China Biobanking Strategy for Integrated Translational Research

Rongxing Gan, Professor, MD, Director Clinical Research Center ISBER 2014; May 21, 2014

31 Outline of Biobank Development in China

32 The strategy for China Biobanking

3 Translational Researches based on Biobank Initiatives Background

Vast resources: clinical specimen on a large scale with clinical information

One of the basic platforms for Translational Medical Research & New Drug Development

Promote the investigation in disease mechanisms & biomarker identification Bench Bedside 2010 Clinical Specimen Repository was initiated in the 1994 The Chinese Academy of context of Significant New Drugs Development with the Medical Sciences started to work on support of the MoH and MoST establishing a bank of immortalized cell lines of Chinese ethnic groups. 2009 Beijing Municipal Science and Technology Commission launched the 1998 The Ministry of Science and construction of Beijing clinical data and Technology of China (MoST) and the sample repository of major diseases. Ministry of Health of China (MoH) drafted Human Genetic Resources 2007.9 NICGR was published online. Managements for Trial Implementation 2012 Human Genetic Resources 1998 The Office of Chinese Human 2006 MoST initiated Standardized Management Regulations (draft) was Genetic Resources Management was set organization, integration and shared formulated by the Office of Chinese under the Ministry of Science and pilot of genetic resources for Human Genetic Resources Technology of China. Significant diseases (2005-2007). Management.

1990-1995 1996-2000 2001-2005 2006-2010 2011-2015

2003 The National Infrastructure of 2008, Shanghai Municipal Science and Technology Commission Chinese Genetic Resources(NICGR) was 2012 Shanghai Biobank initiated as an important part of the launched the project of Shanghai Clinical Biobank Research Center Engineering Research Center has National Science and Technology officially granted as Shanghai Infrastructure Program by the Ministry Municipal Biobank Center by of Science and Technology of China. Shanghai municipal government, and the construction of Shanghai 2010 Shanghai Municipal Science and Technology Clinical Biobank for Major Commission launched a project for the setup preparation of Diseases was launched Shanghai Biobank Engineering Research Center. Year Project 1994 Immortalize Cell Bank of Different Chinese Ethnic Groups Human Genetic Resources Managements for Trial 1998 Implementation 2003 National Infrastructure of Chinese Genetic Resources Standardized organization, integration and shared pilot of 2006 genetic resources for Significant diseases (2005-2007). 2009 Beijing clinical data and sample repository of major diseases. Clinical Specimen Repository in the context of Significant New 2010 Drugs Development Shanghai Biobank Engineering Research Center. Human Genetic Resources Management Regulations (draft) 2012 Shanghai Clinical Biobank for Major Diseases. Shanghai Biobank Engineering Research Center National Diseases-based Biobank Project (2011-2015)

Platform-based Establishment System integration of of Chinese innovation, Specimen government clinical sustainable resources and local biobank and model of sharing resources database development mechanism

New drug discovery Cardio-cerebro- Malignant tumor vascular diseases

Major disease mechanism research Metabolic Neuropsychiat Standardization ric diseases diseases

Reflect the epidemic characteristics

The National Biobank Network in China

Beijing: Shanghai: Other regions: • Peking Union Medical College • Shanghai Clinical Research Center • Guangzhou: China Hospital • Shanghai Cancer Center national gene bank • Xuanwu Hospital, CMSU • • Taizhou: large-scale • Cancer Institute, Tianjin • cohort study University • Obstetrics and Gynecology • Yunnan: Immortalized Cell • Cancer Institute, Beijing Hospital Line Bank University • Reijin Hospital • …….. • Fuwai Hosp. of Cardiovascular • Renji Hospital Diseases, CAMS • Shanghai 6th people’s Hospital • 1st Hospital, Beijing University • Shanghai 9th people’s Hospital • General Hospital of PLA (301 • Xinhua Hospital Hosp.) • Shanghai Chest Hospital • Beijing Anzhen Hospital, CMSU • Shanghai Children’s Medical • …… Center • Shanghai Mental Health Center • Chang Zheng Hospital • Shanghai Pulmonary Hospital • …… Major diseases (2011-2015)

1.잠재 고객 Malignant tumor ( 10 Hospitals) Shanghai Jiao Tong University (14 Hospitals) Metabolic diseases Tongji University (6 Hospitals) Neuro-psychiatric diseases

Shanghai University of Traditional Cardio-cerebro-vascular diseases Chinese Medicine (5 Hospitals)

The 2nd Military Medicine University (3 Hospitals) Other diseases & Cohort Study Clinical Research

Coordination Support Translational Research

Standardization QA & QC Central Storage

Training Central IEC Data & Info Technical service

Public Service Platform (SCRC) 31 Outline of Biobank Development in China

32 The strategy for China Biobanking

3 Translational Researches based on Biobank Initiatives Basic Principles for China National Biobank

Non-profit/independent Services

Medical Government Social Institutions Resources Technical Support Performance Assurance Operating Assurance

• Technical standards • Central Government： • Resource Integration • Standardized sample Plan, Project, Policy • Full-time Staff and data collection • Local Government: • Maintenance • QA/QC Place, Fund, Personnel • Service • Research outcomes • Supervise Platform for National Biobanks

Standard Comprehensive Biological Normal Other specimen diseases information specimen Biobank

Chinese Minority Regional Epidemi Cell Myco- Major gene populati popula- Virus Bacteria -ology line plasma diseases bank on tion

Animal Plant Human

National Biobank Projects supported by MOST and MOH

One of 16 National Key Projects: New Drug Discovery and Development

The National Disease-based Biobanks in China

Step 1: National Biobank in Beijing and Shanghai Step 2: Spread to other regions when matured

Peking Union Medical College Hospital as organizer Urumchi Shenyang Beijing

SCRC as Wuhan Shanghai Chongqing organizer and third-party platform Guangzhou High Quality Sample High Quality data The Working Flow for China National Biobanking

Disease maps for health Hospitals management

The Central Bank

Reference for bio- translational sample research

Key resources for medicine industry National Key Projects: New Drug Discovery & Development

New Drug Discovery & Development for 4 Major Diseases

Peking Union Medical College Hospital Beijing Biobank for Major Diseases

Coalition Hospitals Phase I target (2009-2012)  Clinical cases 45,930, total samples th 6 People’s Hospital, Shanghai 422,489 Xuanwu Hospital, CMSU Promoted 863, NSF, BSF projects Cancer Institute, Tianjin University Phase II target (2013-2015) Cancer Institute, Beijing University 14 biobanks Fuwai Hosp. of Cardiovascular Diseases, 100,000 cases &1,000,000 samples 1st Hospital, Beijing University General Hospital of PLA (301 Hosp.) Collection of high quality specimens Beijing Anzhen Hospital, CMSU Complete clinical information …… Informatics platform Shanghai Disease-based Biobanking Project

Coordinator: Shanghai Shenkang Third Party Service:

Hospital Development Center Shanghai Clinical Research Center

Qualitysystem control Standardized system system Standardized Informatics Third party platform service(SCRC)

Centralized biobank

Entrust Public Backup

Storage Storage Storage

24 hospitals satellite banks Bio -sample Storage

Three Models:

Public Common Disease Storage Sample Sharing

Orphan Disease Backup Special Samples Storage Remote backup

Community Hospital Entrust Institution and Pharma. Storage Storage and Management Quality Management

Works Stage I Stage II QM 1. Normative work flow 1. ISO 9001accreditation Quality System 2. Detailed SOP and forms 2. ISO 27001 accreditation Manual 3. Man、 Machine、Material、 3. ISO 15189/17025 accreditation Environment and Method 4. CAP accreditation Quality 1. ISBER PT program 1. QC items checklist Procedure Files Control 2. DNA Qualification 2. Method Validation & PT 42 Files 3. RNA Integrity 3. Quantitative VS Qualitative 4. Cell Viability 4. Cell Viability 5. Temperature Monitory & Alarms 5. Tissue Antigenicity & Histology SOPs Inspection 1. Professional team 1. Documents / onsite Inspection 107 Files

• BEC-QH-01 Quality Target and Quality Policy for Biobank Record Forms • BEC-PF-01 Confidentiality Control Procedure 102 Files • BEC-PF-10 Preventive Measures Management Procedure • BEC-PF-23 Sample Management Procedure

• BEC-SOP-GA-4007 Liquid Nitrogen Container SOP • BEC-SOP-ML-1004 White Blood Cells Collection SOP • BEC-SOP-ML-1009 Sample Transfer SOP

• BEC-SOP-ML-1005-01 Sample Reception Form • BEC-SOP-ML-1008-01 Sample Delivery Form 17 Technology Support

Clinical Pathology Division Clinical Laboratory Testing Division  Anatomic pathology  Cytopathology  Clinical Immunology Lab  Molecular pathology  Clinical Biochemistry Lab  Clinical Microbiology Lab Central Lab  Clinical Molecular Biology Lab  Hematology/Urianalysis Lab CAP & ISO15189 Molecular Analysis Division  Flow Cytometry Lab  Elemental Analysis Lab  Real-time PCR  Cytogenetics Lab  SNP analysis  Gene sequencing Analytical Chemistry Division

 Pharmacokinetics/dynamics lab  Chemistry/Drug analysis  LC-MS technologies

18 Quality Control

Shanghai Disease-based Biobanking Project (SCRC + up to 24 clinical biobanks)

Working flow

QC protocol Ethical Guidance

Ethics Committee is chaired by Dr. Ching-Li Hu

• Member of the UNESCO International Bioethic Committee; • Senior Adviser and Emeritus Professor, Ruijin Hospital Shanghai Jiaotong University School of Medicine; • Directorof the Advisery Group, Department of Ethics, Legal and Social Issues, Chinese National Human Genome Center at Shanghai; • Member of the Ethics Committee, Ministry of Health; • Former Assistant Director-General &. Deputy Director-

General of the World Health Organization.

 “The Ethics Committee of Shanghai Engineering Research Center of Biobank” established in May, 2012  “The Ethics Guideline for Biobank” is issued in July, 2013 Data Storage and Management

Cloud informatics : > 39 millions cases so far

Software Copyrights: Clinical Specimen Resource Management and Assistance System V1.0 Clinical Specimen SOP Management System V1.0 Clinical Specimen Resource Ethics Audit Management System V1.0

Software Features：  SAAS mode  In reference to Oracle B/S;  In conform to NIH caBIG standards  Project oriented Shanghai Clinical Information Platform

Up to 2014.3 : Clinical Data  38 hospitals in Shanghai  6000 clinic outpatient offices  5100 inpatient offices  2900 clinical Labs  39 millions cases

Appointment system

Patient info. platform Safety alarm for therapeutics

Imagining info. platform Platform data statistics Clinical data Medical Management & management / Coordination Supervision Support system

Patient database Diagnostic database System Validation & Information Security

System Validation： ISO27001：  The computer system  Information Security 搜索感兴趣的样本

提出样本收集需求 validation strategy management manual 科研人员 全局样本 协作网 全局样本  21 CFR Part 11 plan  Corrective Action and 信息索引 主数据库 信息备份 “共享”样本研究数据  Validation of the plan and Preventive Action 临床样本资源 %合作% the confirmation  Computer management 共享与协作网络 协作网IT构架  Risk assessment  Backup management 数据交换 接口

样本基本信息  Software development  Database management 全局资源状况报告 捐献者临床数据

 Validation of the Database  Visit control management 协作信息 数据交互标准

Room 样本存储容器 样本管理人员  Information security 按照样本信息交换规范 进行数据转换

 Quality Validation Plan management system 样本管理规范

样本信息管理  Installation Validation  Business continuity 系统（节点） ………

management system 样本管理机构 样本信息管理 样本信息管理 其他样本信息  Performance Validation 系统（节点） 系统（节点） 管理系统  Operation Validation  Change management  Installation of hardware  Server management and software  … …  Validation of the standard computer configuration  Business continuity plan  Disaster recovery plan  … …

31 Outline of Biobank Development in China

32 The strategy for China Biobanking

3 Translational Researches based on Biobank Initiatives The Science of Biobanking

Ruan. et al.Biopreservation and Biobanking,2014 (under revision) The Research Relevant to Biobank

GWAS in China： Psoriasis、Vitiligo、SLE & Leprosy

GWAS for Psoriasis ： Susceptibility variants within LCE gene cluster at 1q21 The Research Relevant to Biobank The Research Relevant to Biobank

Molecular diagnosis ： Personalized medicine The Research Relevant to Biobank

Data management

Independent Ethics Rev.

Third party bio-storage

3000 cases Project management

A China case as National Children's Study (NCS) in US 259,657 cases

39,938 cases Thanks！

Contact Info: Dr. Rongxing Gan Add: Building 10, 140 Tianlin Road Shanghai 200233, China Tel：86-21-33676368 Email: [email protected] Website: www.scrcnet.org