Cleanroom Testing Standard Management Procedure

1. Purpose: 

To ensure that the clean room meets the regulations and prevent pollution and cross contamination, this clean room test management procedure is specially formulated.

2. Scope of application: 

Applicable to the production or inspection area required by the clean room.

3. Responsible persons: 

Clean room monitoring personnel, production department, engineering department, quality department, and the competent departments of each clean room.

4. Management procedures

4.1 Definition of clean room: 

A room (area) where the number of dust and microorganisms in the environment needs to be controlled

4.2 Classification of air cleanliness levels in clean rooms

• According to the production process requirements and the relevant provisions of the 2010 version of GMP, the clean area is divided into four levels: A, B, C and D

• Cleanliness level standards

  Cleanliness level	Maximum allowable number of suspended   particles/cubic meter
  	Static		Dynamic
  	≥0.5um	≥5.0μm	≥0.5um	≥5.0um
  Alevel	3520	20	3520	20
  Blevel	3520	29	352000	2900
  Clevel	352000	2900	3520000	29000
  Dlevel	3520000	29000	No   regulations	No   regulations

  Cleanliness level	Planktonic bacteria cfu/m3	Settling bacteria (090mm) cfu/4 hours	Surface microorganisms
  			Contact (055mm) cfu/dish	5-finger gloves   cfu/disc
  Alevel	<1	1	<1	1
  Blevel	10	5	5	5
  Clevel	100	50	25
  Dlevel	200	100	50

Remarks:

• Static definition: refers to the state where all production equipment is installed and ready, but there is no production activity and no operators are present

• Dynamic definition: refers to the state where the production equipment is running according to the predetermined process mode and a specified number of operators are operating on site

• The sampling point in the work area is located about 0.8~1.5m above the ground (slightly higher than the work surface).

4.3 Requirements for clean rooms

1.A buffer facility must be set up between the clean room and the non-clean room, and the flow of people and goods must be reasonable;

2.Temperature and Relative humidity: The temperature is 18-26℃℃, and the relative humidity of different products should be controlled according to the process requirements;

3.The clean room (area) must compensate and maintain a certain amount of fresh air required in the room, and the quantity value should take the maximum value of the following Air volume: 10-30 of the total air volume of non-unidirectional flow room, and 2-4 of the total air volume of unidirectional flow room.

4.Static pressure difference in the clean room

• The air in the clean room must maintain a certain positive pressure;

• The static pressure difference between the clean room and the non-clean room, and between clean areas of different levels must be greater than or equal to 10Pa;

• The appropriate pressure gradient should also be maintained between different functional areas (operating rooms) of the same cleanliness level;

• The dust-producing operating room (such as the sampling, weighing, mixing, filling or packaging of powder) must maintain a relative negative pressure with the adjacent room (area) and be equipped with a dust collection device

5.The noise level of the clean room should not exceed 75db (A grade) during dynamic testing. When it exceeds, sound insulation, noise elimination, and vibration isolation measures should be taken. The noise control design shall not affect the purification conditions of the clean room.

6.The illumination of the clean area should not be less than 300lx in the main working area, except that the general area must meet the process requirements.

7.The unidirectional flow system in the A-level area must evenly supply air in its working area, with a Wind speed of 0.36~0.54m/(guide value). There should be data to prove the state of unidirectional flow and be verified

8.Ventilation frequency visit value: C-level and above areas are straight > 25 times/hour, D-level areas should be > 16 times/hour

4.4 monitoring of suspended particles

• According to the results of the cleanliness level and air purification system confirmation and risk assessment, determine the location of the county suspended particle sampling point and conduct daily dynamic monitoring;

• During the entire process of key operations, including the assembly operation of the equipment, the Class A clean area should be monitored for suspended particles. When contamination in the production process (such as living organisms and radiation hazards) may damage the dust particle counter and sampling volume, it should be tested during equipment commissioning and simulation operations. The frequency and sampling volume of monitoring in the Class A clean area should be able to promptly detect all human interventions, incidental events and any system damage. During repackaging, due to the generation of particles by the product itself, it is allowed that the suspended particles of 25.0um at the repackaging point do not meet the standards:

• A monitoring system similar to that of the Class A clean area can be used in the Class B clean area. The sampling frequency and sampling volume can be adjusted according to the degree of influence of the Class B clean area on the adjacent Class A clean area;

• The monitoring system for suspended particles should consider the influence of the length of the tube and the radius of the elbow on the test results;

• The sampling volume for daily monitoring can be different from the air sampling volume when the cleanliness level and air purification system are confirmed:

• In the Class A and Class B clean areas, when suspended particles of 25.0um appear continuously or regularly, an investigation should be conducted;

• After all production operations are completed, the operators withdraw from the production site and self-clean for 30 minutes (guideline value), the suspended particles in the clean area should meet the "static" standard in the table:

• Class C clean areas and Class D clean areas (when necessary) should be dynamically monitored in accordance with the principles of quality risk management. Monitoring requirements, warning limits and correction limits can be determined according to the nature of the operation, but the self-cleaning time should meet the specified requirements.

4.5 Monitoring of microorganisms

• Dynamic monitoring of microorganisms should be carried out to evaluate the microbial status of aseptic production. Monitoring methods include sedimentation bacteria method, quantitative air floating bacteria sampling method and surface sampling method (such as cotton swab method and contact plate method).

• Dynamic sampling should avoid adverse effects on clean areas. The review of finished product batch records should include the results of Environmental monitoring;

• Monitoring of surfaces and operators should be carried out after key operations are completed. In addition to normal production operation monitoring, microbial monitoring can be added after system verification, cleaning or disinfection operations are completed.

4.6 Corrective Action

Appropriate county floating particle and microbial monitoring warning and correction limits should be established. The operating procedures should detail the corrective measures to be taken when the results exceed the standard.

4.7 monitor

The temperature, humidity and pressure difference of the clean room are monitored online; wind speed, air volume or ventilation frequency are monitored once a month; illumination and noise are monitored once a year.

4.8 Filter replacement cycle

The clean area user department replaces the medium efficiency and primary efficiency filters according to the pressure difference indication of its own air conditioning. The high efficiency filter is replaced in time according to the integrity test results. An integrity test is carried out after the high efficiency filter is installed, and then it is tested every six months.

4.9 Firefighting Measures

Regularly check the integrity of fire alarm, emergency lighting facilities and emergency passages.

(Infusion Workshop) Clean area environmental Monitoring Table