Occupational hygiene in the chemical and pharmaceutical industry presentation. How is occupational health implemented in the production of synthetic medicinal substances?

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1. Occupational health in the chemical and pharmaceutical industry

4. Occupational hygiene in the production of antibiotics

6. Occupational hygiene in the production of herbal preparations and finished dosage forms

9. Hygienic characteristics of working conditions during the production of tablets

10. Genetic characteristics of working conditions in the production of dragees

Conclusion

Bibliography

1. OCCUPATIONAL HEALTH IN THE CHEMICAL AND PHARMACEUTICAL INDUSTRY

labor security medicine production

The chemical and pharmaceutical industry is one of the leading sectors of the national economy. It includes a complex of production facilities in which, along with chemical methods of processing materials, biological synthesis of drugs is widely used.

The modern chemical and pharmaceutical industry has a number of features that determine the specifics of its development, for example, high requirements for the chemical purity of products. In addition, for drugs intended for subcutaneous, intramuscular injections and intravenous infusions, complete sterility is ensured. Their quality must strictly comply with the requirements of the State Pharmacopoeia of Russia.

Another feature of the chemical-pharmaceutical industry is the small volume of production of most drugs.

This industry is also characterized by high consumption of raw materials and supplies, which is due to the multi-stage nature and complexity of drug synthesis.

Finally, the chemical and pharmaceutical industry is characterized by a relatively rapid update of the range of drugs. This feature, as well as the small volume of drug production, has led to the widespread use of combined technological schemes that make it possible to produce 2-3 types of drugs or more within a year. In addition, all substances produced by this industry must be processed into finished dosage forms. These features of the chemical and pharmaceutical industry pose a number of new and complex tasks for hygienic science and practice in the field of organizing and conducting health-improving activities.

2. Hygienic characteristics of the main technological processes

There are several groups of enterprises in the chemical and pharmaceutical industry. The leading ones are factories for the production of synthetic drugs, factories for the production of antibiotics and enterprises for the production of drugs and finished dosage forms.

The industrial production of synthetic drugs is based on the widespread use of organic synthesis, which brings these enterprises closer to the basic chemistry industry.

Antibiotic enterprises are united into a special group. This is due to the fact that the basis of the technological process for obtaining these drugs is biological synthesis.

A characteristic feature of factories for the production of herbal pharmaceutical and finished dosage forms is the production of a large number of various medicines in the form of liquid extracts and tinctures, injection solutions in ampoules, tablets, dragees, patches, etc.

In the industrial production of chemical and pharmaceutical preparations, a variety of raw materials are widely used, obtained both from plant and animal products and by chemical synthesis. The most common is chemical raw materials. Mineral raw materials are used for the production of inorganic salts, and also as ingredients for various synthesis of organic compounds. A large number of mineral acids and alkalis are used. The initial organic raw materials are supplied by the coke, petrochemical, aniline dye industries and basic organic synthesis enterprises.

Animal raw materials are also widely used in the production of medicines, in particular, histidine is obtained from the blood of animals, adrenaline from the adrenal glands, insulin from the pancreas, thyroidine from the thyroid gland, etc.

All types of technological operations when obtaining medicinal products can be divided into preparatory, the actual processes of obtaining the medicinal product, final and additional operations.

Preparatory operations - storage, movement of solid, liquid and gaseous materials, their transformation: grinding and crushing of solid raw materials, separation of solids, removal of liquids and gases from them using methods of settling, filtration, centrifugation, cooling, crystallization, vacuum, etc.

The actual processes for obtaining medicines are based on metabolic, thermal, electrochemical, biological processes, electrolysis, etc. At this stage of the technological process, the reactions of sulfonation, nitration and halogenation, amination and oxidation, reduction and oxidation, etc. are widely used.

At the final stage, medications are dried, crushed, tableted, ampuled, packaged and packaged.

Preparatory operations. A significant part of the initial raw materials for the production of herbal and synthetic drugs is in a solid state and is subjected to crushing and grinding. The need for this operation often arises when obtaining dosage forms (tablets, dragees, etc.). Crushing is carried out using jaw, roller, cone, hammer and other crushers. Grinding is carried out using ball and porcelain mills and disintegrators. Small quantities of the medicinal product are crushed in mechanically driven mortars, Islamgulov, Excelsior mills, etc.

Occupational hazards during crushing, grinding and separating pharmaceutical starting products include dust, intense noise and general vibration. Dust is emitted at the point of entry of medicinal raw materials or finished product into crushers and mills and at the point of exit of the crushed substance.

A hygienically unfavorable operation is the separation of materials into fractions. The air separators and mechanical sieves used in this process are significant sources of dust emissions. In the production of small-scale drugs (for example, hormonal drugs), manual rubbing on sieves is often used, which is associated with the release of dust and contamination of the skin and work clothes of workers.

To combat the emission of dust, proper organization of the technological process and equipment, covering of dust emission areas with aspiration of dust-laden air are necessary. Since noise and vibration in crushing and grinding plants may exceed permissible values, this equipment must be located in separate production rooms, and the foundations under them should not be connected to the building structures. In the fight against noise and vibration, it is necessary to use anti-noise and vibration-damping devices and materials. It is advisable to control the grinding and crushing processes remotely.

The transportation of starting components has a significant impact on the level of air pollution in the working area with harmful substances at the preparatory stage. This is due to the heavy load on communication structures, the presence of mechanisms and devices intended for moving substances that do not have effective exhaust devices and the necessary tightness.

During transportation, workers may come into contact not only with vapors and gases, but also with liquid and bulk harmful substances. In some cases, manual transportation, loading and unloading of medicinal raw materials (for example, of plant origin) are still used.

Liquid substances are moved through pipelines using pumps, air or steam pressure, gravity and vacuum. Gaseous substances are transported using compression and vacuum. Supplying raw products with compressed air is associated with an increase in pressure in communication networks, which can lead to the release of harmful vapors and gases through leaks in pipelines, apparatus and containers. It should be noted that the transportation of liquid products using pumps is hygienically imperfect, which is an additional factor contributing to air pollution with chemicals. From this point of view, transportation of liquid products by gravity or using vacuum is most favorable. The main hygienic requirements for equipment are the resistance of pipelines, gaskets and packing materials to the action of liquids, the replacement of gland pumps with sealless and submersible ones.

The supply of solid medicinal raw materials (plant products, organic and mineral substances) from raw material warehouses to preparatory workshops, from one equipment to another is carried out using belt conveyors, elevators, augers, as well as pneumatic and hydraulic systems. The method of transportation is determined by the aggregate state of the substances, their toxicity, the nature of production, etc.

Giving a hygienic assessment of these processes, it should be noted that transportation using belt conveyors, augers, etc. is associated with a significant release of dust. The most hygienic solution is to supply dry raw materials using pneumatic transport.

The actual processes of obtaining medicinal substances.

This technological stage of drug production is characterized by a wide variety of technological processes and operations, equipment and chemicals used. A significant share in the industrial synthesis of intermediates and medicinal substances is occupied by processes associated with the reactions of substitution of hydrogen atoms in the nucleus of aromatic compounds by one or another group of atoms, transformation of substituents already existing in the molecule of an organic compound into others in order to give it new properties and, finally, change carbon structure of the molecule. These are reactions of nitration, sulfonation, halogenation, reduction, alkylation, etc. These processes are carried out in reactors of various types, which got their name depending on the chemical reactions carried out in them (chlorinator, nitrator, sulfator, etc.).

Reactors can operate under conditions of high and normal atmospheric pressure or under vacuum. They can be periodic or continuous. These are steel, lead or cast iron containers with or without stirrers, heated or cooled. Depending on the processes occurring in the reactors, various types of mixers are used: blade, screw, frame, anchor, etc.

The main harmful factor in the reactor compartment is chemically y. Places where toxic substances are released from reactors can be stirrer seals, hatches through which products are loaded and unloaded, measuring glasses, inspection windows, and flange connections. At the same time, the composition and level of harmful substances in the air of the working area depend on the perfection of the equipment used, the type of medicinal intermediate or finished drug obtained, operating mode and other factors. Unfavorable hygienic conditions can be caused by manual operations, for example, when measuring the level of liquids, taking samples. The transfer of equipment to a vacuum process, the use of closed reactors with shielded stirrer motors, as well as automatic control, significantly reduce the release of harmful substances into the air of working rooms.

The processes of separation of chemical components occupy a large share at this stage. The main equipment for carrying out such operations is a distillation apparatus and distillation units. Maintenance of this equipment is associated with the possibility of contact of workers with harmful substances that can enter the air through communication systems, hatches, taps, sampling points, etc.

Filtration and centrifugation processes are widely used to separate suspensions into solid and liquid phases. Filtration is carried out using periodic and continuous filters. The former include nutsch filters, filter presses, sheet filters, and the latter include drum, disk and belt filters. The operation of nutsch filters and filter presses is often accompanied by the release of toxic substances into the air of the working area, is associated with the use of manual labor and the possibility of intense contamination of the skin and work clothes. From a hygienic point of view, drum filters that are sealed and equipped with exhaust ventilation are more favorable.

For rapid separation of medicinal intermediates, batch and continuous centrifuges are used. Batch centrifuges are less advanced and have a number of disadvantages, the main ones being the inconvenience of removing the pressed material, the use of manual labor, and the lack of reliable tightness. These shortcomings cause the release of harmful substances into the air of the working area and contamination of the skin.

Mechanized and closed filters, self-discharging bottom discharge centrifuges, drum vacuum filters and automatic filter presses are hygienically reliable.

A significant part of intermediate products and finished medicines is dried. This process is necessary when obtaining herbal, synthetic drugs, antibiotics, vitamins, etc. Moisture is removed by mechanical (filtration, pressing, centrifugation), physicochemical (absorption by hygroscopic materials) and thermal (evaporation, evaporation and condensation) methods.

In the production of medicines, chamber, drum, spray, shaft and other dryers are most widely used. Servicing most dryers is accompanied by increased heat generation directly at the workplace and the release of toxic substances.

A significant disadvantage of dryers is the insufficient mechanization and sealing of the processes of loading and unloading substances undergoing drying, which causes air pollution of the working area with dust from the finished product. Significantly less harmful substances are released when using continuous dryers (rakes, sprayers, drying drums, etc.), provided with complete sealing and mechanization of loading and unloading processes.

Evaporation and crystallization processes have become widespread in the production of medicinal products. The former are used to obtain more concentrated solutions from less concentrated ones (synthetic and herbal preparations, antibiotics, vitamins, etc.). For this purpose, in most cases, multi-effect evaporators are used. Unfavorable hygienic operations when working with them are the supply of solutions and unloading of the finished product, since they are accompanied by the release of harmful compounds into the air of the working area.

Crystallization processes are used to purify medicinal substances from impurities or isolate them from liquids. These processes are carried out in open and closed crystallizers. The main disadvantage of this equipment is the insufficient sealing and mechanization of the loading and unloading processes of medicinal substances.

More favorable sanitary conditions in the workplace are created when servicing vacuum crystallizers.

The production of finished dosage forms in the form of tablets, dragees, ampoules consists of many preparatory and basic processes and operations carried out in a certain sequence on the appropriate equipment.

Final operations. At the final stage of the technological process, medicinal substances are labeled, packaged and packaged. Dosage forms are packaged in plastic, paper and glass containers. Most operations at this stage are mechanized.

The main unfavorable hygienic factor at this stage of drug production is dust. Workers, as a rule, are exposed to complex dust, since several types of medicines can be filled and packaged simultaneously.

Working with a semi-mechanized and especially manual method of packaging and packing tablets, ampoules, dragees, as well as sealing boxes and coins with strips of cellophane and a number of other operations are associated with a forced position of the body.

3. General characteristics of industrial factors that determine working conditions in the production of medicines

1. Chemical factor. As studies show, the main unfavorable factor in the working environment at chemical and pharmaceutical industry enterprises is pollution of the air of the working area, clothing and skin with harmful organic and inorganic substances.

Air pollution with toxic substances is possible at all stages of the technological process: during preparatory, main and final operations. The main reasons for the content of harmful substances in the air of industrial premises are the imperfection of equipment, violation of technological regimes, the absence or insufficient mechanization of many operations associated with transportation, loading and unloading of materials from devices, the use of leaking equipment, overflows of chemical products when filling devices, etc.

The composition of air pollutants in the working area at most drug production enterprises is complex, due to the simultaneous presence of many chemical ingredients in the form of aerosols, vapors or gases. Depending on the stage of the technological process and the type of drug produced, the air in production premises may be contaminated with initial, intermediate and finished products of chemical synthesis. In this case, harmful substances enter the body mainly through the respiratory tract and, to a lesser extent, through the skin and gastrointestinal tract.

The impact of a harmful substance on the body is possible at various stages of the technological process: during the preparation of raw materials, the actual processes of obtaining the medicinal product, and final operations. At the same time, the severity and nature of the impact of the chemical factor on the workers’ body are determined by the perfection of technology and equipment, the formulation of the medicinal substance, as well as the construction and planning solutions of the premises and the organization of air exchange in them.

The nature of the technological process and, above all, its intermittency play a significant role in air pollution in industrial premises. The implementation of processes according to a periodic scheme is associated with repeated loading and unloading of liquids or bulk materials, and the use of various methods of transporting the processed material. This greatly complicates the organization of effective measures to prevent air pollution. At the same time, the organization of the technological process according to a continuous scheme makes it possible to eliminate a number of processes and operations (unloading, transportation, loading of semi-finished products, etc.) that are a source of air pollution in the working area. In addition, favorable conditions are created for the elimination of labor-intensive and dangerous manual operations.

The level of air pollution with vapors and gases of harmful substances is greatly influenced by the pressure in devices and communication networks. From a hygienic point of view, the most favorable conditions are created during the synthesis of drugs carried out under vacuum, since toxic substances cannot be released from the equipment. Vacuum processes take place in the reactor compartment and are widely used in the drying and isolation of drugs.

At the same time, many chemical processes in the synthesis of intermediates and finished drugs occur at elevated and high pressure, for example, the formation of aniline from chlorobenzene occurs at a temperature of about 200 °C and a pressure of 5.9--9.8 MPa (60--100 atm), Hydrolysis of the amine to phenol occurs at a temperature of 350 °C and a pressure of 19.6 MPa (200 atm).

In such processes, the tightness of the equipment is achieved by using flanged connections of pipes and devices of a special design using fluoroplastic, asbestos-lead and other gasket materials.

As special time-keeping observations have shown, during the production of sulfonamide drugs, an operator on average 10-12% of his working time is in conditions of high levels of harmful substances in the air. The highest levels of contamination with chemicals are observed when the integrity of the process equipment is broken, for example, at the stage of hydrolysis of phenylhydrazine sulfate in the production of amidopyrine, during selection through the open hatch of the apparatus, the concentration of sulfur dioxide can be 4 times higher than the maximum permissible concentration.

2.Dust. Air pollution of working premises by dust is observed mainly at the preparatory and final stages of obtaining medicinal substances. The main sources of dust emissions at the preparatory stage are the delivery of raw materials from warehouses to production shops, as well as operations associated with crushing, grinding, sifting, transportation, loading, etc.

Thus, a significant amount of dust is observed in workplaces when grinding plant materials and crushing the initial components of synthetic products. In this case, the dust level can be 3-5 times higher than permissible.

At the final stage of drug production, high levels of air pollution from dust of the finished drug, several times higher than permissible, are most often observed in the process of tableting, panning, drying, grinding, sifting mixtures, packaging and packaging of finished drugs. Under these conditions, medicinal dust should be considered industrial and considered an industrial poison. The dust content in the air of the working area when working on vibrating sieves and especially during manual sifting can

5 times or more exceed the permissible values. Yes, during
manual packaging dust concentration in the breathing zone of workers
can reach 100 mg/m3 or more.

It is known that the nature of the effect of dust on the body and the severity of biological changes are largely determined by its dispersion. The dust of some medications consists of 85-98% particles less than 5 microns in size. This facilitates the penetration of a large number of medicinal substances into the body through the respiratory tract and digestive organs (with saliva).

3. Microclimate. At chemical and pharmaceutical industry enterprises, the microclimate of production premises must comply with the requirements established by SanPiN 2.2.4.548--96. However, studies show that with insufficient thermal insulation of heated surfaces of devices and communication heating networks, workers may be exposed to chemical factors and the microclimate at the same time. Increased air temperature occurs mainly in drying departments and in devices in which the reaction occurs with the release of heat or at high temperatures (crystallizers, solvents, hydrolyzers, etc.). Thus, in the warm season, the air temperature in these areas can reach 34-38 °C with a relative humidity of 40-60%.

Thus, the thermal microclimate at individual workplaces in the chemical and pharmaceutical industry is an additional factor that aggravates the effect of the chemical factor.

4.Noise. The source of industrial noise in workplaces during the manufacture of medicinal products are many technological devices. These include compressors, vacuum filters, drum dryers, centrifuges, crushers, vibrating screens, vacuum pumps, etc. The noise level in some cases may exceed the permissible level. Thus, at workplaces near centrifuges, noise parameters can exceed the permissible values by 5 dB, at a vacuum pump - by 5-6 dB, at a compressor - by 14-17 dB.

The most unfavorable areas are engine rooms, where the total level of high-frequency noise often exceeds the permissible values by 20-25 dB. It should be noted that industrial noise, even at an acceptable level, can aggravate the adverse effects of chemicals.

4. OCCUPATIONAL HYGIENE IN ANTIBIOTICS PRODUCTION

Antibiotics are substances produced by microorganisms, higher plants and animal tissues in the process of vital activity and having a bactericidal or bacteriostatic effect. There are now about 400 antibiotics belonging to various classes of chemical compounds. The antibacterial properties of antibiotics served as the basis for their widespread use in medicine, in particular in the treatment and prevention of infectious diseases and inflammatory processes.

In addition to their use in medicine, antibiotics have found application in the food and meat and dairy industries for food preservation.

The technological process for producing antibiotics consists of several stages, carried out in a certain sequence and using appropriate equipment:

a) cultivation of seed and biosynthesis of antibiotics (fermentation);

b) pre-treatment of the culture fluid;

c) filtration;

d) isolation and chemical purification (extraction method, ion exchange method, precipitation method);

e) production of finished dosage forms;

e) packaging and packing

The initial technological processes are based on the cultivation of seed material (producer) in flasks and fermenters. For the purpose of further enrichment, the grown production strain of the producer is transferred to special devices - inoculators. The process of growing mushrooms and bacteria in inoculators is carried out under strictly defined conditions, which are provided by heating and cooling systems, air supply, and devices for mixing the production mass. Then the producer goes to fermentation. Fermentation refers to the cultivation (growing) of the producer and the formation of the maximum amount of antibiotic. Antibiotics are synthesized in microbial cells or released into the culture fluid during the biosynthesis process.

Pure antibiotic Basic technological scheme for the isolation and purification of antibiotics.

The main equipment for the fermentation process are fermenters, which are huge containers up to 100,000 liters. They are equipped with heating and cooling systems, supply of a sterile air mixture, mixers, as well as devices for loading and unloading nutrient medium and culture fluid. This stage of the technological process is characterized by the tightness of the equipment used, and therefore the possibility of air pollution with substances used for the biosynthesis of antibiotics, as well as with the biomass itself, which is formed at the end of the fermentation process, is practically eliminated.

Due to the fact that antibiotics form insoluble compounds with many substances present in the culture fluid, to increase the concentration, as well as more complete precipitation of impurities, the culture fluid is acidified to pH 1.5-2.0 with oxalic acid or a mixture of oxalic and hydrochloric acids . The treated culture liquid is filtered from mycelium and precipitated ballast substances to obtain a clear filtrate, called the native solution. Filtration of the treated culture liquid is carried out on open-type frame filter presses, which may result in splashing of the native solution. Manual unloading of filter presses leads to contact of workers with a culture fluid containing an antibiotic.

The next stage of antibiotic production is isolation and chemical purification. At this stage, the antibiotic solution is concentrated and purified to such purity that it can be used to obtain a finished drug. The content of the antibiotic in the native solution is very low, so isolating it in its pure form, purifying it and bringing it to the finished dosage form is a very complex and labor-intensive process: for example, to obtain 1 kg of antibiotic it is necessary to process about 600 liters of culture liquid.

To isolate and chemically purify antibiotics, one of the following methods is used: extraction method using various solvents; deposition method; ion exchange method. The most widely used methods in the biosynthesis of antibiotics are extraction and ion exchange methods, and in recent years the ion exchange method for the isolation and purification of antibiotics has also been used in the production of other drugs. Its main advantage is that it eliminates the need to use toxic and explosive solvents. The method is economically beneficial, since its technology is simple and does not require expensive equipment and raw materials.

Extraction of antibiotics from the native solution is carried out in extractor-separators, the main disadvantage of which is the need for manual unloading, as a result of which the air in the workshops may be polluted with solvents, for example, isooctanol in the production of tetracycline and oxytetracycline.

Along with solvents, oleic acid, caustic soda, oxalic acid, butyl and ethyl alcohols, butyl acetate, etc. can be released into the air at the stage of isolation and chemical purification of antibiotics due to the imperfection of the equipment used.

The ion sorption method is that the native solution is fed using centrifugal pumps into a battery of ion exchange columns loaded with SBS-3 sulfonic cation exchange resin. As a result of ion exchange, the antibiotic is sorbed on the ion exchanger, after which it is desorbed (eluted) with an ammonia-borate buffer solution.

This method has certain hygienic advantages over precipitation and extraction methods. It does not require manual labor when working with sediments, which eliminates the contact of workers with concentrated solutions and sediments of antibiotics. This method does not use toxic organic solvents.

The paste-like products obtained during the chemical purification process are further dried and sifted. The drying process in the production of antibiotics plays an extremely important role, since the quality of the product depends on its organization. Heat-stable antibiotics, obtained in crystalline form with a low moisture content, are usually dried in vacuum drying ovens. Antibiotics obtained after chemical purification in the form of aqueous concentrates are dried in evaporation-drying units and vacuum-freeze dryers. These processes must be carried out under sterile conditions.

The main disadvantage of working in drying departments is the use of manual labor when loading and unloading products. The implementation of these operations, as well as the need to mix the powdery mass and monitor the technological operating mode of drying units, is associated with the possibility of contact of antibiotics working with dust. Insufficient sealing of drying units contributes to the release of certain toxic substances into the air of industrial premises, residual quantities of which may be contained in antibiotics. For example, ready-made chlortetracycline may contain an admixture of methanol, tetracycline - isooctyl alcohol, tetracycline and oxy-tetracycline hydrochlorides - n-butanol and hydrochloric acid.

5. Hygienic characteristics of working conditions and health status of workers in the production of antibiotics

Working conditions in the production of antibiotics are characterized by the possible entry into the air of highly dispersed dust of antibiotics, vapors and gases, chemicals used in the technological process and the release of excess heat. During the fermentation stages, workers may be exposed to phenol and formaldehyde vapors used to sterilize premises and equipment, as well as producer dust.

During the pre-treatment and filtration stages, workers come into contact with vapors of oxalic and acetic acids. Manual operations often lead to contamination of the skin and overalls with culture fluid and native antibiotic solution.

The processes of isolation and chemical purification of the antibiotic, carried out by extraction and precipitation methods, are associated with the possibility of exposure of the body to working vapors and gases of butyl, isopropyl and methyl alcohols, butyl acetate, oxalic, acetic, sulfuric and hydrochloric acids and other substances used in this stage. Concentrations of these substances in the air in some cases may exceed the maximum permissible limits. The main reasons for air pollution in the working area with harmful substances are insufficient tightness of equipment, the presence of manual operations, low efficiency of ventilation devices, etc.

At the final stages, as research shows, the processes of drying, sifting, tableting, packaging and packaging of antibiotics can be accompanied by significant environmental pollution with fine dust from the finished product. In addition, workers in the preparatory workshops, drying department, and fermentation, in addition to the chemical factor, can simultaneously be exposed to excess heat, the main source of which is inoculators, fermenters, drying units, as well as the surfaces of communication networks if they are insufficiently insulated.

A study of the health status of workers in the production of antibiotics shows that under the influence of occupational hazards, disturbances in the functional state of the body, and in some cases, the development of occupational diseases, are possible.

One of the characteristic manifestations of the toxic effect of antibiotics are complaints of persistent itching of the skin, frequent headaches, pain in the eyes, increased fatigue, pain and dry throat. In some cases (for example, when exposed to streptomycin), workers also note decreased hearing and pain in the heart area.

The most common and characteristic symptoms when exposed to antibiotics are complications from the gastrointestinal tract: lack of appetite, nausea, flatulence, abdominal pain. A significant group of complications consists of liver damage, renal dysfunction, cardiovascular and nervous systems.

Currently, significant material has been accumulated on the effect of antibiotics on the blood system: the development of anemia, agranulocytosis, leukopenia, and disturbances in vitamin metabolism.

Antibiotics should be classified as a group of so-called allergens, the sensitizing effect of which is manifested mainly in damage to the skin and respiratory system. Allergies occur both through inhalation into the body and through contact with skin. The development of skin sensitization is facilitated by a violation of the integrity of the skin. Positive allergen tests, for example for penicillin, were detected in 18% of those working with antibiotics, for streptomycin - in 18.5%, for both antibiotics with combined action - in 47%. People who are constantly in contact with antibiotics most often (50%) develop dermatitis, eczema, and urticaria, localized mainly on the hands, forearms, and face. These changes are most often recorded in workers with more than 5 years of experience in the production of biomycin, chloramphenicol, tetracycline, and penicillin. In this case, skin damage begins with diffuse hyperemia and swelling of the face (especially in the eyelid area), hands and forearms. With further contact with antibiotics, acute or subacute recurrent dermatitis may develop, turning into eczema.

Changes in the upper respiratory tract are expressed in the development of hyperemia and atrophy of the mucous membranes, mainly the nose and larynx. As the disease progresses, it can become complicated by asthmatic bronchitis and bronchial asthma. One of the manifestations of the side effects of antibiotics is dysbiosis - a disruption of the normal microflora of the body. Those working in the production of antibiotics are diagnosed with secondary mycoses (usually candidiasis), changes in the gastrointestinal tract and upper respiratory tract, which developed against the background of dysbiosis of the mucous membranes, as well as inhibition of natural immunity factors. Workers experienced constipation, diarrhea, flatulence, erosions and ulcers of the rectal mucosa. The detected changes in health status are to a certain extent reminiscent of the side effects of antibiotics in clinical use.

Along with this, workers experience an increased incidence of influenza, ARVI and diseases of the female genital area.

Preventive measures in the production of antibiotics should be aimed primarily at combating the release of harmful substances into the air of the working area. To this end, the complex of health measures must include automation and mechanization of technological processes, effective operation of general and local ventilation, and compliance with the technological regime. This not only eliminates the effect of released harmful substances on workers, but also eliminates the adverse influence of meteorological factors.

Particular attention in the fight against air pollution by harmful substances should be given to sealing technological equipment and communications, mechanization of processes and operations for loading, unloading and transporting raw materials, semi-finished products and finished products.

An important place in the prevention of the harmful effects of chemical factors should be occupied by laboratory monitoring of the content of harmful substances in the air of the working area, the amount of which should not exceed established standards. Currently, maximum permissible concentrations have been established for the following antibiotics: streptomycin - 0.1 mg/m3, oxacillin - 0.05 mg/m3, florimycin - 0.1 mg/m3, hygromycin B - 0.001 mg/m3, oxytetracycline - 0 .1 mg/m3, ampicillin - 0.1 mg/m3, biovit (according to the content of chlortetracycline in the air) - 0.1 mg/m3, oleandomycin - 0.4 mg/m, phytobacterin - 0.1 mg /m3.

To a large extent, the improvement of the air environment in the production of antibiotics will be facilitated by the replacement of harmful ingredients in the technological formulation with new, less toxic compounds.

In order to prevent allergization of the body and the skin-irritating effect of chemicals, it is recommended to carry out preventive desensitization, use of protective ointments (for example, 2% salicylic), detergents, etc.

Organization of proper diet and rest is important in preventing diseases and promoting health. It is recommended to provide lactic acid colibacterin for the prevention of dyspeptic disorders in workers, as well as enriching food rations with vitamins A, B, PP, C. It is necessary to strictly observe the rules of personal hygiene - wash your hands after each manipulation with antibiotics, take a shower and change clothes after work. In addition, those working in the production of antibiotics must be provided with rational work clothes, underwear, shoes, gloves and mittens, anti-dust respirators such as “Lepestok-5”, “Lepestok-40”, and safety glasses.

6. OCCUPATIONAL HYGIENE IN THE PRODUCTION OF HEALENIC PREPARATIONS AND FINISHED DOSAGE FORMS

The pharmaceutical industry unites enterprises for the production of galenic and new galenic drugs, as well as finished dosage forms (panning, ampuling, tableting, etc.). The enterprises of this industry produce galenic and new galenic preparations, dosage forms such as tinctures, liquid and dry extracts, syrups, solutions, drops, tablets, and patches. A large amount of work is involved in weighing, mixing, crushing and packaging pharmaceuticals, completing first aid kits, etc. The technological process is built on a workshop principle and includes such main workshops as galenic, ampoule, tablet, packaging, coating, etc.

A variety of substances of plant, animal and mineral origin are used as initial medicinal raw materials for the production of galenic and new galenic preparations. The features of this production are a wide range of products, a variety of raw materials, the production of numerous drugs in small quantities (low-tonnage), and a variety of equipment used for basic technological and auxiliary operations. These production facilities often operate according to a combined technological scheme, i.e., the equipment is designed and placed in such a way that it can be used to produce various medications that are similar in manufacturing procedures.

7. Hygienic characteristics of working conditions in the production of herbal medicines

Herbal medicines are obtained from medicinal plant materials. They are divided into two groups: preparations from fresh plants and preparations from dried plant materials. During their production, in the event of a violation of the tightness of the equipment and low ventilation efficiency, workers may be exposed to vapors of extractants (dichloroethane, ethers, alcohols, etc.). Operations involving grinding fresh medicinal herbs should be considered unfavorable from a hygienic point of view, since at this moment droplets of their juice and small particles can enter the respiratory system, onto the skin from covered parts of the body (hands, face), causing skin irritation. and sensitizing effect.

Preparations made from dried plant materials include tinctures and extracts.

Tinctures are alcohol or alcohol-ether extracts from dry plant materials, obtained without heating or removing the extractant. Tinctures are obtained by infusion, percolation (continuous filtration through a filter) and dissolution of extracts.

Extracts are herbal preparations, concentrated extracts from dry plant materials, purified from ballast substances. Based on concentration, liquid, thick and dry extracts are distinguished. The main operations in the technological scheme for obtaining extracts are:

a) extraction of dry plant materials;

b) separation of the liquid phase from the solid by settling, filtering, centrifugation and pressing;

c) distillation of extractants - water, ether, alcohol, chloroform, etc. by evaporation (thick extracts) or drying under vacuum (dry extracts).

There are many extraction methods. In general, they can be classified into static and dynamic.

From a hygienic point of view, the most progressive methods are dynamic extraction, which is based on a constant change of extractant or extractant and raw materials.

Thick extracts are obtained by evaporation (thickening) of liquid extracts in vacuum evaporators at a temperature of 50-60 °C.

Dry extracts are extracts from dry plant materials. They are obtained by further drying the thick extract in a vacuum roll dryer or drying the unthickened extract in a spray dryer.

Working conditions in the manufacture of herbal and new-galenic preparations are characterized by the possibility of workers being exposed to medicinal plant dust released during the crushing of plant materials, sifting, transportation, loading, unloading, etc. Thus, loading medicinal plant materials into percolators is accompanied by air pollution of the working area with medicinal dust herbs Its concentration depends on the type of plant material, the degree of its grinding, weight, etc.: for example, the concentration of Eleutherococcus dust when loading it into percolators was 2-4 times higher than the contamination levels when loading valerian root.

Medicinal dust, depending on its physical properties and chemical structure, can have very different effects on the body: general toxic, skin irritant, allergenic, etc. For example, when loaded, belladonna herb, which contains alkaloids of the atropine group, gets on the skin and causes irritation. With prolonged exposure, especially when the dust of this grass enters the respiratory tract, the toxic effect manifests itself in the form of dizziness, general agitation, increased heart rate and breathing. Dust from red pepper, sage, wormwood, etc. has a skin irritating effect. Cases of allergic lesions upon contact with dust from lemongrass, lycopodium and other herbs have been described.

The production of galenic and new galenic preparations is associated with air pollution in the working area with vapors of extractants and solvents (alcohol, ether, chloroform, dichloroethane, etc.). For example, high concentrations of ethyl alcohol vapor were found at a number of enterprises in the premises for the production of alcohol solutions, where in 20-30% of the samples taken the vapor content in the air of the working area exceeded the maximum permissible concentration.

In combination with the chemical factor in certain areas, workers are simultaneously exposed to a microclimate determined by excess heat and noise.

The nature and severity of the impact of the chemical factor on workers in galenic workshops is determined by the perfection of the technological equipment used, the composition of medicinal raw materials, as well as the construction and planning solutions of the premises and the organization of air exchange in them.

Research shows that in those enterprises where sealed equipment is widely used in the production of galenic and new galenic preparations, and the processes of loading, unloading and transporting semi-finished products and finished dosage forms are mechanized, the concentration in the air of vapors and aerosols of extractants and drugs does not exceed acceptable levels. At the same time, violation of the tightness of equipment and communications, the use of manual labor, the presence of open surfaces, intermittency of technological processes, imperfect ventilation devices are one of the reasons for the high content of harmful substances in the air of the working area, 2-5 times or more exceeding the maximum permissible concentration.

The most important health improvement measure in workshops for the production of herbal medicines is the rationalization of technological processes with the widespread introduction of automation and mechanization. Sealing of equipment, communications, conveyors, etc. is an important condition in the system of preventive measures. Supply and exhaust ventilation is essential in improving working conditions. First of all, it is necessary to equip local exhaust devices at crushers, vibrating screens, places for loading and unloading raw materials, auxiliary ingredients, etc.

An extremely important role in ensuring normal working conditions is played by the planning solutions of galen workshops, taking into account the release of harmful substances and noise sources. Personal protective equipment is of great importance in preventing the harmful effects of production factors. Workers servicing crushers, mills, sieves, screw and belt conveyors and other technological equipment must be provided with special clothing, safety glasses type 03-N, 03-K, gloves, and respirators type ShB-1. In addition, operators who come into contact with organic extractants must have gas masks with a filter box of grade A.

8. Hygienic characteristics of working conditions in the production of medicines in ampoules

The technological process for the production of drugs in ampoules is carried out in the ampoule workshop of a pharmaceutical plant. The production cycle for the manufacture of ampoules consists of the following main operations: manufacturing ampoules, preparing the injection solution and filling ampoules (ampouling), sealing ampoules, sterilization, control, labeling and packaging.

Manufacturing of ampoules. It is produced in the ampoule workshop using special devices (automatic or semi-automatic). Ampoules are made from long, chemically resistant glass tubes called darts. First, the dart is washed, and then mounted on semi-automatic carousel or automatic machines, where ampoules are obtained from it using gas burners. At subsequent stages, ampoules with open capillaries are washed in semi-automatic vacuum machines. For more efficient washing, ultrasonic treatment of ampoules has been widely used in recent years. The washed ampoules are dried with hot air in drying cabinets and then transported to the ampoule filling departments.

Studies have shown that workers in this area are exposed to carbon monoxide and high temperatures (up to 28 °C). The main source of emitted harmful substances is the process of burning natural gas in gas burners of ampoule machines.

If the rules for cleaning premises are violated, in particular when removing dust mechanically and by blowing it off the surface of ampoule machines, the concentration of glass dust during this period may exceed the maximum permissible concentration by 2 times or more. Along with these occupational hazards, workers are exposed to noise, the source of which is ampoule machines. In addition, it must be borne in mind that when washing darts and ampoules, as well as when servicing ampoule machines, there is a risk of injury from glass fragments.

Preparation of solution and ampoule. Preparation of the injection solution begins with processing the solvent, which uses water, various oils (peach, almond, peanut, etc.), synthetic and semi-synthetic compounds. Water for injection is processed using high-performance distillers that ensure its appropriate quality, including non-pyrogenicity.

Ampoulement is carried out using a syringe or vacuum method: with the first, the ampoules are filled with the solution automatically using a syringe, with the second, a vacuum of a certain depth is created in them, after removing which the ampoule, immersed in the injection solution, is filled with a certain volume.

Filling ampoules with a medicinal substance requires ideal cleanliness, therefore, particularly strict sanitary and hygienic requirements are imposed on technological operations, layout, decoration and maintenance of premises. The walls should be tiled or covered with oil paint. The floor material must be resistant to water, disinfectants, organic solvents and other chemicals. These requirements are best met by covering it with a polymer material (polyvinyl chloride tiles, relin, etc.). An important point is air purification (filtration) and disinfection using bactericidal lamps. The room must be systematically wet cleaned.

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In our country, a new branch of the chemical-pharmaceutical industry for the production of antibiotics was created in a short period of time. Currently, the domestic medical industry produces more than 30 types of antibiotics and more than 75 dosage forms. Their share in the overall structure of the medical industry is 18%.

In addition to their use in medicine, antibiotics have found application in the food and meat and dairy industries for food preservation. They are added to the feed of animals and birds in order to increase the rate of weight gain.

The technological process for obtaining antibiotics consists of several stages, carried out in a certain sequence and using appropriate equipment: a) cultivation of seed material and biosynthesis of antibiotics (fermentation);

b) pre-treatment of the culture fluid; c) filtration; d) isolation and chemical purification (extraction method, ion exchange method, precipitation method); e) production of finished dosage forms; f) packaging and packing (Fig. 11.1).

The initial technological processes are based on the cultivation of seed material (producer) in flasks and fermenters. The grown production strain of the producer is transferred into special devices - inoculators, for the purpose of its further enrichment. The process of growing mushrooms and bacteria in inoculators is carried out under strictly defined conditions, which are provided by heating and cooling systems, air supply, and devices for mixing the production mass. Then the producer goes to fermentation. Fermentation refers to the cultivation (growing) of the producer and the formation of the maximum amount of antibiotic. Antibiotics are synthesized in microbial cells or released into the culture fluid during the biosynthesis process.

Pure antibiotic

The main equipment for the fermentation process are fermenters, which are huge containers of up to 100,000 liters. They are equipped with heating and cooling systems, supply of a sterile air mixture, mixers, as well as devices for loading and unloading nutrient medium and culture fluid. This stage of the technological process is characterized by the tightness of the equipment used, and therefore the possibility of air pollution with substances used for the biosynthesis of antibiotics, as well as with the biomass itself, which is formed at the end of the fermentation process, is practically eliminated.

Due to the fact that antibiotics form insoluble compounds with many substances present in the culture fluid, to increase the concentration, as well as more complete precipitation of impurities, the culture fluid is acidified to pH 1.5-2.0 with oxalic acid or a mixture of oxalic and hydrochloric acids. The treated culture liquid is filtered from mycelium and precipitated ballast substances to obtain a clear filtrate, called the native solution. Filtration of the treated culture liquid is carried out on open-type frame filter presses, which may result in splashing of the native solution. Manual unloading of filter presses leads to contact of workers with a culture fluid containing an antibiotic.

The next stage of antibiotic production is isolation and chemical purification. At this stage, the antibiotic solution is concentrated and purified to such purity that it can be used to obtain a finished drug. The content of the antibiotic in the native solution is very low, so isolating it in its pure form, purifying it and bringing it to the finished dosage form is a very complex and labor-intensive process: for example, to obtain 1 kg of antibiotic, about 600 liters of culture liquid must be processed.

To isolate and chemically purify antibiotics, one of the following methods is used: 1) extraction method using various solvents; 2) deposition method; 3) ion exchange method. The most widely used methods in the biosynthesis of antibiotics are extraction and ion exchange methods, and in recent years the ion exchange method for the isolation and purification of antibiotics has also been used in the production of other drugs. Its main advantage is that it eliminates the need to use toxic and explosive solvents. The method is economically beneficial, since its technology is simple and does not require expensive equipment and raw materials.

Extraction of antibiotics from the native solution is carried out in extractor-separators, the main disadvantage of which is the need for manual unloading, as a result of which the air in workshops can be polluted with solvents, for example, isooctanol in the production of tetracycline and hydroxy-tetracycline.

The paste-like products obtained during the chemical purification process are further dried and sifted. The drying process in the production of antibiotics plays an extremely important role, since the quality of the product depends on its organization. Heat-stable antibiotics, obtained in crystalline form with a low moisture content, are usually dried in vacuum drying ovens. Antibiotics obtained after chemical purification in the form of aqueous concentrates are dried in evaporation-drying units and vacuum-freeze dryers (Fig. 11.2). These processes must be carried out under sterile conditions.

Sterile dried antibiotics are packaged in sterile glass vials. Dosing of dry antibiotic into vials, capping, capping and rolling is performed using automatic machines. In some cases, Tekhnolog semi-automatic machines are used for this, in which only the process of filling bottles is automated. The remaining operations are carried out manually, and therefore the air of production premises may be polluted with antibiotic dust, and when two or more types of them are simultaneously packed, workers may be exposed to the combined effects of these products.

For oral administration, antibiotics are produced in the form of tablets and dragees. The tableting process is as follows: all components included in the mixture - antibiotics, fillers (powdered sugar, calcium stearate, talc, etc.) are loaded into a mixer, mixed and moistened with a mixture of sugar syrup, a solution of gelatin, hydrochloric acid and ethyl alcohol. Then the mass is granulated and sent for drying, which is usually carried out in heat dryers. After drying, the granules are powdered with a mixture of talc, calcium stearate and starch to increase flowability, and then pressed on rotary tablet machines and packaged in concurrency bags.

From a hygienic point of view, the tabletting process is characterized by intermittency, lack of tightness and a large number of manual operations. Due to these reasons, antibiotics can be released into the air during almost all tableting operations.

The processes of isolation and chemical purification of the antibiotic, carried out by extraction and precipitation methods, are associated with the possibility of exposure of the body to working vapors and gases of butyl, isopropyl and methyl alcohols, butyl acetate, oxalic, acetic, sulfuric and hydrochloric acids and other substances used in this stage . Concentrations of these substances in the air in some cases may exceed the maximum permissible limits. The main reasons for air pollution in the working area with harmful substances are insufficient tightness of equipment, the presence of manual operations, low efficiency of ventilation devices, etc.

At the final stages, as research shows, the processes of drying, sifting, tableting, packaging and packaging of antibiotics can be accompanied by significant environmental pollution with fine dust from the finished product. In addition, workers in the preparatory workshops, drying department, and fermentation, in addition to the chemical factor, can simultaneously be exposed to excess heat, the main source of which is inoculants, fermenters, drying units, as well as the surfaces of communication networks if they are insufficiently insulated.

Currently, significant material has been accumulated on the effect of antibiotics on the blood system: the development of anemia, agranulocytosis, leukopenia, and disturbances in vitamin metabolism.

Changes in the upper respiratory tract are expressed in the development of hyperemia and atrophy of the mucous membranes, mainly the nose and larynx. As the disease progresses, it can become complicated by asthmatic bronchitis and bronchial asthma. One of the manifestations of the side effects of antibiotics is dysbacteriosis - a disruption of the normal microflora of the body. In those working in the production of antibiotics, secondary mycoses are detected (usually candida - goats), changes in the gastrointestinal tract and upper respiratory tract, which developed against the background of dysbiosis of the mucous membranes, as well as inhibition of natural immunity factors. Workers experienced constipation, diarrhea, flatulence, erosions and ulcers of the rectal mucosa. The detected changes in health status are to a certain extent reminiscent of the side effects of antibiotics in clinical use.

Along with this, workers experience an increased incidence of influenza, ARVI and diseases of the female genital area.

An important place in the prevention of the harmful effects of chemical factors should be occupied by laboratory monitoring of the content of harmful substances in the air of the working area, the amount of which should not exceed established standards. Currently, maximum permissible concentrations have been established for the following antibiotics: streptomycin - 0.1 mg/m3, oxacillin - 0.05 mg/m3, florimicin - 0.1 mg/m3, hygromycin B - 0.001 mg/m3, oxytetracycline - 0 .1 mg/m3, ampicillin - 0.1 mg/m3, biovit (based on the content of chlortetracycline in the air) - 0.1 mg/m3, oleandomycin - 0.4 mg/m3, phytobacterin - 0.1 mg/m3 .

In the production of antibiotics, therapeutic and preventive measures are also important. These primarily include organizing and conducting preliminary and periodic medical examinations. Hiring to work in the preparatory, reactor, drying and other departments must be carried out taking into account the contraindications provided for working in contact with the hazards present in these departments. Carrying out periodic medical examinations is aimed at timely detection of possible occupational diseases. In order to prevent allergization of the body and the skin-irritating effect of chemicals, it is recommended to carry out preventive desensitization, use of protective ointments (for example, 2% salicylic acid), detergents, etc.

The synthetic drug industry produces several hundred different drugs, which can be combined into six groups:

1. Inorganic medicinal substances (preparations of bromine, iodine, potassium permanganate).

2. Medicinal compounds of the aliphatic series (alcohols, ethers, aldehydes, aldehyde acids, carboxylic acids, aliphatic amines, amino acids, etc.).

3. Alicyclic medicinal compounds (terpenoids, vitamins A, K, P, E, D, hormones, blood plasma substitutes).

4. Aromatic medicinal compounds (phenols and their derivatives, aromatic carboxylic acids and their derivatives, sulfonamide drugs, derivatives of aromatic sulfonic acids).

5. Organic medicinal substances (organic compounds of arsenic, antimony, bismuth, mercury, phosphorus, radiocontrast agents).

6. Medicinal compounds of the heterocyclic series (derivatives of five- and six-membered heterocycles with one or two heteroatoms).

The starting materials for synthetic medicines are the distillation products of coal, oil and other substances, the number of which amounts to many hundreds of items. These are a variety of organic and inorganic chemical substances found in liquid, solid and gaseous states. From them, through complex technological processing, organic intermediates are obtained, which are predominantly aromatic, less often heterocyclic and aliphatic compounds, mainly various aromatic amines and nitro compounds, phenols and naphthols, their sulfonic acids and halogenated compounds.

The production of synthetic chemical-pharmaceuticals is usually located in 1-2-3-story production buildings with side light. Housings with top or combined side and top light are very rare.

Organic synthesis of drugs, in terms of the accuracy of the operations performed, is mainly rough work (the size of the object of discrimination is more than 10 mm) or, less often, low-precision work (the size of the object is from 1 to 10 mm), and therefore the KEO values for them are relatively small and should be 0.5% or, less often, 1% (only in laboratory premises the KEO should be equal to 1.5%). However, in these workshops, both on the floor and on the working platforms, a significant amount of equipment is always installed, which, due to its large size, prevents access to daylight into the working areas. Therefore, in such industries it is possible to limit oneself to natural light only on bright days.

Artificial lighting of the main working areas of the chemical and pharmaceutical industry should be carried out mainly with incandescent lamps, and the most appropriate lighting system should be considered a general lighting system. Fluorescent light lighting systems can also be used, which are most appropriate for use in chemical laboratories, as well as in packaging shops. When choosing the type of lamp, you should take into account the environmental conditions in production premises: in case of high humidity and dust in the premises, it is necessary to use moisture-proof and dust-proof lamps. Local lamps in a combined lighting system are used relatively rarely, mainly for lighting control and measuring instruments. When carrying out repair work inside the devices, hand-held portable lamps should be used.

In accordance with the requirements of sanitary rules, the minimum illumination should be 30 lux in chemical shops (at a level of 0.8 m from the floor), 150 lux in control and measuring instruments, 50 lux in packaging shops (when packaging in large containers), in chemical laboratories on tables no less than 150 lux.

Along with general measures, all workers involved in the organic synthesis of medicinal products must be provided with personal protective equipment. The issued protective clothing must correspond to the nature of the harmful factors involved and the working environment. To protect the respiratory system from harmful vapors and gases, each worker is given an individual filter gas mask with a mask corresponding to the size of the face. The type of gas mask must correspond to the nature of toxic impurities that can be released into the air of working areas (from organic vapors, acid gases, etc.). In addition, the workshop must have a sufficient supply of hose gas masks, which should be used when eliminating accidents accompanied by high gas contamination of the premises. Hose gas masks are also necessary when working inside devices in which reactions with highly toxic substances occur (for example, when cleaning them internally). To protect against splashes of acids, alkalis and other caustic products, it is necessary to provide workers with safety glasses, and to protect against inhalation of medicinal and other dust - dust respirators.

At enterprises that produce synthetic drugs, a complex of sanitary facilities is provided (showers, changing rooms, toilets, as well as rooms for repair, degassing, drying and dust removal of work clothes). If work is carried out with highly toxic substances, then this complex of sanitary premises must include a sanitary inspection room.

An important preventative measure is the removal of impurities from the skin. In some cases, when the usual method of hand washing cannot remove stains, special detergents should be used. These include a mixture of soda and calcium hypochlorite, 30 parts each to 940 parts water; a mixture of 3% solution of potassium permanganate with 10% solution of calcium hypochlorite and a number of others.

Finally, it should be noted that everyone entering the enterprise for the production of synthetic chemical-pharmaceuticals must undergo a preliminary medical examination, and periodic medical examinations are also required for workers handling hazardous substances.

Pages: 3

The main production factors that determine working conditions in the industrial production of medicines include harmful chemicals, dust, unfavorable microclimate, noise, vibration, forced body position, tension of individual organs.

The most significant unfavorable factors in the production environment are harmful chemicals of organic and inorganic nature. They can be in the form of aerosols, vapors or gases and pollute the air of the working area, clothing and skin of workers at all stages of the technological process.

Air pollution in industrial premises toxic chemicals occurs due to imperfection and leakage of equipment, disruption and intermittency of technological processes, manual performance of many works, overflow of devices during loading, pressure drops in reactors and communication networks, and emergency situations.

Main source of allocation dust is the transportation of raw materials from storage premises to production workshops, as well as its crushing, grinding, sifting, and loading. Severe air pollution with dust occurs during tabletting, panning, drying, grinding, sifting, filling and packaging of medicines.

Bad influence heating microclimate For those working in the biochemical-pharmaceutical industry, it is observed in drying departments, near crystallizers and hydrolyzers with insufficient thermal insulation of devices and communication heat networks. In some cases, the heating microclimate aggravates the effect of the chemical factor.

Industrial noise and vibration in the industrial production of medicinal products, they are usually created during the operation of compressors, vacuum filters, drum dryers, centrifuges, crushers, vibrating screens, pumps and can exceed the permissible level by 5-25 dB. In engine rooms, high-frequency noise on average exceeds the permissible level by 25-35 dB.

Forced position of the body and tension in the eyes, arms, and torso most often occur during labeling, packaging and packaging of medicinal products.

Workers of synthetic industries producing bromine, iodine, potassium permanganate, alcohols, aldehydes, carboxylic acids, aliphatic amines, amino acids, vitamins A, K, P, E, D, hormones, blood plasma substitutes, organic compounds of arsenic, antimony, bismuth, mercury, phosphorus and other drugs are exposed to vapors and aerosols of toxic substances of the 1st hazard class. Nitrogen oxides, ammonia, vapors of organic solvents, and drug dust can enter the air of the working area.

Biotechnological production produces a large number of antibiotics, hormones, immunoglobulins and other drugs. Dust from the components of the growing medium, culture liquid, antibiotics, vapors of acids, alkalis and organic solvents have a harmful effect on workers. In addition, workers in the preparatory, drying and fermentation departments may be exposed to heating microclimates, including radiant heat.

The toxic effect of antibiotics on the body is manifested by itching of the skin, headache, pain in the eyes and can lead to allergic reactions, decreased hearing acuity, damage to the liver, kidneys, cardiovascular, circulatory and nervous systems. Under the influence of antibiotics, dysbacteriosis, candidomycosis, and an immunosuppressive state can develop.

In the production of herbal and novogalenic preparations, when crushing fresh medicinal plants, droplets of juice and small particles can enter the respiratory system, onto the skin and have an irritating and allergic effect. Personnel may be exposed to dichloroethane fumes.

ether, alcohols and other extraheites. dust of medicinal plants, heating microclimate, increased noise level.

For those working in the production of sterile medicines, occupational hazards include carbon oxide (II), heating the microclimate with a temperature of up to 28 "C, organic solvents, medicinal substances, glass dust.

Strict hygienic requirements are imposed on the production of sterile dosage forms. All technolo! Heating processes are carried out in rooms, which, depending on the purity of the air, are divided into four classes. The cleanest rooms are Class A, which are used for mixing ingredients, unloading and filling sterile ampoules, and capping vials. Class B premises are used for the preparation of solutions, filtering, washing, drying and sterilization of ampoules and vials, class C - washing and sterilization of auxiliary materials, class D - washing of darts, preparation of ampoules and other less critical stages of aseptic production.

In rooms of class A cleanliness, before work, the content of 10 mechanical particles / dm " with a size of 0.5 microns is allowed; there should be no microorganisms in the air. In rooms of class B cleanliness, no more than 375 and 50 are allowed, class C cleanliness - 3575 and 100 mechanical particles / dm 3 and microbial cells/m "respectively. In Class D premises, the content of particles and cells is not standardized.

Personnel in sterile areas must carefully comply with the requirements of industrial sanitation and observe the rules of personal hygiene. In clean areas, workers are not allowed to change clothes or wash themselves, wear watches, jewelry, or use cosmetics.

Strict hygienic requirements are imposed on clothing for workers in clean areas. It must be dust-proof, dust-absorbing, breathable, hygroscopic, resistant to physical and chemical treatment. Clothes should not release lint and fibers or create static electricity. Dacron fabric with cotton satisfies these requirements. Clean, sterile protective clothing, masks and gloves must be provided to every worker in a class A or B area for each shift.

In the production of tablets, the main occupational hazard is dust from various medicinal and auxiliary substances. A feature of tablet production is the presence of mixed dust in the air of the working area, which has an effect on the human body with amplification and summation effects.

The heating microclimate and intense noise from tablet machines also have an adverse effect on workers.

The main occupational hazards in the manufacture of pills are a heating microclimate with a temperature increase of up to 30 °C, intense noise from running motors and mixing medicinal substances, and medicinal dust.

At the enterprises of the biochemical and pharmaceutical industry, at almost all stages of the technological process of drug production, forced working posture, strain of vision and hand muscles are observed.

Improving working conditions at enterprises of the biochemical and pharmaceutical industry is comprehensive in nature and is aimed at preserving the health of workers and preventing occupational diseases and poisoning.

A major role in improving health conditions belongs to labor legislation, the development of maximum permissible concentrations and maximum permissible levels of industrial hazards for the work area.

In accordance with RD 64-125-91 “Rules for the organization of production and quality control of medicinal products (GMP)”, SanPiN 9-108 RB 98 “Sanitary rules and norms for enterprises producing medicinal products”, toxic substances in the formulation are replaced with less harmful ones ; intermittent to continuous operations; transferring open processes to closed ones; high pressure to low. Enterprises are improving equipment, automating and mechanizing production, and introducing remote software control.

In particular, in the production of synthetic drugs, mechanized and closed vacuum filters, self-discharging bottom-discharge centrifuges, drum vacuum filters and automatic filter presses, rake, spray and continuous drum dryers are used. Reactors and mixers are equipped with samplers, eliminating the need to open hatches. Open supply of solutions of toxic substances is not permitted.

In biotechnological production, fermenters must be sealed, and operations for loading, unloading and transporting materials must be mechanized and automated.

When producing drugs in ampoules, it is advisable to control the technological process using optical devices. The outer surface of ampoules and vials is cleaned after they are capped before being sent for inspection using a mechanized method. The removal of defective products from ampoules and vials is also mechanized and taken to separate rooms.

All loading processes are carried out in the tablet and coating shops. unloading and transportation of bulk substances must be mechanized, apparatus and communications must be sealed and thermally insulated. All noisy and vibrating mechanisms are equipped with anti-noise and vibration damping devices, remote control and are placed on insulated foundations.

Enterprises provide the necessary production and sanitary facilities, arrange efficient lighting, ventilation, heating and water supply. In particular, to protect workers from poisoning by toxic substances, nutsch filters are equipped with an exhaust hood with lowered curtains, and sampling valves are placed in a fume hood. In workshops for the production of galenic and new galenic preparations, local exhaust ventilation is installed at crushers, vibrating screens, and places for loading and unloading materials.

The tablet shop must be equipped with general supply and exhaust ventilation, and in addition to it, local exhaust at mixers, granulators, dusters, dryers, and tablet machines. In the coating shop, obductors are equipped with on-board suction. Places for discharging semi-products and finished products into portable containers should be equipped with stationary or mobile local suction.

An important role in the health improvement of workers belongs to preliminary and periodic medical examinations, dispensary observation, examination and treatment in a clinic, sanatorium or dispensary, organization of preventive nutrition, etc.