The area where the lowest concentration of air-borne particles controlled, known as Clean Room and Classification of them depends on several air-borne particles present in the area. Measured in terms of the number of particles per m3 or ft3 for specific particle size.
The requirement of Clean Room and Classification arises because the air-borne particles in the environment can alter the quality of product resulting in contamination. Therefore, sometimes these air-borne particles termed as Contaminants. Some healthcare industries follow stringent clean room requirements to ensure the products manufactured are of high quality and free from contamination. This means the area of manufacturing must have the lowest possibility of the presence of particles.
Two aspects required to control the clean rooms:
- Movement in the environment
Air acts as a carrier for particulate or micro-organisms. Therefore, a controlled environment ensures the air entering the manufacturing area is having the lowest particle count and contamination. Using HEPA (High-Efficiency Particulate Air) or ULPA (Ultra Low Particulate Air) filters with Air Handling Units (AHU) serves the purpose.
* HEPA filter pore size: 0.25 to 0.30-micron particles or larger
* ULPA filter pore size: 0.12 to 0.13-micron particles or larger
These filters are the key component of the HVAC system located on the false ceiling so that air comes into the room from the top and leaves through the riser from the bottom. Application of ULPA filter considered for more stringent requirements. Apart from particles, the following parameters also considered for a controlled environment:
- Relative Humidity
- Differential Pressure between the different areas
Movement In The Environment
Once the environment control is done, the next step deals with the probable ways of contamination from the exterior, which include Process and Personnel movement. A person when enters the controlled area, carries foreign particles with the body. The raw material of the process may do the same thing. Therefore, people working in such an environment require complete training to control contamination which includes gowning, de-gowning, mask-wearing, head-cap wearing, and hand sanitation procedures as these are the potential sources of contamination.
Parameters that are important to control the clean room contamination due to personnel movement:
- Standard Operating Procedure for Entry and Exit for Personnel including list of allowed personnel allowed to enter the area, Personnel Hygiene Practices and Good Manufacturing Practices, etc.
- Ready to use Sterilized gowns (lint-free)
- Head Caps, Beard Masks, Gloves, Hand Sanitizer, Goggle, Booties, and Masks, etc.
- Use of air showers
We must order both the controls to ensure high quality of the end products. If any of the above lacks, the area definitely will get contaminated. Now, let us see the classification.
Clean Room and Classification
Clean room and classification of them considered for lowest particle size of 0.5 micron and higher per m3 or ft3.
Different standards have classified clean rooms as below:
- United States: FED STD 209E: Federal Standard 209E
- United Kingdom: British Standards BS 5295
- International Organization for Standardization: ISO 14644-1
- Europe: European Economic Commission (EEC)
Let us see one by one.
FED STD 209E (FEDeral STandarD)
In November 2001, the United States General Services Administration canceled this standard and superseded by ISO standards. Still, the standard is sometimes given worth consideration, particularly while establishing an equivalence with ISO standards. We’ll see this further.
Table shown below taken from FED STD 209E defines clean room and classification:
Hence, in Class 100,000 area (one Lakh), maximum particle count ranging from 0.5 microns till < 5-micron particle sizes, must not exceed 100,000 particles per ft3 OR 3,530,000 particles per m3. Similarly, for the same class, maximum particle count for 5 micron and higher sizes, not to exceed 700 particles per ft3 OR 24,700 particles per m3.
BS 5295 (British Standard)
BSI defined BS 5295 standard, which specifies clean room and classification. They divided the classification of clean room into 10 classes. However, BS 5295 like FED STD 209E superseding with ISO 14644-1 standard.
ISO 14644-1 (International Organization for Standardization)
ISO classified the area based on number format from 1 to 9. Class 9 of ISO refers to the room air and the number of particles reduces with decreasing ISO numbers. Refer below to the table explaining ISO Clean Room and Classification requirements.
The same kind of understanding would serve the purpose as explained above in the US FED STD 209E. Following formula used to calculate the values mentioned in the table above.
Cn = 10N * (0.1/D)2
N – ISO Class number
D – Diameter of the particle, or size of the particle
Cn – Maximum concentration (Particles per m3)
European Economic Commission (European Standard)
EEC outlined guidelines more stringent than US FED STD 209E and laid down clean room and classification based on two conditions
- During Rest – where installation and operation of equipment with no personnel presence.
- During Operation – where installed equipment working with personnel presence.
EEC uses the term Grade instead of class. However, Clean Room and Classification as per this standard given below.
For Grade A, therefore, requirements considered more stringent as the airflow considered having Laminar Flow profile. Also in the Grade A area, no particles greater than or equal to 5 microns are acceptable both during rest and operation.
– Final product packaging or the processing is done in the Grade A area.
– Final product loading, unloading is done in the Grade B area.
– Downstream Process operations performed in the Grade D followed by the Grade C area.
Equivalency Between EEC and FED STD 209E
Further, to draw an equivalency between the above mentioned standards, refer table below.
In a nutshell, clean room and classification vary as per different regulations yet with a common goal of maintaining the air clean. Rejecting the altered air inside the clean room. Now that you’re well aware about clean rooms and classification, let us get well-acquainted with Design of HVAC systems for Pharmaceutical Industries.
Clean Room Classification: FAQs
How are clean rooms classified?
Different standards have classified clean rooms such as:
United States: FED STD 209E: Federal Standard 209E
United Kingdom: British Standards BS 5295
International Standards Organization ISO 14644-1
Europe: European Economic Commission
The clean rooms are classified based on the number of maximum allowable particles per cubic meter.
What is first air in clean room?
The air freshly entering the clean room from the HEPA filter considered particulate-free and as first air.
What is the meaning of clean room?
Environment involving lower levels of contaminants, air-borne particulates, dust, bacteria, and other micro-organisms may affect the quality of the drug product when comes in contact.
Different regulations outline these low-level requirements for healthcare facilities, including pharmaceuticals, laboratories, etc.
What is a Class 1000 clean room?
Class 1000 of US FED STD 209E i.e. ISO 14644-1 Class 6 represents the requirement for maximum allowable particles as 35,200 (No. of particles/m3) when the size of the particle is greater or equivalent to 0.5 microns and less than 5 microns.
What is a Class 7 clean room?
ISO 14644-1 Class 7 i.e. US FED STD 209E Class 10,000 represents the requirement for maximum allowable particles as 3,52,000 (No. of particles/m3) when the size of the particle is greater or equivalent to 0.5 microns and less than 1 micron.
What is a Class 8 clean room?
ISO 14644-1 Class 8 i.e. US FED STD 209E Class 1,00,000 represents the requirement for maximum allowable particles as 35,20,000 (No. of particles/m3) when the size of the particle is greater or equivalent to 0.5 microns and less than 1 micron.
What is a Class 1 clean room?
Clean room becomes less stringent with the increasing number of classes such as Class 1 represent the cleanest room while Class 9 being the dirtiest.