1. Differences between the new and old versions
In GMP, there is a distinction between dynamic and static control in A, B, C, and D levels, while there is basically no distinction between dynamic and static control in 100-level, 10,000-level, and 100,000-level. There is a clear difference between the two.
The new version of GMP refers to the specific standards specified in ISO14644 as follows: The new version of GMP adopts the A, B, C, and D classification standards of the European Union and the new WHO, and puts forward very specific requirements for the cleanliness level of sterile drug production.
1. Static measurement
Static measurement refers to the state in which all equipment is installed and ready, but not running and there are no operators on site.
2. Dynamic measurement
Dynamic measurement refers to the state in which all production equipment is running according to the predetermined process mode and a specified number of operators are operating on site.
In the new GMP standard, the dynamic and static of zone A and the static of zone B are all required to be Class 100, but their meanings are different. The Class 100 of zone A has its unidirectional flow requirement, while the Class 100 of zone B does not have this requirement. In the new GMP, zone A is similar to the Class 100 in the 1998 GMP, and zone B is very different from the relevant regulations in the 1998 GMP. It is divided into static Class 100 and dynamic Class 10,000. However, my country's GMP only requires Class 100 to be within the background area of Class 10,000.
For the flow rate of unidirectional flow in the Class 100 area (Area A), the standard of the new GMP is 0.45±20%, and the regulation of the 1998 GMP is 0.2~0.5m/s. The room pressure is different. The new GMP requires the pressure difference of adjacent rooms of different levels to be no less than 10Pa, while the 1998 GMP requires no less than 5Pa. There are also different standards for monitoring and sampling of microorganisms.
2. Air cleanliness level of clean area (room) in the new version of GMP in 2010
The "Good Manufacturing Practice for Pharmaceuticals" (GMP) stipulates that the production environment parameters in the clean workshop for pharmaceutical production, such as temperature, relative humidity and pressure difference, are determined by the production process. The general temperature is 18℃~24℃ and the relative humidity is 45%~65%. The implementation guide of the "Good Manufacturing Practice for Pharmaceuticals" (GMP) stipulates more specifically. That is, the temperature and relative humidity in the clean workshop for pharmaceutical production are based on the fact that operators wearing clean work clothes do not feel uncomfortable or uncomfortable.
The clean area required for the production of sterile drugs can be divided into 4 levels. The clean area level of the new version of GMP in 2010 is divided into:
Grade A: High-risk operation areas, such as filling areas, areas where rubber stopper barrels and open packaging containers in direct contact with sterile preparations, and areas for aseptic assembly or connection operations, should use unidirectional flow operating tables (hoods) to maintain the environmental status of the area. The unidirectional flow system must evenly supply air in its working area, with a wind speed of 0.36-0.54m/s (guide value). There should be data to prove the status of unidirectional flow and be verified. In a closed isolation operator or glove box, a lower wind speed can be used.
Class B: refers to the background area where high-risk operations such as aseptic preparation and filling are located in the Class A clean area.
Class C and Class D: refers to the clean area of less important operating steps in the production process of sterile drugs.
II. III. New GMP cleanliness levels A, B, C, D
Class A clean area
The air temperature in the clean operation area should be 20-24℃
The relative humidity of the air in the clean operation area should be 45%-60%
The wind speed in the operation area: horizontal wind speed ≥0.54m/s
Vertical wind speed ≥0.36m/s
The leak detection rate of the high-efficiency filter is greater than 99.97%
Illumination: >300lx-600lx
Noise: ≤75db (dynamic test)
Class B clean area
The air temperature in the clean operation area should be 20-24℃
The relative humidity of the air in the clean operation area should be 45%-60%
The room ventilation frequency is ≥25 times/h, and the pressure difference in the Class B area relative to the outdoor is ≥10Pa. The same as above, different areas are based on airflow The flow direction should maintain a certain pressure difference
The leak detection of high-efficiency filters is greater than 99.97%
Illumination: >300lx-600lx
Noise: ≤75db (dynamic test)
Class C clean area
The air temperature in the clean operation area should be 20-24℃
The relative humidity of the air in the clean operation area should be 45%-60%
Room ventilation frequency: ≥25 times/h
Pressure difference: Class C area is ≥10Pa relative to the outside. Different areas of the same level should maintain a certain pressure difference according to the air flow direction
Leak detection of high-efficiency filters: >99.97%
Illumination: >300lx-600lx
Noise: ≤75db (dynamic test)
Class D clean area
The air temperature in the clean operation area should be 18-26℃
The relative humidity of the air in the clean operation area should be 45%-60%
Room ventilation frequency: ≥15 times/h
Pressure difference: 100,000-level area relative to the outside ≥10Pa
The leak detection of high-efficiency filters is greater than 99.97%
Illumination: ＞300lx-600lx
Noise: ≤75db (dynamic test)
