AVOIDING PITFALLS IN LOGISTICS OF CONTROLLED AND HIGHLY ACTIVE SUBSTANCES IN RUSSIA Logistics of Controlled Substance in Russia is a complicated process, which can be further impacted by the presence of a hidden sub-class of "Highly Active Substances". To date there exist a local paucity of adequate experience among both local and global clinical depots in organizing importation and distribution of these types of goods. In this respect, COREX Pharma Depot proudly stands out, having completed a number of successful projects that had involved full cycle management of Controlled and Highly Active Substances. Handling of Controlled Substances differs significantly from that of other pharmaceutical products and is subject to a separate set of regulations. For a depot to be allowed to handle Controlled Substances, a dedicated license and a distinctively equipped storage facility are required. For the sponsors that are evaluating potential vendors it is paramount to understand that this process requires a very specific skill set. Failure to select a knowledgeable and reliable local partner may lead to significant delays and even failures of clinical trial execution. COREX is one of the very few local vendors that is fully licensed, has the expertise and is equipped in compliance with all applicable requirements that allows it to handle controlled drugs. . Types of Controlled Substances Types of Controlled Substances While classification of both psychotropic and narcotic substances is intuitive and relatively straightforward, figuring out if the investigational product or a comparator drug falls under HAS category can be quite challenging. Below is the translation of the local definition of HAS: Traditionally, Controlled Substances have been divided into three main categories: 1. Potent or Highly Active Substances (HAS) 2. Psychotropic Substances 3. Narcotic Substances. Highly Active Substance – a substance, which is dangerous to life and health in cases when taken in large doses or in presence of medical contraindications. Such substances are able to induce a state of dependence; they may have a stimulating or depressing effect on the central nervous system, resulting in hallucinations or disturbances in motor function or thinking, behavior, perception, etc. A complete list of HAS is contained in Schedule 3, which is published annually by the Government Resolutions. It may come as a surprise that this list includes such substances as Chlorpromazine, Clonidine, Teofedrin, and Chloroform. These examples illustrate the significant discrepancy in designation and terminology between Russian and Western classifications. These drugs that would not immediately be thought of as controlled substances are indeed designated as HAS. It is noteworthy that Section 234 of the Criminal Code of the Russian Federation establishes liability for illegal trafficking of HAS. Therefore, we strongly recommend that before the start of any project the classification of each drug entity is vetted with the local experts. Only when it is has been clearly determined whether or not the drug in question is listed as a controlled substance should subsequent regulatory and logistical steps be undertaken. Regulatory Landscape To obtain permission for importation of HAS the following set of documents is required:  Apostilized power of attorney from the sponsor of the study, with the indication of all the specific responsibilities that are being transferred to the vendor;  The Ministry of Health approval to conduct a study should have a depot listed as a consignee, otherwise you'll have to create a separate annex to the resolution, which may slow down the process. All issues pertinent to importation must be resolved prior to initiation of customs procedures;  In order to obtain a drug importation permit local law requires that a formal international contract (Foreign Trade Contract) between the Sponsor/Actual Sender and the vendor be executed and enclosed with the submission. It is frequently difficult to explain to the sponsors the reasons and the need for such an agreement. It should be understood that the contract is a necessary formality and the parties of the contract are never going to be invoiced or carry any liability under it;  Unlike a standard import license, which is granted within 10-15 business days, receiving an importation permit for HAS and for controlled substances takes up to 2 to 3 months. This is due to the fact that in addition to the submission of documents to the Ministry of Health, an approval from the Federal Service for Supervision in Public Health and Social Development as well as an approval from the Ministry of Industry and Trade of the Russian Federation must be obtained. It is impossible to carry out simultaneous submissions of documents as the Ministry of Industry and Trade requests the full dossier, which must include the approvals of the two other agencies. Customs clearance When the permit for drug importation has been obtained customs clearance is not a complicated procedure. Nevertheless, in order to avoid additional costs and complexities, careful attention should be given to this issue. To minimize the risks of documents' incompleteness or non-compliance with customs requirements we recommend that the responsibility for the transportation of goods is transferred to the accredited local depot that has a customs broker accreditation. This arrangement allows for faster and more seamless importation and prevents unnecessary delays, since the transportation depot has the ability to correct and request all required documents promptly, without reverting back to the sponsor. Storage The storage of HAS and controlled substances has certain specific characteristics. The goods of this class should be stored in locked, sealed areas with reinforced doors and walls. In addition to the segregated areas it is preferable to use fire-resistant safes. The depot should follow all pre-specified federal guidelines that pertain to the substances that are being stored. Transportation The delivery of HAS and controlled substances to research centers must be carried out by two couriers to ensure safety, security and access control (the so-called “double security and safety”). In addition, all boxes and all secondary packaging must be sealed and get the security labeling for the duration of storage. Destruction In most cases the unused drugs are collected from the centers at the end of the study and are subsequently destroyed at a certified destruction facility. There are no specific requirements for the destruction of this class of goods; therefore any licensed vendor can be employed for these services. They must provide valid certificates for destruction upon completion. Appropriate transportation of the drug must be ensured and recalculation of the received materials must be performed before the destruction. We hope that you have found this information useful. For any additional questions please contact: Konstantin Melnikov Managing Director COREX Pharma Depot Address: 1 Komsomolskaya Street, Podolsk, Moscow region, Russia, 142100 Tel: +7 495 532 62 46 Email: [email protected] Website: www.corex-depot.com