Different industries should select appropriate cleanliness levels based on their process requirements. For example:

• Semiconductor/Microelectronics Cleanrooms: ISO 4-6.

• Electronics and Lithium Battery Production: ISO 7-8.

• Pharmaceutical Industry: Commonly requires ISO 5-8.

• Food Industry: ISO 6-8.

• Biomedical: ISO 7-8.

• Hospitaloperating theaters: ISO 5-8.

• Biological Laboratories: ISO 7-8.

Grade A: High-risk areas such as filling, stopper placement, open packaging container areas, and aseptic assembly zones.

Grade B: Background area for high-risk Grade A operations, such as aseptic preparation and filling.

Grade C: Lower-risk steps in sterile drug production.

Grade D: General production operations, such as raw material storage and packaging.

Vertical and horizontal laminar flows are two different airflow patterns, respectively referring to clean air flows from ceiling-mounted filters vertically down through the workspace or horizontally across the workspace to the opposite side. This airflow pattern maintains a single direction and is evenly distributed, reducing airflow cross-contamination and backflow, which helps control airborne particles and microorganisms, suitable for high-cleanliness areas.

Vertical and horizontal laminar flow can be applied to grade A environments in pharmaceutical processes, such as the filling of sterile drugs and the configuration of injections, as well as sterile assembly areas, ensuring the cleanliness of the production environment and effectively guarantee the quality and safety of drugs.‌‌

  During pharmaceutical production, pressure control effectively prevents external air from entering the workspace, reducing contamination risks to ensure product quality and safety. Pressure control also prevents the spread of airborne pollutants and harmful substances from specific zones, preventing cross-contamination with surrounding areas. By maintaining the pressure differential, it is possible to make sure that the air in the clean room flows in the predetermined airflow direction, reducing contamination of the products. Therefore, pressure differential control is crucial for pharmaceutical cleanrooms.‌‌

Controlling microbial contamination in pharmaceutical cleanrooms requires regular or real-time monitoring of cleanliness levels and environmental microbes, with records kept accordingly. Strict controls for personnel, materials, and equipment entering the cleanroom are essential, and measures such as air showers, cleaning, and disinfection should be followed to prevent contamination. Air purification systems should contain qualified filters, which should be cleaned or replaced regularly to guarantee the normal operation. In addition, pharmaceutical cleanroom should be equipped with reasonable and regular disinfection and sterilization methods, such as ozone, ultraviolet sterilization, chemical sterilization, high-temperature sterilization, etc. By doing so, microbial contamination in pharmaceutical cleanrooms can be effectively monitored and controlled.

  To prevent contamination from entering the cleanroom, operators should undergo regular health checks to ensure they are free from infectious diseases. Hygiene training should be completed, and operators should wear clean clothes, hats, and shoes, wash and disinfect hands frequently, and avoid bringing personal items into the cleanroom. Operators should control movement frequency and avoid unnecessary activities within the cleanroom to minimize particle and microbial release. Meanwhile, the layout of the clean area process should be designed reasonably (avoiding frequent back and forth of personnel and materials) and maintain a certain pressure differential, which can effectively reduce the risk of operators bringing pollution into the cleanroom, ensuring the cleanliness of the production environment and product quality.‌‌

HVAC systems are crucial in pharmaceutical cleanrooms in the following ways:

• Ensuring environmental parameters meet production requirements: HVAC systems control and monitor air temperature, humidity, suspended particles, and microorganisms to ensure compliance.

• Differential pressure control: HVAC systems design airflow volume to effectively control pressure differentials, preventing contamination and cross-contamination during production.

• Providing a comfortable working environment: HVAC systems not only control environmental parameters but also offer comfort for operators, reducing operational errors and health issues due to discomfort.

• Meeting GMP validation requirements: HVAC systems are an essential part of GMP standard (4Q validation), ensuring parameters are stable and meet design specifications during operation.

  Major certifications for pharmaceutical cleanrooms include GMP certification and NEBB certification.

  GMP Certification encompasses a comprehensive system of documentation for pharmaceutical production, including Design Qualification (DQ), Installation Qualification (IQ), Operational Qualification (OQ), and Performance Qualification (PQ) documents to ensure production quality.

  NEBB Certification testing includes but is not limited to air velocity and air velocity uniformity tests, filter leakage tests, cleanliness tests, temperature and humidity tests, illumination tests, noise tests, andpressuredifferential tests.

  To achieve these certifications, testing must comply with the standards set by these certificationauthorities (which requires that design and construction meet corresponding specifications). Additionally, participation in training courses to enhance staff competence and meeting any other conditions specified by these certification authorities is essential.