Reference | GMP Testing Requirements for Pharmaceutical Workshops

CELINE-PHARMA

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Testing scope: Clean room environment grade assessment, project acceptance testing, including food, health products, cosmetics, bottled water, milk production workshops, electronic products production workshops, GMP workshops, hospital operating rooms, animal laboratories, biosafety laboratories, biosafety cabinets, clean benches, dust-free workshops, sterile workshops, etc.

Testing items: wind speed and volume, ventilation times, temperature and humidity, pressure difference, suspended particles, floating bacteria, settling bacteria, noise, illumination, etc.

1. Wind speed and volume ventilation times

The cleanliness of clean rooms and clean areas is mainly achieved by supplying sufficient clean air to replace and dilute the particulate pollutants generated in the room. For this reason, it is necessary to measure the air supply volume, average wind speed, air supply uniformity, air flow direction and flow type of clean rooms or clean facilities.

One-way flow mainly relies on clean airflow to push and replace polluted air in the room and area to maintain the cleanliness of the room and area. Therefore, the wind speed and uniformity of its air supply section are important parameters affecting cleanliness. Higher and more uniform cross-sectional wind speeds can remove pollutants generated by indoor processes more quickly and effectively, so they are the main test items of concern.

Non-unidirectional flow mainly relies on the clean air supplied to dilute and dilute pollutants in the room and area to maintain its cleanliness. Therefore, the greater the ventilation times, the more reasonable the airflow pattern, the more significant the dilution effect, and the corresponding improvement in cleanliness. Therefore, the air supply volume and the corresponding ventilation times of non-single-phase flow clean rooms and clean areas are the main airflow test items of concern.

In order to obtain repeatable readings, record the time average of the wind speed at each measuring point.

Ventilation times: obtained by dividing the total air volume of the clean room by the volume of the clean room.

2. Temperature and humidity

The temperature and humidity measurement of clean rooms or clean facilities is usually divided into two levels: general test and comprehensive test. The first level is suitable for the delivery and acceptance test in an empty state, and the second level is suitable for static or dynamic comprehensive performance test. This type of test is suitable for occasions with strict requirements on temperature and humidity performance.

This test is carried out after the air flow uniformity test and after the air conditioning system adjustment. When conducting this test, the air conditioning system is fully operational and all conditions are stable. At least one humidity sensor is installed in each humidity control area, and the sensor is given sufficient time to stabilize. The measurement should be suitable for the actual use purpose. The measurement should be started after the sensor stabilizes, and the measurement time should be no less than 5 minutes.

3. Pressure difference

The purpose of this test is to verify the ability of the completed facility to maintain the specified pressure difference between the surrounding environment and between the spaces within the facility.

This test is applicable to all three occupancy states. This test needs to be conducted regularly.

The pressure difference test should be conducted with all doors closed, from high pressure to low pressure, starting from the inner room farthest from the outside world in the plane layout, and then tested outward in sequence; there should be reasonable airflow direction at the openings of adjacent clean rooms (areas) of different levels that are connected by holes, etc.

Pressure difference test requirements:

(1) The static pressure difference measurement is required to be conducted with all doors in the clean area closed.

(2) It should be conducted in order from high to low cleanliness on the clean plane, and all the way to the room with direct access to the outside.

(3) The measuring pipe mouth can be set anywhere in the room without air flow influence, and the measuring pipe mouth surface should be parallel to the air flow streamline.

(4) The measured and recorded data should be accurate to 1.0Pa.

 

Pressure difference detection steps:

(1) Close all doors first.

(2) Use a micro differential pressure gauge to measure the pressure difference between clean rooms, between clean room corridors, and between corridors and the outside world.

(3) Record all data.

Pressure difference standard requirements: Determine the positive or negative pressure value of the clean room to be tested according to the clean room design or process requirements.

(1) The static pressure difference between clean rooms or clean areas of different levels and non-clean rooms (areas) should not be less than 5Pa.

(2) The static pressure difference between a clean room (area) and the outside should not be less than 10Pa.

(3) For unidirectional clean rooms with air cleanliness levels stricter than level 5 (level 100), when the door is opened, the dust concentration of the indoor working surface 0.6m inside the door should not be greater than the dust concentration limit of the corresponding level.

(4) If the above standards are not met, the fresh air volume and exhaust air volume should be readjusted until they are qualified.

4. Suspended particles

A. Indoor test personnel must wear clean clothes, no more than 2 people, should be located on the downwind side of the test point and away from the test point, and should remain still. When changing points, the movement should be gentle, and the interference of personnel on the indoor cleanliness should be reduced.

B. The equipment should be used within the calibration period.

C. The equipment should be "zeroed" before and after the test.

D. In the unidirectional flow area, the selected sampling probe should be close to isokinetic sampling, and the wind speed entering the sampling probe should not deviate from the wind speed of the sampled air by more than 20%. If this cannot be achieved, the sampling port should face the main direction of the airflow. For sampling points with non-unidirectional flow, the sampling port should be vertically upward.

E. The connecting pipe from the sampling port to the particle counter sensor should be as short as possible.

The sampling points are generally about 0.8-1.2m above the ground, and should be evenly and scientifically distributed, and should avoid the return air outlet. For any small clean room or local air purification area, the number of sampling points shall not be less than 2, and the total number of sampling points can be obtained by taking the root twice according to the area.

5. Planktonic bacteria

The minimum number of sampling points corresponds to the number of suspended particle sampling points. The measuring point in the working area is about 0.8-1.2m above the ground, and the measuring point in the air outlet is about 30cm away from the air supply surface. Measuring points can be added at key equipment or key work activity ranges. Each sampling point is generally sampled once.

After all sampling is completed, the culture dish is placed in a constant temperature incubator for incubation for no less than 48 hours. Each batch of culture medium should have a control experiment to check whether the culture medium is contaminated.

6. Settling bacteria

The measuring point in the working area is about 0.8-1.2m above the ground. The prepared culture dish is placed at the sampling point, the culture dish cover is opened, and it is exposed for the specified time. Then the culture dish is covered and placed in a constant temperature incubator for incubation for no less than 48 hours. Each batch of culture medium should have a control experiment to check whether the culture medium is contaminated.

7. The noise

Measurement height is about 1.2 meters from the ground. For clean rooms with an area of ​​less than 15 square meters, only one point in the center of the room can be measured; for clean rooms with an area of ​​more than 15 square meters, four diagonal points should be measured, each 1 meter away from the side wall, and the measuring points should face each corner.

8. The plane of the illumination

Measurement point is about 0.8 meters from the ground, and the points are arranged at a spacing of 2 meters. The measurement points of rooms within 30 square meters are 0.5 meters away from the side wall, and the measurement points of rooms over 30 square meters are 1 meter away from the wall.

Testing standards:

(1) "Cleanroom Design Specifications" GB50073-2001 (2) "Technical Specifications for Clean Operating Rooms in Hospitals" GB50333-2002

(3) "Technical Specifications for Biosafety Laboratory Construction" GB50346-2004

(4) "Cleanroom Construction and Acceptance Specifications" GB50591-2010

(5) "Test Methods for Suspended Particles in Clean Rooms (Areas) for Pharmaceutical Industry" GB/T16292-2010

(6) "Test Methods for Floating Bacteria in Clean Rooms (Areas) for Pharmaceutical Industry" GB/T16293-2010

(7) "Test Methods for Settling Bacteria in Clean Rooms (Areas) for Pharmaceutical Industry" GB/T16294-2010