Best Practice Guide for Clean Room Cleaning and Maintenance

Standard Guide for Cleanroom Cleaning, Gowning, and Maintenance

Purpose of Maintenance and Management:

For a clean room, design, construction, maintenance and management accounts for 1/3 separately in terms of importance.
Maintenance refers to measures to maintain the original design status.
Management refers to the system for implementing such measures.

The purpose of maintenance and management is:

(1)Control indoor dust and bacteria generation below design requirements.
(2)Make the system and equipment operate normally and effectively achieve the design purpose of preventing dust and bacteria from entering.
(3) The dust and bacteria that have been generated must be removed immediately to prevent them from accumulating and becoming a sudden clean damage, so as to prevent the occurrence of emergencies.

Definition and sources of clean room contamination: 

Clean room pollution refers to any foreign matter and energy that harms products or processes, including particles, ions, molecular pollution, microorganisms, micro-vibration, noise, light pollution, electromagnetic radiation, static charge, etc.

Sources of contamination:
(1) Humans are the largest source of contamination in cleanrooms: skin, hair, oils, clothing fibers, and metabolic products.
(2) Infiltration of polluted air from the surrounding environment.
(3) Intake of air that has not been HEPA filtered.
(4) Dust generation from enclosures and other surfaces.
(5) Dust generation from process equipment and processes.
(6) Dust generation from raw materials, containers, water, gas, solvents, and outer packaging.
(7) A large number of microorganisms that exist in nature and in people’s living environment.

Personnel management system:
Personnel are the core of maintenance and management, and therefore should be well educated and trained first.
(1) The number of people entering the clean production area should be strictly controlled. No unauthorized personnel are allowed to enter the clean production area.
(2) All personnel entering the clean production area shall receive regular training. The training content shall include basic knowledge of cleanliness, hygiene and microorganisms.
(3) Appropriate measures should be taken when the health condition of personnel may increase the risk of microbial contamination.
(4) Personnel entering the clean production area must follow the operating procedures for dressing, handwashing, and disinfection. The quality, style, and wearing method of the work clothes should be appropriate to the production operation requirements and the clean class of the operational area.

â–º Class A/B clean area: Cover all hair and beard with a hood, tuck the hood into the collar, wear a mask, gloves and protective goggles. Wear sterilized foot covers, tuck the pants into the foot covers, and tuck the cuffs into the gloves. Work clothes should be sterilized one-piece work clothes.

â–º Class C clean area: Hair and beard should be fully covered, and a mask should be worn. Work clothes should be sterile one-piece work clothes or two-piece work clothes, and appropriate shoes or shoe covers should be worn.

â–º Class D clean area: hair and beards should be covered, and appropriate work clothes, shoes or shoe covers should be worn.

The dressing room should be divided into two areas: the first area is for changing out of street clothes, and the second area is for changing into cleanroom work clothes.
Additionally, personnel entering and exiting the cleanroom must comply with the following regulations:
(1) Entering the clean room must follow the established purification procedures and routes, and no unauthorized changes are allowed.
(2) Personnel must put on designated clean room shoes before entering the clean area; wearing slippers into the clean room is prohibited.
(3) Outer garments and cleanroom attire should be stored separately in designated areas and lockers. Entering the changing room without removing outer garments is not permitted.
(4) At the entrance to the cleanroom, if there is an air shower room, personnel must pass through the air shower room. After entering, they should close the door as instructed, raise both arms, and slowly rotate their body twice inside the air shower room.
(5) When entering the buffer room, it is necessary to close one door before opening the other.
(6) After entering the cleanroom, personnel must wash their hands as needed, change into work clothes, and then change into sterile clothing after hand disinfection.
(7) Washed hands should be dried with a dryer or wiped with a paper towel that produces less dust.
(8) Wear clean work clothes in a standing position, and do not let the work clothes touch the ground, workbench and other dusty items.
(9) Wash and disinfect your hands after changing work clothes, and do not handle purified items with bare hands.
(10) Do not go to the toilet in clean work clothes. Going to the toilet should be handled according to the procedures for entering and leaving the clean room.

Equipment management system:

Production equipment: The management of cleanroom production equipment can also directly affect the cleanliness.
Key points of equipment cleaning:
(1) Sterile equipment, especially the parts that directly contact the drug, must be sterile and the sterilization date should be marked. Sterilized equipment should be used within 3 days, otherwise it should be sterilized again.
(2) When the same equipment continuously processes the same sterile product, it should be cleaned and sterilized between each batch.
(3) The minimum requirement for washing water is potable water. All water used for final washing should be purified water prepared from potable water. For pre-washing in sterile preparations, purified water should also be used, and the final washing should be done with water for injection prepared from purified water.
(4) Equipment that needs to be cleaned and disinfected should be appropriately selected based on the structure of the machine, the properties of the material and the characteristics of the drug being cleaned.
(5) The conventional cleaning method of solid preparation production equipment should be carried out in accordance with the equipment cleaning operation or specification requirements.
(6) Movable equipment should be moved to the cleaning area for cleaning, and non-movable equipment should have cleaning facilities.
(7) The processing status of the equipment before use should be marked and confirmed.

Air conditioning equipment:

(1) Fan: The fan is the focus of inspection. The main thing to check is whether the belt is slipping or falling off. You can press the belt between the driving wheel and the driven wheel by hand. The amount of pressing should be 1.25-2.5cm. If the belt is too loose, the air volume will decrease. If it is too tight, it is easy to damage the bearing seat. In addition, the bearings should be oiled on time.
(2) Heat exchanger (cooler or heater): Pay attention to whether there is blockage between the blades. Use high-pressure water to clear the blockage in time when it is not too serious. The cooler blades should also be regularly cleaned and sterilized with chemicals because bacteria are most likely to grow here.
(3) Humidifier: Some metal impurities and scale will accumulate in the water tray under the humidifier. These impurities should be removed regularly to ensure the normal operation of the humidifier and avoid contamination. The water baffle should be cleaned frequently, and the drainage point of condensed water should be checked and cleaned. These places are hotbeds for bacteria.
(4) Motor: Insulation inspection should be carried out regularly.
(5)The above equipment should be inspected at least twice a year.

Disinfection and sterilization:

Sterilization refers to the complete extinction of the life of bacteria and viruses, which has an absolute meaning, while in a narrow sense, some bacteria or viruses (usually excluding bacterial spores) are not destroyed due to their resistance to heat or drugs, which has a relative meaning. For example, wiping the surface with disinfectant solution is disinfection, boiling and normal pressure steam are also ways of disinfection, and even ultraviolet irradiation can only achieve disinfection effects.

Disinfection falls under the category of hygiene management, whereas sterilization pertains to aseptic production.

Common cleanroom sterilization methods include:

Dry heat sterilization: A method of heating in dry air. Dry heat sterilization includes air circulation in the sterilization room and maintaining positive pressure. The air entering the sterilization room should be gas that has been treated with a sterilizing filter. (135~200℃ or more, 5h~0.5h)

Moist heat sterilization: A sterilization method using high temperature wet steam (usually saturated steam). Moist heat sterilization is more effective and takes less time than dry heat sterilization. However, it is only applicable to wettable materials and aqueous solutions.

Gas sterilization: A method of fumigation using a certain gas, such as ethylene oxide. The sterilizing gas should not have a destructive effect on the product or equipment, and the conditions and time for removing the gas should be clear.

Radiation sterilization: A method of irradiating items with radiation. It is mainly applicable to the sterilization of heat-sensitive substances or products, but it must be proved that the radiation is harmless to the product. In addition, ultraviolet disinfection shall not be used to replace chemical disinfection.

Indoor cleaning: 
Clean rooms should be cleaned and maintained on a daily basis and supervised and inspected.

Table 14-7  Indoor Cleaning Methods and Timing

Note: â‘ Filtered water or purified water
          â‘¡Prepared by adding 30g of low-residue neutral detergent per liter of water.

                 Table 14-8  Equipment Cleaning Methods and Timing

Note: â‘ Filtered water or purified water
          â‘¡Prepared by adding 30g of low-residue neutral detergent per liter of water.