALDI-TOF-MS


12

“Innovation Center for Medical Redox Navigation”

Redox-drugDiscovery

Redox Diagnosis & Therapy

Molecular Imaging

Non/low Invasive In vivo Analysis

Metabolic Profiling In vitro Analysis

Home-page:www.redoxnavi.com

http://www.jeol.co.jp/index.htm�

Free Radical School in Japan 13

In vivo ESR Spectrometers and Imaging

ESR imaging(mouse lung, BBRC1991)

1.2GHz in vivo ESRI(BBRC,1989)

300 MHz in vivo ESRI（Diabetologia,1998)

Commercialized System from JEOL

14

Picture of 1.5T OMRI

1.5 T OMRI,MRI0.02T ESR x 3

1.5 T OMRI, MRI

0.02T ESR-A1

0.02T ESR-A2

0.02T ESR-B

Magnet & Rotating system

OMRIMRI OMRIMRIPhilips 15mT OMRI Developed 1.5T OMRI

OMRIMRI OMRIMRI

振興調整費Newly developed Overhauser-MRI

15

Pharmacokinetics Imaging of Two DrugsUtsumi H et al., PNAS 103(5):1463-1468(2006)

15N-carbamoyl-PROXYL 14N-oxo-TEMPO

10mM 14N-oxo-TEMPO

300mM 15N-carbamoyl-PROXYL

0.0

0.3

0.6

0.9

0 2 4 6 8 10 12 14time (min)Re

lativ

e In

tens

ity (a

.u.)

Stomach

Bladder

Heart

C)1

2

3

16

OMRI images were obtained (FOV, 32 × 32 mm; matrix, 32 × 32; slice thickness, 30 mm; TR/TE/TESR, 1,200 ms/25 ms/700 ms).

3 h reperfusion

Con.Fiducial markers

Isc. Brain

Redox Imaging of Strokes in Rat BrainYamato et al., Journal of Cerebral Blood Flow & Metabolism (2009)

24 h reperfusion

17

振興調整費

TTC Staining

Fructose-1,6-bisphosphate

Citric acid

N-Acetyl-asparagine

Multi-modality Imaging with OMRI & MS

1.07 min 3.87 min

intensity

6×105

00.7

0D

ecay rate0

11

12

13

0 1 2 3 4 5 (min)

Ln (I

nten

sity

)

DecayCurve

Decay RateImage

control

MS Imaging

control

control

MCAO 24hr

MCAO 24hr

In vivo OMRI

Anal Chem (2010)

J.Cereb.Blood Fl. Met. (2009)

（富士電機と打合せ作成した暫定図面）

Patient APhysician

Examination room

Development of Clinical Overhauser MRI


http://www.fujielectric.com/�

Commercialization of OMRI

Japan Redox Inc.：venture capital

company from Kyushu

University

High Field-type Bench Top-type


20

“Japanese emperor bestows Medal with Purple Ribbon on ARS Editor Hideo Utsumi for

contributions to redox biology”From Dr. Chandan Sen (Chief Editor of ARS)

(November 3, 2011)

Today’s Presentation

1. As a Researcher of Kyushu University“Innovation of Bio-Imaging and Medical Redox Navigation”

- Development of Novel Imaging for Pharmaceutical Researches- Establish of Innovation Center for Medical Redox Navigation

2. As a regulator of PMDA“PMDA’s Future Prospect”

- Eliminate the issue of “Drug Lag /Device Lag”- Improve safety measures for ensuring public safety and reassurance- Advance Regulatory Science

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

in Science & Technology -



System













Establishment of PMDA 22





System













5-Year Strategy 23

1) Concentrated Research Financing2) Nurturing Ventures, etc3) Improvement of the Clinical Research/Trial Environment4) Collaboration with Asian Countries5) Faster and Better Reviews6) Appropriate Assessment of Innovations7) Public-Private Dialogues

24

“Five-Year Strategy for Creation of Innovative Pharmaceuticals and Medical Devices”

To Provide the People with access to the best

pharmaceuticals/medical devices in the world

To boost the pharmaceutical/medical device

industries into the driving force of Japan’s growth

The Measures Aiming at Japanese Origin R&Ds, and Japan’s Participation in International Collaborative R&Ds

April, 2007: MHLW, MEXT, METI, Cabinet Office; Feb, 2009 Revised

25

PMDA Staff Size

0

100

200

300

400

500

600

700

800

2004 2005 2006 2007 2008 2009 2010 2011 2013

Administrative part

Safety Department

Review Department

Planned

751648

605521

426

341319291256

25

Office of Review Administration

Office of Review Management

Office of Medical Devices Ⅰ-Ⅲ

Office of New Drug Ⅰ - Ⅴ

Office of Conformity Audit

Office of OTC/Generic Drugs

Office of Biologics Ⅰ, Ⅱ

Organization Chart of PMDA as of October 2011

Office of Relief Funds

Office of Safety Ⅰ, Ⅱ

Office of GMP/QMS Inspection

Offices of General Affairs/ Financial ManagementOffice of Planning and Coordination

Review

PMS

（Inspections such as GLP/GCP and GPSP）

（GMP/ QMS Inspection)

Chief Executive

Auditor

Auditor

Chief Safety Officer

Staff size: 256 (Apr. ‘04) 648 (as of Apr. ‘11) with ca.1000 external experts

Office of Regulatory Science Operations

Office of International Programs, International Liaison Officers

Chief Management Officer

Chief Relief Officer

JP, StandardsOffice of Standards and GLs Development

26

Senior Executive Director

Executive Director

Executive Director

Director(Center for

Product Evaluation)

Associate Center

Director

Associate Center

Director

Associate Center

Director

Associate Center

Director

Associate Center

Director

2nd Mid-term Plan Targeted review times for New Drug

FiscalYear

Total review time

[months]

Administrative review time

[months]

ApprovedNo.

2007 12.3 4.9 20

2008 15.4 7.3 24

2009 11.9 3.6 15

2010 9.2 4.9 20

Review time for New Drugs（Priority Review items）

Fiscal Year

Total review time

[months]


[months]

2009 11 6

2010 10 6

2011 9 6

2012 9 6

2013 9 6

Review times

27

* The numbers are the medians of the review times of the applications submitted after 2008.

* The targeted review times are the medians of the targeted review times set foreach FY.

2nd Mid-term Plan Targeted review times for New Drug

FiscalYear

Total review time

[months]


[months]

ApprovedNo.

2007 20.7 12.9 53

2008 22.0 11.3 53

2009 19.2 10.5 92

2010 14.7 7.6 92

Review time for New Drugs（Standard Review items）

Fiscal Year

Total review time

[months]


[months]

2009 19 12

2010 16 11

2011 12 9

2012 12 9

2013 12 9

Review times

28

* The numbers are the medians of the review times of the applications submitted after 2008.

* The targeted review times are the medians of the targeted review times set foreach FY.

Pharmaceutical Affairs Consultation on R&D Strategy

Promisingseeds Innovative

medical products

Basic Research

Seeds Search

Seeds ImprovementClinical Trial

Apply for product approval

Pharmaceutical Affairs Consultation on R&D Strategy

Consultation on conducting clinical trials (in operation)

NEW

Necessary CTs / Drug formulation /Efficacy / Validity

( PMDA )

Shorten duration of

study

Improve success

rate

Creation of innovative

medical product

academia ventures

29

Medical Information for Risk Assessment Initiative (MIHARI)

30

Objective: To reinforce / enhance the system for safety information collection and evaluation of medical products

- Ensure access to several kinds of electronic health information

- Develop pharmacoepidemiological methodology to use electronic health information for evaluation of risk for adverse drug reactions

- Develop methodology to use claim data- Make safety information from post marketing studies

electronically available to create a database

31

Development of Electronic Health Information Database of 10 Million Cases

PMDAResearchers

DB

• Electronic Medical Records

• E-Prescription • Lab Test Results

Anonymize

Collaborating Hospitals

Research

Quick Evaluationof Drugs’ Risk &

Benefit

National Supportand Supervision

3rd Party Supervision





System













Promotion of Regulatory Science

For Developments Eying their Exits（Practical Use), for Rapid Processes Leading to Practical Use, and for Ensuring the Efficacy and Safety

Promotion of Regulatory Science Research is Essential

Target for Drug

discovery

SeedsDiscovery

Lead compounds

IdentificationOptimization Non-clinical

Trial Clinical Trial

License out to

IndustryDrug discovery by Academia

R&D by IndustryValley of Death

Regulatory Science is seen as “Science that adjusts science technology outcome to it’s most favorable shape in harmonization between human and society ” that is an essential concept to prove risk/benefit and to ensure safety of pharmaceuticals and medical devices.

Policy recommendations released in 2011 Committee on Pharmaceutical of Science, Science Council of Japan (August 19, 2011)

Promotion of Regulatory Science

33

34

Regulatory Science Research in PMDA

・ Development/Review of Drug/Medical Device

・Safety Measurement

・Relief Service for ADR & Other Infectious Disease

Improve Quality of PMDA’s Operations with More Transparent and Objective Decision based on Clear Evidences

Research & Development

Creation of New Drug

Safety of the people

Venture

BioTech/ Pharma

Patients/Physicians

Public/Payer

Academia

Review

Safety Relief

Program of Collaborative Graduate Schools

35

Yamagata University

University of Tsukuba

Yokohama City UniversityGifu Pharmaceutical

University

Kobe University Chiba University

Musashino University

Agreement with 7 Universities (as of October, 2011)

Visiting Professors:2 Visiting Associated Professor:1

Guest Professor:1 Guest Professor:1

Professor：1

Guest Lecturers：2 Guest Professors:2

(a professorship is scheduled )

36

Thank you for your attention !

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

36

the future prospects of pmda · the future prospects of pmda international symposium on past,...

Documents