Current clinical and regulatory environment in Russia for conducting clinical research. Overview specific regulatory requirements, investigative sites and healthcare. Presentation originated in 2012

1. Clinical and Regulatory Environment
in Russia and Eastern Europe
Aleksandar Skuban, M.D.
August 2012| Philadelphia

2. disclosure
All images used with permission: www.istockphoto.com or
as noted
2

3. I took a speed-reading course and read
War and Peace in twenty minutes.
It involves Russia.
Woody Allen

4. Pharmaceutical R&D and Global CROs
Emerging Markets Development
Clinical Drug Development in Psychiatry
Background
Eastern Europe and United States
Phase II-III global studies including: Russia, Serbia,
Croatia, Hungary, Romania, Bulgaria, Ukraine, Czech
Republic, Slovakia, Poland, Estonia, Slovenia

5. Your Experience in CEE
Expectations
5

6. Presentation Overview
6

7. Overview of Central and Eastern Europe*
Baltic States
Estonia
Lithuania
Latvia
Commonwealth of Independent States
(CIS)
Russian
Federation
Ukraine
BelarusGeorgia
Kazakhstan
(…)
Moldova
7
Central Europe
Czech
Republic
Poland
SlovakiaHungary
Slovenia
Croatia
Balkans
Serbia
Montenegro
FYR MacedoniaRomania
Bulgaria
Bosnia and
Herzegovina
*not all countries in region listed

8. Ongoing Phase 2&3 Studies
(n=4832)
2611
390*
840
173
71
354
US Russia Germany Ukraine Serbia Hungary
Number of Trials
Open industry-sponsored studies at www.clinicaltrials.gov as of 5 August 2012 8
* 63 ongoing pediatric trials

9. Active Phase 1 Trials (n=2043)
1230
159
25 5 2 16
US Germany Russian
Federation
Ukraine Serbia Hungary
Number of Trials
Open studies at www.clinicaltrials.gov as of 5 August 2012 9

10. Regional Considerations for
Global Development
Access to Population with Target
Disease
Diagnostic Reliability
Compatible Treatment Paradigms
Competent Sites & Data Quality
Regulatory and Ethics Framework
Recruitment Speed, Cost, Infrastructure
10

11. Eastern Europe in Clinical
Research: The first 10 years
11Dept. HHS OIG: The Globalization of Clinical Trials: A Growing Challenge in Protecting
Human Subjects (September 2001 OEI-01-00-00190) pp.10 Table 2

12. New Global Trials Initiated in
CEE*
146
213 196
62 47
204
573
725
212
375
Hungary Poland Russia Romania Ukraine
2002 2007
Center Watch Data August 2008 (*selected countries)

13. Growth Rate of New Global Trials
Initiated in CEE*
Center Watch Data August 2008 (*selected countries)

14. Approved marketing applications
FY2008 (FDA): Source of Subjects
Drugs Biologics
Foreign and
domestic subjects
92,859 206,842
Percentage of
foreign subjects
56.9% 86.9%
Foreign and
domestic trial sites
11,227 717
Percentage of
foreign trial sites
54.6% 49.7%
14
Source: "Challenges to FDA's Ability to Monitor and Inspect Foreign Clinical Trials," Dept. of
Health and Human Services Office of Inspector General, June (oig.hhs.gov/oei/reports/oei-
01-08-00510.pdf)

15. Approved marketing applications
FY2008 (FDA): Source of Foreign
SubjectsDrugs Biologics
Number of foreign
subjects
52820 179712
WE, AU, Japan,
NZ, CAN
32761 (62%) 109706 (61%)
New EU members 5474 (10%) 1062(0.5%)
Emerging Countries
(BRICM)
4789 (9%) 19888 (11%)*
Number of Countries 68 38
15
Data from : "Challenges to FDA's Ability to Monitor and Inspect Foreign Clinical Trials," Dept.
of Health and Human Services Office of Inspector General, June
(oig.hhs.gov/oei/reports/oei-01-08-00510.pdf) *No subjects from China or India

16. Leading physicians and Institutions
Early adoption of GCP guidelines
Excellent Data Quality
High Patient recruitment
Enthusiasm for international
R&D collaboration
“Rescue Studies”
Evolving regulatory institutions
Infrastructure challenges
Skilled clinical research professionals
Lower study costs

17. Russia In Global Clinical
Research
17
CEE, CIS, BRIC, Asia,
Emerging Country,
Key Pharmaceutical
Market

18. Russia: Key Facts
Large, diverse, decreasing population: 143 m
Geography across nine time zones
Ethnically and culturally diverse country
Centralized health care system
Accessible patient population
Research concentrated in Moscow, St.
Petersburg
73% population in urban areas
18

19. Health Care in Russia
19

20. Health care expenditure
8.1
7.9
11.5
6
2560
1308
4011
583
United Kingdom*
Hungary
Switzerland
Russian Federation
US$ PPP2 % of GDP
Source: WHO EU Atlas of Health 2008

21. Among Highest in Europe: Hospitals
Beds and Physicians
304
397
431
896
833
806
792
568
966
Hungary
Switzerland
Russian Federation
Hospital beds Nurses Physicians
Per 100000 population Source: WHO Atlas of Health 2008 in Europe

22. Russia Health Statistics (WHO)
1st
Deaths All Causes,
CV, IHD, Pulmonary,
Injury & Poisoning
2nd
Deaths Cancer,
Cerebrovascular,
Suicide
3rd
HIV New Cases
Source: WHO Europe 2008

23. Russia Health Statistics (WHO)
2nd Highest % male
smokers and spirits
consumption
Lowest life expectancy
at birth for men
(59 years)
(Source: WHO Europe 2008)

24. Deaths from diseases of circulatory
system
301.2
175.3
28.6
157.1
47.8
4.9
Russian Federation
Hungary
France
Females Males
Per 100 000 population (25-64 years) Source: WHO Atlas of Health 2008 in Europe 24

25. Deaths from cancer
224.5
301.2
86.8
123.3
157.1
102.5
Russian Federation
Hungary
Sweden
Females Males
Per 100 000 population (25-64 years) Source: WHO Atlas of Health 2008 in Europe 25

26. Regional Health Statistics
*Per 100000 male population Source: WHO Atlas of Health 2008 in Europe 26
Hungary
Russian
Federation
Ukraine
Population(millio
n)
10 142 46
Deaths All
causes*
13th Highest (782.2*) 4th
Circulatory
System
12th Highest (762.2) 4th
Ischemic HD 5th Highest (406.3) 2nd
Cancer Highest
(301.2)
2nd (224.5)
Lung Cancer Highest (99.7) 5th 10th
Suicide 5th (40) 2nd (56.1) 8th
AIDS new cases Low (0.2) Low (0.6) Highest (9.7)

27. Regulatory Framework
New Federal Drug Law “On Drugs
Circulation” 1 Sep 2010
Local study required if no Russian
patients in global Phase 3
program
Need for local study may delay
registration in Russia for 2-3 years
27
http://www.efgcp.eu/Downloads/EFGCPReportFiles/Russ
ia%20definitive.pdf

28. Local Clinical Trial
Requirements
Local Patient Data Needed for New Products,
Line Extensions, New Indications
No specific guidance on design, type of study
or required number of patients
Guidance based on Expert feedback,
Company expertize, informal discussions,
industry benchmarks
28

29. Impact on Product Registration
For timely product registration
consider including Russian sites
in Phase II-III trials
Requirements for Local
Regulatory Studies may further
evolve
Strategy for product launch in
Russia 29

30. Local Ethics Committees (LECs)
LEC at each investigative site
Submission after Russian Ministry of Health
approval
Protocol & documents in Russian
2-4 weeks review cycle
Some with executed clinical trial agreement
Most LECs review without a fee
30

31. Clinical Investigative Sites
700000 physicians
1% involved in clinical studies
900 institutions accredited
by Ministry of Health
31

32. Global Share of Sites and
Patients
Country Density* WW site share
%
United States 120.2 48.7
Germany 51.2 5.7
Japan 15.7 2.7
Russia 7.7 1.5
Hungary 62.5 0.8
Poland 30.9 1.6
32*number of recruiting sites/country population (m) Data selection from Thiers at al: “Trends in the
globalization of clinical trials” Nature Vol.7, Jan 2008 (*as of April 12th 2007)
0.03% population in Russia participated in clinical studies
in 2006

33. Russia in Global Clinical Trials
CV outcome studies from 1990s:
Patient Population and Expertize
Notable Proof of Concept studies:
Alzheimer’s Disease and Schizophrenia
Current Phase II-III landscape:
Oncology, CV, Diabetes, Respiratory, CNS
In 2011 MoH issued 567 approvals-
370 for global studies
33

34. Opportunities and Challenges
Enrollment
Study Cost
Execution Quality
Site Qualification
Diverse patient
population
Multi-specialty large
medical centers
New legislation
Changing reg.
environment
Saturation of Good
Sites
Customs procedures
Logistics
Language Barrier
Infrastructure
POC Phase II Studies
New Legislation34

35. In Sum
Countries with Unique Advantages – Continue to Attract
Clinical Research Opportunities
Evolving regulations and Health Authorities: Local Clinical
Trials for Product Registrations
Experienced and well-qualified investigators: Increasing
local and global competition for quality sites
Build Own Expertise and
Critically Evaluate Expectations
On Regular Basis
35

36. Clinical and Regulatory Environment in
Russia and Eastern Europe
Aleksandar Skuban, M.D.
August 15, 2012| Philadelphia
Thank you