V.I. Nozdrin, G.A. Pyavchenko

A preclinical research includes the study of the specific pharmacological actions and safety assessment. The study of the dermatotropic activity is provided by using morphological and morphometric assessment of histological sections stained with hematoxylin and eosin on the hardware-software complex, which consists of a microscope with TV-adapter, digital camera, an imaging monitor, computer with appropriate software of the company. It includes also immunomorphological studies using monoclonal antibodies (PCNA, a marker of DNA replication; Ki-67, the proliferation marker, etc). In the assessment of drug safety we include: toxicity (acute, subacute, chronic), local irritating and allergenic effects, mutagenicity, carcinogenicity, immunotoxicity, pharmacokinetics, reproductive toxicity. Pre-clinical studies are conducted according to the approved plans and the protocols developed for each kind of the researches. A plan includes: the purpose of the tests, information on the investigational medicinal product and the reference drug (physical, chemical, biological, pharmaceutical, pharmacological properties, the conditions of storage and use), information about the customer and the producer, the experimantal program, data on laboratory animals, circuit of the tests, the method of administration of the substance, information on the care and feeding of animals, the method of killing the animals, the list of documents to be stored, dates and places of storage. The study protocol (look for appendix) contains, in addition to the aforesaid, the terms of registration, performers, methods of statistical analysis and a list of SOPs (Standard Operating Procedure - a written instruction, which describes in detail the sequence of laboratory procedures, approved by the director of the company). The protocol and study plan before approval of the Head Executive (when the study is performed for a third-party organization) submitted for verification committee, which consists of leading specialists of "Retinoids." Preclinical studies conducted on the basis of its own experimental centre (vivarium and histology laboratory). Vivarium includes: quarantine room for new animals, room for separation of animals by species and sex, equipped with multi-tier racks, washing compartment, shower, storage space for feed, cages and litter, the operating room for manipulation with the animals, a room for physiological studies where the devices are installed to record behavioral responses, ECG and other functional studies. The laboratory consists of office space, separate facilities for the preparation of histological preparations (washing, cutting, wiring, staining), facilities for the storage of raw materials, reagents, drugs archive. All rooms have a forced-air ventilation, artificial lighting (vivarium 12:00. Day/12 hour. Night), fire alarm and fire fighting. Along with the purchase of livestock on the order required number of potential drug (PD), which is analyzed on the quality of the project FAE (pharmacopeial article enterprises) in the chemical analytical laboratory. Provided on the PD issued a final protocol analysis, which includes: the series, date of manufacture, the amount of drug shelf life and quality indicators. Contracts entered into with third parties to conduct hematological and biochemical studies. Before signing the contracts audited each laboratory for the presence of the necessary equipment and qualified personnel. After completion of pre-clinical studies PD written report in accordance with GOST 7.32-2001. To apply for state registration of PD formed dossier preparation in accordance with the requirements of the Health Ministry. The main sources of funding for pre-clinical studies are equity (part of the profits from the sale of the products), the means of third-party organizations (orders), the profit from the sale of educational histological preparations. Pre-clinical research is impossible without qualified staff. These studies are conducted by the staff of the scientific department and other departments. Core staff of the scientific department is: Director, Vice-director of science, pharmacologist, toxicologist, morphologists (2 pers.), analyst (part-time), a pharmacist, engineer (part-time), accountant (part-time), the merchant (part-time), the system administrator (part-time), the registrator of substances and drugs, the director of histologycal laboratory, laboratory histologist (3 pers.), the director of the vivarium, a veterinarian (part-time), electrician (part-time), the driver (part-time), graduate and undergraduate students-circle members (out of state). Among them: Professor - 1, MD - 2 and PhDs - 3, specialists with higher education - 10, with secondary special education - 1.