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Building a GMP Facility: 8 GMP Cleanroom Requirements
GMP facilities and GMP cleanrooms are mandatory in various sectors of the pharma, biotechnology, and drug manufacturing industries to ensure high product quality. For example, they are commonly used in drug manufacturing, vaccine manufacturing, 503B outsourcing facilities, biologics, and the cell & gene therapy field.
The GMP requirement will impact your cleanroom and facility design. There are multiple ways to build and design a cleanroom facility that will meet GMP requirements for the sterile manufacturing of drugs. Here is a list of considerations you should know before elaborating on your design.
When designing your GMP facility, prioritize flush design, particularly for windows, walls, ceilings, and doors.
Whether it’s a GMP cleanroom facility or not, the purpose of a cleanroom is to provide a clean environment, with as few contaminants as possible inside the room, to manufacture various drug-related products.
Another advantage of the flush-finish option is that the absence of an edge makes it way easier to clean.
GMP guidelines are stricter than ISO 14644 for particle monitoring and sampling. That’s why a monitoring system is mandatory for sterile drug manufacturing under GMP guidelines with different sampling frequencies for each grade.
The approximate cost for a 21CFR monitoring system (including pressure/temperature/humidity) can range from $50,000 to $1 million for a GMP facility depending on the number of rooms, your specific requirements, and the number of probes you want/need. You will need to take account of this system in your GMP facility’s budget.
In a GMP cleanroom facility, many things need to be monitored. First, there is environmental monitoring, but there is microbiological monitoring as well. Environmental monitoring examines air pressure, humidity, airborne particles, etc.
On the other side, microbiological monitoring includes the microbial assessment of the air quality of laboratory operators, interiors, and surfaces inside the cleanroom. This aims to analyze and control the viable microbial load, also known as bioburden.
cGMP regulations have established recommended limits for microbial contamination for each grade. The Colony Forming Unit (CFU) is the measurement unit for the concentration of microorganisms, bacterial and fungal colonies, inside various test samples.
Here is the GMP chart showing the maximum amount of CFUs that can be found inside the cleanroom area:
Recommended limits for microbial contamination (a)
|Recommended limits for microbial contamination (a)|
|Grade||air sample cfu/m||settle plates (90 mm) cfu/4 hours (b)||contact plates (55 mm) cfu/plate||glove print 5 fingers cfu/glove|
|A||< 1||< 1||< 1||< 1|
For the results of particle and microbiological monitoring, appropriate warning and action thresholds should be defined. If these limitations are exceeded, operating procedures should prescribe corrective action. You will have to think about including alarms and microbiological monitoring devices in your GMP facility & cleanroom design.
A pass-through cabinet is an enclosure installed in a wall between two or more adjacent spaces to facilitate the transfer of materials from one side of the cleanroom to the other. In other words, it’s a smaller airlock inside the wall to transfer material only. The same requirements for MALs, PALs, and doors are necessary for the pass-through to be GMP compliant.
The entries, personnel airlocks, material airlocks, and pass-throughs need to have an interlocking system to be GMP compliant.
The interlocking system is to render the opening of more than one door at a time impossible. In a regulated environment, such as a cleanroom, interlocking systems are designed to provide a safe, efficient, and easy way of opening and closing doors.
Without this system, when both doors are open, it creates a wind corridor, pushing the microorganisms and airborne particles to the cleaner side of the cleanroom. This could be the difference between remaining GMP compliant or not.
An interlock door system will minimize the loss of pressure that happens when two doors are opened simultaneously and allow the HVAC to work in optimal conditions for maintaining the required cleanliness level. This feature will preserve air quality and prevent outside airborne contaminants from entering the manufacturing cleanroom area.
The interlocking door system is not an obligation under the GMP guidelines for sterile drug products, but it is mandatory that two doors cannot be opened simultaneously. A visual and/or audible alarm or signal could be another option to replace the interlocking system.
The GMP guidelines mention that there are 2 different cleanliness levels inside the same room that need to be met. There is the ‘’at rest‘’ and ‘’in operation’’ status.At rest, the cleanroom space is unoccupied (except for the equipment), because no one is working inside.
In operation, the workers are inside, and processes are underway in the cleanroom. For example, if you run a Grade B cleanroom, the ISO 14644-1 cleanliness level equivalent at rest is ISO 5, but it must be equivalent to an ISO 7 area in operation.
|Grade||Maximum permitted number of particles ≥ 0.5 μm/m3
|Maximum permitted number of particles ≥ 0.5 μm/m3
At Rest/In Operation
|Grade A||3 520||3 520||ISO 5/ ISO 5|
|Grade B||3 520||352 000||ISO 5/ ISO 7|
|Grade C||352 000||3 520 000||ISO 7/ ISO 8|
|Grade D||3 520 000||Not defined (CNC)||ISO 8/ – not defined|
Sinks and drains are never allowed in the clean room zone, but they are allowed in the gowning area or anteroom. As mentioned inside our Understanding Grade A, Grade B, Grade C & D article, sinks and drains are prohibited under GMP guidelines for Grade A and Grade B zones. This constraint is applicable only for aseptic processing areas, where they put the sterile aseptic product inside their sterile container.
Air brakes or mechanical devices should be installed between the machine or sink and the drains in areas dedicated to other processes. Backflow should be prevented by using traps or water seals in lower-grade (ex: Grade D) clean rooms.
Obtaining and maintaining GMP compliance with authorities such as the Food and Drug Administration (FDA) is a difficult task. Every part of your cleanroom design should be thoughtfully planned. If you want to build a GMP facility, working with experts and an experienced cleanroom manufacturer will save you time, stress, and money.
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