1. Cleanroom
From Wikipedia, the free encyclopedia
This article is about the manufacturing or research environment.
For the method used to avoid copyright infringement, see Clean
room design. For the software engineering methodology,
see Cleanroom software engineering.
Cleanroom used for the production of microsystems. The yellow
lighting is necessary for photolithography, to prevent unwanted
exposure ofphotoresist to light of shorter wavelengths.
Cleanroom from outside

2. Entrance to a cleanroom with no air shower
Cleanroom for microelectronicsmanufacturing with fan filter
units installed in the ceiling grid
Cleanroom cabin for precision measuring tools

3. Typical cleanroom head garment
A cleanroom or clean room is an environment, typically used
in manufacturing or scientific research, with a low level of
environmental pollutants such as dust,
airbornemicrobes, aerosol particles, and chemical vapors. More
accurately, a cleanroom has a controlled level of contamination
that is specified by the number of particles per cubic meter at a
specified particle size. To give perspective, the ambient air
outside in a typical urban environment contains 35,000,000
particles per cubic meter in the size range 0.5 μm and larger in
diameter, corresponding to an ISO 9 cleanroom, while an ISO 1
cleanroom allows no particles in that size range and only 12
particles per cubic meter of 0.3 μm and smaller. In the
pharmaceutical industry, clean rooms play a crucial role in the
manufacturing of pharmaceutical products which are required to
be free from microbial and particulate contamination and
protected from moisture. Such pharmaceutical products are
manufactured and manipulated in cleanrooms, which are fitted
with HEPAand, if required, ULPA filters as well as
dehumidifier systems.[1]
Contents

4. [hide]
 1 History
 2 Overview
 3 Air flow principles
 4 Personnel contamination of cleanrooms
 5 Cleanroom classifications
o 5.1 US FED STD 209E cleanroom standards
o 5.2 ISO 14644-1 cleanroom standards
o 5.3 BS 5295 cleanroom standards
o 5.4 GMP EU classification
 6 See also
 7 References
 8 External links
History[edit]
The modern cleanroom was invented by
Americanphysicist Willis Whitfield.[2]
An employee of the
Sandia National Laboratories, Whitfield created the initial plans
for the cleanroom in 1960.[2]
Prior to Whitfield's invention,
earlier cleanrooms often had problems with particles and
unpredictable airflows. Whitfield designed his cleanroom with a
constant, highly filtered air flow to flush out
impurities.[2]
Within a few years of its invention in the 1960s,
Whitfield's modern cleanroom had generated more than $50
billion in sales worldwide.[3]
The cleanroom eventually entered
the hospital industry in the United Kingdom, primarily in
hospitalpharmacies.[4]
Overview[edit]

5. Cleanrooms can be very large. Entire manufacturing facilities
can be contained within a cleanroom with factory floors
covering thousands of square meters. They are used extensively
in semiconductor manufacturing,biotechnology, the life
sciences, and other fields that are very sensitive to
environmental contamination.
The air entering a cleanroom from outside is filtered to exclude
dust, and the air inside is constantly recirculated through high-
efficiency particulate air (HEPA) and/or ultra-low particulate air
(ULPA) filters to remove internally generated contaminants.
Staff enter and leave through airlocks (sometimes including
an air shower stage), and wear protective clothing such as hoods,
face masks, gloves, boots, and coveralls.
Equipment inside the cleanroom is designed to generate minimal
air contamination. Only special mops andbuckets are used.
Cleanroom furniture is designed to produce a minimum of
particles and to be easy to clean.
Common materials such as paper, pencils, and fabricsmade from
natural fibers are often excluded, and alternatives used.
Cleanrooms are not sterile(i.e., free of uncontrolled
microbes);[5]
only airborne particles are controlled. Particle
levels are usually tested using a particle counter and
microorganisms detected and counted through environmental
monitoring methods.[6][7]
Some cleanrooms are kept at a positive pressure so if any leaks
occur, air leaks out of the chamber instead of unfiltered air
coming in.

6. Some cleanroom HVAC systems control the humidity to low
levels, such that extra equipment ("ionizers") is necessary to
prevent electrostatic discharge problems.
Low-level cleanrooms may only require special shoes, with
completely smooth soles that do not track in dust or dirt.
However, for safety reasons, shoe soles must not create slipping
hazards. Access to a cleanroom is usually restricted to those
wearing a cleanroom suit.[8]
In cleanrooms in which the standards of air contamination are
less rigorous, the entrance to the cleanroom may not have an air
shower. An anteroom (known as a "gray room") is used to put
on clean-room clothing.
Some manufacturing facilities do not use fully classified
cleanrooms, but use some cleanroom practices to maintain their
contamination requirements.[9]
Air flow principles[edit]
Air flow pattern for "Turbulent
Cleanroom"
Air flow pattern for "Laminar
FlowCleanroom"
Cleanrooms maintain particulate-free air through the use of
either HEPA or ULPA filters employing laminar or turbulent air

7. flow principles. Laminar, or unidirectional, air flow systems
direct filtered air downward or in horizontal direction in a
constant stream towards filters located on walls near the
cleanroom floor or through raised perforated floor panels to be
recirculated. Laminar air flow systems are typically employed
across 80% of a cleanroom ceiling to maintain constant air
processing. Stainless steel or other non shedding materials are
used to construct laminar air flow filters and hoods to prevent
excess particles entering the air. Turbulent, or non
unidirectional, air flow uses both laminar air flow hoods and
nonspecific velocity filters to keep air in a cleanroom in constant
motion, although not all in the same direction. The rough air
seeks to trap particles that may be in the air and drive them
towards the floor, where they enter filters and leave the
cleanroom environment. US FDA and EU have laid down
guidelines and limit for microbial contamination which is very
stringent to ensure freedom from microbial contamination in
pharmaceutical products.[10][11]
Personnel contamination of cleanrooms[edit]
In the healthcare and pharmaceutical sectors, control of
microorganisms is important, especially microorganisms likely
to be deposited into the air stream from skin shedding. Studying
cleanroom microflora is of importance for microbiologists and
quality control personnel to assess changes in trends. Shifts in
the types of microflora may indicate deviations from the “norm”
such as resistant strains or problems with cleaning practices.
In assessing cleanroom microorganisms, the typical flora are
primarily those associated with human skin (Gram-positive
cocci), although microorganisms from other sources such as the

8. environment (Gram-positive rods) and water (Gram-negative
rods) are also detected, although in lower numbers. Common
bacterial genera
include Micrococcus, Staphylococcus,Corynebacterium,
and Bacillus, and fungal genera
include Aspergillus and Pencillin.[7]
Cleanroom classifications[edit]
Cleanrooms are classified according to the number and size of
particles permitted per volume of air. Large numbers like "class
100" or "class 1000" refer to FED-STD-209E, and denote the
number of particles of size 0.5 µm or larger permitted per cubic
foot of air. The standard also allows interpolation, so it is
possible to describe, for example, "class 2000".
A discrete-particle-counting, light-scattering instrument is used
to determine the concentration of airborne particles, equal to and
larger than the specified sizes, at designated sampling locations.
Small numbers refer to ISO 14644-1 standards, which specify
the decimal logarithm of the number of particles 0.1 µm or
larger permitted per m3
of air. So, for example, an ISO class 5
cleanroom has at most 105
particles/m3
.
Both FS 209E and ISO 14644-1 assume log-log relationships
between particle size and particle concentration. For that reason,
zero particle concentration does not exist. The table locations
without entries are nonapplicable combinations of particle sizes
and cleanliness classes, and should not be read as zero.
Because 1 m3
is about 35 ft3
, the two standards are mostly
equivalent when measuring 0.5 µm particles, although the
testing standards differ. Ordinary room air is around class
1,000,000 or ISO 9.[12]

9. US FED STD 209E cleanroom standards[edit]
Class
maximum particles/ft3
ISO
equivalen
t≥0.1 µ
m
≥0.2 µ
m
≥0.3 µ
m
≥0.5 µ
m
≥5 µ
m
1 35 7.5 3 1 0.007 ISO 3
10 350 75 30 10 0.07 ISO 4
100 3,500 750 300 100 0.7 ISO 5
1,000 35,000 7,500 3000 1,000 7 ISO 6
10,000 350,000 75,000 30,000 10,000 70 ISO 7
100,00
0
3.5×106
750,000 300,000 100,000 700 ISO 8
This section may
be confusing or
unclear to
readers. (March 2015)
US FED STD 209E was officially cancelled by the General
Services Administration on November 29, 2001,[13][14]
but is still
widely used. It also specify classes of clean room with respect to

10. their impact on pharmaceutical manufacturing process. 1.Critical
2) Controlled Area. Critical area is meant for manufacture or
manipulate a product require to be free from microbial and
particulate matter or sterile. While controlled area have certain
allowable limit of microbial load, as pharmaceutical product
processed in these area further passes through process of
sterilisation and final filtration which takes care of freedom from
microbial contamination and particulate matter.
ISO 14644-1 cleanroom standards[edit]
Cla
ss
maximum particles/m3
FED
STD
209E
equival
ent
≥0.1
µm
≥0.2 µ
m
≥0.3 µ
m
≥0.5 µ
m
≥1 µm
≥5 µ
m
IS
O 1
10 2.37 1.02 0.35 0.083
0.002
9
IS
O 2
100 23.7 10.2 3.5 0.83 0.029
IS
O 3
1,000 237 102 35 8.3 0.29 Class 1
IS
O 4
10,00
0
2,370 1,020 352 83 2.9
Class
10

11. IS
O 5
100,0
00
23,70
0
10,200 3,520 832 29
Class
100
IS
O 6
1.0×1
06
237,0
00
102,00
0
35,200 8,320 293
Class
1,000
IS
O 7
1.0×1
07
2.37×
106
1,020,0
00
352,000 83,200 2,930
Class
10,000
IS
O 8
1.0×1
08
2.37×
107
1.02×1
07
3,520,0
00
832,00
0
29,30
0
Class
100,000
IS
O 9
1.0×1
09
2.37×
108
1.02×1
08
35,200,
000
8,320,0
00
293,0
00
Room
air
BS 5295 cleanroom standards[edit]
maximum particles/m3
Class ≥0.5 µm ≥1 µm ≥5 µm ≥10 µm ≥25 µm
Class 1 3,000 0 0 0
Class 2 300,000 2,000 30
Class 3 1,000,000 20,000 4,000 300

12. Class 4 200,000 40,000 4,000
BS 5295 Class 1 also requires that the greatest particle present in
any sample can not exceed 5 μm.[15]
GMP EU classification[edit]
EU GMP guidelines are more stringent than others, requiring
cleanrooms to meet particle counts at operation (during
manufacturing process) and at rest (when manufacturing process
is not carried out, but room AHU is on).
Class
maximum particles/m3[16]
At Rest At Rest In Operation In Operation
0.5 µm 5 µm 0.5 µm 5 µm
Grade A 3,500 0 3,500 0
Grade B 3,500 0 350,000 2,000
Grade C 350,000 2,000 3,500,000 20,000
Grade D 3,520,000 29,000 n/a n/a
See also[edit]