pmda updates: approach to making further...

1Pharmaceuticals and Medical Devices Agency

PMDA Updates:Approach to Making Further Progress

Yasuhiro Kishioka, Ph.D. Principal Reviewer

Office of Cellular and Tissue-based Products Pharmaceuticals and Medical Devices Agency (PMDA)

The views and opinions expressed in this presentation are those of the presenter and should not necessarily represent the views and opinions of the PMDA.

CMC Strategy Forum Europe 2015, May 4-6, 2015, Radisson Blu Scandinavia Hotel, Copenhagen, Denmark


Knowledge without wisdom is

a load of books on the back of an ass.(Japanese Proverb)


Introduction Regulatory Updates in Japan Approach to Making Further Progress

Outline


Japan’s Performance on NDA Review

Reference: The impact of the changing regulatory environment on the approval of new medicines across six major authorities 2004-2013. CIRS (Centre for Innovation in Regulatory Science) R&D 55

http://cirsci.org/node/73


3rd 5-year mid-term plan of PMDA (FY2014-2018)

Shortening the time from early development to approval improvement in consultation system, accelerated

review process, etc.

Providing high quality review/consultation services promotion of regulatory science research, etc.

Enhancing safety measures utilization of medical information database

Embracing globalization information transfer with the world


PMDA Staff Size

0

200

400

600

800

1000

1200

2004.4 2005.4 2006.4 2007.4 2008.4 2009.4 2010.4 2011.4 2012.4 2013.4 2014.4 2018

Administrative part Safety DepartmentReview Department Planned

319256

648

521

678605

753

341

426

291

708

1065Administrative part

Review Department

Safety Department

Planned

2005 2006 2007 2008 2009 2010 2011 20122004 2013 2014 2018



Outline


SAKIGAKE strategy MHLW drew up a new strategy to lead the world in the

practical application of innovative medical products in 2014.

http://www.mhlw.go.jp/english/policy/health-medical/pharmaceuticals/140729-01.html


Two Schemes for the Strategy

SAKIGAKE Designation System(Forerunner Review Assignment System)promoting R&D in Japan aiming at early practical application for innovativepharmaceutical products, medical devices, and regenerative medicines.

Scheme for Rapid Authorization of Unapproved Drugsaccelerating the practical application of unapproved/off-label use of drugsfor serious and life-threatening diseases by expanding the scope of theCouncil on Unapproved Drugs/Off-label Use to include unapproved inWestern countries if it satisfies certain conditions and by improving theenvironment for companies to undertake development of such drugs.

http://www.mhlw.go.jp/english/policy/health-medical/pharmaceuticals/140729-01.html


(Image) Forerunner Review Assignment System

Non clinical studies, Clinical studies

Clinical trials I/II

2 m. 12 m.

Practical application of

Innovative medical products

1 m.

6 m.

③ Priority Review

② Prior-review

① Priority Consultations

④Review Partner System

⑤Strengthening Post-Marketing Safety

【Standard】

【Forerunner】

Consultation on Clinical

trialsphase III study Review

Reim-burse-ment

Post-Marke

ting

Pharmaceutical affairs

consultation for R&D strategy

Non clinical studies, Clinical studies

Clinical trials I/II

Consul-tation

on Clinical trials

phase III study

Fore-runner review assign-ment

Prior review (rolling submission) Review

Post-Marke

ting

※ In some cases, may acceptphase III data during review

Reim-burse-ment

Pharmaceutical affairs

consultation for R&D strategy

The pilot implementation will start very soon!


Flexibility in Post-Approval changes

Standard program(Traditional approach)

Know

ledg

e

Product LifecycleApprovalApproval

Standard program(QbD approach)

?

Residual Risk

Control Strategy

Post-Approval

CMC Considerations for Accelerated Programs

Where is the acceptable Minimum Requirement?


2005 2009 2010 2011 2012

Q&A

Somatropin BS [Sandoz]

Epoetin alfa BS [JCR]

2013

Regulatory History and Status of Biosimilars

Filgrastim BS [F], [MOCHIDA]

Filgrastim BS [NK], [TEVA]

• Application Category for biosimilars• Guideline• Nomenclature rules

Q&ARevision of Nomenclature rules

2014

Filgrastim BS [Sandoz]

Infliximab BS [NK], [CTH]

2015

Insulin glargine BS [Lilly]


Approved IndicationsR.P. Biosimilar

Remicade Infliximab BS

Rheumatoid arthritis (incl. prevention of structural joint damage)

Crohn’s disease

Ulcerative colitis

Intractable uveoretinitis in Behcet's disease

Psoriasis vulgaris, Arthropathic psoriasis, Pustular psoriasis, Psoriatic erythroderma

Ankylosing spondylitis

Comparative study

R.P.: Reference product

Indication extrapolation of Infliximab BS


•Crohn’s disease

Re-examination period of Infliximab

2002 Jan: Approved 2012 Jan: End of ReP

•RA

2003 Jul: Approved 2009 May: End of ReP

•RA (prevention of structural joint damage)

2009 Jul: Approved 2013 Jul: End of ReP•Behcet's disease

2007 Jan: Approved 2017 Jan: End of ReP•Psoriasis

2010 Jan: Approved 2014 Jan: End of ReP•Ankylosing spondylitis

2010 Apr: Approved 2020 Apr: End of ReP•Ulcerative colitis

2010 Jan: Approved 2012 Jan: End of ReP

•Crohn, RA, UC2013 Sep: Submission 2014 Jul: Approved

<Biosimilar (Infliximab BS)>

,ReP: Re-examination period


Consultation for Biosimilars

Fiscal year

No.

of c

onsu

ltatio

ns

2006 2007 2008 2009 2010 2011 2012 20130

5

10

15

20

25

Based on date of application

(from April 1 to March 31)

2014

<Number> <Product type>

(65%)mAbs & Fc-fusion proteins



Outline


Key Enablers

International Cooperation

Communication with Industries


ICH PDG IMDRF IGDRP ICCR

ICH: International Conference on Harmonisation PDG: Pharmacopeial Discussion Group IMDRF: International Medical Device Regulators Forum IGDRP: International Generic Drug Regulators PilotICCR: International Cooperation on Cosmetics Regulation APEC LSIF RHSC : APEC Life Science Innovation Forum RegulatoryHarmonization Steering Committee

OECD MAD : OECD Mutual Acceptance of DataHBD: Harmonization By Doing

ICMRA

ICDRA

ICDRA: International Conference of Drug Regulatory Authorities ICMRA: International Coalition of Medicines Regulatory Authorities

HBDAPEC LSIF RHSCChina-Korea-

Japan Tripartite

OECD MAD

Current International Activities


PMDA’s Contributions in the Asia/WorldAt the Nov. 2014 Summit of Heads of Medicines Regulatory Agencies, enhancement of collaboration among Japan/China/Korea was affirmed.

Confidentiality arrangements* Staff posting Joint

symposium

* Confidentiality arrangements: Arrangements to exchange confidential regulatory information retained by each country

Singapore

Thailand

ChinaFrance

Switzerland

Netherlands

U.K.

Ireland

Japan

Taiwan

Indonesia

Australia

U.S.A.

Brazil

Canada.

EU

Italy

Scheduled to take the office of Vice Chair of the OECD Working Group on GLP in 2015.

Korea


Training for Foreign Regulatory Officers

Pharmaceuticals:1st (Nov. 2010) New Drugs Review2nd (Dec. 2011) GMP inspection3rd (Jan. 2013) Post-Marketing Safety & Relief Services4th (Feb. 2014) Generic Drugs Review5th (Oct. 2014) New Drugs ReviewMedical Devices:1st (Mar. 2014) Medical Device Regulation2nd (Feb. 2015) Medical Device Regulation

NADFC (Indonesia) officials: 5 days, 2013 FDA (US) analyst: 6 months, 2014 NPBC (Malaysia) officials: 1 month, 2014 Thai FDA (Thailand) officials: 5 days, 2014 2014 etc.

Individual Training (including OJT)

PMDA Training Seminar


Key Enablers

International Cooperation

Communication with Industries


Many Channels with Industries Regular Meetings for Exchange of Opinions

WG for Review

WG for Consultation

WG for MRCT WG

for Audit

SWG

SWG SWG

Work Request

Progress Report

PMDA

Integrated Project Team

•MRCT project•….•QbD assessment project•Post-Approval Mfg. Changes project

Integrated Project Team in PMDAhttp://www.pmda.go.jp/english/rs-sb-std/standards-development/cross-sectional-project/0003.html


MHLW Sponsored Science Research

(Example) Outputs (in English)

QOS (2.3.P) mockhttp://www.nihs.go.jp/drug/section3/English%20Mock%20QOS%20P2%20R.pdf

Application Form mockhttp://www.nihs.go.jp/drug/section3/English%20mock%20App.pdf

QOS (2.3.S) mockhttp://www.nihs.go.jp/drug/section3/H23SakuramillMock(Eng).pdf

CTD 2.3.P.2 mockhttp://www.nihs.go.jp/drug/section3/QbD_P2_mock_SakuraBloomTab_E_Feb2015.pdf

(Research on Regulatory Science of Pharmaceuticals and Medical Devices)

ICH Training Material for ICH Q8, 9, 10

Academia

Industries PMDA

Implementation of QbD Approach and Description in QOS and Application Form

Real Time Release Testing Design Space Analytical QbD …Etc.


Knowledge without wisdom is

a load of books on the back of an ass.(Japanese Proverb)


Thank you for your attention!

[email protected] and Medical Devices AgencyOffice of Cellular and Tissue-based Products

Yasuhiro Kishioka, PhD.

Acknowledgements• Colleagues in the Office of Cellular and Tissue-based Products• Colleagues in the Office of International Programs

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