Mark PDF

Cleanroom Operation: Personal Behavior
Presented by
Mark Suparat Tang, Ph.D.
May 2006
JENOPTIK Group.
About the Speaker Mark Suparat Tang, Ph.D.

Professional Experience
M+W Zander (Thailand) (10/2003 Present)
Operations Manager
cGMP Quality Systems Specialist
Alpha Therapeutic / Baxter (1/1998 10/2003)

Senior Principal Scientist and Project Manager for Alpha-1 Anti-trypsin
FDA Technical Issues for Drug Approval and Licensing

Yield and Quality Improvement
Cleaning Validation and Process Validation
Senior Principal Scientist Research and Development

Quality Control Laboratory Manager
Quality Assurance Product Release Auditor
Quality Assurance Vendor Auditor
Educational Background
Ph.D. in Biochemistry and Pharmacology (1997)
University of Pennsylvania School of Medicine Department of Pharmacology
Post-doctoral Research Fellow (1/1997- 12/1997)

California Institute of Technology Department of Chemical Engineering
Thai FDA Presenation on Cleanroom Operation 09.05.06
M+W Zander
JENOPTIK Group.
Presentation Agenda: Staff in the Cleanroom

Definition of Cleanroom
Cleanroom Clothing
Behaviour in the Cleanroom
Designing Workplaces in Accordance
with Cleanroom Standards
M+W Zander
JENOPTIK Group.
Cleanroom Technology
Staff in the Cleanroom
1.0 Basics of Cleanroom Technology
2.0 Cleanroom Clothing
1.1
1.2
1.3
1.4
1.5
1.6
1.7
1.8
1.9
2.1
2.2
2.3
2.4
2.5
Definition of Impurities
Particle Sizes and Distribution
Sources of Contamination in the Cleanroom
Paths of Contamination in the Cleanroom
Particle Measuring Technology
Factors Influencing Cleanliness
Classes of Cleanliness
Air Conveyance Systems, Planned Currents
3.0 Behaviour in the Cleanroom

3.1
3.2
3.3
3.4
3.5
Particle Emission from Persons

Function of Cleanroom Clothing
Evaluation Criteria for Cleanroom Clothing
Recommended Cleanroom Clothing
Dressing According to Cleanroom Protocol
M+W Zander
Staff as a Source of Contamination

Selection Criteria for Cleanroom Staff
Behaviour According to Cleanroom Standards
Rules and Guidelines
Cleaning the Materials
JENOPTIK Group.
Cleanroom Technology
4.0 Designing Workplaces in Accordance

with Cleanroom Standards
4.1 Designing Workplaces
4.2 Storage and Transport of Materials
4.3 Airlocks for Materials
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JENOPTIK Group.
Basics of Cleanroom Technology

Definition of Impurities
Particle Measuring Technology
Classes of Cleanliness
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JENOPTIK Group.
Definition of a Cleanroom
What is a Cleanroom?
Important components of a cleanroom
Definition according to ISO 14644 :
incoming
filtered air
A cleanroom is an area set apart

by a wall or similar partition, whose
degree of cleanliness is achieved by
purified air ventilation.
Cleanroom environment is pressurised
to outside area.
ceiling
wall
++
overpressure
+/- 0
balanced
pressure
floor
M+W Zander
JENOPTIK Group.
Definition of Contamination
In cleanroom technology, contaminates are understood to be not only dust

particles in the strict sense, but any disturbing effects of a solid, liquid, gaseous,
thermal or electromagnetic nature capable of having a negative influence on the
course of a process and the quality of a product.
The size of particles is defined in microns (abbreviated m) i. e. small in
Greek. One micron is a millionth of a meter or a thousandth of a millimeter.
As a comparison, one human hair has a diameter of about 60 - 80 microns; all
particles from about 5 microns down are present in the air and are therefore
called suspended particles.
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JENOPTIK Group.
Types of Particles
Fibre Filter
Cloth Filter
Wet Separation
Sieving
Measurement
Methods
M+W Zander
Gravity S eparation
Electron Microscope
Germs
Act. Carbon Filter
0,0001
Microscope
Heavy Dust
0,001
Sinking Dust
Pollen
Gas Molekule
0,01
Viruses
0,1
Tobaco Smoke
Miner al and Metal Dust
Ash
Mist
10
Smog
Particle Diameter (m)
100
Suspended Matter
Rain
1000
Visible to Naked Eye
10000
Separation
JENOPTIK Group.
99,99
99,90
Distribution of Particle Sizes

in Atmospheric Dust
99,00
% < Particle Diameter
95,00
90,00
Concentrat ion(1)
80,00
Curve 1: Concentration of particles

measured with an electron
microscope
70,00
60,00
50,00
40,00
30,00
Curve 2: Projected particle surface,

calculated
20,00
10,00
Surface (2)
5,00
Curve 3: Percentage by weight, measured

through sedimentation, the broken
part of the line was calculated
1,00
Weight (3)
0,10
0,01
0,01
0,1
10
20 m m
Particle Diamet er
M+W Zander
JENOPTIK Group.

Comparisons of Size in Micro-Range I
Conductor
0,8m
0,8 m
0,8m
Dust Particle1m
0,8m
,8
0
0,8m
,8
0
,8
0
Enlargement=10000
Sheet of Paper (Thickness)
80m
1m
Human Hair
60m
Enlargement=1000
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JENOPTIK Group.

Comparisons of Size in Micro-Range II
Smoke particle Slit in Read/Write Head
Dust particle
Fingerprint
Human Hair
Aluminium Bearer Plate
Typical Level of Travel of the

Read/Write Head 0,5m
20000m
60 m
(20Meter)
30m
Magnetic
Coating
1m
5m
5m
60m
50m breit
The read/write head travvels at a speed of more than 200 kilometres per hour across the
magneticplate, at a distance of less than 0,5m, which is smaller than a diameter of a human hair.
M+W Zander
JENOPTIK Group.

Example of Contamination from Large Particles on Printed Circuits
60 60
Enlargement: 100times
60 60 60
Sugar Cr ystal
Accumula tion of Sticky Particles 10-30

Circuit Paths
Enlargement: 5 times
each 1 25
Hair 60 Diam eter
each 125
Cir cuit Paths
Thump- Prin t
25 000
M+W Zander
JENOPTIK Group.
External Impuritities
Internal Impurities
Introduction of contaminated outside air

or circulating air *
Staff
Staff
Process
impure process media or raw materials
Production equipment, machines, tools etc.
Inadequately cleaned materials, tools etc.
Unsuitable building materials, work materials

Mechanical abrasion in the cleanroom
* poor filter quality, not airtight filter seal surfaces, leakage in the ducting system, abrasion in air
recirculation equipment and in the ducting system
M+W Zander
JENOPTIK Group.
Percentage Distribution of the Sources of Contamination
Equipment
People
20 - 30%
30 - 40%
Process-Media
Air
Process
5 - 10%
5 - 10%
20 - 30%
It is important to take the contamination from people into account , which

contributes considerable 30% of the total contamination in the cleanroom.
M+W Zander
JENOPTIK Group.

Emission of Particles by People
making various Movements
without Cleanroom Clothing
Germ emission per minute (according to Botzenhart)

1 000 - 13 000 CFU depending on activity
Particle Emission per

Minute and Person
100 000
Standing and sitting

without moving
500 000
Sitting with gentle movement of

head, hand or lower arm
1 000 000
Sitting with moderate body and

foot movement
2 500 000
Standing up with
full body movement
5 000 000
Slow walking - approx 3,5 km/h
7 500 000
Walking at about 6 km/h
10 000 000
Walking at about 9 km/h
15 - 30 000 000
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Type of Activity
Gymnastics and sports
JENOPTIK Group.
The Contamination of Processes

and Products can occur by:
contact contamination from touching

air-borne particles (aerosols)
contaminants in the process media
(hydrosols)
Contamination can be avoided by:
removing the source of contamination

interrupting the transport mechanism
for contaminants
M+W Zander
JENOPTIK Group.
Particle Measurement Technology

Optical Particle Counter
Condensation Nucleus Counter
Graphic representation:
1 Air intake; 2 observed volumes; 3 lamp; 4 mirror;
5 sensor chambers; 6 sensor chambers;
7 calibration instrument; 8 photomultiplier.
A laser particle counter differs from this instrument
mainly in its source of light.
Graphic representation:
1 aerosol intake; 2 alcohol sump; 3 saturation pipe
(kept at 35C); 4 Dacron felting; 5 condensation pipe
(kept at 10C); 6 image lenses; 7 condenser lenses; 8
lamp; 9 slit (0.1 x 2mm); 10 collector lenses; 11
photodetector; 12 to volume-flow measuring appliance
and pump.
(Source: TSI inc. St. Paul, USA)
M+W Zander
JENOPTIK Group.

Measuring Particles in prescribed Cleanroom of Class 100,000 before Refit I
MeasuringPoint No.
Measuring Location
Measuring
Height in m
Supply air in helical outlet
2,5 m from center of

window-wall
Particles
= 0,5
Particles
= 5
21.300
1,0
2,0
19.100
16.900
0
0
113
55
0,5 m from center of

window-wall, right corner
1,0
2,0
15.300
12.900
0
0
17
29
Lighting device without person

Ditto with working person
1,1
1,1
52.000
57.300
0
0
100
1.120
0
0
Center of room
1,0
2,0
3,0
36.700
117.100
28.800
0
<
0
63
110
72
0
0
0
M+W Zander
0
0
JENOPTIK Group.
Incoming Air
cleanliness class
air speed
air temperature
relative humidity
ionisation
M+W Zander
JENOPTIK Group.
10
Air Current Control

type of cleanroom (turbulent, with low turbulence)
cleanroom layout
arrangement of incoming and outgoing air flows
technological environment
particle-proof room divisions
maintenance of pressure
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JENOPTIK Group.
Staff
rules of behaviour, discipline
speed of movement
organisation of work activities
clothing appropriate for cleanroom
regular decontamination of cleanroom clothing
entry and exit procedures (airlocks)
M+W Zander
JENOPTIK Group.
11

Workplace
cleanroom compliant infrastructure
ergonomic design
arrangement of incoming and outgoing air flows
aerodynamics of equipment
sources of heat
blind-spots in current
cleanliness of surfaces
cleaning throughout production
M+W Zander
JENOPTIK Group.
Materials Handling
forms of movement
logistics of access
robot for local manipulation
automated conveyer systems
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JENOPTIK Group.
12
Process
process layout
sequence of procedures
keeping process media clean (gases, chemicals, DI water, solvents etc.)
process equipment, production fittings
monitoring procedures
inward and outward movement of materials through airlocks
M+W Zander
JENOPTIK Group.
Cleanliness Classes
Concentration of Particles in the Air
Measurement Point
Particle Concentration:
- Particles ( _
> 0,5m) per m 3
Industrial region with SMOG
.....up to 1.000.000.000
Industrial region
30.000.000 to 60.000.000
Metropolitan area
10.000.000 to 100.000.000
Rural area after rain
1.000.000 to 10.000.000
Cleanroom with TMC

Class 10.000-100.000
350.000 to 3.500.000
Cleanroom class 100
up to 3.500
Cleanroom class 01
up to 3,5
M+W Zander
JENOPTIK Group.
13
Cleanliness Classes
Particles
3
per m _> dp
Particles
per ft3 _
> dp
Cleanroom Classes
100 Mio
10 9
According to ISO 14644

10 Mio
10 8
O
o
do
ut
1 Mio
rA
ir
10 7
100 000
10 6
Cla
ss
10 000
C la
1 000
Cla
ss
10
0/
100
Cla
ss
10
/M
10
Cla
s
s1
Cla
s
/M
2.
3.5
ss
1
Cl
as
s1
10
00
00
00
00
0
00
/M
/M
10 5
/M
5.
6.
10 4
5
103
4 .5
10 2
1. 5
s0
101
0,1
0,1
0,2 0,3
0,5
10
Particle Diameters in Micrometer (dp)

M+W Zander
JENOPTIK Group.
Cleanliness Classes
Comparison of Sizes for Class 10 Cleanroom
Class 10 according to ISO 14644 means:
Fewer than 350 particles larger than 0,1 microns per cubic foot.
Scale enlargement by way of illustration
1 Particle 0,1 microns = 1 pinhead 3 millimetres.
3 mm
Accordingly the relevant volume of air rises to 2,160,000,000 m3

(approx. 2 thousand million m3). This would be the volume of
a train from the earth to the moon.
Result:
A pin in 20 million
freight cars
You have to look for ONE pin in 20 million freight cars (approx. 360.000 km),
to comply to class 10 environment!
This would take 200 years, if you need 5 minutes for each freight car.
Comparison of Sizes for Class 10 Cleanroom
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JENOPTIK Group.
14
Air Flow Concepts I
+
-
Unidirectional Flow
for Classes 100/10/1/0.1 M3.5-1
The clean air stream is low in turbulence
"laminar) in the cleanroom for Classes
00/10/1/0.1, M 3.5 - 1 which results in the
sensitive work areas and machines being
exposed to minimal contamination.
M+W Zander
JENOPTIK Group.
Air Flow Concepts II
Air cir culation appliance
Turbulent Dilution Flow

Filter
outlet
The clean air in the case of Class 1,000 to 100,000

is fed into the cleanroom as a turbulent flow
(swirling) and creates a constant diluting effect,
thus cleansing the cleanroom. In this way the
required cleanroom level is maintained.
M+W Zander
JENOPTIK Group.
15
Air Flow Concepts III

Class 100.000 / M6.5
according to
Federal Standard 209D/209E
V=0,017 m/s
air changed 20 times per hour
ULG
ULG
Class 1.000 / M4.5

according to
V=0,1 - 0,2 m/s
*room he ight 3m
ULG = recirculat ion equipment
AL
Class 10.000 / M5.5

according to
V=0,034 m/s
AL
Class100, 10, 1, 0.1 / M3.5-1

according to
V=0,45 m/s
ULG
U LG
AL
AL
AL = outside air in feed
M+W Zander
JENOPTIK Group.
Air Flow Concepts IV
Cleanroom Classes
Class 100.000
turbulent
Specific Air Volume

3
2
m /h .m
Specific Size of Recirculation Equipment
60
Class 10.000
turbulent
120
2x
Class
1.000
turbulent
240
4x
Class
100
laminar
Class
10
laminar
1620
27 x
Class
laminar
Class
0,1 laminar
M+W Zander
JENOPTIK Group.
16
Air Flow Concepts V

Example of Cont amination Levels from Persons in a Cleanroom of Class 100,000 (turbulent)
100 000
Safety Zone
90 000
3
80 000
70 000
Number of particles
60 000
50 000
2
40 000
30 000
20 000
Underlying Contamination
10 000
Time
7.00
1
2
3
4
5
6
7
8.00
9.00
10.00 11.00 12.00 13.00 14.00 15.00 16.00 17.00 18.00 19.00 20.00
Work begins (flexitime)

Coffee break
Service work in t he cleanroom
Lunch break
Afternoon tea
Work en ds
Cleaners at work
7.00 - 8.15
9.00 - 9.15
10.00 - 11.00
12.00 - 13.00
15.00 - 15.15
17.00 - 18.00
19.00 - 20.00
M+W Zander
JENOPTIK Group.
Air Flow Concepts VI

Measuring Particles in prescribed Cleanroom of Class 100,000 before Refit I
MeasuringPoint No.
Measuring Location
Supply air in helical outlet
2,5 m from center of windowwall
Measuring
Height in m
Particles
= 0,5
Particles
= 5
21.300
1,0
2,0
19.100
16.900
0
0
113
55
0,5 m from center of windowwall, right corner
1,0
2,0
15.300
12.900
0
0
17
29
Lighting device without person

Ditto with working person
1,1
1,1
52.000
57.300
0
0
100
1.120
0
0
Center of room
1,0
2,0
3,0
36.700
117.100
28.800
0
<
0
63
110
72
0
0
0
0 Class 10 000 not achieved

M+W Zander
0
0
< Class 100 000 not achieved

JENOPTIK Group.
17
Air Flow Concepts VII

Measuring Particles in prescribed Cleanroom of Class 100,000 before Refit II
MeasuringPoint No.
Measuring Location
Measuring
Height in m
Particles
= 0,5
Waste air to cable conduit
117.700
<
14
0,5 m from No. 5 below

ceiling
186.100
<
54
Brush machine, outlet-side
174.400
<
106
2 m in front of door to hallway
1,0
2,0
284.600
318.500
<
<
39
73
Inspection
Inspection with smoking
(lunch break)
2,0
2,0
84.830
206.200
0
<
109
119
0
0
Particles
= 5
0 Class 10 000 not achieved
< Class 100 000 not achieved
M+W Zander
JENOPTIK Group.
Cleanroom Clothing

Recommended Cleanroom Clothing
Dressing according to Cleanroom Standards
M+W Zander
JENOPTIK Group.
18

Comparison of Particle
Emissions from various
Activities of Movement
with Cleanroom Clothing
or Street Suits
Particle Emission per s
Kind of Movement
Particle Size > 0,5m

Clothing
Cleanroom Suit
One-Piece
Two-Piece
Head, Mouth and

Nose covered
Head covered
Street Suit
Standing
300
100
1800
5500
Sitting
250
120
1800
10000
Head Movement
400
180
2500
15000
Body Movement
500
250
4500
50000
Arm Movement
800
300
5000
50000
650
400
9000
35000
Moving alnd
stretching body
1000
600
10000
50000
Walking slowly
2500
900
17000
50000
Walking fast
4000
1800
24000
90000
Moving Body
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JENOPTIK Group.
Particle emission from persons

Particle Counts for a Class 10.000 Cleanroom Suit
Exposed body parts,
~10.000 particles
Cap, ~320 particles

Mouth area, ~500 particles
Cotton/polyester coat,
~10.017 particles
Wiping cloth,
~9.356 particles
Normal trousers, socks, shirt,
underwear, ~20.000 particles
Approximate number of particles: 50.892/ft3/min.

1 shift = 8 h x 60 min. = 480 mins.
85 persons per shift
Shoes, ~500 particles

3 shifts produce =
50.692/ft3/min. x 480 mins. x 85 persons x 3 shifts = 6.205 x 109 particles/ft3/24 h
M+W Zander
JENOPTIK Group.
19
Particle emission from persons

Particle Counts determined with Particle Counter: Class 100 Cleanroom Suit
Cap, ~128 particles
Facemask, ~200 particles
Exposed body parts,

~2.000 particles
100% Polyester-overall,
~1.807 particles
Arm-length gloves,
~112 particles
Wiping cloth,
~1.574 particles
Approximate number of particles: 6.049/28,2l/min.

1 shift = 8 h x 60 min. = 480 mins.
85 persons per shift
Knee-length boots,
~228 particles
3 shifts produce =
6.049/ft3/min. x 480 mins. x 85 persons x 3 shifts = 740.397.600 x particles/ft3/24 h
M+W Zander
JENOPTIK Group.
Particle Barrier
Physiological Aspects
Protection for the Worker
functions as a
barrier to the
particles emitted
by the human body
as well as fibres
and particles from
undergarments
wearing comfort
resistance to penetration by fluids
warmth and dampness emitted

from garments
resistance to chemicals and solvents
flame resistance
conductivity
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JENOPTIK Group.
20
Materials / Fabrics
synthetics or mixed fabrics (polyester, polyamide, cotton, Goretex)

fabric made from single-filament threads
porosity for particles (densely woven)
low emission of own particles
resistance to wear when worn or washed
flexible strength (softness)
non-tearing
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JENOPTIK Group.
Wearing Comfort
comfortable
permeable to heat and dampness
well fitting (pump action)
collar sealing, sleeve bindings, legs
fastenings (zip or Velcro fasteners, buttons, ribbons)
seams
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JENOPTIK Group.
21

Chemical Resistance
resistance to penetration by fluids
acids, alkaline solutions
solvents
colour fastness (wash, friction and light fast)
Decontamination
wet and chemical cleaning
able to be sterilised
odours
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JENOPTIK Group.
Electrostatic Qualities
conductive fibres in the fabric

treated with anti-static's
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JENOPTIK Group.
22
Recommended Cleanroom Clothing for various Cleanroom Classes
Cleanroom Cleanroom
Class
Clothing
Special
Underwear
according
to Fed.St. 209E
Head Covering
Shoes
Gloves
Change
Frequency
overalls
yes
full protective
hood
long overboots
no powder
or lint
for every entry
10
overalls
yes
full protective
hood
long overboots
no powder
or lint
for every entry
100
overalls
recommended
full protective
hood
long overboots
no powder
or lint
daily
1 000
overalls
no
hood
beard covering
overboots or
overshoes
no powder
or lint
daily
10 000
overalls
no
hood or cap
beard covering
overshoes
as required
dailyor
every 2 days
100 000
white coat
no
cap
overshoes
as required
every 2 days
M+W Zander
JENOPTIK Group.
Dressing according Cleanroom Protocol I
Remove street clothing
Remove all additional items such

as watches, jewellery, rings, etc.
Put on head cover
4
Enter
"controlled
area"
5
M+W Zander
Temporary gloves
JENOPTIK Group.
23
Dressing according Cleanroom Protocol II
Carefully take out the

blister-packed clothes
Put on full hood
and move feet over the

clean side
On the changing bench,

take off clogs etc.
10
Put on mask
Take out new

(cleaned) overalls
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JENOPTIK Group.
Dressing according Cleanroom Protocol III
13
11
Pull on overalls without

letting them touch the floor
12
On the changing bench,

take off clogs etc.
14
Pull overshoes up
over overalls
15
Put on new gloves
Take special care to put

on gloves and overshoes
without contamination
16
M+W Zander
Go to workplace
in cleanroom
JENOPTIK Group.
24
Dressing according to Cleanroom Protocol

Cleanroom - Changing Area
~ 13 m
Laundry
handover
Shower
Clothes
lockers
WC
~6 m
Wash
basins
Outside Area
Cleanroom
clothing
Overpressure maintained
by locking both side s
Cleanroom Area
WC
Air
shower
Wardrobe for coats
Benc h
Put on
cleanroom
shoes
Used clothin g,
waste
Emergency Exit
Clearoom Clothing
C leaning Zone
Street Clothing
M+W Zander
JENOPTIK Group.
Dressing according to Cleanroom Protocol
Cleanroom Zone
Cleaning Zone
M+W Zander
JENOPTIK Group.
25
Behaviour in the Cleanroom
Staff as a Source of Contamination

Behaviour according to Cleanroom Standards
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JENOPTIK Group.
Staff as Source of Contamination

Emission of Particles
1x
5x
10x
25x
100.000 Particles
*(contaminant
emissions
= dust
skin particles,
hair,
germs,
viruses,
smoke etc.)
Size:
0,001 micron to;10 microns
1 micron = 1/1.000 mm
50x
100x
M+W Zander
150x/300x
JENOPTIK Group.
26

Criteria for activities in Cleanroom
age
body size, weight
sensitive vision, hearing, smelling (to recognise hazards)
microscope skills
precision movements
general agility
suitability for shift-work
discipline
team spirit, willingness to co-operate
willingness to keep body clean
M+W Zander
JENOPTIK Group.

Factors limiting Activities in the Cleanroom
skin disorders leading to a greater release of particles
or electrolytic contaminates
hair diseases (hair loss, heavy dandruff)
chronic respiratory illnesses
chronic urinary infections
metabolic disorders
chronic release of bacteria
neurological disorders
emotional disorders (neuroses, claustrophobia etc.)
smoking
M+W Zander
JENOPTIK Group.
27
Behavior according to Cleanroom Standards
movements no faster than air flow

controlled, not abrupt, movements
never taking objects against the air flow
protective clothing always sealed
M+W Zander
JENOPTIK Group.

Inappropriate Behaviour
Fast walking causes turbulences

due to low pressure points.
Seizing something quickly from

above creates turbulences and
contamination outbursts.
M+W Zander
If installations and appliances are set

horizontally to the air current, turbulence is created on the underside.
JENOPTIK Group.
28

13 "Do's" - Behaviour in the Cleanroom
1.
Training
All staff working at a Clean Workplace must be trained

repeatedly in all aspects which are relevant to the work in
question.
2.
Staff
At the Clean Workplace only the required amount of staff

should be present.
3.
Checks
As far as possible, all monitoring and inspections should be

carried out from the outside.
4.
Visitors
If inspectors, service staff or visitors enter the Clean Workplace, the same rules of behaviour apply as for permanent
workers in this area.
5.
Moving about
The movement of people between the Clean Workplace and

the surrounding areas should be kept to a minimum.
M+W Zander
JENOPTIK Group.

6.
Private items
It is not permitted to take food, cigarettes, jewellery and

other personal items to the Clean Workplace.
7.
Materials
Apart from the materials directly needed or the production

goods to be processed immediately, no objects or materials
may be stored in the vicinity of the Clean Workplace
8.
Movements
At the Clean Workplace, the staff must move in a controlled

and considered manner. Since the emission of particles and
germs is related to the workers activity and the type of
movement, quick and abrupt movements might cause a
strong current and thus are to be avoided at all times.
9.
Working clothes
Care must be taken that the prescribed working clothes are

worn in the Cleanroom in the correct way at all times.
M+W Zander
JENOPTIK Group.
29

10. Contacts
In order to avoid contaminating the gloves unnecessarily

(dust, fats, salt, germs), nothing may be touched at the
workplace apart from the appropriate equipment and tools.
(Do not fold arms, do not scratch, do not touch door
handles or telephone receivers.)
11. Communication
Speaking, coughing and sneezing may never take place in

the direction of the critical working area.
12. Jobs
When temporarily not working or merely observing at the

Clean Workplace, the staff must move as far away as
possible from the critical area.
13. Handling
Interventions in the critical work area must take place in

such a way that neither the hand nor the arm of the staff
comes between the HEPA filter and the object.
M+W Zander
JENOPTIK Group.
Put on protective hood
Put on gloves
M+W Zander
JENOPTIK Group.
30
Take out new overalls without contamination and pull on without letting them touch the floor
M+W Zander
JENOPTIK Group.
Pull overshoes up over overalls, put on new gloves and then go to workplace in the cleanroom
M+W Zander
JENOPTIK Group.
31
Manual Cleaning
moist / dry cleaning
wiping down, brushing
solvents according to cleanroom standards
lint-free wiping cloths
central vacuum cleaner
super-clean air pressure
ionic air pistol
M+W Zander
JENOPTIK Group.
Immersion-Bath Cleaning
moderately warm immersion baths
with / without ultrasonics
brushes
hot organic solvents such as trichloroethylene,
xylene, acetone or substitutes
Methane, ethanol, isopropanol
DI-water
M+W Zander
JENOPTIK Group.
32

Ultrasonic Method
25KHz
non-directional sound waves
cleaning effect from forces of cavitation
Megasonic Method
0.8 - 12 MHz
directional sound waves
cleaning effect from forces of cavitation
M+W Zander
JENOPTIK Group.
Cleaning of windows, walls, equipments and

transport materials with moist one-way cloth
M+W Zander
JENOPTIK Group.
33
Designing Workplaces in accordance with Cleanroom Standards
Designing Workplaces
Storage and Transport of Materials
Airlocks for Materials
M+W Zander
JENOPTIK Group.
Design Rules
Outflow (double floor) as opposed to in-flow (filter ceiling)
Fittings which allow air flow to pass through
No blind-spots for current upstream
Avoid uncontrolled dead zones
Distance of about 10 cm from wall
Gap dividing neighboring workplaces about 10 cm
Dense flow around heat sources
M+W Zander
JENOPTIK Group.
34
Fittings which allow flow to pass through

Outflow opposed to inflow
No areas for contamination to collect
due to non-air flow exposure
Dense flow around heat sources
M+W Zander
JENOPTIK Group.
Flow pattern with lateral outflow through wall
M+W Zander
Flow pattern with double floor outflow
JENOPTIK Group.
35
Flow pattern with dividing screen (apron)

with lateral outflow through wall
Flow pattern with dividing screen (apron)

with double floor outflow
M+W Zander
JENOPTIK Group.
Materials for Transport and Storage Containers

PE - Polyethylene
PFA - Polyfluoramide
PP - Polypropylene
PVC - Polyvenyl Chloride
PMMA - Polymethyl Methacrylate
AL - Auminium
M+W Zander
JENOPTIK Group.
36

Storage
open under laminar flow
dustproof boxes, containers
Handling
special tools
tweezers, forceps
vacuum grips
carrier
M+W Zander
JENOPTIK Group.
Transport
dustproof boxes, containers
transport cars with integrated super clean air supply
M+W Zander
JENOPTIK Group.
37
Airlocks for Materials

to store
take sample
internal pallets
dust removal,
external pallets
possible change
of pallets
feed belt
pallet loading point

inward goods
M+W Zander
JENOPTIK Group.
Cleanroom Validation Procedures

Preliminary Considerations
Purpose of Cleanroom: GMP Requirement
All facilities and machinery are correct for the purpose and that they, and the
environment in which they are situated, is properly cleaned and appropriately treated.
User Requirement Specification (URS) for the Cleanroom
1. User-defined requirements for the Manufacturing Environment to comply with the
User-defined Regulatory Requirements.
2. Sufficiently detailed to enable design specifications to be developed.
Room Data Sheet
1. Defines the Cleanroom Specifications.
2. All Cleanroom Specifications are reviewed during GMP review.
3. Basis for the Final Acceptance Tests and Specifications for the Cleanroom.
M+W Zander
JENOPTIK Group.
38
Cleanroom Validation Procedures

Steps of Validation
1. User Requirement Specification (URS) by User
2. Cleanroom and Facility Design by Cleanroom Engineer
3. Design Qualification (DQ) = Commissioning Procurement
4. Installation Qualification (IQ) = Commissioning Installation and Testing
5. Operation Qualification (OQ) = Commissioning Certification
6. Performance Qualification (PQ) = Compliance to Room Data Sheet
7. Cleaning Validation
** DQ can be covered in normal design reviews
M+W Zander
JENOPTIK Group.
Cleanroom Validation Procedures: Design Qualification

Design Qualification (DQ)
The documented evidence that the Cleanroom Design Objectives concerning GMP
and compliance of the project have been properly described in Cleanroom design
documentation, and that the Design if Fit for Purpose
Objective:
To Confirm that the Designs fit the User Required Specification
Specifications
Purchase Orders
Vendor Proposal Documents
Layouts
P&ID/Flowsheets
Contractor Strategy / Interfaces
Executed in Parallel with During Commissioning Procurement
M+W Zander
JENOPTIK Group.
39
Cleanroom Validation Procedures: Installation Qualification

Installation Qualification (IQ)
The documented verification that all aspects of the Cleanroom that can affect final
quality of the Cleanroom environment adhere to approved specifications and are
correctly installed.
Objective:
To demonstrate that the item as installed, conforms to the Design Specification
(Referring to the Design Specification and User Required Specification)
HVAC and other Critical Instruments are still in Calibration
Equipment specifications, drawings, operation and maintenance manuals
Installation check of Critical Components
Critical Component P&ID and Loop Check
Testing and Balancing Report
HEPA filter Integrity Testing Data Review
Executed in Parallel with During Commissioning Installation
M+W Zander
JENOPTIK Group.
Cleanroom Validation Procedures: Operation Qualification

Operation Qualification (OQ)
The documented verification that all aspects of the Cleanroom that can affect the final
Cleanroom quality can operate as intended throughout all anticipated ranges.
Objective:
To demonstrate that the Cleanroom can be operated in conformance to the Design
Specification (Referring to the Design Specification and User Required Specification)
HVAC and other Critical Instruments are still in Calibration
Testing of Critical Alarms and Interlocks
List of Critical Operating Parameters encompassed by Room Data Sheet
Testing for the Specifications detailed in the Room Data Sheet
Standard Operation Protocol for HVAC System Controls
Cleanroom Operation Protocols for Cleanroom Operations
Executed in Parallel with During Commissioning Testing, Balancing, Certification
M+W Zander
JENOPTIK Group.
40
Cleanroom Validation Procedures: Performance Qualification

Operation Qualification (PQ)
A documented program to demonstrate that the Cleanroom, when operating within
the defined parameters, can consistently perform and maintain the Cleanroom
conditions.
Objective:
To demonstrate that the Cleanroom can reliably perform in conformance to the
Design Specification (Referring to the User Required Specification and Room Data
Sheet)
Monitoring and Testing for Particulate Levels (Surface and Airborne)
Static (non-viable) Particulate Monitoring (As-built / At rest)
Static (viable) Particulate Monitoring (Microbial Monitoring) (As-built / At rest)
Dynamic (non-viable) Particulate Monitoring (Sterile Areas) (In Operation)
Dynamic (Viable) Particulate Monitoring (Sterile Areas) (In Operation)
Room Data Sheet is the Cleanroom User Required Specification

Executed after Commissioning Certification
M+W Zander
JENOPTIK Group.
Cleanroom Validation Procedures: Additional Considerations

Worst Case Scenarios
Identify critical operating parameters
Set operational ranges for each critical parameter
Design worst case scenarios to test extremes of ranges
min/max temperatures and humidity
process equipment operational contamination
personnel operational contamination
Equipment maintenance schedule
Operational Considerations
Recovery Time
Cleaning Procedures
Cleaning Validation
Re-testing, Re-Certification, and Re-Validation Schedule
M+W Zander
JENOPTIK Group.
41
About M+W Zander (Thai) Co.

M+W Zander (Thai) is a Consultant Firm Specializing in
Designing Cleanroom Facility, Utility, Building, and Process Equipment and
Executing Turnkey Projects for the Pharmaceutical and Microelectronic Industries
M+W Zander (Thai) has developed its own standard operation procedures.
that are in accordance to above listed international standards and
that can be adjusted to the clients specific requirements.
With Recommendation and Consultancy on scope of the measurements!
M+W Zander (Thai) provides Measurement and Certification services for

Cleanroom and HVAC systems.
Following (DIN EN) ISO 14644-1, VDI 2083, IES-RP-CC006.2 or NEBB
Following Pharmaceutical and Biological Product GMP Requirements
Following the specific process, facility, and client requirements.
M+W Zander
JENOPTIK Group.
42

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Cleanroom Operation: Personal Behavior

About the Speaker Mark Suparat Tang, Ph.D.

Alpha Therapeutic / Baxter (1/1998 10/2003)

FDA Technical Issues for Drug Approval and Licensing

Senior Principal Scientist Research and Development

Post-doctoral Research Fellow (1/1997- 12/1997)

Thai FDA Presenation on Cleanroom Operation 09.05.06

Presentation Agenda: Staff in the Cleanroom

Thai FDA Presenation on Cleanroom Operation 09.05.06

2.0 Cleanroom Clothing

3.0 Behaviour in the Cleanroom

Thai FDA Presenation on Cleanroom Operation 09.05.06

Particle Emission from Persons

Staff as a Source of Contamination

4.0 Designing Workplaces in Accordance

Thai FDA Presenation on Cleanroom Operation 09.05.06

Basics of Cleanroom Technology

A cleanroom is an area set apart

Thai FDA Presenation on Cleanroom Operation 09.05.06

In cleanroom technology, contaminates are understood to be not only dust

Thai FDA Presenation on Cleanroom Operation 09.05.06

Particle Sizes and Distribution

Thai FDA Presenation on Cleanroom Operation 09.05.06

Act. Carbon Filter

Miner al and Metal Dust

Particle Diameter (m)

Visible to Naked Eye

Particle Sizes and Distribution

Distribution of Particle Sizes

% < Particle Diameter

Curve 1: Concentration of particles

Curve 2: Projected particle surface,

Curve 3: Percentage by weight, measured

Thai FDA Presenation on Cleanroom Operation 09.05.06

Particle Sizes and Distribution

Sheet of Paper (Thickness)

Thai FDA Presenation on Cleanroom Operation 09.05.06

Particle Sizes and Distribution

Typical Level of Travel of the

Thai FDA Presenation on Cleanroom Operation 09.05.06

Particle Sizes and Distribution

Accumula tion of Sticky Particles 10-30

Hair 60 Diam eter

Cir cuit Paths

Thai FDA Presenation on Cleanroom Operation 09.05.06

Sources of Contamination in the Cleanroom

Introduction of contaminated outside air

impure process media or raw materials

Production equipment, machines, tools etc.

Inadequately cleaned materials, tools etc.

Unsuitable building materials, work materials

Thai FDA Presenation on Cleanroom Operation 09.05.06

Sources of Contamination in the Cleanroom

Percentage Distribution of the Sources of Contamination

It is important to take the contamination from people into account , which

Thai FDA Presenation on Cleanroom Operation 09.05.06

Sources of Contamination in the Cleanroom

Germ emission per minute (according to Botzenhart)

Thai FDA Presenation on Cleanroom Operation 09.05.06

Particle Emission per

Standing and sitting

Sitting with gentle movement of

Sitting with moderate body and