with contributing author Jon Umarov
This article originally appeared on Michael Tooshi’s FCPA-RUCIS blog and is republished here with permission.
In recent years, clinical trials in Russia have become increasingly common for western pharmaceutical companies and in our opinion, the pharmaceutical sector’s continued development in Russia represents a trend that is set to continue despite the exchange of sanctions between Russia and western governments as a result of the conflict in Ukraine. For example, in 2013, the European Medicines Agency reported that between 2005 and 2011, 62 percent of patients for use in clinical trials were recruited outside the EU and Switzerland, with increasingly prevalent trends in the Commonwealth of Independent States (CIS). The usage of patients from the region rose from less than 1 percent in 2005 to 7.5 percent by 2011. The Center for Drug Evaluation and Research (CDER) of the FDA approved 25 new drugs during Q2 2014, and 10 of them were (or are currently) under study in clinical trials conducted in Russia. According to the latest Orange Paper by the Synergy Research Group, a major clinical trials organization in Russia, the share of multinational, multicenter clinical trials was 42 percent of the total number of clinical trials in Q2 2014, and bioequivalence and local studies amounted to 30 percent and 28 percent respectively.
According to the same report, in Q2 2014, clinical trials in Russia were sponsored by companies from 24 countries. The highest number of trials (89) was initiated by Russian sponsors. American sponsors took the runner-up place, with 29 new studies; they are followed by German and UK sponsors with 11 trials each, Swiss sponsors with 10 studies and Israeli sponsors with nine new studies. The group of leaders is concluded by French sponsors, having seven studies.
The number of Phase I clinical trials remained about the same and stood at eight new studies in Q2 2014. The number of the Phase II trials increased from 21 in Q2 2013 to 29 new studies in Q2 2014. The number of Phase III trials increased from 88 to 92 studies, 5 percent more than in Q2 2013. Phase IV trials showed an increase from five studies in Q2 2013 to six studies in Q2 2014. The number of subjects planned to be enrolled in Phase I to IV trials launched in Q2 2014 is 15,424, representing 22 percent more than in Q2 2013 figure, when 12,677 patients were planned to be enrolled.
Turning to the legal framework in Russia, the Federal Law on “Circulation of Medicines” governs most aspects of clinical trials in the country. The Ministry of Health (or Ministerstvo Zdravoohraneniya) is responsible for regulating the clinical trials process, along with the Federal Service on Surveillance in Healthcare (or Roszdravnadzor), which oversees the safety and registration of medical drugs. Clinical trials in the country are conducted in accordance with Executive Order No. 266 on the “Rules for Clinical Practice in the Russian Federation,” dated June 2003, in conjunction with the “National Standards of GCP in the Russian Federation,” established in 2005.
The Ministry of Healthcare has also issued a series of orders governing the clinical trials process. Under the Law on the “Circulation of Medicines,” medical drugs must be tested in a clinical trial before they can be marketed and sold in Russia. Such requirements apply to any medicines, even if they have already undergone a clinical trial in another country. This requirement has led to increased numbers of multicenter and bio-equivalence studies for drugs that are destined for the Russian pharmaceutical market.
Additionally, medication manufactured abroad cannot undergo its first clinical trial in Russia, a regulatory requirement creating the need for testing the medicine in another state prior to its introduction in Russia, usually the country of manufacture. The requirement serves as an incentive for companies to localize their manufacturing process and serves to bring the clinical trials sector into line with the objectives of Russia’s Pharma 2020 strategy, announced in 2009.
According to the Ministry of Healthcare, clinical trials may be conducted by pharmaceutical companies either directly or through the engagement of a third-party “contract research organization” (CRO). The types of trials can be broken down into International Multicenter Clinical Trials (or IMCTs), local trials of efficacy and safety and bio-equivalence studies. Local trials and bioequivalence studies can be arranged by both local and foreign-based sponsors.
In order to conduct a clinical trial, a sponsor must submit an application to the Scientific Center for the Evaluation of Products for Medical Use and also have it approved by the Ethics Council of the Ministry of Healthcare. The Law on the “Circulation of Medicines” forbids direct interaction between the Ethics Council and pharmaceutical companies. Some have cautioned that this apparent anti-corruption measure is too strict, and has only served to increase the number of applications that are not approved due to technicalities owing to the fact that constructive scientific dialogue between the authorities and manufacturers has become more challenging to achieve.
International investors in Russia should be aware of corruption risks associated with the process in Russia, in addition to familiarizing themselves with the Law on “Circulation of Medicines” and all applicable regulations on clinical trials in Russia. Interactions with public officials are inevitable in clinical trials. FCPA-RUCIS would like to emphasize that although engaging CROs to assist with clinical trials can make navigating the process easier, it could also lead to third-party risks when attempting to overcome the inevitable procedural hurdles in Russia.