Clinical Trials Market in Russia 17 October 2008 ROTOBO - ACTO

Agenda ACTO: objectives, structure, members CROs in Russia: current status and perspectives Market of clinical trials in Russia: current status and perspectives Regulatory system in Russia and its compliance to international guidelines (ICH GCP, FDA, EU)

Association of Clinical Trials Organizations (ACTO) non-commercial organization of the companies/legal entities and clinical research community engaged in clinical trials in Russia

Areas of interest Self-control of the branch Participation in legislative process (dialog with legislative establishment and representing for the industry) Society Legislative AuthorityExecutive Authority Developing and introduction of high standards for clinical trials Developing and forming of public opinion of the industry branch Association

ACTO: The main objectives Further development of Russia as a leading clinical research country/market by engaging in capacity building and activities to shape the professional environment; Generation of awareness of clinical research as a specialty and establishing the high Industry reputation amongst the general public and governmental agencies;

ACTO: The main objectives Representing the interests of the members of the Association; Creating a favorable business environment for the companies conducting the clinical trials in Russia; Maintaining constructive dialogue with regulatory authorities and general public aimed at the development of stable local legislative basis for the clinical trials conduct harmonized with the respective worldwide standards;

ACTO: The main objectives Promoting an ethical business model; Ensure a proper and effective balance between the interests of parties involved in clinical trials including the patients, the medical community, and the general public and governmental agencies.

The members of ACTO: Pharmaceutical Companies: Bristol-Myers Squibb; Janssen Pharmaceutica; Pfizer Candidates: Bayer Schering Pharma AG; Eli Lilly Vostok S.A.; AVINEX LLC Contract Research Organizations: Almedis; ClinStar; Worldwide Clinical Trials (WCT); i3; MB Quest (POI); Parexel; PharmaNet; PRA International; PSI; Quintiles; Synergy

Association management structure General Meeting Board (collective executive body) Committees & Workgroups Executive Director (sole executive body)

Committees & Workgroups Regulatory committee Logistic committee Legislative committee HR Working group

Projects and Activities Analysis of initiatives in changing of legislation Monitoring of Regulatory procedures and timelines Standardization of documents and procedures Preparation of draft national standard Clinical Safety Data Management: Definitions and Standards for Expedited Reporting (an analogue of the ICH E2A)ICH E2A Good Taxation Practice (VAT rate 10%) Salary Survey

Agenda ACTO: objectives, structure, members CROs in Russia: current status and perspectives Market of clinical trials in Russia: current status and perspectives Regulatory system in Russia and its compliance to international guidelines (ICH GCP, FDA, EU)

CROs in Russia About 60 CROs operating now Up to 5 new CROs appear every year 42% of trials have been initiated by CROs and 31% by foreign pharmaceutical companies (Roszdaravnadzor)

Types of CROs in Russia Global CROs established their own offices according to development plans (Quintiles, Icon, PharmaNet, MBQ/POI, PRA) Global CRO bought established local business (WCT, i3, Parexel, Kendle, AAIPharma) Joint venture (PSI) Local CROs (Almedis, Synergy Research Group)

Agenda ACTO: objectives, structure, members CROs in Russia: current status and perspectives Market of clinical trials in Russia: current status and perspectives Regulatory system in Russia and its compliance to international guidelines (ICH GCP, FDA, EU)

Russia – important clinical research (CR) market “Developed Market” Population 143 million Centralized healthcare system Pool of physicians eager to conduct CR Large untapped patient source Number of well established vendors High quality of data

Main areas of operation

2043 Clinical Trials in Global CT Local CTBioequivalence Studies Global CT Total Source: Roszdravnadzor

Structure of CT market Global CT Local CT (Foreign sponsors) Bioequivalence (Foreign sponsors) Bioequivalence (Local Manufactures) Local CT (Local Manufactures) Source: Roszdravnadzor

Phases of CT (Foreign Sponsors) I phase I-II phase II-III phase bioequivalence III phase 2008, III quarters (Total – 315) Source: Roszdravnadzor II phaseIII-IV phase IV phase

Japan in CT in Russia in 2008 Cardiology – 3 studies Neurology – 2 studies Psychiatry – 1 study Infectious diseases – 1 study Infectious diseases / pulmonology - 1 study Pulmonology – 1 study Infectious / skin diseases – 1 study Rheumatology – 1 study Source: Roszdravnadzor

Quality of studies Based on 36 FDA inspection : No Actions Indicated (NAI) – 18 inspections (50%) Voluntary Actions Indicated (VAI) – 17 inspections (47%) Official Actions Indicated (OAI) – 1 inspection (3%) Source: Applied Clinical Trials, Apr. 2008

Agenda ACTO: objectives, structure, members CROs in Russia: current status and perspectives Market of clinical trials in Russia: current status and perspectives Regulatory system in Russia and its compliance to international guidelines (ICH GCP, FDA, EU)

Regulatory system (structure and timelines) Total ~ 122,6 days (147,7) FINAL APPROVAL (Roszdravnadzor) ~ 25, 2 days Ethics Approval (Central Ethics Committee) ~ 44,7 days Expertise of Application for Rzd. (FGU) ~ 73,7 days Import/Export License (Roszdravnadzor) ~ 23,7 days

Laws and Regulations Federal Law “On Medicines“ № 86-ФЗ National Standard of the Russian Federation GOST P “GOOD CLINICAL PRACTICE” Order of Ministry of Health of Russian Federation of № 266 “Procedures of clinical practice in Russian Federation" Order of Roszdravnadzor of № Пр/07 “Statement of Central Ethics Committee"

NATIONAL STANDARD OF THE RUSSIAN FEDERATION GOST P “GOOD CLINICAL PRACTICE” The standard is identical to Consolidated Guideline on Good Clinical Practice, issued by the International Conference on Harmonisation of Technical Requirements to Registration of Pharmaceuticals for Human Use (ICH GCP)

Questions & Answers