In: Cleanroom

Pharmaceutical Cleanroom

Cleanrooms provide an enclosed environment with a controlled level of particulates such as dust, vapors and airborne particles. Setting up a clean room involves a series of steps that include engineering, fabrication and a control strategy. While they are used in a range of medical, scientific and manufacturing application, we will be providing a simplistic overview of cleanrooms for pharmaceutical applications that do not handle a potent chemical or hazards biologicals.

Depending on types of medicinal products you produce and federal standards, you may or may not need a clean room. When manufacturing non-sterile products, clean areas, ventilated with filtered air, could serve as a substitute for a clean room. You should define your standards and procedures for the clean area or room based on federal standards such as US FED STD 209E or international standards such as SO 14644-1 and ISO 14698. For sterile medicinal products, cleanrooms are required to limit airborne particulates and contamination of medicinal products. The standard and requirements for cleanrooms are based on their classification and it is important to classify a room appropriately since operators are required to comply with all requirements and maintain cleanliness standards for a given classification during operation.

Design Considerations

In addition to fabricating the ideal clean area or room, you must give consideration of adjacent spaces such as corridors due to pressure cascade. An example of this would be manufacturing pharmaceutical products such as a capsule or tablet in a positive pressure environment. Due to the pressure differential between the two spaces, the powder could escape out of the clean area and into the corridor. That is why it’s important to design “clean corridors” that inhibit microbial growth if any microorganisms escape. When processing sterile or liquid medicinal products, it is important to keep potential microbes out of the clean room as they will find the environment and media conducive to microbial growth. In this case, the room would be positively pressured, with the adjacent space being a “dirty corridor”

In addition to room and corridor design, consideration must be given to the doors and their orientation since they need to maintain the pressure differential. As a rule, all doors must open into the room with the higher pressure as to prevent leakage. Please note that the springs on double swinging doors gradually weaken over time, causing air to leak beyond the design parameter. Additionally, sliding doors or door with recesses should be avoided since they harbor microorganism and in some cases support microbe growth.

Contamination Sources

As mentioned earlier, cleanrooms are designed to control the level of particulates in the environment. Depending on the room’s classification, there is an acceptable level of particles per cubic foot or meter of air. The main concern for pharmaceutical applications is microbial containments. Since microbial contamination cannot be directly measured in real-time, “all airborne particles” is assumed to include all possible microbial contamination risk.

Maintaining a Cleanroom Environment

While there are many national and international standards for cleanrooms, classification, and requirements, the three main aspects of a cleanroom are the control/quality of the air within the room, the internal surface of the room and equipment, and the how the room is operated.

First and foremost, clean rooms require a constant supply of filtered air at a specific temperature and/or humidity level. Depending on your cleanroom classification, you may require more air as the classification requirements become more stringent. The ratio of “fresh” to recirculated air, depends on the nature of the operation. If the operation generates high levels of vapor, gasses or moisture, the room is supplied with 100% fresh air. To reduce the energy cost associated with air filtering and conditioning fresh air, you can recirculate the internal air by removing particulates as they are generated.

A well-designed system delivers both “fresh” and recirculated clean air into the cleanroom. In a tightly controlled system, the volume of air supplied into a room flushes out an equal amount. To maintain a higher pressure, a higher volume of air is supplied into the room than the volume of air being removed. Overall, a good system keeps air moving throughout the room so that contaminants such as airborne particle and fumes are flushed out of the controlled environment.

Secondly, the internal surfaces of a clean room and the equipment should be smooth and impermeable. They must accessible and easy to clean, with no ledges or recesses that can create an environment that is prone to particulate buildup and microbial growth. In addition to smooth and impermeable, the must be constructed of rigid materials that do not crack or shatter. This prevents and limits the generation of additional containments such as dust or flake within the enclosed environment.

Lastly, cleanroom operation and maintenance are the most effective ways to control air quality. Personnel is considered the highest source of particulate and microbial containments. In order to maintain low particulate, only a limited number of trained personnel should have access to the room at a given time. Additionally, proper cleanroom clothing and gowning procedure should be implemented. Manufacturing operations can also produce particulates, preventing contaminants from being produced and escaping into the environment can help to maintain the controlled environment. Lastly, regular cleaning and maintenance of the facility, equipment, and ventilation system could prevent the build of particulate and microbial growth.

Whether you opt for a clean area or cleanroom, we hope this article helps to provide a general understanding of cleanrooms when it comes to pharmaceutical applications and operations. Please feel free to comment if you have any questions.

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