Reference for food factory purification plant management specifications

1. Purpose

To regulate the management of cleanrooms.

2. Responsibilities

Equipment department: Ensure the normal use of cleanrooms in food workshops.

Using department: Responsible for the management of cleanrooms, ensure the training and implementation of this document,

QC inspector: Responsible for regular monitoring of cleanliness.

QA on-site monitor: Responsible for supervising the implementation of this document.

(Figure 1: Food Factory)

3. Scope of application

This procedure applies to the management of the company's food purification workshops.

4. Related definitions

4.1. Cleanroom

A room (area) where the number of dust particles and microorganisms in the environment needs to be controlled. Its building structure, equipment and use should be able to reduce the introduction, generation and retention of pollutants in the area.

4.2 Airlock

An isolated space with two or more doors set between two or more rooms (such as rooms with different cleanliness levels). The purpose of setting up an airlock is to control the airflow when people or materials enter and exit. The airlock has a personnel airlock and a material airlock.

5. Content

5.1. Requirements for cleanrooms

5.1.1. The workshop should be reasonably laid out according to the production process and the required air cleanliness level. Oral solid preparations should be set up in accordance with the requirements of the Class D clean area in the 2010 version of the GMP Appendix. The QC Microbiological testing room should be set up in accordance with the Class A clean level at the bottom of the Class C in the 2010 version of the GMP Appendix.

5.1.2. The design of the cleanroom should avoid unnecessary entry of management or monitoring personnel as much as possible.

5.1.3. The room air supply and return method should adopt top supply and side return.

5.1.4. In order to reduce dust accumulation and facilitate cleaning, there should be no difficult-to-clean parts on the shelves, cabinets, equipment, etc. in the clean area. The door design should be easy to clean.

5.1.5. The doors on both sides of the airlock room shall not be opened at the same time, and interlocking should be used to prevent the doors on both sides from being opened at the same time.

5.1.6. Under any operating conditions, the clean area should be able to ensure positive pressure to the surrounding low-level areas through appropriate air supply, maintain a good airflow direction, and ensure effective purification capacity.

5.1.7. The entry and exit of personnel and materials should comply with the "SOP for Personnel Entry and Exit of Clean Areas" and "SOP for Materials Entry and Exit of Clean Areas".

5.1.8. The clothing of personnel in the clean area should strictly comply with the "Work Clothes Management Regulations".

5.1.9. The inner surface of the clean area (walls, floors, ceilings) should be flat and smooth, without cracks, tight interfaces, no particles falling off, avoid dust accumulation, and facilitate effective cleaning. Disinfection should be carried out when necessary.

5.1.10. The junction between the wall and the floor of the clean area should be arc-shaped or other measures should be taken to reduce dust accumulation and facilitate cleaning.

5.1.11. Various pipes, lamps, vents and other public facilities in the clean area should be easy to clean.

5.1.12. The clean room area should provide sufficient lighting according to production requirements. The illumination of the main studio should reach 300 lux; the illumination of the auxiliary studio, corridor, airlock room, personnel purification and material purification room should not be less than 150 lux. The factory should have emergency lighting facilities.

5.1.13. The air entering the clean area must be purified, and the "HVAC System Management Procedure" must be strictly implemented to ensure the normal operation of the air conditioning purification system. The "Cleanliness monitoring management Regulations" must be strictly implemented to ensure that the cleanliness level meets the production process requirements.

(Figure 2: People and materials entering and exiting the clean room)

5.1.14. When the clean area with a large amount of dust cannot avoid cross contamination after dust collection, its air purification system shall not use return air. The dust-producing operation room shall maintain a relative negative pressure or take special measures to prevent dust diFFUsion, avoid cross contamination and facilitate cleaning.

5.1.15. The air purification system of a room with a large amount of moisture production shall not use return air when it is working.

5.1.16. The windows, ceilings and the connection parts of the pipes, vents, lamps and lanterns entering the room with the walls or ceilings in the clean area should be sealed.

5.1.17. Spare parts and tools for maintenance stored in the clean area should be placed in a special room or tool cabinet.

5.1.18. The pressure difference between the clean area and the non-clean area and between clean areas of different levels should not be less than 10 Pascals. If necessary, appropriate pressure gradients should be maintained between different functional areas (operation rooms) of the same cleanliness level.

5.1.19. There should be a device to indicate the pressure difference between adjacent rooms (areas) with different air cleanliness levels or between adjacent rooms (areas) that are required to maintain relative negative pressure, and the pressure difference should be recorded. The outdoor pressure difference is inspected by the air conditioning operator; the clean area is recorded by the production site operator; the temperature and humidity pressure difference of the QC microbiological testing room is recorded once before each inspection by the microbiological testing personnel, and problems are dealt with in a timely manner.

5.1.20. In areas with the same air cleanliness level, the dust-producing room should maintain a relative negative pressure.

5.1.21. The temperature and Relative humidity of the clean room area should be compatible with the requirements of the drug production process. If there are no special requirements, the temperature should be controlled at 18~26℃: the relative humidity should be controlled at 45~65%. Quality Department Qc Clean Room: temperature should be controlled at 18~26℃: relative humidity should be controlled at 45~65%.

5.1.22, the pool or floor drain in the clean room area should be properly designed, laid out and maintained, and easy-to-clean devices with air blocking function should be installed to prevent backflow. The connection method with the external drainage system should be able to prevent the invasion of microorganisms.

5.1.23, the entry and exit of personnel and materials between clean rooms (areas) with different air cleanliness levels should have measures to prevent cross contamination. The ultraviolet lamp should be inspected once a quarter according to the "Technical Specifications for Disinfection of the Ministry of Health 2008". If the ultraviolet radiation intensity does not meet the requirements, the ultraviolet lamp should be replaced in time, and the "Ultraviolet Lamp Registration, Activation and Replacement Record" should be written. The purified water system uses ultraviolet germicidal lamps (when running, 24 hours a day), and the "Ultraviolet Lamp Registration Card" and "Ultraviolet Lamp Registration, Activation and Replacement Record" should be written. The replacement cycle is 2000 hours.

5.1.24. An airlock should be set up between the clean room (area) and the non-clean room (area), and the flow of people and goods in the clean room (area) should be reasonable. The doors of the airlock and the transfer chamber cannot be opened at the same time.

5.1.25. According to the requirements of the pharmaceutical production process, the air cleanliness level of the weighing room or preparation room set up in the clean room (area) should be consistent with the production requirements, and measures should be taken to capture dust and prevent cross contamination.

5.1.26. The positive bacteria room and microbial limit test of the QC inspection room should be carried out in separate rooms.

5.1.27. Strictly control the number of people entering the clean area. Except for normal production and cleaning personnel, other personnel must be approved before entering. Outsiders entering the clean area must be accompanied and guided.

(Figure 3: Clean clean room)

5.2. Precautions for operation in the purification plant

5.2.1. When working, the door must be closed tightly to minimize the number of entries and exits.

5.2.2. Various operations in the clean room area should be steady, accurate and light, and no actions unrelated to work should be performed. Various activities (operations) should be limited to a minimum.

5.2.3. Unnecessary items are not allowed to be brought into the clean area. Various utensils, containers, equipment and tools used must be made of dust-free materials, and can enter the clean area through the logistics channel after cleaning and disinfection according to the prescribed procedures.

5.2.4. The use of recessed or protruding ledges, cabinets and equipment that are difficult to clean should be minimized. 

5.2.5. In addition to meeting the cleaning requirements of the general production area, the cleaning room for filter bags in the clean area, the cleaning room for sanitary ware and the cleaning tools should also be ventilated and dry; the material of the cleaning tools should not shed fibers and granular substances, and mops, rags, etc. should be dried in time to prevent the generation of toxic bacteria. Disinfectants should be used alternately to prevent microorganisms from developing drug resistance.

5.2.6. Recording paper and pens must be cleaned and disinfected before they can be brought into the clean room. The paper and pen used should not generate dust. Do not use pencils, erasers, or pens, but sign pens.

5.2.7. Waste generated during the production process should be promptly packed into clean plastic bags, sealed and placed in designated locations, and removed from the clean area after work is completed as required.

5.2.8. The clean area must have enough time for cleaning every day. When changing batch numbers, ensure that there is enough time interval for clearing and cleaning.

5.2.9. The clean area is disinfected once a week.

5.2.10. Cleaning and disinfection of the clean room area strictly implements the company's "Room Cleaning SOP", "HVAC System Cleaning and Disinfection SOP", "Ozone Disinfection SOP" and other documents.