Cleanroom Classifications and Standards

Cleanroom technology has developed into a specialist field with its own technical journals, its own conferences and exhibitions, and its own language of technical terms and classifications.   In a previous article titled, “Airborne Contamination Control” (Food Technology, June 2001) we examined the reason for such environmental control in the food industries.  In this article, we will look at relevant standards and clarify the myriad classification systems.
Cleanroom Standards

The main cleanroom standards of interest in New Zealand are as follows:

AS 1807 series  (25 parts),

AS 1386.5:1989  (Were 7 parts)

The remaining parts of 1386 have been superceded by the AS/NZS ISO 14644 series. Both the 1386 and 14644 have been widely used in New Zealand as a reference for design, operation and validation of cleanrooms.

FED-STD-209E:1992

Until recently, this standard was used throughout the US and by auditors from the US.  It was cancelled in November 2001 in favour of ISO 14644, but its classification system will undoubtedly be used for years to come.

ISO 14644 Cleanrooms and associated controlled environments (7 parts)

ISO 14698 Biocontamination control  (3 parts)

This set of 10 documents has now been fully developed and currently makes up the global cleanroom standard. They are also available in AS/NZS format, which refers to the 1807 test method series of standards.

Cleanroom Classifications

Cleanrooms are classified according to the concentration of airborne particles.  The following table shows the ISO 14644-1 classification for the main particle sizes of interest together with comparable AS1386 and FED-STD-209E classifications.

ISO classes 1-4 are mainly applicable to the semi-conductor industry and we are not aware of any such cleanrooms in New Zealand.  Classes 5, 7 and 8 are most common.

The airborne particle concentration in a cleanroom is highly dependent on the occupancy of the room because occupants are major particle sources.  So the classification of the cleanroom must be defined at one or more of the room’s occupancy states, viz. “as-built”, “at rest”, or “operational”.  For example, a cleanroom may be class 7 (= class 10000 = class 350) in the “operational” state and class 5 (= class 100 = class 3.5) in the “at rest” state.

Good Manufacturing Practice (GMP)

There are two methods by which cleanrooms and semi-clean rooms have been specified in the Food Industry.

MAF have traditionally specified the air filters required.  For example air filtration of EU5 or better for processing areas is specified in the Meat Industry Agreed Standard 2 – Design and Construction (1).  This may be appropriate for low-level clean spaces, but is not ideal.  The filtration efficiency is only one factor determining the cleanliness of the space – the airflow, the room construction, the room pressurisation and the operations in the room are also important factors.  Furthermore, unless the air filters are well manufactured and properly installed, a significant proportion of air can bypass the installed filters.

The other method is to specify the air quality using a cleanroom classification system as described above.   Until recently the Australian Therapeutic Goods Association used the AS1386 classification.  For example, in the code of GMP for medicinal products (2), the general requirement is “Class 7000” which is extrapolated from AS1386.  This requirement is commonly used in New Zealand for food processing areas. We still test rooms to this standard, but new facilities and an increasing number of existing facilities have now been set up or reballanced to comply with the ISO 14644 standard.    Also commonly used in New Zealand is the UK (European) “Orange Guide” (3) which defines 4 grades of cleanrooms for manufacture of sterile medicinal products according to air quality in both the “at rest” and “in operation” states. The Orange Guide has now also been superceded by the P.I.C.Scheme:2009

Beware of using grades for cleanrooms!  Although the definitions above are commonly used, other codes for GMP such as TGA (4) and MAF – ACVM (5) define grades A to D slightly differently.

Testing and Validation of Cleanrooms

When a cleanroom has been classified, it can be tested for compliance with the requirements for the classification.   Generally cleanrooms are tested at least annually by an IANZ accredited test laboratory.  In some situations more regular checks, or even continuous monitoring is required.

References

(1) Industry Agreed Standard 2 – Design and Construction, Animal Products Group, New Zealand Food Safety Authority. Section 5.3

( available on-line at http://www.nzfsa.govt.nz/meatdoc/meatman/manual-2v  )

(2) Australian Code of Good Manufacturing Practice For Therapeutic Goods – Medicinal Products, Therapeutic Goods Association, 1990. Page 11.

(3) Rules and Guidance for Pharmaceutical Manufacturers and Distributors, (known as “The Orange Guide”) Medicines Control Agency, The Stationery Office, London, 1997.  Annex 1.

(4) Australian Code of Good Manufacturing Practice For Therapeutic Goods – Medicinal Products, Therapeutic Goods Association, 1990. Page 56.

(5) ACVM (Agricultural Compounds & Veterinary Medicines) – Guideline for Good Manufacturing Practice, Ministry of Agriculture and Forestry, Wellington, NZ, 1999, Annex 1.

( available on-line at http://www.nzfsa.govt.nz/acvm/publications/standards-guidelines )