CONTROL OF PHARMACEUTICALS — the state control system of pharmaceuticals aimed at providing efficiency of their action, safety of use and appropriate quality.
The term «control of pharmaceuticals» to 30 — the 40th 20 century was used only in relation to the measures aimed at providing control of quality of medicines. Afterwards in connection with the intensive growth of number of pharmaceuticals, increase in their activity and efficiency, and also in connection with increase of danger of their adverse action this term began to be used concerning the measures aimed at providing not only qualities but also efficiency of action and safety of use of pharmaceuticals (see).
In the USSR state To. by hp it is assigned to M3 of the USSR.
Bases of the state system K. hp in the USSR were put by the decree of Council of People's Commissars about the organization of the National commissariat of health care of RSFSR (1918) on which along with other tasks of health protection control of providing the population with the medicinal help on the basis of achievements of science was also imposed.
For the first time some organizational principles K. hp in the USSR were established «By the provision on the nationalized drugstores, the pharmaceutical enterprises, on the organization of management of them and bodies, supplying», the published National commissariat of health care of RSFSR on December 30, 1918 them.
Importance for development of the organizational principles K. had hp in the USSR accepted in 1937. Council of People's Commissars of the USSR the resolution «About Production and Production of New Pharmaceuticals», the Crimea was established that only the state and cooperative enterprises with the permission of the National commissariat of health care of the USSR can produce and sell new medicines. The same resolution provided obligatory representation in the National commissariat of health care by all state and cooperative organizations offering to release new drugs, documents with the indication of the name of drugs, their structure, a way of production, appointment, methods of their testing, protocols of the chemical analysis, these pilot studies and a wedge, observations and also samples of drugs, prospectuses and projects of packagings and labels. Besides, it was specified in the resolution that new pharmaceuticals are entered in the special register allowed for production and release in the USSR of drugs (see the Register state).
The state system K accepted in the USSR. hp represents a complex of the scientific, methodical and organizational actions covering all parties of medical use of pharmaceuticals including control for doklin. and wedge, studying, side effect, nomenclature and quality of pharmaceuticals.
Control of preclinical (experimental) studying of pharmaceuticals is exercised concerning all pharmakol, the substances offered as new drugs, and all of them dosage forms and also concerning those medicinal substances and forms which manufacturing techniques for any reasons change.
The purpose of this type of control is ensuring sufficient efficiency and lack of the expressed toxicity at the drugs offered for a wedge, studying. Control for doklin. by studying it is carried out according to the provisions drafted by Pharmacological committee (see) and approved by M3 of the USSR.
The guideline determining volume doklin. researches of new substances, are «Requirements to documentation provided for obtaining permission to carrying out clinical studying of new pharmaceuticals», the approved M3 of the USSR in 1967 and added with the order M3 USSR No. 1186 of December 16, 1976. «About measures for further improvement of an order of registration of permission to a medical use and transfers for industrial production of new pharmaceuticals». In process doklin. studying are investigated the general pharmakol, properties, specific action, acute and hron, toxicity pharmakol. substances, including specific types of toxicity (embriotoxity, mutagenicity, influence on reproductive functions, teratogenecity, allergenic action). Doklin. studying of new substances shall be carried out in comparison to the famous relatives on action by medicinal substances which by the time of tests can be accepted as standard.
Control of clinical studying of medicinal substances provides strict performance of the established M3 of the USSR of conditions of carrying out a wedge, tests among which the following is essentially important.
Wedge, studying of any medicinal substance is carried out only on permission of Pharmacological committee to a wedge, the bases appointed by it and not dependent on the organizations — producers of medicinal substances. The drugs directed to a wedge, tests are provided a wedge, to bases is free (payment of drugs is made by M3 of the USSR). Studying of drugs on a wedge, bases is carried out also free of charge.
Wedge, studying pharmakol, substances is carried out only on sick people first of all for the benefit of their treatment, and also for obtaining the scientific information allowing to estimate compliance a wedge, given to results doklin. studying, specifications of these results and preparation of recommendations of expediency of use of examinees of substances in medical practice as new pharmaceuticals.
Studying new pharmakol, substances on healthy people (volunteers), as a rule, is not allowed and it is possible only in special cases on special permission of M3 of the USSR.
Klien, studying new pharmakol, substances is led under control of Pharmacological committee, as a rule, to two stages. At the first stage the wedge, studying carry out usually on the groups of adult faces limited by quantity (excepting pregnant women). The purpose of control at this stage is not only assessment to lay down. properties of the studied substance, but also perhaps earlier obtaining information on risk of emergence of side effect. Besides, dosages and schemes of treatment are specified, actions for elimination of the arising by-effects are outlined. The second stage a wedge, studying is carried out on permission of Pharmacological committee on big groups of patients on number.
The purpose of control at this stage is obtaining more complete information about a new pharmakol, substance (efficiency in comparison with drugs, similar on action, detailing of indications and contraindications to use, clarification of by-effects and measures for their elimination, accumulation of observations, further specification of dosages and schemes of use, clarification of an opportunity and need of a combination therapy).
For ensuring comparability of information obtained from various institutions, a wedge, testing are carried out on the basis of the approved M3 of the USSR of «Methodical instructions on clinical studying of new pharmaceuticals». Development of such methodical instructions is carried out by Pharmacological committee together with its specialized centers and other leaders research and a wedge, institutions. Besides, during the carrying out the wedge, tests is provided use of the unified cards of the accounting of a therapeutic effectiveness of new medicine, and also the unified methods of assessment of a condition of patients in dynamics.
By results a wedge, studying new pharmakol, substances the Pharmacological committee makes M3 of the USSR recommendations of permission of use of these substances in medical practice. Such recommendations are made only if in process a wedge, studying of substances along with efficiency and safety of use are established also advantages of these substances before the pharmaceuticals included in the State register.
Administration of new medicines in medical practice is carried out by orders of the Minister of Health of the USSR then Management on implementation of new pharmaceuticals and USSR M3 medical equipment assigns to each new medicine registration number and enters it in the State register of pharmaceuticals.
Control of side effect of pharmaceuticals is established concerning all pharmaceuticals, since the period their wedge, studying, and continues during the whole time of their use in medical practice. This type of control is carried out by the analysis of information on side effect of drugs, edges comes from doctors to the All-Union center for side effect of drugs. For collecting and execution of the specified information the special «Notices on side effect of medicine» approved by M3 of the USSR are used. The data obtained rather side effect of pharmaceuticals (see) are considered by drawing up recommendations of implementation of drugs in practice, and also during the development of instructions and methodical instructions for use of pharmaceuticals.
Control of the nomenclature of the pharmaceuticals which entered the State register is carried out by periodic review of its M3 of the USSR. At the same time the collected data are considered about to lay down. properties and side effect of pharmaceuticals, and also about inclusion in the State register of drugs, new, more effective, less toxic or more convenient for use. Outdated drugs according to the recommendation of Pharmacological committee are periodically excluded by orders of the Minister of Health of the USSR from the State register. So, e.g., orders of the Minister of Health of the USSR from January 1, 1974 till January 1, 1979 from the State register of pharmaceuticals excluded 164 drugs as outdated and ineffective, and also in connection with emergence of more effective substitutes (tab).
Except the pharmaceuticals listed in the table, the order of the Minister of Health of the USSR No. 682 of July 12, 1976 excluded from the State register 12 the containing narcotic substances of medicines which have rather active substitutes: opium in powder, laudanum simple, tincture the opium and benzoic, tablets of opium of 0,01 g, extract of opium dry, drops gastric, solution of Thecodinum of 1% for injections, a candle with extract of opium, the tablet «Bisal», tablet gastric with opium, cough pills for adults opium, the tablets «Pectolum».
For the purpose of reduction of the nomenclature of narcotic pharmaceuticals the order of the Minister of Health of the USSR No. 336 of April 15, 1977 excluded 14 narcotic pharmaceuticals: a hydrocodon phosphate, tablets of a hydrocodon of phosphate of 0,005 g, Demorphanum, lemoranum, solution of lemoranum of 0,2% in ampoules, tablets of lemoranum of 0,002 g, Escodolum solution for injections, Thecodinum, solution of Thecodinum of 2% for injections, tablets of Thecodinum of 0,005 g, tablets of structure: pyramidon of 0,25 g, caffeine-sodium benzoate of 0,1 g, codeine of 0,015 g; tablets of structure: pyramidon and streptocide on 0,3 g, caffeine-sodium benzoate of 0,05 g, codeine of 0,015 g; tablets of structure: pyramidon and analginum on 0,3 g, codeine of 0,015 g, phenobarbital of 0,01 g; Fenadonum. Their production is stopped since May 1, 1977
Due to the review of the nomenclature of the pharmaceuticals applied in kardiol, practice, the order of the Minister of Health of the USSR No. 979 of November 1, 1977 excluded from the nomenclature of pharmaceuticals as less effective, than others kardiol, drugs: anetin, tablets of an anetin of 0,1 g, coated, Diaethiphenum, tablets of Diaethiphenum of 0,025 g, solution of Diaethiphenum of 0,2% for injections, korelborin, tablets of a korelborin of 0,0002 g, solution of a korelborin of 0,025% for injections, korkhorozid, solution of a korkhorozid of 0,033% in ampoules, Coresidum, solution of Coresidum of 0,05% in ampoules, Neriolinum, tablets of Neriolinum of 0,0001 g, solution of Neriolinum of 0,022%, Nitranolum, tablets of Nitranolum of 0,002 g, tincture of a tsimitsifuga, Erysimosidum, tablets of Erysimosidum 0,001 2, solution of Erysimosidum of 0,2%.
Thus, during the period from January 1, 1974 to January 1, 1979 as control of the nomenclature of pharmaceuticals 211 drugs were excluded from the State register.
Control of quality of pharmaceuticals includes preliminary, subsequent, selective and arbitration types of the control exercised State research in-volume on standardization and control of M3 medicines of the USSR. All drugs for the first time produced in lots by each enterprise and also the drugs transferred to this type of control in connection with deterioration in their quality are subject to preliminary control. The subsequent random inspection, all produced drugs are subject to Krom, it is carried out according to the quarterly plans tasks approved by the State inspectorate for control of quality of pharmaceuticals and products of the medical USSR M3 equipment. Pharmaceuticals are exposed to arbitration control in case of disagreements about their quality between the organizations suppliers and consumers.
To. hp is carried out according to requirements of GF USSR and other specifications and technical documentation approved by M3 of the USSR.
System of the organization of control of pharmaceuticals. According to «Bases of the legislation of USSR and federal republics about health care» (1969) state To. hp is assigned to M3 of the USSR, in structure to-rogo for this purpose there are special bodies — Management on implementation of new pharmaceuticals and medical equipment and the State inspectorate for control of quality of pharmaceuticals and products of the medical equipment.
Questions of control for doklin. and a wedge, studying, behind side effect and the nomenclature of pharmaceuticals, and also setting standards of quantity of drugs are under authority of Management on implementation of new pharmaceuticals and the medical USSR M3 equipment. For these purposes at it there are scientific and advisory bodies — Pharmacological committee and Pharmacopoeian committee.
The pharmacological committee develops requirements to carrying out doklin. and the wedge, studying of new medicinal substances, analyzes the data on results of studying coming to it and makes M3 of the USSR recommendations of implementation of new pharmaceuticals in medical practice, and also carries out preparation of drafts of application instructions of pharmaceuticals.
Besides, the Pharmacological committee participates in control of the nomenclature of pharmaceuticals by preparation of recommendations for M3 of the USSR of entering into the State register of new pharmaceuticals or about an exception of it of outdated drugs. Scientific and methodical and organizational support of control of side effect of pharmaceuticals is carried out by Pharmacological committee jointly with the All-Union center for studying of side effect of pharmaceuticals which is under supervision of Management on implementation of new pharmaceuticals and medical equipment.
The pharmacopoeian committee drafts pharmacopoeian articles on medicinal substances and their dosage forms, makes the State pharmacopeia of the USSR.
Pharmacopoeian articles contain the information about chemical composition of drugs and their physical. - chemical properties, the description of methods of the analysis and other normative and technical data necessary for control of quality of drugs.
The state control of quality of all pharmaceuticals both domestic production, and imported from abroad is carried out by the State inspectorate for control of quality of pharmaceuticals and products of medical equipment, edge will organize and directs activity of all control and analytical service in the country, controls observance by the enterprises and organizations of all ministries and departments of the state and industry standards, pharmacopoeian articles, technical specifications and other specifications and technical documentation regulating quality of pharmaceuticals. The state inspection performs the functions assigned to it as directly, and through being under its authority State research in-t on standardization and control of M3 medicines of the USSR and some other research in-you, and also through control and analytical laboratories of system of the head pharmaceutical departments of mines - in health care of federal republics and inspection departments of the enterprises.
Control of quality of blood preparations and blood substitutes is carried out by interrepublican and interregional laboratories under handsovodstvo of the Central laboratory on studying and control of blood preparations and blood substitutes of the Central Order of Lenin in-that hematology and hemotransfusion.
The public institutions responsible for To. hp, exist in the majority of the countries in the form of the relevant managements of mines - in health care or other departments. In the organization state To. hp in the socialist countries is available much in common with system K. hp in the USSR. State To. hp in these countries is carried out min. - you health care through the relevant organizations. The systems K which developed in the socialist countries. hp provide monitoring procedure behind medicinal substances, as a rule, at all stages, beginning from development of drugs and before the termination of their use in medical practice. Control of quality of pharmaceuticals in the field of production and in pharmaceutical warehouses is provided with activity of special in-t of control and control and analytical laboratories of these countries. For acceleration of implementation in medical practice of the new pharmaceuticals developed by member countries of SEV in the socialist countries uniform methodical instructions for experimental and a wedge, studying of drugs are created. Coordination of this work within the countries of SEV is carried out with the assistance of the corresponding groups of specialists. The coordinated requirements to quality of pharmaceuticals join in periodically published collections «Compendium of the Physician Mentor Mind».
In the developed capitalist countries for providing To. hp are created special administrative bodies which regulate hl. obr. processes wedge, studying, medical use and control of side effect of new pharmaceuticals. In the USA, e.g., such body is Management on control of foodstuff and drugs, in England — Committee on assessment of safety of pharmaceuticals, in Canada — Department of health protection at Department of national health care and welfare.
Internationally problems K. hp is engaged in WHO.
One of the directions of this work of WHO is development of recommendations about unification experimental and a wedge, methods of a research of new pharmaceuticals. For this purpose since 1972. The European bureau WHO carries systematically out symposiums on a wedge. - pharmakol. to control of pharmaceuticals. Besides, science team of WHO developed «Recommendations about assessment of pharmaceuticals for their use for the person» (1975) and «The principles of assessment of the pharmaceuticals applied in medicine» (1977).
Other activity of WHO in the area K. hp is development of recommendations about control of quality of pharmaceuticals. The Department of preventive, diagnostic and therapeutic means of WHO which carries out this party of the activity through Committee of experts in specifications on pharm, drugs deals with these issues. With assistance of other organizations by this committee «Rules of production and quality control of pharmaceuticals» which were approved by the 28th session of the World assembly of health care (1975) are developed. Rules recommend carrying out To. hp at all stages of industrial production from the manufacturer, control of the enterprises and sampling inspection of samples of drugs from bodies of health care of the country. Implementation of these rules shall be guaranteed by the country during the export of pharmaceuticals. The committee of experts in specifications on pharm, drugs participates in preparation of the edition of the International pharmacopeia, edge has no legislative character, but serves as material during the development of national standards of quality of pharmaceuticals.
At evaluation test in the course of interchange pharmaceuticals between the countries of SEV consider requirements «The compendium medikamentorum»; England, Belgium, Italy, Luxembourg, France, Germany and Switzerland for this purpose use the European pharmacopeia, in Sweden, Norway, Denmark and Finland — the Scandinavian pharmacopeia.
Table. The list of the drugs excluded by orders MZ USSR from the state register of pharmaceuticals from January 1, 1974 to January 1, 1979.
Bibliography: Residents of Arzamas A. P. and Senov P. L. Standard samples of medicinal substances, M., 1978, bibliogr.; Babayan E. A. The organization of developments and implementation in medical practice of new pharmaceuticals, Pharmacy, No. 1, page 27, 1975; Brutko L. I. and Gritsenko S. V. Guide to quantification of medicines, M., 197*8, bibliogr.; The second symposium on kliniko-pharmacological assessment at control of pharmaceuticals, Copenhagen, WHO, 1975; V. I. Organization's Shouts and economy of pharmacy, page 33, etc., M., 1976; Side effect of pharmaceuticals, under the editorship of A.S. Lopatin, page 18, M., 1976; The Principles of assessment of the pharmaceuticals applied in medicine it is gray. tekhn. dokl. No. 563, Geneva, WHO, 1977; The Role of kliniko-pharmacological assessment at control of pharmaceuticals, Copenhagen, WHO, 1977.
G. A. Ulyanova, M. I. Smirnov.