A clean room is a room in which particles and the viable count is kept within standard and defined ranges. As the name indicates, cleaning is the strict requirement for these rooms and it is necessary to maintain their defined cleaning level all the time. Cleans rooms play an important role in the manufacturing of pharmaceutical products.
In pharmaceutical industries, clean rooms are classified based on the size of particles and the number of particles per cubic meter of air. For each clean room, there are specific limits for particle count, microbial counts and air changes.
Classification of clean rooms
Clean rooms are classified according to following standards,
ISO 14644-1
Federal Standards (FS 209)
European standards
According to ISO 14644-1
ISO classify clean rooms into following
ISO 1
ISO 2
ISO 3
ISO 4
ISO5
ISO 6
ISO 7
ISO 8
ISO 9
In ISO there are 9 classes of the clean rooms from ISO 1 to IOS 9.ISO 1 is cleanest from all classes of ISO and ISO 9 is least clean or dirtiest from all ISO classes but cleaning level of ISO 9 is superior to a regular room. In pharmaceutical Industries following ISO, classes are generally required,
ISO 5
ISO6
ISO 7
ISO 8
According to FS 209
According to the federal standard, FS 209 Clean rooms are classified as,
Class100
Class1000
Class 10,000
Class100,000
According to the EU GMP
Grade A
Grade B
Grade C
Grade D
FS 209 is replaced by ISO 14644-1 but these terms are still in use. In ISO particle are taken as particles/m³ (cubic meter)and in FS 209 particles were taken as particles/ft³(cubic feet)
A simple comparison of clean rooms classification for pharmaceutical industries is as follow,
ISO EU GMP FS
ISO 5 Grade A Class 100
ISO 6 Grade B Class 1000
ISO 7 Grade C Class 10,000
ISO 8 Grade D Class 100,000
Particle Size Range
In pharmaceutical industries, two ranges of particle size are considered for classification of clean rooms one is ≥0.5 micron (equal to or greater than 0.5 microns) and other is ≥5.0 micron (equal to or greater than 5.0-micron particles).
ISO 5 /Grade A
ISO class 5 is cleanest in pharmaceutical industries and particle count limit for this class is 3520 particles/m³ for particle size ≥0.5 micron, and particle count for particles ≥5.0 micron is 29 particles/m³.
Air changes per hour are 240-480.
Microbial count in Grade A according to EU is <1 cfu/m³.
Class A is achieved under laminar airflow hood and critical operations take place in this class,
Filling
Sealing
Aseptic manufacturing(If sterile filtration is not done)
Handling of sterile starting materials.
Manufacturing and filling of sterile creams, ointments,
emulsions and suspension(when Product is exposed and is not subsequently filtered)
ISO 6 /Grade B
ISO class 6 is the second number for cleaning standard in pharmaceutical industries and particle count for particles ≥0.5micron is 35200 particles/m³ and particle count for particles ≥5.0 micron is 293 particles/m³.
Air changes per hour are 150-240.
Microbial count in Grade B according to EU is 10 cfu/m³.
Grade B is the background area of Grade A mean area in which laminar airflow hood is placed.
ISO 7 /Grade C
ISO class 7 is on the third number in pharmaceutical industries and particle count for particles ≥0.5 micron is 352000 particles/m³ and particle count for particles ≥5.0 micron is 2930 particles/m³.
Air changes per hour are 60-90.
Microbial count in Grade C according to EU is 100 cfu/m³.
Grade C is for following operations,
Solution preparation( if sterile filtration is to be done later on)
Manufacturing and filling of creams, ointments,
emulsions and suspension before terminal steralization.
Liquid manufacturing area at rest is Grade C.
ISO 8/Grade D
ISO class 8 is on forth number class in pharmaceutical industries and particle count for particles ≥0.5 micron is 3520,000 particles/m³ and particle count for particles ≥5.0 micron is 29300 particles/m³.
Air changes per hour are 05-48.
Microbial count in Grade D according to EU is 200 cfu/m³.
washing of components.
Handling of components after washing
Tablet,Capsule section(OSD) is Grade D at rest.
Liquid manufacturing area in operation is Grade D.
All clean rooms are separated from each other through the Airlock system. Airlocks maintain the cleaning standard of clean rooms through proper air changes. Air changes are maintained by the HVAC system. in clean rooms, the air is filtered through HEPA filters.HEPA filter stands for High-efficiency particulate air filter.HEPA filters remove particles of 0.3 microns and supply clean air in clean rooms. At Rest At rest mean all the equipment are installed in a clean room and HVAC system is operational but manufacturing activity is stopped. It means the area is cleaned and no operator is performing manufacturing activity. At rest particle count in clean rooms is as follow, Grade A ≥0.5 micron=3520 particles/Cubic meter ≥5.0 micron=29 particles/Cubic meter Grade B ≥0.5 microns=35200 particles/Cubic meter ≥5.0 micron=293 particles/Cubic meter Grade C ≥0.5 microns=352000 particles/Cubic meter ≥5.0 micron=2930 particles/Cubic meter Grade D ≥0.5 micron=3520000 particles/Cubic meter ≥5.0 micron=29300 particles/Cubic meter In Operation In operation means all the equipment are installed in a cleanroom and HVAC system is operational and manufacturing activity is going on in the cleanroom. It means the area is cleaned and operators are performing manufacturing activity in a cleanroom. In Operations particle count in clean rooms is as follow, Grade A ≥0.5 micron=3520 particles/Cubic meter ≥5.0 micron=29 particles/Cubic meter Grade B ≥0.5 microns=352000 particles/Cubic meter ≥5.0 micron=2930 particles/Cubic meter Grade C ≥0.5 micron=3520,000 particles/Cubic meter ≥5.0microns=29300 particles/Cubic meter Grade D ≥0.5 microns=Not Defined. ≥5.0 micron=Not Defined. Note: Refer Reference EU volume 4 Annex 1 and WHO Annex 6 describe 5.0 micron=20 particles/Cubic meter both for at rest and operation.
Comments