アジアにおける開発体制-企業の立場からTomoko Hirohashi. PhD
Director, Clinical Research, Oncology, Pfizer Japan
Miho Yamamoto, Kae Nakashima, Katsushi Namazu

Pfizer Confidential

1Background•

Recently clinical development in China is dramatically growing
Source：Citeline

1000

USJapanChina

900

No. of Industry Trial

800(State Council Doc. No42)700

State Council
Doc. 44

600
500

366

400
276

300
200
100

123
85

177
153

211
175

201

217

2016

2017

02010

•

 Chinese Government initiates
significant regulatory reforms as“ The Innovation Opinion”
containing 36 specific revisions

20142015• Reforming clinical trial management• Accelerating drug device review and approval
process• Balancing development of innovative drugs
and generic drugs• Life-cycle management of drugs and devices• Enhancing drug and medical device review andenforcement force• Implementation of the innovation opinion andcoordination among the relevant
administrative agencies

In addition, basic research and translational research are also advancing
in other Asian countries such as China– China’s 2016-2020 5-year plan prioritizes bio R&D as a key focus area; 2016
allocated 30% of social development budget (Justin C et.al. NEJM. 2014)•Now is the time to think again about
Japan’s position in drug development
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and where should we head

Clinical Research

Basic and Translational Research

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3Clinical Research

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4Clinical Research: Organization and Number of Trials

No. of Ongoing Clinical Trial• ~340 members in Dev-Japan vs 160 members in Dev-China(excluding direct global lines)• Clinical: 50 members in Japan vs 24 members in China
60

5350
40
30

2929JapanChina

209100All DAOncology

Japan has great advantages over China so far;
China has been struggling to participate into global studies
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5Japan has a great advantages over China “ So Far”
<Advantage>：“Matured”• Regulatory advantage– Necessity of Phase 1 before registration trial• Well-organized Japan affiliate (Established reliance from global)– Studies led by Pfizer Japan had “fastest record“ among Project A(project buy-up to protocol finalization and FSFV)• Sufficient capability at study sites– Sufficient experience, including Phase 1 (DLT evaluation etc)
– Speedy start up and commitment (contribution to short cycle time)– GCP compliance and quality• Strong leadership of Japan KOLs in certain areas<Disadvantage>: “COSTLY”• Highest cost for FTE (both internal and CRO cost)• Less performance per CRA/site than other Asian countries• Post marketing requirement (PMS, all case survey etc)
Pfizer Confidential• Regional Specific/Strict requirement
for IVD and CDx

6China has been struggling to participate in global studies
CFDI:Center for Food and Drug Inspections<Advantage>ACLOA: Attributable, Legible, Contemporaneous, Original and Accurate
CCEA: Complete, Consistent, Enduring and Available• Huge potential of enrollment• Performance per a CRA/site is high• Participation into global registration study using Japanese PK &safety data
<Disadvantage>• Slow study start up
One of the KEY focus area of “ The Innovation Opinion” is “Reformingclinical trial management” , which could substantially reduce delays in theapproval of clinical trial applications (Nov 6th, 2017: www.cov.com)• Quality issues (Field inspection detected 28.1% did not meet ALCOA+CCRA)
Intensive training for CRA is requested by the CFDI
The CFDI is expanding and hiring more staff, and the training is more
standardized and consistent (J Evid Based Med. 2018; 11:3-6)• Less experiences of Phase 1 (DLT evaluation)• Biospecimen assay (difficulty to implement companion diagnostics)

Global accepts “Dare To Try” for CHINA
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Now most pharma have strong interest in China

Made the call! China Regulation Reform (SC No. 44/42)• Modernization and standardization to global norms ofregulation• Has shifted from emerging market to innovative
drug/health– Japan is now strengthening use of generics in priority prefectures• Implemented “conditional approval” for innovative drugs
48 products selected as “ Fast Track”
Palbociclib was approved in Aug 2018 with 2 years
acceleration based on Chinese PK study only
• (Will?) improve medical device regulations and harmonize
them with international practices
Global organization proactively includes China into
ongoing/future global registration studies!
Pfizer Confidential1) http://www.ey.com/Publication/vwLUAssets/ey-life-sciences-report-asia-march-2017/$FILE/ey-life-sciences-report-asia-march-2017.pdf

8Considerations•••Advantages• Speed of SSU• Plenty of successful
experiences in clinical
trials (both internal andexternal)••

Advantages
Highest CAGR
Huge potential of accrual
Changing regulatoryenvironments
Big data
Digital health
CAGR: Compound average growth rate

CHINAJAPAN••••

Concerns
Highest FTE (CRO cost)
New drug pricing policy
All case survey
PMSConcerns• Quality (improving!!*)• Custom compliance (importpricing and adjustment)
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9*J Evid Based Med. 2018; 11:3-6

What should we do??
In China, simultaneous development/submission/approval would
become standard like current Japan
Japan needs more cost efficient study management as a first step
– More disruptive idea using IT, digital platform etc• Risk Based Monitoring• eSource, eICD etc..
• More efficient PMS and all case survey to reduce overall cost ofdrug development– More “patients centric approach”

As a next step, Japanese must become global players in globalorganization, not considering only Japan but also the globe

It is a high time
to be a real global role from a region
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Basic and Translational ResearchPartnering with Academia

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11Basic/Translational Research Collaboration/Partnering Model

PI: Principle investigator• One on One Collaboration• CTI (Center for Therapeutic Innovation), “a Joint Project”• Collaboration through the research center consisted of several
academia and Pfizer to conduct drug R&D(from the stage of idea creation to a first in human study)• ITEN (Innovative Target Exploration Network)• Partnering model with selected academic institutions and PIs forearly-stage “research project” that have the potential to deliver
innovative therapeutic targets
Collaboration with multiple institutions/researchers become oneof standard partnering models.
Global is now very interested in collaboration with Asian countries.
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12Summary• Number of clinical trials in Japan is still higher than China• However, huge investment to China has been committed
due to highest CAGR, high potential of accrual, change ofregulatory environments etc.
• Japan performance is good in study start up and quality,
however needs to improve study cost (CRO/CRA cost),
performance per CRA/site using innovative IT tools; morepatient centric approaches should be promoted
proactively• In addition, Japan affiliates need to expand it’s role
– Become a global role (more global assignment of Japanese)– Japan clinical members should be involved in open innovation
activities with daily communications not only on clinical but also
on basic/translational research topics
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