All pharmaceuticals and medical devices are manufactured in clean rooms which have certain levels of cleanliness depending on the activity being performed in the area. Understanding the differences between these environments can help determine the level of requirements that are needed to maintain the area. These requirements often align with regular Good Manufacturing Practices (GMP) in terms of cleaning for manufacturing sterile medicinal products.
The requirements between the spaces differ based on the operations being performed. The requirements are as follows:
- Grade A is a space that is the strictest in terms of cleanliness. Operations contained within these environments are usually high-risk operations. The requirement for these areas is airborne 0.5 μm particulate in the in-operation state less than 3,520 particles per cubic meter and airborne viable microorganisms that are less than 1 CFU per cubic meter. These spaces are normally unidirectional flow with an air velocity of 0.20–0.45 meters per second.
- Grade B is the second most strict space. This type of environment fluctuates between ISO 5 (less than 3,520 particles per cubic meter) at rest while going to an ISO 7 (less than 352,000 particles per cubic meter) when in operation with a 15–20-minute transition period between states. In this environment, the requirement for airborne viable microorganisms is less than 10 CFUs per cubic meter.
- Grade C areas are areas which offer less critical operations such as filling for terminal sterilization. The requirement for these spaces is ISO 7 (less than 352,000 particles per cubic meter) measured when at rest with a 15–20-minute transition period between states. During operations, this environment is classified as an ISO 8 (less than 3,520,000 particles per cubic meter). The requirement for airborne viable microorganisms is less than 100 CFU per cubic meter.
- Grade D/CNC+ (controlled not classified with local monitoring) environments are areas where HVAC systems reduce the airborne contaminants, and the temperature and humidity are controlled tighter than the ambient environment. These are usually ISO 8 at rest only with controls in place for temperature and humidity. Generally, these align with airborne viable microorganisms < 200 CFUs per cubic meter.
If you need support in understanding the differences between graded spaces and the requirements that come with them, the experts at EMMA can help! Call us at 248-987-4497 or email us at email@example.com to learn more.
Farquharson, G. J., & Goldschmidt, N. A. (2022, May 1). Understanding cleanliness classifications for Life Science Facilities. https://ispe.org/pharmaceutical-engineering/march-april-2017/understanding-cleanliness-classifications-life-science