Clean Room Classification

Classifications Of Clean Rooms

Clean rooms are classified by the cleanliness of their air. The method most easily understood and most universally applied is the one suggested in the earlier versions (A to D) of Federal Standard 209 of the USA. In this old standard the number of particles equal to and greater than 0.5 m m is measured in one cubic foot of air and this count used to classify the room. The most recent 209E version has also accepted a metric nomenclature. In the UK the British Standard 5295, published in 1989, is also used to classify clean rooms. This standard is about to be superseded by BS EN ISO 14644-1. Federal Standard 209 This standard was first published in 1963 in the US and titled "Clean Room 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 and Technology 940 East Northwest Highway Mount Prospect, Illinois, 60056 USA Tel: 0101 708 255 1561 Fax: 0101 708 255 1699 e-mail: iest@iest.org: The clean room classifications given in the earlier A to D versions are shown in Table 1. Table 1: Federal Standard 209D Class Limits In the new 209E published in 1992 the airborne concentrations in the room are given inmetric units, (i.e. per m3), and the classifications of the room defined as the logarithm of theairborne concentration of particles ³ 0.5 m m e.g. a Class M3 room has a particle limit forparticles ³ 0.5 m m of 1000/m3. This is shown in Table 2. Table 2: Federal Standard 209E Airborne Particulate Cleanliness Classes 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 e-mail: info@bsi.org.uk Because of the imminent publication of EN ISO 14644-1 parts of this British Standard have a limited life. Parts will be superseded by the ISO standards as they appear as an EN standard. The British Standard is in five parts. These are: Part 0 - General introduction and terms and definitions for clean rooms and clean air devices. (4 pages) Part 1 - Specification for clean rooms and clean air devices. (14 pages) Part 2 - Method for specifying the design, construction and commissioning of clean room and clean air devices. (14 pages) Part 3 - Guide to operational procedures and disciplines applicable to clean rooms and clean air devices. (6 pages) Part 4 - Specification for monitoring clean rooms and clean air devices to prove continued compliance with BS 5295. (10 pages) Part 1 of the standard contains ten classes of environmental cleanliness. Shown in Table 3 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. Table 3 BR 525  Environmental Cleanliness Classes BS EN ISO Standard Because of the large number of clean room standards produced by individual countries it is very desirable that one worldwide standard of clean room classification is produced. The first ISO standard on clean rooms has been published (June 1999) as 14644-1 ‘Classification of Air Cleanliness’. It is about to be adopted as a European standard and hence a standard for all countries in the EU. This standard is available from standard organizations throughout the world and in the UK is available from the BSI. Shown in Table 4 is the classification that has been adopted. Table 4. Selected ISO 209 airborne particulate cleanliness classes for clean rooms and clean zones. The table is derived from the following formula: where: Cn represents the maximum permitted concentration ( in particles/m3 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 4 shows a crossover to the old FS 209 classes e.g. ISO 5 is equivalent to the old FS 209 Class 100. The occupancy state is defined in this standard as follows: As built: the condition where the installation is complete with all services connected and functioning but with no production equipment, materials, or personnel present. At-rest: The condition where the installation is complete with equipment installed and operating in a manner agreed between the customer and supplier, but with no personnel present. Operational: The condition where the installation is functioning in the specified manner, with the specified number of personnel present and working in the manner agreed upon. The standard also gives a method by which the performance of a clean room 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 4. Smaller particles (ultrafine) 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. Fibers 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/m3 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 Clean Room Classification EU GGMP The most recent set of standards for use in Europe came into operation on the 1st of January 1997. This is contained in a ‘Revision of the Annex 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 clean rooms: For the manufacture of sterile medicinal products four grades are given. The airborne particulate classification for these grades is given in the following table. 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. 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. Examples of operations to be carried out in the various grades are given in the table below. (see also par. 11 and 12). Additional microbiological monitoring is also required outside production operations, e.g. after validation of systems, cleaning and sanitization. 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 sterilization should be installed in at least a grade D environment. Guideline on Sterile Drug Products Produced by Aseptic Processing This document is produced by the FDA in the USA and published in 1987. Two areas are defined. The ‘critical area’ is where the sterilized dosage form, containers, and closures are exposed to the environment. The ‘controlled area’ is where unsterilized product, in-process materials, and container/closures are prepared. The environmental requirements for these two areas given in the Guide are as follows: Critical areas ‘Air in the immediate proximity of exposed sterilized containers/closures and filling/closing operations is of acceptable particulate quality when it has a per-cubic foot particle count of no more than 100 in a size range of 0.5 micron and larger (Class 100) when measured not more than one foot away from the work site, and upstream of the air flow, during filling/closing operations. The agency recognizes that some powder filling operations may generate high levels of powder particulates, which by their nature do not pose a risk of product contamination. It may not, in these cases, be feasible to measure air quality within the one-foot distance and still differentiate "background noise" levels of powder particles from air contaminants, which can impeach product quality. In these instances, it is nonetheless important to sample the air in a manner, which to the extent possible characterizes the true level of extrinsic particulate contamination to which the product is exposed. Air in critical areas should be supplied at the point of use as HEPA filtered laminar flow air, having a velocity sufficient to sweep particulate matter away from the filling/closing area. Normally, a velocity of 90 feet per minute, plus or minus 20%, is adequate, although higher velocities may be needed where the operations generate high levels of particulates or where equipment configuration disrupts laminar flow. Air should also be of a high microbial quality. An incidence of no more than one colonyforming unit per 10 cubic feet is considered as attainable and desirable. Critical areas should have a positive pressure differential relative to adjacent less clean areas; a pressure differential of 0.05 inch of water is acceptable’. Controlled areas ‘Air in controlled areas is generally of acceptable particulate quality if it has a per-cubic-foot particle count of not more than 100,000 in a size range of 0.5 micron and larger (Class 100,000) when measured in the vicinity of the exposed articles during periods of activity. With regard to microbial quality, an incidence of no more than 25 colony forming units per 10 cubic feet is acceptable. In order to maintain air quality in controlled areas, it is important to achieve a sufficient airflow and a positive pressure differential relative to adjacent uncontrolled areas. In this regard, airflow sufficient to achieve at least 20 air changes per hour and, in general, a pressure differential of at least 0.05 inch of water (with all doors closed), are acceptable. When doors are open, outward airflow should be sufficient to minimize ingress of contamination’. This information was compiled from various sources including the listed agencies and the handbook ‘Clean Room Technology’ as written by Bill Whyte. Cleanroom Classifications Cleanrooms are classified by how clean the air is. In Federal Standard 209 (A to D) of the USA, the number of particles equal to and greater than 0.5mm is measured in one cubic foot of air, and this count is used to classify the cleanroom. This metric nomenclature is also accepted in the most recent 209E version of the Standard. Federal Standard 209E is used domestically. The newer standard is TC 209 from the International Standards Organization. Both standards classify a cleanroom by the number of particles found in the laboratory's air. The cleanroom classification standards FS 209E and ISO 14644-1 require specific particle count measurements and calculations to classify the cleanliness level of a cleanroom or clean area. In the UK, British Standard 5295 is used to classify cleanrooms. This standard is about to be superseded by BS EN ISO 14644-1. 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 mm or larger permitted per cubic foot of air. The standard also allows interpolation, so it is possible to describe e.g. "class 2000." 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 cubic metre of air. So, for example, an ISO class 5 cleanroom has at most 105 = 100,000 particles per m³. Both FS 209E and ISO 14644-1 assume log-log relationships between particle size and particle concentration. For that reason, there is no such thing as zero particle concentration. Ordinary room air is approximately class 1,000,000 or ISO 9. ^ Back to top ISO 14644-1 Cleanroom Standards Class maximum particles/m3 FED STD 209E equivalent >=0.1 µm >=0.2 µm >=0.3 µm >=0.5 µm >=1 µm >=5 µm ISO 1 10 2 ISO 2 100 24 10 4 ISO 3 1,000 237 102 35 8 Class 1 ISO 4 10,000 2,370 1,020 352 83 Class 10 ISO 5 100,000 23,700 10,200 3,520 832 29 Class 100 ISO 6 1,000,000 237,000 102,000 35,200 8,320 293 Class 1,000 ISO 7 352,000 83,200 2,930 Class 10,000 ISO 8 3,520,000 832,000 29,300 Class 100,000 ISO 9 35,200,000 8,320,000 293,000 Room Air BS 5295 Cleanroom Standards 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 Class 4 20,000 40,000 4,000 ^ Back to top

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

British Standard 5295

ISO Standard

Pharmaceutical Cleanroom Classification

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.

FS209E and ISO Cleanroom Standards

Terra Universal is the leading expert in the design and fabrication of critical-environment applications. We offer a complete range of equipment, furnishing and supplies for cleanroooms and laboratories. Following are the rigorous standards to which Terra Universal adheres.

Before global cleanroom classifications and standards were adopted by the International Standards Organization (ISO), the U.S. General Service Administration’s standards (known as FS209E) were applied virtually worldwide. However, as the need for international standards grew, the ISO established a technical committee and several working groups to delineate its own set of standards.

FS209E contains six classes, while the ISO 14644-1 classification system adds two cleaner standards and one dirtier standard (see chart below). The "cleanest" cleanroom in FS209E is referred to as Class 1; the "dirtiest" cleanroom is a class 100,000. ISO cleanroom classifications are rated according to how much particulate of specific sizes exist per cubic meter (see second chart). The "cleanest" cleanroom is a class 1 and the "dirtiest" a class 9. ISO class 3 is approximately equal to FS209E class 1, while ISO class 8 approximately equals FS209E class 100,000.

By law, Federal Standard 209E can be superseded by new international standards. It is expected that 209E will be used in some industries over the next five years, but that eventually it will be replaced internationally by ISO 14644-1.

Airborne Particulate Cleanliness Class Comparison

ISO 14644-1	FEDERAL STANDARD 209E
ISO Class	English	Metric
ISO 1
ISO 2
ISO 3	1	M1.5
ISO 4	10	M2.5
ISO 5	100	M3.5
ISO 6	1,000	M4.5
ISO 7	10,000	M5.5
ISO 8	100,000	M6.5
ISO 9

Airborne Particulate Cleanliness Classes (by cubic meter):

CLASS	Number of Particles per Cubic Meter by Micrometer Size
	0.1 micron	0.2 micron	0.3 micron	0.5 micron	1 micron	5 microns
ISO1	10	2
ISO2	100	24	10	4
ISO3	1,000	237	102	35	8
ISO4	10,000	2,370	1,020	352	83
ISO5	100,000	23,700	10,200	3,520	832	29
ISO6	1,000,000	237,000	102,000	35,200	8,320	293
ISO7				352,000	83,200	2,930
ISO8				3,520,000	832,000	29,300
ISO9				35,200,000	8,320,000	293,000

In cleanrooms, particulate concentration changes over time — from the construction and installation of equipment to its operational status. ISO delineates three cleanroom classification standards: as-built, at-rest and operational. As instruments and equipment are introduced and particulates rise, an "as-built" cleanroom becomes an "at-rest" cleanroom. When people are added to the matrix, particulate levels rise still further in the "operational" cleanroom.

ISO 14644-2 describes the type and frequency of testing required to conform to certain standards. The following tables indicate mandatory and optional tests.

Required Testing (ISO 14644-2)

Schedule of Tests to Demonstrate Continuing Compliance
Test Parameter	Class	Maximum Time Interval	Test Procedure
Particle Count Test	<= ISO 5	6 Months	ISO 14644-1 Annex A
	> ISO 5	12 Months
Air Pressure Difference	All Classes	12 Months	ISO 14644-1 Annex B5
Airflow	All Classes	12 Months	ISO 14644-1 Annex B4

Optional Testing (ISO 14644-2)

Schedule of Additional Optional Tests
Test Parameter	Class	Maximum Time Interval	Test Procedure
Installed Filter Leakage	All Classes	24 Months	ISO 14644-1 Annex B6
Containment Leakage	All Classes	24 Months	ISO 14644-1 Annex B4
Recovery	All Classes	24 Months	ISO 14644-1 Annex B13
Airflow Visualization	All Classes	24 Months	ISO 14644-1 Annex B7

Today, in addition to ISO 14644-1 and ISO 14644-2, eight other cleanroom standards documents are being prepared. Many are in the final voting stage and can be legally used in the trade (see chart).

ISO Document	Title
ISO 14644-1	Classification of Air Cleanliness
ISO 14644-2	Cleanroom Testing for Compliance
ISO 14644-3	Methods for Evaluating and Measuring Cleanrooms and Associated Controlled Environments
ISO 14644-4	Cleanroom Design and Construction
ISO 14644-5	Cleanroom Operations
ISO 14644-6	Terms, Definitions and Units
ISO 14644-7	Enhanced Clean Devices
ISO 14644-8	Molecular Contamination
ISO 14698-1	Biocontamination: Control General Principles
ISO 14698-2	Biocontamination: Evaluation and Interpretation of Data
ISO 14698-3	Biocontamination: Methodology for Measuring Efficiency of Cleaning Inert Surfaces

The USA source for ISO documents is:

Institute of Environmental Sciences & Technology (IEST)
5005 Newport Drive, Suite 506
Rolling Meadows, IL 60008-3841
http://www.iest.org
Phone: (847) 255-1561
Fax: (847) 255-1699

The source for FS209E documents at the General Services Administration is:

Standards Order Desk
Naval Publications and Forms Center
700 Robbins Avenue
Section D BLD4
Philadelphia, PA 19111
Phone: (215) 697-2667
Fax: (215) 697-2978

ISO and Federal Air Change Rates for Cleanrooms

A critical factor in cleanroom design is controlling air-change per hour (ACH), also known as the air-change rate, or ACR. This refers to the number of times each hour that filtered outside air replaces the existing volume in a building or chamber. In a normal home, an air-conditioner changes room air 0.5 to 2 times per hour. In a cleanroom, depending on classification and usage, air change occurs anywhere from 10 to more than 600 times an hour.

ACR is a prime variable in determining ISO and Federal cleanliness standards. To meet optimal standards, ACR must be painstakingly measured and controlled. And there is some controversy. In an appendix to its ISO 14644-1 cleanliness standard, the International Standards Organization addressed applications for microelectronic facilities only. (ISO classes 6 to 8; Federal Standards 1,000, 10,000 and 100,000.) The appendix contained no ACR standards for pharmaceutical, healthcare or biotech applications, which may require higher ACR regulations.

According to current research, case studies and experiments, using an ACR range (rather than one set standard) is a better guideline for cleanliness classification. This is true because the optimal ACR varies from cleanroom to cleanroom, depending on factors such as internal equipment, staffing and operational purpose. Everything depends on the level of outside contaminants trying to enter the facility versus the level of contaminants being generated on the inside.

The breadth of these ranges reflects how dramatically people and processes affect cleanliness. Low-end figures within each contamination class generally indicate air velocity and air change requirements for an as-built or at-rest facility—where no people are present and no contaminating processes under way. When there are people and processes producing contaminants, more air changes are required to maintain optimal cleanliness standards. For instance, some manufacturers insist on as many as 720 air changes per hour to meet Class 10 standards.

Determining the appropriate number of air changes for a particular application requires careful evaluation of factors such as the number of personnel, effectiveness of garbing protocol, frequency of access, and cleanliness of process equipment.

Rajan Jaisinghani, in his paper "Energy Efficient Low Operating Cost Cleanroom Airflow Design," presented at ESTECH 2003, recommended the following ranges based on FS209E classifications:

FS Cleanroom Class	ISO Equivalent Class	Air Change Rate
1	ISO 3	360-540
10	ISO 4	300-540
100	ISO 5	240-480
1,000	ISO 6	150-240
10,000	ISO 7	60-90
100,000	ISO 8	5-48

Jaisinghani’s recommendations concur with other recent studies of ACR, which criticize some existing air rate standards (developed in the 1990s) as being unscientific because they are based on fans and filters inferior to today’s models. So when these older standards are applied, the resulting ACR is often too high. In fact, some studies have found that reducing the ACR (and its attendant air turbulence) can result in a cleaner atmosphere.

This was demonstrated in a study conducted by Pacific Gas and Electric (San Francisco) and the Lawrence Berkeley National Laboratory (Berkeley). The study measured air change rates in several ISO Class-5 cleanrooms and came to the conclusion that there is "no consistent design strategy for air change rate, even for cleanrooms of the same cleanliness classification."

ACR rates have critical design implications, especially when considering desired cleanliness, fan size and lower energy costs. The PG&E/Berkeley study caused many designers to reduce fan sizes. In short, a lower ACR often resulted in cleaner air.

The study revealed three abiding principles:

• Lower air change rates result in smaller fans, which reduce both initial investment and construction cost.
• Fan power is proportional to the cube of air change rates or airflow. A 30-percent reduction in air change rate results in a power reduction of approximately 66 percent.
• By minimizing turbulence, lower airflow may improve cleanliness.

The study focused on Class-5 cleanrooms, concluding that an ACR range of from 250 to 700 air changes per hour is standard, but that "actual operating ACRs ranged from 90 to 625." It added that all of these optimized cleanrooms were certified and performing at ISO Class-5 conditions with these lower ACRs. Finally, the study concluded that rarely does a Class-5 facility require an ACR of more than 300.

The study also found that the "[b]est practice for ACRs is to design new facilities at the lower end of the recommended ACR range," with variable speed drives (VSDs) built in so that air flow adjustments can be made under actual operating conditions.

In his report "An examination of ACRs: An opportunity to reduce energy and construction costs," Peter Rumsey, PE, CEM, essentially concurred with the PG&E-commissioned study by Berkeley. Rumsey issued a caveat, then brushed it aside by citing research subsequent to Berkeley’s: "Air cleanliness is a critical component of any cleanroom, far outweighing energy saving priorities. Designers and operators need evidence from others who have tried similar strategies in order to address the perceived risks of lowering air change rates."

Rumsey then went on to cite studies done by International Sematech (Austin, Texas); the Massachusetts Institute of Technology (Cambridge, Mass.); Intel (Santa Clara, Calif.); and Sandia National Laboratories (Albuquerque, N.M.), which echoed the Berkeley study.

In summary, current research and thinking on air change rates indicate that some existing standards are too high and can be lowered while still meeting all ACR criteria.

Federal and ISO Ceiling Fan Coverage Specifications

Achieving the optimal air change rate requires proper ceiling fan coverage. The cleanest modular cleanroom incorporates filter/fan units (FFUs) in every 2’ x 4’ (610 mm x 1219 mm) ceiling bay. This near-100% coverage provides a laminar flow of filtered air to quickly remove contaminants from the room, thus meeting FS209E standards for Class 10 and ISO Class 1 standards.

Such coverage, especially in a large cleanroom, can lead to higher energy consumption, thus increasing costs for both initial construction and ongoing operation. In most cases, a smaller percentage of ceiling coverage produces adequate cleanliness.

This table illustrates the percentage of ceiling coverage recommended for each cleanliness class, again as a range:

Class	Ceiling Coverage (Percentage)
ISO 8 (Class 100,000)	5 – 15%
ISO 7 (Class 10,000)	15 – 20%
ISO 6 (Class 1,000)	25 – 40%
ISO 5 (Class 100)	35 – 70 %
ISO 4 (Class 10)	50 – 90%
ISO 3 (Class 1)	60 – 100%
ISO 1-2	80 – 100%

Federal and ISO Airflow Velocity Standards

In addition to ACR and ceiling coverage, the third factor integral to maintaining cleanliness is fan-generated air speed. Again, higher airflow velocity results in a "cleaner" cleanroom. The term "ventilation efficiency" refers to the speed of filtered air passing through the cleanroom in addition to the number of air changes per hour (ACH or ACR).

An earlier chart showed a range of recommended air change rates (ACRs) for different classes of cleanrooms. Ranges are given because as-built and at-rest facilities require a smaller ACR than an operational cleanroom, where both people and equipment are actively engaged. Non-operational cleanrooms are found in the lower range; operational cleanrooms higher.

Combining all three factors—ACR, ceiling coverage and airflow velocity—results in the following table:

Class ISO 146144-1 (Federal Standard 209E)	Average Airflow Velocity m/s (ft/min)	Air Changes Per Hour	Ceiling Coverage
ISO 8 (Class 100,000)	0.005 – 0.041 (1 – 8)	5 – 48	5 – 15%
ISO 7 (Class 10,000)	0.051 – 0.076 (10 -15)	60 – 90	15 – 20%
ISO 6 (Class 1,000)	0.127 – 0.203 (25 – 40)	150 – 240	25 – 40%
ISO 5 (Class 100)	0.203 – 0.406 (40 – 80)	240 – 480	35 – 70%
ISO 4 (Class 10)	0.254 – 0.457 (50 – 90)	300 – 540	50 – 90%
ISO 3 (Class 1)	0.305 – 0.457 (60 – 90)	360 – 540	60 – 100%
ISO 1 – 2	0.305 – 0.508 (60 – 100)	360 – 600	80 – 100%

Before deciding on the appropriate velocity and air changes for your application, Terra Universal recommends careful evaluation of factors such as number of personnel, effectiveness of garbing protocol, access frequency and cleanliness of process equipment. Once the required air change figure is established, the number of required FFUs can be determined using this formula: No. of FFUs = (Air Changes/Hour ÷60) x (Cubic ft. in room÷ 650*)
*CFM output of a loaded FFU

Meeting Class 100 standards using the low-end air change recommendation (240/hour) inside a 12’ x 12’ x 7’ (3302 mm x 3302 mm x 2134 mm) cleanroom, with 1008 cu. ft. of volume, requires 6 FFUs. To meet the same standard using the high-end air change recommendation (480/hour) requires 12 FFUs.

Positive Pressure

Cleanrooms are designed to maintain positive pressure, preventing "unclean" (contaminated) air from flowing inside and less-clean air from flowing into clean areas. The idea is to ensure that filtered air always flows from cleanest to less-clean spaces. In a multi-chambered cleanroom, for instance, the cleanest room is kept at the highest pressure. Pressure levels are set so that the cleanest air flows into spaces with less-clean air. Thus, multiple pressure levels may need to be maintained.

A differential air pressure of 0.03 to 0.05 inches water gage is recommended between spaces. In order to ensure that pressure differentials remain constant when doors are opened, or other events occur, control systems must be in place.

Laminar and Turbulent Air Flow

ISO 5 (Class 100) and cleaner facilities rely on unidirectional, or laminar, airflow. Laminar airflow means that filtered air is uniformly supplied in one direction (at a fixed velocity) in parallel streams, usually vertically. Air is generally recirculated from the base of the walls back up to the filtering system.

ISO 6 (Class 1,000) and above cleanrooms generally utilize a non-unidirectional, or turbulent, airflow. This means the air is not regulated for direction and speed. The advantage of laminar over turbulent airflow is that it provides a uniform environment and prevents air pockets where contaminants might congregate.

What is Federal Standard 209E?

Simply, it's an official document that outlines the classes of air cleanliness. You can read it here. This document is in Adobe's Acrobat PDF format. If you do not have the FREE Acrobat Reader program you may download it here.

 

How is cleanroom cleanliness measured?

Cleanroom cleanliness is measured by how many micron sized particles pass through one cubic foot of air per minute (cfm). This is how a cleanroom's classification is determined.

 

What do the classifications mean?

A Class 10 cleanroom has no more than ten micron sized particles passing through each cubic foot of air per minute. That's really clean. A Class 100,000 may have up to one hundred thousand particles per cubic foot. For comparison, your home has around 300,000 and a hospital operating room has about 1,000.

Clean Room classification

There are certain environments where it is necessary to limit the quantity of airborne particles. This applies, for example, in the pharmaceutical, electronics and food industries and in certain hospital environments.

The international EN ISO 14644-1 standard (classes 1 to 9) is used for the classification of air cleanliness. This is the official standard, but the US Federal standard 209E (classes 1 to 100 000) is also widely spread. The pharmaceutical industry is regulated by Good Manufacturing Practice (GMP) standards (class A to D).