Laminar air flow in cleanrooms. Airway resistance. Lung resistance. Air flow. laminar flow. turbulent flow. Laminar flow formula

Description:

The operating rooms are one of the most critical links in the structure of a hospital building in terms of the importance of the surgical process, as well as providing special conditions microclimate necessary for its successful implementation and completion. Here, the source of release of bacterial particles is mainly medical personnel capable of generating particles and isolating microorganisms when moving around the room.

Hospital operating rooms
Air flow control

Over the past decades, in our country and abroad, there has been an increase in purulent-inflammatory diseases caused by infections, which, according to the definition of the World Health Organization (WHO), are called nosocomial (nosocomial) infections. An analysis of diseases caused by nosocomial infections shows that their frequency and duration are directly dependent on the state of the air environment in hospital premises. To ensure the required microclimate parameters in operating rooms (and industrial clean rooms), unidirectional air diffusers are used. The results of the air environment control and analysis of the movement of air flows showed that the operation of such distributors provides the required microclimate parameters, but often worsens the bacteriological purity of the air. To protect the critical area, it is necessary that the air flow leaving the device remains straight and does not lose the shape of its borders, that is, the flow should not expand or contract over the protected area where the surgical

The operating rooms are one of the most critical links in the structure of a hospital building in terms of the importance of the surgical process, as well as providing the special microclimate conditions necessary for its successful implementation and completion. Here, the source of release of bacterial particles is mainly medical personnel capable of generating particles and isolating microorganisms when moving around the room. The intensity of particles entering the room air depends on the degree of mobility of people, temperature and air velocity in the room. The HBI tends to move around the operating room with air currents, and there is always a risk of its penetration into the unprotected wound cavity of the operated patient. It is clear from observation that it is wrong organized work ventilation systems leads to an intensive accumulation of infection to levels exceeding the permissible.

For several decades, specialists from different countries have been developing system solutions to ensure the conditions of the air environment in operating rooms. The air flow supplied to the room must not only assimilate various hazards (heat, humidity, odors, harmful substances), maintain the required microclimate parameters, but also protect strictly established zones from infections, that is, the necessary cleanliness of indoor air. The area where invasive interventions are carried out (penetration into the human body) can be called the operating area or "critical". The standard defines such a zone as an “operating sanitary protection zone” and means by it the space where the operating table is located, auxiliary tables for instruments and materials, equipment, as well as medical personnel in sterile clothing. In there is the concept of "technological core", referring to the area of production processes under sterile conditions, which in meaning can be correlated with the operating area.

To prevent the penetration of bacterial contaminants into the most critical areas, screening methods through the use of a displacement air stream have become widely used. Laminar air flow diffusers of various designs were created, subsequently the term "laminar" was changed to "unidirectional" flow. Currently, you can find a variety of names for cleanroom air distribution devices, such as "laminar", "laminar ceiling", "operating ceiling", "clean air operating system", etc., which does not change their essence. The air diffuser is built into the ceiling structure above the protection zone of the room and can be of various sizes depending on the air flow. The recommended optimal area of ​​such a ceiling should be at least 9 m 2 in order to completely cover the operating area with tables, equipment and personnel. The displacing air flow at low speeds enters from top to bottom, like a curtain, cutting off both the aseptic field of the surgical intervention zone and the sterile material transfer zone from environment. Air is removed from the lower and upper zones of the room at the same time. HEPA filters (class H according to ) are built into the ceiling structure, through which the supply air passes. Filters trap but do not decontaminate living particles.

Currently, much attention is paid all over the world to the issues of air disinfection in hospitals and other institutions where there are sources of bacterial contamination. The documents set out the requirements for the need to decontaminate the air of operating rooms with a particle inactivation efficiency of at least 95%, as well as air ducts and equipment for climate systems. Bacterial particles emitted by surgical personnel continuously enter the room air and accumulate in it. To ensure that the concentration of particles in the indoor air does not reach the maximum permissible levels, it is necessary to control the air environment. Such control must be carried out after the installation of climate systems, maintenance or repair, that is, in the mode of an operated clean room.

The use of unidirectional flow air terminals with built-in ceiling-type ultra-fine filters in operating rooms has become commonplace for designers. Air flows of large volumes go down the premises at low speeds, cutting off the protected area from the environment. However, many specialists are unaware that these solutions are not enough to maintain the proper level of air disinfection during surgical operations.

The fact is that there are a lot of designs of air distribution devices, each of which has its own scope. The clean rooms of operating rooms within their "clean" class are divided into classes according to the degree of cleanliness, depending on the purpose. For example, general surgical operating rooms, cardiac surgery or orthopedic, etc. Each specific case has its own requirements for ensuring cleanliness.

The first applications of cleanroom air diffusers appeared in the mid-1950s. Since then, it has become traditional to distribute air in cleanrooms in cases where it is required to ensure low concentrations of particles or microorganisms in them, to be carried out through a perforated ceiling. The air flow moves through the entire volume of the room in one direction at a uniform speed, usually equal to 0.3–0.5 m/s. Air is supplied through a group of high-efficiency air filters placed on the ceiling of the clean room. The air supply is organized on the principle of an air piston moving downward through the entire room, while removing pollution. Air is removed through the floor. This air movement pattern helps to remove airborne contaminants from personnel and processes. This organization of ventilation is aimed at ensuring the cleanliness of the air in the room, but requires high air flow and is therefore uneconomical. For clean rooms of class 1000 or class ISO 6 (according to ISO classification), air exchange can be from 70 to 160 times/hour.

In the future, more rational devices of a modular type appeared, much smaller in size with low flow rates, allowing you to choose an air supply device based on the size of the protected area and the required air exchange rates of the room, depending on the purpose of the room.

Analysis of the operation of laminar air diffusers

Laminar devices are used in cleanrooms and are used to distribute large volumes of air, providing for the presence of specially designed ceilings, floor hoods and pressure control in the room. Under these conditions, the operation of laminar flow distributors is guaranteed to provide the required unidirectional flow with parallel flow paths. The high air exchange rate contributes to maintaining close to isothermal conditions in the supply air flow. Ceilings designed for air distribution with large air exchanges, due to the large area, provide a small initial air flow velocity. The operation of floor-level extractors and room pressure control minimize the size of the recirculation zones, and the principle of "one pass and one exit" easily works. Suspended particles are pressed against the floor and removed, so the risk of their recirculation is low.

However, when such air distributors operate in the operating room, the situation changes significantly. In order to maintain acceptable levels of bacteriological purity of air in operating rooms, air exchange values ​​according to the calculation usually average 25 times / h and even less, that is, they are not comparable with the values ​​for industrial premises. To maintain the stability of the movement of air flows between the operating room and adjacent rooms, it is usually maintained at an overpressure. Air is removed through exhaust devices symmetrically installed in the walls of the lower zone of the room. For distribution of smaller air volumes, as a rule, small-area laminar devices are used, which are installed only above the critical zone of the room in the form of an island in the middle of the room, instead of using the entire ceiling.

As observations show, such laminar devices will not always provide unidirectional flow. Since there is almost always a difference between the temperature in the supply jet and the ambient air temperature (5–7 °C), the colder air leaving the air handling unit descends much faster than an isothermal unidirectional flow. For operation of ceiling diffusers used in public institutions, this is a common occurrence. There is an erroneous conventional wisdom that laminars provide stable unidirectional airflow regardless of where or how they are used. In fact, under real-world conditions, the velocity of a low-temperature vertical laminar flow will increase as it approaches the floor. The larger the volume of supply air and the lower its temperature relative to the room air, the greater the acceleration of its flow. The table shows that the use of a laminar system with an area of ​​3 m 2 with a temperature difference of 9 ° C gives an increase in air velocity by a factor of three already at a distance of 1.8 m from the beginning of the path. The air speed at the outlet of the supply unit is 0.15 m/s, and at the level of the operating table it reaches 0.46 m/s. This value exceeds the allowed level. It has long been proven by many studies that at overestimated inlet flow rates it is impossible to maintain its “unidirectionality”. An analysis of air control in operating rooms, carried out by Salvati (1982) and Lewis (Lewis, 1993) in particular, showed that in some cases the use of laminar units with high air velocities leads to an increase in the level of air contamination in the area of ​​the surgical incision with subsequent risk of infection.

The dependence of the air flow rate on the area
laminar panel and supply air temperature
Air consumption, m 3 / (h. m 2) Pressure, Pa Air speed at a distance of 2 m from the panel, m/s
3 °С T 6 °С T 8 °С T 11 °С T NC
Single panel 183 2 0,10 0,13 0,15 0,18 <20
366 8 0,18 0,20 0,23 0,28 <20
549 18 0,25 0,31 0,36 0,41 21
732 32 0,33 0,41 0,48 0,53 25
1.5-3.0 m 2 183 2 0,10 0,15 0,15 0,18 <20
366 8 0,18 0,23 0,25 0,31 22
549 18 0,25 0,33 0,41 0,46 26
732 32 0,36 0,46 0,53 - 30
More than 3 m 2 183 2 0,13 0,15 0,18 0,20 21
366 8 0,20 0,25 0,31 0,33 25
549 18 0,31 0,38 0,46 0,51 29
732 32 0,41 0,51 - - 33

T - difference between the temperature of supply and ambient air

When the flow moves, at the starting point the air current lines will be parallel, then the flow boundaries will change, narrowing towards the floor, and it will no longer be able to protect the area defined by the dimensions of the laminar installation. At air speeds of 0.46 m/s, the flow will capture the stagnant air from the room. Since bacterial particles are constantly released in the room, contaminated particles will be mixed into the air flow coming from the supply unit, since the sources of their release are constantly operating in the room. This is facilitated by air recirculation resulting from the overpressure of air in the room. To maintain the cleanliness of the operating rooms, according to the standards, it is required to ensure an imbalance of air due to the excess of inflow over exhaust by 10%. Excess air is moved to adjacent less clean rooms. In modern conditions, airtight sliding doors are often used in operating rooms, there is nowhere for excess air to go, it circulates around the room and is taken back into the supply unit using fans built into it for further cleaning in filters and secondary supply to the room. The circulating air collects all polluted particles from the room air and, moving near the supply air flow, can pollute it. Due to the violation of the boundaries of the flow, air from the surrounding space is mixed into it and pathogenic particles penetrate into the sterile zone, which is considered to be protected.

High mobility promotes intensive exfoliation of dead skin particles from unprotected areas of the skin of medical personnel and their entry directly into the surgical incision. On the other hand, it should be noted that the development of infectious diseases in the postoperative period is caused by the patient's hypothermic state, which is aggravated by exposure to cold air flows of increased mobility.

Thus, a laminar flow air diffuser, traditionally used and effectively operated in a clean room, may be detrimental to operations in a conventional operating room.

This conversation is true for laminar devices with an average area of ​​​​about 3 m 2 - optimal for protecting the operating area. According to American requirements, the air flow rate at the outlet of laminar panels should not exceed 0.15 m / s, that is, from 1 foot 2 (0.09 m 2) of the panel area, 14 l / s of air should enter the room. In our case, this will be 466 l / s (1677.6 m 3 / h) or about 17 times / h. According to the normative value of air exchange in operating rooms should be 20 times / h, according to - 25 times / h, therefore 17 times / h is quite consistent with the requirements. It turns out that the value of 20 times / h corresponds to a room with a volume of 64 m 3.

According to today's standards, the area of ​​​​a standard operating room (general surgical profile) should be at least 36 m 2. And for operating rooms for more complex operations (cardiology, orthopedic, etc.), the requirements are much higher, and often the volume of such an operating room can exceed 135–150 m 3. The air distribution system for these cases will require a much larger area and air capacity.

In the case of organizing air flow in larger operating rooms, there is a problem of maintaining the laminar flow from the exit plane to the level of the operating table. Several operating rooms have been used to study the behavior of airflow. In different rooms, laminar panels were installed, which were divided by area into two groups: 1.5–3 m 2 and more than 3 m 3, and experimental air conditioning units were installed, allowing you to change the temperature of the supply air. Multiple measurements of the incoming air flow rate were carried out at various flow rates and temperature drops, the results of which can be seen in the table.

Room cleanliness criteria

The right decisions regarding the organization of air distribution in operating rooms: the choice of a rational size of supply panels, ensuring the normative flow rate and temperature of the supply air - do not guarantee absolute air disinfection in the room. The issue of air disinfection in operating rooms was sharply raised more than 30 years ago, when various anti-epidemiological measures were proposed. And now the goal of the requirements of modern regulatory documents for the design and operation of hospitals is air disinfection, where HVAC systems are presented as the main way to prevent the spread and accumulation of infections.

For example, the standard considers decontamination to be the main goal of its requirements, noting: "a properly designed HVAC system minimizes the airborne transmission of viruses, bacteria, fungal spores and other biological contaminants", HVAC systems are given a major role in the control of infections and other harmful factors. The requirement for air conditioning systems in operating rooms is highlighted: "The air supply system must be designed in such a way as to minimize the penetration of bacteria into sterile areas along with air, and also maintain the maximum level of cleanliness in the rest of the operating room."

However, regulatory documents do not contain direct requirements for determining and monitoring the effectiveness of disinfection for various ventilation methods, and designers often have to engage in search activities, which takes a lot of time and distracts from their main work.

In our country, there are quite a lot of different regulatory literature on the design of HVAC systems for hospital buildings, and everywhere there are voiced requirements for air disinfection, which, for a variety of objective reasons, are practically difficult for designers to implement. This requires not only knowledge of modern disinfection equipment and the correct use of it, but, most importantly, further timely epidemiological control of the indoor air environment, which gives an idea of ​​the quality of HVAC systems, but, unfortunately, is not always carried out. If the cleanliness of clean industrial premises is assessed by the presence of particles (for example, dust particles) in it, then the indicator of air purity in clean rooms of medical buildings is live bacterial or colony-forming particles, the permissible levels of which are given in. To maintain these levels, it is necessary to regularly monitor the air environment for microbiological indicators, for which it is necessary to be able to count them. The methodology for collecting and counting microorganisms to assess the purity of the air has not yet been given in any of the regulatory documents. It is important that the counting of microbial particles should be carried out in the operated room, that is, during the operation. But for this, the design and installation of the air distribution system must be ready. The level of disinfection or the effectiveness of the system cannot be established before it starts working in the operating room, this can only be done under the conditions of at least several operational processes. For engineers, this presents great difficulties, since research, although necessary, is contrary to the order of compliance with the anti-epidemic discipline of the hospital.

air curtain

To ensure the required air regime in the operating room, it is important to properly organize the joint work of air inflow and removal. The rational interposition of supply and exhaust devices in the operating room can improve the nature of the movement of air flows.

In operating rooms, it is impossible to use both the area of ​​the entire ceiling for air distribution and the area of ​​the floor for its removal. Floor exhaust units are unhygienic as they get dirty quickly and are difficult to clean. Bulky, complex and expensive systems have not found their application in small-sized operating rooms. For these reasons, the most rational is the "island" arrangement of laminar panels above the critical zone with the installation of exhaust holes in the lower part of the walls. This makes it possible to model airflows similar to an industrial clean room in a cheaper and less cumbersome way. Such a method as the use of air curtains operating on the principle of a protective barrier has successfully proved itself. The air curtain is well combined with the supply air flow in the form of a narrow "shell" of air with a higher velocity, specially organized around the perimeter of the ceiling. The air curtain operates continuously for extraction and prevents the entry of polluted ambient air into the laminar flow.

To understand the operation of an air curtain, one should imagine an operating room with an exhaust fan arranged on all four sides of the room. The supply air coming from the "laminar island" located in the center of the ceiling will only go down, expanding towards the walls as it descends. This solution reduces the recirculation zones, the size of the stagnant areas in which pathogenic microorganisms collect, and also prevents the laminar flow from mixing with the room air, reduces its acceleration and stabilizes the speed, as a result of which the downward flow covers (locks) the entire sterile zone. This helps to remove biological contaminants from the protected area and isolate it from the environment.

On fig. 1 shows a standard design of an air curtain with slots around the perimeter of the room. When organizing the exhaust along the perimeter of the laminar flow, it is stretched, it expands and fills the entire zone inside the curtain, as a result of which the “narrowing” effect is prevented and the required laminar flow rate is stabilized.

From fig. Figure 3 shows the actual (measured) velocity values ​​that occur with a properly designed air curtain, which clearly demonstrate the interaction of a laminar flow with an air curtain, with a laminar flow moving evenly. The air curtain eliminates the need for a cumbersome exhaust system around the entire perimeter of the room, instead installing a traditional hood in the walls, as is customary in operating rooms. The air curtain protects the area immediately around the surgical staff and table, preventing contaminated particles from returning to the primary air stream.

After the design of the air curtain, the question arises of what level of disinfection can be achieved during its operation. A poorly designed air curtain will be no more effective than a traditional laminar system. A high air velocity can be a design error, as such a curtain will "pull" the laminar flow too quickly, i.e. even before it reaches the operating ceiling. The behavior of the flow cannot be controlled and there may be a risk of infiltration of contaminated particles into the operating area from floor level. Likewise, an air curtain with a low suction velocity cannot effectively shield a laminar flow and may be drawn into it. In this case, the air regime of the room will be the same as when using only a laminar supply unit. When designing, it is important to correctly determine the speed range and select the appropriate system. This directly affects the calculation of disinfecting characteristics.

Despite the clear advantages of air curtains, they should not be blindly applied. Sterile airflow generated by air curtains during surgery is not always required. The need to ensure the level of air disinfection should be decided jointly with technologists, who in this case should be surgeons involved in specific operations.

Conclusion

Vertical laminar flow can behave unpredictably depending on its mode of operation. Laminar panels used in cleanrooms generally cannot provide the required level of decontamination in operating rooms. Air curtain systems help to correct the nature of the movement of vertical laminar flows. Air curtains are the optimal solution to the problem of bacteriological control of the air environment in operating rooms, especially during long-term surgical operations and when there are patients with a compromised immune system, for whom airborne infections pose a particular risk.

The article was prepared by A.P. Borisoglebskaya using materials from the ASHRAE journal.

"... laminar air flow: an air flow in which the air velocities along parallel streamlines are the same..."

Source:

"ASEPTIC MANUFACTURE OF MEDICAL PRODUCTS. PART 1. GENERAL REQUIREMENTS. GOST R ISO 13408-1-2000"

(approved by the Decree of the State Standard of the Russian Federation of September 25, 2000 N 232-st)

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At low velocities, the fluid tends to flow without lateral mixing—neighboring layers slide past each other like playing cards. There are no transverse currents perpendicular to the direction of flow, eddies or pulsations.

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1. Breath. Respiratory system. Functions of the respiratory system.
2. External respiration. Biomechanics of respiration. The process of breathing. Biomechanics of inspiration. How do people breathe?
3. Exhale. The biomechanism of exhalation. Exhalation process. How does exhalation take place?
4. Change in lung volume during inhalation and exhalation. Function of intrapleural pressure. pleural space. Pneumothorax.
5. Phases of breathing. The volume of the lung(s). Breathing rate. Depth of breathing. Lung volumes of air. Respiratory volume. Reserve, residual volume. lung capacity.
6. Factors affecting lung volume in the inspiratory phase. Distensibility of the lungs (lung tissue). Hysteresis.
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9. Dependence "flow-volume" in the lungs. Airway pressure during exhalation.
10. The work of the respiratory muscles during the respiratory cycle. The work of the respiratory muscles during deep breathing.

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The movement of air from the external environment through the respiratory tract to the alveoli and vice versa is influenced by the pressure gradient: in this case, air moves from an area of ​​high pressure to an area of ​​low pressure. When inhaling, the air pressure in the alveolar space is less than atmospheric pressure, and when exhaling, the opposite is true. Airway resistance air flow depends on the pressure gradient between the oral cavity and the alveolar space.

Airflow through the respiratory tract can be laminar, turbulent and transitional between these types. Air moves in the airways mainly in a laminar flow, the speed of which is higher in the center of these tubes and lower near their walls. With laminar air flow, its velocity is linearly dependent on the pressure gradient along the airways. In places where the airways divide (bifurcations), the laminar air flow becomes turbulent. When turbulent flow occurs in the airways, a breath noise is produced that can be heard in the lungs with a stethoscope. The resistance to laminar gas flow in a pipe is determined by its diameter. Therefore, according to Poiseuille's law, the amount of airway resistance to air flow is proportional to their diameter raised to the fourth power. Since the resistance of the airways is inversely related to their diameter to the fourth power, this indicator most significantly depends on changes in the diameter of the airways caused, for example, by the release of mucus from the mucous membrane or narrowing of the bronchial lumen. The total diameter of the respiratory tract increases in the direction from the trachea to the periphery of the lung and becomes as large as possible in the terminal airways, which causes a sharp decrease in the resistance to air flow and its speed in these parts of the lungs. Thus, the linear velocity of the inhaled air flow in the trachea and main bronchi is approximately 100 cm/s. At the border of the airway and transitional zones of the respiratory tract, the linear velocity of the air flow is about 1 cm / s, in the respiratory bronchi it decreases to 0.2 cm / s, and in the alveolar passages and sacs - up to 0.02 cm / s. Such a low airflow rate in the alveolar ducts and sacs causes a slight resistance moving air and is not accompanied by a significant expenditure of energy of muscle contraction.

On the contrary, the largest airway resistance air flow occurs at the level of segmental bronchi due to the presence of secretory epithelium and a well-developed smooth muscle layer in their mucous membrane, i.e. factors that most affect both the diameter of the airways and the resistance to air flow in them. One of the functions of the respiratory muscles is to overcome this resistance.

The air of industrial premises is a potential source of drug contamination, therefore its purification is one of the key issues of technological hygiene. The level of cleanliness of the air in the room determines the cleanliness class.

To ensure the production of sterile solutions with dust-free sterile air, both conventional turbulent ventilation systems are used to ensure the sterility of the air in the room, as well as systems with laminar air flow over the entire area of ​​the room or in certain working areas.

With a turbulent flow, the purified air contains up to 1000 particles per 1 liter, when air is supplied with a laminar flow throughout the entire volume of the room, the content of particles in the air is 100 times less.

Premises with laminar flow- these are rooms in which air is supplied towards the working area through filters that occupy the entire wall or ceiling, and is removed through the surface opposite to the air inlet.

There are two systems: vertical laminar flow, at which air moves from above through the ceiling and leaves through the slatted floor, and horizontal laminar flow, in which air enters through one, and leaves through the opposite perforated wall. The laminar flow carries away from the room all airborne particles coming from any sources (personnel, equipment, etc.).

In cleanrooms, laminar flow must be created. Laminar airflow systems must provide a uniform air velocity of about 0.30 m/s for vertical and about 0.45 m/s for horizontal flow. Preparation and control of air for mechanical inclusions and microbiological contamination, as well as an assessment of the efficiency of air filters should be carried out in accordance with regulatory and technical documentation.

On fig. 5.2 shows various schemes for supplying dust-free air to the production room.

Rice. 5.2. Dust-free air supply schemes: A - turbulent flow; B - laminar flow

To ensure the required air purity in the "vertical laminar flow" and "horizontal laminar flow" systems, filtering units are used, consisting of pre-coarse air filters - a fan and a sterilizing filter (Fig. 5.3.).

Rice. 5.3. Air filtration and sterilization unit:

1 - coarse filter; 2 – fan; 3 - fine filter

For the final purification of air from the particles and microflora contained in it, a filter of the LAIK type is used. It uses ultra-fine perchlorovinyl resin fiber as a filter material. This material is hydrophobic, resistant to chemically aggressive environments and can operate at temperatures not exceeding 60°C and relative humidity up to 100%. Recently, high-efficiency particulate air (HEPA) air filters have become widespread.

High purity of the air environment is created by filtering through a pre-filter and then using a fan - through a sterilizing filter with a filtering material of the brand FPP-15-3, which is a layer of ultra-thin fibers made of polyvinyl chloride polymer. Indoors, mobile recirculating air cleaners VOPR-0.9 and VOPR-1.5 can be additionally installed, which provide fast and efficient air purification due to its mechanical filtration through a filter made of ultrathin fibers and ultraviolet radiation. Air cleaners can be used during operation, as do not have a negative impact on the staff and do not cause discomfort.

To create ultra-clean rooms or separate zones, a special block is placed inside it, into which an autonomous laminar flow of sterile air is supplied.

Requirements for personnel and workwear

Equipping production with laminar flow systems and supplying clean and sterile air to the room does not yet solve the problem of clean air, because. the staff working in the premises is also an active source of pollution. Therefore, a minimum number of workers must be present in cleanrooms during work, as provided for by the relevant instructions.

Within one minute, a person, without moving, releases 100,000 particles. This figure rises to 10 million during intensive work. The average number of microorganisms excreted by a person in 1 minute reaches 1500-3000. Therefore, the protection of medicines from human contamination is one of the main problems of technological hygiene and it is solved mainly due to the personal hygiene of employees and the use of technological clothing.

Personnel entering the production area must be dressed in special clothing appropriate for the production operations they perform. Technological clothing of personnel must correspond to the cleanliness class of the area in which they work and fulfill their main purpose - to protect the product of production as much as possible from particles emitted by humans.

The main purpose of technological clothing for workers is to protect the product of production as much as possible from particles emitted by humans. Of particular importance is the fabric from which technological clothing is made. It must have a minimum linting, dust capacity, dust permeability, as well as air permeability of at least 300 m 3 / (m 2 ·s), hygroscopicity of at least 7%, and not accumulate an electrostatic charge.

The following requirements are imposed on personnel and technological clothing intended for zones of different types:

· Class D: Hair must be covered. General protective suit, appropriate footwear or overshoes should be worn.

· Class C: Hair must be covered. Wear a trouser suit (one-piece or two-piece) that fits snugly around the wrists with a high collar and appropriate shoes or overshoes. Clothing and footwear must not emit lint or particles.

· In rooms of cleanliness class A / B, you should wear a sterile trouser suit or overalls, headgear, shoe covers, mask, rubber or plastic gloves. If possible, disposable or specialized technological clothing and footwear with minimal lint and dust capacity should be used. The lower part of the trousers should be hidden inside the shoe covers, and the sleeves should be hidden in gloves.

High standards of personal hygiene and cleanliness must be placed on those working in clean areas. Watches, jewelry, and cosmetics should not be worn in clean rooms.

Of great importance is the frequency of changing clothes, depending on climatic conditions and the time of year. In the presence of conditioned air, it is recommended to change clothes at least once a day, and a protective mask every 2 hours. Rubber gloves should be changed after each contact with the skin of the face, and also in any case when there is a danger of contamination.

All personnel (including those involved in cleaning and maintenance) working in clean areas should receive systematic training in subjects related to the correct manufacture of sterile products, including hygiene and basic microbiology.

Personnel working in "clean" rooms must:

- strictly restrict entry to and exit from "clean" rooms in accordance with specially developed instructions;

Carry out the production process with the minimum necessary number of personnel. Inspection and control procedures should generally be carried out outside "clean" areas;

Limit the movement of personnel in rooms of cleanliness classes B and C; avoid sudden movements in the working area;

Do not be located between the air flow source and the work area to avoid changing the direction of the air flow;

Do not lean over or touch open product or open containers;

Do not pick up or use objects that have fallen on the floor during work;

Before entering the "clean" room (staff training room), remove all jewelry and cosmetics, including nail polish, take a shower (if necessary), wash hands, treat hands with disinfectants and put on sterile technological clothes and shoes;

Avoid talking about extraneous topics. All verbal communication with people outside the production premises must take place through an intercom;

Report all violations, as well as adverse changes in the sanitary and hygienic regime or climatic parameters to your management.

Process Requirements

It is not allowed to manufacture different medicinal products at the same time or sequentially in the same room, except in cases where there is no risk of cross-contamination, as well as mixing and mixing of different types of raw materials, intermediates, materials, intermediates and finished products.

Control in the production process, carried out in production facilities, should not have a negative impact on the technological process and product quality.

At all stages of the technological process, including the stages preceding sterilization, it is necessary to implement measures that minimize microbial contamination.

The time intervals between the start of the preparation of solutions and their sterilization or sterilizing filtration should be minimal and have restrictions (time limits) established during the validation process.

Preparations containing live microorganisms may not be produced and packaged in premises intended for the production of other medicinal products.

Water sources, water treatment equipment and treated water should be regularly monitored for chemical and microbiological contamination, and, if necessary, for endotoxin contamination to ensure that water quality meets regulatory requirements.

Any gas that comes into contact with solutions or other intermediate products during the process must undergo sterilizing filtration.

Materials that tend to form fibers with their possible release into the environment, as a rule, should not be used in clean rooms, and when conducting a technological process in aseptic conditions, their use is completely prohibited.

After the stages (operations) of the final cleaning of the primary packaging and equipment during the further conduct of the technological process, they must be used in such a way that they do not re-contaminate.

The effectiveness of any new methods, replacement of equipment and methods of conducting the technological process must be confirmed by validation, which must be repeated regularly according to the developed schedules.

Process equipment requirements

Production equipment should not adversely affect product quality. Parts or surfaces of equipment that come into contact with the product must be made of materials that do not react with it, do not have absorption properties, and do not emit any substances to such an extent as to affect the quality of the product.

One of the ways to solve these problems is the use of modern automatic lines ampouling of injectables.

The transfer of feedstock and materials into and out of production areas is one of the most serious sources of contamination. Therefore, transfer device designs can vary from single or double door devices to fully sealed systems with a sterilization zone (sterilization tunnel).

Isolators may only be put into service after appropriate validation. Validation should take into account all critical factors of the containment technology (eg air quality inside and outside the isolator, transmission technologies and isolator integrity).

Particular attention should be paid to:

Equipment design and qualification

Validation and reproducibility of clean-in-place and sterilization-in-place processes

The environment in which the equipment is installed

Operator qualification and training

· Cleanliness of technological clothes of operators.

Quality control requirements

During the technological process for the production of injection solutions, an intermediate (stage-by-stage) quality control is necessarily carried out, i.e. after each technological stage (operation), ampoules, vials, flexible containers, etc. are screened if they do not meet certain requirements. So, after dissolution (isotonization, stabilization, etc.) of the medicinal substance, the qualitative and quantitative composition, pH of the solution, density, etc. are controlled; after the filling operation - the volume of filling of vessels is checked selectively, etc.

Incoming raw materials, materials, semi-finished products, as well as manufactured intermediate or finished products immediately after receipt or completion of the technological process, until a decision is made on the possibility of their use, must be quarantined. Finished products are not allowed to be sold until their quality is found to be satisfactory.

Liquid medicinal products for parenteral use are usually controlled for the following quality indicators: description, identification, transparency, color, pH, concomitant impurities, recoverable volume, sterility, pyrogens, abnormal toxicity, mechanical inclusions, quantitative determination of active substances, antimicrobial preservatives and organic solvents.

For liquid medicines for parenteral use in the form of viscous liquids, density is additionally controlled.

For liquid medicines for parenteral use in the form of suspensions, the particle size, content uniformity (in the case of single-dose suspensions), suspension stability are additionally controlled.

In powders for injections or intravenous infusions, the following are additionally controlled: dissolution time, loss in mass on drying, content uniformity or mass uniformity.