ORDER OF THE GOVERNMENT OF THE KYRGYZ REPUBLIC

of April 6, 2011 No. 137

About approval of the Technical regulation "About Safety of Medicines for Medical Application"

According to the Law of the Kyrgyz Republic "About bases of technical regulation in the Kyrgyz Republic" the Government of the Kyrgyz Republic decides:

1. Approve the enclosed Technical regulation "About Safety of Medicines for Medical Application".

2. To the Ministry of Health of the Kyrgyz Republic of the Kyrgyz Republic in accordance with the established procedure to make offers on reduction of regulatory legal acts of the Government of the Kyrgyz Republic in compliance with the Technical regulation specified in Item 1 of this Resolution.

3. This Resolution becomes effective after six months from the date of official publication.

Approved by the Order of the Government of the Kyrgyz Republic of April 6, 2011, No. 137

Technical regulation "About Safety of Medicines for Medical Application"

Introduction

This Technical regulation (further - Regulations) is developed according to the Constitution of the Kyrgyz Republic, the laws of the Kyrgyz Republic "About medicines", "About bases of technical regulation in the Kyrgyz Republic", and also other regulatory legal acts of the Kyrgyz Republic, for the purpose of safety of life and human health in case of use of medicines and preventions of the actions misleading consumers.

In these Regulations the basic normative provisions of the following international documents are considered:

1) Proper laboratory practice (Good Laboratory Practice (GLP), Quality manual of the preclinical (not clinical) researches UNDP/World Bank/WHO, OECD Principles on Good Laboratory Practice);

2) ICH GCP - Management on Proper clinical practice (Guideline for Good Clinical Practice) of the International conference on harmonization of technical requirements to registration of the pharmaceutical means intended for application by the person (International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use, ICH) which is developed taking into account the existing requirements of Proper clinical practice of the European Union, the United States of America and Japan, and also Australia, Canada and the World Health Organization (WHO);

3) directives of the EU Council of March 31, 1992 No. 92/25/EEC "About rules of wholesale of medicines for the person";

4) rules of production of medicines (GMP) of the European Union (GMP of the EU), 4 reviewed edition, the Proper production practice of pharmaceutical medicines of WHO (the official translation into Russian of Good manufacturing practices for pharmaceutical products (Who Technical Report Series, No. 823, the Project for creation of national managements of the CIS countries "Proper production practice of pharmaceutical medicines", the Directive 2001/83/EU "Rules of management on GMP about independent quality control and the Authorized person";

5) WHO/PHARM/DAP/96.1 "The Proper Pharmaceutical Practice (PPP) in Public and Hospital Drugstores". FIP INTERNATIONAL PHARMACEUTICAL FEDERATION Standarts for Quality of Pharmacy Services. Good Pharmacy Practice, Proper pharmaceutical practice in the New Independent States. Management on development and deployment of standards. The special project of WHO on pharmacy in NNG together with the WHO center for medicinal policy and development of pharmaceutical practice.

Chapter 1. General provisions

1. These Regulations are applied for the purpose of safety of medicines and protection of life and health of the person.

2. These Regulations determine mandatory requirements to medicines and govern the relations arising in the course of development, production, production, storage, transportation, realization and utilization of medicines.

3. The basic concepts used in these Regulations:

1) "acclimatization" - process of adaptation to new conditions of the environment;

2) "active pharmaceutical ingredient" (active substance, pharmaceutical substance, active ingredient) - the substances of plant, animal, biotechnological or synthetic origin having pharmacological activity, intended for production and production of medicines and determining their efficiency;

3) "pharmaceutical institution" - pharmaceutical warehouses, drugstores, drugstores of healthcare institutions, pharmaceutical Items, pharmaceutical booths, and also warehouses of medical equipment, shops of medical equipment and-point optics;

4) "pharmaceutical warehouse" - the wholesale company medicines performing acceptance, storage, and realization of medicines;

5) "risk analysis" - evaluation method and descriptions of critical parameters when functioning the equipment or process;

6) "authenticity" - equivalence recognition to other text constituted in other language and having force, identical with it;

7) "balance (production yield)" - comparison of theoretically expected and actual amounts of the made or used products in case of normal variations;

8) "balk-product of medicine (in balk)" - any medicine which passed all stages of engineering procedure, except for stages of packing and/or final packaging and marking;

9) "bacterial contamination" - introduction of superadmissible quantity of bacteria in case of non-compliance with sanitary and hygienic conditions;

10) "safety of medicines" - the characteristic of risk degree of damnification to health and negative influence of medicines on human body;

11) "biologically active agents" - the substances of different origin which are potential sources of receipt of medicines;

12) "biological agents" - microorganisms, including received by methods of genetic engineering, cellular cultures and endoparasites, pathogenic or nonpathogenic;

12-1) "biological medicines" - medicines which contain the active ingredients of biological origin received by way of production from biological source (human, animal, vegetable, microbic or biotechnological);

12-2) "biotechnological medicines" - the medicines containing the active ingredients received by means of methods of biotechnology, such as: genetically engineered technology, cellular engineering, gibridomny technologies, engineering enzimologiya, engineering immunology, etc.;

12-3) "биосимиляр" - the medicine similar to original biotechnological medicine reproduced by means of biotechnologies;

13) "scrap" - not conforming to standards, poor-quality products of production, and also defect (defect) in products;

14) "defective products" - the products which lost quality owing to inadequate storage conditions, transportations and not conforming to requirements of the regulating documentation, officially revealed and documentary fixed;

15) "the brochure of the researcher" - abstract statement of results of preclinical and clinical studying of medicine, significant for its research on the person;

16) "validation" - the documentary action proving that any technique, process, the equipment, raw materials, activities or system really result in the expected results;

17) "probable collateral reaction" - the adverse clinical manifestation including also change of laboratory indicators which is connected on time using medicine, but has no relation to associated diseases or other factors, and regresses after medicine cancellation. Reaction to repeated prescription of medicine is unknown;

18) "possible collateral reaction" - the adverse clinical manifestation including also changes of laboratory indicators which is connected on time using medicine, but which can be explained with availability of associated diseases or use of other medicines or chemicals. Information on reaction in case of cancellation of medicine is not clear;

19) "the owner of the registration certificate" - the legal entity who is responsible for production, quality, safety and efficiency of medicine;

20) "return" - sending medicines to the producer or the distributor, irrespective of whether these products have defect of quality or not;

21) "returned products" - the finished goods returned to manufacturer or the distributor;

22) "air lock" - the limited space with two or several doors between two or several rooms, for example, different classes of purity serving for control of flow of air between these rooms when opening doors. Air locks intend and used for movement, both personnel, and the equipment and products;

23) "intra production supervision (technological, interoperational)" - the checks which are carried out in course of production for the purpose of control and, in case of need, adjustments of parameters of engineering procedure in order that products conformed to requirements of the specification. Control of state of environment or the equipment is also considered as element of interoperational control;

24) "excipient" - pharmacological not active agent of the organic or inorganic nature which is used in production process and production of ready medicine for giving of necessary physical and chemical properties;

25) "secondary isolation" - the system of isolation interfering penetration of biological agents into the external environment or into other production zones (includes use of rooms with special devices of preparation of air, air locks and/or sterilizers for material transfer outside and safety of technological transactions);

26) "release in parameters" - system of release which, being based on information collected in production process and based on compliance to specific requirements of proper production practice in the part concerning release in parameters provides guarantees that these products have required quality;

27) "quality assurance" - set of the systematic and systematic actions providing compliance of carrying out research to proper laboratory practice;

28) "generic medicine" is the medicine which is containing the same active ingredient in the same dose and dosage form and having the same therapeutic action, efficiency and conditions of production of GMP as original medicine;

29) "the main plan" - system of distribution and resource planning when carrying out preclinical (not clinical) researches;

30) "the main bank of cages" - the cellular culture which is (completely characterized), distributed on containers as a result of the single transaction, processed for ensuring total homogeneity and kept in the conditions providing stability;

31) "the main bank of sowing cultures" - the culture of microorganisms distributed on containers from one bulk means as a result of the single transaction so that were provided uniformity and stability and was prevented contamination;

32) "state registration of medicines" - system of the admission of medicines to medical application in the territory of the Kyrgyz Republic based on expert evaluation of the registration file and assessment of results of the carried-out testing of the provided samples of the declared medicine for compliance to quality requirements, efficiency and safety for the person;

33) "the state re-registration of medicines" - the procedure which is carried out for the purpose of prolongation of permission to medical application of medicine in the territory of the Kyrgyz Republic based on risks assessment in case of use of medicines with certain frequency and data of pharmacological supervision;

34) "finished goods" - products which passed all stages of engineering procedure, including the packaging and marking intended for realization;

35) "diagnostic testing" - express diagnostics of functional, physical parameters of health of the person;

36) "agreement" - the written, dated and signed agreement between two or more parties determining the arrangements concerning distribution of amount of works, the rights, obligations, and if necessary, financial questions;

37) "preclinical research" - the chemical, physical, biological, microbiological, pharmacological, toxicological and any other pilot study conducted for the purpose of obtaining by scientific methods of estimates and proofs of efficiency and safety of medicine, which is not including experiments on the person;

38) "the distributor (the wholesale organization, the supplier)" is legal entity who conducts procurement of products at the seller or the producer and organizes subsequent its realization in network of pharmaceutical institutions based on the agreement;

39) "the agreement (contract) in distributor practice" - the written, dated, signed agreement between two or more parties determining the rights and obligations, delivery conditions, transportations, quality assurances of goods and services, payments and other questions concerning proper accomplishment of rules of distribution;

40) "documentation in distributor practice" - set of the documents confirming the operations performed by the distributor on purchase, storage, import, export, realization, response, return, destruction of products, and allowing to trace movement of products from purchase before realization and/or destruction;

41) "documentation in case of performing preclinical and clinical trials" - the records in any form describing, or registering the methods, the organization and/or results of preclinical (not clinical) and clinical trial, factors influencing research and the taken measures;

42) "the yellow card (the map message about collateral reaction or lack of efficiency of medicine in case of medical application)" - form in which doctors of all organizations of health care, irrespective of pattern of ownership, and pharmaceutical workers report about any cases of collateral reactions of medicines;

43) "applicant" - the legal entity who submitted the application for the state registration / re-registration and confirmation of conformity of medicine in the Kyrgyz Republic;

44) "identification of animals" - procedure of identification of animals for documentary individual signs;

45) "the individual card of the examinee" - the printing, electronic or optical document intended for introduction in it of information on each examinee provided by the protocol of clinical trial;

46) "inspection" - the procedure of official check for the purpose of assessment of the obtained data and quality of performing preclinical (not clinical) and clinical trial, material and clinical resources and documents by authorized state body of the Kyrgyz Republic in the field of health care in the field of drug circulation with involvement of specialists of the organization which is carrying out expertize regarding safety, efficiency and quality of medicines;

47) "the informed consent of the examinee" - the voluntary, written consent of the examinee to participation in clinical trial after acquaintance with all features of this research in amount, stipulated by the legislation;

48) "information which identifies case of collateral reaction of medicine" - data on source of receipt of information, the suspected medicine, the patient, the description of collateral reaction;

"Production or engineering procedure" - all transactions connected with medicine production since receipt of raw materials, then processing and packaging and completing 49) receipt of finished goods;

50) "the changes made to the registration file" - changes or amendments which can take place during action of the registration certificate, offered by the applicant, concerning the registered medicine;

51) "the instruction on application" - officially the approved instruction enclosed in medicine packing unit intended for the specialist and containing information necessary for the correct use of medicine;

52) "researched" - the patient who takes part in clinical trial or as a part of group which appoint the researched medicine, or as a part of group which appoint comparison medicine;

53) "researcher" - the physical person who is directly carrying out preclinical (not clinical) and clinical trials;

54) "the researched medicine" - dosage form of active substance or placebo which is determined or used for comparison in clinical testing or for more information on the registered medicine form;

55) "the researched medicine" - dosage form of the active agent or placebo studied or used for control in clinical trial including the medicine allowed for medical application if the method of its application differs from approved; in case of its use according to the new indication or for more information according to the approved indication;

56) "the research "case control" - type of pharmakoepidemiologichesky research which is conducted on two groups of patients at one of which there are specific iatrogenic diseases or collateral reactions, and in another - there are no similar diseases or collateral reactions, for the purpose of identification of cumulative effects in case of long use of medicines and serious collateral reactions;

57) "research laboratory" - the laboratory determined by authorized state body of the Kyrgyz Republic in the field of health care in the field of drug circulation for carrying out preclinical (not clinical) researches based on the recommendation of the organization performing examination regarding compliance of laboratory to requirements of these Regulations when carrying out researches on safety, efficiency and quality of medicines, the actual venue of preclinical (not clinical) research;

58) "the researched material" - biologically active agent, medicine and products equated to them which are exposed to preclinical (not clinical) research;

59) "research on safety the" of medicine allowed for medical application - pharmakoepidemiologichesky or clinical research which is conducted for the purpose of assessment of safety of the registered medicine;

60) "basic data" - the information containing in primary documentation, describing results of observations and other activities, allowing to recreate picture of preclinical (not clinical) and clinical trial and to estimate it;

61) "initial raw materials" - any substance of certain quality used in case of medicine production, except for packaging materials;

62) "quarantine" - the status of initial raw materials, the packaging materials, intermediate, bulk or finished goods isolated physically or other effective methods before decision making about their realization, rejection or conversion;

63) "calibration" - number of the operations performed under certain conditions by means of which establish ratio between instrument readings or systems of measurement, registration and control or the values received in case of physical measurement and the corresponding known sizes of standards; limits of errors of measuring instruments shall be set;

64) "quality of medicine" - set of the properties giving to medicine capability to satisfy consumers according to the appointment and to meet the requirements established by the regulating document;

65) "clinical trial" - any research with the assistance of the person as researched intended for identification or confirmation of clinical, pharmacological and/or other phracodynamic of effects of one or several researched medicines and/or identification of collateral reactions to one or several researched medicines, and/or for studying of absorption, distribution, metabolism and removal of one or several medicines for the purpose of confirmation of its safety and/or efficiency;

66) "clinical base" - the place of direct carrying out clinical testing;

"Cohort research" - type of pharmakoepidemiologichesky research when which carrying out during the certain period of time it is observed two picked-up big groups of patients, one of whom receives the researched medicine, and another - it does not receive 67), for the purpose of identification of collateral reactions;

68) "the examinee's code" - the unique identifier appropriated by the researcher to each examinee for ensuring its anonymity and used instead of surname of the examinee in reports on clinical trial;

69) "coordinating committee" - the body formed at the initiative of the organization developer for the purpose of coordination of performing multicenter clinical trial;

70) "contamination of medicines in distributor practice" - mixing of several types, different series / batches of medicines or substitution of one type of products by others in case of storage, transportation;

71) "contamination" - hit in the medicine of any impurity (radioactive or toxic material, other type or strain of microorganisms) leading to change of properties of medicines;

72) "control in production process (production supervision)" - the checks performed during engineering procedure for the purpose of control and, if necessary, process regulation to provide products compliance to regulating documents (to pharmacopoeian Articles, specifications, etc. ;); control of the environment or the equipment can be also considered as part of control in production process;

73) "confidential registration information" - the scientific and technical information containing in the statement on the state registration / re-registration of medicine and the statement for modification of the registration file throughout action of the registration certificate (except for information which is public, in particular, about trade name of medicine, composition of active ingredients, action force which are brought on packaging, in information on the applicant and/or producer of medicine, the instruction on medical application or leaf insert, in information on dangerous properties of medicine which can do harm to the patient during application);

74) "medicinal vegetable raw materials" - the fresh or dried-up whole herbs or their parts used for production of medicinal substances, production and production of medicines and also for wholesale and retail sale;

75) "leaf insert" - officially the approved instruction enclosed in medicine packing unit intended for the patient and containing information necessary for the correct independent use of medicine;

76) "international non-proprietary name" - the shortened scientific name of medicine on the basis of its active ingredient;

77) "the medical representative" - person representing the pharmaceutical company whose task is: inform doctors and druggists of the most complete information on the offered products, to provide availability of wide range of medicines of the company in drugstores and in regional warehouse of distributor firm, to initiate the considerable sales volume of medicines;

78) "monitor" - the legal entity or physical person designated by the sponsor, controlling performing preclinical and clinical trial according to the protocol;

79) "multicenter clinical trial" - the clinical trial conducted under the single protocol more than in one research center;

80) "meta-analysis" - method of receipt of information on collateral reactions of medicines in case of which statistic analysis for integration of these several independent researches for the purpose of monitoring of medicines and collateral reactions, in particular those which arise through long period of time is used;

81) "the international birth date of medicine" - date of issue to the applicant of the first license for sale of medicine in any country of the world;

82) "monitoring of recipes" - the method of receipt of information on collateral reactions of medicines based on accounting of purposes of medicine when for the established period of time the number of the registered collateral reactions and the number of the patients applying medicine which allows to reveal interrelation between collateral reaction and use of medicine by means of accounting of the written-out recipes is determined;

83) "monitoring of hospital(s)" - method of receipt of information on collateral reactions of medicines which allows to determine the frequency of collateral reactions and to reveal features of interaction of medicines at sick one or several hospitals when during the certain period of time under control there are all patients of hospital(s), all medicines which are appointed, and all suspected collateral reactions which arise are considered;

84) "proper clinical practice (Good Clinical Practice, GCP)" - rules of planning, carrying out, monitoring, audit and documentary registration of clinical trials, and also processings and representations of their results;

85) "proper laboratory practice (Good Laboratory Practice, GLP)" - rules of the organization of process and conditions under which preclinical researches are planned, carried out, controlled are registered, remain and their data are documentary drawn up;

86) "proper practice of wholesale trade (Good Distribution Practice, GDP)" - rules of ensuring safety of medicines in the field of wholesale trade;

87) "proper production practice (Good Manufacturing Practice, GMP)" - rules of production organization and quality control of medicines on industrial enterprise;

88) "proper practice of storage (Good Storage Practice, GSP)" - rules of stores organization of medicines;

89) "proper pharmaceutical (pharmaceutical) practice (Good Pharmaceutical Practice, GPP)" - rules of the organization of pharmaceutical activities for the purpose of ensuring proper quality of the pharmaceutical services rendered by pharmaceutical workers to the population of the Kyrgyz Republic;

90) "proper assessment of potential risks" - systematic process of identification, assessment and control of the possible risks connected with quality of development of medicine, probabilities of emergence of damage and degree of its weight for life and health of the person and/or animal when performing preclinical and clinical trials and directed to their decrease;

91) "substandard medicines" - the medicines not suitable for application owing to discrepancy to the requirements established by the regulating document;

92) "the undesirable phenomena" - any claims or symptoms of disease (including pathological changes of laboratory indicators) revealed at the patient or the examinee who are connected on time with use of the researched medicine, irrespective of availability of causal relationship with its application;

93) "not intervention research" - research in which medicines are appointed regular method in accordance with the terms, specified in the registration file. Involvement of the patient with certain method of treatment in the protocol of research is not provided in group in advance, and prescription of medicine is dictated by modern practice and does not depend on the decision to include the patient in testing. Do not apply supplementary diagnostic or monitoring procedures in relation to patients, and for the analysis of collected data use epidemiological methods;

94) "unexpected collateral reaction" - collateral reaction, nature or weight of which is not approved with the available information on medicine (for example, with the brochure of the researcher for the unregistered medicine or with the leaf insert/instruction for medical application for the registered medicine);

95) "new medicine - medicine which for the first time is registered in the Kyrgyz Republic and is created with use of new substance or is new combination of the known substances;

96) "number of series" - characteristic combination of figures and/or letters by means of which it is possible to identify series on labels, in protocols of series, quality certificates etc.;

97) "regulating document" - the document establishing regulations, characteristics, control methods to medicines;

98) "the responsible person for quality" - person responsible for quality assurance in case of organization activity implementation;

99) "lack of efficiency of medicine" - lack of favorable medical effect of medicine on the current and duration of disease;

100) "the organization of wholesale" - the legal entity performing import, wholesale and storage of medicines;

101) "drug circulation" - the generalized concept of activities including development, preclinical and clinical researches, production, production, storage, packaging, import to the territory of the Kyrgyz Republic, export from the territory of the Kyrgyz Republic, transportation, state registration, standardization and quality control, sale, marking, advertizing, use of medicines, destruction of the medicines which became useless or medicines expired and other actions in the field of drug circulation;

102) "quality assurance of medicines" - set of all organizational actions undertaken for the purpose of satisfaction to quality requirements of medicines according to their appointment;

103) "ensuring compliance of clinical trial" - set of systematically carried out procedures providing performing clinical trials, registration and generalization of the obtained data according to Rules of proper clinical practice and the legislation of the Kyrgyz Republic;

104) "certain collateral reaction" - the adverse clinical manifestation including also changes of laboratory indicators which arises during use of medicine, but cannot be explained with availability of the existing diseases and influence of other factors and chemicals. Manifestation regresses after cancellation of medicine and arises in case of its repeated appointment (if repeated prescription of medicine is possible);

105) "response" - the action directed to withdrawal of medicines of inadequate quality from the organizations to which they were realized;

106) "the report on preclinical (not clinical) research" - the document containing results of preclinical (not clinical) research and their analysis according to requirements of these Regulations;

107) "the report on clinical trial" - the results of clinical trial of medicine submitted in writing including the description of clinical, statistical techniques, and also the analysis of the obtained data in evident type;

108) "the report on cases of collateral reactions in case of medical application of medicines in the medical organizations" - the annual report on all cases of collateral reactions of medicines which is constituted and is given by all treatment-and-prophylactic organizations of health care, irrespective of pattern of ownership;

109) "the report on research of safety of the medicine allowed for medical application" - the results of research of safety of the medicine allowed for medical application reported in writing and their analysis;

110) "periodically updated report on safety (PSUR)" - the written report which contains regularly updated information on safety of the medicine allowed for medical application which is constituted with certain frequency according to the procedure, established by the legislation of the Kyrgyz Republic;

111) "source documents" - outgoing documents, data and records (for example, clinical records, out-patient maps, laboratory records, service records, the diaries researched or questionnaires, magazines of issue of medicines, the printouts of devices verified and the verified copies or disaggregations of soundtracks, photographic negatives, microfilms or magnetic carriers, x-ray pictures, administrative documents, records which are stored in drugstore, laboratory and in department of tool diagnostics of the treatment-and-prophylactic organizations which participate in research);

112) "periodically updated report on safety of the medicine allowed for medical application" - the written report which contains regularly updated information on safety of medicine;

113) "the suspected medicine" - medicine in case of which purpose there is cause and effect relationship between clinical manifestations of any collateral reaction and its medical application;

114) "contract research laboratory" - the legal entity who is carrying out one or several functions connected with carrying out preclinical (not clinical) research within the contract with the sponsor;

115) "advantage" - set of extents of positive influence of medicine on reduction of weight of current or decrease in expressiveness of symptoms of disease and intensity of positive pharmacological reaction to introduction of medicine and its duration;

116) "the amendment to the protocol" - the written modification or formal explanation of the text of the protocol of preclinical (not clinical) research signed by the sponsor and the researcher and approved by the head of research;

117) "checking of measuring instrument" - set of the transactions which are carried out by the public metrological service or other accredited legal entities for the purpose of determination and confirmation of conformity of measuring instrument to the established technical and metrological requirements;

118) "side effects of medicine" - negative reactions, including unexpected, connected with introduction of any dose of the unregistered medicine or the regular doses used for the purpose of prevention, diagnostics or treatment, the registered medicine;

119) "collateral reaction" - any undesirable negative reaction which arises in case of use of medicines in the regular doses recommended for prevention, diagnostics and treatment of diseases or for the purpose of modification of physiological functions of organism;

120) "collateral reaction which is not subject to classification" - the message on collateral reaction cannot be estimated because of insufficient information about collateral reaction or it is contradictory;

121) "hypersensibility" - allergic or other undesirable immunological reaction to introduction of medicine or chemical;

122) "foreseen collateral reaction" - collateral reaction, nature or weight of which is approved with the available information on medicine (for example, with the brochure of the researcher for the unregistered medicine or with the leaf insert/instruction for application for the registered medicine);

123) "comparison medicine" - the researched or commercial medicine (positive control) or placebo used for comparison in clinical trial;

124) "cause and effect relationship between clinical manifestations of any collateral reaction and medical application of medicine" - degree which is determined by certain criteria and specifies coherence of reaction which is observed, using medicine;

125) "production" - serial production (obtaining) of medicines according to rules of production organization, quality control and storage for the purpose of the subsequent realization of medicines by the manufacturing company;

126) "protocol" - the document containing the main objectives, methodology, procedures, statistical aspects, the organization and resource planning of preclinical (not clinical) and clinical trial and also earlier obtained data concerning medicine;

127) "the protocol of research of safety of the medicine allowed for medical application" - the document which describes tasks, methodology, procedures, statistical aspects and the organization of research of safety of the medicine allowed for medical application, and also data on the researched medicine and reasons for research which, as a rule, are earlier obtained;

128) "direct access" - permission to studying, the analysis, check and copying of any documentation and reports of clinical trial;

129) "producer of medicine" - the legal entity who performs at least one of medicine production phases, including packaging;

130) "production compounding" - the document or number of documents in which all types of initial raw materials with indication of their quantity and packaging materials together with the description of techniques and required precautionary measures for production of certain quantity of finished goods, and also technological instructions, including control in production process are established;

131) "promotion of medicines on the market" - complex of the actions of promotional and informational and motivational nature performed by the pharmaceutical companies for the purpose of stimulation of prescription of medicines, their offer, sale and/or use;

132) "intermediate products" - partially processed products which shall pass the subsequent stages of engineering procedure before it becomes finished goods;

133) "protocols of series" - the documents connected with production of series of bulk or finished goods, containing the history of each product series and all circumstances concerning quality of finished goods;

134) "working bank of cages" - the cellular culture received from the main bank of cages and used for preparation of production cellular cultures;

135) "working bank of sowing cultures" - the culture of microorganisms received from the main bank of sowing cultures and corresponding to the appointment in production;

136) "development of new medicines" - scientific search of active agents new pharmacological, with the subsequent studying of pharmacological properties of perspective substances, ready dosage forms regarding their efficiency and safety;

137) "randomization" - process of accidental distribution of examinees on experienced and control groups at clinical trials and the selection process of test systems by method of random check in case of preclinical researches allowing to minimize systematic mistake and bias;

138) "rational use of medicines" - use of medicines according to clinical need for the doses answering to specific features during the adequate period of time, and on bottom price for the patient and society;

139) "the registration certificate (the certificate on state registration)" - the document of the established sample which is permission for medical application of medicine in the Kyrgyz Republic and is issued to the applicant;

140) "registration materials (the registration file)" - set of the documents submitted by the applicant, the containing full range of data on medicine which examination gives the chance to draw conclusions on efficiency, safety and quality of medicine for the purpose of its recommendation to the state registration / re-registration;

141) "registration number" - the specification symbol which is appropriated to medicine in case of state registration under which it is entered in the State register of medicines and remains behind medicine steadily during the entire period of stay of medicine in the pharmaceutical market of the Kyrgyz Republic;

142) "claim" - the claim, the claim of the consumer to the supplier concerning inadequate quality of medicines and/or default on obligations requiring compensation or acceptance of adequate measures;

143) "reproductive toxicity" - toxic effect of the researched material on bodies of reproduction;

144) "the curriculum vitae of the researcher" - the document confirming education, professional training and experience of the researcher;

145) "risk" - data set, confirmed with cause and effect relationship, concerning development of collateral reaction of medicine owing to manifestation of dangerous properties of medicine and dangerous factors in cohort research which applied medicine;

146) "self-inspection" - process of assessment by the competent person (several persons) of the organization on compliance of fulfillment of requirements to the performed activities, the established legislation of the Kyrgyz Republic;

147) "collection" - mix of several types of cut or krupnoizmelchenny vegetable raw materials (except strong plants), sometimes with addition of salts and essential oils;

148) "series" - the certain amount of ready medicine received in one engineering procedure or in a number of consecutive engineering procedures in case of the processing of certain amount of initial raw materials, packaging materials or semi-means having identical indicators of quality in state standard of quality. In case of continued production series shall correspond to certain part of products which is characterized by expected uniformity;

149) "serious collateral reaction" - any adverse clinical manifestation in case of use of medicine (irrespective of dosing) which leads to death, poses threat of life, requires hospitalization or increase in term of hospitalization, results in long or considerable disability or disability, or is congenital anomaly, or lack of development;

150) "system of banks of cages" - system in case of which consecutive product series are made from the cellular cultures belonging to one main bank of cages (which is completely characterized by identity and lack of pollution);

151) "system of banks of sowing cultures" - system according to which suitable series of means are made from one main bank of sowing cultures in case of certain number of resowings (passages);

152) "the quality system in distributor practice" - the complex of actions directed to maintenance of quality of medicines at stage of their realization, including special requirements to transportation, personnel, documentation, rooms, storage conditions, the equipment and supply activity;

153) "warehouse of temporary storage of medicines" - the rooms which are specially allocated and equipped for these purposes adapted for temporary storage of medicines for the period of customs control with obligatory observance of all conditions on their storage;

154) ""blind" method of research" - method of performing clinical trial in case of which one or the parties which were more participating in research do not know what of the researched medicines is appointed to the examinee;

155) "doubtful collateral reaction" - the adverse clinical manifestation including also change of laboratory indicators which arises in the absence of accurate communication on time using medicine. There are other factors (medicines, diseases, chemicals) which can also be origin of collateral reaction;

156) "the message on collateral reaction or lack of efficiency of medicine in case of medical application" - form in which the producer/applicant reports about any serious collateral reactions or lack of efficiency in case of medical application of medicine of its production;

157) "ratio "risk/advantage"" - ratio of quantitative and quality standard of the revealed factors of positive influence of medicine on gravity and weight of course of disease at patients and manifestations of the known dangerous properties of medicine in case of its medical application which worsen the course of disease or are the reason of development of new adverse effects of medicine on organism and quality of life of the patient;

158) "specification" - the regulating document which is in detail describing requirements to which there shall correspond the products or raw materials and materials used or received in production process;

159) "the specification on the researched material" - the document establishing requirements to the researched material;

160) "the specification on test systems" - the document establishing requirements to test systems;

161) "sponsor" - physical person or legal entity, responsibility for its financing being the initiator of preclinical (not clinical) and/or clinical trial of medicine, bearing;

162) "the urgent message" is message on case serious (foreseen or unexpected) collateral reaction of medicine which happened in the territory of the Kyrgyz Republic which consequence the death of the patient was;

163) "standard working technique" - the approved written technique stating instructions for implementation of works, not necessarily specific to this medicine or substance, and having general nature (for example, operation, maintenance and cleaning of the equipment, validation, cleaning of rooms, control of the environment, sampling and inspection).

164) "standard operational procedures (SOP)" - the detailed written instructions providing uniformity of certain functions;

165) "technical documentation on the equipment" - the document establishing requirements to the equipment;

166) "teratogenecity" - capability of the researched material to cause malformations and aberrations in fruit;

167) "test systems" - animals, plants, bodies, cages, substances or the operating analytical equipment used for carrying out preclinical researches;

168) "goods of pharmaceutical assortment" - the products of industrial production intended for the medical, treatment-and-prophylactic, medical and diagnostic and improving purposes, distributed mainly by pharmaceutical institutions;

169) "The commodity nomenclature of foreign economic activity of the Eurasian Economic Union" (further the CN FEA EEU)" - the goods classification system using system of coding for designation of goods and groups of homogeneous goods;

170) "toxicity" - measure of harmful effects of the researched material on organism in the conditions of single or repeated introduction;

171) "toxicity пери / post-natal" - measure of harmful effects on organism of fruit or the newborn in case of single or repeated introduction of the researched material;

172) "subacute toxicity" - measure of harmful effects on organism of experimental animal in case of repeated (up to 6 months) introduction of the researched material in the therapeutic range of doses;

173) "chronic toxicity" - measure of harmful effects on organism of experimental animal in case of repeated (up to 12 months) introduction of the researched material in the therapeutic range of doses;

174) "toksikokinetika" - pharmacokinetic studying of processes of absorption, distribution, transformation, release of the researched material in toxic doses;

175) "conditional collateral reaction" - adverse clinical manifestation, and also changes of laboratory indicators which are difficult for estimating. It is necessary to obtain additional data for assessment or these obtained data are analyzed now;

176) "counterfeited medicine" - pharmaceutical product which purposely and is supplied fraudulent image with false marking concerning its authenticity and/or source of origin. Falsification can belong as to corporate (the trade name), and to generic medicines. Falsification can include product with proper ingredients or with the wrong ingredients, without active ingredients, with insufficient amount of active ingredient or with deceptive package;

177) "pharmacological supervision" - the state system of identification, collection, the analysis and scientific assessment of information on collateral reactions of the medicines registered in the Kyrgyz Republic in case of their medical application for the purpose of adoption of the relevant regulatory decisions concerning ratio of advantage and risk of their application;

178) "pharmakodinamika" - set of the effects caused by medicinal substance and also mechanisms of its action;

179) "pharmacokinetics" - ways of receipt, distribution and metabolism of medicinal substances in organism, and also their removal;

180) "pharmacopoeian Article" - the state regulating document containing list of indicators and methods of quality control of medicine;

181) "pharmacological activity" - capability of biologically active agent to change physiological parameters of organism of experimental animal in case of repeated or single introduction of the researched material;

182) "pharmaceutical service" - field of activity of pharmaceutical institution in which specific need of the patient or the medical organization is satisfied;

Note: Depending on content, pharmaceutical services are subdivided into the main: leave of controlled medicines, leave of medicines according to recipes and without recipe of doctors, according to requirements of the medical organizations, goods issue of pharmaceutical assortment, ex-temporal production of dosage forms, control of their quality, storage; additional: help, information, consulting servicing of the population and health workers, work on booking for goods of pharmaceutical assortment by phone, delivery of medicines and goods of pharmaceutical assortment to the house, hire of objects of patient care, service of the phytobar, self-service.

183) "pharmakoepidemiologichesky research" - the research of efficiency and/or safety of medical application of medicine directed to identification or confirmation its clinical, toxicological, phracodynamic and/or pharmacokinetic properties, collateral reactions inherent in it and interaction with other medicines which can be carried out as not intervention research;

184) "the pharmaceutical file" - the confidential document processed from written consent of the patient in which the complete information about the patient is reflected: the state of health, the revealed side effects, consultations, appointments and recommendations of doctors and druggists about pharmacotherapy, carrying out pharmacotherapy and its results;

185) "fetotoksichnost" - the damaging effect of the researched material on fruit during formation and development of functions which cause adaptation of organism to environmental conditions in late terms of pregnancy;

186) "phototoxicity" - the damaging effect of the researched material on integuments;

187) "the frequency of cases of collateral reaction of medicine" - ratio of number of patients who in certain time had collateral reaction in case of use of medicine to the number of patients who in certain time applied this medicine expressed as a percentage;

188) "net zone" - zone in which the environment on contamination by particles and microorganisms built and operated so that to prevent or reduce penetration, education and preserving contaminants in zone is controlled;

189) "examination of changes" is examination of materials on medicine of which the decision on modification or amendments in registration documents on medicine or about its new registration in accordance with the established procedure is result;

190) "examination of the registration file on medicine" is check, the analysis and specialized assessment of materials on medicine for the purpose of preparation of motivated conclusions for decision making about its state registration / re-registration or about refusal in the state registration / re-registration of medicine;

191) "embriotoxity" - capability of the researched material to cause death of fruit;

192) "ethics" - the correct behavior in the moral relation, including truthfulness and honesty;

193) "ethical criteria" - the universal principles and standards of behavior which can be adapted for national situation, i.e. provision in economy, culture, to social life, education, the local laws, nature of incidence, traditions in medicine and to the level of development of health care system;

194) "ethical council" - the council functioning under authorized state body of the Kyrgyz Republic in the field of health care in the field of drug circulation and healthcare institutions for protection of the rights, advantage, health and security guarantee of patients when carrying out biomedical researches;

195) "efficiency of medicines" - the characteristic of extent of positive influence of medicines on course of disease.

Chapter 2. Scope of the Technical regulation in the field of drug circulation

4. Subjects to regulation of these Regulations are:

1) the medicines released in the territory of the Kyrgyz Republic;

2) processes of development and research, production, production, storage, transportation, realization and utilization of medicines.

5. Requirements and provisions of these Regulations do not extend on:

- the medicines used in veterinary science;

- radionuclides in the form of the isolated sources;

- whole blood, plasma or blood cells of human origin;

- genetically modified medicines;

- means of ensuring of industrial safety, fire safety, explosion safety, chemical safety and safety of other types in case of production of medicines, requirements to which are provided in the legislation of the Kyrgyz Republic.

6. Products types falling under action of these Regulations and their codes on the qualifier of the CN FEA EEU are specified in appendix 1 to these Regulations.

7. These Regulations establish:

1) requirements to safety of medicines in case of development, preclinical and clinical trials, in production process, production, storage, transportation, retail and wholesale and utilization;

2) rules of identification of medicines for the purposes of application of these Regulations;

3) forms of assessment of conformity of medicines to requirements of these Regulations and their deadlines.

8. Features of drug circulation, containing the drugs, psychotropic substances and precursors which are subject to control in the territory of the Kyrgyz Republic are regulated by the legislation of the Kyrgyz Republic in the field of the address of drugs, psychotropic substances and precursors.

9. These Regulations do not pursue the aims on ensuring economic interests of the Kyrgyz Republic or certain subjects (groups of subjects) of the sphere of drug circulation, with ensuring availability of medicines and with the organization of providing the population with medicines.

10. The provisions of other regulatory legal acts of the Kyrgyz Republic concerning scope of these Regulations are applied in the part which is not contradicting these Regulations. Establishment of other requirements for subject of regulation of these Regulations is possible only by modification and amendments of these Regulations.

11. If the international treaty which came in the procedure established by the law into force which participant is the Kyrgyz Republic establishes other rules, than those which are provided by these Regulations are applied rules of the international treaty.

12. Safety of medicines at all stages of lifecycle proves to be true:

- identification of medicines;

- identification of danger of medicines.

13. Identification of medicines is made by establishment:

- identity of the name of medicine;

- lot size;

- these certified testing;

- identity of properties (physical, chemical, biological and others) and methods of their measurement;

- identity of information on medicine presented in the marking form on consumer packaging, the instruction for application, the certificate of conformity;

- codes of the CN FEA EEU according to appendix 1 to these Regulations.

14. Identification of danger of medicines is based on the analysis and risks assessment (types, indicators and criteria of danger) in the way:

1) detection of characteristics of medicines which can cause harmful effects on human body;

2) the analysis of impact of each of the revealed potential dangers on human body and their effects;

3) determinations of measures of restriction of the revealed risks.

15. In the analysis and risk assessment the possibility of harmful effects on life and health of the person is identified. If the available scientific research is insufficient for determination of its degree, the authorized state body of the Kyrgyz Republic in the field of health care in the field of drug circulation has the right to take temporary measures for risk management. Temporary measures for risk management are reviewed during the minimum period of time required for receipt of the scientific data which are clearing up risk degree.

16. Identification of danger of medicines is performed at all development stages of new medicines, including: the production technology (production), determination of storage conditions, the list of indications, contraindications, method of application and mode of dosing of dosage form, identification of all undesirable reactions to human body, and so forth for each stage of lifecycle of medicine. All possible risks shall be identified.

17. Ensuring pharmaceutical safety of medicines by the principles of risk management includes identification, identification and risk management, the caused pharmaceutical factors for all lifecycle of ready medicine.

18. The risk degree of damnification is established on complex risks assessment for all identified dangers in the settlement, experimental and (or) expert way with possibility of its check.

19. The medicines used for medical application and also the raw materials used in production process (production) and the address have risks of damnification to health and human life which include:

- the risks caused by pharmaceutical factors;

- the risks connected with imperfection of development;

- the risks connected with imperfection of engineering procedure of production, control systems of the indicators of quality ensuring safety of medicines;

- the risks connected with contamination of products foreign impurity on production stage and production;

- the risks connected with environmental pollution by emissions of production waste in case of production and in the course of utilization and utilization of medicines;

- risk of use of the medicines provided without recipe of the doctor and/or not to destination;

- risk of use of medicines without proper information support;

- risk of use of medicines with the changed properties in the course of storage, realization, transportation (non-compliance with storage conditions, impact of physical, chemical factors);

- risk in case of use of the medicines falsified and not corresponding to quality.

20. The risks influencing pharmaceutical safety depend from:

- use of initial substances and materials;

- applications of finished pharmaceutical products;

- applications of methods of quality control of initial, intermediate and finished goods;

- applications of the production technology (production).

21. The risks depending on use of initial substances and materials are determined:

- quality of pharmaceutical substance;

- quality of excipients (dyes, preservatives, adjuvants, stabilizers, thinners, baking powder, emulsifiers, korrigenta of taste and smell and others);

- quality of primary package (materials, means of packing, hermeticity of corking system and others).

22. The risks depending on application of finished pharmaceutical products are determined:

- rationality of structure and compatibility of components of medicine;

- optimality of dosage form;

- stability (storage) of ready medicine;

- feasibility of the choice of materials of taroukuporochny system.

23. The risks depending on application of methods of quality control of initial, intermediate and finished goods are determined:

- qualification of the measuring equipment (including accuracy of measurements);

- validirovannost of techniques of testing (pharmacopoeian techniques do not require validation);

- qualification of the personnel which are carrying out testing;

- conditions of carrying out test methods.

24. The risks depending on application of the production technology (production) are determined:

- mechanism of reactions of synthesis of active agents;

- features of engineering procedure of production of medicine;

- changes in engineering procedure of production of medicine;

- control availability in production process;

- qualification of production equipment;

- validirovannost of production processes;

- qualification of the personnel performing production process.

25. Risk management shall be based on the received results of risks assessment, the prevention of possible harmful effects on life and health of the person.

26. Risk management is based on development of complex of the requirements directed to elimination, decrease to admissible (acceptable) level or the prevention of the risks caused by pharmaceutical factors, and shown at all stages of lifecycle of medicine:

1) at stage of development of medicine by observance of rules of proper laboratory practice and rules of proper clinical practice;

2) on medicine production stage by observance of rules of proper production practice;

3) on implementation phase of medicinal products by observance of rules of proper distributor practice and rules of proper pharmaceutical practice, the regulated storage conditions and transportation;

4) observance of rules of leave, application and use of medicines;

5) provision of complete and reliable information about medicine, including in the instruction for application, during the advertizing and promotion of medicines, ensuring necessary marking;

6) at stage of application of finished pharmaceutical products by observance of the regulated preparation method just before introduction (if necessary), conditions and storage duration, period of use of medicine;

7) observance of requirements for use of medicines, taking into account possible factors (side effects) influencing human body;

8) timely detection and non-admission to realization of the counterfeited, expired and not corresponding to quality medicines.

27. The complex of requirements for elimination, decrease or the prevention of the risks proceeding from medicinal substances provides the following:

- medicinal substances shall conform on quality to requirements of the pharmacopeias recognized acting in the Kyrgyz Republic;

- the pharmaceutical substances which are not described in pharmacopeias shall conform on quality to requirements of the standard of the organization (the temporary analytical regulating document, the analytical regulating document);

- quality control of medicinal substances shall be carried out by pharmacopoeian techniques or other validirovanny techniques of testing with use pharmacopoeian standard (chemical and biological) is model;

- the structure of new active agents and their major characteristics shall be confirmed with modern methods of research (physical, physical and chemical, chemical);

- determination of profile of impurity, including connections with genotoksichesky potential, shall be based on deep scientific assessment of the chemical reactions constituting the scheme of synthesis, and also contribution of the impurity brought from raw materials and possible means of decomposition;

- regulation of related impurity shall be carried out not only on content of the identified impurity, content of not identified impurity, but also the amount of impurity;

- regulation of residual solvents shall be carried out according to requirements of pharmacopeia in all cases of use of organic solvents in the course of receipt of medicinal substance;

- stability of medicinal substance shall be confirmed with the researches conducted according to the established requirements;

- medicinal vegetable raw materials shall maintain requirements of radiation control, and also the requirement to content of heavy metals and residual amount of pesticides (for the cultivated plants);

- medicinal vegetable raw materials shall not be infected by granary wreckers and mold;

- in initial substances and materials of animal and human origin (sowing materials, banks of cages, pools of plasma and others) there shall be no pathogenic agents;

- in case of storage of medicinal substances special precautionary measures shall be observed, if necessary.

28. The complex of requirements for liquidation, decrease or the prevention of the risks proceeding from excipients provides the following:

- excipients (dyes, preservatives, stabilizers and others) shall be resolved for use in production of finished pharmaceutical products;

- excipients shall conform on quality to requirements of the pharmacopeias recognized acting in the Kyrgyz Republic, or the regulating documents regulating their application for production of finished pharmaceutical products;

- in excipients of animal and human origin there shall be no pathogenic agents.

29. The complex of requirements for liquidation, decrease or the prevention of the risks proceeding from ready medicine provides the following:

- the dosage form shall be optimum for exception of undesirable collateral impact on organism;

- components as a part of ready medicine shall be compatible;

- finished pharmaceutical products shall conform on quality to requirements of the pharmacopeias recognized acting in the Kyrgyz Republic, or standards of the organization;

- quality control of the biological medicines which are not given in pharmacopeias, acknowledged acting in the Kyrgyz Republic, shall be carried out by techniques and regulations according to WHO recommendations of "The requirement to biological substances";

- specifications of quality shall include testing for safety of finished pharmaceutical products (determination of sterility, pyrogenicity, bacterial endotoxins, microbiological purity, toxicity, foreign impurity, local portability on animals, content of substances of histamine-like action);

- regulation of related impurity shall be carried out not only on content of the identified impurity, content of not identified impurity, but also the amount of impurity;

- regulation of residual solvents shall be carried out according to requirements of pharmacopeia in case of use of organic solvents on the last production stage of medicine;

- specifications of quality shall include identification and quantitative determination of preservatives for establishment of compliance of their content to maximum permissible regulations; for other excipients capable it is negative to influence physiological functions, determination of upper limits of concentration shall be carried out;

- stability of ready medicine shall be confirmed with the researches conducted according to the established requirements and to include the quality indicators influencing safety (the description, related impurity or products of decomposition, microbiological purity, sterility, chromaticity and transparency of solution, toxicity and others);

- the taroukuporochny system (inertness of materials, hermeticity and functionality) shall provide stability of ready medicine during fixed term of storage under the regulated conditions;

- marking of medicine shall conform to requirements of these Regulations;

- the instruction for use of medicine shall conform to requirements of these Regulations.

30. The finished pharmaceutical products released on the territory of the Kyrgyz Republic on indicators of quality shall conform to requirements of the following regulating documents:

- general pharmacopoeian clause;

- pharmacopoeian Article;

- specifications;

- standard of the organization;

- the specification for foreign producer organizations.

31. Regulating documents of medicines are integral part of the registration file and are approved with authorized state body of the Kyrgyz Republic in the field of health care in the field of drug circulation.

32. Regulating documents of medicines shall be reviewed timely taking into account new achievements medical, pharmaceutical and other sciences, and also provisions of pharmacopeias, acknowledged acting in the Kyrgyz Republic, recommendations of the international organizations in the field of pharmaceutical science.

33. In case of development of new medicine, in case of lack of regulating documents on the pharmaceutical substance used for production of the specified medicine along with development of the standard of the organization on medicine the standard of the organization on the pharmaceutical substance used for its production is developed.

34. The quality indicators included in regulating documents of medicines depending on dosage form are given in appendix 19 to these Regulations.

Chapter 3.

Voided according to the Order of the Government of the Kyrgyz Republic of 28.08.2018 No. 405.

Chapter 4.

Voided according to the Order of the Government of the Kyrgyz Republic of 28.08.2018 No. 405.

Chapter 5. Safety requirements in case of production of medicines

79. As guarantee of compliance of the made medicines to the purpose and requirements imposed to them, and also additional guarantee of non-admission of risk for consumers because of violations of conditions of production of medicines serves observance of national and international standards on proper production practice (GMP).

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