Clinical Trials Industry in Russia andUkraine• The first international trial conducted in early 1990-s• Russia: 916 new clinical trials in 2012 - 60% increaseover 2011• 534 studies are ongoing in Russia• 219 studies ongoing in Ukraine• Clinical market in CIS to exceed €700m in 2014
Clinical Trial Costs in Russia and Ukraine• Shorter enrollment period• Lower PI grant expectations• Lower vendor costs• Hourly rates of clinical research specialists inthe region are twice lower than in the USA
Investigator fees vary per region01000200030004000500060007000WesternEuropeCIS Latin America Asia The USAAverage per patient investigator fee ($)
FDA Inspections Since 2005Region Countries #Inspections NAI VAI OAICIS Russia, Ukraine,Georgia 82 69,5% 29,3% 1,2%Europe All EU States 274 54,0% 45,6% 0,4%The US United States 1759 48,7% 44,1% 7,2%India India 33 54,5% 45,5% 0%China China 13 38,5% 61,5% 0%MiddleEast Israel, Turkey 26 34,6% 57,7% 7,7%
High Quality Data in CIS Region• GCP accepted as a National Standard• MDs must complete 6 years of med. school + 1-3years of residency• MDs are re-certified each 5 years.• PI must be certified in the therapeutic area• Requirement of >5 years of experience for PI inclinical trials• Highly qualified staff in CROs
Quick Enrollment• Large patient population:Russia – 143 MUkraine – 49 M• 70% of population located in large cities• Centralized healthcare system• Increasing clinical infrastructure growth• Investigators eager• Established patients’ databases• Patients see trials as opportunity• Large % of drug naïve patients• Fewer competing trials
75% of studies approved in 2012 in Russiaare conducted in 8 therapeutic areas:Oncology(110)Pulmonology(65)Endocrinology(61)Musculoskeletal diseases(45)Infectiousdiseases(45)Cardiology(42)GE(35)Psychiatry(32)
Ensuring Fast Enrollment ThroughFeasibility• Is the disease under study relevant to thepatient population?• Is the study design, comparators, andsubjects’ visits acceptable?• What are the anticipated Regulatory andEthical challenges?• What are the general timelines for studyapproval and site start-up?
IS THE DISEASE UNDER STUDYRELEVANT TO THE PATIENTPOPULATION?
Acceptance of Protocol design• Is comparator drug registeredin Russia and Ukraine?• Is comparator drug used in Russiaand Ukraine as SOC?• Is specific equipment availableat sites?
WHAT ARE THE ANTICIPATEDREGULATORY AND ETHICALCHALLENGES?
Phase I studies in Russia• Phase I in healthy volunteers studies of medicationsproduced outside of Russia are forbidden inaccordance with FZ-61• “1) to establish safety and/or tolerance of medicinalproducts for healthy volunteers, except for the trialsof medicinal products manufactured outside theRussian Federation;”
Pre-clinical Studies for Generics• Comparative acute toxicity in rodents• Comparative sub-acute toxicity inrats/rabbits/dogs
No Scientific AdviseWays to get opinion from RegulatorsUnofficial expert advice• No guarantees• Not legal• QuickOfficial comments after CTA decline• Official and legal• Time consuming
No official guidelines• No definition for biosimilar drugs• No official documents describing regulatoryrequirements for the quality, pre-clinical andclinical studies for biosimilarsBut:Biosimilar and biobetter drugs are underdevelopment in Russia
WHAT ARE THE GENERAL TIMELINESFOR STUDY APPROVALAND SITE START-UP?
Average time from application submission to final study approval (days)Regulatory approval timelinesEstoniaLithuaniaLatviaBulgariaBelarusUkraineRussia30 60 90 1200
Case Study. Ovarian Cancer• FDA and EMA-controlled study• Multinational phase III study of achemotherapy agent in women with ovariancancer• 600 patients enrolled inRussia, Ukraine, Belarus, Latvia, Lithuania andBulgaria within a 3,5 year timeline• Due to the law recruitment rates in WesternEurope, Russia was requested to enroll extra60 Pts.• Total: 658 patients at 70 sites
Case Study. Ovarian Cancer0100200300400500600700Enrolment within 3,5 years6 CEE Countries 8 Western-EU Countries