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1. Purpose
Establish Clean area environmental monitoring management procedures, standardize clean workshop management, and ensure that the production environment of the clean area meets the production process requirements.
(Figure 1: Cleanroom Environmental Management)
2. Scope of application
This procedure applies to the environmental management of clean areas.
3. Responsibilities
The head of the quality department, the head of the production department, and each inspector shall manage the clean area in accordance with this procedure.
4. Clean room environmental management requirements
4.1. Basic requirements
The inner surface of the clean room should be flat and smooth, without cracks, tight interfaces, no particles falling off, and can be cleaned and disinfected. The junction between the wall and the ground should be arc-shaped to facilitate cleaning.
Various pipes, lamps, vents and other public facilities in the clean room should avoid dust accumulation during design and installation.
The air entering the clean room must be purified and divided into clean levels according to the production process requirements. The number of dust particles and microorganisms in the clean room should be monitored and recorded regularly.
The windows, ceilings, pipes, vents, lamps and the edges of walls or ceilings in the clean room should be sealed, and the static pressure difference between adjacent rooms with different air cleanliness levels should be greater than 5 Pa. The static pressure difference between the clean room and the outdoor atmosphere should be greater than 10 Pa, and there should be a pressure difference indication device.
There should be measures to prevent cross contamination when personnel and materials enter and exit clean rooms with different air cleanliness levels.
4.2 Requirements for clean room temperature and humidity control
4.2.1 Basic requirements
Temperature and humidity are very important factors affecting product technology, so during production and storage, temperature and humidity must be controlled to ensure that the product meets the predetermined specifications and standards;
The temperature and relative humidity of the clean area should be consistent with the production process requirements. If there are no special requirements, the temperature should be controlled at 18~26℃ and the relative humidity should be controlled at 45%~65%.
(Figure 2: Clean room humidity control)
4.2.2 Temperature and humidity monitoring instruments and installation locations:
Temperature and humidity monitoring in the clean area is carried out using a digital thermometer and hygrometer, and its temperature and humidity are displayed simultaneously. However, the temperature and humidity are regulated by negative feedback control through the temperature and humidity probe installed on the total return air duct.
The thermometer and hygrometer are installed in the key operation room or area of the clean area. For non-key areas or rooms, the thermometer and hygrometer are not installed.
The thermometer and hygrometer should be installed in a fixed place on the wall of the room. It is strictly forbidden to place it randomly and keep it away from areas with excessive temperature and humidity.
The temperature accuracy of the thermometer and hygrometer is 0.1℃, and the humidity accuracy is 1%. When recording temperature and humidity, the accuracy of the measurement should be followed.
The location where the thermometer and hygrometer are installed, the measured temperature and humidity data should be able to represent the basic temperature and humidity conditions in the room. Do not place it at the coldest or hottest point.
The thermometer and hygrometer should be calibrated to ensure that it is in a controlled state and that the measured data is true and valid.
4.3 Pressure difference adjustment principle
4.3.1 Basic principle
The clean room must maintain a certain positive pressure so that unpurified air from the outside will not enter the clean area to ensure cleanliness. By implementing different pressure difference control for purification areas with different purification levels, the purification zoning can be achieved.
In the clean area of the same clean level, due to the actual production process, some rooms will produce large dust, harmful gases, steam, etc., and under the condition of ensuring a relative positive pressure with the external environment, it should also ensure a relative negative pressure with the adjacent clean area to prevent dust, harmful gases, steam, etc. from spreading and polluting other clean areas.
Clean area pressure difference control is guaranteed by the difference between the supply Air volume and the return air volume or exhaust air volume of the room. However, in any case, the supply air volume of the room must not be less than the return air volume or exhaust air volume, otherwise, it will cause the room and the external environment to be absolutely negative pressure.
Clean area pressure difference adjustment is to determine the pressure difference between the clean area and the external environment, between the rooms in the clean area, and between the rooms and the clean corridor by adjusting the size of the return air volume or exhaust air volume under the determined supply air volume state to ensure that it meets the design requirements.
The pressure difference air volume of each clean room in the clean area that maintains a positive pressure difference needs to be supplemented by outdoor fresh air. The fresh air ratio should be calculated based on the total supply air and total return air in the clean area, and before adjusting the pressure difference, adjust the fresh air ratio to meet the design requirements.
4.3.2 Pressure difference control standard:
Clean room (area) and non-clean area maintain positive pressure, pressure difference>10Pa. Maintain a pressure difference of>5Pa between areas with different cleanliness levels (high-level areas are positive pressure), set up a micromanometer (low-level area of the device), and record the pressure difference (before and after the shift).
Dust, heat, gas and other areas in the clean area maintain negative pressure with adjacent areas, pressure difference>5Pa, set up a micromanometer (set on the outside of the operating room), and record the pressure difference (before and after the shift).
(Figure 3: Clean room pressure difference adjustment)
4.4 Environmental requirements for sterility testing
Sterility testing should be carried out in a local 100-level unidirectional air flow area under an environmental cleanliness level of 10000.
The air between the buffer zone and the external environment, the sterile test room and the buffer zone should maintain positive pressure, and the air between the positive control room and the buffer zone should maintain negative pressure. The static pressure difference between the sterile test room and the outdoor atmosphere should be greater than 10Pa. The room temperature of the sterile test room should be maintained at 18~26℃, and the relative humidity: 45~65%.
The one-way air flow area, work surface and environment of the sterile test room should be regularly monitored for suspended particles, floating bacteria and settling bacteria according to the current national standard of "Test Methods for Suspended Particles, Planktonic Bacteria and Settling Bacteria in Clean Rooms (Areas) of Pharmaceutical Industry". At least once a year.
The number of colonies in the one-way air flow of the ultra-clean workbench should be checked during the sterile test: During each operation, 3 nutrient agar plates are placed on the left, middle and right of the laminar air and the table, exposed for 30 minutes, and cultured at 30~35℃ for 48 hours. The average number of colonies should not exceed 1CFU/plate.
(Figure 4: Sterility test)
4.5 Supervision and management
Equipment, containers, tools and pipelines in the clean area should be kept clean.
Class 100,000 and Class 10,000 clean workshops should be routinely cleaned every day and thoroughly cleaned once a week.
People and materials entering the clean area must follow the clean operation procedures.
The number of people entering the clean area is strictly controlled, and the staff (including maintenance, auxiliary, and personnel) are regularly trained and assessed on basic hygiene knowledge and clean operations: Temporary outsiders entering the clean area should be guided and supervised.
(Figure 5: Cleanroom supervision and management)
4.6 Regular testing
4.6.1. The test items and standards meet the requirements of Table C1 of YY 0033-2000 Sterile Medical Device Production Management Specifications.
4.6.2. Testing frequency
Dust particle count: once a month in the 10,000-level area.
Average colony count: once a week in the 10,000-level area.
Temperature and humidity are tested once per shift.
Air pressure is tested once a month.
Wind speed and wind speed are tested once a month.
4.6.3 test records:
Test results should be recorded.
Test personnel should help analyze the causes and solve problems that occur during the test.
Frequently asked questions
1. What are the CleanRoom Classification standards for pharmaceutical manufacturing?
Users often want to understand the classification system for cleanrooms, such as ISO 14644-1, which defines cleanroom classes (e.g., ISO5, ISO 7, etc.) based on the permissible levels of airborne particulate contamination.
2. What are the key requirements for air quality in pharmaceutical cleanrooms?
This question typically addresses the air quality specifications for pharmaceutical cleanrooms, including the required particulate limits, air changes per hour (ACH), temperature and humidity control, and the need for HEPA or ULPA filters.
3. How do you maintain GMP compliance in pharmaceutical cleanrooms?
Users often search for guidance on ensuring Good Manufacturing Practice (GMP) compliance within cleanrooms, including maintaining cleanliness, personnel hygiene, proper gowning, and adherence to documentation and regulatory standards.
4. What are the gowning procedures for pharmaceutical cleanrooms?
This question focuses on the proper gowning (e.g., gloves, masks, coveralls, shoe covers) and hygiene protocols to minimize contamination risks in pharmaceutical cleanrooms and ensure compliance with industry standards.
5. How do you validate and monitor a pharmaceutical cleanroom?
Users seek information on the validation processes for cleanrooms, including how to conduct particle count tests, monitor airflow, measure pressure differentials, and implement regular re-validation schedules to ensure consistent compliance.
6. What are the recommended air filtration requirements for pharmaceutical cleanrooms?
This question focuses on the types of air filtration systems required, such as HEPA filters, ULPA filters, and the necessary maintenance schedules for these filters to ensure air cleanliness in pharmaceutical production environments.
7. How often should pharmaceutical cleanrooms undergo cleaning and disinfection?
Users want to know the cleaning protocols and frequency for pharmaceutical cleanrooms, including the use of appropriate disinfectants, cleaning agents, and methods for different types of surfaces and equipment.
8. What are the temperature and humidity control requirements for pharmaceutical cleanrooms?
This question refers to the temperature (typically 18-24°C) and humidity (typically 40-60%) control standards required in pharmaceutical cleanrooms to maintain the integrity of the environment and prevent contamination or degradation of products.
