33.What is the State Pharmacopoeia, general and private pharmacopoeial articles.

Pharmacopoeia(from the other gr. φαρμακον - medicine, poison, and other gr. ποιη - I make, I manufacture) - a collection of official documents (a set of standards and regulations) establishing quality standards for medicinal raw materials - medical substances, excipients, diagnostic and medicinal products and preparations made from them.

The provisions of the pharmacopoeia are based on the achievements of pharmaceutical chemistry and its pharmaceutical analysis, its criteria, methods and methods. This document includes instructions for the manufacture and quality control of drugs. Determines the highest doses of drugs and establishes requirements for medicinal raw materials. Compliance with the stated standards and requirements of the Pharmacopoeia in combination with compliance with the requirements of the GMP standard ensures the proper quality of medicinal substances and preparations.

State Pharmacopoeia - pharmacopoeia under state supervision. The State Pharmacopoeia is a document of national legislative force; its requirements are mandatory for all organizations of a given state involved in the manufacture, storage and use of medicines, including herbal ones.

It contains:

descriptions of methods of chemical, physicochemical and biological analyzes of medicines,

information about the reagents and indicators required for this,

descriptions of articles on individual medicinal substances and medicinal products,

lists of poisonous (list A) and potent (list B) drugs,

tables of highest single and daily doses for adults and children.

The first Pharmacopoeia of Russia (“Pharmacopoea Rossica”) was published in 1778.

In subsequent years, the following editions of the Pharmacopoeia were published in Russian: the second in 1871, the third - 1880, the fourth - 1891, the fifth - 1902, the sixth - 1910, the seventh - 1925, the eighth - 1946, the ninth - 1961, the tenth - 1968, the eleventh - 1987 (first issue) and 1990 - (second issue).

Part 1 of the “State Pharmacopoeia of the Russian Federation XII edition” was released in February 2008, and has been put into effect since 2009. Now work continues on the release of the second part.

The compilation, addition and republication of the Pharmacopoeia was previously carried out by the Pharmacopoeia Committee. Currently, the Pharmacopoeia is being prepared by an editorial board, which includes representatives of the Ministry of Health and Social Development, Roszdravnadzor, Roszdrav, FFOMS and leading Russian scientists.

Pharmacopoeial monograph (FS)- this is a regulatory and technical document that establishes requirements for the quality of a medicinal product or medicinal plant raw materials, its packaging, conditions and shelf life, quality control methods, approved by the authorized federal executive body and having the nature of a state standard.

The pharmacopoeial monograph contains: the name of the medicinal plant raw material in both Russian and Latin (in this case, the Latin name of the medicinal raw material serves as an international name)

Pharmacopoeial monographs (types):

Pharmacopoeial monograph of the enterprise (FSP):

This is a quality standard for a medicinal product under a trade name, contains a list of methods and indicators for quality control of a medicinal product produced by a specific enterprise, takes into account the specific technology of this enterprise, which has been examined and registered in the prescribed manner in accordance with the State Pharmacopoeia, pharmacopoeial articles of these standards, and these quality indicators , must not be lower than the requirements found in the State Pharmacopoeia.

The validity period of a pharmacopoeial article (pharmaceutical article) of an enterprise is established upon its approval for no more than 5 years, taking into account the level of the technological process of a specific production of a medicinal product.

General pharmacopoeial monograph (GPM):

This is a state standard for the quality of medicinal products, containing the basic requirements for the dosage form, as well as a description of standard methods for quality control of medicinal products. The general pharmacopoeial article includes: a list of standardized indicators and test methods for a specific dosage form, a description of chemical, physical, physicochemical, biological, biochemical, microbiological methods for analyzing drugs, this also includes requirements for the titrated solutions, reagents, and indicators used.

The pharmacopoeial monograph, general pharmacopoeial monograph and pharmacopoeial monograph of the enterprise are approved by the head of the Department, and then registered with an organization authorized by the Ministry of Health of the Russian Federation, with the obligatory assignment of a designation.

Private pharmacopoeial monograph (PPS):

This is a regulatory and technical document regulating the quality and safety of a medicinal product; a private pharmacopoeial monograph is created for the medicinal product under an international nonproprietary name (if it exists, or under a name that replaces it in a mandatory established manner; this also includes a list of standardized indicators and methods testing of this drug, as well as links to general pharmacopoeial monographs.

Temporary pharmacopoeial monograph:

– this is a regulatory and technical document approved for the period of development of industrial production of a medicinal product and for developing industrial technology of methods for determining the quality or indicators of a new medicinal product for a period of no more than 3 years.

Structure of a pharmacopoeial monograph:

Introductory part. The introductory part (preamble) states:

The time of collection of raw materials (vegetation phase, sometimes a calendar period) and the characteristics of the raw materials according to the mode of their technological processing are necessarily given:

Dried, threshed, freshly harvested, freshly frozen, etc.;

Wild or cultivated plant;

His life form;

Name of the producing plant and family in Russian and Latin.

External signs. The most important indicator of the authenticity and purity of raw materials. This section states:

Composition of raw materials;

Characteristic diagnostic signs, characteristic smell and taste (for non-poisonous species), dimensions of raw materials.

Microscopy. The most important method for determining the authenticity of medicinal raw materials. Section contains:

Diagnostic signs of the anatomical structure of raw materials (fluorescent microscopy is provided for some species);

Type of microslide on which the study is carried out.

Qualitative reactions. The section provides the actual qualitative, histochemical reactions, or chromatographic authenticity tests, for the main groups of active substances, the methodology for their implementation and the results.

Numerical indicators. The section includes specific indicators and their standards:

For whole, cut or powdered raw materials, which are the standard for all types of medicinal plant raw materials and determine its quality;

Quantitation. A method is given for the quantitative determination of the main active substances in the form of total content, in terms of any substance contained in a given raw material. If an individual substance is isolated (for example, platiphylline, etc.), the content of this particular component in the raw material is normalized. If the method of quantitative analysis is set out in the SP XI issue I, then a link to it is provided in the private pharmacopoeial monograph.

Package. The types of packaging and the mass of raw materials per packaging unit are indicated.

Microbiological purity. Method for determining microorganisms and their permissible limits.

Marking. Provided in accordance with the requirements for graphic design of medicines.

Transportation. If necessary, requirements for loading, unloading of products, and handling after transportation are indicated.

Storage. The storage conditions for products are indicated, including requirements for protecting products from the influence of climatic factors.

Best before date. The time during which medicinal raw materials can be used.

Pharmachologic effect. Pharmacological group to which medicinal raw materials are assigned.

34. Basics for ointments, classification and characteristics

Ointment This is a soft dosage form intended for application to the skin, wounds, mucous membranes, consisting of an ointment base and medicinal substances distributed in it.

Requirements for ointments:

1.must have a soft consistency, ensuring ease of application to the skin and mucous membranes

2.maximum dispersion of the leukin and their uniform distribution throughout the ointment (uniformity)

3.storage stability

4.absence of mechanical inclusions

5.should not change its composition during storage and use

6.should not delaminate during storage

7.should not be toxic or allergenic to the skin

8. for eye ointments, for introduction into the body cavity, for newborns, with antibiotics - sterility

9.absence of negative interactions between drugs and excipients

The ointment contains:

1. ointment base (lanolin, petroleum jelly)

2. lek. Ingredients (zinc oxide, sulfur, dermatol, novocaine, protargol, anesthesin, menthol, camphor, furatsilin, sulfacylamides)

Classification of ointments:

1. composition: a) simple

B) complex

2. by the nature of the action:

A) superficial

B) deep

3.at destination:

A) ocular

B) for the nose, etc.

4.consistency:

A) liniment (medicinal form for external use, which is a thick, liquid or gelatinous mass that dissolves at body temperature. From a physicochemical point of view, it is a dispersion system with varying degrees of dispersion and homogeneity)

B) paste (ointments with a powder percentage of 25 or more, suspension and combined types, more difficult to spread, but last longer and stay on the skin)

5.by type of disperse system:

A) homogeneous (single-phase) ointments-alloys (a combination of mutually soluble fusible components), ointment solutions (formed by substances soluble in the base - if the base is petroleum jelly, then homogeneous ointments are formed by: camphor, menthol, phenol), extraction (obtained by extraction with oils raw materials of plant/animal origin))

B) heterogeneous (two-phase) ointments-suspensions (the main task in preparation is to grind the solid substance as finely as possible), ointments-emulsions (containing drugs, soluble in water, but insoluble in the base (protargol, novocaine, collargol, ephedrine hydrochloride), aqueous solutions of drugs and pharmacopoeial liquids (Adrenaline solution, liquid Burov), viscous liquids (ichthyol, tar), combined (contain substances that form different types of ointments, but such an ointment is prepared in one mortar!) )

Most often, combination ointments are prepared in pharmacies.

Concept and characteristics of pharmacopoeia. Structure of a pharmacopoeial monograph. GP quality control requirements. Main types of standard samples. History of domestic pharmacopoeias. State Pharmacopoeia X and XI. Pharmacopoeia of the Russian Federation and the USA.

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Chapter 1. Concept and characteristics of pharmacopoeia

1.1 Definition of pharmacopoeia

The State Pharmacopoeia is the main document regulating pharmaceutical analysis.

Pharmacopoeia (pharmakopiea)- a Greek word containing two roots: Pharmakon- medicine and poieo- I do (the art of preparing medicines).

Pharmacopoeia- this is an official guide for pharmacists (pharmacists), containing a description of the properties, authentication and quality testing, and storage conditions.

The Pharmacopoeia contains mandatory national standards and regulations that regulate the quality of medicines.

The GF consists of general pharmacopoeial monographs (GPM) and pharmacopoeial monographs (FS).

General pharmacopoeial monograph- This is the State Quality Standard for Medicines, containing the basic requirements for the dosage form and/or a description of standard methods for quality control of medicines. The General Pharmacopoeia Monograph includes a list of standardized indicators or test methods for a specific dosage form, a description of physical, physicochemical, chemical, biochemical, biological, microbiological methods for analyzing drugs, requirements for the reagents used, titrated solutions, and indicators.

Pharmacopoeial monograph- this is the State quality standard for drugs under the international nonproprietary name (INN), which is given by the World Health Organization (WHO) for single-component drugs (if available), containing a mandatory list of indicators and quality control methods (taking into account its dosage form) that meet the requirements of leading foreign pharmacopoeias.

General pharmacopoeial monographs and pharmacopoeial monographs must be revised by the Scientific Center for Expertise and State Control of Medicines of the Russian Ministry of Health at least every five years.

Pharmacopoeial monograph of the enterprise- a quality standard for a medicinal product under a trade name, containing a list of indicators and methods for quality control of drugs produced by a specific enterprise, taking into account the specific technology of this enterprise, and has been examined and registered in the prescribed manner.

1.2 Structure of a pharmacopoeial monograph

The structure of a pharmacopoeial monograph for a substance includes the name of the substance in Russian and the chemical name in accordance with IUPAC rules. Below and in the center is the structural formula. In the empirical formula, carbon is written first, then hydrogen, and then all the elements in alphabetical order. If the relative molecular weight of the drug exceeds 400 amu, then it is indicated to the first decimal place, and if less, then to the second. The content of the main active ingredient is indicated in mass fractions, percentages or units of action (antibiotics). The following describes the nature of the drug and its physicochemical properties.

The “Description” section usually provides indicators of the drug’s appearance: its physical state (aggregate - amorphous or crystalline), shape and size of crystals, color, smell. Hygroscopicity and possible changes when stored in air or light are indicated.

The “Solubility” section indicates solubility in water, 95% ethanol, chloroform, ether and other solvents.

In the GF for most drugs, solubility is indicated in conventional terms:

The indicators given in the left column are very arbitrary. No matter how hard the drug researcher tries to remember all the given categories of solubility, in the end he will still have to turn to the classical quantitative (physicochemical) characteristic of solubility. Solubility usually means the concentration of a saturated solution of a substance at a certain temperature. In chemistry, the following solubility characteristics are used: soluble (more than 1 g in 100 g of solvent), slightly soluble (solubility from 1 mg to 1 g in 100 g of solvent), insoluble (solubility less than 1 mg in 100 g of solvent). The Pharmacopoeia considers seven solubility positions.

In the “Authenticity” section, the characteristics of UV and IR absorption spectra or other methods are indicated, as well as 2 - 3 chemical reactions that are most specific for a given drug.

When determining authenticity using chemical color reactions, group or specific reagents can be used. General (group) authenticity reactions can be used, for example, in the detection of aromatic amino compounds with the formation of aniline dyes.

A particular (specific) reaction to authenticity, for example, the determination of sodium ions in sodium chloride, is carried out by qualitative reactions to the presence of sodium ion - with zinccuranyl acetate or by flame color.

Temperature limits for distillation, melting and solidification temperatures, as well as density, specific rotation, specific absorption index, refractive index and other physical constants can be used as indicators of the authenticity and purity of a drug.

The section “Foreign (specific) impurities” provides detection methods and acceptable standards for technological impurities or impurities formed during storage. When using chromatography to detect impurities, indicate the type of sorbent, phase composition, amount of the test substance, development reagent and other chromatographic conditions.

Sources of impurities in medicinal products are varied. There are two types of impurities. “Hereditary” impurities enter drugs from poorly purified reagents, solvents, equipment materials, and excipients. For example, the preparation “Boric acid” may contain impurities of chlorides, sulfates, heavy metals, calcium, iron, arsenic, and borax. “Acquired” impurities are formed when storage conditions are not observed (for example, quinone impurity during the oxidation of phenol in the light). Impurities contained in a drug should not affect its physical, chemical properties and pharmacological activity.

An approximate (within certain limits) assessment of the content of some permissible impurities is carried out using standard solutions.

Reference method is based on the observation, under identical conditions, of the color or turbidity that occurs under the influence of any reagent on the test substance in comparison with a standard solution. The standard is a standard sample containing a certain amount of the impurity being determined. The presence of impurities is determined visually, by photocolorimetric or nephelometric methods. To do this, compare the results of reactions in the standard solution and in the drug solution after adding equal amounts of the corresponding reagents.

For example, for chloride tests, a reference solution is prepared by mixing solutions of sodium chloride and silver nitrate. A standard solution for sulfate ion is prepared by mixing barium chloride and potassium sulfate.

Many private articles of the Global Fund recommend the use of a reference method for determining impurities of organic substances. As a result of dehydration or oxidation under the action of sulfuric acid, colored products are formed. The intensity of the resulting color should not exceed the color intensity of the corresponding color standard.

Standards for determining the color of liquids are prepared from salts of cobalt(II), chromium(VI), copper(II) and iron(III). In this case, standard solutions of brown, yellow, pink and green shades are obtained. The color is observed on a white background.

To determine transparency, the liquid is viewed at an angle of 90° to the direction of the incident light (maximum light scattering according to Rayleigh's law). The test and reference solutions are placed in front of a black screen in comparison with the solvent. The standards for determining the degree of turbidity are suspensions obtained by mixing solutions of hydrazine sulfate and hexamethylenetetramine.

When performing purity tests, the general instructions provided by the Pharmacopoeia must be strictly followed. The water and reagents used must not contain detectable ions; the test tubes must be of the same diameter and colorless; the sample is taken with an accuracy of 0.001 g; reagents are added simultaneously and in equal quantities to the standard and test solutions.

It should be borne in mind that, unlike analytical chemistry, drugs are classified depending on the degree of purity not as “pure” (Pure), “pure for analysis” (analytical grade), “chemically pure” (CP) and “extra pure” ( Pure purity grade), but as substances of “pharmacopoeial quality”.

The section “Residual organic solvents” provides the results of determining the residual amounts of solvents if they were used in the drug manufacturing process.

In the sections “Chlorides”, “Sulfates”, “Sulfate ash and heavy metals” the permissible limits of these impurities are indicated, in the section “Arsenic” the permissible limits or requirements for the absence of arsenic are indicated.

The sections “Weight loss on drying” and “Water” indicate drying conditions, rates of weight loss on drying or moisture content.

One of the quality criteria is consistency of composition PM.

The drug can hydrolyze in the presence of moisture and when heated:

In this case, the composition of the drug changes. Irreversible changes in composition also occur during weathering - loss of crystallization water. In addition, the properties of drugs change when carbon dioxide is absorbed from the air.

The sections “Toxicity”, “Pyrogenicity”, “Content of substances with histamine-like action” indicate test doses, methods of administration, and period for observing the effect.

The section “Microbiological purity” describes the method for determining microorganisms and the permissible limits for their content.

The “Quantitative Determination” section provides a description of the method(s) for quantitative determination of the main substance contained in the drug, its mass fraction as a percentage or activity in units of action per milligram (IU/mg) when converted to the active substance.

This is followed by the sections “Packaging”, “Labelling”, “Transportation” and “Storage”. The last of the listed sections indicates the storage conditions that ensure the safety of the drug, the shelf life, and notes the storage features for drugs classified as poisonous, potent, psychotropic, and narcotic drugs.

The “Application” section contains information about the dosage forms of the drug, methods of administration and dosage.

1.3 Quality control requirements G.P.

All economically developed countries carry out pharmaceutical activities in accordance with GP (Good Practice) criteria. These rules have been applied in the USA since 1963 and relate to both production (GMP - Good Manufacturing Practice) and requirements for laboratory and clinical research or educational activities - GLP, GCP, GEP - (Laboratory, Clinical, Education respectively). The WHO certification system, based on GMP rules, is recognized in 140 countries around the world.

Thus, during the period of rapid development of the pharmaceutical industry, problems arose in the quality of finished medicines that could not be solved only by strengthening pharmacopoeial analysis. Ensuring the quality of drugs became possible only on the basis of GMP rules. The reason for their introduction was the use of thalidomide, a hypnotic with a teratogenic effect (congenital deformities).

In our time, the production of reproduced (generic) drugs, which required specific approaches to quality control, began to rapidly develop. Currently, the quality of finished drugs is determined not only by pharmacopoeial requirements, as was the case in the era of herbal medicines, but also by such pharmacokinetic characteristics as bioavailability and bioequivalence.

According to the GMP rules, the entire process of drug production, including premises, personnel, and documentation, becomes the object of control.

Good quality control practices for pharmaceuticals are ensured by a set of activities during their development and research, taking into account the requirements of not only GMP, but also GLP and GCP. Quality control includes quality control of raw materials, intermediate products, medicinal substances and finished dosage forms.

Each technique must contain a justification for its advantages in comparison with others in the form of presented comparative results of its application (validation).

Method validation includes the following metrological characteristics:

right(accuracy) - the closeness of the results to the true value, which can be carried out by comparison with the results obtained using another previously validated method;

accuracy(precision) - consistency between individual test results (deviation of individual results from the average value - relative standard deviation);

convergence(repeatability) - the accuracy of a technique when performed by the same analyst under the same conditions (reagents, equipment, laboratory);

reproducibility(reproducibility) - the accuracy of a technique when used under different conditions for identical samples taken from the same homogeneous series of material (different laboratories, performers, equipment, time).

reliability(robustness) - the ability of a technique to provide analytical results with acceptable accuracy and precision when operating conditions change for supposedly identical samples from the same homogeneous series of material;

sensitivity(sensitivity) - the ability of a test procedure to detect small changes in concentration (slope of the calibration curve);

detection limit(limit of detection) - the lowest content at which the analyte can be detected.

There is ongoing debate about the role of metrology in testing drugs at the preclinical and clinical levels, and in describing the effects of related substances in a drug, such as optical isomers. In the pharmacopoeial monograph, in the description of these tests, it is necessary to indicate the number of experiments during the analysis.

The issue of analytical reference materials (RMs) does not lose its relevance.

Main types of CO:

official СО - pharmacopoeial standard (state standard sample - GSO). This is a special series (batch) of a medicinal substance prepared in a certain way. GSO can be produced either by independent synthesis or using additional purification of the resulting substance. The reliability of a high degree of purity is established by analytical tests. Such a substance becomes the basis for creating a working standard sample;

working standard sample (RO) - a medicinal substance of established quality and purity, obtained with the help of a basic standard and used as a standard substance in the analysis of certain batches, new medicinal substances and new medicinal products.

Standardization of drugs at the international level (to establish uniformity in nomenclature, research methods, assessment of the quality of drugs, dosage of substances) is carried out by the United Nations World Health Organization (UN WHO), with the participation of which the publication of the International Pharmacopoeia was carried out.

Chapter 2. Pharmacopoeia of the USSR

2.1 History of domestic pharmacopoeias

The history of the creation of the first Russian pharmacopoeias begins in the second half of the 18th century.

In 1765, the Military Pharmacopoeia was published for the first time in Russia, and in 1778 the first official Russian State Pharmacopoeia was published.

The latter contained description 770 LP mineral, vegetable And animal origin, as well as multicomponent dosage forms.

In 1798, the second State Russian Pharmacopoeia was published, published, like the first, in Latin (translated into Russian in 1802).

After 1798, Military Pharmacopoeias (1808, 1812, 1818, 1840), Marine Pharmacopoeia (1864), Pharmacopoeias for the Poor (1807, 1829, 1845, 1860) and Court Pharmacopoeias (1825, 1872) were published in Russia. , 1874).

Each of the pharmacopoeias was a reflection of the level of development of pharmaceutical analysis. The first and second Russian pharmacopoeias recommended mainly organoleptic research methods (determination of color, smell, taste) and provided a description of the most important properties of drugs.

The publication in 1866 of a new edition of the Russian Pharmacopoeia was a historical milestone in the development of domestic pharmacy. This pharmacopoeia included 906 articles that described minerals, alkaloids, glycosides, plant materials, and finished drugs. A feature of the new pharmacopoeia was the inclusion in it, along with organoleptic chemical methods of drug control. The Pharmacopoeia of 1866 contains a list of potent drugs and the rules for their storage.

The Pharmacopoeia of 1866 became the first edition of the Russian Pharmacopoeia. Then II, III, IV, V, VI editions were published in 1871, 1880, 1891, 1902 and 1910, respectively.

The first edition of the Soviet pharmacopoeia, called the VII edition of the State Pharmacopoeia of the USSR (GP VII), was put into effect in July 1926. This pharmacopoeia differed from previous editions by its increased scientific level, the desire for the possible replacement of drugs made from imported raw materials with domestically produced drugs . GF VII included 116 articles on new drugs and excluded 112 articles. Significant changes have been made to the requirements for drug quality control. Instead of organoleptic control, a number of new methods of chemical and biological standardization of drugs were provided, 30 general articles were included in the form of appendices, descriptions of some general reactions used to determine the quality of drugs were provided, etc. Thus, in Global Fund VII, primary attention was paid to improving drug quality control. This principle was further developed in subsequent editions of the pharmacopoeia.

In 1949, the VIII edition was published, and in October 1961, the IX edition of the State Pharmacopoeia of the USSR was published.

The X edition of the State Pharmacopoeia (SP X) came into force on July 1, 1969. It reflected the new successes of domestic pharmaceutical and medical science and industry.

The fundamental difference between GF IX and GF X is the transition to new international drug terminology, as well as a significant update (by 30%) of its nomenclature. In GF X, the requirements for the quality of JIC have been significantly increased, and the scope of application of physicochemical methods has been expanded.

2.2 State Pharmacopoeia X

The tenth edition of the State Pharmacopoeia (GF X) contains an introductory part, two main parts and “Appendices”.

The first part - “Drugs” - includes individual articles that define the quality requirements for individual medicines, and group articles (tablets, injection solutions, extracts, herbs, tinctures, etc.).

The second part of the Pharmacopoeia contains a description of physicochemical, chemical, pharmacological and biological research methods, as well as reagents, titrated solutions and indicators.

The “Appendices” section contains tables of atomic weights, alcoholometric tables, drop tables, etc., as well as the highest single and daily doses of poisonous and potent drugs for adults and children and single, most commonly used doses of drugs for animals.

The tenth edition of the State Pharmacopoeia has a number of differences from the previous, IX edition.

The tenth edition of the State Pharmacopoeia contains 707 individual articles (in GF IX - 754) for various drugs and 31 group articles (in GF IX - 27).

219 private articles and 4 group articles were again included in Global Fund X; 235 articles contained in Global Fund IX are not included. The list of these articles is given on pages 23-25. 28 articles on vaccines and serums used in veterinary medicine were also excluded.

The requirements of GF IX for alcohols 90°, 70° and 40° are combined into one article, as well as the requirements for purified and precipitated sulfur.

The nomenclature of articles of the Global Fund X reflects the successes achieved in the creation and introduction of drugs into medical practice.

Global Fund X includes new synthetic drugs of various therapeutic groups: antibiotics, vitamins, hormones and other drugs. Outdated drugs that have been discontinued are excluded from the list. Also not included in the nomenclature are a number of drugs that have not been discontinued, but have limited use, and the quality of which does not differ from the requirements of the IX edition of the State Pharmacopoeia.

The quality of medicinal products not included in the State Fund X, but produced by industry, must be checked according to the relevant articles of the State Fund IX or the Inter-Republican Technical Specifications (MRTU 42).

GF X does not include tablets of complex composition (containing more than one active ingredient).

The articles in the “Drugs” section are placed in alphabetical order in accordance with their Latin names, with the exception of articles on dosage forms (injection solutions, tablets, ointments), which in this edition are placed after the article on the original medicinal substance.

The following sequence of titles is adopted in the headings of articles:

a) Latin name;

b) Russian name, which is an exact translation of the Latin name; in exceptional cases, names are given that deviate from the exact translation, but are generally accepted in the USSR;

c) synonyms: first - the main Latin and Russian synonyms used in the USSR, then the international Latin non-proprietary names recommended by the World Health Organization (WHO), if they do not coincide with the main Latin name of the Global Fund X.

International names are indicated by the symbol * and left without Russian translation.

In development of the nomenclatural principles laid down in the Global Fund IX, in the X edition of the Global Fund, the Latin chemical name is given as the official name in the headings of articles in accordance with the principles recommended by WHO. Latin names, which were the main ones in GF IX, are included in the X edition of the State Pharmacopoeia as synonyms and are printed in bold below and to the left of the main Russian name. For the duration of the Global Fund X, these synonyms can be used by doctors when prescribing medications along with the main Latin names.

For ease of use of the Pharmacopoeia and the alphabetical index and the greatest correspondence between Latin and Russian chemical names in the headings of articles, the Russian name of the cation is placed first (for example, potassium bromide, sodium sulfate). In the alphabetical index, Russian chemical names are given starting with both the cation and the anion.

The main source of botanical names of species, genera and families given in the Global Fund X is, with rare exceptions, “Flora of the USSR”. In the names of pharmacognostic objects, as a rule, the rooted traditional names of plants are retained, even if they differ from the botanical names adopted in the “Flora of the USSR”.

Latin and Russian names of plant materials are given in the singular, except for “flowers” - Flores, since this term means not only single flowers, but also inflorescences.

Russian names are adopted for reagents.

In order to achieve uniformity and consistency between individual groups of drugs, GF X introduced changes in the rational names and structural images (formulas) of drugs.

For salts of organic bases, the expanded name of the base in the genitive case is written in the first place, and the acid or acid radical in the nominative case is written in the second place.

The nomenclature of sulfonamide drugs remains the same as in SP IX, which corresponds to the generally accepted names of this class of compounds in the domestic chemical literature.

For gross formulas, the international system is adopted: carbon is written first, hydrogen second, the following elements, including metals, are arranged in alphabetical order.

Derivatives of acid radicals are depicted in detail.

The formulas of alkaloids, antibiotics, steroids and glycosides are depicted in planar form, but with a configurative designation.

For ease of use of the Pharmacopoeia, the structure of the articles in the new edition has been slightly changed (with the exception of articles on medicinal plant materials).

The “Properties” section has been replaced with 2 sections: “Description” and “Solubility”.

Due to the inclusion of a general article containing authenticity reactions for 25 ions and functional groups, a link to this article is provided for many drugs in specific articles. Some reactions to authenticity have been unified or replaced by new, more specific ones.

The “purity test” is divided into separate sections (chlorides, sulfates, etc.).

Instead of the two methods of quantitative determination that were available in a number of articles of the Global Fund IX, the new edition, as a rule, provides one method. In some cases, when GF X contains two methods and there are no special instructions, both methods are mandatory.

In GF X, the requirements for the quality of medicinal products have been increased in relation to both testing for purity and the quantitative content of the substance in the drug.

Many analysis methods available in GF IX have been clarified, changed and improved, and a number of new methods have been included.

For the first time, the following articles on methods of analysis are included in the Pharmacopoeia."

"General Reactions to Authenticity"

"Method of combustion in oxygen"

"Spectrophotometry in the infrared region" as a section of the article "Definitions based on measurements of light absorption",

"Fluorometry"

"Polarography"

"Nitritometry"

“Chromatography in a thin layer of sorbent” as a section of the article “Chromatography”

The articles have been revised and significantly changed: “Determination of arsenic”, “Determination of transparency and degree of turbidity of liquids”, “Determination of the color of liquids”, “Determination of density”, “Determination of melting point”, “Determinations based on measurement of light absorption”.

The articles have been updated: “Determination of the viscosity of liquids”, “Determination of the refractive index (refractometry)”, “Determination of optical rotation (polarimetry)”, “Determination of pH”, “Potentometric titration”, “Titration in non-aqueous solvents”, “Complexometric titration” , "Chromatography", "iodine number". The sections “Reagents” and “Indicators” have been expanded.

The use of new methods along with previously used methods for qualitative and quantitative testing of various drugs is envisaged.

The increased use of physicochemical methods of analysis has necessitated the development of reference materials for comparison. Therefore, the X edition of the Pharmacopoeia includes a general article “Reference Standards”, which provides the basic requirements for the quality of reference materials, which are approved by the Pharmacopoeial Committee of the USSR Ministry of Health in the form of MRTU 42 and are not included in the Pharmacopoeia. These requirements are based on the quality of existing international reference standards developed by the World Health Organization.

The new edition of the Pharmacopoeia clarifies and increases the quality requirements for a number of finished dosage forms.

New general articles have been introduced: “Eye drops” and “Granules”.

The rate at which tablets disintegrate has been changed from 10 to 15 minutes. The general article “Tablets” has been supplemented with requirements for enteric tablets. For coated tablets, separate articles indicate the weight of the tablet before coating.

For tablets, dragees, capsules and pills, a unified method for determining disintegration time is indicated.

The title of article GF IX “Dosage forms for injections” was changed to “Dosage forms for injections” and the names of private articles were changed accordingly.

For the articles “Dosage forms for injections” and “Eye drops”, a table of isotonic equivalents of medicinal substances for sodium chloride has been compiled, which is included in the “Appendices” section.

The article “Infusions and decoctions” is supplemented with a table of water absorption coefficients for various types of plant materials.

The article “Suppositories” includes a method for determining the complete deformation of suppositories.

In the article “Grinding and Sifting” the numbering of sieves is left in accordance with state standards.

In GF X, the articles “Techniques of microscopic research” and “Taking an average sample of plant materials” were significantly revised.

The general article on determining the biological activity of antibiotics has been clarified and expanded.

The new, X edition of the State Pharmacopoeia includes articles on some new endocrine drugs. To improve the quality of endocrine drugs, additional physical and chemical indicators have been included in a number of private articles.

Methods for determining the biological activity of insulin and assessing the duration of the effect of long-acting insulin preparations have been reworked. All methods require a mandatory comparison of the activity of the test and standard drugs and statistical processing of the data obtained.

Significant changes have been made to general articles that outline methods for determining the biological activity of endocrine drugs.

The article “Metopes for the analysis of bacterial preparations” was introduced for the first time in the Global Fund X.

Additionally, group-wide articles “Bacterial and Viral Allergens” and “Anatoxins” were included, and a number of new articles on serum-vaccine preparations were introduced. When compiling pharmacopoeial monographs, the requirements contained in the Inter-Republican Technical Specifications for these drugs, approved in 1960-1967, were taken into account. Ministry of Health of the USSR.

For the first time, GF X includes a section outlining methods of chemical analysis used to control vaccines, serums and toxoids.

The article “Biological methods for assessing the activity of medicinal plants and drugs containing cardiac glycosides” includes an additional section “Method of biological evaluation of cardiac drugs in pigeons.” Methods for determining drugs included in SP X for the first time (digitoxin, digitoxin tablets, celanide, etc.) are presented. Statistical analysis is used to evaluate the experimental results.

GF X includes a special general article “Statistical analysis of the results of biological tests”.

This edition has revised lists A (toxic) and B (potent) substances.

TO list A include medicines, the prescription, use, dosing and storage of which, due to their high toxicity, must be carried out with extreme caution. This list also includes drugs that cause addiction.

TO list B include medicines, the prescription, use, dosing and storage of which must be carried out with caution due to possible complications when used without medical supervision.

Storage and dispensing in pharmacies and all other institutions of medicines according to lists A and B are carried out in compliance with the rules given in special instructions approved by the USSR Ministry of Health.

The table of higher single and daily doses of toxic and potent drugs for adults has been revised, clarified and expanded. The table of the highest single and daily doses of poisonous and potent drugs for children has been updated. There is a table of single doses of poisonous, potent and some other medicines widely used in veterinary medicine for adult pets.

In the text of the articles, as well as in the IX edition of the Pharmacopoeia, only the highest single and daily doses for adults are indicated, the remaining doses are indicated in the tables.

At the end of the articles on the substances, instructions are given about the main pharmacological action. However, it should not be assumed that the substance cannot have another type of action or use.

The “Storage” section provides brief information about the conditions under which the drug should be stored (temperature; containers protected from light and moisture, etc.).

The expiration dates of drugs given in Global Fund IX are not indicated in this publication. These data are published in a separate document approved by the USSR Ministry of Health. The exceptions are ether for anesthesia, chloroform for anesthesia and some drugs containing cardiac glycosides, for which there is an indication of the period of re-control.

After the publication of GF X, a significant change in the nomenclature of drugs occurred, the requirements for their quality increased, and new highly effective methods of pharmacopoeial analysis were developed. The number of outdated, ineffective, and insufficiently harmless drugs excluded from the nomenclature was about 1000 items. All this required the Pharmacopoeial Committee to make appropriate additions and changes to the ND and create new FS.

2.3 State Pharmacopoeia X I

Since 1971, the Ministry of Health of the USSR approves a FS or VFS for each new drug and drug approved for use, and general pharmacopoeial monographs (GPM) for general methods of analysis. All of them have the same legal force and legislative character along with the Global Fund X. The work carried out was a preparatory stage for the release of the new, XI, edition of the Global Fund.

Issues have now been published. 1 and 2 GF XI. Vol. 1 by order of the USSR Ministry of Health was put into effect on January 1, 1988. Since that time, all previously valid ND, including the relevant articles of the Global Fund X, replaced by articles no. 1 GF XI.

The remaining materials contained in GF X (taking into account changes made to them in the prescribed manner) remain valid until the publication of the corresponding issues and articles of GF XI.

Unlike previous editions, the present eleventh edition of the State Pharmacopoeia (SP XI) is intended to be published in two parts, consisting of separate volumes with a sequential serial number.

Published individual pharmacopoeial monographs and volumes of the Global Fund XI are legally equivalent and have the same legal force.

Volume I of the State Fund XI "General methods of analysis" includes general articles on physical, physico-chemical, chemical methods of analysis and methods of analysis of medicinal plant raw materials - a total of 54 articles.

For the first time, 9 articles are introduced: "Gas chromatography" as a section of the general article "Chromatography", "High-performance liquid chromatography" as a section of the general article "Chromatography", "Method for determining the degree of whiteness of powdered drugs", "Phase solubility method", "Nuclear magnetic spectroscopy resonance", "Radioactivity", Electrophoresis",

“Emission and atomic absorption flame spectrometry”, “Luminescence microscopy”, “Determination of impurities of chemical elements in radiopharmaceuticals”.

The articles “Definition of the acetyl group” and “Reichert-Meissl number” contained in GF X are not included in GF XI. All other articles contained in the Global Fund X have been revised and supplemented taking into account modern scientific achievements in the field of drug analysis.

The article “Determination of transparency and degree of turbidity of liquids” has been significantly revised. To determine these indicators, new standards have been introduced - suspensions obtained from hydrazine sulfate and hexamethylenetetramine. A table for the preparation of standards and a diagram for viewing the transparency and degree of turbidity of liquids are provided.

The article "Complexometric Titration" has been revised and expanded to include a new indicator - calcone carboxylic acid, which has recently become widespread in pharmaceutical analysis. Complexons are increasingly used in analytical chemistry. Methods for determining cations of aluminum, bismuth, calcium, lead, magnesium and zinc have been introduced.

The article “Method of combustion in a flask with oxygen” includes methods for determining chlorine, bromine, fluorine, sulfur and phosphorus, which are currently widely used in analysis.

The article “General reactions to authenticity” has been significantly expanded. New sections have been introduced into it: “Iron oxide” and “Sulfites”; new identification methods are included in the sections “Iodides”, “Carbonates”, “Nitrates”, “Citrates”.

The article “Definitions based on measurements of the absorption of electromagnetic radiation” (section “Spectrophotometry in the ultraviolet and visible regions”) contains additions regarding the spectrophotometric analysis of multicomponent systems and includes a method of differential spectrophotometry.

The article “Determination of the color of liquids” has been significantly revised: a method for preparing 4 basic solutions from 4 initial solutions has been introduced; a ferric chloride solution was added to prepare one of the stock solutions.

The section “Measurement of viscosity on rotational viscometers” has been added to the article “Determination of the viscosity of liquids”. In the section "Measuring Viscosity with a Falling Ball Viscometer" the determination of viscosity using a Heppler viscometer is provided.

The article “Determination of volatile substances and water” has been revised and expanded: the sections “Drying method” and “Determination of water” have been clarified.

The section "Method of titration with K. Fisher's reagent" is supplemented with a method for determining the end of titration by electrometric titration "until the current completely stops."

The article “Determination of temperature limits of distillation” introduces a new device of the TPP type, with the help of which more accurate and reproducible results are obtained.

The article “Determination of Melting Point” introduces a PTP device with electrical heating to determine the melting point with a measurement range from 20 to 360 °C.

The articles have been updated: “Determination of the refractive index”, “Fluorimetry”, “Determination of pH”, “Polarography”, “Solubility”, “Nitritometry”, “Iodine number”.

The article “Electrometric titration methods” in the section “Amperometric titration with two indicator electrodes (titration method “until the current completely stops”)” includes an addition to the measuring circuit, which allows, along with sensitive microammeters, to use industrially produced pH meters or ionometers.

In the article “Test for purity and permissible limits of impurities” the methods “Test for ammonium salts” and “Test for heavy metal salts” have been revised.

The article "Polarimetry" has been revised and clarified.

In the article “Determination of Nitrogen in Organic Compounds,” a change was made to the description of the device for determining nitrogen due to the improvement of the “funnel for introducing alkali.”

The article “Determination of solidification temperature” additionally indicates substances capable of supercooling.

The article "Statistical analysis of biological test results" has been significantly revised. The section "Statistical processing of chemical experiment results" has been added.

The section “Methods for analysis of medicinal plant raw materials” includes 7 group articles that define the main diagnostic characteristics for morphological groups of raw materials: “Leaves”, “Herbs”, “Flowers”, “Fruits”, “Seeds”, “Bark”, “Roots”, rhizomes, bulbs, tubers, corms", in which new sections "Luminescent microscopy" and "Histochemical reactions" are introduced (except for the article "Flowers"), and modern botanical terminology is also taken into account.

The article “Rules for the acceptance of medicinal plant raw materials and methods of sampling for analysis” includes for the first time the section “Sampling of packaged products.”

In the article “Determination of essential oil content in medicinal plant raw materials,” along with the three methods adopted by the State Fund X, a fourth determination method (Clevenger’s method as modified) was introduced.

All other articles have been revised and supplemented taking into account modern requirements for the quality of medicinal plant raw materials.

Issue 2 of the State Fund XI includes 2 sections: “General methods of analysis” and “Medicinal plant raw materials”.

The section “General methods of analysis” includes 40 articles, 6 of which are for the first time: “Determination of the activity of enzyme preparations”, “Determination of protein in enzyme preparations”, “Methods for the quantitative determination of vitamins in dosage forms”, “Aerosols”, “Suspensions” and "Test for microbiological purity."

The remaining articles have been revised and supplemented taking into account modern advances in the field of drug analysis. Thus, for the first time, the article “Sterilization” additionally introduced the method of sterilization through membrane and depth filters, as well as the radiation method.

In the article “Determination of the grinding of powders and sieves,” for the first time, along with silk fabric for sieves, the use of nylon fabric is provided. The article describes the characteristics of the sieves used for analysis when determining the grinding of medicinal plant raw materials.

In the article “Determination of Zinc in Insulin Preparations,” instead of the photocolorimetric method with dithizone, the spectrophotometric method with zincone and atomic absorption method were introduced.

In the article “Determination of preservatives in hormonal preparations,” the gas chromatography method was first introduced to determine phenol and nipagin.

The article “Reference Standards” provides definitions of the terms “State Standard Samples” (GSO), “Working Standard Samples” (RSO) and “Reference Standard Samples of Witness Substances”, indicating their areas of application and requirements for their quality.

The article “Titrated solutions” has been revised in connection with the introduction of the SI system and IUPAC recommendations. The basic SI unit of quantity of a substance is the mole, so “normal” solutions are converted to “molar” solutions. This article, in the “General Notes” section, provides definitions of molarity, titer, mole, a definition of the term “conventional particle” (CP), and basic instructions for the preparation and storage of molar solutions.

The article “Indicators” has been revised and clarified: a definition of the concept “indicators” has been introduced, requirements for the preparation and storage of indicator solutions and dry indicator mixtures, and safety rules when working with indicators. The section "Indicator paper" has been introduced; The documentation for the indicators is provided.

The article "Reagents" has been revised and clarified. A “Note” has been introduced indicating which reagent grade should be used when analyzing medicinal products. Documentation for reagents is provided.

Due to the fact that the articles “Titrated solutions”, “Indicators” and “Reagents” of the 2nd issue of the State Pharmacopoeia of the USSR XI edition include titrated solutions, indicators and reagents given in the 1st issue, but in an updated version, it follows When using private pharmacopoeial monographs, be guided by the relevant articles published in the 2nd issue.

The general article "Granules" includes a description of coated granules; a requirement has been introduced to determine moisture (in accordance with private articles). The disintegration and dissolution of granules is intended to be determined using the devices specified in the article “Tablets”.

The article “Injectable dosage forms” introduces a requirement for the manufacture of medicines for parenteral use under conditions that maximally prevent contamination of the finished product by microorganisms and foreign substances.

A requirement has been introduced for individual injection solutions to be isohydric and isotonic; the type of excipients has been specified. Some excipients have permissible amounts; for example, for substances like chlorobutane, cresol, phenol - up to 0.5%; sulfites - up to 0.2%.

A requirement is included on the inadmissibility of the presence of preservatives in drugs for intracavitary, intracardiac, intraocular administration or in injection dosage forms administered into the spinal canal, as well as for a single dose exceeding 15 ml. It is prohibited to introduce the suspension into blood and lymphatic vessels, as well as the introduction of suspensions and emulsions into the spinal canal.

The article "Injectable dosage forms" provides a definition of clarity in comparison with water for injection or an appropriate solvent.

Additional requirements have been introduced for testing for toxicity, as well as for pyrogenicity, with a single dose volume of 10 ml or more, as well as with a smaller dose, if indicated in a private article.

Requirements have been introduced regarding dosing accuracy and permissible deviations in the mass of a substance in a dose of dry medicines for parenteral use. For contents weighing 0.05 g or less, a dosage uniformity test is required.

For suspensions administered parenterally, the time of sedimentation stability is indicated, and instructions are given for passage into the syringe through a needle No. 0840.

For the first time, a requirement has been introduced for the mandatory application of a batch number on an ampoule (vessel) of any capacity.

The article “Eye Drops” introduces a method of sterilization and sterility testing; The list of excipients has been expanded. Additional requirements for the packaging of drops are given.

The article “Capsules” includes a definition of the average weight for capsules containing 0.05 g or less of a medicinal substance.

A test for dosage uniformity is also provided, the definition of disintegration is clarified, and a definition of dissolution (release) is included.

The general article “Ointments” provides the actual ointments, pastes, creams, gels and liniments. The classification of ointment bases is given; in the absence of indications on the base, it is recommended to choose it taking into account the physical and chemical compatibility of the ointment components. The article contains instructions on the sterility of eye ointments. A microscopic method has been introduced for determining the degree of dispersion of the solid phase in suspension ointments.

The article “Suppositories” provides for the standardization of the weight of suppositories for children (from 0.5 to 1.5 g) and their size (with a diameter of no more than 1 cm). For suppositories made on hydrophilic bases, a new “dissolution” indicator has been introduced. The requirements regarding the determination of the deviation of the suppository weight from the average value have been clarified. For suppositories made on polyethylene oxide bases, a requirement is included for the need to wet the suppositories before insertion into the body cavity.

The article “Tablets” has been supplemented with requirements for tablets for parenteral use and an indication of the sterility of tablets for implantation. The list of excipients has been updated. The permissible norm for aerosil content has been introduced.

The requirements for fluctuations in the average weight of tablets and the content of medicinal substances have been clarified. Dosage uniformity testing is included for uncoated tablets containing 0.05 g or less of drug substance and for coated tablets containing 0.01 g or less of drug substance. A determination of the abrasion strength of uncoated tablets has been introduced.

The definition of disintegration has been clarified and a definition of dissolution (release) has been included.

The article “Biological methods for assessing the activity of medicinal plants and preparations containing cardiac glycosides” provides a general description of methods for biological assessment in frogs, cats and pigeons, and a detailed description of methods for determining the biological activity of each of the medicinal plants and preparations containing cardiac glycosides is given in private pharmacopoeial monographs.

Statistical processing of the results of biological tests is carried out taking into account the requirements of the Global Fund XI, no. 1, art. "Statistical processing of the results of chemical experiments and biological tests."

In the article “Determination of the biological activity of insulin,” along with the ferricyanide method, the glucose oxidase method for determining blood glucose was introduced for the first time as the most specific and widespread.

In comparison with the article of the State Pharmacopoeia X, some changes and additions have been made to the article “Toxicity Test” related to the ever-increasing requirements for the quality of medicines and, accordingly, the standardization of their test conditions. The mass of animals on which the test is carried out (both initial and repeated) has been increased. To more strictly standardize the test results, the conditions for keeping the animals are indicated, as well as the period of observation for them (48 hours). The article includes a "Sampling" section.

The article “Pyrogenicity Test” contains an indication that the use of albino rabbits is inadmissible. Testing for the reactivity of rabbits intended for drug testing for the first time has been introduced. The section on the possibility of reusing rabbits to determine pyrogenicity has been clarified.

The section “Methods for microbiological control of medicinal products” includes articles “Test for sterility”, “Nutrient media”, “Test for microbiological purity” and “Quantitative determination of microorganisms”. The articles unify sampling for analysis, incubation temperature, methods for determining the antimicrobial effect of drugs, recording results, etc.

A membrane filtration method has been introduced to determine the sterility of drugs with a pronounced antimicrobial effect and drugs produced in containers larger than 100 ml.

The article “Sterility Test” has been significantly revised and supplemented. To determine this indicator, two nutrient media were added (thioglycolate and Sabouraud), and the incubation time of the crops was increased to 14 days.

The article “Test for microbiological purity” provides for the determination of the total number of bacteria and fungi in non-sterile medicinal products, as well as the identification of contaminating flora - representatives of Escherichia coli and staphylococcus, the presence of which is excluded. The limits of permissible microbial contamination in relation to bacteria and fungi are given.

The article “Determination of the antimicrobial activity of antibiotics by diffusion in agar” has been revised and expanded, in which two methods are presented (three-dose and using a standard curve) and determination conditions are given.

The second section, “Medicinal plant materials,” includes one general and 83 specific articles on medicinal plant materials, widely used in medical practice for the preparation of herbal infusions and decoctions, as well as for the production of medicines in industrial production.

Compared to the X edition of the State Pharmacopoeia of the USSR, the nomenclature of medicinal plant raw materials has been significantly expanded, species not included in previous editions are included, as well as new species approved for medical use: rhizomes with roots of Rhodiola rosea, shoots of wild rosemary, common spruce cones, seaweed , rhizomes with madder roots, etc.

For some types of medicinal plant raw materials, along with those used, other botanical species of the same genus, approved for medical use, are included (for example, various types of hawthorn, rose hips).

The name of the raw material is given in the plural (leaves, roots, etc.).

The nomenclature of the names of producing plants is unified and brought into line with their modern scientific Russian and Latin names (Article 3 of the rules of the International Code of Botanical Nomenclature, 1980 edition). In a number of cases, the interpretation of the taxonomic volume of some genera and species has changed: large polymorphic taxa are considered as narrower ones (Padus avium = P. avium + P. asiatica) and, conversely, previously understood as isolated closely related taxa, are combined into species or genera of enlarged volume (Aralia mandshurica) --> A. elata).At the same time, taking into account the established traditional names of raw materials, in this edition of the pharmacopoeia it was decided not to change them, but in some cases to give a second Latin name according to the genus and species of the producing plant.

Pharmacopoeial monograph of the enterprise

Every company that produces medicines has a quality standard. It involves the use of drug control methods at all stages of production. Typically tested and registered technology is used

During production, all standards must be used, not lower than the requirements contained in the state document. A pharmacopoeial monograph has a validity period, which is approved upon its adoption. Usually the period is no more than 5 years. The technological process must be taken into account.

OFS

The general pharmacopoeial monograph is the state standard for the quality of medicines. It specifies the requirements for drugs, as well as a description of control methods. The main information is:

list of indicators and testing methods;
chemical, physical, biological properties;
requirements for drugs.

The pharmacopoeial monograph is accepted by the management of the department, and then is registered with the organization that produces medicines.

CHFS

Private pharmacopoeial monographs are documents that specify the quality and safety of drugs. They are published for drugs under an international nonproprietary name.

Temporary pharmacopoeial monograph

This document is issued during the development of industrial production of the drug. It is necessary to process methods for establishing the quality or performance of a new drug for a period of no more than 3 years.

What does the article consist of?

A pharmacopoeial monograph includes a lot of important information. In the introductory section you can find information about the period of collection of raw materials, as well as its characteristics. According to processing, products can be dried, threshed, freshly harvested, or freshly frozen. Plants can be wild or cultivated. The life form and name are indicated.

Mandatory information includes external signs that serve as confirmation of the purity and quality of the product. The composition of raw materials and characteristics should be included in the pharmacopoeial monograph. Medicines are also assessed by microscopy, which allows us to establish the authenticity of the product. This section includes characteristics of the structure of the raw material, as well as the type of microclimate where the study was carried out.

Alcohol according to pharmacopoeial monographs, as well as other drugs, are tested for various reactions or tests. This is necessary to verify the authenticity of the product. Qualitative reactions determine how the test is performed and the results.

Numerical indicators

The section consists of specific indicators and their standards:

whole, cut, powdered raw materials are determined for quality; All medicinal raw materials must be checked;
presence of active ingredients, total and insoluble ash in the preparations.

Quantity

It is imperative to carry out a method for determining the main active components in the form of a sum per any amount of a specific component. When an individual substance is obtained, its content is standardized.

Other characteristics

The document indicates the drugs required for all, as well as the mass of the substance needed for one box. Using microbiological purity, the level of microorganisms and their quantity are determined.

Labeling, carried out on the basis of generally accepted graphic design requirements, is important. The necessary information includes requirements for loading and unloading. The rules for proper transportation, which does not change the properties of the product, are also indicated.

The document contains information about the storage conditions of medicines, including protection from exposure to natural factors. Important information includes the expiration date during which the medicine can be used for its intended purpose. It is unacceptable to do this after it, as it poses a health hazard. The pharmacological action section includes information about the group to which the medicine belongs.

Storage

The article contains information about proper storage of products. Special premises must comply with all standards to ensure the preservation of the quality of medicines.

The complex of premises should consist of:

acceptance areas where unpacking and packaging of drugs takes place;
fund selection zones;
quarantine facilities;
area for storing special drugs;
premises for defective and expired goods.

Each zone must be designated. It is important that the premises comply with sanitary and hygienic requirements. Legislation establishes the need to support the climate regime based on accepted standards of temperature and humidity.

The documentation contains information about monitoring air exchange in the room for storing medicines. Such rooms should have natural and artificial lighting. If required, sun protection is installed. With the help of these and other rules, the production, storage and release of medicines occurs.

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ORDER of the Ministry of Health of the Russian Federation dated 01-11-2001 388 ON STATE QUALITY STANDARDS FOR MEDICINES (2019) Relevant in 2018

LIST OF SECTIONS OF PHARMACOPEIAL ARTICLES AND PHARMACOPOEIAL ENTITLES FOR MEDICINES OF SPECIFIC ENTERPRISES - DRUG MANUFACTURERS

2. International nonproprietary name (INN) in Russian

3. Chemical name according to IUPAC requirements

4. Structural and empirical formulas and molecular weight

6. Description

7. Solubility

6. <*>Vacuum (shielding gas, sealing)

7. <*>Weight loss on drying

8. <*>Sterility or microbiological purity

9. Specific activity

10. Packaging, labeling, transportation, storage

11. Expiration date

12. Purpose

Bacteriological culture media

1. Introductory part

2. Description

3. Solubility

4. Transparency

5. Chroma

6. pH of the solution (extract - for media containing agar)

7. Weight loss on drying

8. <*>Total nitrogen

9. Amine nitrogen

10. Chlorides

11. <*>Carbohydrates

12. Strength of medium jelly (for dense media)

13. Specific activity (sensitivity of the medium, growth rate and stability of the basic biological properties of microorganisms, inhibitory, differentiating properties, the set of which and the methods used depend on the purpose of the medium)

14. Packaging, labeling, transportation, storage

15. Expiration date

16. Purpose

Nutrient media, solutions and growth factors for cell culture

1. Introductory part

2. Description

3. Solubility (for dry preparations)

4. Transparency

5. Chroma

7. Loss of weight upon drying (for dry preparations)

8. <*>Chlorine ion

9. <*>Glucose

10. <*>Amine nitrogen

11. <*>Protein

12. <*>Buffer capacity

13. <*>Osmoticity

14. <*>Osmolarity

15. Sterility

16. <*>Toxicity

17. Specific activity

18. <*>Impurities

19. Packaging, labeling, transportation, storage

20. Expiration date

21. Purpose

XVI. Human blood products

Liquid dosage forms of blood products

1. Name of the drug in Russian

4. Description

5. Transparency

6. Chroma

8. Authenticity, including confirmation of homology to human blood proteins

9. Quantitative determination of the main protein component

10. Fractional protein composition

11. Specific activity

12. Molecular parameters of the main protein component

13. Hemagglutinins (anti-A and anti-B)

14. Thrombogenicity (for drugs with coagulolytic action)

15. Prekallikrein activator

16. Anti-complementary activity

17. Thermal stability

18. Electrolytes (sodium, potassium, citrate, calcium, aluminum, etc.)

19. Foreign matter

20. No mechanical inclusions

21. Nominal volume

22. Pyrogenicity

23. Bacterial endotoxins

24. Toxicity

26. Test for the absence of antigens (antibodies) of hepatitis viruses, human immunodeficiency viruses, and other possible contaminants of human blood

27. Sterility

28. Packaging, labeling, transportation, storage

29. Expiration date

30. Pharmacological group

Dried and frozen dosage forms of blood products

1. Name of the drug in Russian

4. Characteristics of the accompanying solvent, activator, plasticizer

5. Description of the finished dosage form, as well as after its dissolution (thawing)

6. Solubility or dissolution time in accompanying solvent (for dry preparations)

7. Transparency

8. Color (hempigments)

9. pH of the solution

10. Authenticity, including confirmation of homology to human blood proteins

11. Quantitative determination of the main protein component

12. Fractional protein composition

13. Specific activity

14. Molecular parameters of the main protein component

15. Hemagglutinins (anti-A and anti-B)

16. Thrombogenicity (for drugs with coagulolytic action)

17. Prekallikrein activator

18. Anti-complementary activity

19. Thermal stability

20. Electrolytes (sodium, potassium, citrate, calcium, aluminum, etc.)

21. Foreign matter

22. Loss of weight during drying

24. No mechanical inclusions

25. Nominal volume

26. Pyrogenicity

27. Bacterial endotoxins

28. Toxicity

30. Test for the absence of antigens (antibodies) of hepatitis viruses, human immunodeficiency, and other possible contaminants of human blood

31. Sterility

32. Packaging, labeling, transportation, storage

33. Expiration date

34. Pharmacological group

In accordance with the Law of the Russian Federation of June 10, 1993 N 5154-1 “On Standardization” (with amendments and additions: Gazette of the Congress of People's Deputies and the Supreme Council of the Russian Federation, 1993, N 25, Art. 917; Collection of Legislation of the Russian Federation, 1996, N 1, Art. 4), Federal Law of June 22, 1998 N 86-FZ “On Medicines” (as amended and supplemented: Collection of Legislation of the Russian Federation, 1998, N 26, Art. 3006; 2000, N 2, Art. 126), Regulations on the Ministry of Health of the Russian Federation, approved by Decree of the Government of the Russian Federation of June 3, 1997 N 659 (as amended and supplemented: Collection of Legislation of the Russian Federation, 1997, N 23, Art. 2691; 1999, N 47, Art. 5706; 1997, N 51, Art. 5809), I order:

Approve Industry Standard OST 91500.05.001-00 “Quality Standards for Medicines. Basic provisions" (appendix).
Control over the implementation of this Order is entrusted to the Deputy Minister of Health of the Russian Federation A.V. Katlinsky.

Minister Yu.L.SHEVCHENKO

Application

Approved

By order of the Ministry of Health

Russian Federation dated 01.11.2001 N 388

The procedure for constructing and presenting state quality standards for medicines

INDUSTRY STANDARD. DRUG QUALITY STANDARDS. BASIC PROVISIONS OST 91500.05.001-00

General provisions

1.1. Industry standard 91500.05.001-00 “Quality standards for medicines. Basic provisions" (hereinafter referred to as OST) was developed in accordance with the Law of the Russian Federation dated June 10, 1993 N 5154-1 "On Standardization", Federal Law dated June 22, 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 dated 06/03/1997 N 659 (as amended and supplemented).

1.2. This OST establishes the procedure for the development, registration, examination, coordination, approval, assignment of designation, registration of state quality standards for medicines and amendments to them.

1.3. Real OST does not apply:

on blood and its components used in transfusiology;
for raw materials of animal origin, used only for the preparation of products subject to further industrial processing for the preparation of medicines;
for foreign-made medicines;
for medicines manufactured in pharmacies.

Terms and Definitions

For the purposes of this OST, the following terms with corresponding definitions are used:

Excipients- these are substances of organic or inorganic nature that are used in the production of finished dosage forms to give them the necessary properties. The list of excipients is extensive; depending on the type of dosage form, these may be substances that increase viscosity, surface active and buffering agents, flavoring agents, preservatives, stabilizers, fillers, disintegrants, glidants, etc.;

homeopathic medicines- single- or multicomponent preparations, usually containing microdoses of active compounds, produced using special technology and intended for oral, injection or topical use in the form of various dosage forms;

state standard sample- this is a standard sample, the quality parameters of which are regulated by a pharmacopoeial monograph approved in the prescribed manner. In the analysis of finished dosage forms, working standard samples of medicinal substances (substances) can be used;

state pharmacopoeia— collection of pharmacopoeial articles;

production of medicines— manufacture of medicines in a pharmacy institution that has a license for pharmaceutical activities, according to the rules for the manufacture of medicines approved by the federal body for quality control of medicines;

immunobiological drugs— medicines intended for immunological prophylaxis and immunological therapy;

Article 4 of the Federal Law “On Medicines”.

blood components— blood cells and formed elements, blood plasma obtained from blood and intended for administration to the recipient;

blood- a liquid obtained from a human donor, consisting of cellular elements and plasma and used after proper testing to obtain individual components and administer to the recipient;

medicines- substances used for the prevention, diagnosis, treatment of disease, prevention of pregnancy, obtained from blood, blood plasma, as well as organs, human or animal tissues, plants, minerals by synthesis methods or using biological technologies. Medicines also include substances of plant, animal or synthetic origin that have pharmacological activity and are intended for the production and manufacture of medicines;

*> Article 4 of the Federal Law “On Medicines”.

medications- dosed drugs in a specific dosage form;

dosage form— a state given to a medicinal product or medicinal herbal raw material that is convenient for use and in which the required therapeutic effect is achieved (definitions of dosage forms that can be used in the preparation of state quality standards for medicinal products are given in Appendix No. 1 to this OST);

international nonproprietary name (INN)— the name of the drug adopted by the World Health Organization (WHO);

circulation of medicines- a generalized concept of activities, including development, research, production, manufacturing, storage, packaging, transportation, state registration, standardization and quality control, sale, labeling, advertising, use of medicines, destruction of medicines that have become unusable, or medicines with expired shelf life and other actions in the field of circulation of medicines;

Article 4 of the Federal Law “On Medicines”.

organization— drug developer - an organization that has patent rights to a drug and copyrights to the results of its preclinical studies;

Article 4 of the Federal Law “On Medicines”.

enterprise - manufacturer of medicines— an organization engaged in the production of medicines in accordance with the requirements of this Federal Law;

Article 4 of the Federal Law “On Medicines”.

blood products- medicinal products obtained from human blood, produced in liquid, dry and frozen form;

patented medicines— medicines, the right to produce and sell which is protected by the patent legislation of the Russian Federation;

Article 4 of the Federal Law “On Medicines”.

working standard sample- this is a sample of a serial substance that meets the requirements of the relevant quality standard for medicinal products;

series- a certain amount of a medicinal product obtained as a result of one technological cycle. The main requirement for a series is its homogeneity;

standard samples- these are substances used to control the quality of medicinal products, with which the tested medicinal products are compared when analyzing them using physico-chemical and biological methods. Standard samples are divided into chemical and biological; the same standard sample, in accordance with the instructions of the pharmacopoeial monograph, can be used for both physicochemical and biological analyses;

best before date— the period during which the medicinal product must fully satisfy all the requirements of the relevant state medicinal product quality standard;

substance- a substance of plant, animal, microbial or synthetic origin that has pharmacological activity and is intended for the production and manufacture of medicinal products;

pharmacopoeial monograph— state standard for a medicinal product, containing a list of indicators and methods for quality control of the medicinal product.

Article 4 of the Federal Law “On Medicines”.

The procedure for preparing state quality standards for medicines

3.1. State quality standards for medicines are developed and approved in the following types:

general pharmacopoeial monograph (GPM);
pharmacopoeial monograph (FS);
pharmacopoeial monograph for a medicinal product of a specific enterprise - a medicinal product manufacturer (FSP).

3.2. State standards for the quality of medicines must ensure the development of high-quality, effective and safe medicines.

3.3. State quality standards for medicines must be revised in a timely manner, taking into account new achievements in medical, pharmaceutical and other sciences and the provisions of leading foreign pharmacopoeias, recommendations of leading international organizations in the field of pharmaceutical science.

3.4. A general pharmacopoeial monograph includes a list of standardized indicators or test methods for a specific dosage form, a description of physical, physicochemical, chemical, biochemical, biological, microbiological methods for analyzing drugs, requirements for the reagents used, titrated solutions, and indicators.

3.5. A pharmacopoeial monograph is developed for a medicinal product under an international nonproprietary name, if available (for monocomponent medicinal products), and contains a mandatory list of indicators and methods of quality control (taking into account its dosage form), corresponding to the provisions of leading foreign pharmacopoeias.

3.6. The development of a pharmacopoeial monograph for an original (patented) medicinal product during the validity period of the patent protection and its inclusion in the State Pharmacopoeia is possible only in agreement with the developer of the medicinal product or is carried out after the expiration of the patent.

3.7. General pharmacopoeial monographs and pharmacopoeial monographs constitute the State Pharmacopoeia.

3.8. The State Pharmacopoeia is published by the Russian Ministry of Health and is subject to reissue every 5 years.

3.9. A pharmacopoeial monograph for a medicinal product of a specific drug manufacturer contains a list of indicators and methods for quality control of a medicinal product produced by a specific enterprise and is developed taking into account the requirements of the State Pharmacopoeia and this standard.

The quality requirements for medicinal products contained in the FSP must be no lower than the requirements set out in the State Pharmacopoeia, taking into account the requirements of this standard.

3.10. The validity period of the FSP is established taking into account the level of the technological process of a specific production of a medicinal product, but not more than 5 years.

3.11. When developing a new drug, in the absence of a state drug quality standard for the substance, simultaneously with the development of the FSP for the drug, the FSP for the substance used for its production is developed.

When developing a new immunobiological medicinal product, the FSP for the substance for its production is developed if necessary.

3.12. General pharmacopoeial monographs and pharmacopoeial monographs are developed by an organization authorized by the Russian Ministry of Health.

The procedure for constructing and presenting state quality standards for medicines

4.1. The title of the state medicinal product quality standard gives the name of the medicinal product.

4.2. The list of the main sections of the FS and FSP and the sequence of their presentation, taking into account specific dosage forms, is given in Appendix 2 to this OST.

4.3. All quality indicators contained in the FSP must be presented in a summary table (specifications). The specification is a mandatory component of the FSP.

4.4. The procedure for constructing state quality standards for medicinal products for substances, medicinal preparations and medicinal plant raw materials is given in Appendices 3 - 5 to this OST.

4.5. Title pages of the OFS, FS, FSP must be drawn up in accordance with Appendices 6, 7 and 8 to this OST.

The last sheet of the FSP must be drawn up in accordance with Appendix 9 to this OST.

4.6. The numbering of sections of the OFS, FS and FSP is not indicated.

4.7. The presentation of the text should be brief, without repetition, and should exclude the possibility of different interpretations.

4.8. Abbreviations of words in the text and inscriptions under drawings, diagrams and other illustrations are not allowed, with the exception of abbreviations used in the legislation of the Russian Federation.

4.9. In the text part of the standards, the requirements for the quality of medicines are stated in an imperative form.

When setting out mandatory requirements, norms and methods, the words “must”, “should”, “necessary” and derivatives from them are used in the text.

4.10. Section headings are placed on a red line and are highlighted in bold or underlined.

4.11. If requirements, norms, methods, etc., applicable to a medicinal product, are established in the State Pharmacopoeia, other state or industry standards, then instead of repeating their text, a link to the source should be provided.

4.12. The presentation of the text about the substance used in the production of the medicinal product must be accompanied by a link to the regulatory document under which it is produced.

4.13. If the text of the General Pharmacopoeia, Physics, and FSP contains references to reagents, auxiliary materials, etc., which are produced according to other regulatory documentation, the designation of this documentation should be indicated

The procedure for submitting state quality standards for medicines for examination, approval and approval

5.1. The draft state quality standard for a medicinal product, signed by its developer, is submitted along with the following documentation:

cover letter;
explanatory note;
a table of analytical data confirming the numerical indicators given in the draft state standard for the quality of medicines on at least 5 series of samples (for immunobiological medicines - on 3 series of samples);
a table of analytical data confirming the shelf life of the drug in accordance with the requirements of the relevant industry standard;
draft instructions for use of a medicinal product (for a new medicinal product or a generic medicinal product for which the medicinal product is being developed for the first time);
a table comparing the indicators provided for by the draft state drug quality standard with similar indicators of domestic and foreign pharmacopoeias, if available;
a sample of the drug in a labeled package;
certificate of metrological assurance of quality control of the medicinal product.

5.2. The explanatory note to the draft state quality standard for a medicinal product must contain the following information:

name of the enterprise - manufacturer (developer) of the medicinal product;
a brief description of the synthesis or technology for obtaining the drug;
a detailed justification of the research methods, indicators and standards given in the project, as well as a description of other methods by which the analysis of this medicinal product or substance was carried out;
how many samples were used to develop the draft state drug quality standard and based on what technological documentation;
if there are deviations from the general requirements of the State Pharmacopoeia, a detailed justification is given;
in which foreign pharmacopoeias or other sources a similar medicinal product is described with data on its quality in comparison with foreign medicinal products, and if the medicinal product is new or original, then there should be an indication of this.

5.3. The explanatory note and tables of analysis results are signed by the head of the enterprise - manufacturer (developer) of the medicinal product or a person authorized by him.

5.4. The examination of the draft quality standard for medicines and its approval is carried out by organizations authorized by the Russian Ministry of Health.

If necessary, in agreement with the manufacturer of the medicinal product, the Ministry of Health of Russia may involve specialized organizations to conduct experimental checks of the state quality standard of the medicinal product.

5.5. During the examination, the scientific and technical level of the draft state drug quality standard and its compliance with modern requirements for regulatory documentation for drugs are checked, including:

— compliance of indicators and quality standards of the medicinal product and consumer packaging with the requirements of the State Pharmacopoeia;
— validity of the list of indicators, optimality of the values of quality standards and shelf life of the medicinal product;
— accuracy and unambiguity of the terms, definitions, chemical nomenclature and units of physical quantities used.

5.6. Persons participating in the procedures for the examination and approval of a pharmacopoeial monograph for a medicinal product of a particular drug manufacturer must ensure the confidentiality of information obtained in the process of this work.

5.7. An organization authorized by the Russian Ministry of Health to conduct an examination of the state quality standard of a medicinal product, after the examination, sends documents for approval to the Russian Ministry of Health.

The procedure for assigning designations and registering state quality standards for medicines

6.1. OFS, FS, FSP, after approval, are registered in an organization authorized for this by the Ministry of Health of Russia, with the assignment of a designation.

6.2. The designation of the OFS and FS must consist of the abbreviated name of the type of state quality standard of the medicinal product, the index of the Ministry of Health of Russia, the registration number assigned to the document, and the last two digits of the year of approval or revision, separated by dashes.

For example: OFS or FS 42-00001-00, where

OFS or FS - the abbreviated name of the category of the quality standard of the medicinal product;

42 - index assigned to the Russian Ministry of Health to designate standardization documents; 00001 — document registration number; 00 - the last two digits of the year the document was approved (00-2000, 01-2001, 02-2002, etc.).

6.3. The FSP designation must consist of the abbreviated name of the type of state quality standard for the medicinal product, the index of the Ministry of Health of Russia, the enterprise code, the registration number of the document and the last two digits of the year of approval of the standard, separated by dashes.

For example: FSP 42-0001-00001-00, where:

FSP is the abbreviated name of the type of state quality standard for a medicinal product;

42 - index assigned to the Russian Ministry of Health to designate standardization documents; 0001 - four-digit company code; 00001 — document registration number; 00—the last two digits of the year the document was approved.

6.4. The registration number is assigned in sequential numbering order, starting with the number 00001.

6.5. The enterprise code is formed from four characters, starting with the number 0001.

An enterprise code is assigned to an enterprise - manufacturer or organization - developer of medicines when submitting an application for approval of the first FSP.

The procedure for making changes to state quality standards for medicines

7.1. Amendments to state standards for the quality of medicines are made in cases where an increase in the scientific and technological level makes it possible to improve the quality of the medicine or clarify quality indicators. The changes made should not entail a deterioration in the quality of medicines.

7.2. The first page of changes to the quality standard of a medicinal product is drawn up in the form of Appendix 10.

7.3. The texts of sections (subsections or paragraphs) in the old and new editions are given in full.

Examination and approval of changes made to state quality standards for medicinal products are carried out in the manner established for the examination and approval of state quality standards for medicinal products.

Annex 1

DOSAGE FORMS. TERMS AND DEFINITIONS

Aerosols- dosage form, which is solutions, emulsions, suspensions of medicinal substances, under pressure together with propellants in a sealed package equipped with a valve-spray system (dosing or non-dosing).

An aerosol that releases the contents of a package using air is called a spray.

Aerosols are intended for inhalation (inhalation). A type of inhalation is powders for inhalation (inhalers), which can be produced in special packaging and dispensing devices such as rotodiscs, ventodiscs, etc.

Aerosols can also be intended for applying a medicinal composition to the skin, mucous membranes, and wounds.

Briquettes- a solid dosage form obtained by pressing crushed medicinal plant materials or a mixture of various types of plant materials without the addition of excipients and intended for the preparation of infusions and decoctions.

Granules- solid dosed or non-dosed dosage form for internal use in the form of agglomerates (grains) of spherical or irregular shape, containing a mixture of active and auxiliary substances.

Granules can be coated with shells, including gastro-resistant ones; uncovered; effervescent; for the preparation of oral liquids and with modified release of active ingredients.

Packaging with non-dosed granules can be equipped with a dosing device.

Dragee- a solid dosage form obtained by layer-by-layer application of active ingredients onto microparticles of inert carriers using sugar syrups.

Drops- a liquid dosage form containing one or more active substances dissolved, suspended or emulsified in an appropriate solvent, and dosed in drops.

There are drops for internal or external use.

Capsules- a dosage dosage form consisting of a hard or soft gelatin shell containing one or more active ingredients with or without the addition of excipients.

Among the capsules there are: hard, soft, microcapsules, gastro-resistant, pellets:

gastro-resistant - capsules that ensure the release of drugs in the intestinal juice;
microcapsules - capsules consisting of a thin shell made of polymer or other material, spherical or irregular in shape, ranging in size from 1 to 2000 microns, containing solid or liquid active ingredients with or without the addition of excipients;
soft - solid capsules of various shapes (spherical, ovoid, oblong, etc.) with liquid or paste-like substances;
solid - cylindrical capsules with hemispherical ends, consisting of two parts that fit into one another without forming gaps. Capsules can be filled with powders, granules, microcapsules, pellets, tablets.

Pellets- coated solid spherical particles containing one or more active ingredients with or without the addition of auxiliary substances, having dimensions from 2000 to 5000 microns.

- sterile dosage forms for parenteral use in the form of solutions, suspensions, emulsions, as well as solid medicinal substances (powders, tablets, porous masses), which are dissolved in a sterile solvent immediately before administration. There are small volume injections up to 100 ml and large volume injections of 100 ml or more (infusions):

powders for injection - sterile solid medicinal products used for the preparation of solutions or suspensions for injection;
solutions for injections - sterile aqueous or non-aqueous solutions of medicinal substances in an appropriate solvent;
injection suspensions - sterile highly dispersed suspensions;
emulsions for injection - sterile highly dispersed emulsions.

Ointments- a soft dosage form intended for application to the skin, wounds and mucous membranes and consisting of a base and medicinal substances evenly distributed in it.

According to the type of dispersed systems, ointments are divided into homogeneous (alloys, solutions), suspension, emulsion and combined, depending on the consistency properties - into ointments themselves, creams, gels, liniments, pastes:

gels- ointments with a viscous consistency that can retain their shape and have elasticity and plasticity. Based on the type of dispersed systems, hydrophilic and hydrophobic gels are distinguished;
creams- ointments of soft consistency, which are emulsions such as oil in water or water in oil;
liniments- ointments in the form of a viscous liquid;
pastes- ointments of dense consistency, the content of powdery substances in which exceeds 25%.

Tinctures- a liquid dosage form, which is alcoholic and aqueous-alcoholic extracts from medicinal plant materials, obtained without heating and removing the extractant.

Solutions- a liquid dosage form obtained by dissolving liquid, solid or gaseous substances in an appropriate solvent.

Solutions are used for internal and external use, as well as for injection.

Medicinal fees- mixtures of several types of crushed, less often whole medicinal plant materials, sometimes with the addition of salts and essential oils.

Syrups- a liquid dosage form for internal use, which is a concentrated solution of various sugars, as well as their mixtures with medicinal substances.

Suppositories- a solid dosage form, consisting of a base and medicinal substances, melting (dissolving, disintegrating) at body temperature.

Suppositories are intended for rectal (suppositories), vaginal (pessaries, balls) and other routes of administration (sticks).

Suspensions- a liquid dosage form, which is a dispersed system containing one or more solid medicinal substances suspended in an appropriate liquid.

Suspensions are used for internal and external use, as well as for injection.

Pills- a solid dosage form obtained by pressing powders and granules containing one or more medicinal substances with or without the addition of excipients.

Among the tablets there are: uncoated, effervescent, coated, gastro-resistant, modified release, for use in the oral cavity:

gastro-resistant - tablets that are stable in gastric juice and release the drug substance or substances in the intestinal juice.

Obtained by coating tablets with a gastro-resistant coating (enteric-soluble tablets) or by pressing granules and particles previously coated with a gastro-resistant coating, or by pressing medicinal substances mixed with a gastro-resistant filler (durules);

uncoated - single-layer or multilayer tablets obtained by single or multiple compression. In multilayer tablets, each layer may contain a different drug substance;

coated - tablets coated with one or more layers of various substances, such as natural and synthetic materials, carbohydrates, possibly with the addition of surfactants. A thin coating (constituting less than 10% of the tablet weight) is usually called a film coating.

A sugar coating containing one or more medicinal substances and applied to microparticles of inert carriers makes it possible to obtain a dosage form - dragees;

effervescent - uncoated tablets usually containing acidic substances and carbonates or bicarbonates that react rapidly in water to release carbon dioxide; they are intended to dissolve or disperse the drug in water immediately before administration;

for use in the oral cavity - usually uncoated tablets obtained using a special technology in order to release a medicinal substance or substances in the oral cavity and provide a local or general resorptive effect (buccal tablets, sublingual tablets, etc.);

modified release - coated or uncoated tablets containing special excipients or obtained using a special technology that allows you to program the rate or location of release of the drug.

Extracts- concentrated extracts from medicinal plant raw materials or raw materials of animal origin, which are mobile, viscous liquids or dry masses. There are: liquid extracts (mobile liquids); thick extracts (viscous masses with a moisture content of no more than 25%); dry extracts (loose masses with a moisture content of no more than 5%).

Elixirs- a liquid dosage form, which is a transparent mixture of alcohol and water extracts from medicinal plant materials with the addition of medicinal substances, sugars and flavorings.

Emulsions- a liquid dosage form, which is a dispersed system containing two or more mutually insoluble or immiscible liquids, one of which is emulsified in the other.

Emulsions are used for internal and external use, as well as for injection.

MAIN GROUPS OF MEDICAL IMMUNOBIOLOGICAL DRUGS

Allergens, allergoids- substances of antigenic or hapten nature, used for hyposensitization and allergy diagnostics.

Anatoxins- bacterial exotoxins that have lost their toxicity as a result of exposure to an inactivator (for example, formaldehyde), but have retained their antigenic properties.

Bacteriophages- viruses that can penetrate a bacterial cell, multiply in it, cause its lysis or transition to a state of lysogeny (phage carriage).

Vaccines- medicines obtained from live attenuated strains or killed cultures of microorganisms or their antigens, intended for active immunization.

Diagnostic immunobiological medicinal products- medicines intended for the diagnosis of infectious diseases.

Immunoglobulins (antibodies)— an immunologically active protein fraction of human or animal blood serum (plasma), containing antimicrobial and/or antitoxic antibodies.

Immunomodulators- substances that change the level of the body’s immune response, including cytokines, interferons, etc.

Probiotics- bacteria apathogenic for humans, which have antagonistic activity against pathogenic and conditionally pathogenic bacteria, ensuring the restoration of normal microflora.

Heterologous serums- blood serum obtained from animals immunized with a particular antigen and containing the corresponding antibodies to it.

Appendix 2

to the Industry Standard OST 91500.05.001-00 “Quality Standards for Medicines. Basic provisions"

LIST OF SECTIONS OF PHARMACOPOEIAL ARTICLES AND PHARMACOPOEIAL ARTICLES

FOR MEDICINES OF SPECIFIC ENTERPRISES - DRUG MANUFACTURERS

Medicinal substance (substance)

International nonproprietary name (INN) in Russian
Chemical name according to IUPAC requirements
Structural and empirical formulas and molecular weight
Content of active substance (in percent or units)
Description
Solubility
Authenticity
Melting (decomposition) point, or Solidification point, or Boiling point
Density
Specific rotation
Specific absorption rate
Refractive index
Solution transparency
Solution color
Mechanical inclusions
Purity indicators (chlorides, sulfates, sulfate ash and heavy metals, etc.)
or Water determined by K. Fischer method
Residual organic solvents (if used at the last stage of the technological process)
Pyrogenicity or bacterial endotoxin content (LAL test)
Toxicity
quantitation
Package
Marking
Transportation
Storage
Best before date
Pharmacological group
Precautionary measures

Note. Sections 1, 3 — 8, 18, 20, 25 — 32 are mandatory. The inclusion of other sections depends on the nature of the medicinal substance (substance), the technology for its preparation and the dosage forms that will be prepared from this substance.

Dosage forms for injections

(solutions for injections)

INN in Russian
Compound
Description
Authenticity
Transparency
Chroma
pH or Acidity or Alkalinity
Mechanical inclusions
Density
Viscosity
Foreign matter (related compounds)
Nominal volume
(LAL test)
Toxicity
Content of histamine-like substances
Sterility
quantitation
Package
Marking
Transportation
Storage
Best before date
Pharmacological group
Precautionary measures

Note. Sections 1 — 6, 9, 13, 17 — 24 are mandatory. The inclusion of other sections depends on the nature of the medicinal substance (substance), the technology for obtaining this dosage form and the method of its use.

Dry dosage forms for injections (powders for the preparation of solutions, suspensions for injections)

Name of the drug in Russian
INN in Russian
Compound
Description
Authenticity
Transparency
Chroma
pH or Acidity or Alkalinity
Mechanical inclusions
Foreign matter (related compounds)
Weight loss on drying or Water
Toxicity
Content of histamine-like substances
Sterility
Dosing uniformity
quantitation
Package
Marking
Transportation
Storage
Best before date
Pharmacological group
Precautionary measures

Note. Sections 1 — 7, 10, 18 — 24 are mandatory. The inclusion of other sections depends on the nature of the medicinal substance (substance), the technology for obtaining this dosage form and the method of its use. If necessary, the Solubility section is also included, which indicates the time for complete dissolution when preparing the solution in accordance with the instructions for use.

Eye drops

Name of the drug in Russian
INN in Russian
Compound
Description
Authenticity
Transparency
Chroma
pH or Acidity or Alkalinity
Mechanical inclusions
Viscosity
Osmolality
Foreign matter (related compounds)
Nominal volume
Sterility
quantitation
Package
Marking
Transportation
Storage
Best before date
Pharmacological group

Note. Sections 1 - 6, 8 - 11, 14 - 21

Liquid dosage forms for internal and external use (solutions, suspensions, syrups, emulsions)

Name of the drug in Russian
INN in Russian
Compound
Description
Authenticity
pH or Acidity or Alkalinity
Density
Viscosity
Foreign matter (related compounds)
Nominal volume
Microbiological purity
quantitation
Package
Marking
Transportation
Storage
Best before date
Pharmacological group

Note. Sections 1 — 5, 10 — 18 are mandatory. The inclusion of other sections depends on the nature of the medicinal substance (substance).

Aerosols

Name of the drug in Russian
INN (for monocomponent medicinal products) in Russian
Compound
Description
Authenticity
Pressure check
Checking the tightness of the cylinder
Valve device testing
Dose weight
Number of doses in a cylinder
Determining the yield of package contents
Particle size
Foreign matter (related compounds)
Microbiological purity
Dosing uniformity
quantitation
Package
Marking
Transportation
Storage
Best before date
Pharmacological group

Note. Sections 1 — 8, 11, 15, 17 — 23 are mandatory. The inclusion of other sections depends on the nature of the medicinal substance (substance) and dosage.

Tablets and dragees

Name of the drug in Russian
INN in Russian
Compound
Description
Authenticity
Average weight and uniformity by weight
Talc, aerosil, titanium dioxide
Microbiological purity
Dosing uniformity
quantitation
Package
Marking
Transportation
Storage
Best before date
Pharmacological group

Note. Sections 1 — 6, 8 — 10, 12 — 18

Capsules (microcapsules)

Name of the drug in Russian
INN in Russian
Compound
Description
Authenticity
Average content weight and uniformity by weight
Dissolution or Disintegration
Foreign matter (related compounds)
Microbiological purity
Dosing uniformity
quantitation
Package
Marking
Transportation
Storage
Best before date
Pharmacological group

Note. Sections 1 — 7, 9, 11 — 17 are mandatory. The inclusion of other sections depends on the nature of the medicinal substance (substance) and dosage. If the Dosage Uniformity test is available, the Mass Uniformity test is not carried out.

Suppositories

Name of the drug in Russian
INN in Russian
Compound
Description
Authenticity
Average weight and uniformity by weight
Melting point, or Time of complete deformation, or Time of dissolution
Foreign matter (related compounds)
Microbiological purity
Dosing uniformity
quantitation
Package
Marking
Transportation
Storage
Best before date
Pharmacological group

Note. Sections 1 — 7, 9 — 16 are mandatory. The inclusion of other sections depends on the nature of the medicinal substance (substance) and dosage. If the Dosage Uniformity test is available, the Mass Uniformity test is not carried out.

Ointments (creams, gels, liniments, pastes)

Name of the drug in Russian
INN in Russian
Compound
Description
Authenticity
Weight of package contents
pH of aqueous extract
Particle size
Foreign matter (related compounds)
Microbiological purity or Sterility
quantitation
Package
Marking
Transportation
Storage
Best before date
Pharmacological group

Note. Sections 1 — 6, 10 — 17 are mandatory. The inclusion of other sections depends on the nature of the medicinal substance (substance).

Medicinal plant raw materials and preparations

(packaged products: briquettes, bags, filter bags, cut - pressed, etc.)

Name of the drug in Russian and Latin
Latin and Russian name of the producing plant(s) and family
Authenticity test for whole and crushed raw materials:

3.1. External signs;
3.2. Microscopy, illustrated with a microphotography or drawing;
3.3. Qualitative and/or histochemical reactions; chromatographic samples

Numerical indicators for whole and crushed raw materials:

4.1. Content of pharmacologically active substances or biological activity;
4.2. Weight loss on drying;
4.3. General ash;
4.4. Ash is insoluble in a 10% solution of hydrochloric acid;
4.5. Acceptable impurities: crushed (sieve analysis), particles of raw materials that have changed color, other parts of the plant that are not subject to harvesting, organic impurity, mineral impurity

Microbiological purity
Packaging of whole and crushed raw materials (angro), packaged products (packs, bags, briquettes, cut - pressed, filter - bags, etc.)

Labeling of whole and crushed raw materials, packaged products (packs, bags, briquettes, cut - pressed, filter - bags, etc.). Additionally it is indicated: “The product has passed radiological control SanPiN 2.3.2560-96”
Storage
Best before date
Pharmacological group

Note. Assessment of the quality of packaged products in briquettes and cut-pressed products includes an additional determination of disintegration and deviations in mass.

Tinctures, elixirs

Name of the drug in Russian
INN in Russian
Compound
Description
Authenticity
Heavy metals
quantitation
Alcohol content or density
Dry residue
Nominal volume
Microbiological purity
Best before date
Pharmacological group

Extracts (liquid, thick, dry)

Name of the drug in Russian
INN (for monocomponent medicinal products) in Russian
Compound
Description
Authenticity
Heavy metals
quantitation
Alcohol content or density (in liquid extracts)
Dry residue
Weight loss on drying (in thick and dry extracts)
Nominal volume
Average weight (in dosed extracts)
Granulometric composition (in dry extracts)
Microbiological purity
Packaging, labeling, storage
Best before date
Pharmacological group

Homeopathic medicines

Dosage forms for injections

Name of the drug in Russian
Description
Authenticity test
Color (evaluation method and reference)
Transparency (assessment method and benchmark)
solution pH
Mechanical inclusion test
Pyrogenicity test (test - dose) (if necessary)
Sterility
quantitation
Packaging, labeling, storage
Best before date

Liquid dosage forms for internal and external use

Name of the drug in Russian
Composition indicating homeopathic dilutions of the included components and their quantities, as well as all excipients and preservatives
Description (appearance, color)
Authenticity test
pH (if necessary)
Density
Viscosity
Particle sizes (in case of suspension, emulsion)
Determination of nominal volume
Determination of alcohol (for alcohol-containing preparations)
quantitation
Microbiological purity
Packaging, labeling, storage
Best before date
Pharmacological action (only for complex drugs)

Suppositories

Name of the drug in Russian
Composition for one suppository indicating homeopathic dilutions of the included components and their quantities, as well as all excipients
Description
Average suppository weight, permissible deviations
Authenticity test
Melting point, or determining the time of complete deformation, or dissolution
Determination of uniformity
quantitation
Microbiological purity
Packaging, labeling, storage
Best before date
Pharmacological action (only for complex drugs)

Ointments

Name of the drug in Russian
Composition indicating homeopathic dilutions of the included components and their quantities, as well as all excipients
Description
Authenticity test
Weight of package contents
pH of aqueous extract (if necessary)
Determination of ointment uniformity or particle size
quantitation
Microbiological purity
Packaging, labeling, storage
Best before date
Pharmacological action (only for complex drugs)

Tablets and dragees

Name of the drug in Russian
Composition for 1 tablet indicating homeopathic dilutions of the included components and their quantities, as well as all excipients and fillers
Description
Average weight of tablets and deviations from the average weight
Authenticity test
Disintegration
quantitation
Microbiological purity
Packaging, labeling, storage
Best before date
Pharmacological action (only for complex drugs)

Granules (grains)

Name of the drug in Russian
Composition for 1 granule indicating homeopathic dilutions of the included components and their quantities, as well as all excipients
Authenticity test
Description
Number of pieces weighing 2 g
Disintegration
Weight of package contents and weight deviations
Weight loss on drying
Microbiological purity
quantitation
Packaging, labeling, storage
Best before date
Pharmacological action (only for complex drugs)

Note. The need to introduce sections “Authenticity” and “Quantitative Determination” for homeopathic drugs is decided on a case-by-case basis depending on the composition of the drug and the detection limit of the constituent components.

Immunobiological drugs

(allergens, allergoids, toxoids, bacteriophages, vaccines, immunoglobulins (antibodies), immunomodulators, diagnostic drugs)

Vaccines and toxoids

Introductory part
Description
Authenticity
; disintegration (for tablets)
Transparency
Chroma
(for drugs administered parenterally)
Weight loss on drying
Chemical indicators (protein; total protein nitrogen; nucleic acids; polysaccharides, etc.)
Sterility (absence of foreign microorganisms and fungi - for live vaccines)
Microbiological purity (for non-injectable forms)
Pyrogenicity or bacterial endotoxins
Toxicity
Specific safety
Specific activity (immunogenicity)
Antigenic activity
Completeness of sorption (for sorbed drugs)
Thermal stability
Impurities
Production strains
Substances included in the drug
Antibiotic content
Best before date
Purpose

Human immunoglobulins

Introductory part
Description
Authenticity
Solubility (for dry preparations)
Transparency
Chroma
No mechanical inclusions
Weight loss on drying
Vacuum (shielding gas, sealing)
Protein
Electrophoretic homogeneity
Molecular parameters
Factional composition
Thermal stability (for liquid preparations)
Sterility
Pyrogenicity or bacterial endotoxins
Toxicity
Specific activity (for specific antiviral, antibacterial or antitoxic Ig content of antibodies, expressed in ME, titers, etc.; for drugs enriched with immunoglobulins of classes A or M - their quantitative content; for antiallergic drugs - antiallergic activity, etc. .depending on the drug)

Specific safety:

a) control for the absence of HBsAg, AT to HIV-1 and HIV-2 (other human blood contaminants if necessary) (all drugs);
b) anti-complementarity (for Ig intended for intravenous administration);
c) hypotensive effect (for histaglobulin, histaserotoglobulin, etc.)

Packaging, labeling, transportation, storage
Best before date
Purpose

Heterologous serums

Introductory part
Description
Authenticity
Solubility (for dry preparations)
Transparency
Chroma
No mechanical inclusions
Vacuum (sealing)
Protein
Sterility
Pyrogenicity or bacterial endotoxins
Toxicity
Specific activity
Specific activity
Substances included in the drug
Solvents supplied with the drug
Packaging, labeling, transportation, storage
Best before date
Purpose

Bacteriophages

Introductory part
Description
Authenticity
Average weight (for tablets and suppositories)
Disintegration - for tablets. Solubility - for candles
(for tablets, suppositories, ointments)
Toxicity
Specific activity
Production strains
Packaging, labeling, transportation, storage
Best before date
Purpose

Immunomodulators

Introductory part
Description
Authenticity
Solubility (for dry preparations)
Transparency
Chroma
Weight loss on drying (for dry preparations)
Vacuum (shielding gas, sealing)
Chemical indicators (protein; protein nitrogen, total; nucleic acids; polysaccharides, etc.)
Sterility
Pyrogenicity
Bacterial endotoxins
Toxicity
Specific safety
Control for the absence of HBsAg, AT to HIV-1 and HIV-2 (other human blood contaminants if necessary)
Specific activity
Impurities
Substances included in the drug
Packaging, labeling, transportation, storage
Best before date
Purpose

Allergens and allergoids

Introductory part
Description
Authenticity
Protein nitrogen
Sterility
Toxicity
Specific activity
Substances included in the drug
Solvents and reagents supplied with the drug
Packaging, labeling, transportation, storage
Best before date
Purpose

Probiotics

Introductory part
Description
Authenticity
Solubility (disintegration)
Average weight (for tablets, suppositories, capsules)
Weight loss on drying
Vacuum (shielding gas, sealing)
Harmlessness
Absence of foreign microorganisms and fungi or microbiological purity
Specific activity
Production strains
Packaging, labeling, transportation, storage
Best before date
Purpose

Diagnostic drugs

Introductory part
Description
Authenticity
Solubility (for dry preparations)
Vacuum (shielding gas, sealing)
Weight loss on drying
Sterility or microbiological purity
Specific activity
Production strains
Substances included in the drug
Packaging, labeling, transportation, storage
Best before date
Purpose

Test - immunoenzyme and PCR-based systems

Introductory part
Description
Authenticity
Solubility
Vacuum (shielding gas, sealing)
Weight loss on drying
Sterility or microbiological purity
Specific activity
Packaging, labeling, transportation, storage
Best before date
Purpose

Bacteriological culture media

Introductory part
Description
Solubility
Transparency
Chroma
pH of the solution (extract - for media containing agar)
Weight loss on drying
Total nitrogen
Amine nitrogen
Chlorides
Carbohydrates
Medium jelly strength (for dense media)
Specific activity (sensitivity of the medium, growth rate and stability of the basic biological properties of microorganisms, inhibitory, differentiating properties, the set of which and the methods used depend on the purpose of the medium)
Packaging, labeling, transportation, storage
Best before date
Purpose

Nutrient media, solutions and growth factors for cell culture

Introductory part
Description
Solubility (for dry preparations)
Transparency
Chroma
Weight loss on drying (for dry preparations)
Chlorine ion
Glucose
Amine nitrogen
Protein
Buffer capacity
Osmoticity
Osmolarity
Sterility
Toxicity
Specific activity
Impurities
Packaging, labeling, transportation, storage
Best before date
Purpose

Human blood products

Liquid dosage forms of blood products

Name of the drug in Russian
Content of the active component in % or units of specific activity
Compound
Description
Transparency
Chroma
Fractional protein composition
Specific activity
Prekallikrein activator
Thermal stability
Foreign matter
No mechanical inclusions
Nominal volume
Pyrogenicity
Bacterial endotoxins
Toxicity
Sterility
Packaging, labeling, transportation, storage
Best before date
Pharmacological group

Dried and frozen dosage forms of blood products

Name of the drug in Russian
Content of the active component in mg or units of specific activity
Compound
Characteristics of accompanying solvent, activator, plasticizer
Description of the finished dosage form, as well as after its dissolution (thawing)
Solubility or dissolution time in accompanying solvent (for dry preparations)
Transparency
Color (hempigments)
solution pH
Authenticity, including confirmation of homology to human blood proteins
Quantitative determination of the main protein component
Fractional protein composition
Specific activity
Molecular parameters of the main protein component
Hemagglutinins (anti-A and anti-B)
Thrombogenicity (for coagulolytic drugs)
Prekallikrein activator
Anti-complementary activity
Thermal stability
Electrolytes (sodium, potassium, citrate, calcium, aluminum, etc.)
Foreign matter
Weight loss on drying
No mechanical inclusions
Nominal volume
Pyrogenicity
Bacterial endotoxins
Toxicity
Content of hemolytic substances
Test for the absence of antigens (antibodies) of hepatitis viruses, human immunodeficiency, and other possible contaminants of human blood
Sterility
Packaging, labeling, transportation, storage
Best before date
Pharmacological group

Appendix 3 BUILDING QUALITY STANDARDS ON SUBSTANCES

to the Industry Standard OST 91500.05.001-00 “Quality Standards for Medicines. Basic provisions"

CONSTRUCTION AND PRESENTATION OF STATE QUALITY STANDARDS FOR MEDICINES ON THE SUBSTANCE

The name of the substance in Russian, the international nonproprietary name (INN) and the chemical name in accordance with the rules of the International Union of Pure and Applied Chemistry (IUPAC) are indicated in the following sequence:

- Russian name;
— international nonproprietary name;
- chemical name.

Below the name, in the center, the structural formula should be located, shown in accordance with IUPAC rules.
In the empirical formula, which is given on the left under the structural formula, carbon is written first, hydrogen second, the following elements, including metals, are arranged in alphabetical order: for example, C12H17CIN4OS x HCI.
Relative molecular weights must be given at the latest international atomic weights and given to the second decimal place for relative molecular weights not exceeding 400 and to the first decimal place for relative molecular weights greater than 400. The content of the main active ingredient is indicated in percentages or units actions.
Depending on the content, the text of the quality standard for the substance should be presented in the form of sections and, if necessary, have an introductory part. The composition of the sections and their content should be determined in accordance with the characteristics of the physico-chemical properties or nature of the drug.
Individual sections can be combined, and if necessary, other sections can be introduced (preparation, construction of a calibration graph, preparation of a standard solution, etc.). Methods of measurement (control) must be expressed in the third person plural. The “Description” section is presented in narrative form.

In the “Description” section, indicators of the appearance of the drug (physical state, color, smell), possible changes during storage in air, in light (indication of hygroscopicity, relation to the action of light and air) are established. For poisonous and potent medicines, the odor is not indicated.
In the “Authenticity” section, the characteristics of ultraviolet (UV) and infrared (IR) absorption spectra, etc., and, if necessary, 2–3 reactions that are most specific for this drug are indicated.
In the “Solubility” section, solubility indicators in water, 95% alcohol, chloroform and ether are indicated (if the substance is practically insoluble in ether, ether is excluded from the list of solvents). If necessary, specify other solvents. Descriptive terms of solubility and the meanings of the terms are given in accordance with the general article of the State Pharmacopoeia “Solubility”. In cases where the exact solubility of a drug has been established, the ratio of the mass of the solute and the volume of the solvent is given.
Temperature limits for distillation, melting or solidification, as well as density, specific rotation, specific absorption index, refractive index and other physical constants are given in the form of separate sections in which the upper and lower limits of these standard indicators are indicated.
The transparency and color of solutions are given for a certain concentration; in the case of colored solutions, the number of the color standard and the letters of the scale or the corresponding characteristics of the absorption spectra of these solutions are indicated.
When establishing the limits of acidity and alkalinity of solutions using indicators, solutions of acids or alkalis with a concentration of 0.01 M to 0.1 M are used, the pH is determined potentiometrically.
The section “Foreign (specific) impurities” provides a detection method and acceptable standards for compounds of a technological nature or subsequently formed during storage. When using chromatographic methods for these purposes, the type of sorbent, the composition of the phases, the amount of the test substance being chromatographed, the amount of the standard sample (witness), the chromatography time, the reagent used for development, as well as all other conditions that determine the chromatography process should be indicated.
The section “Residual organic solvents” should indicate color standards that normalize the permissible amount of organic impurities, or other modern methods, for example, chromatographic methods. Control of residual amounts of solvents is introduced in the case of the use of toxic solvents in the manufacturing technology of the drug, as well as in the case of the use of organic solvents at the last stage of obtaining the drug.
The sections “Chlorides”, “Sulfates”, etc. indicate the permissible limits of these impurities related to production technology.
The sections “Weight loss on drying” and “Water” indicate the sample weight of the drug, the method for determining the end of the titration according to K. Fischer, drying conditions and the norms of weight loss on drying or moisture content.
The section “Sulfate ash and heavy metals” indicates the weight of the drug and the permissible limits for impurities of sulfate ash and heavy metals.
The “Arsenic” section specifies the permissible limits of arsenic impurities or requirements for its absence.
The sections “Toxicity”, “Pyrogenicity”, “Content of substances with histamine-like action” indicate the test - doses, methods of administration and observation period for the tested drugs.
The “Sterility” section is introduced in cases where it is impossible to sterilize the dosage form. The section “Microbiological Purity” describes the method for determining microorganisms and their acceptable limits.
The section “Quantitative Determination” describes the method for quantitative determination of the main substance contained in the drug. This section also gives the percentage of the main substance or activity in units of action in milligrams (IU/mg) when converted to the active substance.
In the “Packaging” section, indicate the primary packaging (individual packaging: cans, ampoules, bottles, bags, etc.), the number of units of products in the primary packaging (for example: the number of tablets in a bottle), secondary (consumer packaging) and the number of primary packaging in it, methods of sealing, etc. For group and transport packaging (containers), a link is given to the relevant regulatory documents. The packaging must ensure the safety of the medicinal product within the established expiration date.
The “Labelling” section is drawn up in accordance with the requirements of regulatory documents on the graphic design of medicines.
The Transport section provides a link to the current standard. If necessary, requirements related to the peculiarities of loading and unloading of products and requirements for handling products after transportation are indicated (for example, the need to hold at room temperature after transportation at subzero temperatures, etc.).

In the “Storage” section, you should indicate the storage conditions for products that ensure the preservation of their quality and presentation, and, if necessary, requirements for protecting products from the influence of the external environment (moisture, sunlight, temperature conditions) and storage features for medicines classified as toxic, strong, psychotropic, narcotic drugs and their precursors (according to the relevant current lists, including lists A and B).
The “Shelf life” section indicates the time during which the medicine can be used.
In the section “Pharmacological (biological) action” the pharmacological group of the drug is indicated.
Paragraphs 23, 24, 25, 27 are not indicated in pharmacopoeial monographs.

Appendix 4 BUILDING QUALITY STANDARDS FOR MEDICINES

to the Industry Standard OST 91500.05.001-00 “Quality Standards for Medicines. Basic provisions"

CONSTRUCTION, CONTENT AND PRESENTATION OF STATE QUALITY STANDARDS FOR MEDICINES

The title of the standard gives the name of the drug in Russian.
In the name of the medicinal product, the first word should be the name of the active substance (in the nominative case) or the trade name (in the nominative case), and the subsequent words should be the name of the dosage form, dosage (concentration), volume. For example: Analgin tablets 0.5 g or Analgin injection solution 25%.
Individual sections can be combined, and if necessary, others can be introduced (acid number, saponification number, iodine number, ether number, toxicity, pyrogenicity, content of substances with histamine-like effects, sterility, etc.).
The standard must have an introductory part. The introductory part indicates the chemical name of the active substance (for a one-component drug); Russian and Latin name of plant material, producing plant and family (for tinctures and extracts).
When describing the composition of a medicinal product, the quantitative content of active substances and the qualitative composition of excipients are indicated in the form of a list with reference to the relevant regulatory documentation containing requirements for their quality.
In the “Description” section, organoleptic indicators of the appearance of the finished medicinal product (color, smell) are established. The definition should not be used: azure, egg, etc. The main color is placed at the end of the definition, for example, greenish blue (blue color with a slight greenish tint).
The “Disintegration” section indicates the time for complete disintegration of a tablet or capsule in a liquid medium (under the conditions given in the State Pharmacopoeia).
The “Authenticity” section is set out in full in the scope of paragraph 9 of Appendix 3 to this OST.

For drugs of complex composition, after the description of the required definition, the identifiable ingredient is indicated in parentheses.

In the “Transparency” and “Color” sections, the transparency (turbidity) and color of the medicinal product are established in comparison with the solvent or the corresponding standard.
Section “Acidity”, “Alkalinity” or “pH” is set out in full in the scope of paragraph 13 of Appendix 3 to this OST.
In the sections “Dry residue”, “Alcohol content”, “Boiling point”, “Density”, “Refractive index”, “Angle of rotation”, “Viscosity” the upper and lower limits of these standard indicators are indicated in the corresponding units of measurement.
The “Dissolution” section establishes the amount of active substance that, under given conditions, must go into solution over a certain time.
The section “Quantitative Determination” describes the method for quantitative determination of the main substance contained in the medicinal product.

This section also indicates the percentage of the main substance or activity in units of action or micrograms per milligram in terms of the active substance (IU/mg) or (µg/mg) in the medicinal product or its dosage forms. For tablets, the limits for the content of the main substance are indicated in grams per tablet, based on the average weight of the tablet, in suppositories - in grams per suppository, in dragees - in grams per pill, in solutions for injections - in grams per 1 ml.

The section “Microbiological purity” is set out in the scope of paragraph 21 of Appendix 3 to this OST.
Sections “Packaging”, “Labelling”, “Transportation” and “Storage” are set out in the scope of paragraphs 23 - 25 of Appendix 3 to this OST.
Section “Pharmacological action” is set out in the scope of paragraph 28 of Appendix 3 to this OST.
In pharmacopoeial monographs, paragraphs 6, 15, 16 are indicated if necessary.

Appendix 5 BUILDING QUALITY STANDARDS FOR MEDICINAL PLANT RAW MATERIALS

to the Industry Standard OST 91500.05.001-00 “Quality Standards for Medicines. Basic provisions"

CONSTRUCTION, CONTENT AND PRESENTATION OF QUALITY STANDARDS FOR MEDICINAL PLANT RAW MATERIALS

The title of the standard gives the name of the medicinal plant material in Russian and Latin.
Russian and Latin names of medicinal plant materials are given in the plural.

In the name of medicinal plant raw materials, the first word should be the name (in the nominative case) or trade name (in the nominative case), and the subsequent words should indicate the form (collection, briquette, etc.).

The standard must have an introductory part. The introductory part indicates: the name and area of application of medicinal plant raw materials, the producing plant and family (in Russian and Latin).
The section “External characteristics” provides a brief description of the morphological characteristics of whole and crushed raw materials.
The “Microscopy” section provides a description of the diagnostic characteristics of raw materials, illustrated with microphotographs or drawings.
The section “Qualitative reactions” provides methods for microchemical, histochemical and other reactions or chromatographic tests.
In the “Numerical indicators” section, standards are established for the percentage of active substances (pharmacologically active substances) or biological activity, moisture standards (mass loss during drying), total ash and insoluble ash in a 10% solution of hydrochloric acid, acceptable impurities and grinding.
The section “Quantitative determination” provides methods for determining the content of active substances.
The section “Microbiological purity” is set out in accordance with paragraph 21 of Appendix 3 to this OST.
Sections “Packaging”, “Labelling”, “Transportation” and “Storage” are set out in the scope of paragraphs 23 - 26 of Appendix 3 to this OST.
The “Shelf life” section is set out in the scope of paragraph 27 of Appendix 3 to this OST.
Section “Pharmacological action” is set out in the scope of paragraph 28 of Appendix 3 to this OST. Section headings are placed on a red line and are highlighted in bold or underlined.
In pharmacopoeial monographs, paragraphs 10, 11, 12 are indicated if necessary.

Appendix 6 FORM OF THE TITLE SHEET OF THE GENERAL PHARMACOPOEIAL MOUNTING

to the Industry Standard OST 91500.05.001-00 “Quality Standards for Medicines. Basic provisions"

FORM OF THE TITLE SHEET OF THE GENERAL PHARMACOPOEIAN ARTICLE MINISTRY OF HEALTH OF THE RUSSIAN FEDERATION

—————————————————————-

I APPROVED

FULL NAME.

"__" ___________ ____ G.

State quality standard

medicine

General pharmacopoeial monograph

Name OFS 42-ХХХХХ-ХХ

General pharmacopoeial monograph

──────────────────────────────────────────────────────────────────

Expiration date set

with "__" _____________ ____ g.

to "__" ____________ ____

──────────────────────────────────────────────────────────────────

Appendix 7 FORM OF THE TITLE LIST OF THE PHARMACOPOEIAL MOUNTING

to the Industry Standard

OST 91500.05.001-00 “Quality standards for medicines. Basic provisions"

FORM OF THE TITLE SHEET OF THE PHARMACOPOEIAL MONETARY MINISTRY OF HEALTH OF THE RUSSIAN FEDERATION

—————————————————————-

I APPROVED

FULL NAME.

"__" ___________ ____ G.

State quality standard

medicine

Pharmacopoeial monograph

──────────────────────────────────────────────────────────────────

Name FS 42-ХХХХХ-ХХ

medicine

──────────────────────────────────────────────────────────────────

Expiration date set

with "__" _____________ ____ g.

to "__" ____________ ____

──────────────────────────────────────────────────────────────────

Appendix 8 FORM OF THE TITLE LIST OF THE COMPANY'S PHARMACOPOEIAL MOUNTING

to the Industry Standard OST 91500.05.001-00 “Quality Standards for Medicines. Basic provisions"

FORM OF THE TITLE SHEET OF THE PHARMACOPOEIAL NUMBER OF THE ENTERPRISE MINISTRY OF HEALTH OF THE RUSSIAN FEDERATION

—————————————————————-

I APPROVED

FULL NAME.

"__" ___________ ____ G.

State quality standard

medicine

Pharmacopoeial monograph of the enterprise

(name of the enterprise - manufacturer (developer)

medicine; indicated in the nominative case)

──────────────────────────────────────────────────────────────────

Name FSP 42-ХХХ-ХХХХХ-ХХ

medicine

──────────────────────────────────────────────────────────────────

Expiration date set

with "__" _____________ ____ g.

to "__" ____________ ____

──────────────────────────────────────────────────────────────────

Appendix 9 FORM OF THE LAST SHEET OF THE COMPANY'S PHARMACOPOEIAL MONITOR

to the Industry Standard OST 91500.05.001-00 “Quality Standards for Medicines. Basic provisions"

FORM OF THE LAST SHEET OF THE COMPANY'S PHARMACOPOEIAN MOUNTING

Head of the manufacturer

medicines

(developer organization) _________ Full name

(signature) M.P. date

Agreed

Head of the body (organization),

who carried out the examination of the FSP _________ Full name

(signature) M.P. date

Appendix 10

to the Industry Standard

OST 91500.05.001-00

"Quality standards

medicines.

Basic provisions"

FORM OF COVER SHEET CHANGES

PHARMACOPOEIAN ARTICLE AND FSP

MINISTRY OF HEALTH OF THE RUSSIAN FEDERATION

—————————————————————-

I APPROVED

FULL NAME.

"__" ___________ ____ G.

__________________________________________________________________

(designation FS or FSP)

__________________________________________________________________

(name of FS or FSP)

__________________________________________________________________

(name of the enterprise - manufacturer (organization -

developer) of the medicinal product;

indicated in the nominative case)

Change N ___

The deadline for introducing changes from “__” is ______________ ____.

──────────────────────────────────────────────────────────────────

Old edition New edition

──────────────────────────────────────────────────────────────────

Text Text

──────────────────────────────────────────────────────────────────

Concept and characteristics of pharmacopoeia. Structure of a pharmacopoeial monograph. GP quality control requirements. Main types of standard samples. History of domestic pharmacopoeias. State Pharmacopoeia X and XI. Pharmacopoeia of the Russian Federation and the USA.

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Chapter 1. Concept and characteristics of pharmacopoeia

1.1 Definition of pharmacopoeia

The State Pharmacopoeia is the main document regulating pharmaceutical analysis.

Pharmacopoeia (pharmakopiea)- a Greek word containing two roots: Pharmakon- medicine and poieo- I do (the art of preparing medicines).

Pharmacopoeia- this is an official guide for pharmacists (pharmacists), containing a description of the properties, authentication and quality testing, and storage conditions.

The Pharmacopoeia contains mandatory national standards and regulations that regulate the quality of medicines.

The GF consists of general pharmacopoeial monographs (GPM) and pharmacopoeial monographs (FS).

General pharmacopoeial monographs and pharmacopoeial monographs must be revised by the Scientific Center for Expertise and State Control of Medicines of the Russian Ministry of Health at least every five years.

1.2 Structure of a pharmacopoeial monograph

In the “Authenticity” section, the characteristics of UV and IR absorption spectra or other methods are indicated, as well as 2 - 3 chemical reactions that are most specific for a given drug.

When determining authenticity using chemical color reactions, group or specific reagents can be used. General (group) authenticity reactions can be used, for example, in the detection of aromatic amino compounds with the formation of aniline dyes.

A particular (specific) reaction to authenticity, for example, the determination of sodium ions in sodium chloride, is carried out by qualitative reactions to the presence of sodium ion - with zinccuranyl acetate or by flame color.

Temperature limits for distillation, melting and solidification temperatures, as well as density, specific rotation, specific absorption index, refractive index and other physical constants can be used as indicators of the authenticity and purity of a drug.

An approximate (within certain limits) assessment of the content of some permissible impurities is carried out using standard solutions.

For example, for chloride tests, a reference solution is prepared by mixing solutions of sodium chloride and silver nitrate. A standard solution for sulfate ion is prepared by mixing barium chloride and potassium sulfate.

Standards for determining the color of liquids are prepared from salts of cobalt(II), chromium(VI), copper(II) and iron(III). In this case, standard solutions of brown, yellow, pink and green shades are obtained. The color is observed on a white background.

The section “Residual organic solvents” provides the results of determining the residual amounts of solvents if they were used in the drug manufacturing process.

In the sections “Chlorides”, “Sulfates”, “Sulfate ash and heavy metals” the permissible limits of these impurities are indicated, in the section “Arsenic” the permissible limits or requirements for the absence of arsenic are indicated.

The sections “Weight loss on drying” and “Water” indicate drying conditions, rates of weight loss on drying or moisture content.

One of the quality criteria is consistency of composition PM.

The drug can hydrolyze in the presence of moisture and when heated:

In this case, the composition of the drug changes. Irreversible changes in composition also occur during weathering - loss of crystallization water. In addition, the properties of drugs change when carbon dioxide is absorbed from the air.

The sections “Toxicity”, “Pyrogenicity”, “Content of substances with histamine-like action” indicate test doses, methods of administration, and period for observing the effect.

The section “Microbiological purity” describes the method for determining microorganisms and the permissible limits for their content.

The “Quantitative Determination” section provides a description of the method(s) for quantitative determination of the main substance contained in the drug, its mass fraction as a percentage or activity in units of action per milligram (IU/mg) when converted to the active substance.

The “Application” section contains information about the dosage forms of the drug, methods of administration and dosage.

1.3 Quality control requirements G.P.

Chapter 2. Pharmacopoeia of the USSR

2.1 History of domestic pharmacopoeias

The history of the creation of the first Russian pharmacopoeias begins in the second half of the 18th century.

In 1765, the Military Pharmacopoeia was published for the first time in Russia, and in 1778 the first official Russian State Pharmacopoeia was published.

The latter contained description 770 LP mineral, vegetable And animal origin, as well as multicomponent dosage forms.

In 1798, the second State Russian Pharmacopoeia was published, published, like the first, in Latin (translated into Russian in 1802).

After 1798, Military Pharmacopoeias (1808, 1812, 1818, 1840), Marine Pharmacopoeia (1864), Pharmacopoeias for the Poor (1807, 1829, 1845, 1860) and Court Pharmacopoeias (1825, 1872) were published in Russia. , 1874).

The Pharmacopoeia of 1866 became the first edition of the Russian Pharmacopoeia. Then II, III, IV, V, VI editions were published in 1871, 1880, 1891, 1902 and 1910, respectively.

In 1949, the VIII edition was published, and in October 1961, the IX edition of the State Pharmacopoeia of the USSR was published.

The X edition of the State Pharmacopoeia (SP X) came into force on July 1, 1969. It reflected the new successes of domestic pharmaceutical and medical science and industry.

2.2 State Pharmacopoeia X

The tenth edition of the State Pharmacopoeia (GF X) contains an introductory part, two main parts and “Appendices”.

The first part - “Drugs” - includes individual articles that define the quality requirements for individual medicines, and group articles (tablets, injection solutions, extracts, herbs, tinctures, etc.).

The second part of the Pharmacopoeia contains a description of physicochemical, chemical, pharmacological and biological research methods, as well as reagents, titrated solutions and indicators.

The “Appendices” section contains tables of atomic weights, alcoholometric tables, drop tables, etc., as well as the highest single and daily doses of poisonous and potent drugs for adults and children and single, most commonly used doses of drugs for animals.

The tenth edition of the State Pharmacopoeia has a number of differences from the previous, IX edition.

The tenth edition of the State Pharmacopoeia contains 707 individual articles (in GF IX - 754) for various drugs and 31 group articles (in GF IX - 27).

219 private articles and 4 group articles were again included in Global Fund X; 235 articles contained in Global Fund IX are not included. The list of these articles is given on pages 23-25. 28 articles on vaccines and serums used in veterinary medicine were also excluded.

The requirements of GF IX for alcohols 90°, 70° and 40° are combined into one article, as well as the requirements for purified and precipitated sulfur.

The nomenclature of articles of the Global Fund X reflects the successes achieved in the creation and introduction of drugs into medical practice.

The quality of medicinal products not included in the State Fund X, but produced by industry, must be checked according to the relevant articles of the State Fund IX or the Inter-Republican Technical Specifications (MRTU 42).

GF X does not include tablets of complex composition (containing more than one active ingredient).

The articles in the “Drugs” section are placed in alphabetical order in accordance with their Latin names, with the exception of articles on dosage forms (injection solutions, tablets, ointments), which in this edition are placed after the article on the original medicinal substance.

The following sequence of titles is adopted in the headings of articles:

a) Latin name;

b) Russian name, which is an exact translation of the Latin name; in exceptional cases, names are given that deviate from the exact translation, but are generally accepted in the USSR;

c) synonyms: first - the main Latin and Russian synonyms used in the USSR, then the international Latin non-proprietary names recommended by the World Health Organization (WHO), if they do not coincide with the main Latin name of the Global Fund X.

International names are indicated by the symbol * and left without Russian translation.

Latin and Russian names of plant materials are given in the singular, except for “flowers” ​​- Flores, since this term means not only single flowers, but also inflorescences.

Russian names are adopted for reagents.

In order to achieve uniformity and consistency between individual groups of drugs, GF X introduced changes in the rational names and structural images (formulas) of drugs.

For salts of organic bases, the expanded name of the base in the genitive case is written in the first place, and the acid or acid radical in the nominative case is written in the second place.

The nomenclature of sulfonamide drugs remains the same as in SP IX, which corresponds to the generally accepted names of this class of compounds in the domestic chemical literature.

For gross formulas, the international system is adopted: carbon is written first, hydrogen second, the following elements, including metals, are arranged in alphabetical order.

Derivatives of acid radicals are depicted in detail.

The formulas of alkaloids, antibiotics, steroids and glycosides are depicted in planar form, but with a configurative designation.

For ease of use of the Pharmacopoeia, the structure of the articles in the new edition has been slightly changed (with the exception of articles on medicinal plant materials).

The “Properties” section has been replaced with 2 sections: “Description” and “Solubility”.

Due to the inclusion of a general article containing authenticity reactions for 25 ions and functional groups, a link to this article is provided for many drugs in specific articles. Some reactions to authenticity have been unified or replaced by new, more specific ones.

The “purity test” is divided into separate sections (chlorides, sulfates, etc.).

Instead of the two methods of quantitative determination that were available in a number of articles of the Global Fund IX, the new edition, as a rule, provides one method. In some cases, when GF X contains two methods and there are no special instructions, both methods are mandatory.

In GF X, the requirements for the quality of medicinal products have been increased in relation to both testing for purity and the quantitative content of the substance in the drug.

Many analysis methods available in GF IX have been clarified, changed and improved, and a number of new methods have been included.

For the first time, the following articles on methods of analysis are included in the Pharmacopoeia."

"General Reactions to Authenticity"

"Method of combustion in oxygen"

"Spectrophotometry in the infrared region" as a section of the article "Definitions based on measurements of light absorption",

"Fluorometry"

"Polarography"

"Nitritometry"

“Chromatography in a thin layer of sorbent” as a section of the article “Chromatography”

Latin and Russian names of plant materials are given in the singular, except for “flowers” - Flores, since this term means not only single flowers, but also inflorescences.