China Biobanking Strategy for

Integrated Translational Research

Rongxing Gan, Professor, MD, Director

Shanghai Clinical Research Center

ISBER 2014; May 21, 2014

Outline of Biobank Development in China 3 1

3 2

3 3

The strategy for China Biobanking

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

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

1994 The Chinese Academy of

Medical Sciences started to work on

establishing a bank of immortalized

cell lines of Chinese ethnic groups.

1998 The Ministry of Science and

Technology of China (MoST) and the

Ministry of Health of China (MoH)

drafted Human Genetic Resources

Managements for Trial Implementation

1998 The Office of Chinese Human

Genetic Resources Management was set

under the Ministry of Science and

Technology of China.

2012 Human Genetic Resources

Management Regulations (draft) was

formulated by the Office of Chinese

Human Genetic Resources

Management.

2003 The National Infrastructure of

Chinese Genetic Resources(NICGR) was

initiated as an important part of the

National Science and Technology

Infrastructure Program by the Ministry

of Science and Technology of China.

2008, Shanghai Municipal Science

and Technology Commission

launched the project of Shanghai

Clinical Biobank Research Center

2012 Shanghai Biobank

Engineering Research Center has

officially granted as Shanghai

Municipal Biobank Center by

Shanghai municipal government,

and the construction of Shanghai

Clinical Biobank for Major

Diseases was launched 2010 Shanghai Municipal Science and Technology

Commission launched a project for the setup preparation of

Shanghai Biobank Engineering Research Center.

2007.9 NICGR was published online.

2010 Clinical Specimen Repository was initiated in the

context of Significant New Drugs Development with the

support of the MoH and MoST

2009 Beijing Municipal Science and

Technology Commission launched the

construction of Beijing clinical data and

sample repository of major diseases.

2006 MoST initiated Standardized

organization, integration and shared

pilot of genetic resources for

Significant diseases (2005-2007).

Year Project

1994 Immortalize Cell Bank of Different Chinese Ethnic Groups

1998 Human Genetic Resources Managements for Trial

Implementation

2003 National Infrastructure of Chinese Genetic Resources

2006 Standardized organization, integration and shared pilot of

genetic resources for Significant diseases (2005-2007).

2009 Beijing clinical data and sample repository of major diseases.

2010

Clinical Specimen Repository in the context of Significant New

Drugs Development

Shanghai Biobank Engineering Research Center.

2012

Human Genetic Resources Management Regulations (draft)

Shanghai Clinical Biobank for Major Diseases.

Shanghai Biobank Engineering Research Center

Platform-based

integration of

government

and local

resources

Establishment

of Chinese

clinical

biobank and

database

System

innovation,

sustainable

model of

development

Specimen resources

sharing

mechanism

Malignant tumor Cardio-cerebro-

vascular diseases

Neuropsychiatric diseases

Metabolic

diseases

New drug discovery

Major disease

mechanism research

Standardization

Reflect the epidemic

characteristics

National Diseases-based Biobank Project (2011-2015)

The National Biobank Network in China

• Peking Union Medical College

Hospital

• Xuanwu Hospital, CMSU

• Cancer Institute, Tianjin

University

• Cancer Institute, Beijing

University

• Fuwai Hosp. of Cardiovascular

Diseases, CAMS

• 1st Hospital, Beijing University

• General Hospital of PLA (301

Hosp.)

• Beijing Anzhen Hospital, CMSU

• ……

Beijing: Shanghai:

• Shanghai Clinical Research Center

• Shanghai Cancer Center

• Zhongshan Hospital

• Huashan Hospital

• Obstetrics and Gynecology

Hospital

• Reijin Hospital

• Renji Hospital

• Shanghai 6th people’s Hospital

• Shanghai 9th people’s Hospital

• Xinhua Hospital

• Shanghai Chest Hospital

• Shanghai Children’s Medical

Center

• Shanghai Mental Health Center

• Chang Zheng Hospital

• Shanghai Pulmonary Hospital

• ……

Other regions:

• Guangzhou: China

national gene bank

• Taizhou: large-scale

cohort study

• Yunnan: Immortalized Cell

Line Bank

• ……..

Standardization QA & QC

Public Service Platform (SCRC)

Central Storage

Central IEC

Support Coordination

Data & Info

1.잠재 고객

The 2nd Military Medicine University (3 Hospitals)

Shanghai University of Traditional

Chinese Medicine (5 Hospitals)

Tongji University (6 Hospitals)

Shanghai Jiao Tong University (14 Hospitals)

Fudan University ( 10 Hospitals) Malignant tumor

Metabolic diseases

Neuro-psychiatric diseases

Cardio-cerebro-vascular diseases

Other diseases & Cohort Study

Major diseases (2011-2015)

Clinical Research

Translational

Research

Technical service

Training

Outline of Biobank Development in China 3 1

3 2

3 3

The strategy for China Biobanking

Translational Researches based on Biobank Initiatives

Non-profit/independent

Services

Medical Institutions Government Social

Resources

Technical Support

• Technical standards

• Standardized sample and data collection

• QA/QC

• Research outcomes

Performance Assurance

• Central Government：Plan, Project, Policy

• Local Government: Place, Fund, Personnel

• Supervise

Operating Assurance

• Resource Integration

• Full-time Staff

• Maintenance

• Service

Basic Principles for China National Biobank

Chinese

gene

bank

Platform for National Biobanks

Standard specimen

Virus Bacteria Cell line

Animal Plant Human

Myco-plasma

Comprehensive diseases

Major diseases

Biological information

Normal specimen

Other Biobank

Epidemi

-ology

Minority

populati

on

Regional

popula-

tion

National Biobank Projects supported by MOST and MOH

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

Step 1: National Biobank in Beijing and Shanghai

Step 2: Spread to other regions when matured

The National Disease-based Biobanks in China

Shanghai

Beijing

Shenyang Urumchi

Chongqing Wuhan

Guangzhou

Peking Union

Medical College

Hospital as

organizer

SCRC as

organizer and

third-party

platform

High Quality Sample

High Quality data

Hospitals

The Central Bank

bio-

sample

Disease maps

for health

management

The Working Flow for China National Biobanking

Reference for

translational

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

Collection of high quality specimens

Complete clinical information

Informatics platform

Coalition Hospitals

6th People’s Hospital, Shanghai

Xuanwu Hospital, CMSU

Cancer Institute, Tianjin University

Cancer Institute, Beijing University

Fuwai Hosp. of Cardiovascular Diseases,

1st Hospital, Beijing University

General Hospital of PLA (301 Hosp.)

Beijing Anzhen Hospital, CMSU

……

Beijing Biobank for Major Diseases

Phase I target (2009-2012)

Clinical cases 45,930, total samples

422,489

Promoted 863, NSF, BSF projects

Phase II target (2013-2015)

14 biobanks

100,000 cases &1,000,000 samples

Informatics

platform

Centralized biobank

Third party

service(SCRC)

Public

Storage Entrust

Storage

Backup

Storage

24 hospitals satellite banks

Sta

ndard

ized s

yste

m

Quality

contro

l syste

m

Shanghai Disease-based Biobanking Project

Coordinator: Shanghai Shenkang

Hospital Development Center

Third Party Service:

Shanghai Clinical Research Center

Bio-sample Storage

Public

Storage

Common Disease

Sample Sharing

Three Models:

Backup

Storage

Entrust

Storage

Orphan Disease

Special Samples

Remote backup

Community Hospital

Institution and Pharma.

Storage and Management

17

Quality Management

Works Stage I Stage II

QM

System

1. Normative work flow

2. Detailed SOP and forms

3. Man、 Machine、Material、

Environment and Method

1. ISO 9001accreditation

2. ISO 27001 accreditation

3. ISO 15189/17025 accreditation

4. CAP accreditation

Quality

Control

1. ISBER PT program

2. DNA Qualification

3. RNA Integrity

4. Cell Viability

5. Temperature Monitory & Alarms

1. QC items checklist

2. Method Validation & PT

3. Quantitative VS Qualitative

4. Cell Viability

5. Tissue Antigenicity & Histology

Inspection 1. Professional team 1. Documents / onsite Inspection

SOPs

107 Files

Record Forms

102 Files

Quality

Manual

Procedure Files

42 Files

• BEC-QH-01 Quality Target and Quality Policy for Biobank

• BEC-PF-01 Confidentiality Control Procedure

• 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

18

Clinical Laboratory Testing Division

Clinical Pathology Division

Central Lab

Analytical Chemistry Division

Clinical Immunology Lab

Clinical Biochemistry Lab

Clinical Microbiology Lab

Clinical Molecular Biology Lab

Hematology/Urianalysis Lab

Flow Cytometry Lab

Elemental Analysis Lab

Cytogenetics Lab

Anatomic pathology

Cytopathology

Molecular pathology

CAP & ISO15189

Pharmacokinetics/dynamics lab

Chemistry/Drug analysis

LC-MS technologies

Molecular Analysis Division

Real-time PCR

SNP analysis

Gene sequencing

Technology Support

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

“The Ethics Committee of Shanghai Engineering

Research Center of Biobank” established in May, 2012

“The Ethics Guideline for Biobank” is issued in July,

2013

• 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.

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

Data Storage and Management

Cloud informatics : > 39 millions cases so far

Shanghai Clinical Information Platform

38 hospitals in Shanghai

6000 clinic outpatient offices

5100 inpatient offices

2900 clinical Labs

39 millions cases

Up to 2014.3 :

Medical

Coordination

Management &

Supervision

Patient database Diagnostic database

Appointment system

Patient info. platform

Imagining info. platform

Clinical Data

Safety alarm for therapeutics

Platform data statistics

Clinical data

management /

Support system

Information Security management manual

Corrective Action and Preventive Action

Computer management

Backup management

Database management

Visit control management

Information security management system

Business continuity management system

Change management

Server management

… …

ISO27001： System Validation：

The computer system validation strategy

21 CFR Part 11 plan

Validation of the plan and the confirmation

Risk assessment

Software development

Validation of the Database Room

Quality Validation Plan

Installation Validation

Performance Validation

Operation Validation

Installation of hardware and software

Validation of the standard computer configuration

Business continuity plan

Disaster recovery plan

… …

协作网IT构架

临床样本资源共享与协作网络

样本信息管理系统（节点）

样本信息管理系统（节点）

样本管理人员

样本管理规范

样本存储容器

样本管理机构 样本信息管理系统（节点）

其他样本信息管理系统

………

按照样本信息交换规范进行数据转换

全局样本信息索引

全局样本信息备份

科研人员

搜索感兴趣的样本

提出样本收集需求

“共享”样本研究数据

样本基本信息捐献者临床数据

%合作%

全局资源状况报告

协作信息数据交互标准

协作网主数据库

数据交换接口

System Validation & Information Security

Outline of Biobank Development in China 3 1

3 2

3 3

The strategy for China Biobanking

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

A China case as National Children's Study (NCS) in US

Data management

Independent Ethics Rev.

Third party bio-storage

Project management 3000 cases

39,938 cases

259,657 cases

Thanks！

Contact Info: Dr. Rongxing Gan

Add: Building 10, 140 Tianlin Road

Shanghai 200233, China

Tel：86-21-33676368

Email: rongxing.gan@scrcnet.org

Website: www.scrcnet.org