Cleanroom and Critical Environment

A cleanroom is an enclosed manufacturing space that is designed to protect specialty consumer goods such as microelectronics, pharmaceuticals, food, or aerospace equipment from particulate contaminants. Complex or large-scale productions may require sizable, state-of-the art cleanrooms, while in other circumstances, modular designs may suffice. What all cleanrooms have in common is that the room itself is under positive pressure and the air is filtered.

Air Regulations in Cleanrooms

The air in a cleanroom is processed constantly to scrub the protected environment of microscopic particulates. This is accomplished by forcing the air in a laminar or turbulent direction through HEPA or ULPA filters until it meets the maximum allowable particulate size and count for the cleanroom’s ISO (International Organization for Standardization) Standards classification. Starting at ISO Class 3, the lower the cleanroom class is, the cleaner it must be, therefore the higher the rate of air change needs to be.

The ISO 14644 Standards series is a comprehensive guidance for the "standardization of equipment, facilities, and operational methods for cleanrooms and associated controlled environments." Additional standards by ISO, the Food and Drug Administration (FDA) Current Good Manufacturing Processes (CGMP), and the European Union’s Guidance on Good Manufacturing Practice (GMP) include requirements for processes and pharmaceuticals that must exclude microbes during production.

Cleanroom Classes and Standards

• ISO 14644-1 (International Organization for Standardization) gives guidance for general cleanrooms (see Table 1). Zero particle concentration does not exist, so values are rounded to the nearest whole number. This standard does not specify limits for microorganisms. Required and optional cleanroom testing are shown in Table 2 and Table 3, respectively.
• Federal Standard 209E was replaced by ISO 14644 in 2001 and is still being phased out of use. Equivalents to ISO 14644 are listed in Table 1.
• ISO 14698 is applied when biological contamination could be an issue in a cleanroom.
• FDA’s Aseptic Processing Guidance details classification parameters for manufacturing sterile drug and biological products using aseptic processing to meet CGMP regulations (see Table 4).
• EU GMPs Annex 1 sets particulate limits for aseptically processed products destined for Europe (see Table 5).

Table 1: Air Cleanliness Classes for Cleanrooms - ISO 14644-1

Classification	FED STD 209E Equivalent	Maximum Concentration Limits (particles/m3)
		≥0.1µm	≥0.2µm	≥0.3µm	≥0.5µm	≥1µm	≥5µm
ISO 1	NA	10	2	0	0	0	0
ISO 2	NA	100	24	10	4	0	0
ISO 3	Class 1	1,000	237	102	35	8	0
ISO 4	Class 10	10,000	2,370	1,020	352	83	0
ISO 5	Class 100	100,000	23,700	10,200	3,520	832	29
ISO 6	Class 1,000	1,000,000	237,000	102,000	35,200	8,320	293
ISO 7	Class 10,000	N/A	N/A	N/A	352,000	83,200	2,930
ISO 8	Class 100,000	N/A	N/A	N/A	3,520,000	832,000	29,300
ISO 9	Standard Room	N/A	N/A	N/A	35,200,000	8,320,000	293,000

Table 2: Required Testing for Cleanrooms (ISO 14644-2)

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

Table 3: Optional Testing for Cleanrooms (ISO 14644-2)

Test Parameter	Class	Maximum Time Interval	Test Procedure
Installed Filter Leakage	All Classes	24 Months	ISO 14644-3 Annex B6
Containment Leakage	All Classes	24 Months	ISO 14644-3 Annex B4
Recovery	All Classes	24 Months	ISO 14644-3 Annex B13
Airflow Visualization	All Classes	24 Months	ISO 14644-3 Annex B7

Table 4: FDA’s Classification Guidance for Aseptic Processing

Air Classifications Clean Area Classification (0.5 um particles/ft3)	ISO Designation	>0.5 μm Particles/m3	Microbiological Active Air Action Levels (cfu/m3)	Microbiological Settling Plates Action Levels (diam. 90mm; cfu/4 hours)
100	5	3,520	1	1
1,000	6	35,200	7	3
10,000	7	352,000	10	5
100,000	8	3,520,000	100	50

Table 5: EU GMPs Annex 1 Recommended Limits for Particulate Contamination

	Max permitted number of particles/m3 equal to greater than tabulated size
	At rest		In operation
Grade	0.5 μm	5.0 μm	0.5 μm	5.0 μm
A	3,520	20	3,520	20
B	3,520	29	352,000	2,900
C	352,000	2,900	3,520,000	29,000
D	3,520,000	29,000	Not defined	Not defined

Engineer Your Lab to be Free of Debris

Ensuring that dirt and dust from humans, equipment, and tools are kept out of the cleanroom is another part of the equation for keeping the air inside as pure as possible. From the paint and panels that line the floor and walls of a cleanroom, to the pencils used to record data, all aspects of a cleanroom are specially engineered to keep impurities out of susceptible manufactured goods.

Lab Pro offers a wide selection of cleanroom manufacturing supplies to help you maintain your cleanroom:

• Easy-to-clean equipment and storage solutions that are designed not to shed particulates, such as shelving, cabinets, work benches, gowning racks, and thermal holding and transport
• Supplies to minimize dust and dirt, like sticky mats, cleanroom vacuums, IPA wipes, shoe covers, and static control tools
• PPE to protect from human shedding (dander, skin cells, and spittle) such as frocks, coveralls, lab coats, bouffant caps, face masks, and sleeves
• A plethora of cleanroom hand tools, like tweezers, brushed, cutters, scissors, and pliers

Whether you make solar panels, culture stem cells, or compound doses of remdesivir, stocking up on cleanroom supplies is vital for your essential business.

For over 40 years, Lab Pro Inc. has been committed to providing cleanroom apparel and supplies in California and worldwide. To learn more, visit the biggest Lab Supply showroom in California, or contact us online or at 888-452-2776.