The nature of the participation of industries in the production of final products determines the features of the relationship between them, their integration and, consequently, the features of forecasting intersectoral integration processes. There are several types of intersectoral national economic complexes.

The peculiarity of the first type of complexes is that it contains the main, leading industry that produces the final products of the complex, while other industries produce means of production for this leading industry or provide it with various types of production services. This integration basis is typical for agro-industrial, investment complexes. In each of them, depending on the functions performed, three groups of industries are distinguished: the first, the main one, is agriculture and capital construction; the second and third are the service industries of the first (in the agro-industrial complex, these are the industries that produce agricultural machinery, fertilizers, and the industries engaged in the harvesting, transportation, storage of agricultural products, in the investment complex, the industries that produce Construction Materials, construction equipment, and industries producing equipment to be assembled, installed at facilities under construction).

The second type of intersectoral complexes can be called technological, since its integration is based on the technological dependence of one industry on another.

IN technological complexes the functioning of each industry is a separate stage of the general technological process of manufacturing the final product of the entire complex, and the final product of one industry is a semi-finished product for the manufacture of the final product of another industry. In other words, all industries can be arranged in a certain order, corresponding to the sequence of stages of the general technological process. This nature of the integration basis is clearly manifested in the mining and metallurgical, fuel and energy, chemical and forestry complexes.

The integration basis of the third type of complex is transport- other, mostly indirect. It manifests itself in the fact that all the transport sectors that form this complex (railway, road, water, sea and river, pipeline, aviation, horse-drawn) produce a homogeneous type of service - carry out freight and passenger transportation, but use different vehicles for this. The homogeneity of the functions performed by the transport sectors determines the feasibility of combining them in one complex, since many management issues, rational transport services can only be solved on the scale of the totality of all transport sectors, and not each separately. Such issues may be: the need for a rational distribution of freight and passenger traffic between different modes of transport, achieving maximum compliance with the production capacities (throughput and carrying capacity) of various modes of transport in conditions of mixed transport.

The following type of intersectoral complexes is presented mechanical engineering. It differs from the previous ones in that, firstly, it is the largest and most complex complex in terms of composition. If the previous complexes consist of several branches, then the machine-building complex includes several dozen branches. Secondly, an essential feature of the complex is that the indirect nature of the relationship between its branches is manifested to a greater extent than in the transport complex. Each machine-building branch produces, independently of the other, different, as a rule, non-interchangeable types of products. The indirect relationship between them is manifested as follows:

a) using the same raw material - metal;

b) in the similarity of manufacturing technologies in various engineering industries. The degree of similarity can be very high, for example, in the production of combines, tractors and automobiles, and relatively low, for example, in the instrument and heavy engineering industries;

c) in the similarity of labor tools, for example, in many branches of engineering, lathes, milling, rotary, grinding, machine tools with numerical control are used;

d) in the similarity of schemes of organizations for the production of various types of machine-building products (large-scale, serial, small-scale);

e) all engineering industries produce various types of tools.

The expediency of combining engineering industries into a single complex is determined by the fact that many issues of their development can be optimally resolved only at the level of the entire set of industries or their individual groups, for example, issues of using the results of scientific and technical progress (saving metal and other raw materials, organizing production and using high technologies) .

The formation of intersectoral national economic complexes in the Russian Federation is a long, complex, developing process that requires state management (regulation). The development of complexes is manifested in the improvement of the relationship between the branches of each of them and overcoming the difficulties and problems that have arisen in recent years.

Among the general problems, first of all, it is necessary to single out: stabilization of production and ensuring its growth; activation of the processes of renewal of fixed production assets; improvement economic indicators economic activity industries - labor productivity, capital productivity, material consumption, profitability, cost and increased investment activity.

Other problems reflect the specifics of each complex: economic, organizational, structural and technological. Thus, for the sectors of the machine-building complex, the problems of increasing the equipment shift ratio, updating active production assets, machine park, improving the quality characteristics of products to a level that allows them to compete in world markets are very relevant. For the agro-industrial complex, the problems of increasing the efficiency of agricultural production are relevant - increasing yields, productivity, labor productivity, reducing the cost of agricultural products, increasing the volume of its production, improving the economic relations of agricultural enterprises with enterprises producing agricultural machinery, fertilizers, fuels and lubricants and other products for agriculture, elimination of intersectoral disproportions .

The development of forecasts for the development of intersectoral complexes is aimed at solving the problems that have arisen in the shortest possible time. To do this, the causes of problems are identified, the mechanisms of their action are analyzed, the causes of those difficulties that hinder the development of production. Some of them are objective and can be eliminated through appropriate measures of public administration, in particular through the improvement of tax, credit systems, and the price mechanism. Other causes of difficulties are subjective and can be eliminated as experience in managing in new conditions is accumulated.

The forecasts also reveal the possibility and expediency of further strengthening integration processes, improving economic relations between economic entities various industries inside complexes, changes in organizational forms of management, management schemes for complexes.

For example, in the agro-industrial complex, a new, integration form of organizing production and selling final products is developing - agricultural firms. As part of agricultural firms, there are agricultural enterprises that produce crop and livestock products, enterprises that transport, store, process, manufacture and sell the final products of the complex. Such a combination of functions can significantly reduce the cost of producing the final product (due to a sharp reduction in intermediary functions, transportation agricultural raw materials, semi-finished products, finished products, saving fixed costs) and bring the process of selling products directly to the consumer.

Each intersectoral forecast contains a justification, calculation of quantitative indicators of the complex, which reflect the dynamics of production volumes, the scale of economic activity. In the agro-industrial complex, such indicators are primarily indicators of the volume of agricultural products - crop production and animal husbandry.

An indicator of the volume of crop production is the gross grain harvest. This is a natural indicator. Its forecast value is determined as the product of the forecast values ​​of yield and sown areas.

Initially, the dynamics of productivity is calculated - the main source of increasing the gross harvest. For this, it is used factor method. The main factors influencing yields are variety, seed quality, soil preparation quality, fertilizer application, organization of sowing operations, quality of crop care, organization of harvesting operations, reduction of grain losses during its harvesting, transportation and storage.

After determining the composition of factors, it is calculated degree of influence each and the total influence of all factors on the yield dynamics in the forecast period.

Forecast calculations of dynamics should be supplemented by calculations economic efficiency. To do this, the value of the increase in agricultural products as a result of the action of each factor is compared with the cost of resources. For example, the yield increase is determined as a result of an increase in the applied fertilizers. It is calculated on the basis of scientific agrotechnical research, practical experience regarding each type of soil, each type of fertilizer. Then additional costs are calculated for the purchase of fertilizers, their introduction into the soil.

After calculating the yield dynamics, the size of sown areas and their structure are predicted. Given the volume of the gross grain harvest and the calculated yield value, the predicted value of the sown area can be determined as the quotient of dividing the gross harvest by the yield. At the same time, one should take into account the rational distribution, the use of sown areas for growing various types of crops, and focus on the optimal variant of the structure of sown areas. The significance of this task is determined by the fact that agricultural land is interchangeable, i.e. on one piece of land can be grown different cultures, but their yield is usually not the same. Therefore, it is necessary to justify and focus on such a variant of specialization of agricultural land, in which the yield of all types of crops is maximum. For this purpose, the balance method is used in forecasting, land balances are developed, which reflect the resources of each type of agricultural land, soil type. Comparison of land balance information with the country's needs for various types crop production allow to substantiate the optimal variant of the structure of sown areas.

The volume of livestock production depends on the number of livestock and the productivity of each of its species. Forecasting the dynamics of livestock productivity is carried out by the factorial method.

The main factors influencing the dynamics of productivity are the breed, age composition and structure of the herd, the quality of fodder, the availability of farms with it, the quality of livestock care, feeding. After calculating the influence of each factor and the total influence of all factors, the dynamics of productivity in the forecast period is substantiated. The predicted size of the livestock population is determined by its type - large cattle, small cattle, pigs. Its dynamics depends on the rate of reproduction of the herd, which is influenced by a large number of factors, the most significant of which are the age, breed structure of the herd, the quality of care for the younger generation. The degree of influence of each factor and the total influence of all factors can also be calculated based on the results of studies of the relevant scientific institutions.

In developing a forecast for the development of the investment (construction) complex, substantiation of the main indicators of its functioning is of particular importance: the volume of capital investments, the commissioning of production capacities and fixed assets. In forecasting capital investments, it is important to determine the size of their required and possible volume.

To justify the first value, it is required to determine the need for capital investments. Their size depends on the scale of activity, i.e. the projected volume of increase in production capacity, as well as the scale of the necessary renewal of fixed assets. The calculations use the norms of specific capital investments, which are set per unit of increase in production capacity and are differentiated by branches of material production and the social sphere.

The predicted value of the required volume of capital investments can be calculated as the product of the norms of specific capital investments by the predicted increase in production capacities.

IN modern conditions The need of the Russian economy and its social sphere for capital investments is very high due to the huge scale of the past reduction (decline) in production and, in particular, the volume of capital investments due to the high level of depreciation of fixed assets in the national economy. Over the past 6 years, the volume of capital investments has decreased by more than 70%, and the level of depreciation of fixed assets in industry, taking into account the moral factor, has reached more than 60%.

The dynamics of the predicted value of the possible volume of capital investments in a market economy is influenced by two groups of factors. The influence of the first group determines the availability of funds from the main investors. The second group of factors influences the interest in investing and renewing fixed assets. Both groups of factors act in the direction of reducing the volume of capital investments, while the main investors are enterprises and firms in the non-state sector.

"Pannuvladinum" - sresies.

VFS RK 42-1257-04.

Tetracycline

Tetracycline

active substances:

tetracycline 10 mg;
Excipients:

lanolin anhydrous

Description.

Microscopy.

Indications for use.

Blepharitis (inflammation of the eyelids);

Contraindications

Children's age up to 8 years

Side effects

allergic reactions

Hyperemia and edema of veins

Methods of application and doses

Overdose

Not identified

Storage conditions

Best before date

Terms of dispensing from pharmacies

Without recipe

Chemical scheme of production

In the production of the collection of medicinal plant raw materials "Pannuvadin" chemical transformations do not occur.

Technology system production

Tetracycline Lanolin Vaseline Tubalards

toltyruga dayyndau

Өlsheu Өlsheu Өlsheu Zhuu

Balkytu Sterildeu

Sterildeu

Negizdin kuramyna engizu

Homogenizationlau

Sapasyn bagalau

Bolshekteu

Oramdau cardboard pack

Dayyn onim

Hardware scheme of production and specification of equipment

VR-I. Raw material preparation

VR-I. 2. Grinding and sieving of medicinal

vegetable raw materials

Crushers of the KDU-2m type are used for grinding vegetable raw materials. Sifting pieces of leaves and stems of various shapes is carried out through a sieve with a hole with a diameter of 3-4 mm.

Before operation, the crusher and the set of sieves are freed from dust and mechanical impurities. Be sure to check the grounding of the equipment and the presence of casings. Operators servicing this equipment must be provided with respirators or gauze bandages that protect the upper respiratory tract, as well as goggles.

a) Grinding and sifting peppermint leaves

4 kg of peppermint leaves with a moisture content of not more than 14% enter production at the stage VR-1.2 “Crushing of medicinal plant materials”. After crushing and sifting, 3.96 kg of crushed peppermint leaves were obtained.

Losses amounted to 1%.

b) Grinding plantain leaves

4 kg of plantain leaves with a moisture content of not more than 14% enter production at the stage VR-1.2 “Crushing of medicinal plant raw materials”. Crushers of the KDU-2m type are used for grinding vegetable raw materials. Sifting pieces of leaves and stems of various shapes through a sieve with a hole with a diameter of 3-4 mm. After crushing and sieving, 3.96 kg of crushed plantain leaves were obtained.

Losses amounted to 1%.

c) Grinding herb wormwood

20 kg of wormwood herb with a moisture content of not more than 13% enters production at stage VR-1.2 “Crushing of medicinal plant raw materials”. Crushers of the KDU-2m type are used for grinding vegetable raw materials. Sifting pieces of leaves and stems of various shapes through a sieve with a hole with a diameter of 3-4 mm. After crushing and sifting, 3.96 kg of crushed wormwood herb was obtained.

Losses amounted to 1%.

d) Grinding the grass of Gerard's rush

4 kg of Sitnik Gerard herb with a moisture content of not more than 12% enters production at the stage VR-1.2 “Crushing of medicinal plant raw materials”. Crushers of the KDU-2m type are used for grinding vegetable raw materials. Sifting pieces of leaves and stems of various shapes through a sieve with a hole with a diameter of 3-4 mm. After crushing and sieving, 3.96 kg of crushed herb Sitnik Gerard was obtained.

Losses amounted to 1%.

e) Grinding herb cochia broom

4 kg of cochia broom herb with a moisture content of not more than 14% enters production at the stage VR-1.1 “Crushing of medicinal plant raw materials”. Crushers of the KDU-2m type are used for grinding vegetable raw materials. Sifting pieces of leaves and stems of various shapes through a sieve with a hole with a diameter of 3-4 mm. After crushing and sifting, 3.96 kg of crushed kochia broom herb was obtained.

Losses amounted to 1%.

Large inclusions of stems and roots of plants larger than 10 mm after sifting through sieves with a diameter of 7 mm amounted to no more than 1% of the mass of the processed medicinal raw materials. This fraction in the form of waste is taken out by road to the dump.

Gathering "Pannuvladin"

The collection is packaged with a mass of 10 g in plastic bags according to GOST 12302. Eight plastic bags placed in a pack of cardboard type chrome-ersatz TU 13-0281020-97-90 or cardboard for consumer packaging in accordance with GOST 7933-89. The packs are wrapped with a film of the PC-2 brand (Certificate of Conformity No. KK.646092.01.0107279).

Group and shipping containers in accordance with GOST 17768-90.

Marking. On the pack indicate the Republic of Kazakhstan, Aldiyar-Pharm LLP, TsAAMB LLP, the legal address of the manufacturer, the name of the collection in the state, Latin and Russian languages, the method of application, storage conditions, the amount of the drug in grams, the inscription "Products passed radiation control ”, series, expiration date.

Packages that do not meet the requirements are torn apart. Raw materials are released from packaging, inspected and repackaged.

Product losses during packaging are 3%, i.e. 0.6 kg.

Packing angro 50 kg. Packed in fabric bags according to GOST 19317-73 or flax-jutokenaf according to GOST 18225-72. When packing raw materials in double bags, one bag is first inserted into the other. Bags filled with raw materials must be sewn manually with bast fiber twine in accordance with GOST 17308-85 or linen threads in accordance with GOST 14961-85 stitches at least 2 cm or machine-made with a chain double seam.

When sewing the bag by machine, a comb with a width of at least 5 cm must remain above the seam. When sewing the bag manually, two ears with a length of at least 10 cm must be made in the upper part of the bags. When packing raw materials in double bags, both bags are sewn simultaneously. Bags must be sewn with a cross seam: first they are sewn in one direction, then in the opposite direction - with stitches at a distance of no more than 4 cm. The mass of raw materials packed in a bag must be 50 kg net. Shipping container marking in accordance with GOST 14192-96.

Transportation in accordance with GOST 17768-90.

material balance

environmental protection

Air emissions

Characteristics of the final product of production

Pannuvladin – d¸ðiëiê ¼ñiìäiê shikiçattardy» zhyynty¹û.

Pannuvladin - collection of medicinal plant materials

"Pannuvladinum" - sresies.

VFS RK 42-1257-04.

Tetracycline

Tetracycline

Composition per 1 g of the drug, in milligrams:
active substances:

tetracycline 10 mg;
Excipients:

lanolin anhydrous

Description.

Microscopy.

Vaseline - Homogeneous, odorless ointment mass stretching with threads, from white to yellow. When smeared on a glass plate, it gives an even, non-slip film. When melted, it gives a clear liquid with a slight odor of paraffin or oil.

Lanoloin - A thick, viscous yellow or brownish-yellow mass, with a peculiar smell, melting at a temperature of 36 - 42 ° C. It differs from other waxes by its high content of sterols (in particular, cholesterol). It is well absorbed into the skin and has a softening effect. The composition of lanolin is very complex and has not been fully studied to date. Basically, it is a mixture of esters of macromolecular alcohols (cholesterol, isocholesterol, etc.) with higher fatty acids (myristic, palmitic, cerotinic, etc.) and free macromolecular alcohols. According to its properties, lanolin is close to human sebum. In chemical terms, it is quite inert, neutral and stable during storage. The most valuable property of lanolin is its ability to emulsify up to 180-200% (of its own weight) of water, up to 140% of glycerol and about 40% of ethanol (70% concentration) to form water/oil type emulsions. Additives of a small amount of lanolin to fats and hydrocarbons sharply increase their ability to mix with water and aqueous solutions, which led to its widespread use in the composition of lipophilic-hydrophilic bases.

Numerical indicators. Essential oil not less than 0.5%; polysaccharides not less than 3%; loss in mass during drying is not more than 10%; total ash no more than 10%; ash insoluble in 10% hydrochloric acid, not more than 3%; parts of plants that have changed their original color, not more than 1%; particles that do not pass through a sieve with holes of 7 mm, not more than 10%; particles passing through a sieve with a hole diameter of 0.5 mm, not more than 10%; organic impurities not more than 1%; mineral impurities not more than 0.5%; heavy metals not more than 0.001%.

Microbiological purity. The collection must meet the requirements of GF X1, vol. 1, p. 193.

In 1 g of raw materials, no more than 10 7 aerobic bacteria and 10 5 yeast and mold fungi (total), Escherichia coli no more than 10 2 are allowed.

Methods of qualitative reactions and quantitative determination are presented in VFS RK 42-1257-04.

pharmacological properties. Hepatoprotective, anti-inflammatory agent:

It has a reparative stabilizing effect on liver cells;

Favorably affects the detoxifying function of the liver;

Helps protect the liver tissue and activate the processes of its recovery;

Improves the outflow of bile through the intrahepatic passages and ducts;

Increases the intensity of the antioxidant system of the liver;

Reduces the activity of liver enzymes in the blood serum.

Indications for use.

Conjunctivitis (inflammation of the mucous membrane of the eye);

Blepharitis (inflammation of the eyelids);

Keratitis (inflammation of the cornea of ​​the eye);

Trachoma (infectious eye disease).

Contraindications

Hypersensitivity to the components of the drug

Renal and liver failure

Pregnancy, lactation

Children's age up to 8 years

Side effects

allergic reactions

Hyperemia and edema of veins

Transient blurred vision

Methods of application and doses

Locally, lay for the lower eyelid 3-5 times a day.

Blepharitis: 3-4 times a day for 10 days.

Bacterial keratitis, keratoconjunctivitis: 2-3 times a day for 10 days. If the condition does not improve within 3-5 days, you should consult your doctor.

Meibomite (barley): at night until the symptoms of inflammation disappear.

Trachoma: every 2-4 hours or more often for 1-2 weeks. The duration of the course of treatment of trachoma should not exceed 1-2 months.

Overdose

Not identified

Storage conditions

To store in the place protected from light, at a temperature no more than 15 °C.

Best before date

Storage after the first opening of the package is no more than 5 weeks.

Do not use after the expiration date

Terms of dispensing from pharmacies

The experimenter carries out an active dialogue with the computer. Information is used on the adjustment indicators of the estimated demand for the type of product and its final production by the industry. If the indicator exceeds one, then the demand for the product is higher than the supply, if it is less than one, then vice versa. Corrective indicators and growth rates of gross output by industry are analyzed by the experimenter from the standpoint of their tolerance.

The survey was conducted during the period when the industry worked under the conditions of a 6-day working week with an 8-hour working day, therefore, if the distribution of gas consumption by hours of the day does not currently differ fundamentally from that which took place during the survey, then the distribution by day of the week is significantly has changed (except, of course, for production with a continuous technological process). In this regard, the data in Table. Tables IX-14 have been adjusted based on expert judgment for a 5-day working week (Table IX-15).

The starting point for the deployment of macroeconomic indicators is the volume of the annual aggregate production of goods and services. In the national accounting system, this indicator is called the gross national product (GNP). GNP can be defined as the total market value of the entire annual volume of final production of goods and services in the economy of a given state. The criterion for the final production of goods and services means that those economic benefits that are already included in the cost of the costs of final products are not included in GNP. Such goods are called intermediate products.

First, GNP is the total market value of the entire final production of goods and services in an economy over a given period (usually a year).

Let us consider the distribution channels through which goods from final production through a system of distribution centers enter final consumption (Fig. 48).

Enterprises representing a combination of productions, which are successive stages of one technological process, are classified, as a rule, by final production. For example, enterprises of the extractive industry, in which, along with the extraction and primary processing of minerals, their subsequent processing into products is carried out, they belong to one or another industry for the processing of extracted materials. But in cases where the production of the final product plays a subordinate role in the overall output of the enterprise and the products of one of the intermediate industries (semi-finished products) are predominant in it, this enterprise belongs to the industry for this intermediate production.

When planning chemicalization, which includes the stages of creation, manufacture and application of chemical materials and technologies, it is of particular importance to establish indicators for the development of chemical industries based on the economic purpose of its products, which are mainly objects of labor, i.e. intermediate products. Therefore, these indicators should be determined on the basis of an analysis of the goals and objectives of the final industries using chemical materials, and the possibilities of their effective application.

Balance Value of work in progress final production

Production and sale of intermediate and final Production and sale of intermediate, but not sale of final

The second is the contradiction between the raw material content of exports and the orientation of imports towards final products. This is easy to see in the example of a multi-level structure. modern economy 1 - a level that generates a stream of innovations and new designs 2 - rapidly updated individualized production 3 - mass large-scale production 4 - release of basic resources for large-scale production 5 - traditional slowly updated production (agricultural sector, etc.). Higher levels also have a higher added value.

Under ideal market conditions, the forest rent formed at different stages of timber processing should be the same value. In practice, in domestic conditions, due to the disparity in prices for primary products and products of final production, a large part of forest rent is accumulated at the upper stages of timber processing, which is appropriated by producers of secondary forest products.

Of course, one should not forget that high discipline is the result of not only convictions and suggestions. The rigid demands placed today on anyone who seeks to win or maintain his place in the ranks of the employed are no less effective. But whatever the high respect for labor inherent in the absolute majority of the Japanese nation is dictated by the economic imperatives of our days or the dramatic and tenacious struggle of the peasant against nature, which every now and then took away from him a piece of land and a roof over his head, one conclusion cannot be drawn. tasks for the development of production, without subordinating them to the idea of ​​forming a high culture and labor discipline.

The scourge of modern production, especially mechanical engineering, is local vibration. Local vibration is mainly exposed to persons working with hand-held power tools. Local vibration causes spasms of the vessels of the hand, forearms, disrupting the supply of blood to the extremities. At the same time, vibrations act on nerve endings, muscle and bone tissues, cause a decrease in skin sensitivity, the deposition of salts in the joints of the fingers, deforming and reducing the mobility of the joints. In these cases, workers complain of aching, aching, pulling pains in their hands, often at night. Low frequency fluctuations cause a sharp decrease in capillary tone, and high frequency fluctuations cause vasospasm.

At present, complex computer programs have been developed that can calculate the probability of an accident at an enterprise, determine the magnitude and nature of hazardous emissions, take into account meteorological conditions, terrain, the location of roads and settlements, and ultimately build maps (isolines), risk distribution (Fig. 5.2) in industrial and residential areas. At the same time, special attention is paid to the sources of major accidents at nuclear power plants, gas pipelines, chemical industries, etc. Beryllium oxide, hydrogen, chlorine, ammonia, sulfur dioxide, flammable gases, etc. are emitted as substances with negative properties.

A fire, as a phenomenon, can take many forms, but they all ultimately come down to a chemical reaction between combustible substances and atmospheric oxygen (or another type of oxidizing environment). For a fire to start, the presence of three components of a combustible substance, oxygen (or other oxidizing agent) and an initial source of heat with energy sufficient to start a combustion reaction is necessary. Fuel and oxidizer must be in certain ratios with each other. Most fires are associated with the combustion of solid substances, although the initial stage of a fire may be associated with the combustion of liquid and gaseous combustible substances, which are used in large quantities in modern industrial production.

Production as an expedient human activity in order to obtain the material benefits needed by society, ultimately consists in the transformation of raw materials into finished products by changing their size, shape, composition or spatial arrangement.

private ownership of the means of production, the contradictory interests of the owners of enterprises, large monopolistic associations, the desire of each of them to maximize profits do not allow the economy to be carried out systematically. By expanding or reducing the production of one product or another, capitalist enterprises (firms, monopolies) can focus only on the market, on fluctuations in prices and stock prices. In other words, the economy of capitalism develops spontaneously, anarchically. It is characterized by periodic crises, production downturns, unemployment, underutilization of production capacity. Naturally, in such

With a centralized form of repair, its quality is increased, as well as higher labor productivity and minimal repair costs are achieved, which ultimately ensures an increase in production efficiency.

The need for a proportional development of the economy also exists, of course, in capitalist society. However, under capitalism, private ownership of the means of production, the conflicting interests of business owners, big monopoly associations, the desire of each of them to maximize profits do not allow the economy to be carried out systematically. By expanding or reducing the production of one product or another, capitalist firms can focus only on the market, on fluctuations in prices and stock prices.

Under socialism, the working people jointly own the means of production. Ultimately, the workers are at the same time the rulers and the ruled. Before the socialist revolution

A technique for managing a project (work), the main purpose of which is to ensure that work schedules and deadlines are met. It is based on the assumption that the duration of events can be estimated quite accurately.

Kanban (see [K 13]) and MCI (see [M 126]). The OPT system, like the Kanban system, belongs to the class of "pull" (see [C 95]) systems for organizing supply and production. Some Western experts, not without reason, believe that OPT is actually a computerized version of the Kanban system, with the essential difference that OPT prevents the occurrence of bottlenecks in the supply-production-sales chain, and Kanban allows you to effectively eliminate bottlenecks that have already arisen. . The main principle of the OPT system is the identification of bottlenecks in the production system or, in the terminology of its creators, critical resources. As critical resources, for example, stocks of raw materials and materials, machinery and equipment, technological processes, personnel can act. The efficiency of the production system as a whole depends on the efficiency of the use of critical resources, while the intensification of the use of other resources, called non-critical, has practically no effect on the development of the system. The loss of critical resources has an extremely negative impact on the production system as a whole, while the saving of non-critical resources does not bring real benefits in terms of final results. The number of critical resources for each production system averages five. Based on the principle discussed above, firms using the OPT system do not seek to provide one hundred percent utilization of workers employed in non-critical operations, since the intensification of the labor of these workers will lead to an increase in work in progress and other undesirable consequences. Firms encourage the use of the working time reserve of such workers for advanced training, holding meetings of quality circles (see [K 179]), etc. In the OPT system on a computer, a number of problems of operational management of production are solved, including the formation of a production schedule for one day, a week, etc. When forming a production schedule close to optimal, the following criteria are used: 1. The degree of satisfaction of the production need for resources. 2. Efficiency in the use of resources. 3. Funds withdrawn from funds of work in progress. 4. Schedule flexibility, i.e. the possibility of its implementation during emergency shutdowns of equipment and undersupply of material resources. When implementing the schedule, the OPT system controls the use of production resources for the manufacture of ordered products for fixed time intervals. The duration of these intervals is determined by an expert. During each interval, decisions are made on the operational management of the production process. To facilitate decision-making, the priorities of each type of product are determined programmatically using weight functions, the so-called management coefficients (order rate, production time, etc.) and other criteria (allowable level of insurance stocks, date of shipment of manufactured products, etc.) . Based on the list of product priorities, the computer plans the maximum provision of resources for products that have the highest (zero) priority, and the provision of all other products - in descending order.

The most important factor determining the nature and level of specialization is, first of all, the size of production (concentration level) of certain types of products. It is established during design or during the planning of a production program. In addition, the level of specialization is significantly affected by the labor intensity of products, which determines the possible loading of equipment in the production of products of this range. Finally, the degree of specialization also depends on the constancy of the range and volume of output, which should, of course, be regarded as relative.

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Positive and negative sides of tablets. Basic requirements for the manufacture of tablets. Technology for the manufacture of tablets of prolonged action. The basic scheme for the manufacture of tablets. Dosing accuracy, mechanical strength of tablets.

term paper, added 03/29/2010

1. Characteristics of the final product of production 5

2. Chemical scheme of production 5

3. Technological scheme of production 6

4. Hardware scheme of production and specification of equipment 7

5.Characteristics of raw materials, materials and semi-finished products 15

6. Description of the technological process 17

VR-1. Preparation of premises, equipment, personnel, air 17

VR-1.1. Room preparation 17

BP-1.2. Equipment preparation 18

BP-1.3. Personnel training 20

VR-1.4. Air preparation 22

VR-2. Preparation of pharmaceutical substances and auxiliary materials 23

VR-2.1. Weighing sodium chloride 23

VR-2.2. Obtaining water for injection 23

VR-2.3. Preparing filters and filter materials for work 24

TP-1. Preparing and filtering the solution 25

TP-1.1. Dissolution of sodium chloride in water for injection 25

TP-1.2. Solution filtration 25

TP-2. Ampoule 25

TP-2.1. Ampoule cutting 25

TP-2.2. Stacking ampoules in cassettes 26

TP-2.3. Washing, drying ampoules 26

TP-2.4. Ampoule filling and sealing 27

TP-3. Sterilization and Leak Testing 27

TP-3.1. Sterilization 27

TP-3.2. Leak test 28

TP-4. View ampoules 28

TP-5. Standardization 29

No mechanical inclusions 29

Sterility 29

Uniformity of dosage units 31

Bacterial endotoxins 31

Pyrogenicity 33

Abnormal Toxicity 35

Determination of recoverable volume of parenteral drugs

funds 36

UMO-1. Labeling and packaging of ampoules 37

UMO-1.1. Ampoule marking 37

UMO-1.2. Packaging of ampoules in a secondary container 37

UMO-1.3. Group packing 37

UMO-1.4. Shipment of ampoules to the warehouse 37

7. Material balance 38

8. Processing and disposal of production waste 42

9. Production control 43

10. Safety, fire safety and industrial sanitation 44

11. Environmental protection 46

12. Information materials 47

13. Conclusions and proposals for improving the technology of the dosage form 48

References 49

Characteristics of the final product of production

Sodium chloride solution 0.9% for injection

Solutio Natrii chloridi 0.9% pro injectionibus

Composition (per 1 liter of solution):

Sodium chloride - 9 g

Water for injection up to 1 l

Description. Colorless, clear liquid with a salty taste.

Authenticity. 5 ml solution, stripped off to 1 ml, give a characteristic reaction to sodium. 2 ml solution give a characteristic reaction to chlorides.

pH 5.0-7.0 (potentiometrically).

Pyrogenicity test. The amount of injected solution - 10 ml for 1 kg the weight of the animal.

Quantitation. 10 ml the solution is titrated with 0.1 N. silver nitrate solution until orange-yellow color (indicator - potassium chromate).

1 ml 0.1 N silver nitrate solution corresponds to 0.005844 G NaCl, which in 1 ml solution should be 0.0087-0.0093 G.

Package. Produced in ampoules of 5 ml, 10 ml and 20 ml, in vials of 250 and 400 ml.

Storage. In a well sealed container.

Application. Maintains appropriate osmotic pressure of plasma, blood and extracellular fluid. Used for dehydration and detoxification.

Chemical scheme of production

In the process of producing a solution of isotonic sodium chloride 0.9% for injection, no chemical transformations occur.

Technological scheme of production

ВР.1 Preparation of premises, equipment, personnel, air.

BP 1.1 Preparing the premises.

Sterile products must be produced in clean areas that must be accessed by personnel and/or equipment and supplies through airlocks. Clean areas (rooms) should be maintained in such a way that they meet the standard of cleanliness; they must be supplied with air that has passed through filters of appropriate efficiency.

Clean areas (rooms) in the production of sterile medicinal products are divided into four classes.

Class A: Local area for operations that pose a high risk to product quality, for example: areas for filling (packing), sealing, opening ampoules and vials, mixing, as well as connecting parts of equipment in aseptic conditions. As a rule, such conditions are provided by laminar air flow in the workplace. Laminar air flow systems should provide a uniform air velocity in the range of 0.36 to 0.54 m/s (standard) as applicable to an outdoor cleanroom environment. Laminar maintenance must be proven and validated. Closed isolators and glove boxes can use unidirectional airflow at lower velocities.

Class B: Area immediately surrounding a Class A area and intended for aseptic preparation and filling.

Classes C and D: Clean areas for less critical steps in the production of sterile products.

Table. The maximum allowable number of particles in 1 m 3 of air

In clean areas, all exposed surfaces should be smooth, impervious and undamaged to minimize the formation and accumulation of particles or microorganisms, and to allow repeated use of detergents and, if necessary, disinfectants.

To reduce dust buildup and facilitate cleaning, rooms should be free of non-cleanable recesses and should have as few protruding edges, shelves, cabinets, and equipment as possible. Doors must be constructed without recesses inaccessible to cleaning; for the same reason, it is undesirable to use sliding doors.

Suspended ceilings must be airtight to prevent ingress of contamination from the space above them.

The installation of pipelines, air ducts and other equipment should be carried out in such a way that there are no areas and surfaces that are not accessible for cleaning, as well as leaking recesses and holes.

It is prohibited to install sinks and drains in Class A/B areas where products are manufactured under aseptic conditions. In other areas, a jet break must be provided between the equipment and the sewer pipe or drain. Floor drains in lower grade cleanrooms should be provided with traps or water traps to prevent backflow.

Do not open both airlock doors at the same time. To prevent more than one door from opening at the same time, an interlock system or a visual and/or audible warning system must be in operation.

The filtered air supply must maintain a positive pressure drop relative to the lower grade surrounding areas under all operating conditions, as well as efficient air flow around the controlled area. Adjacent rooms with different cleanliness classes should have a pressure drop of 10-15 Pa (normative value).

VR 1.2 Equipment preparation.

The design, installation and location of equipment, connection points and service areas should provide for the possibility of working with equipment, its maintenance and repair from the outside. clean zone. If sterilization is necessary, then it should be carried out after the equipment has been installed as completely as possible.

If during the maintenance of equipment inside the clean area the required level of cleanliness (sterility) was violated during this work, then before resuming the production process, it is necessary to clean, disinfect and / or sterilize this equipment (zone) (depending on what is suitable ).

The receipt of water of the required quality must be guaranteed by the design, construction, installation and maintenance of water treatment and distribution systems. It is not allowed to operate water treatment equipment in excess of the design capacity. The preparation, storage and distribution of water for injection should be carried out in such a way as to prevent the growth of microorganisms, for example, by constantly circulating water at a temperature above plus 70 ° C.

All critical equipment (sterilizers, air preparation and filtration systems, air and gas filters, water preparation, storage and distribution systems, etc.) are subject to certification (validation) and scheduled maintenance. Their re-commissioning should be allowed in due course.

Manufacturing equipment should be designed, located and maintained in such a way that it is suitable for its intended purpose.

Repair and maintenance work on the equipment must not pose a risk to product quality.

Manufacturing equipment should be designed to be easy and thorough to clean. Cleaning should be carried out in accordance with detailed documented procedures; The equipment should only be stored in a clean and dry condition.

Equipment (equipment) used for washing and cleaning should be selected and used so that it does not become a source of contamination.

The equipment must be installed in such a way as to prevent the risk of errors or contamination.

Production equipment must not pose any danger to the product. Parts of the production equipment that come into contact with the product must not react with it, release or absorb substances to such an extent that the quality of the product could be affected and thus create any hazard.

For production and control operations, scales and measuring equipment with the appropriate range and accuracy must be available.

Measuring instruments, balances, recording and control devices at regular intervals should be calibrated and checked by appropriate methods. Records of such tests should be maintained and retained.

Fixed pipelines should be clearly marked with their contents and, where possible, the direction of flow.

Pipelines for distilled, deionized and, as appropriate, other water should be sanitized in accordance with documented procedures that detail established limits for microbial contamination and the necessary measures.

Defective equipment, if possible, should be removed from production areas and quality control areas, or at least marked accordingly.

BP 1.3 Staff training.

All personnel (including cleaning and maintenance personnel) who work in such areas should be regularly trained in disciplines related to the proper manufacture of sterile products, including hygiene and basic microbiology. If it is necessary for unauthorized workers who have not received such training (for example, contract builders or equipment adjusters) to be in the cleanroom, they should be given detailed instructions and should be closely supervised.

Personnel handling animal tissue materials or microorganism cultures that are not used in the current process are not allowed to enter sterile product areas, except in special cases in which established procedures for entering these areas must be followed.

The requirements for personal hygiene and cleanliness must be observed. Personnel involved in the production of sterile medicinal products should be instructed on how to notify management of any factors that increase the level of contamination beyond the acceptable limit. The health of the staff should be monitored. The actions to be taken in relation to personnel who may become a source of microbial contamination should be determined by a designated competent person.

In clean areas, personnel are prohibited from wearing watches and jewelry, as well as using cosmetics.

Dressing and washing should be done in accordance with written instructions to minimize the risk of contamination of clean area clothing and to avoid contamination of clean areas.

Clothing and its quality must correspond to the technological process and the class of the working area. Clothing should be worn in such a way as to protect the product from contamination.

The following requirements are imposed on clothing intended for zones of each cleanliness class.

Class D: Hair and beard (if any) must be covered. Normal protective clothing and appropriate footwear or overshoes should be worn. Appropriate measures must be taken to prevent any contamination of the clean area from outside.

Class C: Hair and beard and mustache (if any) must be covered. It is necessary to wear a jumpsuit or pantsuit that fits snugly at the wrists and has a high collar, as well as appropriate shoes or overshoes. They should practically not separate fibers or particles.

Class A / B: headgear must completely cover the hair, as well as the beard and mustache (if any); it must be tucked under the collar of the suit; a face mask must be worn to prevent the spread of droplets. Appropriately sterilized and powder-free rubber or plastic gloves and sterilized or disinfected shoe covers should be worn. The lower edges of the trousers should be tucked into shoe covers, and the sleeves of clothing should be tucked into gloves. Protective clothing should release little or no fibers or particles and should contain particles that are shed from the body.

Street clothing must not be brought into changing rooms that lead to Class B and C rooms. Clean, sterile (sterilized or appropriately sanitized) protective clothing must be provided to each worker in a Class A/B area for each shift. Gloves must be disinfected regularly during work. Masks and gloves must be changed at least every shift.

Cleanroom clothing should be cleaned and handled in such a way that it does not subsequently become a source of contamination. These operations must be carried out in accordance with written instructions. To prepare such clothes, it is desirable to have separate laundries. Improper processing of clothing leads to damage to the fibers of the fabric, which increases the risk of separation of particles.

The enterprise should develop detailed programs on occupational health, taking into account the characteristics of a particular production. The rules should contain procedures regarding health, hygiene and dressing of personnel. Each employee whose duties involve being in production and control areas must understand and strictly observe these rules. The management of the enterprise should promote the development of hygiene programs, which should be widely discussed during training.

Every new employee must undergo a medical examination. It is the responsibility of the manufacturer to have procedures in place to ensure that it is informed of health conditions of employees that may affect the quality of the product. After the first medical examination subsequent ones are held periodically, as well as in cases where it is necessary for the work or health of personnel.

Measures must be taken to ensure, as far as possible, that no employee with an infectious disease or injury on exposed body parts will be allowed to manufacture medicines.

Protective clothing included in industrial premises(zones) must correspond to the purpose of the premises and the operations performed.

In production areas and storage areas, smoking, eating, drinking, chewing gum, as well as storing food, drinks, tobacco products or personal medicines. Any activity that violates hygienic requirements in production premises (zones) or in other places, which may adversely affect product quality, is not allowed.

Direct contact between the operator's hands and the exposed product and any part of the equipment that comes into contact with the product should be avoided.

Staff should be trained in handwashing.

BP 1.4 Air preparation

Manufacturing facilities must be effective system supply and exhaust ventilation with air flow control equipment and devices for measuring temperature and air humidity.

In accordance with the requirements for premises for the production of medicines in aseptic conditions RDP 46-3-80, all production premises are divided into 4 classes depending on the purity of the air.

Table. The maximum allowable number of particles in 1 m³ of air

Premises of the 1st class of cleanliness are intended for operations that pose a high risk to product quality.

(Zones for filling, packaging, capping, opening ampoules and vials) Solutions are prepared and ampoules are filled in class 2 rooms. Room of the 3rd class - for washing and sterilization of auxiliary materials. In class 4 premises - operations with primary packaging and materials after washing.

Air overpressure is created between rooms of different cleanliness classes and sluice connections are installed. When entering the 1st class premises, personnel must pass through the vestibule, where an air shower is installed.

In "clean" rooms it is necessary to maintain a certain temperature and humidity in accordance with GOST 12.1.005-76, use bactericidal lamps. The room must be sealed. Air is supplied through a pre-filter and then through a sterilizing filter with material grade FPP-1. The air flow rate over the entire section of the room is 27.5 m/min ± 20%.

VR2. Preparation of sodium chloride, filters and containers, obtaining water for injection

BP 2.3 Preparing filters and filter materials

The fungus filter works under vacuum. It is a perforated funnel, on which the filter material is wound (two layers of coarse calico, a layer of cotton wool, etc.). Filters should be of the highest quality; trap very small particles and microorganisms; have high mechanical strength to prevent the release of fibers and mechanical inclusions; counteract hydraulic shocks and change their functional characteristics; do not change physical and chemical composition and properties of the filtrate; do not interact with medicinal, excipients and solvent; withstand heat sterilization.

TP 1 Solution preparation

TP 2. Ampoule.

Process 2.1 Ampoule cutting.

The operation is carried out so that the ampoules are of the same height. This is important for the accuracy of their vacuum filling. The ends of the capillaries at the place of opening should have even and smooth edges to reduce the contamination of ampoules with glass dust and to ensure high-quality sealing.

We will open the capillaries of ampoules using an attachment for cutting ampoules to a glass-forming machine. The principle of operation of this device is as follows: ampoules from the tray of the glass-forming machine enter the feeder with the help of transport lines of the attachment. Using a rocker arm with an oil damper, the ampoules are smoothly brought to the disk knife, which makes a circular incision on the capillary, at the site of which an opening occurs due to thermal shock when heated by the first burner. Before applying a circular incision, the ampoule is driven by a roller. Then, on the second burner, the tip of the capillary is melted, and the ampoules fall into the hopper for collecting ampoules in cassettes.

Process 2.3 Washing and drying of ampoules

Ampoule washing includes external and internal washing.

Ø Outdoor is carried out on semiautomatic devices AP-2M-2. Semi-automatic machines have a free-rotating stand, on which a cassette with ampoules is installed, a showering device in the upper part of the chamber supplies hot filtered water, under the influence of water the cassette with ampoules rotates and the ampoules are evenly washed from the outside.

Ø Internal washing is carried out with a syringe method.

Principle of operation: a hollow needle is inserted into the ampoule, oriented with the capillary downwards, through which water is supplied under pressure. A turbulent jet of water from a syringe washes the inner surface of the ampoule and is removed through the gap between the ampoule and the capillary opening.

TP - 4. Viewing ampoules

Carried out by viewing the vessels on a black and white background under illumination of 60 watts. On a black background, transparency and the presence of mechanical impurities are checked - glass dust, fibers of filter materials, undissolved particles of a medicinal substance, etc.; on white - the color of the solution, the absence of black mechanical inclusions and the integrity of the glass product. The method has disadvantages: the subjectivity of the controlled - visual acuity, work experience, controller fatigue, etc. The allowable error of the method is 30%.

TP - 5. Standardization

A solution of sodium chloride 0.9% for injection is tested according to the GF RB for:

· Absence of mechanical inclusions;

· Sterility;

Uniformity of dosage units;

Bacterial endotoxins;

Pyrogenicity;

Abnormal toxicity;

· Determination of recoverable volume of parenteral medicinal products.

No mechanical inclusions:

Ø Carried out by viewing the vessels on a black and white background under 60 W illumination.

Ø On a black background, transparency and the presence of mechanical impurities are checked - glass dust, fibers of filter materials, undissolved particles of a medicinal substance, etc.;

Ø On white - the color of the solution, the absence of black mechanical inclusions and the integrity of the glass product.

The method has disadvantages:

Ø Subjectivism of the controlled - visual acuity, work experience, controller fatigue, etc.

Ø The allowable error of the method is 30%.

Sterility

The test may be carried out using the membrane filtration method or by direct inoculation of the growth medium with the test product.

Membrane filtration.

Membrane filters with a nominal pore size not exceeding 0.45 µm shall be used with a specified bacterial retention capacity. For example, cellulose nitrate filters are used for aqueous, oily and dilute alcohol solutions, while cellulose acetate filters are used in particular for solutions with a high alcohol content.

The filtration apparatus and membrane are sterilized in a suitable manner.

A small amount of a suitable sterile solvent that does not inhibit the growth of microorganisms, for example, a neutral solution of meat or casein peptone at a concentration of 1 g/l (pH 7.1 ± 0.2), is placed on the membrane of the apparatus and filtered.

The contents of the container to be tested are transferred to the membrane and filtered. Then the whole membrane is transferred to a nutrient medium or, under aseptic conditions, it is divided into two equal parts, each of which is placed in two suitable media. In addition, the medium may be applied to the membrane in the apparatus.

Liquid thioglycol medium is intended primarily for the cultivation of anaerobic bacteria, but also detects aerobic bacteria. The medium based on soybean hydrolysates and casein and Sabouraud medium are suitable for cultivating both fungi and aerobic bacteria. Media is incubated for at least 14 days.

Bacterial endotoxins

Bacterial endotoxin testing is performed to determine the presence or amount of endotoxins originating from gram-negative bacteria using amoebocyte lysate from horseshoe crab Limulus polyphemus or Tachypleus tridentatus. There are three principles for conducting this test: the principle of a gel clot, based on the formation of a gel; turbidimetric principle based on turbidity as a result of the splitting of the endogenous substrate; chromogenic principle based on the appearance of color after cleavage of a synthetic peptide-chromogenic complex. This section describes six methods:

Method A. Gel clot method: limit test.

Method B. Gel clot method: semi-quantitative test.

Method C. Turbidimetric kinetic method.

Method D. Chromogenic kinetic method.

Method E. Chromogenic endpoint method.

Method F. Turbidimetric endpoint method.

The test is performed by any of these six methods. In doubtful and controversial cases, the final decision is made based on method A, unless otherwise prescribed in a private article. The test is performed under conditions that do not allow contamination by extraneous endotoxins.

Gel-clot principle (Method A): Gel-clot methods measure the presence and amount of endotoxins and rely on the clotting effect of the lysate in the presence of endotoxins. The concentration of endotoxins required to clot the lysate under standard conditions is the labeled sensitivity of the lysate.

Prepare standard solutions of at least four concentrations equivalent to 2λ, λ, 0.5λ, and 0.25λ by diluting the stock endotoxin standard solution with water for IBE. In each of the test tubes, mix the lysate solution with an equal volume of one of the standard solutions (for example, 0.1 ml each). The reaction mixture is incubated for a certain period, in accordance with the recommendations of the manufacturer of the lysate (usually 37±10C for 60±2 minutes), avoiding vibration. Examine the integrity of the gel: if tubes are used, each tube is removed from the incubator in turn and inverted approximately 180° in one smooth motion. If a solid gel forms and remains in place after inversion, the result is recorded as positive. The result is negative if no intact gel is formed. The test results are considered reliable if the lowest concentration of standard solutions in all repetitions gives a negative result. The end point is the last positive result in the descending series of endotoxin concentrations.

Pyrogenicity

pyrogens- macromolecular substances from 50 to 1 microns lipopolysaccharides sorbed by the protein carrier, contain carbohydrates, nitrogen, phosphorus, ash substances.

Various substances that cause febrile conditions when administered intravascularly.

Properties: soluble in water, insoluble in alcohol and acetone, resistant to high temperatures, changing the pH of the solution does not affect the stability.

Are divided into:

Ø Endogenous (cellular tissue, formed under certain conditions);

Ø Exogenous (contained in microorganisms and released by them in the process of life).

Sources:

Ø microorganisms (gram and gram bacteria, fungi and viruses);

Ø some chemical substances(products of thermal-oxidative degradation of plastics and fluoroplasts).

There are three degrees of severity of pyrogenic reactions:

Ø Light degree (slight increase in temperature 370С)

Ø Medium degree (chills, headache, fever up to 390C, disappears within a few hours)

Ø Severe degree (severe chills, back pain, vomiting, shortness of breath, fever up to 400C, death is possible, improvement occurs in a day)

Control methods for non-pyrogenicity

Ø Biological test

Ø LAL test (highly sensitive and specific)

biological test
The test consists of measuring the increase in body temperature induced in rabbits by intravenous administration of a sterile solution of the test sample.

Ø Use healthy adult rabbits of both sexes weighing at least 1.5 kg, fed a complete balanced diet, not including antibiotics, whose body weight has not decreased during the week preceding the test.

Ø Room for animals. Rabbits are kept individually in a quiet room at a uniform, suitable temperature. The test is carried out in a quiet room where animals can be aroused and in which the temperature is maintained at a level not more than 3 °C different from the temperature maintained in the place where the rabbits are permanently kept. Animals are placed in cages at least 1 hour before the first temperature measurement and remain there throughout the test.

Ø Use a thermometer or electrical device showing the temperature to the nearest 0.1°C, inserting it into the rectum of the rabbit to a depth of about 5 cm. The depth of insertion is constant for each of the rabbits during each of the tests.

Pretest:

Ø injected intravenously pyrogen-free solution of 9 g/l sodium chloride R. Heated to a temperature of 38.5 0C in the amount of 10 ml per kilogram of body weight. The temperature of the animals is recorded, starting at least 90 minutes before administration and continuing for 3 hours after administration of the solution. Animals whose temperature fluctuates more than 0.6°C are not used in the main test.

Main test:

Ø Carried out using a group of three rabbits.

Ø The test solution is slowly injected into the extreme ear vein of each of the rabbits for no more than 4 minutes.

Ø After testing on a group of 3 rabbits, if necessary, repeat it on other groups of 3 rabbits (total up to 4 groups, depending on the results obtained).

Ø If the summed result obtained in the first group does not exceed the value given in the second column of Table 5, the product is deemed to pass the test.

Ø If the summed result exceeds the value given in the second column of Table 5, but does not exceed the value given in the third column of the table, the test is repeated as above.

Ø If the summed result exceeds the value given in the third column of the table, the product is considered to fail the test.

Table 5: Values ​​for the biological test for pyrogenicity

Ø Rabbits that were used in the pyrogenicity test, if the temperature rise was 1.2°C, are excluded from further testing.

Ø Disadvantage: the relative duration of the experiment, different sensitivity to pyrogens in rabbit and human, cannot be quantified.

LAL test:

Ø It is based on the physicochemical interaction of the lysate of cells of horseshoe crabs with endotoxin.

Ø As a result, a gel of different density is formed.

Ø The presence of endotoxin can be determined and quantified.

Ø Lead time 1 hour.

Ø Test for bacterial toxin is carried out to determine its presence or amount (source of endotoxin Gr-bacteria).

There are 3 principles of testing:

1. The principle of gel clot (based on the formation of a gel);

2. Turbidimetric method (based