GMP Cleanroom Levels and Requirements
According to the relevant standards of the FDA , they have formulated strict and precise regulations for drug manufacturers in the pharmaceutical industry. Good Manufacturing Practices (GMP) for the manufacture of sterile pharmaceutical products are designed to ensure that drugs are safe and contain the ingredients and quantities claimed for them. These standards are designed to reduce the risk of microbial, particulate and pyrogen contamination. Also known as Current Good Manufacturing Practices (cGMP), the regulations cover production processes, quality control, packaging, personnel and GMP facilities. So what are the GMP clean room levels and requirements?
Cleanrooms do not completely remove contaminants; they merely reduce the contaminant particles to tolerable levels. This requires a higher clean environment to ensure product quality. In the manufacturing of non-sterile drugs and medical devices, high-level clean rooms are generally not required. However, for the production of sterile drugs, such as molecular drugs and synthetic drugs, a high-level clean room - GMP cleanroom - is inevitably required. We can define the environment in which sterile pharmaceuticals and biologics are produced according to GMP clean air classes and classifications. According to the relevant requirements of GMP regulations, the production of sterile drugs or biological products is mainly divided into four levels: A, B, C, and D.
Level A
A cGMP-A-level environment is equivalent to ISO 5, whether stationary or operating. This means that the cleanliness inside the cleanroom must maintain a Class A level (ISO 5) regardless of whether employees are working or not. The level of cleanliness required for Class A areas can be achieved using laminar flow cabinets or laminar flow hoods (LAF). A laminar flow cabinet can achieve a Class A cleanliness rating if the surrounding air is retained and classified as Class B. To achieve Class A- cleanliness, the number of particles smaller than 0.5 microns in the air must not exceed 3,520 particles per cubic meter. Class A areas are dedicated to high-risk operations such as filling/finishing (filling area), stopper bowls, open ampoules, vials and making sterile connections.
Level B
A Class B clean room is equivalent to an ISO 7/class 10000 cleanroom environment when operating and an ISO 5 clean room when stationary. In a static state, a Class B cleanroom is required to meet a maximum of 3,520 particles (0.5μm) per cubic meter. During operation, the number of airborne particles allowed per cubic meter of air increases to 352,000 (0.5 μm). Sinks and drains are not permitted in Class A and B areas. Class B rooms in GMP facilities must be equipped with particle monitoring systems, including alarms when limits are exceeded. Class B cleanroom environment of GMP facility is used for aseptic preparation and filling.
Common Class B clean room projects:
- Clinical Manufacturing Facility for Cell and Gene Therapy – GMP Clean Room
- Vaccine Manufacturing Facilities (GMP)
- CGMP Cleanrooms and Biotech Cleanrooms for Stem Cell Manufacturing – Theranostics
- Cell and gene therapy cell processing laboratory (GMP-B level)
Level C
Class C cleanroom spaces are used to perform less stringent sterile product manufacturing steps. Class C (stationary and running) airborne particle classifications are equivalent to ISO 7 and ISO 8 respectively. At rest, the number of particles allowed per cubic meter is 352,000, while when operating it is 3,520, 000. Monitoring of Level C areas should be implemented in accordance with quality risk management principles, which are a systematic approach to assessing, controlling, communicating and reviewing quality risks throughout the life cycle of a pharmaceutical product.
Class C cleanroom projects include:
- cGMP modular cleanroom for vaccine plastic components
- GMP cell banking cleanroom for vaccine production
Level D
For Class D, the particle classification in the air is equivalent to an ISO 8 cleanroom at rest. At runtime, particle classification is not predefined; it will depend on the nature of the processes occurring within the region. This is what we call the Clean Non-Confidential (CNC) area. Like a Class C cleanroom in a GMP facility, a Class D area is used to perform less critical steps in manufacturing sterile pharmaceuticals. A Class D environment can be a background area, depending on how the cleanroom is designed. This is the least clean area of the GMP requirements for sterile products.
Precautions：
- (a) To achieve Class B, C, or D air classes, the number of air changes should be related to the size of the room, the equipment and personnel in the room. Air systems should be equipped with appropriate filters such as HEPA Class A, B, and C.
- (b) The guidelines given for the MAX allowable particle number under "resting" conditions roughly correspond to US Federal Standard 209E and the ISO classifications are as follows: Classes A and B correspond to Class 100, M 3.5, ISO 5; Class C 10000, M 5.5, ISO 7 and Class D 100000, M 6.5, ISO 8.
- (c) The requirements and restrictions in this area will depend on the nature of the operations being conducted.