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Test method for suspended particles in clean rooms (areas) of pharmaceutical industry

  • Author:Jason Peng

  • Cleanroom Engineering Technology Manager of Deiiang Company.

    Product R&D Manager of GDC Inc. Cleanroom Equipment Manufacturing Company.

    Executive Director of Guangdong Cleanroom Industry Association of China.

    Engaged in R&D of related products for 15 years, with rich relevant technical experience

  • 2024-11-22  |  Visits:

The counting concentration method is used, that is, by measuring the number of suspended particles greater than or equal to a certain particle size in a unit volume of air in a clean environment, to assess the suspended particle cleanliness level of the clean room (area).

Considerations for Validating Aseptic Manufacturing Processes.


Key points of testing

1. After the instrument is turned on, it can be calibrated according to the provisions of the instruction manual only after it is preheated to a stable state. (Self-test, self-calibration, zero count)

2. When the sampling tube mouth is placed at the sampling point for sampling, continuous reading can be started only after confirming that the count is stable.

3. The sampling tube must be clean and leakage is strictly prohibited.

4. The length of the sampling tube should be based on the allowable length of the instrument. Unless otherwise specified, the length shall not exceed 1.5 m. (Our instrument does not have a sampling tube)

5. The counter sampling port and the working position of the instrument should be at the same air pressure and temperature to avoid measurement errors.

6. The instrument must be calibrated regularly according to the calibration cycle of the instrument. (Depending on the characteristics of the instrument itself, the frequency of use, the use environment, etc.)

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Test conditions

1. The temperature and Relative humidity of the clean room (area) should be consistent with its production and process requirements. (Temperature: 18-24℃; humidity 45-60%)

2. The pressure difference between clean rooms (areas) with different air cleanliness levels should be ≥4.9Pa. Clean rooms (areas) with high air cleanliness level requirements generally require a relative positive pressure to the adjacent clean rooms (areas) with low air cleanliness levels.

3. During static testing, there should be no more than 2 testers in the room, and the test report should indicate the state used during the test.

4. For unidirectional flow, the test should start at least 10 minutes after the purification Air conditioning system has been operating normally, and for non-unidirectional flow, it should start at least 30 minutes after.


Number of sampling points and their arrangement

1. Minimum number of sampling points

aera㎡Cleanliness   level
10010,000100,000
<102   ~ 322
≥10~< 20422
≥20~<40822
≥40~<1001642
≥100~<20040103
≥200~<40080206
≥400~<10001604013
≥1000~<200040010032
200080020063
Note:   The area in the table refers to the air supply area for unidirectional clean   rooms and the room area for non-unidirectional clean rooms.

2. Location of sampling points

Sampling points are generally evenly arranged on a horizontal plane 0.8m above the ground; when there are more than 5 sampling points, they can also be arranged in an area 0.8m to 1.5m above the ground, but there should be no less than 5 points on each floor.

3. Limitation of sampling points

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 times shall not be less than 5. The number of sampling times for each sampling point can be more than 1, and the number of sampling times for different sampling points can be different.

4. Sampling volume

Cleanliness levelSampling   volume, L/time
≥0.5um≥5um
1005.66_
10,0002.838.5
100,0002.838.5

Note: Sampling should be carried out after confirming that the air supply volume and pressure difference of the clean room (area) meet the requirements; for unidirectional flow, the sampling tube mouth of the counter should face the direction of the airflow; for non-unidirectional flow, the sampling tube mouth should face upwards; when arranging sampling points, the return air outlet should be avoided; when sampling, the tester should be on the downwind side of the sampling port.


Calculation of results

1. Average particle concentration at sampling point

A=C1+C2+…+Cn
N

Where: A —— average particle concentration at a certain sampling point, particles (pieces)/cubic meter;

Ci—— particle concentration at a certain sampling point (I=1,2,3,…,n), particles (pieces)/cubic meter;

N—— number of samplings at a certain sampling point, times.

2. Mean of average values

M=A1+A2+…+An
L

Where: M —— mean of average values, i.e. average particle concentration of clean room (area), particles (pieces)/cubic meter;

Ai—— average particle concentration at a certain sampling point (I=1,2,3,…,n), particles (pieces)/cubic meter;

L—— total number of sampling points in A Clean Room (area), pieces.

3. Standard error

SE=(A1-M)2+(A2-M)2+…(AL-M)2
L(L-1)

Where: SE—— standard error of the mean of average values, particles (pieces)/cubic meter.

4. Upper confidence limit

If the upper limit of the estimated value calculated by the given confidence level (here 95%) of the actual mean obtained by sampling from the normal distribution will be greater than the actual mean, then the upper limit of the estimated value of the mean calculated is called the upper confidence limit.

UCL=M+t×SE

Where: UCL——95% upper confidence limit of the mean value, particles (pieces)/cubic meter;

t——t distribution coefficient of the 95% upper confidence limit, see the table below.

Sampling  points L
2
3
4
5
6
7
8
9
>9
t
6.31
2.92
2.35
2.13
2.02
1.94
1.9
1.86
Note: When the number of sampling points is more than 9, it  is not necessary to calculate UCL.


Result evaluation

The cleanliness level of suspended particles should be determined based on the following two conditions:

  • The average particle concentration of each sampling point must be lower than or equal to the specified level limit, that is, Ai≤level limit.

  • The 95% upper confidence limit of the average particle concentration of all sampling points must be lower than or equal to the specified level limit, that is, UCL≤level limit.

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