9/2/2017

Introduction & Classification

Mohd Akmal bin Azhar

akmalba@ump.edu.my

What is cleanroom?
• Room in which the concentration of airborne
particles is controlled, and which is
constructed and used in a manner to
minimize the introduction, generation, and
retention of particles inside the room and in
which other relevant parameters, e.g.
temperature, humidity, and pressure, are
controlled as necessary
ISO standard 14644-1

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How to achieve
• Supplied with filtered air (using HEPA)
• Built with correct materials
• Personnel used correct clothing

Cleanroom applications

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The needs for cleanroom

• In semiconductor – particle can cause electrical
short circuit
• Nanotechnology – small contamination will
effect the system
• Healthcare – prevent infection or contamination
from microbes.

Types of cleanroom
1. Non-unidirectional airflow – turbulently
ventilated
2. Unidirectional airflow – laminar flow

• Unidirectional use more air

• Give superior cleanliness

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Non-unidirectional airflow
• Receive air form
filter in ceiling
• Mix with room air
• Extract at the
bottom of the wall
• Air exchange rate =
20/hour

Unidirectional airflow
• Filter installed
across ceiling
• Air sweep down to
the room
• Remove airborne
contamination by
exit through the
floor
• Velocity: o.3 m/s –
0.5 m/s (60ft/min –
100 ft/min)

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History of cleanrooms
• Joseph Lister’s contribute for the first
cleanrooms in hospital
• He used carbolic acid to spray into the air of
operating room (antiseptic method)

• Lister’s spray –
1889
• Operating room
in late 1890s –
start wear
gowning
• 1907 – start
showing aseptic
precaution

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Cleanroom classification standard

History
• 1st cleanroom standard – American air force,
march 1961 (Technical manual TO 00-25-
203)
• For aerospace facility
– Cleanroom design
– Airborne particle standard
– Entry procedure
– Cleaning procedure
• Basis of ISO 14644-1 and Federal standard
209

Cleanroom classification standard

Federal standard 209 (1963)
• Discussed both unidirectional and non-
unidirectional airflow
• Requirement to measure particle of ≥ 0.5µm
• Suggested velocity – 90-100 ft/min
– Normal fan 50-200 ft/min

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Particle diameter
• Unit of measurement – micrometer

Federal standard 209

• Published on 1963 in USA
• Particle measure in one cubic foot (ft3) of room air

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ISO standard 14644-1:1999

• Published on 1999
• Cover wide variety of issue such as classification, design,
testing, operation and bio-contamination
• Particle measure in cubic meter (m3)

Comparison between FS209 & ISO

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Definition of condition
• As built : condition where building and service connected
is complete but no production equipment, material or
personnel
• At-rest: condition where complete with equipment but no
personnel present (no operation)
• Operational: condition where installation is functioning
with specified number of personnel and working in
manner agreed

Pharmaceutical cleanroom
classification
• Cleanroom for pharmaceutical have their
own standard
• The most widely used are EU & FDA
guidelines.

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1. European Union guidelines to GMP

• Grades of airborne cleanliness for sterile
medicinal product:-
• Grade A – Local zone for high risk
preparation (filling, open ampoule and vial,
aseptic connection)
• Grade B – aseptic preparation and filling
(background environment of grade A)
• Grade C & D – clean area for carrying out
less critical stages in the manufacture of
sterile product

Maximum particle requirement for

EU GMP

• Particles ≥0.5 μm and ≥5.0 μm should be measured both at rest

and in operation.
• For grade A, min sample volume of 1m3 should be taken per
sample location.
• Which class the grade A,B,C & D belong if compare with ISO
standard?

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Examples of operation

Recommended limit for microbial

contamination

• Settling plates can be used and exposed for about 4 hours

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2. FDA guidance for industry – sterile

drug produced by aseptic processing
• FDA differ from EU where FDA only
required classification in the operational
condition.
• They also not required counting particles
≥5.0 μm

Another classification of cleanroom

• Classification of cleanroom with airborne
chemical contamination.
– ISO 14644-8:2006
– Acid, base, biotoxic, corrosive, total organic, etc
• Classification of cleanroom with surface
contamination.
– ISO 14644-9 & ISO 14644-10

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