SID & GP MINPROMTORG OF RUSSIA Corporate Communication Center IV ALL-RUSSIA GMP CONFERENCE Experience in implementing GMP rules in Russia and the history of creating a domestic GMP inspectorate

The situation in Russia before the creation of the GMP inspectorate The situation in Russia before the creation of the GMP inspectorate. Problems raised by the industry: Lack of an effective GMP regulatory system: lack of equal mandatory requirements for all manufacturers, clear and understandable regulatory documents, lack of understanding of the control and supervision system, inspection. Weak harmonization with international requirements in the field of pharmaceutical production. Lack of effective international cooperation between Russia and countries with a higher level of regulation of the pharmaceutical industry. Shortage of professionals in the field of ensuring the quality of production of medicines, inspectors, etc. The lack of an inspectorate and the institution of qualified persons in the field of GMP. ?! ?! ?! General partner: Strategic partners: Official partners: Regional partners:

Solutions proposed to the pharmaceutical industry by the Ministry of Industry and Trade of Russia and the Federal State Institution “State Institute of Drugs and Good Practices” 1. Development and approval of regulatory legal acts in the field of ensuring and monitoring GMP rules in the Russian Federation and EAEU. Joint inspections in the EAEU countries. 2. Collaboration between the Federal State Institution “State Institute of Drugs and Good Practices” and the global pharmaceutical community. Establishment in the Federal State Institution “State Institute of Drugs and Good Practices” of a strong staff of GMP experts and inspectors of international level. Continuous training and exchange of experience with foreign regulators. 3. All-Russia GMP Conference. All-Russia Interuniversity GxP Summit with international participation. Educational programs developed by the Federal State Institution “State Institute of Drugs and Good Practices”. General partner: Strategic partners: Official partners: Regional partners:

Milestones of creation of GMP Inspectorate of the Federal State Institution “State Institute of Drugs and Good Practices”… 2008 2014 2015 2016 Federal State Institution “State Institute of Blood Substitutes and Medicines” transferred to the Ministry of Industry and Trade of the Russian Federation. The Institute was renamed into the Federal State Institution “State Institute of Drugs and Good Practices” (FSI “SID&GP”). FSI “SID&GP” is accredited as an expert organization involved in licensing of pharmaceutical manufacturers located in the Russian Federation as part of a commission of the Ministry of Industry and Trade of Russia. FSI “SID&GP” is authorized to inspect manufacturers of medicinal products for human use, the manufacture of which is carried out outside the Russian Federation, for compliance with the requirements of GMP rules in order to issue statements on the compliance of the manufacturer of drugs with the requirements of the Rules of Good Manufacturing Practice. Start of inspecting manufacturers of drugs for human use, the production of which is carried out outside the Russian Federation and whose products are supplied to the pharmaceutical market of Russia, for compliance with the requirements of the Rules of Good Manufacturing Practice. General partner: Strategic partners: Official partners: Regional partners:

Milestones of creation of GMP Inspectorate of FSI “SID&GP”: Legislative activity. 2013 2014 2015 2016 Preparation of amendments to FZ-61 “On Circulation of Medicines” (amending as per 429-FZ as of 12/22/2014): Production of DP according to GMP. The publication of the Order of the Ministry of Industry and Trade of Russia No. 916 dated June 14, 2013 “On Approval of the Rules for the Organization of Production and Quality Control of Drugs”. The publication of the Order of the Ministry of Industry and Trade of Russia N 1997 dated December 12, 2013 “On Approval of Recommendations on the Organization of Production and Quality Control of Drugs”. Entry into force of the Russian GMP Rules. Decree of the Government of the Russian Federation N 1314 dated December 03, 2015 "On Determining the Compliance of Drug Manufacturers with the Requirements of the Rules of Good Manufacturing Practice." Decree of the Government No. 1025 dated September 28, 2015, the extension of the authority of the Ministry of Industry and Trade: inspection of pharmaceutical manufacturers for compliance with the GMP standards. Order of the Ministry of Industry and Trade of the Russian Federation N 4184 dated December 21, 2015 "On Determination of the Federal Budget Institution" State Institute of Drugs and Good Practices“ of the Ministry of Industry and Trade of the Russian Federation as an authorized institution for conducting inspections." The following documents have been prepared: draft issuance of statements; project for the organization of inspections of pharmaceutical enterprises; administrative regulations, etc. The beginning of inspection of foreign manufacturers of drugs for compliance with the GMP requirements. General partner: Strategic partners: Official partners: Regional partners:

Structure of the GMP Pharmaceutical Inspectorate Ministry of Industry and Trade of the Russian Federation  First Deputy Minister of Industry and Trade of the Russian Federation Sergey Anatolyevich Tsyb MINPROMTORG OF RUSSIA Department of Pharmaceutical and Medical Industry Development Director - A.V. Alekhin Deputy Director of Department of Pharmaceutical and Medical Industry Development of the of the Ministry of Industry and Trade of Russia - Deputy Head of the Russian State GMP Inspectorate E.V. Denisova Director of FSI “SID&GP”, Deputy Head of the Russian State GMP Inspectorate V.N. Shestakov Pharmaceutical Production Inspection and Expert Evaluation Department N.N. Chadova … other departments … other departments Pharmaceutical Production Inspection Division Drug Manufacture Licensing and Inspecting Department - G.V. Grosheva Expert Evaluation Division General partner: Strategic partners: Official partners: Regional partners:

GMP Pharmaceutical Inspectorate today. I Q. inspectors inspectors inspectors inspectors General partner: Strategic partners: Official partners: Regional partners:

GMP Inspector Requirements Higher education in one of such majors (areas of training) as biology, biotechnology, veterinary medicine, clinical medicine, radiation, chemical and biological protection, pharmacy, basic medicine, chemical technology and chemistry. Work experience of at least 5 years in the field of production and (or) quality control of drugs. Continuing education (internal and external). Mentoring and internships. Regular qualification monitoring. The participation of foreign regulators during the inspection. General partner: Strategic partners: Official partners: Regional partners:

countries inspected in 2018 Geography of GMP Inspections 57 countries inspected in 2018 667 inspections of foreign manufacturers conducted around the world in 2018 General partner: Strategic partners: Official partners: Regional partners:

GMP inspections in the Russian Federation Today, the number of organizations that have valid licenses for the production of medicines for human use in the Russian Federation is 492. 325 inspections conducted in 2018 Based on the results of the licensing control and on the basis of applications from manufacturers of pharmaceuticals for human use, 166 Russian pharmaceutical manufacturers obtained statements of compliance with GMP requirements for 381 production sites (of which there are 201 valid statements). General partner: Strategic partners: Official partners: Regional partners:

International activity Cooperation Agreements / Memoranda of Understanding: MHRA; AEMPS; Bulgarian Drugs Agency (BDA); CECMED ISP Chile. International organizations: 1. EDQM 2. EMA 3. WHO 4. PIC/S 5. ISPE 6. PDA and other. General partner: Strategic partners: Official partners: Regional partners:

GMP and GLP interrelations examples. Quality control (Chapter 6, paragraph 225 (6.22) of the Rules of Good Manufacturing Practice). “Animals used for components control, raw materials or products shall, if necessary, be quarantined before working with them. Animal care and control should be organized in such a way as to ensure their suitability for intended use. Animals must be labeled, and data on previous work with them must be documented. ” Production of biological (including immunobiological) pharmaceutical substances and drugs. (Appendix No. 2 to the Rules of Good Manufacturing Practice, paragraph 33.(19)) “Different types of animals are used the production of biological drugs. Two large groups of sources can be distinguished: a) live animals. For example, monkeys (polio vaccine), horses, sheep and goats (immune serums against snake and tetanus poisons), cats (allergens), rabbits, mice and hamsters (rabies vaccine), goats, cattle (transgenic products); b) tissues and cells of animal origin extracted from killed animals (sheep and pigs) used for the production of high-tech medicines or as raw materials for enzymes, anticoagulants and hormones. Animals are also used for quality control in accordance with specifications (pyrogenicity, toxicity, harmlessness, specific activity).” General partner: Strategic partners: Official partners: Regional partners:

GMP and GDP interrelations examples. GMP inspections include inspection of: Warehouse areas Chapter 3 of the Rules of Good Manufacturing Practice. Premises and equipment. Chapter 5 of the Rules of Good Manufacturing Practice. Production. Materials management and storage. Measures for handling raw materials, packaging materials, bulk and finished products, including sampling, quarantine, issuance of permits for release and storage, and transportation. Measures for handling rejected materials and products. General partner: Strategic partners: Official partners: Regional partners:

The competencies of FSI “SID&GP” cover all relevant pharmaceutical practices throughout the life cycle of DP Promotion for the development of pre-clinical (GLP) and clinical (GCP) practices. Promotion for the development of distribution practices (GDP) – currently, there are 12 trained employees in the staff of FSI “SID&GP”. Development of conceptual projects for pharmaceutical industries including GMP-critical sections (technological solutions, architectural and planning solutions, heating, ventilation and air conditioning). etc. General partner: Strategic partners: Official partners: Regional partners:

Thank you for your attention. GCP Thank you for your attention. GLP GMP GxP EAEU GDP GACP GVP General partner: Strategic partners: Official partners: Regional partners:

Concept of GLP and PCT. Good Laboratory Practice GLP: The system of requirements for organizing, planning and conducting preclinical (non-clinical) studies of substances / drugs, reporting results and quality control of these studies. Pre-clinical (non-clinical) trial: Chemical, physical, biological, microbiological, pharmacological, toxicological and other experimental studies or a series of studies to study the test substance / drug or physical effects, means, methods and technologies for the prevention, diagnosis and treatment of diseases by applying scientific methods of assessment in order to study a specific action and / or evidence of safety for human health [EAEU Good Laboratory Practice Rules]. General partner: Strategic partners: Official partners: Regional partners: