Clinical Trials in Russia FROM A CENTRAL LAB PERSPECTIVE

Tomasz Anyszek, Synevo Central Labs DirectorMichal Dysko, Head of Business Development

Business Review Webinars26th November, 2014

Agenda

• Speakers’ Introduction

• Clinical Trials Industry in Russia

• Central Lab in Clinical Trials

• Lab’s Key Challenges in Russia

• Overcoming the Challenges

• Decentralized Central Lab Services

• Summary and Conclusions

• Questions & Answers

Tomasz AnyszekMD, PhD, EurClinChem

• Synevo Central Labs’ Directorsince 2009

• Synevo Poland’s General Director and Board Member since 2014

• Responsible for clinical trials operations of the whole network

• Previously worked for Covance managing Virtual Central Laboratory (VCL) initiative since 2000

• PhD from Jagiellonian University Poland

Michał Dy śkoMBA Degree

• Head of Business Development at Synevo Central Labs since 2008

• Responsible for sales and marketing operations of the whole network

• Previously worked for 2 European CROs

• 11+ years of experience in clinical research

• MBA Degree at University of Quebec at Montreal and Warsaw School of Economics

Poll Question # 1

What is your main concern while planning to include Russia in your clinical study?

• Regulatory

• Quality

• Patient retention

• Import and export procedures

Why Russia?

• Requirement of trials in Russia for local MA

• Very large population

• Clinical sites accredited by MOH

• High recruitment rates

• Confirmed high quality

• Highly competitive costs

Registered Clinical Trials

Source: www.clinicaltrials.gov

Total: 178,738

Registered Trials in Russia

Source: www.clinicaltrials.gov

1,6 % of clinical trials

registered around the world

Clinical Trials in Russia

• $200 million market in 2012

• Expected to reach $300 million by 2016

• 791 new clinical trials approved in 2013

• 358 (45%) international, multicenter trials

• Sponsored by companies from 31 countries

• 57,609 patients recruited in 2013

Clinical Trials in Russia 2004 -2013

523

447

507

563

615577

482

567

915

791

252279

324

369 364 348

246

370 369 358

0

100

200

300

400

500

600

700

800

900

1000

2004 2005 2006 2007 2008 2009 2010 2011 2012 2013

Approved CT International Multicentre CT

Source: www.acto-russia.org

Trials Sponsors by Country

Russia41%

USA17%

Switzerland7%

Germany4%

India4%

UK4%

Other23%

Country of Origin No of Trials

France 27

Israel 22

Belgium 19

Hungary 12

Denmark 12

Austria 11

Sweden 11

Poland 9

Czech Rep 7

Other 49

Source: www.synrg-pharm.comc

Trials by Therapeutic Areas -2013

Oncology20%

Pulmonology12%

Cardiology10%

Endocrinology10%

Musculoskeletal diseases

9%

Infecious diseases8%

Neurology6%

Psychiatry5%

Other20%

Source: www.synrg-pharm.com

Number of Patients by PhasePhase I

2%

Phase II12%

Phase III80%

Phase IV6% Study Phase No of

Patients

Phase I 902

Phase II 7,076

Phase III 46,101

Phase IV 3,530

TOTAL 57,609

Source: www.synrg-pharm.com

Patient Recruitment

• 140+ million population

• Naive-treatment

• Centralized healthcare system

• Low healthcare standards

• Disciplined patients

• High retention rates

Quality of Trials in Russia• FDA approved 53 new drugs during 2013 that were

tested at least in part in Russia

• EMEA approved 86 new drugs in 2013 that were tested in Russian sites.

• Two FDA inspections were conducted in Russia during 2013 with only VAI results

NAI (No Action

Indicated)

VAI (Voluntary

Action

Indicated)

OAI (Official

Action

Indicated)

Number of FDA

inspections

2008 7 6 0 13

2009 10 3 0 13

2006-2009 28 12 0 40

Study Costs in Russia

• Investigator’s fee

• Local insurance requirements

• Customs clearance costs

• Courier services

• Costs of miscellaneous

• Study management

Lab Data in Clinical Trials*

Efficacy Data

• e.g. Cholesterol level in Hyperlipidemia patients

• e.g. Plasma Glucose in Diabetes patients

Safety Data

• Hematology• Chemistry• Urinalysis

Special Data

• PK/PD data• Genomic data• Biomarkers

*60-80% of the data generated during the conduct of clinical trials are produced by laboratories

Central Lab Role in Clinical Trials

Project Management

Laboratory Testing

Investigator Support

Sample Management

LogisticsData Mgmt and

Reporting

• Routine and safety analysis

• Advanced diagnostics

• Method development and validation

• Analytical expertise

• Dedicated and locally based staff

• Real-time query resolution

• Trainings

• Multilingual help desk

• Lab manuals and instructions

• Study-specific kits building

• Packaging and labels

• Quality Control

• In-house frozen logistics support

• Kits inventory monitoring

• Planning, tracking and reporting

• Ambient, refrigerated, frozen and combo shipments

• Ready shipping documents

• Couriers management

• Network of own couriers

• Integrated single database

• Standardized reference ranges and units of measure

• Electronic Data Transfer

• 21CFR Part 11 –compliant reporting technology

Full Coordination and Accountability

Challenges

• Regulatory environment• Lengthy importation procedures• Permits and paperwork• Many time and temperature zones• Language barriers• Poor transportation

infrastructure• Complex logistics

Import of Study Material

• Import permit (28 days on average)• Can’t be sent directly to a study site• Import license holder have to be involved• Complicated customs clearance procedure• Study supplies require

certification• Customs invoice

Export of Biological Samples

• Export permit issued by MoH• 34 days on average• On behalf of license holder• Ready-shipping documents from license

holder for investigator

Import/export permit application

• Information about the clinical trial• Name of the nation state• Purpose of the imported biological materials• Type of the biological samples• Number of units• Type of packing• Permit to conduct the trial• Corporate entity docs

Poll Question # 2

What would be your main concern regarding laboratory part of a clinical trial in Russia?

• Quality of lab results

• Samples quality

• Export of samples

• Courier costs

Decentralized Model

Overview:Locally-based central labswithin a country or a geo-cultural region

Characteristics:• Standardized testing platform

• Consistent test methodologies

• Compatible result reporting

• Single database

Synevo Central Labs

NEW LOCATION

• Wholly-owned• Fully-harmonized• Decentralized model• Full-service central lab• Single database • ISO and GCLP

accreditations

Levels of Harmonization

ITAnalyticalQuality

AssuranceOperations

• Equipment

• Reagents

• Reference ranges

• CLIM

• Data Management

• Clinical Trial Lab

Management

System

• ISO standards

• SOPs

• Quality Metrics

• Lab supplies

• Site support

• Logistics

Analytical Harmonization

Reference lab

selection

Referral samples

preparation(CEQAL*)

Baseline assessment

Monitoring of analytical

precision

Critical analytes

assessment

Ongoing external

monitoring programme

*CEQAL – Canadian External Quality Assessment Laboratory

IT & DM Harmonization

Online access to results

• Proprietary software21CRF part 11 compliance

• Web-based and secured• Real-time & 24/7 access• Color-coded results• Reporting:

• Cumulative or incremental• Abnormal• Trends• Custom

Data Transfer

Data formats

- ASCII data files- CDISC format- Client specified format

Transfer methods

- Directly into eCRF- Sponsor FTP server- Couriered CD- Secure email attachment file

Reports

- Patient recruitment- Abnormal results- Missing patients visits- Parameter trend analysis

Integrated Single Database

Quality A

ssurance

High-quality services

ISO 15189:2007quality standards

SOPs compliant with GCP and GCLP

External Quality Assurance Programs

Internal Quality Control

Key suppliers audit

Client audits are w

elcome

DocsProcesses

and procedures

Information Technology

(IT)

Communica-tion skills Experience

QA Harmonization

• Selection and qualification of regional laboratory based on audit:

• GCP, GCLP and EN ISO 15189 trainings for local laboratory team

• Implementation of documents and templates/forms

Kits production

and distribution

Sample shipment

and storage

Sample registration

Results reporting

Operations Harmonization

• Harmonization and implementation of standard procedures:

• Defining the study team and responsibilities• Implementation and validation of Clinical trials

Laboratory management System (CTMLS)

The Model Benefits

• Significant logistics cost reduction

• faster access to laboratory results

• Harmonized clinical lab data

• Access to large patient population

• Local support

Conclusions

• Russia is a very attractive region to conduct clinical trials

• Complex customs and regulatory legislation• Clinical supply chain in Russia is highly

fragmented• To overcome the region challenges

use experienced local partner• Limit the number of inbound

and outbound shipments

BRUSSELS

HQ

Michal Dysko, MBAHead of Business DevelopmentT: +48 602 443 552E: michal.dysko@synevo.eu

Tomasz Anyszek MD, PhD, EurClinChemSynevo Central Labs DirectorT: +48 609 917 552 770E: Tomasz.anyszek@synevo.eu

Questions ?