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TB 2010 9
TB 2010 9
Cleanroom Operations
Background
Cleanrooms are defined as a
room or suite of rooms, in which
the concentration of airborne particles is maintained within established parameters and where other
factors are controlled to within
specified limits. These rooms are
designed to provide control of environmental factors including:
Viable and non-viable airborne
particles
Air flow patterns
Temperature and humidity
Air pressure differential
Containment of hazardous
aerosols
Applications include the manufacture of sterile and non-sterile
pharmaceutical and biotech products, medical devices, and implants. These rooms are also used
to manufacture sensitive electronics. However, the requirements for
these latter applications are not
the objective of this article. GMP
requirements from the different
Boards of Health, including the
US Food and Drug Administration
(FDA), for sterile pharmaceutical,
biotech, medical devices and implants require the manufacture of
these products are performed in
clean environments that meet the
requirements of standards such as
ISO EN146441.
Compliance Requirements:
FDA Guideline Sterile Drug
Products Produced by Aseptic
Processing2
European Union (EU) GMP
Annex 13 Manufacture of Sterile
Medicinal Products
Other Helpful Documents:
ISO EN14644-1, -2
International Society for Pharmaceutical Engineering (ISPE4)
People Activity
Sources of Contamination
100,000
5,000,000
Horseplay
100,000,000
Table 2
Maximum permitted
Old Fed Std 209E ISO EN14644 EU GMP Annex 1 particles per m3 equal to or
greater than tabulated size
At rest
In operation
0.5
0.5
Maximum Microbiological
Active Air Action Levels
(cfu/m3)
100
ISO 5
Class A & B*
3,520
3,520
1,000
ISO 6
---
35,200
---
10,000
ISO 7
Class C
352,000
3,520,000
10
100,000
ISO 8
Class D
100
*Requirements for particle counts during operation are different from class A, 35,200 particles at 0.5
2010 Particle Sciences, Inc. All rights reserved.
= Air Flow
Z = HEPA
Filtered Air
Gowning Area
Z = P2
Definitions
HEPA Filter - High Efficiency
Particulate Air Filter
Viable - a particle capable of
living, developing, or germinating
under favorable conditions, i.e.,
bacteria.
Non-viable - typically dust or liquid
particles
Airborne - carried by or through the
air
Cleanrooms for Handling Potent
Compounds
For handling potent compounds,
i.e., toxic materials, in addition to
the requirements described for a
cleanroom, precautions need to
be taken to avoid spreading the
toxic material to adjacent areas.
This may be achieved by maintaining a negative pressure differential between the cleanroom
and adjacent area so any hazardous powder or aerosol is contained
within the cleanroom, i.e., P3 ~
P2 > P1 (Figure 1). This is accomplished by designing the facility with HEPA filtered incoming
air and providing HEPA filtration
at the exhaust. Also providing a
higher flow through the exhaust
filters to assure proper flow, pressure differential and sufficient
air changes in order to meet the
required room classification; this
setup does not allow air from the
cleanroom to enter into adjacent
areas. Additionally, by providing
localized exhaust or incorporating isolators onto manufacturing
equipment, the control of aerosols
and dust from handling powders
is increased. Note that personnel
enter the cleanroom through the
gowning area whereas equipment
and materials are brought through
the air lock.
References
1. ISO EN 14644-1, -2, -5, -9
International Standards Organization Cleanroom Standards
2. FDA Guidance for Industry
Sterile Drug Products produced by
Aseptic Processing CGMP September 2004
3. EU GMP Annex 1- Manufacture of Sterile Medicinal Products
Air Lock
Z=P3