Shogo Nakamori 4th NCGM seminar Dec. 2018 final · 2019-06-06 · 7lpholqh lv suhvhqwhg edvhg rq...

CONFIDENTIAL © 2018 PAREXEL INTERNATIONAL CORP.

TREND OFCONDUCTINGCLINICAL TRIALIN ASIA

Dec 21st, 2018, Tokyo, JAPAN

Shogo Nakamori

PAREXEL International

© 2018 PAREXEL INTERNATIONAL CORP. / CONFIDENTIAL2

• Acquisition of APEX International, CRO Asia’s leading contract service provider in drug development, in Asia-Pacific in 2007.

• PAREXEL has more than 7,548 employees located in Asia Pacific.

• Asia-Pacific presence

• 28 office locations in 13 countries

• PAREXEL has a strong presence in Asia and provides the following services in the region:

• Project management• Regulatory affairs• Study coordination and monitoring• Data management• Statistical analysis• Medical writing

PAREXEL ASIA-PACIFIC OVERVIEW


HISTORY OF PAREXEL

Founding of PAREXEL

1982 1993 2006 2008 201620121995

40+ Acquisitions Since PAREXEL’s Inception

Files S-1 & registers with SEC to become publicly traded company

Founding of Perceptive Informatics

PAREXEL supporting the top 10 biotech and top 20 pharma companies, and has supported most of the top 50 drugs on the market

Launch of Perceptive MyTrials®

Wins Clinical Research Team of the Year at Scrip Awards

Completion of public offering

CRO Leadership Award

Launch of BioPharm Unit

2000

Opening of PAREXEL’s first office in Japan

2007

Acquisition of APEX expands services in Asia-Pacific

1997

Launch of Medical Imaging services

Acquisition of EDYABE expands services in Latin America

2001 2010

Launch of Strategic Partnerships

2014

Opening of European Hub expands supply and logistics

PAREXEL supports fastest drug development to date, for anti-HIV compound

10 million calls placed through ClinPhone®

RTSM

20091998

Acquisition of MIRAI B.V., a full-service CRO with access to patients and clinicians in Central and Eastern Europe

Named to Forbes America’s Best Employer’s list

Acquisition of the Los Angeles Early Phase Clinical Unit

2008 2012 2013 2014

ClinPhone LIQUENT HERON ClinIntel QSI

Commercialization ServicesConsultancy

RTSM Pharmacovigilance Services

Regulatory Information ManagementSolutions

Randomization & Trial

SupplyManagement(RTSM) and DataLabs EDC

2016

Health Advances & ExecuPharm

Life Sciences Consultancy &

2015

Functional Services Provider

2017

The Medical Affairs Company

2017

New Real-World Data Services

Medical Affairs Outsourcing Services

PAREXEL Acquired

by Pamplona


28 offices based on 13 countries

PAREXEL APAC REACH OFFICE LOCATIONS (TOTAL EMPLOYEES)(AS OF 30 JUN 2018 )

4

Japan (1,299)Tokyo *3OsakaKobe

India(4,388)BengaluruChandigarh *2Hyderabad Mumbai MohaliNew Delhi

Taiwan (464) – Taipei

Hong Kong (29)

Australia (119)North Ryde

PAREXEL has 7,548 employees in Asia Pacific

Leading CRO in Asia Pacific

China (916)BeijingChengduGuangzhouShanghai *2Shenyang

S. Korea (152) Seoul

Indonesia (3)Jakarta

Malaysia (29)Petaling Jaya

Singapore (63)Singapore

Thailand (37)Bangkok

Vietnam (6)Ho Chi Minh City

Philippine (43)Manila


PAREXEL THERAPEUTIC EXPERIENCE (INCLUDING TECHNOLOGY SERVICES) – PAST FIVE YEARS


ALLIANCE MEMBERS IN APAC (AS OF JUL 2018)

Countries Alliance Members

Australia 4

China 24

Hong Kong 2

Japan 6

Malaysia 5

Philippines 4

S. Korea 12

Singapore 1

Taiwan 7

Thailand 6

Please note: The number refer to PAREXEL Actual Site Alliances member in APAC

Total Number of Alliance members

in Asia Pacific:

71


REGULATORY ENVIRONMENT


0

24

12

12

12

8

6 16

8

12

16

16

0 4 8 12 16 20 24

Vietnam

Indonesia

Malaysia

Hong Kong

Philippines

India

Thailand

Taiwan

Korea

Singapore

HA/EC parallel HA(Health Authority)EC(Ethical Committee) HA+EC (parellel submission, sequential approval)

(Weeks)

REGULATORY REVIEW PROCESS/TIMELINE FOR CLINICAL TRIAL APPLICATIONS (CTA)

• Best scenario- no major comment from HA/EC, 1st approval of HA (if applicable), selection of simple sites, etc.

• Timeline is presented based on experience if there is no official timeline announced • Timelines cover HA/EC review and IL applications, but dossier preparation, CSA, etc. are not included


REGULATORY TREND

• Global Harmonization

Harmonization vs. Convergence

PIC/S GMP- Indonesia, Korea, Malaysia, India, Hong Kong, Thailand, and Vietnam

• Data protection/ subject rights

Relevant law/regulation protects not only data of subjects, but also site staff- Korea, Taiwan, Hong Kong, etc.

Stringed requirement on subject specimen

• Clinical trial registry

Clinical trial registry: China, India, Malaysia, Philippines, Taiwan, Korea, Singapore, Thailand (referring to other country’s registry but not mandatory)

• E-submission (paperless submission)

• Submission fees (increasing trend too)


MANAGING CLINICAL TRIALS IN ASIA


AGENDA

• Introduction

• Key considerations

• Lessons learned

• Conclusion


TOKYO, JAPAN

INTRODUCTION


THE GLOBAL LANDSCAPE- 16% ASIAFROM CLINICAL TRIALS.GOV 16 MAR 2017

South Asia (3672)- Afghanistan, Bangladesh, Bhutan, India (3040), Nepal, Pakistan, Sri Lanka

Pacifica (5985)- Australia, New Zealand,

Southeast Asia (4818)- Cambodia, Indonesia (314), Lao, Brunei, Malaysia (911), Myanmar, Philippines (830), Singapore (1758), Thailand (2101), Vietnam (303)

Japan (4476)

East Asia (24254)- China (9264), Hong Kong (1318), Korea (7868), Mongolia, Taiwan (4728)

Canada

US

Mexico

Central America South

America

EU

Africa

North Asia

Middle East


THE GLOBAL LANDSCAPE- 16% ASIAFROM CLINICAL TRIALS.GOV 18 NOV 2018 East Asia (31166)

- China (13056), Hong Kong (1752), Korea (9568), Mongolia, Taiwan (5727)

South Asia (4357)- Afghanistan, Bangladesh, Bhutan, India (3531), Nepal, Pakistan, Sri Lanka Pacifica (5985)

- Australia, New Zealand,

Southeast Asia (5797)- Cambodia, Indonesia (415), Lao, Brunei, Malaysia (1094), Myanmar, Philippines (909), Singapore (2128), Thailand (2411), Vietnam (399)

Japan


REGISTERED TRIALS- NOV 2018

South America,

3.27Canada,

6.66

US, 40.17Europe, 28.28

Africa, 2.68

Asia, 16

Japan, 1.8

South America Canada US Europe Africa Asia Japan

South America, 4.26

Canada, 5.53

US, 36.82

Europe, 24.77

Africa, 8.04

Asia, 18.74

Japan, 1.12

Infectious Disease

South America Canada US Europe Africa Asia Japan1110

688621 609

438

192 167 155 14193 84 50

0

200

400

600

800

1000

1200

Infectious disease study


TOKYO, JAPAN

KEY CONSIDERATIONS


OPPORTUNITIES- WHY ASIA?S

cie

ntic

Inve

stm

ent

• Thriving Industry from government and business support.

• Building of infrastructure -construction of R&D facilities & large hospitals

• Greater investment in training of investigators specialists in different TA.

• Increasing pool of trained CRC

• CRO expanding to cater to the pharma’s needs

Ide

al p

atie

nt p

opu

latio

n • Go where the patients are

• High rate of urbanization

• Increasing lifespans

• Shift from infectious to chronic diseases

• 4.5 billion people with unmet health needs and genetically diverse.

• Ability to recruit treatment naïve patient

Co

st &

Tim

e S

avi

ng

s • Start-up timelines have become more favorable (other than China)

• Increasingly robust and efficient regulatory and ethics processes

• Cost of clinical trials in Asia is relatively lower than in US/EU

• Low operating cost in some regions

Qu

ality • Quality

improvements resulting from massive investments in research infrastructure and human resources.

• LOW Regulatory actions in Asian Countries compared to US. (Source: FDA)


INITIATIVES TO PROMOTE CT IN ASIAFASTER APPROVAL TIMELINES

•Fast track approval process for Taiwanclinical trial notification (CTN) and SingaporeCTN. China regulatory has become more competitive after reform

•Resurgent India, where regulatory reform has reawakened clinical development opportunities in the country of 1.3 billion people

•Central Ethics and Centralized CSA review for all public hospitals in Malaysia ease for faster study start up. Regular dialogues with HA, Central MREC and other government bodies coordinated by Clinical Research Malaysia, provide avenue to smoothen CT processes.

•Vietnam: Upcoming! Release of revisedregulations by Apr 2017 with shortened RA turnaround time (30wd vs 60 wd)

•Philippines: A Single Joint Review Committee to review multi-centric trials streamline review of protocols with 3 or more participating sites and a reference guide harmonizing review and approval of clinical study contracts.. Upcoming! Revision of CT national guidelines for faster review and approval

SUPPORT TO BUILD CLINICAL TRIALS

•Government investments to enhance innovation capability!

• India to top 5 pharmaceutical innovation hub by 2020 and launching drug discovery in India at global level. Other initiative include weighted tax deduction for R & D expenditure.

• Malaysia 25 Billion investment to healthcare including upgrading hospitals.

•Korea aim to be top 7 global pharmaceutical producing countries by 2020.

•¥• Taiwan aim to help local companies roll out 20 new medicines and 80 medical devices launch overseas market and develop 10 biotech and health service brands by 2025.

•China Estimated US$118 billion USD of Pharmaceutical sales 2016. Forecasted as #2 pharmaceutical market by 2020. Focused on nurturing medical companies and developing medical equipment.

INVESTMENTS IN TRAINING

•Training programs for clinical trials specialist e.g. Korean National Enterprise for Clinical trials (KNECT) / Clinical Research Malaysia (CRM).

•Changing the way clinical trials are run in India to support the local environment. The Union Health Ministry is working to provide accreditation to clinical trial centers and Investigators and ECs.

•The Philippine National Health Research System Act of 2013 has been institutionalized in the country to promote health research and provides ample support to capacity-building, training and education of stakeholders in all areas of health research


SWOT ANALYSIS OF ASIAN CLINICAL TRIALS MARKET


LESSONS LEARNED


KOREA

Environment• Large and vigorous pharmaceutical industry, a mature healthcare system, a well-

trained clinical workforce with global exposure and an advanced scientific and technological base.

• Top 3 causes of death: Cancer, Cardiovascular, Cerebrovascular disease• Average life expectancy is 80 yrs. Chronic elderly disease treatment: 25.5% of

Pharmaceutical market

Key Success• Well established regulatory environment: Transparent and efficient review process;

Governmental support for clinical research from early phase (e.g. FIH)• Well established clinical trial centers: Good infra-structures: compliant IRB, study

coordinators, pharmacy, and validated EMR system.• Patient pools centralized at big university hospitals in Seoul: Good access to patient

pool regardless of disease incidence rate

Lessons Learned• Investigators site budget to be available upfront (required for IRB submission). Need

to account for current market rate to avoid amendment downstream• Prompt provision of core documents to accelerate regulatory approval (a rate-limiting

step in start-up)


TAIWAN

Environment• Internationally acclaimed medical infrastructure and Regulatory framework. • Top five disease burden prevalence: Malignant Neoplasms; Heart Disease; Cerebrovascular

Diseases, Pneumonia and Diabetes Mellitus. • Strong medical infrastructure including Centers of Excellence with ICH-GCP compliance• Taiwan medical technology is internationally renowned: Ranked 3rd in the world and 1st in

Asia

Key Success• Accredited and adequately operated IRB:

• 6 IRBs are AAHRPP accredited & 23 IRB are FERCAP certified• 96.6% of c-IRB submissions got review results within 20 working days

• Conducting clinical trial in Taiwan may assist Sponsors in gaining higher reimbursement price• Bridge to China

Lessons Learned• Legal requirements have impact on ICF language for indemnification. • Genetic bio-sample is not allowed to be exported for genetic analysis unless Taiwan has no

capability for the certain genetic test or is deemed as necessary.• Many sites require Sponsor to contract with an SMO for study coordinator services.


THAILAND

Environment• Large naïve patient population across many disease profiles i.e. oncology, vaccine, HIV,

Hepatitis• Top 5 TA Trend for ongoing trials: Oncology (especially NSCLC); Infectious disease,

Autoimmune inflammation, Cardiovascular and CNS

Key Success• Sponsors/drug developers are finding Thailand more and more cost effective in terms of

recruitment, fast regulatory approvals and quality • Well-established regulatory requirements and standards; similar to other Western countries in

detail and application. Previous sequential submission (EC and then RA) changed to partial parallel submission. Startup timelines could potentially be improved.

• Benefits from the establishment of a Central Research Ethics Committee (CREC) in 2014 to rapid study approval & start-up timeline with the collaborations with MOPH hospitals

• Increase resource of FDA reviewer to control IL approval timeline to be more committed and reliable.

Lessons Learned• Limited experience in early stage trials• High demand of skilled professional• Recommend to start the translation of required documents (partial protocol, ICF, subject

material) for initial EC submission as early as possible to ensure the package can be submitted and met the EC meeting timeline.

• CSA translation into Thai may be required in some sites but very rare case.• License Per Invoice (LPI) is required for each IP shipment and to have translated COA in

place can be shorten for LPI approval timeline within 1 day.


MALAYSIA

Environment• Parallel RA and EC submissions and both follow strictly to committed timelines.• MOH hospitals (~80% of sites) have Centralized EC and Centralized legal review that

reduces start up timelines significantly.• Ethnically diverse and has a high prevalence of diseases in therapeutic areas such as

Oncology (including NSCLC), Hematology, Infectious Disease, Endocrinology and Metabolism, Cardiology, Neurology and Psychiatry, Rheumatology. High interest in biologics and vaccines clinical trials

• Multiracial; English (widely used and understood amongst site staff and patients).

Key Success• The Malaysian government is highly supportive of clinical trials and its objectives is to reach

1000 trials by 2020. Establishment of a central body (Clinical Research Malaysia) in 2012 to facilitate, promote and oversee the conduct of clinical trials in the country.

• Strong government collaboration to bring clinical trials into Malaysia and to centralize processes, building infrastructure at site and shortening the study start up timeline.

• Recently approved Phase 1 Research Guidelines by RA and accredited phase 1 sites to conduct Phase 1 studies including First-in-human studies.

Lessons Learned• Clear understanding of HA document requirements (i.e. GMP certificate requirements,

sufficient stability data).• Study Budgets to be provided as early as possible to avoid potential start up delays.• CSA parties should be of local signatories. Essential to understand the CSA parties upfront.


PHILIPPINES

Environment• 104 million population with highly trained investigators, sub-investigators, SCs and availability

of nurses/ pharmacists working in the CT industry. • Wide availability of qualified hospital sites and healthcare professions. • High literacy rate – no translations required for protocol and CRFs• Top 5 Disease Prevalence : cardiovascular diseases, cerebro-vascular diseases, malignant

neoplasms, pneumonia and diabetes mellitus

Key Success• Open, transparent collaborative industry – with consultations and RTDs (round-table discussions)

among Clinical Trial Players and Stakeholders to streamline clinical research processes• Accreditation of IRBs on a national-level• Accreditation of Sponsors and CROs in the country for better accountability of clinical trial conduct• Faster contracting with Philippine-specific recommendations on study contracts

Lessons Learned• Open communication of issues and challenges can be raised to hospital administrators and

government agencies in-charge of regulating clinical research• Tri-partite CSA is preferred; multiple-payee system for the CSA• Full monitoring and tracking of activities and corresponding documents to meet study

deliverables


SINGAPORE

Environment• Key therapeutics areas for clinical trials conducted was in oncology, dermatology,

ophthalmology, cardiology and Infectious disease.• Phase I facilities available with trained staff. Mature phase 1 clinical research environment.• Well-trained Study Coordinators and Clinical Trial Centre staff to support investigators and

studies.• Streamlined parallel approach to EC and Regulatory processes.• Investigators motivation from Scientific merit- publication

Key Success• Singapore is a popular destination for pharmaceutical and biopharmaceutical companies due to

its many advantages including rigorous regulatory framework, well-established logistics infrastructure as well as strong intellectual property protection. Its stable and civic environment has made it the preferred location for the Asian headquarters of many global pharmaceutical giants.

Lessons Learned• If there are no agreed contract template previously with site, contract negotiation may take a

long time. Site budget likely higher than other Asian countries and will be at the higher range of most grant plans resulting in some time lengthy negotiations.

• Given the high density of clinical trials, there is fierce competition for patients and investigators to participate in trials of certain indications.


HONG KONG

Environment•Hong Kong is one of the most popular cities in Asia for industry-sponsored clinical trials. Hong Kong has a well-established and high quality medical infrastructure. Clinical trials are run and facilitated in full compliance with international guidelines.

•Top 5 disease burden prevalence: Malignant Neoplasm, Pneumonia, Disease of heart, Cerebrovascular diseases and Chronic Lower respiratory disease.

Key Success•Proactive government support and incentives to promote research: Investments of approximately USD $5.4 million in setting up two Phase I and IIa units with a focus on first-in-human and proof-of-concept studies

•Establishment of a regional center for traditional Chinese medicine and herbal drugs•Presence of regional and global key opinion leaders in fields such as diabetes mellitus, cardiology and hematology, who can serve on steering committees

Lessons learned•Potential for lengthy contract negotiations if there is no agreed contract template previously between sponsor and Hospital Authority

•To mitigate issues related to contracts, sponsors are encouraged to have contract templates with two university-affiliated hospitals and the Hospital Authority, and to minimize revision of these templates

•Face-to-face qualification visits is preferred by PI.•RA approval is longer and stringent on new sites without prior clinical trial experience (need to accept the risk).

•Evidence that the trial medication is manufactured in accordance with Good Manufacturing Practices (GMP) (GMP Certificate of the manufacturing site) is mandatory for RA approval


INDONESIA

Environment•The largest population pool among Southeast ASIAN countries. •Top 3 causes of death: Stroke, IHD, DM•Active therapeutic areas for clinical trials including oncology, endocrinology and metabolism, cardiology•Shifting disease trend from infectious diseases to non-communicable diseases due to lifestyle changes

Key Success•Large patient population•Cost per patient are relatively lower/competitive compared to other Asian countries•The country is trying to attract R&D investments in global clinical research by ensuring strict compliance with Good Clinical Practice standards in all trial supporting teams. Meanwhile, the lower costs of research as well as the relatively large population of potential patients provide opportunities to speed up recruitment efforts and shorten project timelines. This will also help patients access new and innovative medicines and devices.

Lessons Learned•Material Transfer Agreement is required to export specimens out of the country. Recommend to look into local centralized lab that is accredited. This would ease the study start up and would provide access to a large population pool.

•Varying site staff experience. Would require more oversight for more naïve sites out of Jakarta


VIETNAM

Environment•Vietnam has seen continuous growth in clinical trial capabilities, encouraged by local authorities.•A greater number of hospitals and investigators in the country are now getting involved in Good Clinical Practice trials, including Phase I studies.

•High prevalence of respiratory, infectious and CV diseases, cancers at late stage.

Key Success•More knowledge and experience by sites and investigators in source documentation•Improvement of LEC’s management via training and accreditation program by local Regulatory authorities•Revised regulations in October 2018 to be effective from 1st Jan 2019 that facilities the growth of clinical trial capacities with:

- shortened RA turnaround time (25 wd vs 60 wd)- the use of commercial IRB/IEC and commercial CRUs- acceptance of CTA package in English

Lessons Learned•CSA still needs to be translated into the local language as legal documents•10% administrative fees for MOH and 30% overhead fee included in CSA•Need of having local vendor/broker for shortening IL review process for study specific auxiliaries like ECG, EPRO

•Requirement of renewing IL yearly and renewing EL for biosamples every 6 months•Restriction of relabeling IMP/non-IMP at sites for shelf-life extension•CSR submission requirement for closing study in the country


CONCLUSION

• Asia presents tremendous opportunities for global drug development and becoming the driver of pharmaceutical growth.

• Consider all of Asia. All present opportunities for Clinical Trials development and offers unique advantages.

• Conducting clinical trials in Asia can be highly complex without the local knowledge and experience.

Deep local knowledge and continuous intelligence is critical to keep abreast of constant change.

Developing and maintaining expertise in the region is critical to ensure success of programs.

Adjusting strategies based on site specific needs in each country is important.


THANK YOU



CHINAEnvironment• World’s largest population, wide therapeutic experience, lower operating costs.• High prevalence of hepatitis, hypertension, diabetes, lung cancer, gastrointestinal

cancer, colorectal cancer, liver cancer, esophageal cancer and neural tube defects.

Key Success• Increasing CFDA quality governance: In 2016 CFDA started reform to shape a better

environment for clinical trials: to address application backlogs, to accelerate innovative drug review, to streamline clinical trial application and approval process etc.

Lessons Learned• Include China early in the strategy planning due to long Regulatory approval.• Financial payment procedures and new VAT (Value added Tax) invoice requirement.• SMO cooperation and CRC management need to be well implemented.• Risk based monitoring strategy need to be balanced under current China regulation

environment.• Non-transparent regulation procedures and long approval duration Impact of HGRAC

(Human Genetic Resource Administration of China) submission and approval to study timelines.

• Long SSU circle time due to complexity of site review process and limited CFDA accredited site capacity to accommodate increasing number of clinical trials.


INDIA

Environment • A fast emerging clinical trial hub with unique qualities.• A tremendous diversity of population, a varied genetic pool and huge geographic expanse• English being a widely spoken language. All sites uses English as a business language.• India’s regulatory environment is robust to enable rigorous, fool-proof monitoring of studies and scientific reporting of results.

Key Success• Regulatory reformation to facilitate clinical development and trial opportunities. • The government has been undertaking policy initiatives for growth of the pharmaceutical industry. One such initiative is tax breaks and

weighted tax reduction for R & D expenditure.• Ethics Committee have been empowered and made more accountable now to ensure close oversight of trial conduct at sites.

Lessons Learned• Robust Regulatory system to monitor Clinical Trial conduct. • Single Regulatory Approval layer, only Subject Expert Committee (SEC) to review applications submitted to DCGI. Provision in place within the

system for APEX Committee to get involve in case of decision conflicts. This move substantially reduces approval timelines.• Robust management of SAEs and Deaths by MoH including compensation provisioning for clinical trial injury. Clear formula to derive

compensation amount in place.• 50% of identified /selected sites should come from government/public hospitals • Audio-Visual Recording of Informed Consent Process only be mandatory for cases where vulnerable population is involved & the trial is of

New Chemical Entity or New Molecular Entity.• For clinical trials of Anti-HIV and anti-Leprosy drugs, only audio recording of the informed consent process shall be mandatory.

Shogo Nakamori 4th NCGM seminar Dec. 2018 final · 2019-06-06 · 7lpholqh lv suhvhqwhg edvhg rq...

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Transcript of Shogo Nakamori 4th NCGM seminar Dec. 2018 final · 2019-06-06 · 7lpholqh lv suhvhqwhg edvhg rq...