Designing a pharmaceutical compounding cleanroom requires adherence to regulations, attention to the activities and personnel inside the cleanroom, environmental monitoring and air management, proper materials and surfaces, and standard operating procedures for every process. To help make this information more digestible, we’ve broken down the essential components for designing a pharmaceutical cleanroom below.
Core Design Layout for Cleanrooms
Pharmacies and other locations that compound prescriptions must be designed according to whether they perform sterile compounding, non-sterile compounding, or both. Each category has distinct environmental and cleanliness requirements defined by United States Pharmacopeia (USP) standards.
Sterile Compounding Cleanrooms
Sterile compounding involves preparations intended to be free of microorganisms and is governed by USP <797> and, when hazardous drugs are involved, USP <800>.
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USP <797> cleanrooms are required for sterile, non-hazardous compounding. These cleanrooms must include an anteroom that meets ISO 8 air cleanliness standards, be fully enclosed on all sides, and meet minimum size requirements, including at least 72 square feet of cleanroom work area and 300 square feet of prescription preparation space. Additional requirements address air changes per hour, pressure differentials, and environmental monitoring.
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USP <800> cleanrooms apply to sterile compounding of hazardous drugs. While many structural and air-quality requirements mirror those of USP <797>, USP <800> adds controls specifically aimed at protecting personnel and the environment from hazardous drug exposure, such as negative pressure rooms and externally vented exhaust systems.
Non-Sterile Compounding Areas
Non-sterile compounding, which includes preparations such as capsules, creams, ointments, and oral solutions, does not require ISO-classified cleanrooms but must still comply with USP <795> and, if hazardous drugs are involved, USP <800>.
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USP <795> non-sterile compounding areas must be designed to minimize contamination and mix-ups. Requirements typically include designated compounding spaces, smooth and cleanable surfaces, adequate ventilation, and physical separation from dispensing and administrative areas.
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USP <800> non-sterile hazardous compounding areas require additional engineering controls, such as containment primary engineering controls (C-PECs) and appropriate room pressure relationships, even though ISO-classified cleanrooms are not required.
Facilities Performing Both
Facilities that compound both sterile and non-sterile preparations must maintain separate, clearly defined areas for each activity and ensure that hazardous and non-hazardous processes do not overlap in a way that could compromise safety or compliance.
ISO & GMP Classifications
All pharmacy cleanrooms must meet or exceed International Organization for Standardization (ISO) and Good Manufacturing Practice (GMP) classifications to ensure cleanrooms are safe, effective, and achieve their intended purposes.
GMP specifications relate to everything from quality control, finished products, processes, personnel, hygiene, and appropriate documentation. ISO requirements vary based on the specific activities within a room, but in general, a USP <797> cleanroom will require ISO class 8 for the ante room, ISO class 7 for the buffer room, and ISO class 5 for the BSC or primary compounding area. USP <800> cleanrooms need ISO class 7 in the hazardous drug buffer room as well as the ante room.
HVAC & Air Management
To meet the ISO requirements of a pharmaceutical compounding cleanroom, proper design is essential, not only in the layout of the room and stations, but in air management. This includes air pressure differential, which is especially important in pharmaceutical cleanrooms.
Using HEPA-filtered air entering the room through supply vents, every section of a USP <797> cleanroom must have positive air pressure relative to its adjacent space. In a USP <800> cleanroom, however, there are multiple air-pressure differentials. The ante room needs positive air pressure compared to adjacent rooms, whereas the hazardous drug buffer room and hazardous drug storage room need negative air pressure compared to adjacent rooms.
In both cases, the airflow needs to be in a direction that flows away from critical and clean areas, preventing any contaminants from going where they should not go.
Materials & Surfaces for the Cleanroom
All surfaces in the cleanroom should be smooth, non-porous, corrosion-resistant, and easy to clean and sanitize. This includes walls and ceilings made of modular panels, vinyl or polyurethane floors, and stainless steel for equipment, tables, benches, and workstations.
Using these materials keeps the cleanroom safe, efficient, and well in line with ISO and GMP specifications
Establishing a System to Monitor Quality
Designing, building, and using a pharmaceutical compounding cleanroom naturally comes with the need to ensure it is operating at maximum effectiveness at all times, which is why quality assurance is so important.
From our USP <797> checklist, you need:
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SOPs for all critical processes
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Routine internal audits and gap assessments
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A CAPA system in place for deviations
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Records of environmental monitoring, cleaning, and training
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Ongoing review of USP <797> updates and staff retraining
For a USP <800> cleanroom, again, we refer to our checklist:
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SOPs for all cleanroom activities
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Environmental monitoring logs
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Pressure differential logs
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Cleaning and maintenance records
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Incident and spill reports
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Annual review of compliance with USP <800> standards
Of particular note is the need to not only create and follow the SOPs for every process, but to enforce those SOPs. Even the slightest lapse in a single process can compound into detrimental conditions, so making sure all personnel adhere to the SOPs keeps the cleanroom operating exactly as it should.
Partner with Flow Cleanrooms to Ensure Your Cleanroom Meets Regulations
There’s a lot to consider when designing a cleanroom. Again, the main goal is to prevent contamination, and we do this by complying with regulations and designing a layout that best fits what you’re doing, who and how many people are doing it, and what needs to move where. It can sound complex, but it’s what we do. Connect with the team at Flow Cleanrooms to ensure your pharmaceutical cleanroom meets regulations.
