Fundamentals of General and Pharmaceutical Hygiene - Dykyi I.L. 2003

Hygiene of Pharmaceutical Production
Hygienic assessment of working conditions at pharmaceutical enterprises. Environmental safety of pharmaceutical production

According to the international Classification (US Environmental Protection Agency), chemical and pharmaceutical enterprises are classified as environmentally hazardous industries.

Pharmaceutical manufacturing is based on multi-stage processes of organic or biological synthesis involving A wide variety of raw Materials, which is accompanied by environmental and health pollution through organic and inorganic chemical emissions. Therefore, studying the environmental safety of pharmaceutical manufacturing, assessing working conditions, and developing health and safety measures are of paramount importance.

A hazardous occupational factor is defined as an environmental or work-process factor whose influence on an employee under certain conditions (intensity, duration, etc.) can cause occupational diseases, temporary or permanent disability, increase the frequency of somatic or infectious diseases, or lead to impaired offspring health.

The main occupational hazards in industrial drug manufacturing include: Chemical factors (harmful organic and inorganic substances in the form of dust, vapors, gases, and aerosols); biological factors (products of microbiological synthesis—Antibiotics, antibiotic-containing drugs, biological products, etc.); unfavorable microclimate; noise; and vibration.

These factors can cause health disorders and The Development of occupational diseases in workers, presenting a specific symptom complex. For instance, prolonged contact with Solvents, acids, alkalis, Alkaloids, Vitamins, and antibiotics can cause acute and chronic Skin diseases (dermatitis, eczema, toxicoderma), follicular apparatus disorders, melanoderma, Bronchial Asthma, and other occupational diseases. Furthermore, the thermal microclimate at certain workstations in chemical and pharmaceutical enterprises acts as an additional factor that exacerbates the effects of chemicals.

Health and safety measures encompass legislative, administrative, organizational, technological, sanitary-technical, and therapeutic-prophylactic measures, as well as The Use of personal protective equipment.

Sanitary and hygienic inspection of a pharmaceutical enterprise is carried out according to specially designed programs reflected in inspection checklists (see below).

Objective: to understand the main occupational hazards and master the assessment of working conditions in industrial drug manufacturing; to learn how to develop specific measures aimed at improving working conditions, preventing occupational diseases, and enhancing work capacity.

QUESTIONS FOR SELF-STUDY

1. METABOLISM/2.html">THE CONCEPT OF occupational hazards in pharmaceutical enterprises.

2. Main occupational hazards in pharmaceutical enterprises.

3. Specifics of working conditions in The production of synthetic, phytochemical, immunobiological drugs, antibiotics, and vitamins.

4. Toxicological characteristics of industrial poisons: organic solvents, mineral acids, caustic alkalis, chlorine, nitrogen oxides, hydrogen sulfide, ammonia.

5. Factors influencing the Toxic effects of industrial poisons.

6. Occupational dust and the Specific features of its impact on the body.

7. Hygienic characteristics of noise, vibration, and ultrasound at pharmaceutical enterprises.

8. Hygienic CHARACTERISTICS OF THE industrial microclimate.

9. Measures to improve working conditions in the manufacturing of medicinal products.

10. The purpose and Structure/175.html">Implementation of preliminary and periodic medical examinations at enterprises manufacturing medicinal products.

11. Environmental safety of pharmaceutical production.

Assignment. Prepare an essay on one of the topics from the section

“Occupational Health in Industrial Drug Manufacturing,” covering the following issues:

— brief description of technological processes;

— hygienic characteristics of the main occupational hazards (assessment of microclimate, chemical factors, noise, vibration, ultrasound, etc.);

— The Nature of The impact of occupational hazards on the workers' bodies;

— health-improving measures.

Essay Topics

1. Occupational hygiene in the production of synthetic drugs.

2. Occupational hygiene in the production of antibiotics.

3. Occupational hygiene in the production of herbal remedies.

4. Occupational hygiene in the production of biological products.

5. Occupational hygiene in the production of injectable dosage forms.

6. Hygienic characteristics of working conditions in the production of aerosol dosage forms.

7. Hygienic characteristics of working conditions in the manufacture of tablets and dragees.

When writing an essay, as well as when conducting a sanitary and hygienic

inspection of a pharmaceutical manufacturing enterprise, special sanitary inspection charts should be used.

SANITARY INSPECTION CHART OF THE ENTERPRISE (general)

1. Name of the enterprise.

2. List of main workshops and a brief Description of the production process as a whole.

3. Composition of workers and employees (by number, gender, and age).

4. Work schedule (number of shifts, breaks).

5. Enterprise Class. Industrial hazardous substances released into the atmosphere. Sanitary protection zone, standardized and actual. Its condition.

6. Mutual Location OF THE enterprise and residential areas, taking into account the prevailing wind direction.

7. Characteristics of the terrain and soil of the production site (elevation, relief, groundwater table).

8. Characteristics of the Water body located near the enterprise.

9. Territory of the enterprise, adequacy of size, presence and nature of surface pavement, its maintenance, landscaping, availability of storage areas for raw materials, products, fuel, etc., and stormwater drainage systems.

10. Layout of the industrial site, location of buildings (relative to each other and to the prevailing wind direction), distances between buildings from the perspective of occupational health and fire safety.

11. In-plant transport, yard roadways, pedestrian walkways, rail sidings, inter-shop transport, and traffic safety.

12. Operations carried out in the yard of the enterprise, their Organization.

13. Lighting of the yard, roadways, and walkways.

14. Drinking and industrial water supply of the enterprise: water sources, their capacity (yield), adequacy of water supply, water distribution and storage system, drinking water quality, availability of water Treatment and disinfection facilities.

15. Characteristics of solid waste and Methods of its disposal. Composition and volume of wastewater, treatment, disposal, and neutralization system.

16. General plant, auxiliary, and amenity facilities (laundry rooms, canteens, etc.). Their dimensions, adequacy, operating schedule, and sanitary condition.

17. Organization of Medical care: medical and sanitary unit, polyclinic, health post, and workshop medical stations. Is the demand for medical care fully met?

18. Brief general sanitary Conclusion regarding the state of the enterprise.

19. Record of Changes in the sanitary condition of the enterprise.

SANITARY INSPECTION CARD FOR INDIVIDUAL WORKSHOPS

1. Name of the workshop.

2. Number of workers, their gender and age distribution.

3. Operating schedule: number of shifts, breaks.

4. Building type, construction material, type of roofing, number of spans. On which floor is the workshop located?

5. Room dimensions: length, width, height; total and usable area; cubic capacity; usable cubic capacity per worker.

6. Brief description of the production process; characteristics of equipment and machinery.

7. Meteorological conditions in the workshop at the main workstations: Temperature, relative humidity, air velocity. Thermal radiation: sources, intensity. Measures to mitigate unfavorable meteorological conditions and evaluation of their effectiveness.

8. Dust levels at the main workstations: dust sources, peak dust emission periods, Chemical composition of dust, quantitative dust characteristics. Preventive measures.

9. Emission of harmful vapors and gases: sources, peak emission periods, chemical composition, and concentrations. Preventive measures.

10. Ventilation.

11. Presence of industrial noise (sources, sound pressure level, spectrum, continuous or intermittent noise), vibration (nature of oscillatory movements, constancy). Noise and vibration control measures, evaluation of their effectiveness.

12. Presence of short-wave radiation sources; radiation characteristics; protection measures (radio-frequency electromagnetic fields, ultraviolet and infrared radiation, laser radiation, static electricity).

13. Risk of traumatic injuries: clutter in the workshop, occupational safety measures. In-plant transport, safety measures.

14. General sanitary condition of the premises, cleaning system.

15. Heating: system, characteristics of heating devices, their placement. Sanitary and Hygienic evaluation of the heating system.

16. Lighting.

17. Drinking water supply system for workers, its sanitary characteristics.

18. Auxiliary and amenity facilities, adequacy according to the nomenclature, dimensions, sanitary condition, and operating schedule.

19. Physiological features during technological operations: working posture (standing, sitting, forced body position); monotony of working movements (their frequency per unit time).

20. Personal hygiene of workers.

21. General sanitary conclusion on the condition of the workshop.

22. Hygienic recommendations.

TASKS FOR INDEPENDENT WORK

1. Knowledge testing.

2. Solving situational tasks.

3. Abstracts (as assigned by the instructor).

TESTS

1. According to GMP principles, to ensure the quality of a medicinal product, it is essential to prevent cross-contamination, which refers to its contamination by:

A. Microorganisms.

Б. Toxins.

B. Another type of product.

Г. Pyrogens.

2. A "cleanroom" is defined as a production area whose air:

A. Lacks microorganisms.

Б. Contains microorganisms within regulated limits.

B. Lacks particulate matter.

Г. Contains particulate matter within regulated limits.

3. During manufacturing and storage, medicinal products can be contaminated by microflora, the sources of which are differentiated into 1) exogenous and 2) endogenous. Indicate them (match the numbers with the letters):

A. Room air.

Б. Personnel hands.

B. Medicinal raw materials.

Г. Workwear.

Д. Primary packaging.

E. Water.

F. Equipment.

4. Occupational health is a system for ensuring workers' health in the course of their employment, which includes:

A. Socio-economic measures.

B. Legal measures.

C. Sanitary and hygienic measures.

D. Therapeutic and prophylactic measures.

E. Rehabilitation measures.

5. A harmful occupational factor is an environmental or work-process factor that may cause:

A. Temporary decrease in working capacity.

B. Occupational pathology.

C. Persistent decrease in working capacity.

D. Increased incidence of somatic diseases.

E. Increased incidence of infectious diseases.

F. Long-term effects of exposure.

6. Working conditions that preserve the health of workers and create prerequisites for maintaining a high level of working capacity are called:

A. Permissible.

B. Optimal.

C. Safe.

D. Hazardous.

A. Harmful.

B. Optimal.

C. Extreme.

D. Permissible.

8. One of the effective health-improving measures at pharmaceutical enterprises is the Introduction of so-called "clean" technologies. Which principle is not characteristic of them?

A. Equipment sealing.

Б. Remote control.

B. Continuous technologies.

Г. Intermittent technologies.

Д. Process automation.

9. Health and safety measures at chemical and pharmaceutical enterprises include a range of activities. To which group does the installation of efficient ventilation belong?

A. Organizational.

Б. Therapeutic and prophylactic.

B. Administrative.

Г. Sanitary and technical.

Д. Technological.

10. Occupational hazards are differentiated into:

A. Mechanical.

Б. Physical.

B. Chemical.

Г. Biological.

11. Chronic benzene poisoning is characterized by the following manifestations:

A. Paresis.

Б. Bronchitis.

B. Paralysis.

Г. Neurotic symptoms.

Д. Asthenic symptoms.

Е. Hemorrhagic symptoms.

12. Chronic sulfur dioxide poisoning is characterized by:

A. Encephalopathy.

B. Tooth decay.

C. Acidosis.

D. Rhinitis.

E. Bronchitis.

F. Parkinsonism.

13. Lead poisoning is typically characterized by the following manifestations:

A. Basophilic stippling of erythrocytes.

B. Hemorrhagic syndrome.

C. Raynaud's syndrome.

D. Sciatic neuritis.

E. Drowsiness and memory impairment.

14. Chronic manganese poisoning is characterized by:

A. Sciatic neuritis.

B. Drowsiness and memory impairment.

C. Impaired motor coordination.

D. Emotional lability.

E. Hemorrhagic syndrome.

15. The purpose of routine medical examinations at pharmaceutical enterprises is:

A. Detection of early signs of disease.

B. Disease Prevention.

C. Treatment of diseases.

16. In drug synthesis reactors, the sources of harmful emissions are:

A. Manholes.

B. Observation windows.

C. Agitator shaft seals.

D. Flanged joints.

17. From a hygienic standpoint, the most favorable method for feeding solid raw materials from the warehouse is:

A. Screw conveyor.

B. Conveyor belt.

C. Pneumatic transport.

D. Elevator.

18. Occupational hazards associated with crushing and grinding processes:

A. Dust and gases.

B. Noise and vibration.

C. Unfavorable microclimate.

D. Dust.

19. Indicate the most hygienically favorable method for the isolation and chemical purification of antibiotics:

A. Precipitation.

B. Extraction.

C. Ion sorption.

20. Indicate the filters that best meet hygienic requirements:

A. Filter presses.

B. Rotary drum filters.

C. Leaf filters.

D. Nutsche filters.

SITUATIONAL PROBLEMS

1. Identify the primary occupational hazards in this production facility.

2. Determine the class of working conditions according to the degree of harmfulness and danger.

3. Describe the Nature of the harmful factor's effect on the body.

4. Standardization of the factor.

5. Propose measures to improve working conditions.

Example of solving a situational problem

Working conditions at a pharmaceutical plant during the production of sulfa drugs were studied. A medical examination of 18 workers revealed allergic dermatitis in 14, Complaints of nausea, and leukopenia and agranulocytosis in four workers. It was established that workers manually unload Nutsche filters and change the filter cloth. Local exhaust ventilation is lacking. Workers are not provided with work clothes, and personal protective equipment is issued irregularly.

Solution.

1. The primary occupational hazard in this production process is chemical.

2. According to the accepted classification, the working conditions in this facility can be classified as Class 3 (2nd or 3rd degree), which is characterized as harmful.

3. Allergic dermatitis results from workers coming into contact with crystalline sulfa drugs and solvents. The irregular use of personal protective equipment facilitates contact of chemicals with the skin and mucous membranes. Nausea, as well as leukopenia and agranulocytosis detected in some workers, may also be consequences of exposure to sulfa drugs and solvents.

4. The maximum allowable concentration of sulfa drugs in the air of the working zone is 1.0 mg/m³ (for sulfalene, 0.1 mg/m³).

5. Measures to improve working conditions:

— improvement of the technological process, replacing batch Nutsche filters with continuous hermetic drum filters;

— providing workers with work clothing;

— regular use of personal protective equipment (respirators, safety goggles, etc.);

— periodic medical examinations at least once a year.

Problem 1.

Working conditions at a pharmaceutical plant during the production of chlorpromazine were studied. The concentration of chlorpromazine dust in the working area air at the coating and Reactor operator stations was 10 mg/m³. Medical examination revealed allergic conditions of the eczema type, with complaints of photophobia, redness and Swelling of the eyelids, and a cutting pain in the eyes. Blood tests showed decreased levels of Histidine, Methionine, Tryptophan, leucine, Arginine, and Tyrosine.

Problem 2.

Working conditions at a pharmaceutical plant during the production of antipyretics were studied. Increased concentrations of ethyl alcohol, dimethyl sulfate, and sulfur dioxide compared to normal levels were detected in the air. In some areas (First and Second methylation processes), high air temperature and humidity were noted, and dust concentrations of various antipyretics in the working zone exceeded established maximum permissible limits. Some operations are performed manually (unloading, transportation, loading). Out of 14 examined individuals, 10 showed allergic diseases (dermatitis, Conjunctivitis, rhinitis), and 5 exhibited functional Disorders of the cardiovascular and nervous systems. Complaints of headaches were noted.

Problem 3.

During a periodic medical examination of workers engaged in the production of morphine, pantopon, and codeine, cases of asthmatic attacks were identified; workers in contact with the drugs showed lesions on exposed areas of the body (hands and face), with complaints of dry Mouth, chills, and fever. Health deviations were most frequently encountered among operators working on the purification and drying of the drug.

Problem 4.

Working conditions in the tablet workshop of a pharmaceutical plant during analgin production were studied. The concentration of analgin dust in the air during the grinding, powdering, drying, and pressing stages was 105 mg/m³. In the drying department, the air temperature was 38 °C. Drying is carried out in shelf dryers, and samples are taken openly. The impulse noise level exceeds permissible values by 40 dB. Personal protective equipment is used irregularly. During interviews, all workers complained of dryness and irritation of the mucous membranes and skin, as well as headaches. Dermatitis, conjunctivitis, and rhinitis were found in 60% of the workers.

Problem 5.

Working conditions in the tablet workshop of a pharmaceutical plant during amidopyrine production were studied. The concentration of the drug in the air at the grinding, powdering, drying, and pressing stages was 160 mg/m³. In the drying department, the air temperature was 38 °C. Drying is carried out in shelf dryers, and samples are taken openly. The impulse noise level exceeds permissible values by 20 dB. Personal protective equipment is not used. During interviews, all workers complained of dryness and irritation of the mucous membranes and skin, as well as headaches. Dermatitis, conjunctivitis, and rhinitis were found in 80% of the workers.

Problem 6.

Working conditions in the synthesis of synthetic drugs at the synthesis stage were studied. It was found that the most frequent operation is sampling intermediates and finished substances through an open hatch of the apparatus, monitoring the acid-base reaction and liquid level. This operation is short-term, lasting no more than 5 minutes. During amidopyrine production at the Hydrolysis stage, the sulfur dioxide concentration during sampling was 20 mg/m³. Personal protective equipment is not used consistently. Medical examination revealed Upper Respiratory Tract mucosal atrophy in 25% of the workers, and workers with over 5 years of service exhibited dental destruction and acidosis.

Problem 7.

Working conditions in Vitamin C production were studied. Dichloroethane vapors (70 mg/m³), acetone (280 mg/m³), and ethyl alcohol (1005 mg/m³) were detected in the air of the working zone. The noise level in some areas exceeds the permissible limit by a factor of two. Workers in this production facility perform various manual operations, with physical exertion being intermittent and short-term. Medical examination of the workers revealed chronic Diseases of the upper respiratory tract in 37%, as well as functional disorders of the cardiovascular (tachycardia) and nervous systems. Many complain of general weakness, headaches, and Sleep disturbances. Workers with more than 5 years of employment history showed signs of Liver and Kidney damage, and anemia.

Problem 8.

Working conditions in the production of the antibiotics tetracycline and chloramphenicol were studied. Phenol and formaldehyde vapors were detected in the air of the working zone at the Fermentation stage at concentrations of 20 and 50 mg/m³, respectively. Significant contamination of the workers' hands and workwear with culture fluid and native antibiotic solution was found during filtration. In the fermentation and drying departments, the air temperature was 36 °С. At the tabletting stage, the concentration of tetracycline dust in the working zone air was 10 mg/m³, and chloramphenicol dust was 20 mg/m³. A medical examination of 18 workers revealed allergic dermatitis in 12 (affecting the hands, forearms, and face), while 10 workers complained of flatulence and diarrhea. Leukopenia and agranulocytosis were detected in 5 workers.

Problem 9.

Working conditions at a galenical pharmaceutical plant during the production of belladonna and schisandra tinctures were studied. The concentration of raw material dust in the working zone air during loading into the percolator was 8 and 10 mg/m³, respectively, and ethyl alcohol vapor was 1500 mg/m³. The noise level exceeded the permissible limit by a factor of 2. Personal protective equipment is used intermittently. Medical examination revealed allergic dermatitis in 50% of the workers, and workers with more than 3 years of employment history complained of dizziness, increased excitability, tachycardia, and shortness of breath.