text:
Are you sure?
This action might not be possible to undo. Are you sure you want to continue?
©2006 RM Consulting
1.0 Politics and Economics .......................................................................................................... 5 1.01 Background ....................................................................................................................... 5 1.02 The Economic Situation ................................................................................................... 6 1.03 Risks ................................................................................................................................... 9 1.03.1 Political....................................................................................................................... 10 1.03.2 Security ...................................................................................................................... 11 1.03.3 Legal .......................................................................................................................... 11 1.03.31 Intellectual Property Rights.................................................................................. 11 1.03.4 Foreign Direct Investments........................................................................................ 13 1.04 Demographics ................................................................................................................. 13 1.05 Infrastructure ................................................................................................................... 17 1.05.1 Transportation............................................................................................................ 17 1.05.2 Communication .......................................................................................................... 18 2.0 Pharmaceutical Market ......................................................................................................... 19 2.01 History .............................................................................................................................. 19 2.02 Pharmaceutical Expenditures........................................................................................ 21 2.03 VAT on Medicines ........................................................................................................... 22 2.04 Market Segmentation ...................................................................................................... 23 2.05 Market Drivers & Restrainers......................................................................................... 25 2.06 Pharmaceutical Regulation ............................................................................................ 26 2.07 Drug Registration ............................................................................................................ 27 2.07.1 Documents Requirements for Registration of Foreign Drugs.................................... 28 2.08 Certification Requirements ............................................................................................ 30 2.09 Pharmaceutical Promotion and Advertising ................................................................ 31 2.10 GMP .................................................................................................................................. 31 3.0 Healthcare in Russia ............................................................................................................. 33 3.01 Healthcare Policy ............................................................................................................ 33 3.02 Healthcare Spending....................................................................................................... 35 3.03 Structure of the Healthcare System .............................................................................. 37 3.03.1 Provision of Primary Care .......................................................................................... 39 1
3.03.11 Health Posts ........................................................................................................ 39 3.03.12 Health Centres..................................................................................................... 39 3.03.13 Polyclinics ............................................................................................................ 39 3.03.2 Hospitals .................................................................................................................... 40 3.03.3 Health Institutions ...................................................................................................... 40 3.03.4 Sanatoriums and Health Resorts............................................................................... 40 3.04 Health of the Nation ........................................................................................................ 41 3.04.1 Population Demographics.......................................................................................... 41 3.04.2 Life Expectancy and Causes of Death....................................................................... 42 3.05 Disease Prevalence......................................................................................................... 43 3.05.01 Cardiovascular Disease ........................................................................................... 44 3.05.02 Cancer ..................................................................................................................... 45 3.05.03 Tuberculosis............................................................................................................. 46 3.05.04 Diabetes ................................................................................................................... 46 3.05.05 Drug Addiction and Alcoholism................................................................................ 47 3.04.06 Mental Disorders...................................................................................................... 48 3.04.07 Sexually Transmitted Disease (STD)....................................................................... 48 3.04.08 HIV ........................................................................................................................... 49 3.04.09 Dermatologic Diseases ............................................................................................ 50 3.04.10 Injuries, Poisoning and Other Accidents.................................................................. 50 3.04.11 Hepatitis ................................................................................................................... 50 4.0 Clinical Trials in Perspective................................................................................................ 52 4.01 History of Clinical Trials in Russia ................................................................................ 52 4.02 Growth in Trials ............................................................................................................... 54 4.03 The Russian CRO Industry............................................................................................. 55 4.04 Why Conduct Clinical Trials in Russia? ....................................................................... 56 4.04.01 Benefits of the Post-Soviet System ......................................................................... 57 4.04.02 Access to Investigators ............................................................................................ 58 4.04.03 Cost Saving Opportunities ....................................................................................... 59 4.04.04 Access to Patients ................................................................................................... 59 4.04.05 Fast Recruitment Rates ........................................................................................... 60 4.04.06 Patient Compliance.................................................................................................. 61 4.04.07 Quality of Work ........................................................................................................ 61 5.0 Clinical Trial Issues ............................................................................................................... 63 5.01 Study Costs ..................................................................................................................... 63 5.01.1 Investigator's Fees..................................................................................................... 63 5.01.2 Equipment Expenses ................................................................................................. 64
5.01.3 Monitoring Expenses ................................................................................................. 64 5.02 Language ......................................................................................................................... 64 5.03 Logistics........................................................................................................................... 65 5.03.1 Travel ......................................................................................................................... 65 5.03.2 Mail and Courier Services.......................................................................................... 66 5.03.3 Communication .......................................................................................................... 67 5.04 Background Therapy ...................................................................................................... 67 5.05 Cultural Differences ........................................................................................................ 68 5.06 Recruitment Issues ......................................................................................................... 68 5.07 Logistics and Local Support .......................................................................................... 69 5.08 Monitoring........................................................................................................................ 69 5.09 Data Management............................................................................................................ 70 6.0 Study Set-Up .......................................................................................................................... 71 6.1 Regulatory Compliance - the Federal Drug Law ............................................................ 71 6.2 Selection of a CRO and External Vendors...................................................................... 72 6.3 Site Identification/ Investigator Selection....................................................................... 73 6.31 Medical Institutions ....................................................................................................... 75 6.4 Local IECs .......................................................................................................................... 76 6.5 Protocol and CRF Design ................................................................................................ 76 6.51 Protocol ......................................................................................................................... 76 6.52 CRF............................................................................................................................... 77 6.6 Legal Issues, Insurance and Contracts .......................................................................... 77 6.61 Patient Information and Informed Consent Form ......................................................... 78 6.62 List of Documents to be Submitted to Local IRB/IEC or Regulatory Authority ............. 78 6.63 Local Insurance Policy .................................................................................................. 79 6.64Contracts with Investigators and Investigative Sites ..................................................... 80 6.7 Study Approval.................................................................................................................. 80 6.8 Patient Recruitment .......................................................................................................... 81 6.9 Site Training....................................................................................................................... 82 7.0 Importing Clinical Trial Materials ......................................................................................... 83 7.10 Importing the Study Drug ............................................................................................... 83 7.10.1 A Centralised Approach ............................................................................................. 84 7.20 Importing Other Materials .............................................................................................. 85 7.20.1 Study Documents....................................................................................................... 85 7.20.2 Devices ...................................................................................................................... 85 7.20.3 Laboratory Kits........................................................................................................... 85 7.20.4 Packing Materials....................................................................................................... 85
................................... 86 7.THE HEALTHCARE.................................................. 87 4 ...................40 Export of Other Clinical Trial Materials....................50 Summary ........................... PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA 7......... 86 7................................................................................30 Exportation of Biological Media ...........................................
Personal 30%. frequent changes. Mikhail Gorbachev came to power and introduced many reforms in an attempt to modernize the economy and make the Communist Party more democratic. especially with the US but also with Western Europe and Japan. surrounded by corrupt oligarchs. Used to enrich a few at the expense of economic development. Serious concerns about law. New managers are installed and motivated to carry out real restructuring and value creation for shareholders. consistent.THE HEALTHCARE. in supplies of oil and in the fight against terrorism. In 1985. Figure 1. Parliament aligned to Presidential Administration policies and priorities. These reforms ultimately led to the break up of the USSR and the end of the one-party Communist rule. ownership and commercial contracts. International Perception of Russia Government Oligarchs Industry Restructuring Policy Continuity Corporate Governance Major abuses the norm. Continuing strong influence of the Communists in the Duma. Putin's priority. Taxes FDI 5 . calling foul. Increasing importance of the new entrepreneurial class. More consistent. surrounded by technocrats from young professional elite.01: Changes in the Macro-Environment 1997 President Boris Yeltsin: ill. Centralisation and consolidation of power under Putin. Dominant in all important sectors. Improved relations. Corruption Pervasive. Corporate 24% and major simplification of tax codes. World Status Uncertain 'engagement' with US and NATO. Small group with enormous economic power and political influence. Risky emerging market. Policy engaged to reduce corruption through restructuring. Discussions in place on closer relations with NATO and membership of the WTO. Smaller group with increasing economic power but decreasing power and influence in politics.01 Background By the 1980s. Partner with the West in business. Personal 13%.75 billion investment for 50% of TNK. corporate governance and legal reform. Unstable. communism in the USSR was not working. Major conflicts within parliament and the Regions. 2003 Vladimir Putin: fit. BP announces $6. stable and reliable. Asset shifts with very little attention to value creation.0 Politics and Economics 1. BP at "war". Corporate 35% and dozens of hidden taxes. pragmatic. following Cold War. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA 1. erratic. Regional governors brought into check. Progress will be gradual but significant improvements have been made already. Focus on (conflicting) personal agendas.
1 Key Economic Performance Indicators 45 40 Persentage (unless mentioned) 35 30 25 20 15 10 5 0 -5 2001 2002 2003 2004 2005p 2006e 2007e 2008e GDP Growth % Imports (G+S) % Change Inf lation (CPI) % Local Currency to US$ Consumer Spending % Change Exports (G+S) % Change Population Growth % Local Currency to Euro p – preliminary results. Many multinational giants have expanded their operations into Russia covering industries such as: energy and power. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA With Boris Yeltsin came democracy. manufacturing. 1. was his failure to establish strong political institutions enforcing the economic and financial stability of the country.THE HEALTHCARE.02. but. He helped bring down the communist system. e – estimates Source: World Market Analysis: Global Insights – Russia. In August 1998 the Russian Financial crisis occurred causing a major downturn in worldwide financial markets as the rouble was devalued. Russia 6 . both for Russia and for himself.02 The Economic Situation In recent years positive economic growth in Russia has attracted much attention form international markets. After this event. Following the election of Vladimir Putin many reforms to the legal system and political infrastructure have been implemented. foreign investments in the country were virtually non-existent negatively impacting not only on the economy but also on the reputation of Russia itself. healthcare and many others. Many in the West saw him as a democrat and reformer. The Economist – Country Profile. retail. economically. The confidence of foreign investors has returned and the overall picture has changed considerably since the 1980s . Figure 1. socially and commercially and is now one of the fastest growing economies in the world.Russia has become more stable politically. his biggest mistake.
THE HEALTHCARE.2 Source: DataStream Slowing growth in imports is a direct result of current government policy and reform .02.3 Source: DataStream In 2005. GDP per capita. 7 . Figure 1. however. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA The gradual slow down in GDP growth is a natural result of the economy reaching maturity. real disposable income was on the rise as were corporate profits fuelling an increase in investments in fixed capital. However. shows no signs of slower growth suggesting a further increase in the standards of living in Russia. Figure 1.the import substitution program aims to start substituting imports with domestic production thus supporting the domestic manufacturers and strengthening the economy.02. it must be noted that growth is still positive thus encouraging foreign investments into the country.
January 2006 outlook 8 .8% in 2004. January 2006 As was the case in 2004.5 1 Source: Bank of Russia.real consumer spending grew by 10. Although.THE HEALTHCARE.02. slower growth is predicted . PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA Figure 1. January 2006 1 The Bank of Russia. The share of household money income spent on the purchase of goods and services rose by 1.9%. there are no clear signs of a deterioration in consumer spending.02. consumer spending grew faster than household income in 2005 while the propensity for consumption increased and the share of household spending on savings declined.7% in 2005 (year on year) compared to 11. Figure 1. The increase in consumer spending was accompanied by rapid growth in bank lending to individuals.1 percentage points in 2005 (year on year) to 70.4 Source: Bank of Russia.
January 2006 While the pace of economic growth has been enviable over the past several years. but unlocking this potential will require dedicated. is not in doubt. or even an attempt to roll back some elements of privatization in the interest of increasing the direct influence of the State over strategic sectors of the economy. 9 .THE HEALTHCARE. The enormous long-term potential for Russia. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA At the same time consumer prices grew by 10. uninterrupted structural economic reforms and astute macro-economic management.03 Risks The principal risks to a modestly optimistic medium-term forecast for Russian economic growth are varied. the Central Bank has been unable to rein in inflation effectively.02. Oil prices have boosted export earnings. but this has been accompanied by an upward pressure on the currency and domestic prices.9% in 2005 compared to 11.6 Source: Bank of Russia. Additional major concerns include the failure of the Russian government and Parliament to manage key unfinished elements of structural reform effectively. With a dual focus on the exchange rate and inflation. thus supporting rising consumer confidence and affordability. based on its abundant natural resources and human capital. which would threaten investment growth as well as the country's fiscal situation. the signs are now clear that record-high world market oil prices are not enough to maintain this momentum.7% in 2004. Figure 1. They include an extended period of sharply lower world-market oil prices. 1.
The decision is made by the President and administration.03.03.1 Political During his first term. the long-planned reform of energy systems and of the provision of communal services and utilities is beginning to be put into action. and ever-more aggressive policy in favour of the wealthy. pension reform was initiated (aiming to turn all pensions over to privately held investment funds). And those problems. under which those problems that it is possible to solve democratically are solved by democratic means. Dec 2003). This includes promoting the role of special services. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA 1.1: Russian Political System The Presidency (Administration) Federal Assembly (Legislature) Higher Courts (Judiciary) Prime Minister Federal Council Constitutional Court Council of Ministers (Government) State Duma Supreme Court Supreme Arbitration Court The State Duma is the lower house of the Russian parliament with United Russia (Edinaya Rossiya) being the dominant party. V. "Russian elections". 2 10 . not susceptible to democratic solutions are solved by authoritarian means. (World Socialist Web Site. a general attack on democratic and civil rights. Volkov.THE HEALTHCARE. Three years of Putin's rule have achieved much in this direction: − − − 13% income tax was introduced. Figure 1." 2 The strengthening of authoritarian tendencies has been accompanied by reinforcement in the apparatus of repression. The continued predominance of United Russia in the State Duma and the positive public support of President Putin and his reforms gives the government Managed democracy' is a system. aggregate social benefits tax was reduced by 5%. − − the diminution of already threadbare social programs and benefits continues. Putin worked hard at bolstering his authority and that of his presidential administration in engineering a system that is regarded as a "managed democracy.
31 Intellectual Property Rights Russia's laws on the protection of intellectual property protection are well drafted and meet many international standards. trademarks. at least on paper. and the 11 . PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA the strength that it needs to bring stability to the country in the short-term. Nevertheless. with overhauls of land. 1.03. Nevertheless. High oil prices have allowed the government to balance the budget.3 Legal There has been rapid legislative reform since the election of President Vladimir Putin and a more compliant parliament.03. 1. 1. Better intellectual property legislation was passed in 2002 as Russia prepared its bid to join the WTO. The post-1991 period has witnessed a real explosion in organised criminal and semi-legal activity. The election of a new president in March 2008 will present the biggest opportunity for real change. tax and company law bringing much-needed changes. the inherent conservatism of the United Russia party has the potential to become an obstacle to reform in the medium-term. In line with economic development and growth there is still concern that around 45% of consumer goods and services fall into the shadow economy.2 Security Organised crime is one of the main drawbacks of doing business in Russia. (until the 2008 Presidential elections at least). Government bureaucracy is at the moment one of the main issues for foreign investors as it creates unofficial inter-regional trade barriers and the power of the regional authorities may get in the way of business development. Russia's record on the actual protection of intellectual property has been inadequate at best in the past decade. but this has masked the fact that liberal economic reforms are needed to create long-term stability.THE HEALTHCARE. despite the apparent dominance of Putin and his genuine desire to implement these reforms. The problem is worsened by widespread corruption in the police force. Today control over this activity is tightening as the government is constantly working towards the elimination of organised crime. this situation is changing in a positive direction as regional governors will now be appointed by the President instead of being elected as before. There is concern over whether or not the Duma elections in 2007 will allow liberal and reformist politicians fair representation or sufficient power to act on their agenda. Russia also belongs to most of the international conventions on patents. copyrights and other intellectual property. However. labour.03.
Russian Customs can help trademark and brand name owners to combat counterfeit goods coming into Russia from other countries. innovative product market (around 70% of market share in dollar terms). It is recommended that a wider description of the invention or product be used. Infringement of intellectual property rights is a nationwide problem but the situation is especially poor in the Russian Far East. practically all medicines of commercial interest regardless of their brand names have been targeted at some point. According to official reports. omitting insignificant details in the patent formula when patenting a product or invention in the Russian Patent Department. and may also impose a penalty.where counterfeit drugs can seriously harm their users . It should be mentioned that Russian pharmaceutical companies produce mostly low-cost/high volume generic drugs and are therefore generally not targets for counterfeiters – it is the imported. the IPR owners can apply to several different agencies to enforce the protection of their rights. The Coalition for Intellectual Property Rights (TSIPR) estimates that counterfeit drugs account for about 15% of total pharmaceutical market resulting in large amounts of lost profits for legal companies. To stop illegal usage of a trademark. In addition. In the event of an infringement of intellectual property rights. and to conduct raids of pirate plants.the government has worked successfully with companies to counter this grave danger to public health. To reimburse lost profit and restore the company's reputation through the mass media. If a company intends to patent a process. video products (~ 85%). it should also patent the end product of this process. The trademark/brand name owner should file an application with the State Customs Committee requesting assistance in protecting the owner's intellectual property rights. that is affected. nevertheless. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA country is on the 301 watch list for IPR infringements. The top 3 industry sectors to be affected by counterfeiting include: the music business (~ 75%). and computer software (~ 97%). the main entrance points of the goods into Russia. 12 . to allocate law enforcement resources for combating IPR crime. In the pharmaceutical industry . It is also recommended that companies consult with patent agencies before filing a patent application. a company should apply to the local Commercial (in Russia called Arbitration) Court. Authorities have taken steps to strengthen relevant legislation. 63 counterfeit medicines were discovered in 2004. The applicant should also provide such documentation as identification data for the goods to be protected. and a list of authorised dealers and distributors.THE HEALTHCARE. a company should contact the Regional Department of the Ministry of Antimonopoly Policy and Business Support (MAPBS). The MAPBS will send a written order instructing the infringing party to stop illegal usage of a trademark.
is attracting more FDI into the country. Roughly 75% of people live in the European part of Russia (west of the Urals).04 Demographics In 2005. there has been much activity across all sectors. over 50% of 23 major foreign pharmaceutical companies (Pfizer. Bureaucratic barriers include: − − − − − − unexpected changes to tax laws. Sanofi-Aventis. Novartis. GlaxoSmithKline. harassment by the authorities. inter-regional trade barriers. the population in Russia was estimated at around 145 million. Petersburg and into Russia's regional centres. unexpected changes in trade policy. While the government continues to implement reforms and to encourage greater inflows of FDI. A study conducted by the Association of International Pharmaceuticals Manufacturers (AIPM) and PricewaterhouseCoopers released in August 2005. customs authorities. about 33 percent of these companies plan to bring their local production subsidiaries on-stream in the next two-three years.4 Foreign Direct Investments While the vast majority of FDI in Russia remains in the natural resource sector. 1. This is mainly due to the high level of trade and industry in the region leading to better work prospects and generally better living conditions. Highest on the list of complaints by foreign businessmen is the pervasive influence of government bureaucracy in all areas of business operations. while 19 percent plan to do so within the next five years. as well as unofficial barriers imposed by regional authorities and the arbitrary application of the rule of law. most of the industrial cities with over 1 million inhabitants are also located in the European part. political and industrial development in Russia. Specifically. notably in the retail sector. fundamental outstanding issues continue to plague investment confidence. 13 . According to this study. in addition. suggested that the more progressive reforms in conjunction with improved economic. the retail banking sector and in the food and beverage sector which is set to expand from Moscow and St. to name a few) operating through representative offices in Russia are planning to set up local production within the next five years.03. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA 1.THE HEALTHCARE. tax authorities.
St. 14 . however. historical. Fig 1. All global companies from all industries are represented here. scientific and business centre. The Russian capital . Most global companies in most industries are represented here.ru The second largest city and the largest seaport in Russia. Very good healthcare infrastructure.04. High industrial and economic development.2004.THE HEALTHCARE. an influx from the Baltic countries has helped Russia to compensate for population losses .mosreg. architectural.2: Summary of the 10 Major Russian Cities The largest city in Russia.04. Moscow Population > 10 million Very good transportation and telecommunication infrastructure. cultural and scientific centre. 5.1: Major Russian Cities Fig 1.for the period of 1989 .7 million people left the country while around 10 million migrated into Russia.1 million A major rail junction and industrial. Petersburg Population ~ 5.its political. Location of all major research institutions and scientific centres. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA The Russian population is in decline due to natural causes as well as migration form former USSR. www.
2 million One of the main ports on the Volga river. large scientific Novosibirsk Population > 1. Good transportation and telecommunication infrastructure. A highly industrial and resource rich city. industrial city with a healthy growing economy and relatively high consumer income levels.ru A centre of scientific and technological progress. Flight time to Moscow: around 1h www. Yekaterinburg Population ~ 1. Flight time to Moscow: 2h 45 min http://www. High industrial and economic development.5 million scientific research laboratories. Good transportation and telecommunication systems.adm. There are several affiliates of the Russian Academy of Science.government. High industrial and economic infrastructure Flight time to Moscow: 3h 5 mins www.ru/eng/ A large Port on the Volga River with a developed transportation and telecommunication infrastructure. High level of FDI. Samara Population > 1.ekburg.4 million institutions and laboratories.nnov.3 million Healthcare system well structured and one of the most advanced in the country. Flight time to Moscow: 1h 30 mins http://www.ru The main industrial and cultural centre of the Ural region. Well organised healthcare system. 15 .spb.THE HEALTHCARE. Developed rail and air transport systems.nso. Lack of research institutions and laboratories. Well organised healthcare system. and about 100 Nizhny Novgorod Population > 1.ru/ A dynamic. High industrial and economic development. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA High industrial and economic development. An entire scientific region inside the city comprised of universities.
Flight time to Moscow: 1h 45 mins www. Azov and Caspian).ru A significant Volga river port. A number of research institutions. Well developed telecommunication structure and good transportation system. High industrial and economic development.THE HEALTHCARE. The third largest city in imports/ exports turnover with good transportation and telecommunication infrastructure.adm. A major passenger-oriented and industrial shipping port. Good industrial and economic development. Rostov – on – Don Population > 1 million Located in the heart of trade routes connecting 3 seas (Black.rostov-gorod.volganet.ru A city of commercial and cultural importance being located on the coast of the Don river. Chelyabinsk Population > 1 million Well organised healthcare system. 16 . High economic and industrial development Flight time to Moscow: 1h 45 mins www.ural-chel. Scientific research mainly done by the State Medical Academy. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA 10 pharmaceutical manufacturers. Developed transportation and telecommunication sectors.ru Irkutsk Population ~ 1 million Industrial and scientific city in the heart of Siberia.samara. Volgograd Population > 1 million Well organised healthcare supported by local government. Flight time to Moscow: 2h 30 mins www.ru One of the major industrial centres in Russia. Good industrial and economic development. Well developed transportation and telecommunication sectors. Flight time to Moscow: 1h 35 mins www.
the conditions and service are not perfect for long-distances.05. whereas the fast train takes around 6-7 hours. Petersburg to Moscow is just over 1 hour. A 2 hour flight would typically cost around 3000-5000 roubles (US$ 103173 economy class) depending on the airline. The best and fastest way to travel around the country is by air . The car is the second best mode of transport but traffic conditions can be notoriously bad. Flight time to Moscow: 5h 35 mins http://www1. there are a variety of low-cost carriers available that make air travel more affordable to the wider population. the transportation system in Russia is good regardless of whether you are travelling around the country or just within a city. Nevertheless. the flight from St.all cities in Russia and almost every town can be reached by air. Good industrial and economic infrastructure. transitioning from a centrally managed system with lack of private initiative to a Western-type model. the transportation network has undergone significant changes in the past ten years. railways and power stations are around 45-50 years old. Moreover. the lack of investment in recent decades has had a negative effect on its quality. trains take much longer than air travel . Money is being spent on improving the quality of the road network. Overall. Trains tend to be cheaper than air travel (depending on the "class" of travel) and relatively reliable.ru/ 1. while ports and railways are being reconstructed to attract more business and investments. st rd 17 . The transformation has led to a rapid increase in quality and a more diversified infrastructure and service. The main problems are delays and relatively old technical support systems.THE HEALTHCARE. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA Local government supports and develops the healthcare system. the flight to Novosibirsk is around 3.for example. The majority of Russian ports. Inner city travel is generally pretty good barring a few delays. A number of scientific research centres.5 hours while the train takes 48 hours and will cost between US$400 (1 class) and US$70 (3 class). airports. however.irkutsk.05 Infrastructure 1. however. Air travel is most popular for long distances (for example to Siberia or Asian Russia).1 Transportation Although Russia's infrastructure is vast.
receiving or shipping parcels. TNT. as well as under-financing of this sector by local government. this is not common in the major cities. there are prepaid calling cards that can help to make these calls more affordable. Although long-distance and international calls are quite expensive by Russian standards. one can good quality dial-up and broad band services. Moreover. electrical supply can be a problem. the internet is mostly dial-up which is not very reliable. Fixed line and mobile networks are present in every city speeding up business processes. Consequently.2 Communication The country's telecommunication infrastructure is patchy in terms of both quality and geographical coverage. Fed-Ex. The IT market has grown by an average 30% per annum over the last few years. but in more developed areas.05. the Russian mail system can be used although it is generally not as reliable as the courier system. but is generally confined to the main urban centres with Moscow making up as much as one-quarter of users. DHL offices are located in almost every town and city. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA 1. whereas Fed-Ex and TNT have more limited coverage. although. In the smaller cities. however. In the major cities. providing a fast and reliable way for companies to import goods and materials into the country. 18 . or in communication. It should be noted that in the 10 aforementioned major cities the communications infrastructure is very well developed and one would not experience any constraints in sending. All major world couriers are present in Russia: DHL. Internet providers exist in every Russian city. in mobility. Due to an undersupply and scarcity of electricity resources. and the citizens of St Petersburg coming in next. fax transmissions can be unreliable. new wireless internet technology is slowly coming onto the market. in some areas the electricity is turned off for a period of time in the day ("veer").THE HEALTHCARE.
the pharmaceutical market was viewed as being relatively successful in Russian terms. Stabilisation of the exchange rate against inflation means that people have more cash available to spend on more effective and expensive drugs. Nowadays. Economist Intelligence Unit Post-crisis.3billion (55%) and Russian production was $1. which in turn has led to the substitution of Russian produced medicines by foreign ones.20% annual growth and reaching $7. consumption of pharmaceuticals had overtaken pre-reform levels and the market reached $3. Growth can be attributed to both a rise in real production volume and an increase in buying power.THE HEALTHCARE. the Russian pharmaceutical market has witnessed a steady and fast recovery. Total imports during the first six months of 1999 amounted to $0. Fig: 2.01 History Prior to the financial crisis of 1998. however. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA 2. equivalent to about 40% of the 1998 level for the corresponding period.0 Pharmaceutical Market 2. By 1997. Thus.1billion in terms of ex-manufacturers prices.1bn (45%). Imports accounted for $1. Consumer spending shrivelled.4billion. along with federal and regional funding for healthcare. The 1998 economic crash made a huge impact on the market.1: Russian Pharmaceutical Sales 2003a 2002a 2001a 2000a 1999a 1998a 0 500 1000 1500 2000 US$ million 1713 1624 2330 2500 2039 2297 3124 3000 3500 Source: US Census Bureau. the Russian Pharmaceutical market consists of two main segments: the retail pharmacy sector (80%) where over 40% of pharmacies are privately owned and provide an 19 .33billion. by Western standards it was considered underdeveloped. exhibiting 10 .4billion in retail price terms in 2005 – and it is still growing.01. by 2004 the market share of imported pharmaceuticals reached 60% of the total market in dollar value. and the value of the market tumbled to an estimated $2.
Boston Consulting Group. domestically produced drugs continue to dominate the market in terms of volume of sales.3: Market Share of Imported vs. $ Domestic Imported Share. LCP However. Petersburg) precludes them from buying expensive imported pharmaceuticals. imported products. it must be noted that cheap. Domestic Drugs 29 75 75 76 71 25 June 29 29 71 71 25 July 24 August June July August Share. and the hospital segment (20%) which mainly focuses on relatively inexpensive generic drugs. Fig: 2. Fig: 2. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA excellent outlet for expensive. packs Source: Retail Audit of Russian Pharmaceutical Market by DSM Group.THE HEALTHCARE. This is due to the fact the majority of healthcare expenditure is financed on an "out-of-the-pocket" basis and that the income of an average citizen (excluding Moscow and St.01. 2005 20 .2: Russian Pharmaceutical Market 8 6 $bn 4 2 0 2000 2001 2002 2003 2004 2005e Ex-works prices Retail prices Wholesale prices Linear (Retail prices) Source: Brunswick UBS Warburg.01.
the per capita consumption of pharmaceuticals and healthcare products in Russia is expected to increase in the long-term.02.1: Drug consumption per capita (August '00 – August '01) 500 450 400 350 452 381 $ per capita 300 250 200 150 100 50 0 223 184 177 160 152 138 127 89 67 53 26 26 te d Un i te d Un i Source: World Health Organization: * GDP for Russia is estimated for 2001.almost 5 times less compared to Poland and 47 less than in the US.THE HEALTHCARE. ** Including hospitals 2. Privately Funded Pharmaceuticals 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Au s tra lia /N ew 19 95 19 96 19 97 19 98 19 99 20 00 20 01 Source: Russian Ministry of Health 02 E 20 03 E 20 04 E 20 05 E 20 06 E 20 ai n Ze al an d Ar ge nt in a Po la nd M ex ic o Br az il Ru ss ia * Privately purchased drugs (Pharmacy) Reimbursed drugs (Pharmacy) Hospitals St at es Ja pa n* * Fr an ce Ca na da G er m an y Ita ly om gd Ki n Sp 21 . Fig: 2.02. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA Fig: 2. In spite of this fact.2: Reimbursed vs.02 Pharmaceutical Expenditures Russians spend very little on pharmaceuticals compared to Western populations and Central Europeans .
which holds that an import license and a letter indicating that a product is undergoing re-registration should be sufficient to qualify for the reduced 10 percent rate. The introduction of the VAT was more or less conducted according to the original plan. and the majority of patients pay the full price for prescribed drugs. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA 2. introduced a reduced 10 percent rate on drugs (provided that the drug in question has a valid registration certificate). people with HIV. Such lack of consistency or coordination between the two government agencies is causing substantial damage to importers. Those eligible for reimbursement include the disabled. they are subject to the 20 VAT percent rate.03 VAT on Medicines The levying of VAT on pharmaceuticals was seen as an important source of revenues in the Russian government's efforts to render the major changes in Russia's new tax regime revenue neutral. Application of the new reduced rate of VAT on pharmaceuticals became the source of much misunderstanding at customs posts. The customs authorities' actions contradict the MoH position. customs officials are charging a 20 percent VAT. Chernobyl liquidators. Previously. issued by the MoH. and cancer and diabetes patients. passed by the Duma in December 2001. import permits for the pharmaceuticals were the only documents necessary for importation. Some customs inspectors began to request registration certificates for the drugs. Russia is not unique in having a VAT on pharmaceuticals. Such a policy has few opponents in the West since medical insurance often covers the cost of prescribed drugs. many of whom will be forced to sacrifice on other basic necessities to buy medicines. Many Western countries levy 15-17 percent VAT on all goods and services. Many pharmaceutical industry analysts believe that VAT on medicines is stimulating another problem – because of the high price of all medicines. the levying of VAT on pharmaceuticals is an unpopular measure among consumers and manufacturers. Not surprisingly. In cases. making copycat 22 . Russian consumers have little disposable income. particularly imported ones. including pharmaceuticals.THE HEALTHCARE. The compromise amendment to the Tax Code. Some analysts worry that VAT on pharmaceuticals will harm Russia's numerous poor and pensioners. and have difficulty meeting the increased price levels. 2002. The Customs Committee issued instructions to all customs posts clarifying that the 10 percent VAT rate should be levied on pharmaceuticals as of January 1. Consequently the pharmaceutical companies will be obliged to absorb some of the additional costs of VAT in order to maintain the market. the war veterans. This has caused problems for pharmaceutical products undergoing periodic re-registration. and families with many children. Russia does not have a developed system of government reimbursement for drugs. since in the absence of a valid registration certificate. where such registration certificates are not provided.
2.04. Hospitals and polyclinics are encouraged to restrict themselves to the administration of drugs on this essential list. The prices for these drugs must be registered with the State.1: Market Segmentation Comparisons. these mainly manufacture generics drugs. Western Europe vs. Of the 800 pharmaceutical producers. There have also been attempts to encourage the prescribing of "generic" generics. Many also import bulk tablets/capsules for blister packing.100 products. but compliance is incomplete.04 Market Segmentation Market segmentation in Russia is considerably different to Western Europe. Russia Segment OTC Western Europe 35 – 40% Russia 35 – 40% • Trend Western goods substituted by low cost providers after crash • "Comfort" products unlikely position • Innovative Brands 50 – 55% 5 – 7% • • OTC segment growing in general Not affordable to wider population Stable. containing 7. consumer group with modest growth prospects Branded Generics "Generic" generics • 5 – 10% 25 – 30% 5 – 10% 30 – 35% • • • High level of customer/patient loyalty Most promising segment Western products vulnerable to low cost alternatives Will continue to be an unstable segment to regain There are about 800 companies who manufacture pharmaceutical products in Russia. A list of essential drugs was compiled by the MoH. but secondly because a new wave of "more informed" patients with increasing amounts of disposable income are emerging who want to use branded products. using imported APIs. only 300 are domestically owned. with branded generics the strongest growth segment. 23 . Firstly because the supply of unbranded products is unreliable. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA drugs and selling them in Russia has become a highly profitable business for counterfeiters who have already captured around 15% of the total market share. and some 70. but this has been problematic. Fig 2.THE HEALTHCARE. if small.000 pharmacies.
Russia. they supply around 16.THE HEALTHCARE.imports help to address this problem.1ml 26. $ (1Q 2005) Veropharm Nizhpharm Moskhimpharmpreparaty Otechestvennye Lekarstva Akrikhin Bryntsalov Biokhimik Biosyntez Dalhimpharm 28. The largest companies are Protek (2003 revenue of US$900m.2: Top Russian Manufacturers and Top Foreign Importers Top Russian Manufacturers Sales.2ml 10. 2005 24 .8ml 7. Together.3ml 18ml The wholesale sector is highly consolidated. 1 Fig 2.3ml 5. 26. $ (3Q 2004) Sanofi-Aventis Berlin-Chemie Pharmastandard Gedeon Richter Pfizer International Inc Novartis Pharma Servier KRKA Nycomed 42. 3 The State owns 35% of all pharmacies and around 100 domestic pharmacy chains operate in the country – the pharmacy market is so fragmented that the top ten chains control a mere 10% of market share.8ml 4.3ml 21. 3 The Economist Intelligence Unit.7ml 26.5ml 21ml 19. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA Collectively.7ml 3.7ml 18.3% market share).6% market share) and SIA International (2003 revenue of US$755m. 1 Local production cannot meet pharmaceutical demand .05. and around half of these are part of a chain.000 pharmacies and hospitals.7ml 6. but there is still a large unsatisfied demand for many classes of medicine. 22. private pharmacies account for 59% of the market. the top eight domestic producers account for around 60% of total domestic pharmaceutical output (by volume) and for about 15% of the entire pharmaceutical market by value.8ml 10.9ml Top Foreign Importers Sales. The company 36.5ml 34ml 27. In Moscow.6 is Russia's largest domestic pharmaceutical retailer by turnover.
with the wealthiest inhabitants (on average) residing in Moscow and St.5 Percentage (%) of Total Demand 18. with large cities boasting higher than average income. the level of pharmaceutical spending. The income per-capita is disproportionately distributed. The amount of disposable income and. − Lifestyle changes combined with positive attitudes towards new products and services have led to alterations in consumer consumption. therefore. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA Fig 2.8 4.hccp. Market restrainers can be generally attributed to the fact that healthcare is a low government priority: 25 . have grown substantially since 1990.7 Source: http://www. the social and cultural factors which are driving the positive development of the Russian economy are very favourable for the development of the pharmaceuticals market in general and the pharmaceutical distribution market in particular: − − The population of the Russian Federation has been and remains an ageing population.05.3 9.2 16.htm 2.3 3.ru/business/export/farma_market. Psychotherapeutic and Central Nervous System Stimulants Antivirus Antihistamine Preparations Purgatives (Laxatives) Digestive Aides Other Pharmaceuticals 5. Petersburg.8 7.2 3.0 17 14.05 Market Drivers & Restrainers Overall. 2003 Drug Class Cardiovascular Analgesics.3: The Best Selling Drug Classes in the Russian Pharmaceutical Market.THE HEALTHCARE. Antiseptics and Anti-Inflammatory Drugs Antibiotics Vitamins Tranquilizers. − The level of consumerism has increased significantly.
narcotic and psychotropic preparations which includes: − − − − − Licensing of their production and imports. the Ministry of Industry. quality.06 Pharmaceutical Regulation Russia has developed a system of State control over the circulation of drug. State Customs Committee. and Organisation of manufacturing and wholesale trade. and Issuing licenses for the wholesale trade of pharmaceutical products. supported by various regional and local certification committees. the MoH has the lead in developing actual certification standards. The main government body involved in the regulation of the pharmaceutical industry is the Ministry of Health (MoH). Nevertheless.THE HEALTHCARE. The MoH maintains control over practically every aspect of regulatory activity and is supported by a number of other agencies involved in regulating specific areas of the market – for example: the State Standards Committee. Russia still lacks a solid legislative base and regulation of the pharmaceutical sector has suffered as a result of decentralisation and is no longer as coherent as it was in the 1980s. the Ministry of Economic Development and Trade. narcotics and psychotropic substances. efficiency and safety. Science and Technology. A poor national insurance system with underdeveloped private health insurance and a crippled obligatory State health system. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA − − − − There is a corresponding low level of healthcare financing. State control over standards. Obligatory and voluntary certification of such products. is responsible for: − − − Registration of pharmaceutical products. and the Ministry of Antimonopoly Policy. 2. State regulation of pricing. Certification standards have to be approved and coordinated by the State Standards Committee. Outside of the major centres exists a cash-strapped population with low purchasing power. The MoH. 26 . However. Far fewer than 50% of those entitled to reimbursed medicines can actually realise their right. the State Patent Office. State registration and certification. − VAT introduction on medicines introduced an added burden on price.
laboratory and other tests required for registering a drug.the Federal State Enterprise "Scientific Centre for Expert Assessment of Medical Products". these licenses have to be approved by the MoH in advance.000 while the fee for a domestically produced drug is $6. the Russian drug registration system is very different from the practices adopted in major developed countries. clinical. further clinical trials to demonstrate safety and efficacy – although. In addition. 27 . however. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA The Ministry of Industry. 2. The registration is valid for 5 years. The cost of registering a single foreign drug is around $12.07 Drug Registration Generally. cultural and language barriers often become a challenge to foreign companies attempting to register pharmaceuticals by themselves without appropriate legal advice or help from experienced distributors or consultants. toxicological.THE HEALTHCARE. There are many grey areas in registration procedures and the system continues to lack clarity and transparency. It is a complicated process which includes a patent search and potentially. drugs can be registered without a trial having been conducted in the country.000. the only way to accomplish registration of a pharmaceutical product in Russia is through one of the following types of companies: − − a company incorporated in Russia and belonging to the foreign parent company. The registration and clinical trial period for bringing a single product to the Russian market for the first time can take anything up to two years or more. The "Centre" conducts reviews and expert assessments of the registration documents and directs all required stages of the registration process. pre-clinical. The "Centre" works in close cooperation with a number of expert committees. It should be noted that this fee does not include any costs of trials which might be assigned to a drug. a Russian distributor/authorized agent or a consulting company. The registration procedure begins with the signing of a contract and the submission of a number of required documents to a special entity affiliated with the MoH . as well as research institutes on conducting reviews of the documents. All imports of medicines must be accompanied by an import license issued by the Ministry of Economic Development and Trade. and the Committee on Ethics. The import license requires approval from the MoH. As the registration procedure is quite complicated and because the documents tend to change due to constant changes in the regulatory requirements. Science and Technology is responsible for issuing licenses for drug manufacture. including the Pharmacology and Pharmacopoeia Committees.
in-house Russian-speaking registration personnel or via a regulatory contact permanently based in Russia. 2. v. scientific name in Latin. vi. The original Certificate of analysis of the drug and its active substance (must be signed and stamped by manufacturer). v. including international non-proprietary name.07. Description of the drug and its packaging. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA The registration certificate is issued by the Department of State Control over Drugs and Medical Equipment of the Ministry of Health. Foreign manufacturers should perform registration either through an authorized agent or distributor. vii. A copy of the GMP certificate (must be notarised and apostilled). vi. Recommended dosage. Certificates: i. Again. 28 . The good thing about the system is that it is pretty centralised and the applicant needs only to deal with a few departments within the MoH. Power of Attorney issued by the manufacturer to the authorised company for carrying out registration procedure (notarised original with apostil). iii. trade name and main synonyms. iv. Registration cannot be conducted by phone. Information of registration of the drug in the country of manufacture and other countries. e-mail or any type of correspondence and involves establishing direct contact and an ongoing working relationship with an expert from the Centre. ii. iii. shelf life and storage conditions. Application for the State registration of a pharmaceutical including the name and contact information of the manufacturer. legal advice and assistance from the distributor is strongly recommended. instructions for use. A copy of the Free Sales Certificate (must be notarised and apostilled).THE HEALTHCARE. Many foreign companies have established good working relations with the MoH and have successfully overcome difficulties in registering or re-registering medical products in Russia. A copy of the license of pharmaceutical manufacture (must be notarised and apostilled). ii. iv. The name of the pharmaceutical preparation.1 Documents Requirements for Registration of Foreign Drugs General: i. A copy of the Certificate of manufacturer registration in their own country (must be notarised and apostilled). List of active ingredients and components. A copy of the Certificate of trade mark (must be signed and stamped by the manufacturer).
xi. Instruction for use (must be signed and stamped by the manufacturer). Test report of the drug toxicity (acute. x. Confidentiality of the files provided by the applicant cannot be guaranteed and the registration system has been unable to prevent counterfeit drugs and low-quality (sometimes 29 . viii. Information on packaging materials: Certificates of packaging materials (must be signed and stamped by the manufacturer). The registration procedure is not transparent. Copies of publications of medicine usage after its registration in the country of origin. iv. v. Samples and packaging: i.by date. Test report of specific influences (carcinogenicity. in comparison with other analogous medicines. The colour and design of internal and external packages (Original and Russian version). Standard and referenced samples of the drug for the binding examination of quality (must be in the standard package). determines whether existing regulatory approval documents are sufficient for an exemption of the drug from clinical and other testing in Russia before issuing a registration certificate. iii. Stability data of three drug series . Summary of method of drug manufacture (must be signed and stamped by manufacturer). Report on the pharmacological (specific) activity study substantiating the indications for use which are described in the instruction. ii. iv. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA Information and test reports: i.THE HEALTHCARE. The MoH. Summary information on side effects. vi. The complete description of the quantitative and qualitative control methods with references to the pharmacopoeia and specification (must be signed and stamped by manufacturer). Samples of active substance for quality control. used for the same indications. Lists of registered drugs are published (but often incomplete). Trial report of the medicine usage in the clinic. ix. sub-chronic. Pharmacokinetics and bioequivalence data. sub-acute. mutagenic and teratogenic effects. xii. ii. embryotoxicity. chronic toxicity). vii. allergic and local-irritative effects). Spectral and chromatogram data. information on drugs under registration and on the status of the registration are not available. at its own discretion. iii. however. Officially Russia does not recognise FDA and EU certificates.
This new certification system was intended as a tool to combat counterfeit drugs as well as a means of toughening control over imported drugs. Certificates previously required at each stage of the sales chain were replaced by a single certificate issued when the product enters the market.THE HEALTHCARE. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA dangerous) products entering the market. Both the Association of International Pharmaceutical Manufacturers (AIPM) and the American Chamber of Commerce in Russia have been actively working to eliminate this administrative barrier for foreign manufacturers. Yekaterinburg. Vitamins and biologically active additives in the majority of cases are registered and certified in the same way as ordinary drugs. batch-based certification at each stage of their circulation in the market.000 (US$ 103) for foreign firms. The Ministry of Health together with the State Standards Committee accredited 8 regional certification centres located in Moscow. Nizhny Novgorod.000 roubles (US$ 69) for domestic companies and 3. To combat these problems. The certification. To expedite the certification procedure for well-established pharmaceutical suppliers. The hygiene certificate is valid for three years. According to MoH's new legislation. requires total control and inspection of locally made and imported medicines. Khabarovsk and Rostov-on-Don. required now for each and every batch of medicines entering the market costs 2. Certificates for foreign drugs were issued based on quality certificates provided by the manufacturers. imports of these products should be accompanied by a certificate of hygiene which is issued by the Institute of Nutrition of the Russian Academy of Medical Sciences. a new certification system was introduced which applies to all domestically produced and imported drugs. Well-established Russian and foreign drug manufacturers may undergo simplified certification procedures. Novosibirsk. Previously the drugs were subject to selective. The MOH publishes a list of qualifying companies . 2. the MoH introduced a new decree into existing certification rules. Government Resolution #287 added medicines to the List of Products subject to mandatory conformity assessment (certification) in Russia. 30 . This new certification system led to additional costs associated with the storage of products in bonded warehouses while tests were carried out. All other companies must undergo full-scale quality and safety testing prior to customs clearance. Testing could take up to several months and these increased costs led to an increase in retail drug prices. 2002.around 60% of which are foreign.08 Certification Requirements In April. The new certification system which came into effect on December 15. However. 2002. St. Petersburg. in certain cases the number of trials and tests for quality can be reduced if the producer has extensive experience and there have been no concerns regarding its products over a given period of time.
a fact that has prevented them from competing in the international arena. Because pharmaceutical companies are barred from selling directly to patients and doctors and cannot advertise medicines on mainstream television. as in other major pharmaceutical markets. These Laws state: i. Advertising of prescription drugs as well as the promotion of medical products and technology can only be placed in specialised medical and pharmaceutical publications. promoting and adhering to strict ethical standards when marketing pharmaceutical products is essential. In addition. 2. the transition period to the new system will take seven years. 2. clear-cut standards and manufacturers certificates of conformity. Pharmaceutical advertising should not position products as unique. Two pieces of legislations regulate the marketing and advertising of pharmaceutical products: the Federal laws "About Advertising" and "About Pharmaceutical Products". there is a lot of uncertainty about which international standards Russia will accept. According to the law. which came into effect in the summer of 2003 was aimed at reforming the existing certification system and will bring the process into compliance with international standards by making a shift from obligatory certification to technical regulations. 31 . ii. It is also forbidden to make comparisons between similar pharmaceutical products. radio and print media. However. the most effective or the safest. which standards should be obligatory and which voluntary.10 GMP Most Russian pharmaceutical companies do not operate in accordance with GMP standards.THE HEALTHCARE. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA The new Law on Technical Regulations.09 Pharmaceutical Promotion and Advertising Appropriate promotion and advertising of pharmaceuticals is of critical importance to the development of the Russian healthcare system. Only pharmaceuticals that have the appropriate license and which are registered in Russia can be advertised. a lot of issues still remain unresolved. the industry relies on medical representatives to network with medical professionals and institutions to create demand. Advertising of non-prescription products is allowed provided that the manufacturer produces registration and license documents and that the advert clearly states all side-effects and does not give any medical guarantees. However. and what the role of the government body should be in development and enforcement of the standards.
and lobbying for changes in legislation. 32 . 2005 or their licenses would be recalled. Ufa-Vita. Pharmsynthez. GMP implementation is an expensive process (costing at least $5ml) and not all domestic producers can afford to pursue this strategy – thus smaller firms have two options: either to become part of larger entity or to exit the industry. The association's goals include: bringing Russian producers up to GMP and ISO production standards. Some of the larger Russian manufacturers have grouped together to drive through change. Veropharm. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA With Russia's move toward WTO accession. On upside. therefore. and eventually 200 to 300 inspectors for GDP. Consolidation in the industry is expected to rise with a corresponding increase in competitive intensity in the marketplace. This drive to bring Russian manufacturers up to international standards has been hampered by delays in writing and implementing new legislation which remains ongoing. a mandate that was supported by President Putin. and the chemicalpharmaceutical factory Akrihin comprise the newly-formed Association of Russian Pharmaceutical Manufacturers (ARPM) whose mission is to develop the Russian pharmaceutical industry. developing staff. Otechestveni Lekarstva. Plans are to recruit 60 inspectors during 2005 and 2006 for GMP. in the interim the MoH has developed a voluntary system of manufacturing process certification as a means of effective control over production. supporting research. poor quality producers will be eliminated boosting consumer confidence in locally produced products. the MoH mandated that all Russian manufacturers should switch to GMP standards by January 1. Nizhpharm. The National Pharmaceutical Inspection unit (NPI) has recently been established. actively fighting counterfeits. The strengthening of domestic production has public health implications and is expected to improve the overall health situation in Russia. control over the manufacturing process in compliance with GMP standards became an important issue.THE HEALTHCARE.
Emergency healthcare. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA 3. The newly restructured Russian Ministry of Health and Social Development has announced modernisation of the Mandatory Medical Insurance system as one of its primary goals.01 Healthcare Policy Historically healthcare in Russia has been the responsibility of the Russian Ministry of Health (MoH). State-financed medical insurance policies – with one-third of the 2.0 Healthcare in Russia 3.000 Russian insurance companies working with the State on the mandatory medical insurance programs. The MoH oversees the healthcare system and is responsible for central policy formation. the management of federal level health facilities. which in turn regulates the Territorial Mandatory Health Insurance Funds (TMHIFs). the training of medical personnel. More than 100 million Russians are covered by free. largely due to the high degree of autonomy of provincial and municipal governments. but in some cases to basic healthcare treatment. It is also in charge of initiating federal health programs. health monitoring and planning. In the best case scenario the government will be able to bring more order into the system and to create a clear-cut list of free services guaranteed by the government. The current Mandatory Medical Insurance system is inadequate and unable to guarantee access for the population not only to quality. Hospital care (via referral). and the regulation of pharmaceuticals and medical devices. wide regional differences in the provision and scope of care exist. Preventative healthcare. and Pharmaceuticals used in in-patient care. Major capital investments within the health sector are funded at State level although decisions regarding the setting of budgets for overall health spending have gradually shifted to the regions. the provision of care is uniform throughout the country. This list should be complemented 33 . Under current legislation every Russian citizen is entitled free access to a basket of basic healthcare services including: − − − − − Primary healthcare. In theory. The government believes that sound GNP growth supported by tax reform will provide sufficient revenues for the Mandatory Insurance Funds. The MoH supervises the Federal Mandatory Health Insurance Fund (FMHIF). analysts predict that the Government won't be able to significantly increase funds available to cover free medical treatment.THE HEALTHCARE. In practice. However.
In addition. all citizens have the right to receive free healthcare. results in an underdeveloped national healthcare infrastructure. Because public financing of healthcare is insufficient and voluntary health insurance coverage is very limited and does not include serious. Because preventive care has never been an objective. Wealthy citizens spend significantly more out-of-pocket on healthcare than the less wealthy.THE HEALTHCARE. According to the Constitution of the Russian Federation. the research showed that only one-third is really paid under the table while two-thirds are channelled through cashiers. and informal payments usually complement formal ones. the population has to resort to hospitalbased care. At the same time half of the families which need in-patient treatment are also forced to pay out-of-pocket. There are also several channels through which drugs. Low wages and inadequate training for primary care physicians who do not have full access to the latest medical technology. doctors are interested in unofficial payments as their wages are generally very low (in the region of $100-200 a month). a common current practice. to attending physicians who are assigned to supervise the patient for in-patient care. disease prevention and family planning remain low priorities. Public health programs for health promotion. precluding investments in other segments of the system. supplies and medical devices. According to research conducted by the Independent Institute for Social Policy. There are several major categories of informal payments: − − − − to medium level personnel for conducting procedures such as injections and so on. the Russian population is forced to pay out of pocket to cover a significant portion of the cost of drugs and healthcare services. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA by a list of fee-based services. Other categories include payments for drugs. one-third of the families which need out-patient treatment pay for it out-of-pocket. the level of legalisation of private services in the system is quite high. to personnel conducting diagnostic tests. Despite the common myth that the major part of out-of-pocket money is paid unofficially to doctors under the table. supplies and devices are sourced by the patients: they 34 . to operating surgeons. However this right in the majority of case exists in name only. Generally. which generally makes the Russian healthcare system inefficient and very expensive. The government has actually admitted that it will have to take measures to legalise private healthcare services so that the payment for these services is based on invoicing and carried out through a cashier versus unofficial payments directly to doctors. Unofficial payments are more common in in-patient hospitals than in out-patient clinics. life threatening diseases.
2% decline in the number of district medical centres resulting from the closure of under-performing. suburban hospitals and general clinics. Russia is an ageing nation with a demographic structure mirroring much of Western Europe. in pharmacies. small. reform will only be able to clarify the existing system of guarantees. lists of free services and standards of free healthcare. The overall efficiency of the remaining polyclinics has increased and the number of emergency services remains unchanged.02 Healthcare Spending It is difficult to estimate total healthcare expenditure in Russia. there is a high mortality rate amongst the working-age population. The main aim is to decrease the number of low-budget and poor performing polyclinics and hospitals. Problems with the existing underfunded. The need to increase the cost effectiveness of healthcare delivery is now the main driver behind the current primary care restructuring program taking place throughout the country. Because paying doctors directly. The entire system needs massive reforms. under-equipped and overstretched health system will be subject to even further funding pressure in coming years as diminishing numbers of workers have to fund a growing class of pensioners. out-of-pocket coverage of services will remain significantly high. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA can be purchased from doctors. Namely. In addition.THE HEALTHCARE. The government will be forced to legalise increasing portions of the healthcare treatment by enforcing the list of paid services. but taking into account the realities. the country has a highly urbanised population and declining fertility. As voluntary medical insurance is underdeveloped. middlemen or informally from the clinics themselves. 35 . Healthcare provision for the elderly and handicapped remains poor. analysts predict that it will be an inevitable trait of the Russian healthcare system in the future. Since 2004 there has been a 2. both under the table and legal payments has deep roots in Russian culture. 3. their provision procedures. Central government health budgets are usually very small and inefficiently administered and it is not unusual for actual government expenditure to be lower than the budgeted figure. The existing insurance system is definitely inadequate and chances that coverage by the Mandatory Insurance Funds will increase in the foreseeable future are low. but the situation is being addressed with a focus on home healthcare and further restructuring of the system to increase the bed count in specialised centres thus giving these patients better access to priority treatments.
The share of healthcare expenditure in the consolidated budget of the Russian Federation has increased over the past years; however, Russia still spends less than 4% of GDP on healthcare, well below the OECD average of more than 8%. Public spending makes up about three-quarters of total health spending.
Fig 3.02.1
Trend in Healthcare Spending
1000 490 160 100 112 122
10 6.1
4.2 1 1998a 1999a 2000a 2001a 2002a 2003a
Healthcare Spending (Rb bn) Healthcare Spending (US$bn) Physicians (per 1000 population)
Healthcare Spending (% of GDP) Healthcare Spending (US$ per head)
Source: US Census Bureau; Economist Intelligence Unit; a – actual
In December 2005, parliament approved the State healthcare budget for 2006 after a third and final reading. Some 113.4 billion roubles (US$ 3.9bn) was set aside for the budget, of which 40.6 billion roubles (US$1.4bn) will be used specifically at the territorial (regional) level for much awaited improvements. The president announced that healthcare spending will be increased by 60% in 2006. A planned increase in the rate of unified social tax from 0.8% to 1.1% will partly fund the budget as well as profits from high oil prices. The vast majority of health expenditure is funded through the public sector via the central budget and a mandatory insurance system. The Federal Mandatory Health Insurance Fund (FMHIF) oversees the insurance system and monitors the activities of the Territorial Mandatory Health Insurance Funds (TMHIFs). At a local level the TMHIFs were expected to appoint independent, private sector insurance companies to purchase care and promote competition between third-party payers in a bid to reduce the cost of healthcare. In cases where there are no private purchasing companies the TMHIFs have the responsibility of establishing so-called branch funds (BMHIF) to act as short-
The consolidated budget consists of federal budget and regional budgets.
term insurers for the local population and make provision for those not covered under the mandatory system. Generally simple and primary medical services are the only ones provided free via the State system, with public health policy of little help to those patients requiring a serious operation or for those in receipt of long-term, expensive and/or sophisticated treatment. The lack of coverage of the mandatory health insurance has resulted in the burden of healthcare spending becoming increasingly the responsibility of employers or citizens themselves - with outof-pocket spending and private insurance driving growth in healthcare expenditure. Out-of-pocket spending increased from 27.5bn (US$ 0.95bn) roubles in 2000 to 87bn (US$ 3bn) in 2004, and is growing at a faster pace than total government spending. Moreover, the low income population are becoming victims of this trend being forced to undergo longer, more painful and lower quality treatments. However, the situation is changing for those entitled to social benefits. At the beginning of 2005, the government introduced a new system of drug reimbursement for these people called Additional Pharmaceutical Provisions (DLO in Russian). Under the old system, people on benefits were entitled to free healthcare and free medications; but due to a lack of financing, the system did not work well especially on a regional basis. As a result, beneficiaries were unable to receive medications and treatments in time or were finding hospitals and polyclinics being short of supply. The new scheme - which provides compensation for medicines from a list of over 1,800 - has seen cash payments to those on social benefits replaced via a discount-card system. These patients can now receive timely medications by purchasing drugs in pharmacies and polyclinics at discounted prices using the money equivalent of their benefits. The price differences are reimbursed to the manufacturer by the government. A lot of pharmaceutical companies are now fighting for the right to supply products under the DLO scheme.
3.03 Structure of the Healthcare System
In recent years, the healthcare system has gradually become more decentralised with more responsibility afforded to the federal regions – although the MoH retains a considerable hold over healthcare policy. Russia has 89 federal units comprising republics, provinces and regions with smaller subdivisions at the local level. Federal health departments report to the MoH and are responsible for funding over half of all healthcare expenditure. District Health Authorities (DHAs) play an executive role at local level although, again, their remit varies greatly across the country.
The lack of the enthusiasm and motivation of many healthcare workers in Russia is noticeable and can be attributed in the main to low levels of pay. The Ministry of Health estimated that the average salary of a doctor in 2004 was 4730 roubles per month (approximately $169). There is of course, much variation from region to region – for example doctors practicing in St. Petersburg and Moscow receive around twice that amount, while doctors in smaller cities and rural areas receive in the region of $100 - $135 per month. Salary also depends on the specialisation of the doctor, experience and the institution in which he/she works.
Fig 3.03.1: Russian Healthcare System
The Ministry of Health of the Russian Federation
Federal Mandatory Health Insurance Fund (FMHIF)
Territorial Mandatory Health Insurance Funds (TMHIF)
Federal Health Departments
District Health Authorities
Local Insurance Funds
Health Centres
Sanatoriums & Health Centres
Health Posts
There are rumours that low remuneration is leading to a decline in the number of doctors in Russia. However, according to the Minister of Health - M. Zubarov - the actual number of doctors
in the country has grown by 10% over the past 8 years (from 550,000 to 610,000) – hence today there are around 6 doctors per 1000 citizens. Statistics indicate that around 60% of physicians are specialists, 20% work in the primary care sector and a further 20% hold administrative and/or research positions.
3.03.1 Provision of Primary Care
The primary care network overlaps slightly with secondary and tertiary care. General practitioners and other primary care personnel are employed by the facilities in which they work and contracted indirectly to local government, which provides the core funding for primary care services. Some primary care facilities also secure contracts with local insurance funds in order to obtain compensation for services provided to insured patients. It should be noted that many patients in Russia have no primary care physician. Patients have the right to visit any specialist (hospital or polyclinic) without any referral from a GP or nurse.
3.03.11 Health Posts Often found in rural areas, health posts offer immunisation services, basic health examinations and routine examinations. Health posts often treat minor injuries and make home visits or offer emergency services. 3.03.12 Health Centres Generally staffed by a general practitioner, a paediatrician and often a gynaecologist, health centres offer a range of primary health services including the treatment of minor ailments and the supervision of chronic conditions. Physicians at health centres, who are supported by nurses, are permitted to prescribe pharmaceuticals. Health centres offer a limited supply of beds, which can be used to carry out minor in-patient procedures. 3.03.13 Polyclinics Polyclinics offer first line treatment for acute and chronic conditions and longer term chronic care. Staff at polyclinics comprise of a number of general physicians supported by auxiliary staff, as well as other specialists in areas of cardiology, oncology and obstetrics/gynaecology. Patients are assigned to polyclinics by postcode.
The World Market Analysis, Russia, Healthcare Infrastructure
Nevertheless. These facilities are mostly used for: − − − prophylactic treatments. establishment of private health facilities remains complex due to bureaucracy and licensing issues. there are around 10. Health centres and sanatoriums have become more popular over the last few years due to the stabilisation of the economy and rising disposable income.4 Sanatoriums and Health Resorts There are many sanatoriums and health centres in Russian that have few analogues in the rest of the world (aside from Germany).4 thousand sanatoriums spread around the country providing around 450 thousands beds – the majority being located in the wealthier. many hospitals and other facilities would require heavy capital investment and increased funding for modern diagnostic and medical equipment to bring them in-line with Western standards. institutions also provide outpatient facilities. 3. There are more than 2.2 Hospitals According to the Russian statistics agency (Goskomstat). and for those undergoing long-term treatment for chronic diseases. the Vivalov State Optical Institute.THE HEALTHCARE. Statistics 40 . PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA 3. A large number were established to cater for diplomatic personnel. although the number of Russian patients has increased gradually over the last decade. European part of the country.03. 3. etc. Many private clinics and hospitals are costly facilities with high-quality equipment and personnel established by Western firms. Here patients are treated using only natural medicines and therapies.000). the number of beds has been on the increase thus suggesting growth and strengthening of this particular sector of the healthcare system. However. recovery support.700 hospitals throughout the country staffed with highly trained personnel.03. clinics and other health facilities (around 3.03. businessmen and ex-patriots. According to a report issued by the MoH. There are a few thousand private hospitals. which are located in larger urban areas and offer Western standards of care.3 Health Institutions A feature of the Russian healthcare system is the existence of huge specialised institutions dedicated to a specific area of medicine. conduct research and are usually involved in teaching. These institutions are well respected and are considered to provide the best of care. for example the Institute of Oncology. the Research Institute of Cardiology.
1 Population Demographics For much of the last decade. 38% of patients treated in these centres and resorts were sponsored by government. 3. and the general average-to-low standards of living and lack of government benefits outside major cities. there has been much investment in constructing new centres and re-developing existing facilities – this activity has also attracted much foreign investment. and in the next 50 years it could fall by 30% to 100 million.1 Source: EarthTrends 2004. in 2004. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA shows that in 2004. The number of private sanatoriums and health resorts is also on the rise. high alcohol consumption. Russia There are many contributing factors to the population decline including: poor diet. over 5. The latter being the major concern discouraging people from starting a 41 .THE HEALTHCARE. given that its gross domestic product (GDP) is the lowest of all the G8 countries (the eight most industrialised countries). With rapid ageing of the population. Russia's population declined from 149 million in 1992 to 143 million in 2003.3 million in 2003. the country has suffered a population decline unprecedented for an industrialised state outside of wartime.04 Health of the Nation 3.04.04. Because health resorts and sanatorium are so popular amongst the Russian population. Fig 3. Country Profile. According to Rosstat (Russian Statistics database). this fall is increasing the dependency ratio (the ratio of the economically dependent part of the population to the productive part) and producing an economic burden that Russia may not be able to afford.7million patients received treatment at various health resorts compared to around 5. 12% were sponsored by their employer and 22% of patients financed their stay as an out-of-pocket expense.
04.7 1564. 3.9 2003 1636. and differences in life expectancy can be as much as 18 years. accounting for 52% of all deaths nationally each year. At 994 per 100 000.4 204 913 204. mean that Russia's overall population is rapidly becoming smaller and sicker.THE HEALTHCARE. The picture is different for women.6 per 100 000. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA family.2 Life Expectancy and Causes of Death Russia is one of the few developed countries where life expectancy has fallen in recent years. multiple drug resistant tuberculosis. is double that in EU and G8 countries. at 20. when the burgeoning epidemics of HIV infection.000 citizens 2001 Total Includes: Circulatory diseases Cancer and cancer related problems 869. as well as in many rural areas due to both environmental conditions and low incomes. Russia has one of the highest death rates from cardiovascular disease in the world. the rate of traffic injuries. Russia's total life expectancy of 66 years lags behind that of Japan by 16 years. and the United States by 12 years. homicide. Mortality for Russian men substantially exceeds that in countries with similar per capita income levels.2: Causes of Death in Russia Causes of Death Per 100.5 895.in Russia are three to five times higher than average rates in the European Union. High mortality and morbidity from non-communicable diseases. Morbidity and mortality from non-communicable diseases and injuries . mortality varies fourfold between regions. The situation is compounded by the stresses related to economic transition . and the rates for cancer mortality.5 2004 1596 42 . along with a low birth rate. small cities and towns are becoming wealthier as more and more employment opportunities are created. sexually transmitted disease.5 202.4 201.04. the severity of Russia's health crisis is magnified substantially.4 2002 1627. The situation is at its worst in the Far North and Far East. Massive regional variations in life expectancy exist. poor diet. the European Union by 14 years.5 927. and hepatitis C are also taken into account. However. intravenous drug use. because the Russian economy is developing fast. Similarly. and sedentary lifestyles.the leading causes of death .collapse of the social safety net. lack of strict road safety measures. Furthermore. and suicide far exceed EU levels. Within Russia. Fig 3. who live about 14 years longer than men – much greater than the average gender gap of eight years found in other G8 nations.
accounting alone for 16.5 28. and tobacco use.000 citizens) Tuberculosis (per 100. Around 75% of deaths and 46% of the disability adjusted life years (DALYs) in Russia can be attributed to high blood pressure.5 28. high serum cholesterol.9 482 24.5 31.3 64.9 21.7 29. every year around 1million people become registered as disabled.5% of the total DALYs lost in 2002.000 citizens) Malignant tumour & other oncology (per 100.3 21.8 65. Fig 3. 2004 In 2003. 3. Russia.every year there are around 200 million new disease registrations. and injuries accounted for 15.1 236.840 326 43 . but alcohol is also a big killer.6 30.1 34.8 25.2 million lost years of potential life.3 27.3 36.05: Number of Registered Patients.THE HEALTHCARE. cancer.1 29. and digestive disorders (8%).8 31. 2004 Disease Type Total Number of Registered Patients Cardiovascular (per 100. Healthcare.1 38.000 citizens) 81. cardiovascular disease (11%). deaths from cardiovascular disease.7 25. Lifestyle ailments like heart diseases and diabetes are on the increase.4 30.4 Source: World Market Analysis. Moreover.8 21.9 70. Six out of 20 men smoke. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA External causes Out of which: Alcohol poisoning Road accidents Suicide Murder Respiratory disease Digestive disorders Certain infections Includes: Tuberculosis 230.2 29.7 29.9 29. the most frequent being: − − − respiratory disease (26%).1 70.5 52.3 25.5 56.7 20 21.05 Disease Prevalence All patients with diagnosed pathologies are registered in regional databases .6 59.6 227.8 233.3 39.
232 2004 21 841. for example.754.329. tobacco smoking and a more sedentary lifestyle with very little focus on any exercise other than walking.000 adults were newly registered bringing the total number of patients registered with cardiovascular disease to 24.05.000 860. Because many of the elements associated with the surging mortality rate are connected to social behaviour and the need for education.3 5.346 2004 24. the age-adjusted decline between 1965 and 2000 was over 56%. Western Europe and North America have fallen very sharply. with its regionally limited medical infrastructure.8 million in this year. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA Diabetes Drug Addiction Alcoholism Mental Disorders Sexually Transmitted Diseases HIV/AIDS (estimated) Hepatitis 2.3ml 342. However. improvements in the quality of diagnostic procedures have resulted from the development and implementation of regional healthcare programs.867.776 2.099 7.639.05.000 (>1.945.000 >3.525. suffered an explosion of cardiovascular deaths over the same period. Fig 3. The increase in cardiovascular mortality has been attributed to stress brought on by the social and economic changes. In 2004.20 147.000 citizens 2003 20216. In the US.803 2. Russia.877 6.50 146 2. by contrast.4 6.01: Number of Patients with Circulatory Diseases Disease groups and other illnesses Absolute Numbers 2003 Blood circulation disorders Hypertension Ischemic heart disease Out of which: Stenocardia Acute myocardial infarction 2.429.151 5.5ml 7.714 Per 100.262. will be able to incorporate enough changes to slow or stop the trend in the near future.6 6.193.956.814 166.577 163.90 44 .THE HEALTHCARE.01 Cardiovascular Disease Over the last 40 years cardiovascular disease (CVD) and stroke mortality rates in Japan.358 6.671.166. which is on the rise in both men and women.3ml) >5ml Source: The Russian Ministry of Health statistics 3. 285.1 5.2 22.7ml >730. there is little hope that the government. alcoholism.883.
000 citizens) Localisation Per 100. Currently. obliterating endarteritis Other 24.5 5.443.4 4.4 2.201 6.321 5.50 388.460 21.02 Cancer A major unmet need in Russian healthcare is the development of a system that allows for the early detection and diagnosis of cancer.2 8. Fig 3.471 2.5 17. 39.6 21.406. thromboangitis.60 416 3.THE HEALTHCARE.603.3 41. Around 18% of malignant tumours are treated by radiotherapy.3 5 30.262 435.000 citizens 1999 Total malignant tumours Oesophagus Stomach Colon Rectum Pancreas Trachea. 57% of intestinal cancers.6 4 -6. 3% of cases).05.5 40.548 3.9 9.500 471.5 11. lungs 302.2 2004 326.3 5.794 24.819.805 3.5% of cervical cancers.3 15.1 % Change* 45 .8 20. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA Repeated myocardial infarction Complications following myocardial infarction Other major ischemic conditions Cerebro-vascular disease Endarteritis.817 45. Surgery is the most popular treatment for malignant tumour (44. a large percentage of different cancers are only detected at very late stages (III-IV): − − − 69. Patients themselves are partially to blame .around 30% of patients only present at late stages (there exists a mentality of not wanting to "bother" the doctor).6% of cases receive chemotherapy simply because the money is not available to pay for it.02: Number of First-Time Patients with Malignant Tumour (per 100.5 44.9 43. Drug treatment is quite rare and only used in about 6% of cases .169.812 50.4 14.8 Source: The Russian Ministry of Health statistics 3.2 6.4 33.966.9 -8 16.20 3.5% of mouth and throat cancers.996. bronchial.305 2.on average only around 2.8 2.05.499.
it is currently estimated that diabetes is present in approximately 9. Improvements in the standard of living in the poorer areas are needed to offer the hope of further stabilisation of the tuberculosis situation in the country. but according to the International Diabetes Federation (IDF). unhealthy diets high in fatty foods and alcohol over-consumption all contribute to health complications in the Russian population.03 Tuberculosis Tuberculosis remains a problem in Russia.1 4.1 37.THE HEALTHCARE. however. As a result.7 8.05.3 5.8 13.8 10. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA Skin .05.6 8.7 5. Such a large number of unregistered cases can be attributed to a lack of awareness on the part of people with diabetes and of healthcare professionals. most cases of diabetes are only detected by general practitioners when patients present with other health concerns.9 21 8 17. 46 .4%) in the tuberculosis epidemic over the past 4 years.2 16.04 Diabetes Russia occupies third place in the 'top 10' of countries with the highest number of people with diabetes in the world – obesity is on the increase.3 million patients registered with the diabetes. there were 2.613 million people .4 13. In general. of which 260 thousands were registered with type I diabetes.90% of which have diabetes type II. In 2004. a new and more thorough system has been put into place to control the spread of the disease through earlier diagnosis and more effective treatments.malignant melanoma Other malignant skin tumours Kidney Bladder Thyroid gland Lymphatic and haematopoietic tissue 4 31. 3.2 24. there has been a significant reduction (8.8 15.8 8.9 * The percentage change has been adjusted for disease dynamics for the 5 year period Source: The Russian Ministry of Health 3.
the alcohol addiction growth rate is 47 .7 1800 2000 Number of patients with Diabetes Type II per 100 000 people Source: The Ministry of Health of Moscow region.2 122.2 132.9 249.1 579.4 714.5 75.05.05 Drug Addiction and Alcoholism Another burden on the health system is the spread of addictive disorders . with spirits comprising three quarters of the total alcohol consumption. 2004 Fig 3. 2004 3.around 2.5 1242.1 156.6 112.1 1345.4 185. Diabetes epidemiology report. However.1 1671.8 839.9 1266.5 685.9 817.9 1744.3 78 102.2 175.041: Prevalence of Diabetes Type I in Selected Russian Regions Bryansk Region Mari-El Republic Kalmikija Tambov Region Nizhny Novgorod Region Perm Region Moscow Region Komi Republic Orlov Region Tver Region Saratov Region 0 50 66.05.042: Prevalence of Diabetes Type II in Selected Russian Regions Tver Region Bryansk Region Orlov Region Kalmikija Mari-El Republic Tambov Region Perm Region Komi Republic Saratov Region Nizhny Novgorod Region Moscow Region 0 200 400 600 800 1000 1200 1400 1600 112. Alcoholics account for the majority (over 84%) and in 2004.1 100 150 200 250 300 Number of patients with Diabetes Type I per 100 000 people Source: The Ministry of Health of Moscow region.THE HEALTHCARE. Diabetes epidemiology report. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA Fig 3.05.4% of the total Russian population are affected. it was estimated that about 70% of men and 47% of women were drinkers.
The increase was mainly driven by the rise in hospitalisations due to alcoholic connected disorders (1% increase).04. But STDs are now on the decline – the number of registered patients is almost 3 times less than in 2001. Russia experienced a rapidly increasing incidence of syphilis and gonorrhoea sterility caused by STD is also the hidden factor behind the collapse of Russia's birth rate. as people delay seeking treatment for economic reasons .9% increase from 2003 to 2004). the mental health of Russia's population has deteriorated considerably over the past decade and the number of newly registered patients is on the increase (4. 3. Drug addiction is also a growing concern – with the majority (88%) being addicted to opium. The total number of hospitalisations due to addictive disorders has been on the increase and amounted to 707 thousand in 2004. Not all people have access to psychiatric assistance in Russia. low population density.most of those being over 18 years of age. The recent rapid expansion of commercial medical services offering anonymous treatment without registration removes an increasing proportion of cases from the statistics.06 Mental Disorders In 2004. experts do not believe that this reflects reality. Overall. The trouble is that the official figures are based on records generated by the system of state registration of diseases inherited from Soviet times. At the same time. out of fear of losing their job if their employer finds out that they are syphilitic. Moreover. these plans are not being implemented as fast as wished to date. it is planned to open psychiatric rooms in polyclinics and psychotic sections in hospitals. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA reported to be slowing down – 8. standing at around 730 thousand in 2004. The reason for that is the high number of regions. Psychological diseases caused by the alcoholism are also on the increase. there were over 7. However. even where registration does still occur it tends to be at a later stage of the disease.7 million patients registered with mental disorders . 48 . However." To achieve this goal. and the low level of development of transport networks.04. but a significant number of 0 -14 year olds (>800 thousand) also suffer with some form of psychological disease.07 Sexually Transmitted Disease (STD) In the 1990s. 3. This shift also biases the figures downward.4% in 2003 compared to 4.in particular.3% in 2004. the ongoing State program for the development of psychiatric services is aimed at "making psychiatric assistance available to the wider population. In addition. psychiatric clinics receive only about 50% of the funding to which they are entitled.THE HEALTHCARE.
more than 10 times greater than in Europe – and the younger the age group.5 times among adults.04.000 52. most of who are of childbearing age). which is largely preventable. the faster the spread of syphilis within it.04. presumably because the economic motives for concealment do not apply to children. Many HIV/AIDS cases are among the young (18 – 29 years) and the problem is no longer limited to injecting drug users. 49 . those for child syphilis have continued their upward trend in the last few years.699 Thousands 40 30 20 10 0 2002 33.342 2003 2004 Source: UNAIDS Russia has one of the fastest growing Aids epidemics in the world. Thus between 1992 and 1998 the prevalence of syphilis increased by 5. but by 17 times among children under 15. women and their infants are being affected (roughly 40% of all new registered cases of HIV in 2004 were women. with 100 new infections every day and accounting for 70% of all cases in the Eastern Europe and Central Asia region. There were an estimated 860.08 HIV Fig 3. is high because many infected pregnant women are treated inadequately or too late in their pregnancy.3 million HIV infected individuals in the country.THE HEALTHCARE. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA The number of people carrying and suffering from syphilis in Russia remains very high . The incidence of congenital syphilis. There is also a developing concern in the country about treatment resistant Chlamydia trachomatis and human papilloma virus (HPV). but it is widely acknowledged that this figure is vastly underestimated and there could be closer to 1.08: HIV Registrations Number of new HIV cases registered in Russia 60 50 39. 3.000 people living with HIV at the beginning of 2004. Unlike the figures for adult syphilis. Increasingly. Alternative treatments to antibacterial drugs need to be approved and included in treatment lists for Chlamydia and there is a growing need for the early diagnosis and treatment of HPV.
poisoning and other accidents has been constantly rising. This reduction could be due to fewer people being tested. hepatitis in particular. Mass vaccination of children against hepatitis B and support for the development of a vaccine for hepatitis C are needed to control these diseases. Poisoning and Other Accidents Over the last few years the number of injuries.04. 3. or it could be that HIV prevalence rates have reached saturation point amongst injecting drug users.04. Over the past 10 years there has been a 16% rise in dermatological disorders with almost 9 million dermatologic patients registered in 2004 – this equates to 6% of the total population and around 7% of all diseases.349 new cases in 2002 and 39. The number of injuries/poisoning amongst the teenaged population is the greatest being 6% more than that amongst children and 12% more than that amongst adults. some even claim there to be terrorist links. with 88.THE HEALTHCARE.699 cases in 2003. Yet the population does not participate in vaccination programs actively. the absolute number of injuries was in excess of 13 million. In 2005. but the rates of hepatitis B and hepatitis C increased steadily. and a vaccine against hepatitis costs about $100 which not everyone can afford. 3. This event was associated with the consumption of contaminated food and liquids.10 Injuries. 52. 50 . 9 -10 are receiving injuries that require medical help or even hospitalisation. the fact that vaccinations will be funded by the State from 2006 will help to improve the situation.577 new cases reported in 2001. 3. The rates of hepatitis A decreased during the 1990s thanks to improvements in water supply and better quality food stuff. Half the patients with acute hepatitis B and hepatitis C are 11 to 30 years of age.09 Dermatologic Diseases The prevalence of dermatologic disease is considered an epidemic.04. Out of every 100 people. This figure continues to rise. the healthcare system was stretched by another hepatitis A outbreak. and high-risk sexual behaviour. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA The number of new HIV cases being reported is falling however. In 2004. Nevertheless. the reason being that in most cases they have to fund it at their own expense. Reasons may be a sharp increase in intravenous drug use. lack of hygiene. or it could be that there is a real reduction in the growth rates of HIV amongst adults resulting from heavy anti-AIDS campaigns.11 Hepatitis There is a high incidence of infectious disease in Russia.
as well as the underlying socio-economic conditions. and hepatitis C. In 2004.with hepatitis B forming around 10% of cases. 80% of cases. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA It is estimated that about 200 thousand carriers of the hepatitis virus and about 75 thousand people with chronic hepatitis are identified in Russia every year. 51 . The numbers of newly registered cases and of chronic forms of the disease are growing. The incidence of all forms of hepatitis vary on a regional basis and depend largely on the availability of emergency and hospitalisation services. in excess of 5 million people were registered with hepatitis in Russia .THE HEALTHCARE.
The major driver for the increased interest by Western pharmaceutical companies to include Russian sites in multinational projects has been the enormous enrolment potential which offers a solution to the competition for patients among clinical trials in North America and Western Europe. and no money exchange points. no private foreign economic activity. However. as though they were specifically designed for clinical research. Foreign pharmaceutical companies had no representative offices in Russia. no customs regulations were in place – therefore.01 History of Clinical Trials in Russia Large-scale clinical trials have been conducted in Russia since 1989.0 Clinical Trials in Perspective 4. Things have changed drastically. and nowadays an established system of national regulations for drug development and clinical research exists. These medical centres may have modest interiors but this does not preclude their clinicians from doing quality work. any drug could be imported. The whole process took so long because domestic regulators did not want to accept international rules. That same year the Russian language version of GCP . which protected patients' rights. There are a large number of hospitals that are huge and highly specialised. regulators and the medical research community were largely unaware of good clinical practice (GCP) and clinical trials were not governed by any regulations – anyone could do anything. at the end of the 80's. back in 1989 when interest in Russia first began. The situation was even worse in the field of communications. A decade later in 1999. no hard currency transfers from abroad. More than a hundred foreign pharmaceutical companies are now accredited in Russia. mostly 52 . when it was finally agreed by a new generation of Russian officials that it was not wise to continue operating the double system. At the same time. Faxes and copy machines were prohibited by law. they wanted to produce their own national GCP guidelines in support of Russian drug companies who did not have the resources to conduct well-designed clinical studies. the official text of ICH GCP in Russian was published. but that was it. ethics committees had yet to be established.became a part of national regulations on clinical research. instead. The Clinical Pharmacological Research Institute (CPR) carried out the first translation of the GCP guidelines in 1989. and RussianGCP for poor domestic drug manufacturers. In the interim. It was up to each customs-house officer to decide what could cross the border. There was the Constitution of the USSR.THE HEALTHCARE. double standards operated – GCP for Western pharmaceutical companies. until in 1999. a close translation of ICH GCP .National Standard OST 42-511-99. There were no automatic phone connections. with clinical trials being approved in a way similar to that in the West. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA 4.
while undertaking scientific research projects and developing new technologies. especially the numbers of Russian CROs. also engage in large programmes for helping practical healthcare – such as clinical research and drug discovery. and CROs of Russian origin. 53 . Moreover.01: Medical Institutions Involved in Clinical Trials in Russia. 31. 29.01.20% Clinical hospitals and outpatient clinics.ru Companies involved in the organisation of clinical trials in Russia include: representative offices of pharmaceutical companies. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA located in Moscow. Fig 4.02: Companies Involved in Clinical Trials in Russia 2000-2005 55% 35% 37% 21% 10% 42% 29% 25% 46% 2000-2003 2004 2005 (Q 1-3) Local pharmaceutical and biotechnological companies International pharmaceutical and biotechnological companies Contract Research Organizations Source: www. In addition.01.THE HEALTHCARE.regmed. some federal medical and science institutions.ru The number of these companies has grown amazingly fast during the last few years. 2005 Educational institutions. representative offices of the international CROs. there are several local CROs. Fig 4. Many major CROs have opened representative offices and in addition.20% Scientific institutions. 39.regmed.60% Source: www. many international companies which do not have representation in Russia still conduct clinical trials there.
the number of trials outsourced to specialised CROs is also growing allowing international companies to benefit from local recourses.02.THE HEALTHCARE. 54 . Interestingly. 1992-2005 250 200 150 100 50 0 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 (Q1-3) Source: www.ru/ The slight decline in the number of clinical trials approved between 2003 and 2004 can be attributed to the increase in the number of mergers and acquisitions in the healthcare sector worldwide at that time. Post-integration companies focus on internal reorganisation – thus we see an increase of number of trials in 2005 as these new entities resume normal operations.01: International Clinical Trials Approved in Russia. Fig 4. intelligence and expertise. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA 4.02 Growth in Trials The number of clinical trials conducted in the country has increased considerably over the past 10 years and this trend continues with on average close to 100 new trials being approved every year.regmed.
14. 9. 9. foreign pharmaceutical companies had no representatives in the country. 20. they started to work through local groups of researchers.9% Cardiology. PSI Pharma Support Inc. 7.the first three were: − − − The Clinical Pharmacological Research (CPR) Institute (St. The first CROs began to appear around 1990 . and Innopharm (Smolensk). 2005 Gastroenterology. The role that these first three played in shaping the clinical research market in Russia cannot be underestimated. 55 . 15. implemented the most reliable communication technologies.0% Infectious diseases. In the early days. Thus.THE HEALTHCARE. established data management systems.03 The Russian CRO Industry When clinical trials first came to Russia.1% Source: www. They created comprehensive standard operating procedures (SOPs) and invented effective project management technology. there was no competition – each CRO worked in its own niche.6% Oncology.7% Rheumatology.8% Psychiatry. Petersburg). The second half of the 1990s was marked with rapid development of local CROs as well as an invasion of international ones. They translated GCP guidelines and introduced them to regulators. Petersburg).02. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA Fig 4. 6. 10.6% Endocrinology. (St.6% Other.regmed. and implemented modern methods of statistical analysis.02: Multi-Centre Clinical Trials in Russia by Therapy Area. 5.ru 4. Petersburg which later became the CPR Institute.7% Pulmonology. medical professionals and the community. The first group was based in the Research Institute of Cardiology in St.
a CRO with head office in St. Russian CROs provide the full spectrum of services including regulatory submissions. InnoPharm has since expanded into an independent CRO offering a wide range of services across Russia and Ukraine. most highly experienced professionals. 4. − OCT (Outsourcing Clinical Trials) . Petersburg and performs clinical research across the breadth of the Russian Federation. Russia. With offices in St. Pertersburg. originally as an SMO. from Kaliningrad in the Far West to Yuzhno-Sakhalinsk in the Far East. in monitoring. − RCT Global . 56 . The main difference between Russian CROs (including the Russian offices of international CROs) and CROs in other countries is that in Russia all clinical research associates (CRAs) are medical doctors. and many are also members of international professional organisations such as DIA and ACRP. Russian CRAs are trained in GCP.established by a group of research professionals in 2001. and so forth. medical writing. and can therefore select the best. in the former Soviet Republics and in Eastern Europe. this independent CRO operates in Russia and in the countries of the former USSR. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA There are currently around 10 international and domestic CROs in Russia – the largest domestically owned companies include: (for a more detailed profile see the Appendix) − PSI Pharma Support . the Republic of Georgia. Siberia. Moscow. OCT expanded its operations into Latvia and Lithuania.now the largest CRO in Russia and CIS running trials across 11 times zones.THE HEALTHCARE. reporting. and Ukraine the company has moved its corporate headquarters to California. Bulgaria and Eastern Europe. At the beginning of 2006. project management. Many CRAs speak fluent English. − Innopharm Ltd – founded by the faculty members of the Department of Clinical Pharmacology of Smolensk Medical Institute. The company was founded to provide services to Pharmaceutical companies interested in conducting clinical trials in Russia.04 Why Conduct Clinical Trials in Russia? Russia ranks highly among other Eastern European countries on the availability of basic medical resources for conducting clinical trials. USA in order to better serve study sponsors. Ukraine. handling clinical trial supplies. − Congenix – based in Moscow. now called Evidence-CPR . the company is located in St. which helps a great deal in communication between investigators and sponsors. and so on. − CPR Institute.the first CRO to conduct multinational clinical trials in Russia and Eastern Europe. Petersburg. medical monitoring. in reporting. Baltic States. The CRO is able to pay much higher wages than government owned medical institutions.
8 4.4 Source: the Imformer GmbH.04.04.2 4. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA Fig 4.01 Benefits of the Post-Soviet System The 'Soviet' structured central healthcare system created large medical institutions specialising in specific therapeutic areas. have large patient pools to draw from making enrolment in clinical trials very accessible to the patient and rapid for the sponsor.2 3. most clinical trial work is conducted in Moscow and St. 57 .6 5 4 2 2 55 3 18 8.02: Potential Russian Sites 4.7 9.1 8 10.4 3. higher population and the presence of major research centres).2 3.01: Medical Resources in Selected Eastern European Countries Country Major Cities Physicians per 1000 inhabitants Medical Universities Hospital Beds per 1000 inhabitants Czech Republic Hungary Latvia Lithuania Russia (European part) Slovak Republic Ukraine 1 1 0 0 13 (9) 0 5 3. Petersburg (owing to better infrastructure.04.6 8. remain largely underused.6 3. Newsletter. both general and therapeutically aligned.THE HEALTHCARE. June 2003 At present.2 13. Fig 4. These institutions. while the wellequipped academic sites located to the east from the Ural Mountains in Siberia to the Far East (rich regions due to their enormous natural gas and oil resources).4 8.
many of the medical practices in Russia call for hospitalisation. Petersburg alone). In summary benefits of post-Soviet system include: − − A centralized medical system with a chief specialist in each major area. when in the West the same treatment may be done in an outpatient setting. The additional level of attention is helpful in informing the patients of their obligations in the trial and providing the opportunity to more closely monitor and instruct the patients early on. Large number of hospitals in cities (> 50 in St. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA In addition. Licensed every 5 years by the authorities. for example: Cardiology Oncology Infectious disease Psychiatry − − Giant multipurpose hospitals in regional centres. 58 . thus helping to facilitate compliance. and are members of European and American professional societies. around 60% possess PhDs and at least 90% have more than 10 years of professional experience.02 Access to Investigators Access to experienced. Hospital costs. Second. attend international conferences. directly or indirectly. Huge specialized research centres. with the international medical community from which they were almost entirely excluded during the Soviet era. do not add to the trial expenses. Investigators are highly motivated to participate in multinational clinical trials for several reasons.04. 3 years of specialisation.THE HEALTHCARE. taking part in a global project gives them an opportunity to interact. 4. 2 years in residency. Certified in GCP and experienced in clinical trials. as part of standard practice. First. − Many speak English fluently. At least 40% are University professors. Russian clinicians are scientifically curious and the pioneering essence of a new drug always presents an additional incentive for them. highly motivated and compliant investigators: − − − − Minimum of 6 years in medical school.
Approximately 150 million people live in the Russian Federation and about one half of those live in town. 2002 (millions) Russia.at least annually. 4. while still providing experienced MDs as project managers and monitors. compared with those in the West.50%. 2003 59 . Finally. 4. This is why the GCP concept is normally readily accepted by clinicians who have had no prior practical experience with the guidelines. 150 Sour ce: EVI DEN European Newly Independent States. 168 h. 394 CE Clini cal & Phar mac eutic al Res earc Candidates to EU. There are more than 10 cities in Russia with a population exceeding one million people. It is no secret that many physicians in Russia are grossly underpaid. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA Third. 80 Non-members.04. Understandably. and are realising the financial responsibilities of that growth. most investigators are very eager to get familiar with new quality standards and methodological approaches. Experienced regional CROs can provide savings upwards of 20 . the financial component of sponsored clinical trials is extremely important.03 Cost Saving Opportunities Man-hours are much less expensive in Russia than in the West. and data on newly diagnosed patients is collected within these databases on a regular basis .040: Patient Reservoirs. investigator fees represent vital support to both investigators and ancillary personnel. Although some Russian CROs have begun to globalise. Almost all patients with diagnosed pathologies are registered in databases managed by their regional healthcare administrations. so labour can be found at significantly reduced rates.04 Access to Patients The demographic setting in Russia can be termed as 'fast recruitment-friendly'. there are still many local CROs that can provide significant savings in clinical fees. Fig.04. 34 European Union. 4.THE HEALTHCARE.04.
Given the overall healthcare situation of Russia. averaging between 2 – 4 months ahead of sites in more developed areas. Typically. These patients tend to make all the planned appointments and comply with treatment as directed – they take all the required medication.041: Profile of Russian Patients Academic Degree. respiratory and infectious diseases. This huge and well-educated patient population participates in clinical trials because of a specific medical need. 7% University. Unlike Western patients. 5% Secondary. 9 (11):11-14 4.Varshavsky et al..04. As a result. The protocol requirements for complete physicals and more personal interaction with the investigator may in itself offer incentive enough to join a trial. Russia often participates in multi-national mega-trials contributing thousands of patients. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA The region offers huge numbers of treatment naïve patients particularly in oncological. They usually spend their whole lives in the place they were born. Patients in Russia are both eager to participate and extremely compliant. it is not difficult to understand why patient enrolment continues to be so strong.05 Fast Recruitment Rates The pace of patient enrolment is rapid. 50% Source: S. cardiovascular. 38% High School. the treatment provided in clinical research is better than the standard of care available through the national health services. Combined with the additional incentives of Western medicines and therapies. and only very rarely do they withdraw their consent. 4.THE HEALTHCARE.04. neurological. 60 . it is easy to see why the prospective patients are excited to participate. Russian patients hardly ever move from place to place. Fig. That is good for research and follow-up purposes. they fill in the questionnaires and diaries. GCPJ 2002.
Low drop out and low lost to follow-up rate. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA Individual patient benefits combined with social factors (a centralised healthcare system. the combination of a greater respect for authority compared with the West and a settled way of life provides an explanation for a higher level of compliance among patients in Russia.06 Patient Compliance Many patients in Russia require specific treatments that are beyond their reach. Cultural differences between East and West result in: − − − − Higher acceptance rates.07 Quality of Work Despite rumours and existing prejudice. Increased compliance with physician instructions. More disciplined patients. acupuncture. and Potentially the best medications (if it is not a placebo). which they consider more than acceptable. In addition. a lack of competition due to the low number of clinical trials in Russia) makes for a fast recruitment environment. and Russian doctors use autopsy several times more frequently than in the West. 4. particularly physical therapy. It is worth mentioning two other cultural differences: firstly Russian patients use alternative medicine.04. 4. The high educational level in general with no illiteracy means that there is a high level of understanding in the nature of research and the need to follow treatment regimens.04. Their only cost is to be compliant. herbs. and massage far more frequently than their Western counterparts. The best physicians. Russia remains a solid and reliable arena for conducting clinical trials – cases of fraud in general. have been found to be much less frequent than in the United States. 61 .THE HEALTHCARE. Participation in clinical trials is a good opportunity for them to get the appropriate long-term treatment because it offers patients free access to: − − − − The best medical facilities The best diagnostic methods.
Any correction is left to the investigator to take voluntarily. Country Number of Inspections Czech Republic Croatia Hungary Poland Romania Russia Slovenia Total 2 2 6 5 1 6 1 23 NAI 1 0 2 4 1 4 1 13 Observations VAI 3 4 8 1 0 7 0 23 OAI 0 0 0 0 0 0 0 0 NAI = no action indicated. 2002. OAI =official action indicated. Fig: 4.fda. VAI = voluntary action indicated (objectionable conditions found but justifying only local measures and not any further regulatory action).04. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA The European Forum for GCP (EFGCP) supports initiatives for developing better conditions for clinical trials in and around Europe – since 2000 it has been supporting efforts in Russia to conduct trials to world quality standards thus paving the way for today's sponsors from the research-based pharmaceutical industry to place their studies in the region with confidence. FDA audit data suggests that data quality in Russia is at least as good as that from other regions around the world. January 1 1994 to March 31.THE HEALTHCARE. Source: http://www.07: Summary of FDA inspections performed in Eastern European countries.gov 62 .
01. but local insurance requirements.g. it is advisable to do as much locally as possible. a filing cabinet. it may be important to supply concomitant medication to the sites in order to standardise therapy across participating centres. The cost of concomitant treatment in combination with additional equipment may well push study costs over the level incurred in more developed countries. aside from particular local circumstances. To minimize costs. This might be a modern fax machine. or because of a perceived need to pay all investigators in a multi-country clinical trial the same (or similar within a tight range). biopsy needles. On the other hand. vacutainer tubes and the like. tend to keep the price down. it would be wrong to imply that the cost of clinical studies in Russia is lower than in the United States or Western Europe.01 Study Costs On average. It is still possible to save on investigator's fees. However.0 Clinical Trial Issues 5.1 Investigator's Fees To date fees in Russia have not been higher than in the West . these added costs are outweighed by the speed of study completion – often shaving weeks. Sponsors are often uncomfortable that an investigator in the United States may receive three times the pay per patient for the same work compared to those in Russia. clinicians taking part in large projects are now learning to reinvest a portion of their studyderived income in computers.THE HEALTHCARE. CRAs) and management (such as negotiation with investigators and local providers). a laptop. either due to a lack of local knowledge in negotiating. 5. in general. Involvement of the sponsor's local affiliate in negotiations will.often they are much lower but the amount paid will depend on a number of factors. the imposition of customs duties (including 20% VAT). if not months off overall study times in comparison to the United States or Western Europe – and time costs more than money. communication systems and new diagnostic equipment. Nevertheless. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA 5. telephone. 63 . investigator grants are tangibly smaller than in the West and this may represent a substantial saving when a large number of patients are allocated to Russian sites. both in terms of basic resourcing (e. will even out the differences. along with the higher cost of courier services. sponsor or CRO head office's involvement will tend to raise the price (although this is not often recognised). In some studies. and internet communications. Pharmaceutical sponsors should also be prepared to bear additional costs for miscellaneous items such as installation of additional equipment at study sites. On the other hand.
2 Equipment Expenses Instances may arise where investigators. A third party can always be hired to perform certain tests or else a possible solution is to supply equipment to such high recruitment potential sites prior to the study. considerable local expertise is required when choosing such an approach. modem) will follow international prices. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA Lastly. who will be able to negotiate a fair. but the lack of particular equipment or means of communication (such as internet lines. and not be cheaper locally. without engendering any bad feeling. (e. 5.01. however a Western monitor travelling on a co-monitoring visit may well experience prices similar to what they are used to in the West. Patient information and Informed Consent Form (ICF). low (compared to Western investigators) but motivational price. and it should be noted that most equipment costs (such as a laptop. the time cost involved for a Western monitor on a co-monitoring visit or QA auditor must be considered. with arrangements for the payment of the equipment from investigators' grants.3 Monitoring Expenses Monitoring expenses will be much lower for a local monitor.02 Language Usually the following documents must be translated into Russian: i. a flow-cytometer. Also. careful thought must be given when considering sites away from principal cities. whose medical qualification and access to adequate patient population would make them perfect performers. 5. and 64 . as they will tend to stay in international hotels at standard rates.) could present an obstacle. scanners etc.g. an approach which can be beneficial to both the sponsor and the investigative site. The monitoring travel time can be considerable. CAT-scan. this is always best handled by local agents. In addition the site may lack some diagnostic equipment that is absolutely necessary for the conduct of the study. 5. The equipment and experience then qualifies the site for future trials. Study protocol and investigators brochure. fax machine.THE HEALTHCARE. one must consider the investigator's expectations based on previous experience with Western sponsors (which will again tend to inflate the price). As with so many issues. as even local monitors can be reluctant to fly on some local airlines. iii. fax machines. As stated above. Of course. ii. computerised treadmill. etc).01. Labels of the investigational product.
then do not be ask them to make free-text CRF entries in English. 65 . will further expedite the processes. Investigators' and site contracts. pronunciation. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA iv. Russian investigators may often hesitate to speak English because they are afraid of misperceptions due to their accents. which in turn will impede in-house review and data entry. preferably within the population centre. communicate in the local language. Among medical professions. − It may also be appropriate to offer translation assistance during investigator meetings – even where individuals can read and comply with the protocol. This will significantly increase interest in the study. Travel arrangements in Russia. Local-based support both for monitoring and other issues.03 Logistics Good communication is a key factor in the success of any clinical trial. notably outside major cities. to encourage the investigators to speak out and to pose questions. particularly in the study newsletters. are important to success when operating in Russia. 5.03. telephonic.THE HEALTHCARE. and any requirements for more advanced IT services. communications (postage and telecoms). CRFs can remain in English but templates in Russian are very helpful.1 Travel Getting patients and CRAs to the right place at the right time is a fundamental concern in a study. although their general knowledge of English is very good. language skills among study staff can be a problem: − − − − Good enough for reading. can be interesting and should be reviewed carefully before committing to a particular site. Although the vast majority of investigators are fluent in English. therefore. 5. If you wish to attract the attention of Russian investigators. Training in Russian is an important requirement for setting up studies. and attention to communications: written. but not for listening or fluent verbal communication. The results could be partially or totally incomprehensible records. Working in large population centres will optimize logistical considerations in relation to travel (for both subjects and the sponsor). or poor vocabulary. and travel. because improvement of language skills is acquired mainly through reading of scientific papers and not through personal contacts. If investigators do not have a good command of English. knowledge of spoken language is usually weaker than written. It is important.
with their high-density populations. Journeys are shorter. there are 8 further major cities that have a highly developed communications infrastructure and populations in excess of 1 million. rural populations have greater travel requirements than city dwellers. the value of each site to the study needs to be considered carefully to ensure that any travel difficulties or increased travel costs are compensated for by the contribution of the site to the study. Once diagnosed. The key point here is that study subjects in Russia expect to travel to large specialist centres for treatment.primary and specialist care is organized around very large hospitals serving very large populations. patients are quickly referred to specialists for treatment. 5. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA Throughout the world. the postal and delivery infrastructures may not perform to service standards common elsewhere. Close local attention to this is essential. and may be completely lacking. 66 . This is of considerable advantage for clinical trials. Petersburg enjoy the best infrastructure in the Russian Federation and also have high populations (>10 million and >5 million. sometimes due to the courier's own organisational issues and sometimes due to "paperwork. even if a Western courier's headquarters have given assurances of support and service levels. Courier services may not be able to guarantee delivery times. If courier times are long or unreliable. While robust in general.03. and this is the same in Russia." of which customs clearance is the most significant.2 Mail and Courier Services Careful consideration must be given to confirming how mail.THE HEALTHCARE. CRAs undertaking their monitoring duties also benefit from these arrangements. or they can go directly to the specialist without a referral. and other deliveries or pickups will be made. and to offer study teams clear approaches to balancing scheduled with unscheduled work. In conclusion. The problem is often the number of study subjects to be reviewed. It is therefore natural to focus on principal cities as the starting point for site and patient recruitment. time on site more productive. however. respectively). Contingency planning will help here to both respond to these issues should they arise. Familiarity with the specialist needs of clinical trials by Russian courier services is often not as well developed. Moscow and St. and critical samples have to be transported under particular conditions back to a central lab. and several sites are often within easy reach within a single day. Perhaps more important from a patient point of view is the practical organisation of the Russian healthcare system . and plans are in place to respond to the requirements of unforeseen travel. packages. prior understanding of how this can be achieved is essential to success.
it is often as good as comparable Western systems. etc. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA 5. Situations such as this may cause problems if.) using direct connections are widely available and are now often based on the best available technologies. If the telephone system itself is satisfactory.03. for example) checks on speed.04 Background Therapy Background therapy may not be marketed or not available: − − − Check this well in advance. it is still the case that large variations in equipment and service levels occur. In the absence of fax. Involve local partner in protocol review. In some instances there is limited access to long distance and international lines but a solution here is to provide pre-paid calling cards. private clinics) or in more remote locations. provision of dedicated additional lines may result in a bureaucratic exercise with telecom providers. older systems may still be present and need to be accommodated (buildings where the exchange has been upgraded. facsimile transmission will usually be unproblematic. In private buildings (field CRA locations. 67 . Mobile phone services such as laptop connectivity should be checked if essential for supporting monitoring visits. for example. Where the telephone infrastructure has been upgraded. however.3 Communication While considerable progress has been made over the past 10 years to improve the communications infrastructure. an IVRS randomisation system is to be used. sites rely on scanning and email. TCP/IP (Internet)-based services (email. and may not be usable in some areas. It should not be expected that mobile phone services will be available in rural or even some urban areas. stability and configurations are essential prerequisites to initiating and training sites. especially when Internet (TCP/IP)-based services are required.THE HEALTHCARE. as the service levels provided can be mixed. Discuss unification of background therapy with local partner. but the distribution to individual locations has not). The general telephone (voice) infrastructure does not usually present an issue. 5. and if the reliance required is high (for EDC tools. say. But if fax technologies are essential to the study. It is therefore essential to review the electronic communications requirements against study requirements. The types of coverage can vary widely. Web browsing. Services for mobile phones are generally well supported in the principal cities.
particularly physical therapy. the demand for clinical studies lags behind the potential supply. The request is likely to be satisfied simply due to goodwill shown by fellow physicians.06 Recruitment Issues Currently. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA 5. and the spirit of fellowship among physicians is very high. Therefore. It is very important to allocate more time for communication and socialisation in comparison to Western investigators. For example. should be taken into consideration. − − Less AEs are reported by investigators. acupuncture. The use of alcohol is also higher than in the West and this factor along with dietary differences. Certain side effects may thus seem more apparent in Western European or US studies: − Patients may not report "minor" problems because they do not want to bother their doctors with a complaint like a headache or dry mouth. 68 . herbs. It is also worth mentioning that Russian patients very often use alternative medicines . Investigators must be made aware of the problem. the big trial sites in the major cities are beginning to get busy – notably in Moscow and St. However.05 Cultural Differences Lack of familiarity with cultural differences may lead to poorer quality data being collected.THE HEALTHCARE. This has the potential to interfere with the trial results and should be taken into consideration. the competition between investigational sites for contract research projects and patients is not particularly fierce. Russian patients tend to have greater tolerance to pain. the importance of relationships should not be underestimated: − − Investigators show hospitality and respect. In addition. It is not uncommon for respectable clinicians to ask their colleagues from other hospitals to refer patients with a certain diagnosis to them. however. and massage. 5. It should also be noted that there are no recruitment companies in the market (no SMOs and advertising for patients is a new concept). this is not expected to hamper recruitment rates in the short to mid-term. Petersburg.
5. Some clinical centres are not equipped for long-term storage of large amounts of study drugs. the monitor will have to withstand being "talked down to" by the investigator. Failing to build mutual respect at the outset often does not result in a second chance. It is not enough for monitors to just memorize the protocol.an experienced investigator will sense this right away. especially of biotech products that require very stringent storage conditions. The reasoning behind this is not just the necessity for recurrent quality control. Most Russian investigators are also scientists and the monitor's ability to competently discuss pet scientific ideas of the investigator is often the best way to win his/her respect. A strategy of monitoring sites with Western frequencies that have high patient recruitment rates is often a route cause of sponsor dissatisfaction with Russian sites. That is why it is generally advisable that a senior monitor or seasoned project manager should recruit investigators. Sometimes a stand-by car is needed for transporting blood samples from hospitals to contract labs. The consequence is that the 69 . For this same reason. more patients per week at each site will take more time. in order to establish the right rapport with the investigator. they should be able to provide scientific and methodological rationale for any feature of the study design. Russia is not the place where studies can be efficiently monitored by nurses . Longer visits at Western frequency will not have the same efficiency as an increased numbers of visits. instead of the fruitful peer relationship.07 Logistics and Local Support It is often critical to develop an infrastructure to support multicentre studies. For large projects a regulatory interface with healthcare authorities is recommended both to expedite regulatory review and to facilitate importation of clinical supplies. Sending an inadequately trained freelancer will not build respect . PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA 5.THE HEALTHCARE.08 Monitoring It is critical for the monitor to establish a productive working rapport with the investigator.monitors need to be a physician. preferably with a clinical background. As a result. Most investigators who have little prior experience with international clinical projects feel insecure about their performance in the beginning of the study and often need reassurance and guidance from the monitor. the monitoring frequency may need to be as much as two to four times higher in Russia than in the West. Often. To resolve this problem a buffer storage for supplies and accompanying GMP-compatible paper work needs to be set up. In addition. more importantly. due to the large number of subjects per centre and the increased centre support required (in areas such as ongoing investigator training). and issues will accumulate more quickly. This should be done from the very beginning of the investigator-monitor relationship.
in certain respects. Coding of concomitant medications may become a nightmare when not familiar with numerous combination products used in Russia.09 Data Management CRF reviews should be conducted in Russia. a profound knowledge of the local medical community. peculiarities remain therefore for the time being Russian sites should preferably be monitored by Russian CRAs. CROs having Russian offices have a definite advantage in this regard. There have been clinical studies successfully or semi-successfully monitored from abroad. which are not listed in international drug databases. For successful conduct of quality studies in Russia. 5. Local CRAs are much more efficient in deciphering obscure CRF records and facilitating query resolution.THE HEALTHCARE. practices. The importance of local expertise in setting up and conducting clinical studies has to be stressed. and the language is of paramount importance. customs. Russia is rapidly becoming more and more internationally minded but. 70 . PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA number of visits may need to increase – but it may be that during the study a judgement can be made that the higher level of support can be reduced as confidence increases. but those incidents are infrequent.
− Only medical institutions licensed and approved by the Federal Drug Agency may participate in clinical trails .0 Study Set-Up 6.e. Vladkovshki per. the local IEC. which provides ethical expertise. Within its structure. which is responsible for the pharmacological (scientific) content of the study. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA 6. 1998. The assigned supervisor must be familiar with the results of pre-clinical trials of the study drug and has the right to ask for any additional information regarding the same. Implications of the Federal Drug Law include: − Only one government body – the Federal Drug Agency of the Ministry of Health – approves clinical trials. It regulates all aspects of clinical studies from ethics compliance to subject's rights and reporting. The NEC is constituted in strict accordance with ICH 71 . − Trial subjects must be covered by health insurance acquired locally – in addition to any global insurance policies already held by the sponsor.the Federal Drug Law The Federal Drug Law. established a legal basis for drug development and clinical trials and brought the Russian system closer to Western standards. Efficacy and Safety of Medicinal Products and Medical Devices from the Russian Ministry of Health (commonly known as the Russian Drug Agency or the Federal Drug Agency) issues approvals for a clinical trial. and the National Ethics Committee guidelines.THE HEALTHCARE. − The head of the medical institution must approve the study protocol and assign a supervisor which must be a medical doctor with no less than 2 years experience in medical research/clinical trials. 18/20 Moscow 101431 Tel: +7 095 973 1735 Administration for State Control of Drugs and Medical Equipment (NEC).1 Regulatory Compliance . − The Federal Drug Agency requires approval from the National Ethics Committee before a trial can commence. It should be noted that regulatory requirements in Russia are subject to constant change and require close examination in order to ensure compliance and smooth study conduct. According to this law only the Department of Quality.licenses are only issued to GCP. − The study plan/protocol must be developed in conjunction with the Ethics Committee of the institution performing clinical trial – i.compliant establishments. the agency has the State Pharmacological Committee (SPC).
however. especially for smaller pharmaceutical and biotechnology companies. Pregnant women . 72 . However. firstly.e.i. the obligations for AE reporting are not transparent . if any norm in Russian legislation disagrees with the internationally accepted norm. there is still a need for reliable partners in the management and monitoring of clinical trials in the country.unless the drug under trial is being developed especially for paediatrics. with the absence of the appropriate norms in Russian legislation the international legislation comes into power. or when the aim of the trial is to collect better data for this patient group. an individual shipment license must be acquired for each specific shipment of the study drug from the Federal Agency." No subject can be involved in a study without written informed consent. Military personnel. how and to who the report should be made. In the latter case. Clinical trails cannot be conducted on: Orphans. Many large pharmaceutical companies have established their own clinical research units in Russia due to the obvious benefit of conducting clinical research in this region. − Any adverse events (AE) must be reported to the authorities. It is worth mentioning that according to current legislation. however.2 Selection of a CRO and External Vendors Selection of a CRO is an important part of the study set up process.unless the drug is being developed for this patient population and when there is absolutely no risk to the woman or the unborn child. international agreements in which Russia is participating take priority over and above Russian legislation for in-country projects. it is not quite clear when. Prisoners – unless they provide a written agreement and that the appropriate authorities are notified. − − − Drugs for clinical trials must be clearly marked "For Clinical Trial. Secondly.THE HEALTHCARE. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA − Non-registered drugs can be imported for clinical trails purposes. then the trial should follow the latter. 6. the trial has first to be conducted in an adult population. Under-aged children (under 18 years) . − Only drugs manufactured in Russia can be exported thus all unused clinical trial material must be destroyed by Central Pharmacy or specially accredited local companies. This means that.
for example in oncology or cardiology. Such laboratories have been found to meet the most advanced standards in laboratory procedures. but they do have skilled physicians and well-equipped facilities . The cities themselves may lack five-star hotels and have fewer cellular phones per capita. Contracting a local/central pharmacy is a much more effective drug shipment and distribution process. when considering a drug trial in one of the most actively researched indications. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA It is important to check whether a CRO has a physical presence in Russia – many Western CROs still operate via partners. However. it is recommended to set-up one central pharmacy in Russia to distribute the study drug to the sites. but they provide the full spectrum of services and many domestic CROs now operate across CEE/CIS borders. the most prominent investigators in these large cities are often overloaded with protocols and the best hospitals are already busy beyond their capacity. a very inefficient and time-consuming process. Knowledge of local specific regulations and language is a key success factor and use of local expertise is essential in the smooth running of any study – there is great value in familiarity with the capabilities of local sites and the frequently changing regulations. Where this cannot be ascertained it is strongly advised to explore other locations. sponsors usually contract a central laboratory based in a Western European country.in some instances.THE HEALTHCARE. the sponsor should ensure that there will be a qualified physician capable of investing the time necessary to secure smooth performance of the study and that study documentation will be appropriately stored and kept out of other monitors' sight. However. Contract research organisations may represent a new phenomenon in Russia. There are a large number of good clinical sites in other Russian cities. 6. Petersburg. one may significantly decrease the study cost by contracting a Russian laboratory as the central laboratory for the entire region. To avoid long custom clearance procedures.3 Site Identification/ Investigator Selection More often than not. When it comes to a central laboratory. 73 . In such situations. project managers first look for experienced investigators in Moscow and St. sponsors may have to invest extra time in educating these investigators to GCP and training them in various clinical trial procedures but the flipside of this is that these investigators will be less spoiled by the courtship of large Pharmacos and more motivated to partake in clinical studies. There are many licensed pharmaceutical warehouses in full compliance with GMP and GCP guidelines. Study drugs sent by courier directly to the hospital (from abroad) must be cleared through customs by hospital administration. Those far-sighted enough to do some educational work in advance will be in a more advantageous position to recruit investigators and provide for quality performance on a pan-Russian scale.
THE HEALTHCARE. In this instance sponsors often prefer a less prominent but more effective investigator who will seek subjects personally. but in such a setup it is difficult to accurately estimate the enrolment potential. Investigators would be competing for the same patients resulting in fierce inter-departmental competition – the results could be poor recruitment rates. the study may experience a series of delays and never sail through at this site. This option is generally employed when the sponsor's priority is marketing goals and the clinical trial would benefit by being associated with big names. Study monitors would be wise to observe any "diplomatic" protocol and think ahead. promptly answer phone calls and work closely with the study monitor. They probably will not do the work themselves. When working with a clinical centre for the first time. but will hire a couple of investigators who will also require salaries. complete all forms on time. instead of providing much needed assistance when needed. The investigator is likely to know very well how the local power structure works and sponsors should allow their investigators to navigate them through this hierarchical maze. They may not be good practicing physicians either. Sponsors who are unobservant of. it is very important to be aware of the hierarchy . there are generally two options available: − The opinion leader . centre staff will club together to give a united front of carefully calculated inaction. but there may be numerous nuances that cannot be fully appreciated as an outsider. or − A less prominent but more enthusiastic individual. a policy maker and often a full professor.the complexity of which should not be underestimated. usually a departmental head or an assistant professor. Another problem with the opinion leader or policy maker is that they conduct multiple clinical trials simultaneously – sometimes competitive ones – so they have less time to devote to each study and lower motivation. In the worst-case scenario. When selecting an investigator. or insensitive to whatever subordinate relationships there might be. If the study is mostly about the drug's efficacy. or director of a hospital.a well-known physician. opinion leaders are not necessarily good investigators. The general rule is "don't bypass the boss". In some respects. a head of the chair. will pay the price. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA There are a number of clinical centres in Russia that are so large and highly specialised that it would be possible to open several study sites at one particular centre. Project managers often strive to recruit opinion leaders but this approach is more expensive because the opinion leader or policy maker expects higher fees. Moreover. reliable hard-working investigators capable of doing a quality job and staying on schedule in terms of patient enrolment are needed. 74 . this scenario presents organisational advantages. For example. attend all meetings.
but also be a contractual party in the study agreement. However. Institute of Oncology. 6. but they neither deal with subject consent or complete study forms.g. − Huge multi-purpose regional hospitals covering almost all medical specialities in a certain geographic area and each with an outpatient facility. − In most cases. The hospitals are well equipped. Centre for Cardiology. such as injections or taking blood samples. this system is still very Moscow-centric. 75 . have more-or-less modern diagnostic and treatment capabilities. the study drug is kept at the investigator's office – not in the hospital pharmacy – and pharmacists are usually not involved in the clinical trial at all. two categories of medical institutions of interest for conducting clinical studies: − Huge specialised institutions in each field of medicine – e. Saint Elizabeth Hospital.g. There are in general. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA Individual projects will require a trade-off between the advantages of the two approaches to decide which one to implement. Such hospitals will be named after a Saint or by number – e. Hospital # 32. When it comes to conducting clinical trials. the medical system in the country is highly centralised – a heritage of the Soviet past.g. each will also be a teaching and research hospital with outpatient facilities. chief cardiologist of Moscow. Each area of medicine has a "chief specialist" and this is also true for geographical areas – e. Feedback suggests that a mixture of both approaches is the most effective way to conduct a study in Russia. etc. and are staffed with highly trained personnel.31 Medical Institutions As already discussed.THE HEALTHCARE. chief oncologist of North West Russia. there are a few major differences in the Russian compared to the Western model: − Nurses are much less involved in the process of medical care and are hardly ever involved in clinical trials – they may perform study procedures. Both types of institution have in general between 500 and 1500 beds and process tens of thousands of inpatients and hundreds of thousands of outpatients annually. − The hospital administration should not only be notified about the clinical trial. Normally.
out-patient clinic or medical university has its own institutional review board or ethics committee. A Russian version of the study protocol must be submitted as part of the "clinical trial package" to the Federal Drug Agency for review and approval. The members of these IECs are entitled to review and approve clinical trials in the regions where they work. unless dealing with truly experienced investigators. They are usually located at medical universities or at the largest hospitals of the region. but. today. This is the case for all sites involved in the clinical trial and this function must be co-ordinated when dealing with multiple sites. Experienced investigators often accept an outline protocol that leaves a lot of details to their own discretion. the local IEC – and approved by the head of the medical institution. This may seem a trivial issue. However. it is strongly advised to provide the 76 . there are one or more IECs in every region of Russia. When preparing a Russianlanguage version of the protocol.5 Protocol and CRF Design 6. regrettably.51 Protocol The study protocol must be developed in conjunction with the Ethics Committee of the institution performing clinical trial – i. sponsors should be aware of the potential disastrous consequences of hiring a translation bureau. Some pharmaceutical sponsors also choose to provide investigators with a Russian translation of the protocol.THE HEALTHCARE. and the professionalism and skills of their members are improving continuously. but the less seasoned investigator is much more comfortable with a protocol that is explicit rather then implicit about almost every element of the study. the situation has changed remarkably since the early 1990s when there were no institutional review boards (IRBs) or IECs at all. 6. prior to the commencement of the study. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA 6. The number of these committees is on the rise constantly. that the protocol should be somewhat more detailed than an ordinary protocol for a purely Western study. when it comes to purely clinical decisions the investigator should apply his/her best medical judgement rather than anything else.e. this is not a hypothetical situation – many sponsors have fallen foul of this process and ended up with protocols that are not only unintelligible and laughable due to faulty translation but also full of statements that are entirely wrong and may be detrimental. Translation by a non-medic may quite literally ruin the protocol.4 Local IECs Although not every hospital. Ideally the study protocol should preferably be translated by a physician and in addition. the monitor should emphatically explain that although the protocol as such should be meticulously adhered to. It is generally advisable. to the study as a whole. if observed. Usually.
many may still get lost in an English-language CRF. Especially in the beginning of the study. or in the Europe to follow all of them . In situations where the investigator does not have a very good command of English. This is not to say that the CRF should be overcrowded. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA investigator with the original English-language protocol. List of documents to be submitted to the IRB/IEC or to the Regulatory Authorities. then he/she can always look it up in the original text. Insurance and Contracts This is often the most important factor.S.52 CRF Although the vast majority of investigators and CRAs are fluent in English. This would make the CRF substantially bulkier. but would probably be worth it if the study covers a large number of sites in Russia. Finally. 77 . If. If the CRF cannot be sufficiently instructional by itself. some statement in the translated version does not make much sense.6 Legal Issues. which in turn will impede in-house review and data entry. in the investigator's view. Local regulations impact mainly four areas of a clinical study: i. There are many local regulations and it is sometimes difficult for a central Project Manager based in the U.this is another good reason to rely on local staff based in the country. An alternative solution could be to have a Russian-language template that could be superimposed on the original form prior to making entries. Unless the CRF is entirely self-explanatory. then he/she should not be asked to make free-text CRF entries in English as the result could be partially or totally incomprehensible records. it should contain various tips prompting the correct completion of a particular form. which impacts the whole process and can significantly delay completion of a project. if he/she had a clear supplementary document to consult. which would both confuse the investigator and complicate subsequent in-house review and data entry. 6. ii. then a CRF instruction manual would be a good idea. Patient information and informed consent form. 6.THE HEALTHCARE. frequently overlooked by Western sponsors. the investigator would feel much more confident about filling out the CRF. an additional solution that has worked well in Western Europe would be to have the white CRF page in Russian and the other pages in English. One possible solution is to prepare an entirely bilingual English/Russian CRF. which is rare.
The clinical trial package should contain the following core documents: − study protocol and amendments. commodity translation often carried out by translation bureaus can be disastrous . one should review the local regulations.S. but Russian specifics and laws should be observed and incorporated into the translated ICF. lawyer to the ICF text. Insurance policy (need for a local insurance policy). When hiring a third party to translate the informed consent form it should be noted that as with the study protocol poor. usually favourable to the sponsor. There are two elements in the patient information document that frequently cause problems. 78 . Such a statement. the sponsor is required to submit a clinical trial regulatory package to the Department of State Control of Quality. but it needs to be prepared for submission of a sample of the investigational product. To gain study approval.62 List of Documents to be Submitted to Local IRB/IEC or Regulatory Authority A Good Manufacturing Practice (GMP) certificate for the product manufacturer (drug or placebo) is required. despite including all GCP-required elements. and Safety of Drugs at the Ministry of Health of the Russian Federation (Federal Drug Agency). producing a Russia-specific ICF. often does not fulfil expectations of the local IRB/IECs and does not usually comply with ethical principles. Efficacy. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA iii. indemnity issues. Some sponsors transfer a statement directly prepared by a U. The second misunderstanding is specifying the jurisdiction. which significantly delays the study start through double submission. 6.THE HEALTHCARE.61 Patient Information and Informed Consent Form The master informed consent form (ICF) should not be translated word-for-word. Instead. It is more reasonable to refer in the ICF text to the insurance policy or outline the insurance/indemnity situation. 6. and Contracts with investigators and their institutions. This is the worst strategy. such approach discredits the sponsor in the eyes of the local IRB/IEC or Regulatory Authority. One is the indemnity statement. The internal (sponsor's) approval process of the country-specific version should follow applicable standard operating procedures (SOPs). One cannot assume that the ICF master text is perfect if it contains all GCP-required elements. This is unacceptable for high-standard clinical research. Moreover. where a claim can be submitted outside the patient's country of residency. iv.the translation should be scrutinised by native Russian speakers to ensure that nothing has been missed or inverted.
the cost may reach $80 per patient. pharmacokinetics. insurance policy from a Russian insurance company. information for patients and consent form. whereas in Phase IV. although very familiar with the legal aspects. may not appreciate the specifics of the clinical research process. Many international insurance brokers. All consented patients must be insured. list of investigative sites. no trial can be approved without an additional insurance policy issued by a local insurance company and should include civil and product liability. 6. the investigator's brochure). even if they have 79 .e. Sponsor representatives and researchers must be insured in addition to patients. This insurance is the full responsibility of the sponsor and the sponsor is fully liable for all adverse patient reactions to the study drug(s) regardless of the fact that patients are made fully aware of the trial specifications and risks. and curriculum vitae of the principal investigator. but there is a requirement for a full insurance policy to be submitted (an insurance certificate is not enough). Usually there is no indemnity limit. Problems may arise in cases of termination of some sites during the study and the recruitment of additional sites which requires the need for a new policy – this generates additional costs. The local insurance policy should be the first document to be arranged while approaching the study set-up phase.e. The documents should be translated into Russian in full (i. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA − investigator's brochure – containing data on pharmacology. delays progress and increases the complexity of documentation. and previous clinical trials. it may be around $40 per patient. data collection forms for patients (diaries. This is a situation where local representation is highly recommended. No IEC will accept any submission or start to review the planned study if a local insurance policy does not accompany the study protocol. the protocol. For Phase I studies. questionnaires). The cost of such insurance will vary depending on the phase of the study: the earlier the phase the higher the price. toxicity.THE HEALTHCARE.63 Local Insurance Policy Many study sponsors have global product liability insurance in place issued by an international insurance company. − − − − − − case report form and other data collection forms. patient information and informed consent forms) or partly (i. however.
Ideally. When the agreement is signed by the Centre. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA not been randomised (i. The signed contract must be in Russian. Every paragraph (or sentence) in English should be followed by identical text in Russian. In the case of a vaccine study. the contract negotiation is usually a time-consuming process and requires a lot of effort. the sponsor should mail the master contract template to the local staff. Following such process. Both the letter and agreement should be in Russian. the Immunology Committee may also become involved. To process the documents the Agreement should be signed by the study site(s) and the organisation which submits the package (CRO or pharmaceutical company). asking them to customise it to meet local standards.64Contracts with Investigators and Investigative Sites Even with the best local team. if not well prepared. If it is a CRO. copies of the clinical trial package are simultaneously sent from the site to the State Pharmacological Committee (SPC) and to the National Ethics Committee (NEC).000 is charged for processing the documents.THE HEALTHCARE. all patients who have signed the consent form). stating that both versions are identical. Regulatory Authority) is sequential.e. 6. 6. Cost also varies from company to company. the sponsor is required to submit a clinical trial regulatory package to the Federal Drug Agency who then forwards the package to the Federal Scientific Centre for Evaluation of Medicinal Products (the Centre). additional customisation is minor and can be changed without further delay. The submission process usually does not exceed two to four months and the process flow (Ethics Committee vs. often in a different font style. Then. Prepare a bilingual contract template. This presents another challenge for legal advisers based outside the country. A fee of about $1. the country-specific template should be reviewed by the sponsor's legal adviser and submitted to the investigators and their institutions. there should be a notarised 'delegation of authority letter' from the sponsor pharmaceutical company (manufacturer of the study drug) in place before the Centre signs an agreement. Or: ii.7 Study Approval Approvals for clinical trials are based on the Federal Drug Law and issued by the Federal Drug Agency. 80 . Below are two possible solutions to this problem: i. As already discussed. Prepare a local language version and obtain an official certificate from a CRO or other institution in charge of customisation. after such customisation.
It is a well known fact that Russian study sites recruit patients quickly as Russian patients are less reluctant to take part in high-standard clinical trials as patients in Western Europe. Hence. It works effectively and the review procedure does not exceed more than one month in most cases. For many of them. 81 . 6. that there are no meetings from mid-June until mid-September. The most common issue with the NEC is the wording of the 'informed consent form'. with a population totalling approximately 145 million. Although in theory it is possible to apply to the Regulatory Authorities without involvement of the local staff operating in these countries. The Agency lists the investigation sites and the total number of patients to be consented (patients who must sign the consent form). Local representatives can communicate with authorities in the native language. the Russian Drug Agency issues a general approval for the clinical trial. is the most advanced CIS country having been active in international clinical trials since the late 1980s. The National Ethics Committee is established in strict accordance with the ICH GCP. Such individuals usually are more familiar with the procedures of the regulatory authorities. no issues usually occur during the NEC review. Many local CROs offer regulatory and clinical trial approval services . PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA The SPC provides scientific expertise on the study. after approval from the Safety and Efficacy Committees is obtained. When both the SPC and NEC approve the study. international clinical projects sponsored by Western companies.this greatly facilitates the process for international companies planning on conducting trials in the country. They expect more advanced diagnostic procedures.8 Patient Recruitment Russia. Petersburg and some sites are getting very busy while well-equipped sites in the rest of the country remain underused. a new approval should be obtained – this is something to bear in mind. If the study has already been approved for US or Western European sites. it is not recommended. At all other times of the year. which facilitates a more effective dialogue and helps to prevent delays from miscommunication. It should therefore be noted. if there is any change or addition to the sites during the study. Most clinical trial work is conducted in Moscow and St. The SPC usually has its meetings every two weeks. except in summer months when most members are on vacation. are synonymous with state-of-the-art medical technology. SPC approval is normally issued within approximately two months. guaranteeing a more effective follow-up of the regulatory review.THE HEALTHCARE. or if the number of enrolled patients increases. yet its huge human resources are still underutilised.
Audit checks usually only occur once during a trial and the length of the audit process depends on the complexity of the study but usually lasts several days. 6. the informed consent of a legal representative must be obtained and the interests of the patient must prevail over those of science and society.THE HEALTHCARE.9 Site Training As already mentioned. and possible results of the trial as well as to the possible risks and disadvantages of participation. methods. Participants must be informed on their right to decline and/or abrogate the contract at any time. the physician in charge must provide a written agreement stating the candidate has been fully informed and accepted all the terms and conditions of the trial. no subject can be involved without written informed consent. In addition to gaining ethical approval prior to the commencement of a study. sites are also inspected for ethical compliance while studies are ongoing. 82 . language skills among study staff can be a problem. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA immediate access to modern medical equipment. Regardless of the type of study. and supervision and/or monitoring of the process by international professionals. therefore. Administration of the medicinal product must be expected to produce a benefit to the patient. All patients must be fully informed on the reasons. For all trial patients. Ethical monitoring teams examine compliance with GCP. as well as with local and international rules. Particular effort should be made to educate investigators and to monitor clinical sites – this is particularly important for sites new to clinical research. training in Russian is a must. Local CROs working in the region often spend substantial time counselling investigators about site management to ensure that work is done properly and that investigator grants are fairly distributed among the team members to maintain efficient site performance. For trial subjects unable to give informed legal consent. aims.
PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA 7. The process normally takes between two and three weeks in total but complications can arise.THE HEALTHCARE. Customs clearance usually takes between two and five days. Thus. it is necessary to get Ministry of Health import approval for each shipment. it should be stored at a certain temperature (typically +40C). including the study drug. In the worst case scenario. two things should be done: completion of the customs declaration and processing the payment of fees. Customs fees depend on the declared value for customs and the shipping cost. The selection of a courier is important: the shipping company chosen to deliver the drug to Russia should have strong local representation. It should match exactly the shipment content and must be identical to the pro-forma invoice submitted to the MoH for drug shipment approval. 7. Otherwise the study drug may be embargoed at the Russian customs. It is also recommended that a dry run test is performed prior to the shipment of a real drug. one should expect to spend about 35 . which then should be signed by the Deputy Minister of Health and sealed by the Permanent Committee on Narcotic Drugs.0 Importing Clinical Trial Materials When the study has been approved by the authorities. A fee of 20% VAT and the cost of a customs broker must also be added on. waiting for the completion of the paperwork. Gaining such approval is a multi-step process. If a temperature-sensitive drug is to be imported. It should be noted that specific proforma invoice requirements can vary according to the courier employed. it is strongly recommended that a shipment begins only when the letter with all the signatures and seals is ready.40% of the declared value. collection of the signatures and seals may take weeks. which regulates imports of the study drug to the Russian Federation. Once all the papers are ready. The next step for study drug importation is customs clearance. A pro-forma invoice needs to be prepared for each shipment of clinical supplies. As a result.10 Importing the Study Drug According to the Federal Drug Law. a detailed pro-forma invoice should be submitted to the Russian Drug Agency along with the petition to approve importation. The Drug Agency issues an import approval letter. and a special 83 . it is necessary to obtain approval for the importation of the clinical trial materials (CTM) from the Ministry of Health – it should be noted that study approval does not include an import license. This approval is specific for each shipment and should be obtained every time the study drug is shipped to Russia. First.
accountability. The centralised approach utilised in Russia involves the use of a Central Pharmacy and dramatically cuts down the time and costs associated with the importation. where multiple shipments of the study materials to the sites are associated with time-consuming multiple pro-forma invoices. Sponsor companies are not legally obliged to use this approach. retention. packing. A centralised method of importation avoids the difficulties arising from this position. inventory and distribution. which will allow one to deliver drugs to the storage. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA agreement with the customs office should be prepared at the entry point. Most major courier companies such as DHL. each site will be obliged to do all customs clearance by itself. temperature control. satisfying the required conditions before clearance is completed. it is important to bear in mind that if materials are sent direct to the sites. 7. The drug is then sealed in a quarantine area until the clearance paperwork is done. Central Pharmacy should guarantee limited access.1 A Centralised Approach There are two ways of dealing with the importation of the study materials: centralised methods and decentralised methods. security. alarm systems. multiple customs clearances and so on. and an uninterruptible power supply. but. The study materials are sent to the sites from the Central Pharmacy based on the needs of the sites and patient recruitment. destruction and accountability of the study drug. 84 . Fed-Ex and TNT. while waiting for customs clearance. one time customs clearance and so on. offer their services in Russia. A centralised approach allows for some flexibility if the study materials cannot be stored at customs due to the special requirements for the study drug storage. labelling. the study drug can be shipped to the sites. It is helpful to know the specifics of each courier operation in Russia in order to be able to deliver the study materials to the sites within 24 hours. As soon as the paper work is done. There are obvious advantages of using a centralised approach rather than a decentralised one. There is one very important issue relating to the importation of the study drug and other materials into Russia: it is strongly recommended that materials are not shipped directly to the study sites but via a central depot in charge of importation. The following procedures can be performed at Central Pharmacy: storage. In this case it is possible to receive permission from customs to store the study drug in the Central Pharmacy sealed.THE HEALTHCARE. With the centralised approach only one drug shipment needs to be made to the Central Pharmacy with one pro-forma invoice being completed.10.
2 Devices Regulations for the importation of the investigational devices are not clearly defined. Unregistered clinical trial materials included in the laboratory kits (such as glass tubes and needles) can be imported into Russia. 7. but in this case you would pay for every month the goods are in Russia. but the importation rules depend on the content of the kit. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA 7.20.4 Packing Materials There are no specific regulations for the importation of packing materials. 7. If the device is not registered in the country. but nevertheless.20. A good solution for the importation of devices and laboratory kits can be temporary importation. All these material types are subject to customs fees. This general approach can be used for packing materials (such as cooler boxes and coolers). general study equipment (ECG machines. If possible. Temporary importation might be a solution. treadmills and so on) and concomitant medications as well. Customs fees vary for different kinds of packing materials and depend on the weight and content of the package. Customs clearance is simple and the customs fee depends mainly on the weight of delivery and the shipping cost.20 Importing Other Materials 7.1 Study Documents This process is much easier than the importation of the study drug. which may take months or even years to obtain.THE HEALTHCARE. There may be a requirement for an import license and a certificate of safety has to be obtained in most cases. the National Bureau of Standardisation will still have to issue an approval letter in this case. 7. Additional approval from the National Bureau of Standardisation may be required. There are neither specific conditions.20. it requires approval from the National Bureau of Standardisation. 85 .20.3 Laboratory Kits The situation with laboratory kits is similar to that of devices in that there are no regulations for unregistered materials. nor any need for importation approval. some packing materials should be purchased in Russia – this saves both time and money as it is generally much cheaper to purchase these materials locally than to import them.
40 Export of Other Clinical Trial Materials There are no obstacles to exporting study documents or CRFs. information on whether the materials are contaminated or not. Investigational drugs for in-hospital use may be labelled in English. only drugs manufactured in Russia can be exported. 7. diskettes. labelled 'For Clinical Trial'. Petersburg and Moscow to central labs located in Europe or the US. Sudden changes in regulations may put the entire study at risk. In order to do this. The petition for this approval consists of the detailed description of material including size and/or volume.30 Exportation of Biological Media In most international clinical trials there is a need for exportation of blood samples and other biological materials to the central laboratories in Western Europe or in the US. GCP and sponsors requirements. Therefore. otherwise samples can be spoiled or lost. It is important to know that only developed film can be exported. CDs and so on is regulated. It is important to get this approval before the study commences. Drugs for clinical trials must be clearly marked. This media may be monitored by customs to confirm that it does not contain information or materials prohibited for export (such as classified information). the selection of a good courier service and intensive everyday monitoring of the regulations is the only way to avoid serious problems. the export of information on videotapes. The Ministry of Health will issue one approval (export license) for the specified number of samples per study. Thus. and such control may cause delays in delivery. and 36 to 72 hours from the other cities. the unused study drug cannot be returned to the sponsor and must be destroyed by the Central Pharmacy or local companies with special accreditation. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA 7. for example. but study drugs for outpatient use should have instructions for the patients in Russian.THE HEALTHCARE. There are several companies available who can conduct study drug destruction in accordance with the local regulations. Some sponsors consider using Russian central laboratories to cut down the time and cost associated with the exportation of biological samples. According to the Russian Federal Drug Law. and the total quantity of samples for the entire study. It takes 24 hours to deliver biological samples from St. However. Ministry of Health export approval for the entire study is required. 86 .
prior to shipment of clinical trial materials – a dry run test prior to real shipment is recommended − If a sponsor has no local affiliate.THE HEALTHCARE. it is of crucial importance to employ a reliable CRO with strong experience in Russia and an excellent record of conducting successful clinical trials in Russia – knowledge of local requirements is a must − − For importation of CTM. PHARMACEUTICAL AND CLINICAL TRIAL ENVIRONMENT IN RUSSIA 7. it is better to use a 'centralised' approach Wise selection of courier service is very important – one with strong local presence in Russia is recommended − It is recommended not to export the unused study drug and to avoid circulation of the study materials among different countries 87 .50 Summary Useful tips to successful importation of CTM: − All approvals should be prepared in advance.