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Introduction to Dust Control Measures in Biopharmaceutical Clean room

2023-08-25

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Marya

The clean room is at the core of pharmaceutical factory production, and its cleaning effect directly affects the quality of drugs. The environment of a clean room is affected by fine dust, making it difficult to ensure the quality of drugs. This article explores relevant measures for controlling micro dust in clean rooms.

The clean room is at the core of pharmaceutical factory production, and its cleaning effect directly affects the quality of drugs. The environment of a clean room is affected by fine dust, making it difficult to ensure the quality of drugs. Such drugs can delay or exacerbate the patient's condition, bringing huge physical harm and negative social impact. Therefore, the control of micro dust in clean rooms must be taken seriously and strictly implemented by pharmaceutical factories. This article explores relevant measures for controlling micro dust in clean rooms for reference. In order to effectively control the environment of clean rooms, it is necessary to maximize the control of the sources of micro dust that produce particles and microorganisms. The measures to control micro dust can be taken from various aspects, such as controlling the types of micro dust, controlling the production process, and so on. From the perspective of production related objects and people, the environment, personnel, facilities, and materials in which production is carried, contaminated, adhered to, or generated particles and microorganisms become sources of micro dust. This article will analyze these aspects.

一、Air conditioning cleaning system

 

The entire process of controlling a clean room essentially revolves around the control of dust production and effective dust removal to control micro dust. The environment of a clean room includes the structure, wall materials, water system, air conditioning clean system, etc. The validated air conditioning cleaning system can meet the cleanliness requirements under normal working conditions. The micro dust generated by the air conditioning cleaning system can be divided into two types: one is the micro dust objectively caused by the system operation, and the other is the micro dust that does not meet the control factor standards.

1.1 Micro dust objectively caused by system operation - refers to the accumulation of dust particles and moisture (or high humidity) in certain areas that may breed microorganisms after the operation of the air conditioning cleaning system. The particle size of microbial metabolites is very small, which can easily enter the clean room through filters, causing a rapid decrease in cleanliness. Pharmaceutical factories cannot completely control microorganisms through single air filtration, and regular disinfection of the air should be carried out. The commonly used methods for air disinfection include direct ultraviolet radiation, ozone disinfection, spraying disinfectant, electrostatic adsorption, and other technologies. When using disinfectants, drug resistance should be considered and at least two combination disinfection methods should be adopted. Special attention should be paid to the fact that the disinfection effect of disinfectants cannot be sustained and can easily cause secondary micro dust, while other disinfection methods have certain drawbacks. Therefore, in order to avoid dust retention problems, hoses and soft joints should not be used, and it is necessary to regularly clean the components of the air conditioning system to avoid the generation of micro particles, moisture, and local high humidity.

1.2 Control of dust caused by factors - GMP has clear requirements for temperature, humidity, air pressure, lighting, and noise in clean rooms. The air conditioning system affects these indicators by controlling positive pressure, air change frequency, and suspended particles to meet cleanliness requirements.

1.2.1 Insufficient positive pressure in the clean room and adjacent rooms - Test method: Test in the sampling area at the same point within two meters from the door. If the test exceeds the standard when the door is opened, and the test is qualified after 20 minutes of closing the door, it can be determined that the positive pressure in the clean room and adjacent rooms is insufficient. If the positive pressure value does not meet the standard, the external atmosphere will pour back, bringing a large amount of dust and bacteria, seriously damaging cleanliness. At this point, the solution can be achieved by increasing the positive pressure to a point where there is sufficient external airflow at the moment of opening the door to prevent the invasion of fine dust. It is possible to consider increasing the amount of fresh air, but it may be necessary to add new air units, which is a significant one-time investment. In addition, a more economical and applicable method is to adjust the resistance of all levels of filters, while ensuring the filtering effect, to minimize the filter resistance as much as possible. In addition, it is necessary to replace the initial and intermediate efficiency filters in a timely manner, clean and maintain the condenser and cold and hot water coils in a timely manner.

1.2.2 The number of air changes in the clean room is unreasonable - whether it is the dilution effect during turbulent flow or the displacement effect during single-phase flow, it is necessary to control and achieve various parameters of the clean room based on the amount of clean air. Therefore, the number of air changes in the clean room cannot be too low. If the number of air changes in a clean room is too large, it will increase operating costs and may not necessarily improve the level of the clean room accordingly. The number of air changes in a clean room depends on the indoor heat balance calculation. The conventional requirement for a clean room with a 10000 level air change rate is at least 25 times per hour, while a 100000 level air change rate is at least 15 times per hour. The air supply volume of the clean room should take the maximum of the following three values:

(1)The air supply volume to ensure air cleanliness level;
(2)The air supply volume determined based on the calculation of heat and humidity loads;
(3)The amount of fresh air supplied to the clean room.

The amount of fresh air should be taken as the larger of the following two items: the sum of the amount of fresh air required to compensate for the internal exhaust air volume and maintain the indoor positive pressure value; Maintain a fresh air supply of no less than 40 cubic meters per person per hour in the clean room.

二、People are an important source of fine dust in clean rooms

 

The metabolism of the human body produces micro dust, which is carried by the human body. When people move in a clean room, a large amount of micro dust is generated and emitted. According to the analysis of test results, the source of micro dust in the clean room is about 80% of the workers. The dust in and out of the clean room increases significantly, and when someone is moving, the cleanliness deteriorates significantly, confirming that humans are the main cause of micro dust in the clean room. As a source of fine dust and the main medium of transmission in drug production, human beings always come into direct or indirect contact with drugs, which affects the quality of drugs. This impact comes from two aspects, one is the original physical condition of the personnel. The second is personal hygiene habits. Therefore, the management and supervision of human health should start from the following aspects.

2.1 The necessity of establishing health records indicates that pharmaceutical factories have a general understanding of the health status of their employees when recruiting them. Pharmaceutical factories also need to establish physical examination rules and regularly conduct physical examinations for employees. Personnel working in the clean room will come into direct contact with drugs and undergo a physical examination at least once a year. Those who do not pass the examination should be immediately transferred from their positions. Pharmaceutical factories establish personal health records to facilitate inspection, understanding, and tracking of personal health status.

2.2 Cultivate good personal hygiene habits. Personnel engaged in the drug production process should wash their hands and bathe frequently, maintain cleanliness of their hands and other parts of the body, and break bad hygiene habits. Before entering the clean room, one must change clothes (the clean room must use protective clothing made of anti-static materials) and clean people through clean facilities. During drug production, it is also necessary to cover the body, especially the mouth, nose, and hair. Protective clothing protection can not only protect operators from adverse factors in the production environment, but also prevent human dust from affecting the quality of drug production.

2.3 Control the number of people in the clean room. Although it is necessary to change clothes before entering the clean room, there is still a certain amount of dust generated during walking and operation in the clean room, which needs to be carried away by the downdraft of the clean room. When the dust production exceeds the cleanliness capacity of indoor airflow, the cleanliness will rapidly decrease. When these excess people (or objects) exit the clean room and pass through the self-cleaning ability of the air conditioning cleaning system, the cleanliness will return to normal. According to GMP regulations, the number of microbial particles and dust particles in the air of clean rooms should be regularly monitored, and the monitoring results should be recorded and archived. During the production process, if these data differ significantly in a short period of time, it indicates that people (or objects) in the clean room have exceeded the purification capacity of the clean room.

2.4 The practice of clean room work procedures and GMP has shown that a large number of micro dust problems are caused by insufficient employee hygiene training and non-compliance with relevant hygiene regulations. Pharmaceutical factories should provide relevant hygiene training for employees around controlling micro dust, and also emphasize the requirements of working in clean rooms. Personnel working in the clean room should move as slowly as possible, avoid significant movements, and prohibit loud noise. It is prohibited to bring food and other unrelated items into the clean room. Staff should try not to work with illness. Sneezing and coughing can cause 0.2-50% of the surrounding air pollution μ The sudden increase of dust particles in m damages the cleanliness level. In addition to the basic content mentioned above, pharmaceutical factories can develop appropriate procedures based on actual situations.

 

三、Dust control of production materials

 

The production facilities in the clean room also generate fine dust, and the design and installation should consider the impact of facility work on the environment and regular cleaning work in the future. The following mainly explains the precautions for controlling the micro dust of production materials in the clean room.

3.1 Material cleaning measures require effective elimination of particles and microorganisms on the external surface before entering the clean room. For this purpose, the material cleaning room should include a cleaning room, air lock room, or transfer window. Remove the outer packaging of the materials in the outer packaging cleaning room and place them in a clean container for future use. In addition, it should also pass through the air lock room or transfer window before entering the clean room, and the materials sent to the sterilization room should be sterilized in advance. The transfer window is a device used to temporarily cut off airflow when transferring items between indoor and outdoor or clean rooms of different cleanliness levels to prevent damage to cleanliness. The conveyor belt for conveying materials shall not be transported from areas with low cleanliness levels to areas with high cleanliness levels. Generally, it can only be transported in sections on both sides of the transfer window.

3.2 The material passage, material cleaning path, and human cleaning path are separately and independently set up. The entrance and flow direction of materials must also be separated from the flow of people, so as not to cross back and forth as much as possible to avoid logistics passing through the area being operated. A large comprehensive production plant can consider setting up multiple material entrances, but they must not affect each other. The production operation area should not be used as a passage for material transfer, and the space in the production site should minimize the opening of doors to ensure the airtightness and cleanliness of the operation room.

四、Conclusion

 

Micro dust control runs through the entire pharmaceutical production activity, and the micro dust control in the clean room should also be implemented in all aspects. From design to construction, installation, operation, and cleaning, it is a continuous process. In the past, the management of clean rooms in pharmaceutical factories often focused more on hardware investment, neglecting the role played by people themselves. In fact, the quality of the clean room during design and construction determines the upper limit of high quality for future production. After passing the validation in the clean room, specific dust control measures become more meaningful. In daily production activities, strictly follow the key requirements of the clean room, cultivate good hygiene habits, and carefully observe the changes in indicators recorded in the clean room. This can better ensure cleanliness and reduce the number of abnormal situations in the clean room. During the initial stage of use (usually three months) in the clean room, careful observation and intensive recording of various indicators can provide key points and change cycles suitable for the supervision of dust control in our factory, serving as operational guidance for pharmaceutical factory production.