Quality control of medicines with examples of recipes. Quality control of drugs
Introduction
Quality is a combination of the characteristics of the object relating to its ability to satisfy the established and intended needs.
Quality assurance medicines - The primary task of the state. This requires federal laws of the Russian Federation "On Medicines" and "On Consumer Protection".
To assess the technical level of production and quality of medicines by the World Health Organization (B03) ("WORLD HEALTH ORGANIZATION" - WHO was created "The system of quality certificate of pharmaceutical preparations in international trade", currently the option of which was adopted in 1992
- To participate in the system, it is necessary to have the presence of three conditions in the country:
-Regular state inspection of pharmaceuticals of reducts;
- Compliance of existing production requirements GMP rules
GMP Rules (Good Manufacturing Practice - Good Manufacturing Practice) were developed in 1963 in the United States, then, starting from the 70s of the last century, were widespread all over the world, with the exception of the Soviet Union.At the beginning of the XXI century, individual Russian pharmaceutical companies have improved their production processes and successfully passed audits for GMP compliance. The deadlines for the introduction of compulsory compliance of all Russian farm. Enterprises GMP rules were constantly transferred. On the this moment There is no accurate information about the number of pharmaceutical enterprises that completely switched to work on GMP. According to some data, we are talking about 30 sites out of 400 with excessive enterprises.
Since 2009, negotiations have been negotiated on the accession of the Russian Federation to the international system of cooperation in inspectors on GMP and work has begun on preparation for entry. However, many enterprises are aimed at the introduction of GMP rules, but for further delaying the control deadlines.
In certain speeches, representatives of specialized departments are supported by such a course. It does not take into account the fact that international GMP rules are rapidly developing and complicated. In this regard, the further transfer of the timing of the transition to work on international rules of GMP will not only facilitate this transition, but, on the contrary, it makes it difficult or will do at all impossible. Under these conditions, vigorous measures are needed to clarify the modern GMP concept among managers and specialists of enterprises of the industry, as well as among government officials related to this issue.
The intermediate result of the discussion regarding the establishment of the requirements of the GMP rules as a mandatory in the manufacture of drugs can be considered a statement by the Minister of Health and social Development Tatiana Golikova, made during the round table, which took place in the State Duma on March 11, 2010: January 1, 2014 - the final date to which domestic manufacturers should go to the European standard quality standard. In case the production does not meet the requirements of GMP by January 1, 2014, the production license will no longer act. "
The goal of the course work is to explore the organization of quality control medicinal preparations, general requirements To the quality of drugs, the GMP system.
During the writing course, the following tasks were made and resolved:
1. Investigate scientific literature and regulatory documentation on the quality control of drugs; deepen theoretical knowledge on this topic;
2. Agreement of the current state of the topic.
3. Support the regulatory and legal regulation of the quality control of medicines (state control authorities, regulatory documents);
4. Examine the GMP system . (Requirements for the production and quality control of medicines);
5. Examine the organization of intensive control (quality indicators, types of control );
.
Main part
1. Regulatory legal regulation.
1.1. State control bodies for medicinal quality.
The quality of medicines in Russia controls federal Service on oversight in health and social development (Roszdravnadzor) subordinate to the Ministry of Health and Social Development Russian Federation. The quality control system of drugs and drugs is headed by the Department of State Control of Efficiency and Safety of Medicines and Medical Technology of the Ministry of Health and Social Development of Russia-Scientific Center for Expertise and State Control.
In most major cities of Russia, control laboratories and drug quality control centers work. Their main task is to check the trade-selling organizations (compliance with numerous storage and sale of medicines), as selective (and in some regions and total) control of drugs. Based on these regional centers, Roszdravnadzor will be accompanied by decisions on the taking of a particular medicinal product.
State regulation of relations arising in the field of state control of production, manufacturing, quality, efficiency, LS safety is considered in the II chapter of the Law "On Medicines". The structure and functions of the state quality control system, efficiency and safety J1C are reflected in Chapter III of the Federal Law. The law establishes that all JTCs are subject to state control, both produced in the territory of the Russian Federation and imported from abroad.
The federal authority authorized by the government is independent and the only one in the Russian Federation, which carries the full responsibility for the implementation of state quality control, efficiency and safety of LS in the Russian Federation. It can create territorial bodies In the constituent entities of the Russian Federation or to transfer them part of their authority to control the quality of LS.
The federal body exercises the expertise of the quality, efficiency and safety of all LS, both produced and imported into the territory of the Russian Federation. He holds their state registration, drawing up the state register of the drug, the assertion of the texts of the FS, the preparation and publication of the GF, the preparation of the LAN lists released without a doctor's prescription, supervises the pharmaceutical activities and the implementation by enterprises of the rules for organizing production and control their quality, conducts certification and Certification of specialists engaged in the field of HPP, as well as other powers assigned to him by the Government of the Russian Federation.
The state control of the production of drugs in the Russian Federation is carried out by the federal and territorial bodies of Quality Control. The federal body develops and approves the rules for organizing production and quality control of drugs, conducts an inspection of manufacturers' enterprises, makes a conclusion on the compliance of their activities approved rules. Territorial bodies (on behalf of the federal body) are subject to similar control of the activities of producers located on their territory. The federal and territorial bodies can carry out various measures to improve the quality of drugs produced up to the prohibition of the sale of LS produced.
1.2 State laws and regulations governing the quality of medicines .
- 1.2.1.
Federal laws.
The Federal Law of the Russian Federation "On Medicines" regulates relations in the territory of the Russian Federation in the entire field of HPP, many of its provisions are directly related to the problems of ensuring the state system of quality control, safety and efficiency of drugs. It should be noted that the law establishes the priority of state control of production, quality, efficiency and safety of drugs.
1.2.2. Regulatory documentation systems
In accordance with the Law of the Russian Federation of 10.06.1993 N 5154-1 "On Standardization", Federal Law of 22.06.1998 N 86-FZ "On Medicines", Regulations on the Ministry of Health of the Russian Federation, approved by Decree of the Government of the Russian Federation of 03.06.1997 N 659 The Ministry of Health of the Russian Federation, an order was established from November 1, 2001 N 388 "On state quality standards of medicinal products".
Under the standardization of product quality, the process of establishing and applying standards is understood. The standard is the standard or sample taken for the source, to compare with other similar objects. Standard as a regulatory document establishes a set of standards or requirements for standardization object. Application of standards contributes to improving product quality.
The main task of standardization is the definition of a unified system of product quality indicators, methods and means of its testing and control. This task is solved by creating a system of regulatory documentation (ND), which determines the requirements for manufactured products, its production and application. No less important is the control over the correctness of the use of ND.
The following categories of ND are installed in the Russian Federation:
- State Standards (GOST),
- Course standards (OST),
- Republican standards (RS.T)
- Technical conditions (TU).
The LS standards are FS, which regulates their quality, as well as production regulations, normalizing their technology.
FS - regulatory documents defining a complex of quality norms and methods for their definition. These documents provide the same efficacy and safety of drugs, as well as constancy and uniformity of their production regardless of the series. The main document that normalizes the quality of drugs produced in our country is State Pharmacopoeia (GF). Regulatory documents reflecting additional technical requirements for production, control, storage, labeling, packaging, LS transportation, are industry standards (osce).
State Pharmacopoeia (GF) - a collection of mandatory national standards and regulations normalizing the quality of LV. It is based on the principles of domestic healthcare and reflects modern achievements In the field of pharmacy, medicine, chemistry and other adjacent sciences. Its requirements for HP are mandatory "for all enterprises and institutions that are manufactured, stored, control the quality and use LS (regardless of the forms of ownership and departmental subordination).
Vol. 1 GF XI includes 54 general articles on physical, physico-chemical, chemical methods of analysis and methods for analyzing medicinal plant raw materials. In "Introduction", all changes that are made to general pharmacopoeia articles are indicated, compared with XF X. There are sections containing the rules for the use of pharmacopy articles, units of measurement and abbreviations adopted in GF XI. Four items were additionally introduced. and the definition of impurities of chemical elements in radiopharmaceutical preparations.
In 1990, I walked out. 2 GPH1 containing two sections: " General methods Analysis "and" Medicinal Raw Material "(LRS).
All of these changes are preliminarily substantiated by deep studies conducted in Nisalshls and Dougi Research Institutions and Training Pharmaceutical Universities. Developed and approved new Offices and FS are the basis for the creation of GF XII.
Since June 2000, the sectoral standard "Rules for organizing production and quality control LS" has been enacted in Russia. This is a standard identical to the international rules of the CMR.
In addition to the specified standard, which ensures high-quality drugs, a standard normalizing the quality of drugs, regulating the procedure for creating a new and improving the current regulatory documentation for the LANs. It was approved by the Ministry of Health of the Russian Federation on November 1, 2001 (Order No. 388), and is a sectoral standard OST 91500.05.001-00 "Drug quality standards. Basic provisions. " Previously operating the Standard OST 42-506-96 lost its strength.
The new OST provides for the presence of two categories of quality standards:
I. State quality standards of drugs (GSKLS), which include: General Pharmacopoeial article (Office) and pharmacopoeial article (FS);
II. Quality standard (SKLS); Pharmacopoeial article of the enterprise (FSP).
The content of these standards is different from each other.
Offs Contains the main general drug requirements or a description of standard LS control methods. OFS includes a list of normalized indicators and test methods for a specific LF or a description of methods for analyzing drugs, reagent requirements, titrated solutions, indicators.
FS. Contains a mandatory list of indicators and methods of quality control of the drug (including its LF) corresponding to the requirements of leading foreign pharmacopy.
Offs and FS are developed and revised after 5 years Scientific Center Examination and state control of drugs, and on immunobiological drugs - a national control of MIBP.
Offs and FS are a state pharmacopoeia (GF), which is published by the Ministry of Health of the Russian Federation and is subject to reprint every 5 years.
FSP - This is a quality standard that contains a list of indicators and methods for controlling the quality of drugs produced by a specific enterprise, taking into account the features of technology of this enterprise and the past examination and registration in the prescribed manner. The FSB is being developed taking into account the requirements of the OST, GF and Office. The validity period of the FSP is established taking into account the level of the technological process at a particular enterprise, but not more than 5 years. Responsibility for the content and validity of standards of quality standards in the FSP and their compliance with the modern level of science and production are managers of developers and manufacturers of this LAN.
Organization-holder of original Office, FS, FSP is the Ministry of Health of the Russian Federation. The Holder of the SSP originals is also the appropriate enterprise-manufacturer or organization-developer.
- 2. The quality of drugs.
Pharmaceutical production is a complex technological process, and on how carefully it is worked out and its numerous stages are performed, it depends on which a mixture of chemicals is contained in serial packaging taken by the patient. Often, different phases of pharmaceutical production are performed at different enterprises - for example, the manufacture of substance (or the "active substance") - on one, and the manufacture of the finished dosage form is on the other, which acts as a medication manufacturer.
High quality medication implies:
the high chemical purity of the active substance (there is always impurities, the question is how many of them are in percentage of the total composition and there are no harmful among them even in very small quantities);
the exact match of the content of the active substance declared (for example, obsolete equipment cannot ensure the accuracy of the dosage during serial manufacture or unscrupulous manufacturers can "save" on the content of the active substance and therapeutic effect drugs may decline - which not only causes financial damage to consumers, but may be simply dangerous to health);
high quality and safety "fillers" (most dosage forms consists not only of the active substance, but also from additional ingredients serving for proper administration active substance in the body - the so-called "delivery mechanism");
the quality of the packaging, the compliance of the real and declared date of production, the correctness of transportation and storage (most chemicals are transformed over time, for example, camsheet, disappears, enters into chemical reactions from the effects of temperature, light, oxygen and the moisture of the atmosphere, etc.);
2.1. GMP system.
Standards of advanced pharmaceutical companies exceed the state requirements for the quality of drugs.
In most developed countries in the world, pharmaceutical production is conducted in accordance with GMP standards (Good Manufacturing Practice - Proper Industrial Practice). Companies - drug manufacturers pass the GMP certification procedure, which is the inspection by independent authorized organizations compliance with the company's production processes with GMP requirements. They are aimed at ensuring a high level of quality and safety of drugs and ensuring that the drug is manufactured in accordance with its formula (composition), does not contain extraneous inclusions, labeled properly, packed and retains its properties during the entire shelf life.
In our country, GMP rules ("Rules for organizing production and quality control of medicines" of the RD 64-125-91) were first developed in 1991, taking into account international, regional and national rules operating at the time different countries. In February 1998, the joint order of the Ministry of Health of Russia and the Ministry of Economy of Russia came into force on the introduction of the Standard of the OST 42-510-98 industry "Rules for the organization of production and quality control of medicines", which established that from July 1, 2000, an acceptance of commissioning again Created and reconstructed manufacturers of medicines and pharmaceutical substances, issuing licenses for production, storage and distribution of products only in case of compliance with the GMP standard in its Russian version.
The Russian GMP standard was prepared by the Association of Microlls Control Engineers (Asincom) and in 2004 by Resolution of the State Standard of Russia dated March 10, 2004 No. 160-state was approved by GOST R 52249-2004 "Rules of production and quality control of medicines", which is harmonized with the rules GMP (Good Manufacturing Practice for Medicinal Products) of the European Union. The GMP certification system is preparing for mandatory use in Russia.
Some russian manufacturers Already brought some of their production facilities to world quality standards and received the Certificates of GMP confirming this fact. Approved by Decree of the State Standard of Russia dated March 10, 2004 N 160-ST Date of introduction - January 1, 2005 National Standard of the Russian Federation Rules for the production and quality control of the Good Manufacturing Practice for Medicinal Products (GMP) GOST R 52249-2004
GMP rules establish requirements for quality management system, quality control, personnel, premises, and equipment, documentation, product production and testing of contracts, advertising, product relevance and self-technical organization.
APPLICATION AREA
This standard establishes the requirements for the production and quality control of medicines for humans and animals.
The standard applies to all types of drugs and establishes general requirements for their production and quality control, as well as special requirements for the production of individual types of drugs.
The standard does not apply to industrial safety, fire safety, explosion safety, chemical safety and safety of other types of drugs, requirements for which are given in other regulatory documents.
2.1.1. Quality control
The quality assurance system (quality system) in the production of medicines should guarantee the following:
I. Drugs are designed to meet the requirements of this standard and the requirements for the work of laboratories.
II. All production and control operations have developed documentation in accordance with this standard.
III. Responsibility and obligations of all workers are clearly defined.
IV. There are measures to ensure the production, supply and use of the source and packaging materialscorresponding to the specified requirements.
V. Control of intermediate products and technological process (internal production control), certification (validation) of processes and equipment are carried out in the required amount.
Vi. Production and control of finished products meet approved instructions (methods).
VII. The sale of drugs before issuing an authorized person permit to issue is excluded. The authorized person must confirm that each product series is manufactured and verified in accordance with the established requirements.
VIII. The existing system of measures provides the level of quality of medicines when they are stored, shipping and subsequent circulation throughout the expiration date.
IX. The procedure for conducting self-technical and / or quality audit makes it possible to regularly assess the effectiveness of the quality assurance system.
2.1.2. Requirements for the production and quality control of medicines
This standard is included in the quality system and is aimed at ensuring the guarantee that production and quality control of products constantly comply with the requirements established in the documentation.
Primary requirements:
I. All production processes should be clearly regulated and periodically revised taking into account the accumulated experience. It should be monitored by the stability of drug production with a given quality in accordance with the specifications on them.
II. Attestation (validation) of critical stages of production processes should be carried out, including when making significant changes to the technological process.
III. All necessary conditions should be ensured to meet the requirements of this Standard, incl. Including:
a) trained and certified personnel;
b) the necessary premises and areas;
c) appropriate equipment and maintenance systems;
d) materials, packaging and labeling tools that meet the specified requirements;
e) approved instructions and techniques;
f) required storage and transportation conditions.
IV. Instructions and techniques must be specific, are set out clearly and unambiguously in writing.
V. The staff must be trained to properly implement instructions.
Vi. In the process of production, protocols should be drawn up (filled in handwritten form and / or using technical means), documenting the actual implementation of the technological stages provided for by the instructions and obtaining products of the required quality in an amount corresponding to the established standards. All deviations must be investigated and operating in full.
VII. Protocols for a series, incl. Documentation on the sale of products should be able to trace the manufacture of each product series and should be stored in full in an affordable form.
VIII. The procedure for implementing (wholesale) products must minimize any risk for its quality.
IX. You should organize the recall system of any product series from sale or delivery.
X. Advertising on product quality should be carefully considered, and the reasons for the deterioration of quality investigate with the adoption of appropriate measures to prevent them.
2.1.3 Quality Control
Quality control includes sampling, testing (analyzes) and design relevant documentation. Instructions for the organization, documenting and issuing permits for the release of products should include carrying out all necessary tests and prohibit the use of raw materials and materials and the sale of finished products before confirming the quality conformity to the established requirements. The purpose of quality control is to use or implement materials or products that do not meet the quality requirements. Quality control service performs research, checks and participates in the adoption of any solutions regarding product quality. The fundamental principle of ensuring quality control is the independence of the quality control department.
At each enterprise producing medicines, there must be a quality control department independent of other units. The head of this department should have the necessary experience and qualifications. The quality control department includes one or more control laboratories. To fulfill its functions, the department must be provided with all the necessary resources.
The main responsibilities of the head of the quality control department are described above. The Division also imposes obligations to develop, certification (validation), the implementation of all instructions (methods) on quality control; Storage of mothers control samples.
2.1.3.1. Quality control requirements
I. The presence of the necessary premises and equipment, trained personnel, approved methods for the selection of samples, verification and conducting tests of initial and packaging materials, intermediate, non-fascinated and finished products, control ambient If necessary.
II. Conducting sampling of the initial and packaging materials, intermediate, non-self-installed and finished products of certified personnel in accordance with the techniques approved by the quality control department.
III. Conducting tests certified (validated) methods.
IV. Drawing up protocols (filled with handwritten method and / or with the use of technical means) confirming the actual conduct of all necessary sampling, checks and testing, as well as the registration of any deviations and investigations in full.
V. Confirmation that the finished products contain the active ingredients according to the qualitative and quantitative composition corresponding to the registration dossier, it has the required purity, is properly packed and marked.
Vi. Registration of protocols of testing of raw materials and materials, intermediate, non-self-installed and finished products, their analysis and comparison with specifications. Product rating includes the study of all the necessary production documentation and analysis of deviations from the established requirements.
VII. Getting permission for the sale or delivery of any product series only after confirming the authorized face of its compliance with the registration dossier.
VIII. Preserving a sufficient number of samples of source materials and products for possible verification if necessary. Product samples should be stored in their final packaging,
with the exception of large packages.
2.1.3.2. Staff
The organization and functioning of production and the system for ensuring the quality of medicines depend on the personnel. The company must be equipped with the staff of the necessary number and qualifications. Official duties of each employee must be documented and learned by each employee. All employees should also know the requirements of this Standard (GMP rules) relating to the sphere of their activities, and undergo initial and re-learning in the required amount, incl. According to the rules of personal hygiene.
- The main responsibilities of the manufacturer of production:
II. Approval of instructions related to the production process and ensuring their accurate execution.
III. Control over the consideration and signing of all production protocols by persons who have the necessary powers before passing them to the quality control service.
IV. Control over the work of its division, premises, operation and maintenance of equipment.
V. Control over the work on certification (validation).
Vi. Organization of primary and subsequent training personnel
- The main responsibilities of the quality control service manager.
II. Assessment of protocols on a series of products.
III. Conducting the necessary tests.
IV. Approval of specifications, sampling instructions, test methods and other quality control techniques.
V. Admission to the work of specialist analysts working under the contract, and control over their activities.
Vi. Control of the subordinate department, maintenance of its premises and equipment.
VII. Control of certification (validation).
VIII. Organization of primary and subsequent training personnel of the subordinate department.
2.1.4. Documentation
Properly compiled documentation is an important part of the quality assurance system. A clear design of documentation allows you to prevent errors that are possible with oral communication, and trace all stages of production of a specific series of products. Specifications, Industrial Regulations, Instructions, Methods and Protocols of the Product Series must be executed properly and should not contain errors.
Types of documents:
specification (specification): A document containing requirements for materials and products used or obtained in production, which is the basis for assessing the quality of drugs;
industrial Regulations, Technological Instructions and Packaging Instructions (Manufacturing Formulae, Processing and Packaging Instructions): Documents that determine all the source materials and production operations and packaging operations;
instruction, Methodology, Procedure (Procedure): A document containing instructions for performing certain types of operations (for example, cleaning, dressing, environmental control, sampling, testing, operation of equipment);
protocol on the series (Record): a document reflecting the production of each product series, incl. Permission to implement it, and all factors affecting the quality of finished products.
2.1.5. Production
To obtain products of the required quality, technological operations should be performed according to industrial regulations and relevant instructions, the requirements of this standard, regulatory documents and a registration file.
2.1.5.1. General provisions
1. The production process and its control must be carried out by qualified personnel.
2. All operations with materials and products (for example, acceptance, quarantine, sampling, storage, marking, preparation, preparation, packaging and shipment) must be executed according to written instructions or methods and, if necessary, log.
3. All incoming materials must be checked for compliance. Tar and packaging should be cleaned and marked.
4. Facts of damage to the packaging and packaging, which can have a negative impact on the quality of the materials, should be investigated and logged with a subsequent message to the quality control department.
5. The incoming materials and finished products must be immediately placed in quarantine, operating on the principle of separate storage or by organizational measures, and is contained in it before receiving permission to use or shipping.
6. Acceptance of intermediate and non-self-installed products is carried out according to the rules operating for the source materials.
7. All materials and products should be stored in the appropriate conditions defined by the manufacturer, in order ensuring separation of production series and its turnover in stock.
8. In order to guarantee the lack of deviations for permissible limits, it is necessary to control the product output and a quantitative comparison of it with industrial regulations.
9. It is not allowed simultaneous or consistent operations with various products in the same room in the absence of protection against risk of confusion or cross-contamination.
10. Products and materials must be protected from microbial and other types of pollution at all stages of production.
11. When working with dry materials and products, it is necessary to make special precautions to prevent the formation and distribution of dust, especially when working with potent and sensitizing substances.
12. In the course of the technological process on all materials, packages with non-compatible products, the main equipment and premises should be notation (marking) with an indication of products or material, its dosage (if necessary) and series numbers. If necessary, indicate the stage of the technological process.
13. Designations (marking) on \u200b\u200bpackaging, equipment or premises must be clear, unambiguous, installed form. In addition to applying alphabetic designations, it is recommended to use the color marking indicating the status of products (for example, "quarantine", "accepted", "rejected", "pure", etc.).
14. It is necessary to control the correct connection of pipelines and other equipment that serves to transport products from one zone to another.
15. Deviation is not allowed from instructions. If necessary, a written permission to deviate from the instructions should be obtained from the competent persons and the quality control department.
16. Only personnel with access to them can be included in production facilities.
17. As a rule, indoors and equipment intended for the production of drugs are not allowed to manufacture nonysine products.
2.1.5.2. Performance of cross-pollution in production
18. The possibility of pollution of the source materials or products by other materials or products should be eliminated. In the process of production, the risk of random cross-contamination occurs with an uncontrolled allocation of dust, gases, evaporation, aerosols or microorganisms from materials (products) and from residual pollution on the equipment and clothing of people. The degree of risk depends on the type of pollution and product exposed to pollution.
The most dangerous pollutants include sensitizing substances, biological preparations containing live microorganisms, some hormones, cytotoxins and other potent substances. Particularly dangerous pollution of injectionary preparations, as well as drugs intended for admission in large doses and / or for a long time.
19. To prevent cross-pollution, the following technical and organizational measures should be provided:
a) production in the isolated zones (compulsory for penicillins, living vaccines, bacterial preparations from living microorganisms and some other biological preparations) or the separation of production cycles in time with appropriate cleaning of the room and equipment between cycles;
b) the organization of air gateways and exhaust devices;
(c) Reducing the risk of pollution caused by recycling or re-entering unprocessed or insufficiently treated air;
(d) Storage of protective (special) clothing within the products of production with high risk of cross-pollution;
(e) The use of highly efficient cleaning and processing methods to eliminate insufficient purification, which is often the cause of cross-contamination;
(f) The use of "closed systems" production;
g) control of the presence of residues of the previous product or detergents and labeling equipment indicating the status of purity.
20. It is possible to periodically verify the effectiveness of measures to prevent cross-pollution in accordance with the approved instructions.
2.1.5.3. Attestation (Validation)
21. Certification (Validation) is aimed at improving the efficiency of work and is carried out in accordance with the approved techniques. Its results should be documented.
22. When approving a new industrial regulation or method of production, their suitability for mass production should be checked. It should be confirmed that this process used materials and equipment allows you to constantly produce products of the required quality.
etc.................
In our country, there is a system providing for quality control of drugs at all stages of manufacturing products and leave.
In pharmacies, the quality control of drugs is carried out by processing technologists and analysts. Medicinal preparations are also analyzed in control and analytical laboratories, certification institutions and quality control of these drugs.
The quality of drugs depends on the quality of drugs (substances), therefore, they establish special quality standards for them (quantitative content of the substance, permissible content of impurities, etc.). Impurities B. medicinal substances These may fall when they are synthesized, imperfect methods of purification, etc. in quantities exceeding the norm, they can have a toxic effect on the human body or affect the stability of drugs. In addition to the toxic effect of impurities, they can affect the quality of drugs, cause the formation of precipitation in solutions during sterilization, etc.
Drug quality standards are indicated in Pharmacopoeial articles of GF, which represent NDs that establish requirements for the quality of medicines or medicinal plant materials, and are the nature of the state standard. Other regulatory document is a VFS - a temporary pharmacopoeial article approved for a limited period (no more than 3 years).
The quality of the manufactured drug can only be provided with the unconditional fulfillment of all the requirements of these NDs. In addition, a number of ND must contain directly normalized quality indicators:
Medicines, such as the presence of impurities, humidity, pyrogenicity, quantitative content;
Auxiliary substances, dispersion media, for example, permissible impurities, pH;
At the stages of manufacture - homogeneity (powders, ointments, suppositories), particle size (powders, suspension ointments), lack of mechanical inclusions (solutions for injection, ophthalmic solutions, etc.);
The preparation made (deviation in the mass of powders, the volume of mixtures, the time of complete deformation or dissolution of the suppository, the decomposition of the pill).
When monitoring at the time of vacation, the drug from the pharmacy is checked:
the correctness of the accompanying documents (written control passports, recipe or signature);
compliance with packaging and closure materials properties of a manufactured drug;
the correctness of the labeling and design (the presence of a properly decorated label, preventive inscriptions or labels, signatures for drugs with substances that are on the subject and quantitative accounting), the presence of a sedentary printing of the pharmacy (in the case of content in the preparation narcotic substances Or substances of the list a).
Attention should be paid to the study of the orders of the Ministry of Health of Russia "On control of the quality of drugs manufactured in pharmacies", "On the norms of deviations permissible in the manufacture of drugs and phasing of industrial products in pharmacies", guidelines "Uniform rules for the design of drugs manufactured in pharmacy institutions (enterprises) various shapes Property.
Inportal control in accordance with the order of the Ministry of Health of Russia "On the quality control of medicines manufactured in pharmacies" includes next species:
1) Written control (written control passport - * SC). Written control passport is issued after
preparation of underrranted dosage forms (mixtures, ointments, suspensions, emulsions) or before separating the doses of doses (powders, suppositories, pills), or simultaneously with the manufacture (if it works and controls the drug the same specialist);
2) Poll control. The oral survey of the pharmacist or provisor-technologist is carried out to confirm the qualitative and quantitative composition of propusions no later than after the manufacture of five preparations;
3) physical control. Check the compliance of volume, mass, size, melting point, disintegration time, deformation time, solubility, etc.;
4) chemical control - high-quality and quantitative analysis of the manufactured drug;
5) Organoleptic control: the smell, taste (selectively in children's dosage forms), appearance, chromaticity, transparency, homogeneity, lack of mechanical inclusions (in accordance with the properties of the ingredients), the correctness of the packaging and capping. The packaging must match the mass (volume) and the type of dosage form, as well as the properties of incoming ingredients.
Quality control of the intranshappy blank is carried out as follows. In the presence of a dialer-analyst or provision of a technologist ("under observation"), fragrant water and an intrapensive preparation of drugs for external use containing tar, ichthyol, sulfur, naphthalan oil, collodes, water lead and other substances, chemical Analysis of which cannot be implemented in a pharmacy. Also, "under observation" manufacture drugs for newborns, which do not require methods of high-quality and quantitative analysis.
In accordance with the instructions for assessing the quality of drugs manufactured in pharmacies, two terms apply to assess the quality of manufactured products: "Satisfies the requirements of the GF, orders and instructions of the Ministry of Health of Russia" (forgenous products) and "Does not satisfy the requirements of GF, orders and instructions of the Ministry of Health of Russia "(Marriage).
In accordance with the Law of the Russian Federation "On Certification of Products and Services" of 10.06.1993 No. 5151 -1 as amended from 07/31/1998 with change From 11/22/2001 Regional quality control centers are certified by drugs in order to create conditions for the activities of enterprises, institutions, organizations, entrepreneurs in the Unified Commodity Market of the Russian Federation and in international trade, the protection of consumers from the unscrupulousness of the manufacturer, the health control for the environment, life , health, confirmation of product quality indicators declared by the manufacturer.
The quality of medicines is determined by the regulatory and technical documentation. Regulatory and technical documentation includes the state pharmacology of the Russian Federation, certificate of conformity, sanitary and epidemiological conclusion, registration certificate. State Pharmacology of the Russian Federation (GF) recommends the quality of drugs defined as a formistant. In addition to the official drugs, there are nephoochny drugs. The quality of nephocal drugs determine: certificate of conformity, sanitary and epidemiological conclusion, registration certificate. The State Pharmacology of the Russian Federation is a meeting of mandatory national standards and provisions that determine the quality of drugs. State pharmacology of the Russian Federation is legislative. Pharmacology is written for persons who have passed special trainingWith qualification, therefore, the material in it is presented in essentially, without unnecessary details. The XF XI consists of several parts: the introductory, two main ("preparations" and "general methods of physicochemical, chemical and biological research") and applications. The introductory part includes the rules for the use of GF XI, lists of new drugs, a list of poisonous and potent drugs, etc.
The chapter "Preparations" contains requirements for the quality of the medication, in the second part of the "general methods of physicochemical, chemical and biological research" the above research is set.
Direct quality control of drugs manufactured by pharmacies, as well as drugs coming from suppliers carries out a monitoring and analytical laboratory.
The control and analytical laboratory is a health care institution, is organized by the main pharmacy department of the Ministry of Health of the Russian Federation.
with an amount of analyzes equal to 4,000 per year - I category;
The monitoring and analytical laboratory has an angular stamp and a round print indicating its name.
In addition, the laboratory has appropriate equipment and analyzes in accordance with the approved requirements (equipment, inventory, reagents for clinical analyzes, scientific I. reference information According to pharmacy and state pharmacology).
Control and analytical laboratories organize control and analytical cabinets during pharmacies, as well as analytical tables. Control and analytical cabinets are organized in pharmacies with 200,000 copies of the EXTEMPORAL formulation.
Analytical tables are organized in pharmacies where the pharmacy and 2 pharmacists are consisting in the state.
Medicinal quality control is carried out at all stages of pharmacy under observation of responsible persons.
This uses the following types of internal control.
Preventive control.
Warning activities include:
compliance with the sanitary regime in pharmacies (including disinfection, quality control of laboratory dishes;
systematic verification of the health and accuracy of weights, devices;
systematic briefing of pharmacy workers manufacturing medicines and checking their work;
creature required conditions storage of medicines and monitoring their storage time;
strict control of the implementation of the rules of drug making technology;
compliance with the rules for the storage and vacation of narcotic, poisonous and potent drugs (on back side The recipe recipe controller writes the amount of substance issued, is signed in the issuance of narcotic, poisonous or potent substance, and the assistant - in the reception of the appropriate drug).
Control by polling.
A provisional technologist calls the first ingredient, which is part of the drug, after that the assistant calls the remaining ingredients and their number. Control by oral survey is carried out immediately after the preparation of drugs. In addition to this method Checks, you can enjoy a dime control type - checking the compliance of the recipe recipe records on the control pass. Filling the coupons is made by memory after the preparation of the medication indicating the recipe number and the assistant data.
Organoleptic control - assessment of taste, smell, colors and homogeneity of the mixture.
Evaluation of the taste and smell of Sanpina:
lack of smell and taste - 0 points;
the minimum value that the experimental voutorer determines is 1 point;
the value that the consumer determines when focusing on this attention - 2 points;
the value that the consumer defines clearly defines, but the level of consumption is not reduced - 3 points;
involuntary reduction in consumption levels - 4 points;
the magnitude causing a person's sense of disgust is 5 points.
Taste check drugs for internal use at the discretion of the controller.
Physical Control - Check total weight And individual doses to the sample several times during the day.
Qualitative analysis.
The essence is to confirm the authenticity of the drug or separate ingredientsincluded in its composition.
Chemical control.
Its essence consists in confirming the authenticity of the qualitative and quantitative composition of multicomponent drugs by express analysis.
Such control is made with the help of periodic seizure of exempher products and internally preparations. The withdrawal of drugs is carried out by the employees of laboratories and representatives of the Health with the participation of the pharmacy manager. The withdrawal is subject to medicines consisting of 1-2 and more ingredients, concentrate, semi-finished products. The results of this work are recorded in the appropriate log of records with the signature testing and indicating the date.
The most practical express method of quantitative analysis is refractometric. The essence consists in calculating the concentration of the drug on the value of the preparation of the resulting solution and the solvent at the same temperature.
The concentration of the solution is calculated by the formula:
X \u003d n - n 0 / F, where
H. - concentration of solution (%);
n.
n 0 - the refractive value of distilled water;
F. - Factor of refractive value.
According to this formula, working with one-component solutions.
For a two-component solution for calculating the content of the second component, the following formula is used:
X \u003d n - (n 0 + C 1 x F 1) / Fn, where
H. - the content of a certain ingredient (%);
n.- the refractive value of the solution;
n 0
C 1 - concentration of the drug obtained chemical method (%);
F 1. - factor in the refractive value of the solution of the drug obtained by the chemical method;
FN. - factor in the refractive value of the solution of the determined ingredient.
Accordingly, such a formula is used for multicomponent solutions:
X \u003d n - (n 0 + C 1 x F 1 + C 2 x F 2 + ...) / Fn, where
X. - the content of a certain ingredient;
n.- the refractive value of the solution;
n 0 - the refractive value of distilled water;
FN. - factor in the refractive value of the solution of the determined ingredient;
C 1, C 2 - concentrations of drugs found by a chemical method (%);
F 1, F 2 - Factors of the refractive index of solutions of drugs obtained by a chemical method.
For quantitative analysis also used volumetric method, Present accurate calculation Volumes of solutions of substances in an equivalent amount with a certain concentration of one of them. Percent required component Calculate by the formula:
X \u003d a x k x t x 100 / n, where
H. - concentration of solution (%);
BUT
TO - correction factor;
T.- the titer of the studied substance;
N. - Snack for titration.
When recalculating the grams of the studied substance use the following formula:
X \u003d a x k x t x v / n, where
H. - the amount of substance;
BUT - the amount of consumed titled solution;
TO - correction factor;
T. - the titer of the studied substance;
N. - Snack for titration;
IN - Total mass of the drug.
For liquid drugs, a method for determining the amount of studied substance under testing is used, i.e. A certain indicator is added to a certain volume of the studied solution, after which the standard solution is titrated (for example, 0.1 N NaOH solution). In terms of the amount of completed titrant, the content of the studied substance in solution is calculated directly.
The approximate volume of titrant can be calculated by the formula:
V \u003d M / T, where
V.- the amount of consumed titrated solution (titrant);
m.- the mass of the component under study (g);
T.- Titress (g / mg).
A complete chemical analysis of exempher products and internal preparations is carried out by a pharmacy analyst.
In addition, the analyst is responsible:
control of the execution of the rules of internal control (high-quality and quantitative analysis of various medicines, reliable analysis of the tests, etc.);
control of the execution of drug storage rules in the pharmacy;
fixing incorrectly manufactured medicines in the book of accounting, reports on mistakes in the preparation of drugs at meetings;
control of the execution of the rules of disinfection and washing pharmacy dishes;
check the quality of non-storing and perishable drugs (ammonia-anise porridge, iodine solution, lime water, etc.);
monitoring the state of the burent system and pipettes (assembly, purity);
control of the preparation of sterilized solutions, infusions, decoctions, etc.;
a monthly report on its work on a generally accepted form in two copies, one of which is given to the control pharmacy, and the other is sent to the control and analytical laboratory.
Analyst in its work is focused on methodical development Control and analytical laboratories and complies with administrative subordination towards the control pharmacy. In order to assess the quality of medicines, two terms are used: "satisfies" and "does not satisfy" the prescriptions of state pharmacology and the requirements of the GAPU (the main pharmacy) Ministry of Health of the Russian Federation.
In control and analytical laboratories, all medicines are divided into two groups:
"Delivered in order of supervision";
"Delivered in order of doubt."
Medicines, "delivered in doubt", are not included in the general account, are considered separately.
Distinguish the following criteria unsatisfactory.
In authenticity - a random replacement of drugs; Disadvantage or, on the contrary, the extra ingredient of the medication, the use of related drugs without specifying this.
By physical properties - insufficient mechanical processing (rubbing, grinding, mixing) of individual components of drugs; Availability different impurities (fillers).
According to changes in weight, the inaccuracy of the total weight or weight of individual ingredients, changes in the wrestle.
All changes in drugs (quantity, form) are indicated in the signature. Otherwise, the medicine is considered unsatisfactory.
The technical conditions for industrial medical products (medical devices, medicines, ready-made dosage forms, drugs, technical raw materials) provides a technical control department (SW). This unit is monitored by the quality of raw materials and materials delivered to the enterprise.
Intelligent laboratories are subject to OTV.
Thus, a variety of departments participate in ensuring the quality of drugs. The obligation of the regulatory department includes a compliance check medical preparations Mounted quality standard, compliance technical Conditions In production, requirements that contribute to the compliance of products established standards up to the moment of delivery to the consumer. All this can be implemented only in the presence of compulsory licensing products, manufacturers. Any product intended to be introduced into a person's body with a diagnostic or medical and prophylactic goal proposed for sale is subject to control. But in reality it does not happen. Mandatory licenses apply only to drugs included in the National Pharmacological Directory. But ideally, the control should cover all medicines entering local sales markets. The purpose of the licensing system is to ensure the quality of products, safety and efficiency. License is legal documentdetermining the composition and shape of the product, its interchangeability, shelf life, installation and label.
For new drugs, there is a pre-sale check with the help of pharmaceutical, biological and clinical trials. In addition, the supervision of new drugs is preserved in the after-sales period by controlling their properties. Clinical trials are carried out only after the official resolution of the relevant structures and only subject to the principles of the Helsinki Declaration of the World Medical Association.
The rights and obligations of the regulatory department are determined by the charter and adopted rules. Rights of the Regulatory Office:
give licenses with a variety of drug sales structures to ensure that their work is conforming to the established rules;
issue and cancel the licenses for drugs depending on their quality, efficiency and safety;
control the license conditions (composition and form of product, expiration date, packaging and labels).
The regulatory agency for the development of a large amount of documentation has administrative premises and the necessary stationery. The work of the regulatory department is based on the definition of standards and monitoring. Previously before issuing a license for products, a technical assessment should be made.
Thus, the entire procedure includes three stages:
acceptance of applications from the manufacturer;
conclusion of the competent standing commission on the possibility of permission to implement the product;
immediately issuing a license (or refusal to issue), drawing up a license content.
In addition to quality criteria, safety and efficiency, there are cost indicators due to national policies.
Licenses are issued for a limited period. It is recommended to revise them every 5 years. Pharmacodynamic studies are conducted in cases where it is impossible to reliably determine the amount of drug in plasma or urine, as well as in cases where the concentration of the drug does not reflect safety and efficiency against the human body. Pharmacodynamic studies are conducted on a voluntary basis on healthy and sick people. With their implementation, it is necessary to comply with the conditions that meet the requirements of highly efficient clinical practice (WCP).