CLASSIFICATION
OF CLEANROOMS AND CLEANROOM STANDARDS
Reproduced with
permission from "The Scottish
Society for Contamination control" website
Cleanrooms are
classified by the cleanliness of their air. The method most easily
understood and universally applied is the one suggested in the earlier
versions (A to D) of Federal Standard 209 in which the number of particles
equal to and greater than 0.5 m m is measured in one cubic foot of
air and this count is used to classify the room. The most recent 209E
version has accepted a metric nomenclature.
INDEX
Federal
Standard 209
This standard
was first published in 1963 in the USA and titled "Cleanroom
and Work Station Requirements, Controlled Environments". It was
revised in 1966 (209A), 1973 (209B), 1987 (C), 1988 (D) and 1992 (E).
It is available from:
Institute of Environmental
Sciences
940 East Northwest Highway
Mount Prospect
Illinois, 60056
USA
Tel: 0101 708 255 1561
Fax: 0101 708 255 1699
e-mail: Instenvsci@aol.com
The cleanroom
classifications given in the earlier 209 versions are shown in Table
2. In the new 209E the airborne concentrations in the room have been
given in metric units, i.e per m^3 and the classifications of the
room defined as the logarithm of the airborne concentration of particles ³ 0.5 m m
e.g. a Class M3
room has a particle limit for particles ³ 0.5 m m of 1000/m^3.
This is shown in Table 3.
Table
2 Federal Standard 209D Class Limits
CLASS
|
MEASURED
PARTICLE SIZE (MICROMETERS)
|
0.1
|
0.2
|
0.3
|
0.5
|
5.0
|
1
|
35
|
7.5
|
3
|
1
|
NA
|
10
|
350
|
75
|
30
|
10
|
NA
|
100
|
NA
|
750
|
300
|
100
|
NA
|
1,000
|
NA
|
NA
|
NA
|
1,000
|
7
|
10,000
|
NA
|
NA
|
NA
|
10,000
|
70
|
100,000
|
NA
|
NA
|
NA
|
100,000
|
700
|
Table
3 Federal Standard 209E Airborne Particulate Cleanliness Classes
Class
Name
|
Class
Limits
|
|
|
0.1m
m |
0.2m
m |
0.3m
m |
0.5m
m |
5m
m |
|
|
Volume
Units |
Volume
Units |
Volume
Units |
Volume
Units |
Volume
Units |
SI |
English |
(m^3) |
(ft^3) |
(m^3) |
(ft^3) |
(m^3) |
(ft^3) |
(m^3) |
(ft^3) |
(m^3) |
(ft^3) |
M
1 |
|
350 |
9.91 |
75.7 |
2.14 |
30.9 |
0.875 |
10.0 |
0.283 |
-- |
-- |
M
1.5 |
1 |
1
240 |
35.0 |
265 |
7.50 |
106 |
3.00 |
35.3 |
1.00 |
-- |
-- |
M
2 |
|
3
500 |
99.1 |
757 |
21.4 |
309 |
8.75 |
100 |
2.83 |
-- |
-- |
M
2.5 |
10 |
12
400 |
350 |
2
650 |
75.0 |
1
060 |
30.0 |
353 |
10.0 |
-- |
-- |
M
3 |
|
35
000 |
991 |
7
570 |
214 |
3
090 |
87.5 |
1
000 |
28.3 |
-- |
-- |
M
3.5 |
100 |
-- |
-- |
26
500 |
750 |
10
600 |
300 |
3
530 |
100 |
-- |
-- |
M
4 |
|
-- |
-- |
75
700 |
2
140 |
30
900 |
875 |
10
000 |
283 |
-- |
-- |
M
4.5 |
1
000 |
-- |
-- |
-- |
-- |
-- |
-- |
35
300 |
1
000 |
247 |
7.00 |
M
5 |
|
-- |
-- |
-- |
-- |
-- |
-- |
100
000 |
2
830 |
618 |
17.5 |
M
5.5 |
10
000 |
-- |
-- |
-- |
-- |
-- |
-- |
353
000 |
10
000 |
2
470 |
70.0 |
M
6 |
|
-- |
-- |
-- |
-- |
-- |
-- |
1
000 000 |
28
300 |
6
180 |
175 |
M
6.5 |
100
000 |
-- |
-- |
-- |
-- |
-- |
-- |
3
350 000 |
100
000 |
24
700 |
700 |
M
7 |
|
-- |
-- |
-- |
-- |
-- |
-- |
10
000 000 |
283
000 |
61
800 |
1
750 |
With a little
thought it can be appreciated that the airborne contamination level
of a given cleanroom is dependent on the particle generating activities
going on in the room. If a room is empty, a very low particle concentration
can be achieved, this closely reflects the quality of air supplied
by the high efficiency filter. If the room has production equipment
in it and operating, there will be a greater particle concentration
but the greatest concentrations will occur when the room is in full
production. The classification of the room according to FS 209D may
therefore be carried out when the room is:
(a) as built,
ie complete and ready for operation, with all services connected and
functional but without production equipment or operating personnel.
(b) at rest, ie
complete, with all services functioning and with equipment installed
and operable or operating, as specified but without personnel in the
facility.
(c) operational,
ie in normal operation, with all services functioning and with equipment
and personnel, if applicable, present and performing their normal
work functions in the facility.
Federal Standard
209 is a document which mainly gives information on the airborne particle
limits that are required to specify the airborne quality of cleanrooms
and also gives the methods used to check what concentrations are present.
It does not give any information on how a cleanroom should be operated.
This information had been included in a series of Recommended Practices
which are written by the same Institute as has written the Federal
Standard 209, namely the Institute of Environmental Sciences. Some
of the RP's which are of particular interest to those who test and
run cleanrooms are discussed later in this document.
British
Standard 5295:1989
This standard
is available from:
B S I Standards
389 Chiswick
High Road
London W44
AL
Tel 0181
996 9000
Fax 0181
996 7400
The British Standard
is in five parts. These are:
Part 0
- General introduction and terms and definitions for cleanrooms and
clean air devices. (4 pages)
Part 1
- Specification for cleanrooms and clean air devices. (14 pages)
Part 2
- Method for specifying the design, construction and commissioning
of cleanroom and clean air devices. (14 pages)
Part 3
- Guide to operational procedures and disciplines applicable to cleanrooms
and clean air devices. (6 pages)
Part 4
- Specification for monitoring cleanrooms and clean air devices to
prove continued compliance with BS 5295. (10 pages)
The contents of
the above parts are as follows:
Part 0 -
'General introduction, terms and definitions for cleanrooms and clean
air devices'
The definitions
have been drawn together and presented in this section. This part
also provides a basic introduction to the main parts of the standard,
particularly for those unfamiliar with cleanrooms or the standard
itself.
Part 1 -
'Specification for cleanrooms and clean air devices'
The Standard contains
ten classes of environmental cleanliness. Shown in Table 4 are the
classes given in the standard. All classes have particle counts specified
for at least two particle size ranges to provide adequate confidence
over the range of particle size relevant to each class.
Some classes of
rooms, except for 0.3 m m particles, have an identical specification.
For example, Class F is equivalent to Class E except for the 0.3 m
m particle specification. This is deliberate, as many users, e.g.
pharmaceutical manufacturing, do not wish to be associated with the
small particle technology that is not appropriate to their industry.
Table
4 BS 5295 Environmental cleanliness classes
|
Maximum
permitted number of particles per m^3 (equal to, or greater
than, stated size) |
Maximum
floor area per sampling position for cleanrooms (m^2) |
Minimum
pressure difference* |
Class
of environmental cleanliness |
0.3
m m |
0.5
m m |
5
m m |
10
m m |
25
m m |
Between
classified areas and unclassified areas (Pa) |
Between
classified area and adjacent areas of lower classification
(Pa) |
C |
100
|
35
|
0
|
NS
|
NS
|
10
|
15
|
10
|
D |
1
000
|
350
|
0
|
NS
|
NS
|
10
|
15
|
10
|
E |
10
000
|
3
500
|
0
|
NS
|
NS
|
10
|
15
|
10
|
F |
NS
|
3
500
|
0
|
NS
|
NS
|
25
|
15
|
10
|
G |
100
000
|
35
000
|
200
|
0
|
NS
|
25
|
15
|
10
|
H |
NS
|
35
000
|
200
|
0
|
NS
|
25
|
15
|
10
|
J |
NS
|
350
000
|
2
000
|
450
|
0
|
25
|
15
|
10
|
K |
NS
|
3
500 000
|
20
000
|
4
500
|
500
|
50
|
15
|
10
|
L |
NS
|
NS
|
200
000
|
45
00
|
5
000
|
50
|
10
|
10
|
M |
NS
|
NS
|
NS
|
450
000
|
50
000
|
50
|
10
|
NA
|
BS 5295:1989 identifies
three states of operation similar to FS208E:
-
as
built - on completion, prior to moving in
-
unmanned
- operational but not in use
-
manned
- in full operational use
-
Also
given in the specification of Part 1 are other requirements for
cleanrooms to comply with. These are:
-
minimum
pressure difference between the cleanroom and adjacent areas (see
Table 4)
-
filter
installation test leakage
-
freedom
of leakage from construction joints or openings
Testing to satisfy
the requirements of Part 1 of the British Standard is discussed later
in this document in that section which deals with the testing and
validation of cleanrooms.
Part 2 -
'Method for specifying the design, construction and commissioning
of cleanrooms and clean air devices'
A major consideration
in the rewrite of BS 5295 was to ensure its usefulness as a purchase
and operational specification and as supporting documentation to a
contract. Part 2 has therefore been restructured into a format which
enables a purchaser to specify what type of room or device is required
and, where relevant, how it is to be achieved. To assist with its
use as part of contractual documentation it has been given specification
status, i.e. it is mandatory.
Part 3 -
'Guide to operational procedures and disciplines applicable to cleanroom
and clean air devices'
This incorporates
guidance for those drawing up procedures for personnel, operations,
cleaning, garments and garment laundering.
Part 4 -
'Specification for monitoring cleanrooms and clean air devices to
prove continued compliance with BS 5295: Part 1'
Cleanroom and
clean air equipment standards have for many years defined classes
of cleanliness and how they are to be assessed. However there has
never been any requirement to test a cleanroom at any point in its
often very long lifetime, other than at the time of handover from
supplier to purchaser. Once accepted from the supplier, the facility
then repaid its capital cost, over a life span of ten to twenty years,
sometimes without ever being tested. Yet over this period customers
were provided with products which were stated to be 'produced under
Class X'. This can no longer be the case.
The tests specified
are those contained in Part 1, thus providing a continuity back to
the original purchase specification. The intervals between tests are
related to the class of room or device and are given later in this
manual in that section relating to the validation and testing of cleanrooms.
ISO
Standard
Because of the
large number of cleanroom standards produced by individual countries
it is very desirable that one world-wide standard of cleanroom classification
is produced. The International Standards Organisation is producing
such a document. Because of the number of countries involved and the
problems with translation it may be over a year before it is published.
However, it is unlikely that it will be different from table 5.
Table
5. Selected ISO 209 airborne particulate cleanliness classes for cleanrooms
and clean zones.
numbers
(N) |
Maximum
concentration limits (particles/m^3 of air) for particles
equal to and larger than the considered sizes shown below |
|
0.1m
m
|
0.2m
m
|
0.3m
m
|
0.5m
m
|
1m
m
|
5.0m
m
|
ISO
1
|
10
|
2
|
|
|
|
|
ISO
2
|
100
|
24
|
10
|
4
|
|
|
ISO
3
|
1
000
|
237
|
102
|
35
|
8
|
|
ISO
4
|
10
000
|
2
370
|
1
020
|
352
|
83
|
|
ISO
5
|
100
000
|
23
700
|
10
200
|
3
520
|
832
|
29
|
ISO
6
|
1
000 000
|
237
000
|
102
000
|
35
200
|
8
320
|
293
|
ISO
7
|
|
|
|
352
000
|
83
200
|
2
930
|
ISO
8
|
|
|
|
3
520 000
|
832
000
|
29
300
|
ISO
9
|
|
|
|
35
200 000
|
8
320 000
|
293
000
|
The table is derived
from the following formula:
where:
Cn represents
the maximum permitted concentration ( in particles/m^3 of air ) of
airborne particles that are equal to or larger than the considered
particle size. Cn is rounded to the nearest whole number.
N is the ISO classification
number, which shall not exceed the value of 9. Intermediate ISO classification
numbers may be specified, with 0.1 the smallest permitted increment
of N.
D is the considered
particle size in m m.
0.1 is a constant
with a dimension of m m.
Table 5 shows
a crossover to the old FS 209 classes e.g. ISO 5 is equivalent to
the old FS 209 Class 100.
The standard also
gives a method by which the performance of a cleanroom may be verified
i.e. sampling locations, sample volume etc.. These are similar to
FS 209. It also includes a method for specifying a room using particles
outside the size range given in the table 5. Smaller particles (ultra
fine) will be of particular use to the semiconductor industry and
the large (³ 5m m macro particles) will be of use in industries
such as parts of the medical device industry, where small particles
are of no practical importance. Fibres can also be used. The method
employed with macro particles is to use the format:
'M(a; b);c'
where
a is the maximum
permitted concentration/m^3
b is the equivalent
diameter.
c is the specified
measurement method.
An example would
be
'M(1 000; 10m
m to 20m m); cascade impactor followed by microscopic sizing and counting'.
Pharmaceutical
Cleanroom Classification
The most recent
set of standards for Europe has come into operation on the 1 January
1997. This is contained in a 'Revision of the Annexe to the EU Guide
to Good Manufacturing Practice-Manufacture of Sterile Medicinal Products'.
The following
is an extract of the information in the standard that is relevant
to the design of cleanrooms:
'General
The manufacture
of sterile products should be carried out in clean areas, entry to
which should be through airlocks for personnel and/or for equipment
and materials. Clean areas should be maintained to an appropriate
cleanliness standard and supplied with air which has passed through
filters of an appropriate efficiency.
The various
operations of component preparation, product preparation and filling
should be carried out in separate areas within the clean area. Manufacturing
operations are divided into two categories; firstly those where the
product is terminally sterilised, and secondly those which are conducted
aseptically at some or all stages.
Clean areas
for the manufacture of sterile products are classified according to
the required characteristics of the environment. Each manufacturing
operation required an appropriate environmental cleanliness level
in the operational state in order to minimise the risks of particulate
or microbial contamination of the product or materials being handled.
In order to
meet "in operation" conditions these areas should be designed
to reach certain specified air-cleanliness levels in the "at
rest" occupancy state. The "at-rest" state is the condition
where the installation is complete with production equipment installed
and operating but with no operating personnel present. The "in
operation" state is the condition where the installation is functioning
in the defined operating mode with the specified number of personnel
working.
For the manufacture
of sterile medicinal products normally 4 grades can be distinguished.
Grade A:
The local zone for high risk operations, e.g. filling zone, stopper
bowls, open ampoules and vials, making aseptic connections. Normally
such conditions are provided by a laminar air flow work station. Laminar
air flow systems should provide an homogeneous air speed of 0.45 m/s
+/- 20% (guidance value) at the working position.
Grade B:
In case of aseptic preparation and filling, the background environment
for grade A zone.
Grades C
and D: Clean areas for carrying out less critical stages in the
manufacture of sterile products.
The airborne
particulate classification for these grades is given in the following
table.
|
maximum
permitted number of particles/m^3 equal to or above
|
Grade
|
at
rest (b)
|
in
operation
|
|
0,5m
m
|
5m
m
|
0,5m
m
|
0,5m
|
A
|
3
500
|
0
|
3
500
|
0
|
B(a)
|
3
500
|
0
|
350
000
|
2
000
|
C(a)
|
350
000
|
2
000
|
3
500 000
|
20000
|
D(a)
|
3
500 000
|
20
000
|
not
defined (c)
|
not
defined (c)
|
Notes:
(a) In order
to reach the B, C and D air grades, the number of air changes should
be related to the size of the room and the equipment and personnel
present in the room. The air system should be provided with appropriate
filters such as HEPA for grades A, B and C.
(b) The guidance
given for the maximum permitted number of particles in the "at
rest" condition corresponds approximately to the US Federal Standard
209E and the ISO classifications as follows: grades A and B correspond
with class 100, M 3.5, ISO 5; grade C with class 10 000, M 5.5, ISO
7 and grade D with class 100 000, M 6.5, ISO 8.
(c) The requirement
and limit for this area will depend on the nature of the operations
carried out.
Examples of
operations to be carried out in the various grades are given in the
table below. (see also par. 11 and 12).
Grade |
Examples
of operations for terminally sterilised products. (see par.
11) |
A |
Filling
of products, when unusually at risk. |
C |
Preparation
of solutions, when unusually at risk. Filling of products. |
D |
Preparation
of solutions and components for subsequent filling. |
Grade |
Examples
of operations for aseptic preparations. (see par. 12) |
A |
Aseptic
preparation and filling. |
C |
Preparation
of solutions to be filtered. |
D |
Handling
of components after washing. |
The particulate
conditions given in the table for the "at rest" state should
be achieved in the unmanned state after a short "clean up" period of 15-20 minutes (guidance value), after completion of operations.
The particulate conditions for grade A in operation given in the table
should be maintained in the zone immediately surrounding the product
whenever the product or open container is exposed to the environment.
It is accepted that it may not always be possible to demonstrate conformity
with particulate standards at the point of fill when filling is in
progress, due to the generation of particles or droplets from the
product itself.
Additional
microbiological monitoring is also required outside production operations,
e.g. after validation of systems, cleaning and sanitisation.
Recommended
limits for microbial contamination (a)
|
GRADE
|
air
sample cfu/m^3
|
settle
plates (dia. 90 mm), cfu/4 hours(b)
|
contact
plates (dia.55 mm), cfu/plate
|
glove
print. 5 fingers.cfu/glove
|
A
|
< 1
|
< 1
|
< 1
|
< 1
|
B
|
10
|
5
|
5
|
5
|
C
|
100
|
50
|
25
|
-
|
D
|
200
|
100
|
50
|
-
|
Notes:
(a) These are
average values.
(b) Individual
settle plates may be exposed for less than 4 hours.
(c) Appropriate
alert and action limits should be set for the results of particulate
and microbiological monitoring. If these limits are exceeded operating
procedures should prescribe corrective action.
Isolator
and Blow Fill Technology (extract only)
The air classification
required for the background environment depends on the design of the
isolator and its application. It should be controlled and for aseptic
processing be at least grade D.
Blow/fill/seal
equipment used for aseptic production which is fitted with an effective
grade A air shower may be installed in at least a grade C environment,
provided that grade A/B clothing is used. The environment should comply
with the viable and non viable limits at rest and the viable limit
only when in operation. Blow/fill/seal equipment used for the production
of products for terminal sterilisation should be installed in at least
a grade D environment.
Terminally
sterilised products
Preparation
of components and most products should be done in at least a grade
D environment in order to give low risk of microbial and particulate
contamination, suitable for filtration and sterilisation. Where there
is unusual risk to the product because of microbial contamination,
for example, because the product actively supports microbial growth
or must be held for a long period before sterilisation or is necessarily
processed not mainly in closed vessels, preparation should be done
in a grade C environment.
Filling of
products for terminal sterilisation should be done in at least a grade
C environment.
Where the product
is at unusual risk of contamination from the environment, for example
because the filling operation is slow or the containers are wide-necked
or are necessarily exposed for more than a few seconds before sealing,
the filling should be done in a grade A zone with at least a grade
C background. Preparation and filling of ointments, creams, suspensions
and emulsions should generally be done in a grade C environment before
terminal sterilisation.
Aseptic
preparation
Components
after washing should be handled in at least a grade D environment.
Handling of sterile starting materials and components, unless subjected
to sterilisation or filtration through a microorganism retaining filter
later in the process, should be done in a grade A environment with
a grade B background.
Preparation
of solutions which are to be sterile filtered during the process should
be done in a grade C environment; if not filtered, the preparation
of materials and products should be done in a grade A environment
with a grade B background.
Transfer of
partially closed containers, as used in freeze drying, should, prior
to the completion of stoppering, be done either in a grade A environment
with grade B background or in sealed transfer trays in a grade B environment.
Preparation
and filling of sterile ointments, creams, suspensions and emulsions
should be done in a grade A environment, with a grade B background,
when the product is exposed and is not subsequently filtered.'
Comparison
of Various Standards
Shown in Table
6 is a comparison of the classes given in the standards discussed
above.
Table
6: A comparison of international standards
Country
and standard
|
U.S.A.
209D
|
U.S.A.
209E
|
Britain
BS 5295
|
Australia
AS 1386
|
France
AFNOR X44101
|
Germany
VD I.2083
|
ISO
standard
|
Date
of current issue
|
1988
|
1992
|
1989
|
1989
|
1972
|
1990
onwards
|
1997
|
|
|
|
|
|
-
|
0
|
|
|
1
|
M1.5
|
C
|
0.035
|
-
|
1
|
3
|
|
10
|
M2.5
|
D
|
0.35
|
-
|
2
|
4
|
|
100
|
M3.5
|
E
or F
|
3.5
|
4
000
|
3
|
5
|
|
1
000
|
M4.5
|
G
or H
|
35
|
-
|
4
|
6
|
|
10
000
|
M5.5
|
J
|
350
|
400
000
|
5
|
7
|
|
100
000
|
M6.5
|
K
|
3500
|
4
000 000
|
6
|
8
|
The above information
on cleanroom standards have been extracted from the handbook 'Cleanroom
Technology' written by Bill Whyte.