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Derek Mowlds e: derek.mowlds@pmg.ie
designing
BUILDING SERVICES an introduction to cleanroom technology Substantial foreign investment by top international companies over a 40-year period has created a significant international pharmaceutical sector in Ireland. Since the late 1950s in particular, foreign direct investment in Ireland has been attracted by low rates of corporate tax and this has contributed significantly to the development of the sector. Other contributory factors are:— — High skill base and third level graduates; — Excellent compliance record (FDA etc); — Access to large European Market; — Presence of top International design firms. In this article we give an overview of the pharmaceutical industry in Ireland and give a brief description of cleanroom technology which is critical to the successful operation of the sector. What is a Cleanroom? A cleanroom is a room in which the concentration of airborne particles is controlled, and which is constructed and used in a manner to minimise the
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introduction, generation, and retention of particles inside the room. Other relevant parameters such as temperature, humidity and pressure are controlled as necessary to meet product, personnel and safety requirements. The only way to control contamination is to control the total environment. Air flow rates and direction, pressurisation, temperature, humidity and specialised filtration all need to be tightly controlled. The sources of these particles also need to be controlled or eliminated whenever possible. There is more to a cleanroom than HEPA filters. Cleanrooms are planned and constructed using strict protocol and methods. They are frequently found in electronics, pharmaceutical, biopharmaceutical, medical device industries and other critical manufacturing environments. Clean areas for the manufacture of sterile products are classified according to the required characteristics of the
environment. Each manufacturing operation requires an appropriate environmental cleanliness level in the operational state in order to minimise the risks of particulate or microbiological contamination of the product or materials being handled (from Annex 6, WHO Technical Report Series, No: 902, 2002). Cleanroom Standards The standard of cleanrooms is defined by the number and size of particles that are permitted per unit volume of air. Previously there were a number of different standards in use around the world, making it difficult to compare cleanrooms in different locations. For this reason an ISO standard has been developed (Table A). The ISO 14644-1 standards 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. When stating the classification of a cleanroom using the ISO system, one must specify the occupancy state at a particular
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an introduction to cleanroom technology class. For example: — “As built” – no process equipment or people; — “At Rest” – process equipment, no people; — “Operational” — process equipment and people; – Particle size(s) — ISO Class 5 alone is meaningless — ISO Class 5 “As Built” at 0.2 and 0.5 microns — ISO Class 7 “At Rest” at 0.5 and 5.0 microns HVAC Design for different classifications Typical air change rates for various classifications are given in Table B (see page 22). While these are not prescribed in the ISO standard, they have been shown to achieve the required particulate levels when applied. An early assessment of the HVAC systems required for a particular installation is highly recommended. These may be affected by process equipment requirements, temperature and humidity, containment and air distribution. Air handling units and ductwork tend to require a lot of plant space and need to be incorporated into the facility design in advance of planning. High air change rates may dictate the type of system selected based on installation cost, building arrangement, energy usage and flexibility for the future. Some typical HVAC
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Table A particles/m3 Class
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
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
Table A: ISO 14644-1 cleanroom standard
arrangements are described here:— (A) Fan filter units (FFU) and make up air handling unit (MAU): For the higher ISO classes (Class 5 – Class 2), 100% filter coverage is required at ceiling level, provided by fan filter units which take recirculated air from a common plenum and deliver it in a unidirectional/laminar pattern to the clean room. The air displaces down through the cleanroom and is returned via a
raised floor or sidewall registers to the common plenum. Cooling and fresh air make up is provided to the plenum only via a central AHU. The option reduces large and lengthy duct runs and allows the use of low pressure fans. Fan filter units may also be used in lower grade areas. They allow flexibility in that they can be easily relocated without interruptive works to ductwork etc. It is also possible to raise the classification of an area by
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an introduction to cleanroom technology adding more fan filters. Fan filter units tend to be most effective in large manufacturing areas with large ceiling areas; individual room temperature and RH control is more suited to a ducted system. (B) Ceiling HEPA Filters, recirculation AHU’s with common MAU: Where a common plenum arrangement is difficult to achieve, a ducted system may be employed to distribute supply and return air to the cleanroom. Ceiling HEPA filters are distributed to achieve a reasonable distribution of filtered, conditioned air to the space, the pattern of which tends to be random and does not provide unidirectional flow throughout. This arrangement is most common in Class 8 rooms. Most of the air is handled via recirculating AHU’s, each unit serving a zone or number of zones and will provide sensible heating and cooling. Fresh air and moisture content is handled via a common MAU serving the re-circ units. (C) Ceiling HEPA Filters, central AHU: In a variation to option (B), some facilities prefer to install standalone air handling units to serve an area or areas. Each AHU provides conditioned air to the space and also provides fresh air as required. This option allows
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each area to remain autonomous and can remain active, even if an adjacent area is not operational. Room Pressure Control Cleanroom pressures are usually positive relative to uncontrolled areas. Generally, a value of 12.5 Pa pressure for the clean space relative to unclassified areas is recommended. Higher pressures tend to result in whistling noises and make doors difficult to open or close. In cleanroom installations with multiple ISO classes, the trend is to maintain a positive pressure of a minimum of 5 Pa between adjacent clean spaces of differing ratings, with the higher pressure in the space at the higher cleanliness rating.
Other factors affecting pressurisation are product protection, containment and personnel protection. It is advisable to allow adequate capacity in air handling plant to achieve the correct room pressures during commissioning. Room pressure calculations are based on theoretical door crack dimensions and air tight construction. Derek Mowlds is a Project Manager at PM Group (Project Management Group), Ireland’s largest full service A&E firm, providing professional services in project and construction management, architectural and engineering design, and technical consultancy.
Table B ISO Class
Velocity
Air Changes
Class 2 Undirectional
0.43 to 0.51 m/s 510
600
Class 3 (1) Undirectional
0.36 to 0.43 m/s 420
510
Class 4 (10) Undirectional
0.30 to 0.36 m/s 360
420
Class 5 (100) Undirectional
0.23 to 0.28 m/s 270
330
Class 6 (1000) Undirectional
0.13 to 0.18 m/s 150
210
Class 7 (10,000) Undirectional
0.04 to 0.09 m/s 50
100
Class 8 (100,000) Undirectional
0.02 to 0.04 m/s 25
35
Table B: HVAC design for different classifications
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