On approval of the procedure for the implementation of state control of the quality of medicines on the territory of the Russian Federation. Directions of state control of medicines State control of the quality of medicines when applying
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The instruction establishes that the state quality control of chemical-pharmaceutical, hormonal, vitamin, enzyme preparations, antibiotics, drugs obtained from animal and vegetable raw materials, radiopharmaceuticals, diagnostic kits is carried out by the Department of the Ministry of Health of the Russian Federation through control and analytical laboratories (CCCL), NIIKLS and others Research Institute. All drugs produced both by domestic enterprises, regardless of ownership and subordination, and imported through pharmacy bases (warehouses) are subject to state control.
State control of drugs is carried out in the form of:
- preliminary, those. control of the first 5 batches of the medicinal product, produced for the first time by this enterprise or
transferred for any reason to this type of control by the Department of the Ministry of Health of the Russian Federation;
- selective(subsequent), i.e. control of any series of medicinal products withdrawn from the warehouse of the manufacturer,
from a place of storage or from a pharmacy;
- arbitration control, conducted in case of disputes about the quality of medicines between the supplier and
consumer.
Analysis of samples received for state control must be carried out within no more than 30 days. In the event of a defect, the Department issues an order to seize the defective drugs.
State control is also carried out in the process certification drugs and during inspection. Inspection checks consist in planned control over the quality of drugs at enterprises and organizations that produce, store and sell drugs, regardless of their organizational and legal status.
The "Instructions on the procedure for conducting state control of the quality of drugs used in the territory of the Russian Federation" provides for common features and differences in the procedure for conducting state control of domestic and foreign drugs for all three of its types: preliminary, subsequent selective and arbitration.
From domestic drugs preliminary sampling control are subject to: for the first time permitted for medical use or for the first time mass-produced at this enterprise; mass-produced at this enterprise according to a modified technology or upon obtaining a license for production; transferred to this type of control by the Department of the Ministry of Health of the Russian Federation in connection with the transition to the use of imported substances. Transfer (reverse) from preliminary to subsequent sampling control is allowed by the Department if its quality meets all the requirements of RD for at least five series in a row.
Subsequent sampling all mass-produced drugs are subjected (according to the plans-tasks of the Department). LP samples with a cover letter and an act of taking an average sample are sent to NIIKLS. If the results of the analysis are positive, NIIKLS notifies the manufacturing enterprise from which the samples were taken. If a discrepancy between the quality of the samples and the requirements of RD is revealed, NIIKLS sends a written conclusion with the analysis protocol to the same address.
Arbitration control conducted by NIIKLS. Medicinal product samples for arbitration analyzes are sent to the research institute with a cover letter, an act of taking an average sample, an analysis protocol for all ND indicators and a written conclusion of the manufacturer about the refusal to satisfy the consumer's claims.
Foreign medicinal products also go through all the indicated stages of state control.
The first three series of drugs purchased for the first time are subject to preliminary control. Samples for its implementation are sent by the pharmacy base (warehouse) within ten days from the moment they are received.
Antibiotics, hormonal, enzymatic and other medicinal products from animal raw materials are subjected to subsequent control for all ND indicators; chemical and pharmaceutical preparations that require testing for sterility and pyrogenicity (selectively for these indicators, as directed by the Department of the Ministry of Health of the Russian Federation). The remaining purchased drugs are subject to subsequent control selectively according to the NIIKLS plan.
All batches of foreign drugs are subject to arbitration control, the quality assessment of which revealed deviations from the requirements of the regulatory documents. Samples for analysis are sent to NIIKLS by the organization that has identified the non-compliance of the medicinal product with the requirements of the ND, a claim is made to the manufacturer.
5.6.3. Selection of an average sample for state control
When sampling (sampling) medicines, they are guided by the requirements of the Global Fund XI (issue 2, p. 15) and the requirements of the Federal Assembly (FSP).
Samples (samples) are taken from individual series (batches) of drugs after an external examination, only from packaging units that are undamaged, sealed and packed in accordance with the requirements of ND. When sampling poisonous and narcotic drugs, it is necessary to follow the rules provided for by the relevant orders, regulations, instructions approved by the Ministry of Health of the Russian Federation.
To test drugs for compliance with the requirements of ND, multi-stage sampling (sampling) is carried out. In this case, the sample is formed in stages and drugs in each stage are randomly selected in proportional quantities from the units selected in the previous stage. The number of steps is determined by the type of packaging:
1st stage: selection of packaging units (boxes, bags, boxes, etc.);
2nd stage: selection of packaging units in packaging (boxes, bottles, cans, etc.);
3rd stage: selection of products in primary packaging (ampoules, vials, tubes, etc.).
From the packaging units selected at the last stage, after control in appearance, a sample is taken to control the quality of the drug for compliance with the requirements of ND. The number of drugs should be sufficient to conduct 4 complete analyzes for all sections of the FS (FSP). The sampling procedure for drug control for sterility, pyrogenicity, toxicity and other special types of control is specified in the OFS (GF X1, v.2) or FS (FSP).
The selection of the average sample is completed by drawing up the “Act of the selection of the average sample”, which indicates the name of the drug, the batch number, the total number of drugs, the number of drugs taken. The act is drawn up and signed by a commission, which includes the head of the Quality Control Department, a representative of the KanL (or the customer).
The Control and Permit System (CPC) is a set of measures to ensure the quality of drugs, medical devices, medical equipment, dietary supplements and other goods.
Tasks:
- protection of consumers from the negative consequences of the use of drugs;
-improvement of the quality of drugs;
- expansion of drugs and quick change of assortment;
Types of state control over the quality of medicines (project of the Ministry of Health of the Russian Federation No. 137 of 2003)
Preliminary: - medicines produced in the Russian Federation, medicines produced for the first time, medicines produced according to a modified technology are subject;
- selective: - are subject to drugs of domestic and foreign production, which are in the sphere of circulation in the Russian Federation;
- repeated selective: - in case of disputes about their quality;
- quality control of substances of various origins intended for the production of drugs;
- Periodic control of the production of drugs located on the territory of the Russian Federation.
Certification of drugs, types of certificates.
Certification is an activity to confirm the conformity of products to the norms, rules, and characteristics established in the process of standardization.
The documents:
- No. 36 of 2002 “Rules for Certification”;
Decree of the Government of the Russian Federation No. 1013 of 1997 “On approval of the list of works and services subject to mandatory certification.
2 types of drug certification:
Certificate of Conformity for Production - a document certifying, on the basis of the conclusion of a special commission, that the drug production system meets the established requirements. Issued by certification bodies: registration chamber, GNIISKLS. Expiration date - until the expiration date on the drug.
Certificate of conformity of drugs - a document that certifies the safety and compliance of the quality of drugs with the requirements of regulatory documents. Issued by certification bodies accredited by the Federal Service for Technological Regulation. Expiration date - while the product is being produced. This is where the registration certificate comes in.
Sampling for certification analysis is carried out from the manufacturer's warehouses. Sampling is carried out in accordance with the requirements of pharmacology XI ed. and in accordance with Order No. 383 of 2002.
To obtain a certificate of conformity, submit:
-registration certificate;
- a license for the right to sell drugs;
- an act of taking an average sample;
Report of the analysis of the control services of the manufacturer for domestic drugs, or a certificate of the manufacturer with an accurate translation for foreign drugs;
- protocol for the analysis of CAL.
The certificate of conformity has watermarks, w, barcode.
Certification of medical products, immunobiological preparations.
The documents:
1) Project No. 217 of 1998 Ministry of Health of the Russian Federation “On the hygienic assessment of the production, supply and sale of goods”
Etc. No. 274 of 1999 “On the procedure for registration of medical products. appointments and honey. technology."
For each item, a registration certificate is approved with a shelf life of 5 years, for metal and plastic inventory - 10 years.
Certificate of conformity. These documents are issued by the Federal Service for Technological Regulation and Metrology.
A hygienic certificate is also issued for hygienic products - this is a document that gives permission for the production, import and sale of products. Issued by the Federal Service for Supervision of Consumer Rights Protection and Human Welfare (Rospotreb.nadzor).
A certificate of conformity should be obtained: dressings, disposable syringes, rubber products.
Certification of immunobiological preparations. (UPS).
In accordance with the Federal Law “On Immunoprophylaxis of Infectious Diseases”, all domestic and foreign immunobiological preparations are subject to certification:
-certificate of the manufacturer for a specific series. Issued by the registration chamber and the GNII them. Tarasevich;
- certification certificate;
- certificate of conformity for a specific series of the drug. Issued by the GNII them. Tarasevich.
INTRODUCTION
Quality is a set of characteristics of an object related to its ability to satisfy stated and implied needs.
Ensuring the quality of medicines is the primary task of the state. This is required by the federal laws of the Russian Federation "On Medicines" and "On Protection of Consumer Rights".
To assess the technical level of production and quality of medicines, the World Health Organization (B03) (“World Health Organization” - WHO) created the “Certification System for the Quality of Pharmaceuticals in International Trade”, the current version of which was adopted in 1992.
- To participate in the System, three conditions must be met in the country:
-Regular state inspection of pharmaceutical enterprises;
- Compliance of existing production facilities with the requirements of 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, they became widespread throughout the world, with the exception of the Soviet Union.At the beginning of the 21st century, some Russian pharmaceutical companies improved their production processes and successfully passed GMP audits. The timing of the introduction of mandatory compliance of all Russian pharmaceuticals. enterprises GMP rules are constantly transposed. At the moment, there is no exact information on the number of pharmaceutical enterprises that have completely switched to work according to GMP. According to some reports, we are talking about 30 sites out of more than 400 enterprises.
Since 2009, negotiations have been underway on the accession of the Russian Federation to the international system of cooperation of GMP inspectorates and work has begun on preparations for entry. However, many enterprises are not focused on the introduction of GMP rules, but on further delaying the deadlines.
Separate speeches by representatives of relevant departments contain support for such a course. This does not take into account the fact that international GMP rules are rapidly evolving and becoming more complex. In this regard, further postponement of the transition to work under international GMP rules will not only not facilitate this transition, but, on the contrary, will make it difficult or even impossible. Under these conditions, vigorous measures are needed to explain the modern concept of GMP among the leaders and specialists of industry enterprises, as well as among employees of state authorities related to this problem.
An intermediate result of the discussion regarding the establishment of the requirements of GMP rules as mandatory in the manufacture of medicines can be considered the statement of the Minister of Health and Social Development Tatyana Golikova, made during a round table that took place in the State Duma on March 11, 2010: “January 1, 2014 - the final the date by which domestic producers must switch to the European quality standard. If the production does not comply with GMP requirements by January 1, 2014, the production license will cease to be valid.”
The purpose of the course work is to study the organization of quality control of medicines, the general requirements for the quality of medicines, the GMP system.
In the course of writing the course work, the following tasks were set and solved:
1. Examine the scientific literature and regulatory documentation on the issue of quality control of medicinal products; deepen theoretical knowledge on this topic;
2.Evaluate the current state of the topic.
3. To study the regulatory and legal regulation of quality control of medicines (state control bodies, regulatory documents);
4. Learn the GMP system . (Requirements for the production and quality control of medicines);
5. To study the organization of intra-pharmacy control (Quality indicators, types of control );
.
Main part
1. Legal regulation.
1.1. Bodies of state control over the quality of medicines.
The quality of medicines in Russia is controlled by the Federal Service for Supervision of Health and Social Development (Roszdravnadzor), subordinate to the Ministry of Health and Social Development of the Russian Federation. The quality control system for medicines and preparations is headed by the Department for State Control of the Efficacy and Safety of Medicines and Medical Equipment of the Ministry of Health and Social Development of Russia - the Scientific Center for Expertise and State Control.
In most large cities of Russia there are control laboratories and Centers for quality control of medicines. Their main task is to check the organizations selling medicines (observance of numerous norms for the storage and sale of medicines), as well as selective (and in some regions even total) control of medicines. Based on the data from the regional centers, Roszdravnadzor will make decisions on the rejection of a particular drug.
State regulation of relations arising in the field of state control of production, manufacture, quality, efficiency, safety of drugs is considered in Chapter II of the Law "On Medicines". The structure and functions of the state J1C quality, efficiency and safety control system are reflected in Chapter III of the federal law. The law establishes that all JTC, both produced in the Russian Federation and imported from abroad, are subject to state control.
The federal body authorized by the Government is independent and the only one in the Russian Federation that bears full responsibility for the implementation of state control over the quality, efficacy and safety of drugs in the Russian Federation. He can create territorial bodies in the subjects of the Russian Federation or transfer to them part of his powers to control the quality of medicines.
The federal body carries out an examination of the quality, efficacy and safety of all drugs, both manufactured and imported into the territory of the Russian Federation. He carries out their state registration, compiling the state register of drugs, approving the texts of the FS, compiling and publishing the Global Fund, compiling lists of drugs dispensed without a doctor's prescription, supervises pharmaceutical activities and the implementation by manufacturers of the rules for organizing production and controlling their quality, conducts certification and certification of specialists involved in the field of drug circulation, as well as other powers vested in him by the Government of the Russian Federation.
State control of drug production in the Russian Federation is carried out by federal and territorial drug quality control authorities. The federal body develops and approves the rules for organizing the production and quality control of medicines, inspects the activities of manufacturing enterprises, draws up a conclusion on the compliance of their activities with the approved rules. Territorial bodies (on behalf of the federal body) exercise similar control over the activities of manufacturing enterprises located on their territory. Federal and territorial authorities can take various measures to improve the quality of manufactured drugs, up to the prohibition of the sale of drugs that have already been 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 Russian Federation in the entire area of drug circulation, many of its provisions are directly related to the problems of ensuring the state system for monitoring the quality, safety and effectiveness of drugs. It should be noted that the law establishes the priority of state control over the 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", the Federal Law of 06.22.1998 N 86-FZ "On Medicines", the Regulation on the Ministry of Health of the Russian Federation, approved by the Decree of the Government of the Russian Federation of 03.06.1997 N 659 of the Ministry of Health of the Russian Federation, established by ORDER dated November 1, 2001 N 388 "ON STATE STANDARDS FOR THE QUALITY OF MEDICINES".
Product quality standardization refers to the process of establishing and applying standards. A standard is a standard or sample taken as a reference for comparing other similar objects with it. The standard as a normative document establishes a set of norms or requirements for the object of standardization. The application of standards contributes to the improvement of product quality.
The main task of standardization is to determine a unified system of product quality indicators, methods and means of its testing and control. This problem is solved by creating a system of normative documentation (ND), which defines the requirements for manufactured products, their production and use. Equally important is the control over the correct application of ND.
The following categories of RD are established in the Russian Federation:
-State standards (GOST),
-industry standards (OST),
- republican standards (RS.T)
- technical conditions (TU).
The standards for drugs are FS, TU that regulate their quality, as well as production regulations that normalize their technology.
FS - regulatory documents that define a set of quality standards and methods for their determination. These documents ensure the same efficacy and safety of drugs, as well as the constancy and uniformity of their production, regardless of the series. The main document that regulates the quality of drugs produced in our country is State Pharmacopoeia (GF). Regulatory documents reflecting additional technical requirements for the production, control, storage, labeling, packaging, transportation of drugs are industry standards (OSTs).
State Pharmacopoeia(GF) - a collection of mandatory national standards and regulations that regulate the quality of drugs. It is based on the principles of national health care and reflects modern achievements in the field of pharmacy, medicine, chemistry and other related sciences. Its requirements for drugs are mandatory for all enterprises and institutions that manufacture, store, control quality and use drugs (regardless of ownership and departmental subordination).
Issue. 1 SP XI includes 54 general articles on physical, physico-chemical, chemical methods of analysis and methods of analysis of medicinal plant materials. The "Introduction" to the release indicates all the changes that have been made to the general pharmacopoeial monographs, compared to SP X. There are sections containing the rules for using pharmacopoeial articles, units of measurement and abbreviations adopted in SP XI. For the first time, 10 articles and sections on such methods of analysis as gas chromatography, high performance liquid chromatography, method for determining the degree of whiteness of powdered drugs, phase solubility method, NMR spectroscopy, radioactivity, electrophoresis, emission and atomic absorption flame spectrometry, luminescence microscopy and determination of impurities of chemical elements in radiopharmaceuticals.
In 1990, the issue was published. 2 GFKh1, containing two sections: "General methods of analysis" and "Medicinal plant materials" (MP).
All these changes are preliminarily substantiated by in-depth research conducted at NIISKLS and other research institutes and educational pharmaceutical universities. The developed and approved new OFS and FS are the basis for the creation of GF XII.
Since June 2000, the industry standard "Rules for organizing the production and quality control of drugs" has been put into effect in Russia. This is a standard identical to the international SMP rules.
In addition to the specified standard, which ensures the production of high-quality drugs, a standard has been put into effect that normalizes the quality of drugs, regulates the procedure for creating new and improving existing regulatory documentation for drugs. It was approved by the Ministry of Health of the Russian Federation on November 1, 2001 (order No. 388), and is an industry standard OST 91500.05.001-00 “Quality standards for medicines. Basic Provisions. The previously valid standard OST 42-506-96 has lost its force.
The new OST provides for two categories of quality standards:
I. State standards for the quality of medicines (GSKLS), which include: general pharmacopoeial article (GPM) and pharmacopoeial article (FS);
II. Quality standard (SKLS); pharmacopoeial article of the enterprise (FSP).
The contents of these standards differ from each other.
OFS contains the main general requirements for the dosage form or a description of standard methods for drug control. The OFS includes a list of standardized indicators and test methods for a specific drug product or a description of drug analysis methods, requirements for reagents, titrated solutions, and indicators.
FS contains a mandatory list of indicators and methods for quality control of a medicinal product (taking into account its dosage form) that meet the requirements of leading foreign pharmacopoeias.
OFS and FS are developed and revised after 5 years by the Scientific Center for Expertise and State Control of Medicines, and for immunobiological preparations - by the National Control Authority of MIBP.
OFS and FS make up the State Pharmacopoeia (SP), 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 particular enterprise, taking into account the peculiarities of the technology of this enterprise and having passed the examination and registration in the prescribed manner. The FSP is being developed taking into account the requirements of the OST, GF and OFS. The validity period of the FSP is set 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 the standards of quality standards in the FSP and their compliance with the modern level of science and production is borne by the heads of the development institutions and manufacturing enterprises of this drug.
The organization-holder of the original OFS, FS, FSP is the Ministry of Health of the Russian Federation. The holder of the originals of the FSP is also the corresponding manufacturer or organization-developer.
- 2. The quality of medicines.
Pharmaceutical production is a complex technological process, and how carefully its many stages are worked out and carried out depends on which particular mixture of chemicals is contained in the serial package taken by the patient. Often, different stages of pharmaceutical production are performed at different enterprises - for example, the manufacture of a substance (or "active substance") - at one, and the manufacture of a finished dosage form - at another, which acts as a drug manufacturer.
High quality medicine means:
high chemical purity of the active substance (there are always impurities, the question is how many of them as a percentage of the total composition and whether any of them are harmful even in very small quantities);
exact correspondence of the content of the active substance to the declared one (for example, outdated equipment cannot ensure dosage accuracy in mass production or unscrupulous manufacturers can "save" on the content of the active substance and the therapeutic effect of the drug may decrease - which not only causes financial damage to consumers, but may simply be dangerous for health);
high quality and safety of "fillers" (most dosage forms consist not only of the active substance, but also of additional ingredients that serve for the correct introduction of the active substance into the body - the so-called "delivery mechanism");
packaging quality, compliance with the actual and declared production dates, correct transportation and storage (most chemicals transform over time, for example, decompose, volatilize, enter into chemical reactions from exposure to temperature, light, oxygen and atmospheric moisture, etc.);
2.1. GMP system.
The standards of the leading pharmaceutical companies exceed the state requirements for the quality of medicines.
In most developed countries of the world, pharmaceutical production is carried out in accordance with GMP (Good Manufacturing Practice) standards. Drug manufacturing companies undergo the GMP certification procedure, which consists in checking by independent authorized organizations the compliance of the company's production processes with GMP requirements. They are aimed at ensuring a high level of quality and safety of medicinal products and ensuring that the medicinal product is manufactured in accordance with its formula (composition), does not contain foreign inclusions, is properly labeled, packaged and retains its properties throughout the entire shelf life.
In our country, the GMP rules (“Rules for the organization of production and quality control of medicines” RD 64-125-91) were first developed in 1991, taking into account the international, regional and national rules of different countries that were in force at that time. In February 1998, a joint order of the Ministry of Health of Russia and the Ministry of Economy of Russia came into force on the introduction of the industry standard OST 42-510-98 "Rules for the organization of production and quality control of medicines", which established that from July 1, 2000, acceptance into operation again established and reconstructed manufacturing enterprises of medicines and pharmaceutical substances, the issuance of licenses to these enterprises for the production, storage and distribution of products is carried out only if they comply with the GMP standard in its Russian version.
The Russian GMP standard was prepared by the Association of Engineers for the Control of Micropollution (ASINCOM) and in 2004, by the Decree of the State Standard of Russia of March 10, 2004 No. 160-st, GOST R 52249-2004 "Rules for the production and quality control of medicines" was approved, which is harmonized with the GMP (Good Manufacturing Practice for medicinal products) of the European Union. The GMP certification system is being prepared for mandatory use in Russia.
Some Russian manufacturers have already brought some of their productions up to world quality standards and received GMP certificates confirming this fact. APPROVED by the Decree of the State Standard of Russia dated March 10, 2004 N 160-st Date of introduction - January 1, 2005
GMP rules establish requirements for the quality management system, quality control, personnel, premises and equipment, documentation, production and analysis of contracts, claims, product recall procedures and organization of self-inspections.
APPLICATION AREA
This International Standard specifies requirements for the manufacture and quality control of medicinal products for human and animal use.
The standard applies to all types of medicinal products and establishes general requirements for their production and quality control, as well as special requirements for the production of certain types of medicinal products.
The standard does not apply to ensuring industrial safety, fire safety, explosion safety, chemical safety and safety of other types in the production of medicines, the requirements for which are given in other regulatory documents.
2.1.1. Quality control
The quality assurance system (quality system) in the manufacture of medicines must ensure the following:
I. Medicinal products are developed taking into account the requirements of this standard and the requirements for the work of laboratories.
II. For all production and control operations, documentation has been developed in accordance with this standard.
III. The responsibilities and duties of all employees are clearly defined.
IV. Measures are in place to ensure that source and packaging materials are produced, supplied and used in accordance with specified requirements.
V. Control of intermediate products and the technological process (in-house control), certification (validation) of processes and equipment are carried out to the extent necessary.
VI. Production and control of finished products comply with approved instructions (methods).
VII. The sale of medicinal products prior to the issuance of a release permit by the Authorized Person is excluded. An authorized person must confirm that each batch of products is manufactured and tested in accordance with the established requirements.
VIII. The existing system of measures ensures the level of quality of medicinal products during their storage, shipment and subsequent handling throughout the entire shelf life.
IX. The procedure for conducting self-inspection and/or quality audits allows you to regularly evaluate the effectiveness of the quality assurance system.
2.1.2. Requirements for the production and quality control of medicines
This standard is part of a quality system and aims to provide assurance that the production and quality control of products consistently comply with the requirements established in the documentation.
Primary requirements:
I. All production processes should be clearly regulated and periodically reviewed in the light of experience gained. The stability of the production of drugs with a given quality in accordance with their specifications should be monitored.
II. Certification (validation) of critical stages of production processes should be carried out, including when significant changes are made to the technological process.
III. All necessary conditions should be provided to comply with the requirements of this standard, incl. including the presence of:
a) trained and certified personnel;
b) necessary premises and areas;
c) related equipment and service system;
d) materials, means of packaging and labeling that meet specified requirements;
e) approved instructions and procedures;
f) required storage and transport conditions.
IV. Instructions and procedures should be specific, set out clearly and unambiguously in writing.
V. Personnel must be trained to follow instructions correctly.
VI. During the production process, protocols should be drawn up (filled in handwritten form and / or using technical means) documenting the actual implementation of the technological stages provided for in the instructions and the receipt of products of the required quality in a quantity that meets established standards. All deviations must be investigated and recorded in full.
VII. Series protocols, incl. product sales documentation, must allow traceability of the production of each batch of products and must be kept in full in an accessible form.
VIII. The procedure for the sale (wholesale) of products should minimize any risk to its quality.
IX. A system should be in place to recall any batch of product from sale or supply.
X. Complaints about product quality should be carefully considered, and the causes of quality deterioration investigated and appropriate measures taken to prevent them.
2.1.3 Quality control
Quality control includes sampling, testing (analysis) and execution of relevant documentation. Instructions for organizing, documenting and issuing a permit for the release of products should include all necessary tests and prohibit the use of raw materials and materials and the sale of finished products until the quality is confirmed to meet the established requirements. The purpose of quality control is to prevent the use or sale of materials or products that do not meet quality requirements. The quality control service performs research, checks and participates in making any decisions regarding product quality. The fundamental principle of ensuring quality control is the independence of the quality control department.
Every pharmaceutical manufacturing facility should have a quality control department that is independent from other departments. The head of this department must have the necessary experience and qualifications. The quality control department includes one or more control laboratories. To perform its functions, the department must be provided with all the necessary resources.
The main responsibilities of the head of the quality control department are outlined above. The department is also responsible for the development, certification (validation), implementation of all instructions (methods) for quality control; storage of maternal controls.
2.1.3.1. Basic requirements for quality control
I. Availability of necessary premises and equipment, trained personnel, approved procedures for sampling, inspection and testing of starting and packaging materials, intermediate, bulk and finished products, environmental control, if necessary.
II. Carrying out sampling of initial and packaging materials, intermediate, bulk and finished products by certified personnel in accordance with the methods approved by the quality control department.
III. Testing by certified (validated) methods.
IV. Preparation of protocols (filled in by hand and/or using technical means) confirming that all necessary sampling, inspections and tests have actually been carried out, as well as recording any deviations and investigations in full.
V. Confirmation that the finished product contains active ingredients in terms of qualitative and quantitative composition, corresponding to the registration dossier, has the required purity, is properly packaged and labeled.
VI. Registration of protocols for checking raw materials and materials, intermediate, bulk and finished products, their analysis and comparison with specifications. Product evaluation includes the study of all necessary production documentation and analysis of deviations from established requirements.
VII. Obtaining permission to sell or supply any series of products only after confirmation by the Authorized Person of its compliance with the registration dossier.
VIII. Retention of a sufficient number of samples of raw materials and products for possible verification if necessary. Product samples should be kept in their final packaging.,
except for large packages.
2.1.3.2. Staff
The organization and functioning of the production and the quality assurance system of medicines depend on the personnel. The enterprise must be staffed with personnel of the required number and qualifications. Job responsibilities of each employee must be documented and learned by each employee. All employees must also be aware of the requirements of this standard (GMP Rules) related to their field of activity, and undergo initial and repeated training to the extent necessary, incl. according to the rules of personal hygiene.
- Key Responsibilities of a Production Manager:
II. Approval of instructions related to the production process and ensuring that they are followed accurately.
III. Control over the review and signing of all production protocols by persons with the necessary authority, before transferring them to the quality control service.
IV. Supervise the operation of his unit, the maintenance of premises, the operation and maintenance of equipment.
V. Control over the work on certification (validation).
VI. Organization of primary and subsequent training of production personnel
- Key Responsibilities of the Quality Assurance Manager.
II. Evaluation of protocols for a series of products.
III. Carrying out the necessary tests.
IV. Approval of specifications, sampling instructions, test procedures and other quality control procedures.
V. Admission to the work of analysts working under the contract, and control over their activities.
VI. Supervision of the work of the subordinate department, maintenance of its premises and equipment.
VII. Control of certification (validation).
VIII. Organization of primary and subsequent training of personnel of the subordinate department.
2.1.4. Documentation
Proper documentation is an important part of a quality assurance system. Clear documentation allows you to prevent errors that may occur during oral communication and trace all stages of the production of a particular product series. Specifications, industry regulations, instructions, procedures and protocols for a product series must be properly formatted and must not contain errors.
Document types:
specification: a document containing requirements for materials and products used or obtained in production, which is the basis for assessing the quality of medicinal products;
industrial regulations, technological instructions and packaging instructions (manufacturing formulae, processing and packaging instructions): documents defining all raw materials used and operations for the production and packaging of products;
instruction, methodology, procedure (procedure): a document containing instructions for performing certain types of operations (for example, cleaning, changing clothes, environmental control, sampling, testing, operating equipment);
protocol for a series (record): a document reflecting the progress of the production of each series of products, incl. permission for its implementation, and all factors affecting the quality of the finished product.
2.1.5 Production
To obtain products of the required quality, technological operations should be performed in accordance with the industrial regulations and relevant instructions, the requirements of this standard, regulatory documents and the registration dossier.
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, labeling, preparation, preparation, packaging and shipment) must be carried out according to written instructions or procedures and, if necessary, recorded.
3. All incoming materials must be checked for compliance with the order. Containers and packaging should be cleaned and labelled.
4. Facts of damage to containers and packaging, which may have a negative impact on the quality of materials, should be investigated and recorded, followed by a report to the quality control department.
5. Incoming materials and manufactured finished products must immediately be placed in quarantine, operating on the principle of separate storage or through organizational measures, and kept there until permission for use or shipment is received.
6. Acceptance of intermediate and bulk products is carried out according to the rules in force for starting materials.
7. All materials and products should be stored under appropriate conditions specified by the manufacturer, in a manner that ensures the segregation of product series and its circulation in the warehouse.
8. To ensure that there are no deviations beyond the permissible limits, it is necessary to ensure the control of the output of products and its quantitative comparison with the data of the industrial regulation.
9. Simultaneous or consecutive handling of different products in the same room is not allowed unless there is protection against the risk of mix-up or cross-contamination.
10. Products and materials must be protected from microbial and other types of contamination at all stages of production.
11. When working with dry materials and products, special precautions must be taken to prevent the formation and spread of dust, especially when working with potent and sensitizing substances.
12. In the course of the technological process, all materials, packages with bulk products, main equipment and premises must be marked (labeled) indicating the product or material being manufactured, its dosage (if necessary) and the batch number. If necessary, the stage of the technological process should be indicated.
13. Designations (marking) on the packaging, equipment or premises must be clear, unambiguous, of the established form. In addition to the use of letters, it is recommended to use color coding indicating the status of the product (for example, "Quarantine", "Accepted", "Rejected", "Clean", etc.).
14. The correct connection of pipelines and other equipment used to transport products from one area to another should be controlled.
15. Deviation from instructions is not allowed. If necessary, written permission to deviate from the instructions must be obtained from the competent persons and the quality control department.
16. Only personnel who have the right to access them can enter the production premises.
17. As a rule, the production of non-medical products is not allowed in the premises and equipment intended for the production of medicines.
2.1.5.2 Prevention of cross-contamination during production
18. The possibility of contamination of starting materials or products with other materials or products should be excluded. In the manufacturing process, the risk of accidental cross-contamination arises from the uncontrolled release of dust, gases, fumes, aerosols or microorganisms from materials (products) and from residual contamination on equipment and people's clothing. The degree of risk depends on the type of contamination and the product affected.
The most dangerous contaminants include sensitizers, biological preparations containing live microorganisms, certain hormones, cytotoxins, and other potent substances. Contamination of injectable preparations, as well as preparations intended to be taken in large doses and / or for a long time, is especially dangerous.
19. To prevent cross-contamination, the following technical and organizational measures should be provided:
a) production in dedicated areas (mandatory for penicillins, live vaccines, live bacterial preparations and some other biological products) or segregation of production runs over time, with appropriate cleaning of premises and equipment between runs;
b) organization of air locks and exhaust devices;
c) reducing the risk of pollution caused by recirculation or re-entry of untreated or insufficiently treated air;
d) storage of protective (special) clothing within production areas with a high risk of cross-contamination;
e) the use of highly effective cleaning and treatment methods to avoid insufficient cleaning, often a cause of cross-contamination;
f) use of "closed systems" production;
g) monitoring for residues of previous product or detergents and labeling equipment with cleanliness status.
20. The effectiveness of measures to prevent cross-contamination should be checked periodically in accordance with approved guidelines.
2.1.5.3. Attestation (validation)
21. Certification (validation) is aimed at improving the efficiency of work and is carried out in accordance with approved methods. Its results must be documented.
22. When approving a new industrial regulation or production method, their suitability for mass production should be checked. It must be verified that the process, materials and equipment used are capable of consistently producing products of the required quality.
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In recent years, state control of the circulation of pharmaceutical products has undergone significant changes. At the moment, more advanced drug research methods are being used. Specialized control and analytical laboratories help to carry out proper quality control of medicines.
The regulator of the law pays great attention to this, because the life and health of millions of citizens depend on it. The quality of pharmaceutical products is understood as the compliance of a pharmaceutical product with physical, chemical, biological and other characteristics and standards approved by the legislator. In most cases, the consumer cannot independently verify the good quality. Quality control of medicines is carried out in accordance with GOST.
History of offenses in the field of pharmaceuticals
Over the past 7-8 years, the number of measures to control the quality of medicines has increased significantly. The average increase in inspections was 35%. About 15% of all pharmaceutical products that are involved in circulation are supervised by representatives of Roszdravnadzor. Specialized methods and analyzes using advanced equipment make it possible to carry out the study of pharmaceutical products in the liquid and tablet state at the proper level.
In the course of state control of the quality of medicines, almost the same violations are revealed. They are mainly associated with violations of storage conditions and non-compliance with the requirements of GOST. All this poses a potential threat to the life and health of citizens. In fact, many pharmaceuticals do not have the desired pharmaceutical effect.
Tasks of Roszdravnadzor in the field of control and quality of medicines
According to the supreme supervisory authority, the guarantee of maintaining the quality of products sold is compliance with the pharmaceutical procedure, competent organization of intra-pharmacy control and compliance with the rules and terms of storage of pharmaceutical products. Pharmacies and medical institutions should ensure that preparations are adequately protected from light, exposure to moisture, high temperatures and the disinfectants used.
Audits in the field of the state drug quality control system
This year there has been a significant increase in inspections. This is due to the activation of the pharmaceutical segment, the liquidation of some pharmacies and the emergence of others. Despite the fact that more inspections have been carried out, it is not possible to properly exercise state control in the field of drug circulation. The problem lies in the modest human resource, because there are about a little more than 1,000 employees of the supervisory unit throughout the country.
- Licensed. They are a check of the company's activities for the availability of permits.
- Federal state supervision. It consists in checking documentation and pharmaceutical products.
- Selective quality control. These activities are carried out in accordance with 61 Federal Laws and current regulatory legal acts. During the serial sampling control, more than 7.5 million packages of pharmaceutical products that did not meet the quality were identified.
If quality problems are fixed in the course of verification activities in two batches in a row, then state control is mandatory, and pharmaceutical products are checked in the laboratory. All this makes it possible to exclude the introduction of low-quality pharmaceuticals into circulation.
Which divisions carry out quality control of the medicinal product?
- Department of State Quality Control of the Efficiency and Safety of Pharmaceutical Products.
- Committee for new medical technology, scientific centers for the examination of state supervision.
- Centers for certification of pharmaceutical products.
- Centralized laboratories that control the quality of drugs in a pharmacy.
Among the additional divisions, one can single out specialized institutions that are engaged in research activities in the field of pharmacy and the development of standards. Among all the main bodies, pharmacopoeial and pharmacopoeial state committees can also be distinguished. The leading role of supervisory authorities is the approval of relevant standards and control over their observance.
Legal regulation of drug quality control
- Federal Law No. 61 "On the circulation of pharmaceutical products".
- Legislative regulation "On consumer protection".
- Law on the rules of certification.
- Order of the supervisory authority on quality control of medicines.
- Legislative provision on licensing the production of pharmaceutical products.
Bodies and units in the field of supervision should be guided by the above laws and regulations. All medicinal products must comply with approved standards. These include the pharmacopoeial standard, which includes compliance with the requirements of approbation and evaluation of the quality of pharmaceutical products. Recently, adjustments have been made to the relevant order on quality control of medicines, as more and more new drugs based on synthetic components appear.
In 2017, the supreme supervisory authority received the right to carry out test purchases. This was done in order to properly monitor medicines by Roszdravnadzor.
Officials have the following powers:
- Receive responses to sent motivated written requests.
- Freely check buildings and structures.
- Perform sampling of pharmaceutical products.
- Send to the authorized bodies the necessary documentation related to violations of mandatory requirements.
Among the new powers, one can single out the possibility of conducting a test purchase. In this case, the supervisory authorities do not need to warn representatives of pharmaceutical companies and pharmacy institutions about the audit. Currently, the legislative framework affecting the procedure for conducting test purchases is still being worked out.
The public oversight sector has various means of verifying pharmaceutical products in its arsenal. They are mainly aimed at checking the quality and compliance with labeling requirements. Strengthening supervision by the state body is primarily aimed at realizing the rights of citizens and includes the provision of effective and safe therapeutic treatment using drugs.
So, in our country there is a huge system that oversees the safety of medicines, from the pharmacopoeial state committee to the central zonal laboratories. Improving the standardization of drugs and the implementation of proper supervision is the key to the introduction of high-quality and safe pharmaceutical products into circulation.