Clean Room Behaviour

1

JENOPTIK Group.

Cleanroom Operation: Personal BehaviorCleanroom Operation: Personal Behavior

May 2006

Presented by Mark Suparat Tang, Ph.D.

© M+W ZanderThai FDA Presenation on Cleanroom Operation 09.05.06 JENOPTIK Group.

About the Speaker – Mark Suparat Tang, Ph.D.Professional Experience

M+W Zander (Thailand) (10/2003 – Present)Operations ManagercGMP 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 DevelopmentQuality Control Laboratory ManagerQuality Assurance Product Release AuditorQuality Assurance Vendor Auditor

Educational BackgroundPh.D. in Biochemistry and Pharmacology (1997)

University of Pennsylvania School of Medicine Department of PharmacologyPost-doctoral Research Fellow (1/1997- 12/1997)

California Institute of Technology Department of Chemical Engineering

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Definition of Cleanroom

Cleanroom Clothing

Behaviour in the Cleanroom

Designing Workplaces in Accordance with Cleanroom Standards

Presentation Agenda: Staff in the Cleanroom


Cleanroom Technology

Staff in the Cleanroom

1.0 Basics of Cleanroom Technology

1.1 Definition of Cleanroom1.2 Definition of Impurities1.3 Particle Sizes and Distribution1.4 Sources of Contamination in the Cleanroom1.5 Paths of Contamination in the Cleanroom1.6 Particle Measuring Technology1.7 Factors Influencing Cleanliness1.8 Classes of Cleanliness1.9 Air Conveyance Systems, Planned Currents

2.0 Cleanroom Clothing

2.1 Particle Emission from Persons2.2 Function of Cleanroom Clothing2.3 Evaluation Criteria for Cleanroom Clothing2.4 Recommended Cleanroom Clothing2.5 Dressing According to Cleanroom Protocol

3.0 Behaviour in the Cleanroom

3.1 Staff as a Source of Contamination3.2 Selection Criteria for Cleanroom Staff3.3 Behaviour According to Cleanroom Standards3.4 Rules and Guidelines3.5 Cleaning the Materials

3


Cleanroom Technology

4.0 Designing Workplaces in Accordance with Cleanroom Standards

4.1 Designing Workplaces4.2 Storage and Transport of Materials4.3 Airlocks for Materials


Basics of Cleanroom Technology

Definition of Cleanroom

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

4


Definition of a Cleanroom

What is a Cleanroom?

Important components of a cleanroomDefinition according to ISO 14644 :

A cleanroom is an area set apart by a wall or similar partition, whose degree of cleanliness is achieved bypurified air ventilation. Cleanroom environment is pressurisedto outside area.

incomingfiltered air

ceiling

wall

+/- 0balanced pressure

floor

+ +overpressure


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 µm) 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 thereforecalled suspended particles.

5



Siev

ing

Act.

Car

bon

Filte

r

Gra

vity

Sep

arat

ion

Clot

h Fi

lter

Wet

Sep

arat

ion

Fibr

e Fi

lter

Mic

rosc

ope

Elec

tron

Mic

rosc

ope

Visi

ble

to N

aked

Eye

Toba

co S

mok

eAs

h

Ger

ms

Mis

tSm

og

Gas

Mol

ekul

eMin

eral

and

Met

al D

ust

Susp

ende

d M

atte

r

Viru

ses

Sink

ing

Dus

tH

eavy

Dus

t

Polle

n

Types of Particles SeparationMeasurementMethods

0,0001

0,001

0,01

0,1

10000

10

100

Parti

cle

Diam

eter

(m

)µ

1

1000

Rai

n



0,010,01 0,1 10 20 mm1

0,10

1,00

5,00

10,00

20,0030,0040,0050,0060,0070,00

80,0090,00

95,00

99,00

99,90

99,99

Concentrat ion(1)

%<

Parti

cle

Diam

eter

Weight (3)

Surface (2)

Particle Diameter

Distribution of Particle Sizes in Atmospheric Dust

Curve 1: Concentration of particles measured with an electron microscope

Curve 2: Projected particle surface, calculated

Curve 3: Percentage by weight, measured through sedimentation, the brokenpart of the line was calculated

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0,8µm

0,8µm

0,8µm

Comparisons of Size in Micro-Range I

0,8µ

m

0,8µ

m

1µm 80µm 60µm

Enlargement=10000

Enlargement=1000

0,8µ

m

0,8µ

m

0,8µ

m

Dust Particle 1µmConductor

Human HairSheet of Paper (Thickness)

1µm



60µm

60µm

30µm30µm

5µm

1µm

5µm

Typical Level of Travel of the Read/Write Head 0,5µm

20000µm

(20Meter)

Magnetic Coating

Smoke particleDust particle

Slit in Read/Write HeadFingerprint

Human Hair

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 0,5µm, which is smaller than a diameter of a human hair.

Aluminium Bearer Plate

Comparisons of Size in Micro-Range II

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Example of Contamination from Large Particles on Printed CircuitsEnlargement: 100times

Enlargement: 5 times

Sugar Crystal

Thump- Print

Circuit Paths

Circuit Paths

Accumulation of Sticky Particles 10-30µ

Hair 60µ Diam eter

25 000µ

60µ

each

125

µea

ch 1

25µ

60µ

60µ

60µ

60µ

25 000µ



External Impuritities

Introduction of contaminated outside air or circulating air *

Staff

impure process media or raw materials

Inadequately cleaned materials, tools etc.

* poor filter quality, not airtight filter seal surfaces, leakage in the ducting system, abrasion in air recirculation equipment and in the ducting system

Internal Impurities

Staff

Process

Production equipment, machines, tools etc.

Unsuitable building materials, work materials

Mechanical abrasion in the cleanroom

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It is important to take the contamination from people into account , which contributes considerable 30% of the total contamination in the cleanroom.

Percentage Distribution of the Sources of Contamination

People

30 - 40%

Process

20 - 30%

Equipment

20 - 30%Process-Media

5 - 10%Air

5 - 10%



Standing and sitting without moving

Sitting with gentle movement of head, hand or lower arm

Sitting with moderate body andfoot movement

Standing up with full body movement

Slow walking - approx 3,5 km/h

Walking at about 6 km/h

Walking at about 9 km/h

Gymnastics and sports

Type of ActivityParticle Emission perMinute and Person

100 000

500 000

1 000 000

2 500 000

5 000 000

7 500 000

10 000 000

15 - 30 000 000

Emission of Particles by Peoplemaking various Movementswithout Cleanroom Clothing

Germ emission per minute (according to Botzenhart)1 000 - 13 000 CFU depending on activity

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Paths of Contamination in the Cleanroom

contact contamination from touching

air-borne particles (aerosols)

contaminants in the process media (hydrosols)

removing the source of contamination

interrupting the transport mechanism for contaminants

The Contamination of Processes and Products can occur by:

Contamination can be avoided by:


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 35°C); 4 Dacron® felting; 5 condensation pipe (kept at 10°C); 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)

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Air Conveyance Systems, Planned Currents

Measuring Particles in prescribed Cleanroom of Class 100,000 before Refit I

Measuring-Point No.

0

1

2

3

4

Measuring Location

Supply air in helical outlet

2,5 m from center of window-wall

0,5 m from center of window-wall, right corner

Lighting device without person Ditto with working person

Center of room

Measuring Height in m

1,02,0

1,02,0

1,11,1

1,02,03,0

Particles= 0,5µ

21.300

19.10016.900

15.30012.900

52.00057.300

36.700117.10028.800

0

00

00

00

0<0

Particles= 5µ

1

11355

1729

1001.120

6311072

00

00

000



Incoming Air

cleanliness class

air speed

air temperature

relative humidity

ionisation

11



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



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)

12



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



Materials Handling

forms of movement

logistics of access

robot for local manipulation

automated conveyer systems

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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


Cleanliness Classes

Cleanroom with TMC Class 10.000-100.000

Industrial region

Cleanroom class 100

Industrial region with SMOG

Metropolitan area

Measurement Point

10.000.000 to 100.000.000

up to 3.500

.....up to 1.000.000.000

350.000 to 3.500.000

30.000.000 to 60.000.000

Particle Concentration:- Particles ( _> 0,5µm) per m 3

Concentration of Particles in the Air

Rural area after rain 1.000.000 to 10.000.000

Cleanroom class 01 up to 3,5

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Cleanliness Classes

per ft >_ dp3

Particle Diameters in Micrometer (dp)

Class 1 000/M 4.5

Class 100/M 3.5Class 10/M 2.5Class 1/M 1.5

Class 0

Cla ss 100 000/M 6.5

0,1 0,2 0,3 0,5 1 3 5 10

100 Mio

10 Mio

1 Mio

100 000

10 000

1 000

100

10

1

0,1

109

108

107

106

105

104

103

102

101

Particles Particles

Class 10 000/M 5.5

Outdoor Air

per m >_ dp3

Cleanroom ClassesAccording to ISO 14644


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.

Accordingly the relevant volume of air rises to 2,160,000,000 m3(approx. 2 thousand million m3). This would be the volume ofa train from the earth to the moon.

Result: A pin in 20 millionfreight 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

3 m

m

15


Air Flow Concepts I

Unidirectional Flowfor 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 thesensitive work areas and machines beingexposed to minimal contamination.

+-


Air Flow Concepts II

Turbulent Dilution Flow

The clean air in the case of Class 1,000 to 100,000is 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.

Air cir culation appliance

Filter outlet

16


Air Flow Concepts III

ULG

ULGULG

AL

ALULGAL

AL

*room he ight 3m ULG = recirculat ion equipment AL = outside air in feed

Class 100.000 / M6.5 according toFederal Standard 209D/209E V=0,017 m/sair changed 20 times per hour

Class 10.000 / M5.5 according toFederal Standard 209D/209E V=0,034 m/sair changed 40 times per hour

Class 1.000 / M4.5 according to Federal Standard 209D/209E V=0,1 - 0,2 m/sair changed 80 times per hour

Class100, 10, 1, 0.1 / M3.5-1 according toFederal Standard 209D/209E V=0,45 m/sair changed 540 times per hour


Air Flow Concepts IV

60

120

240

1620

1

2 x

4 x

27 x

Class 100.000 turbulent

10.000 turbulent

1.000 turbulent

100 laminar

10 laminar

1 laminar

0,1 laminar

Class

Class

Class

Class

Class

Class

Specific Air Volumem /h .m3 2

Cleanroom Classes Specific Size of Recir-culation Equipment

17


Air Flow Concepts V

10 000

7.00 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

20 000

30 000

40 000

50 000

60 000

70 000

80 000

90 000

100 000

7.00 - 8.159.00 - 9.1510.00 - 11.0012.00 - 13.0015.00 - 15.1517.00 - 18.0019.00 - 20.00

1 2

3

4 5

6

7

Example of Contamination Levels from Persons in a Cleanroom of Class 100,000 (turbulent)

1 Work begins (flexitime)2 Coffee break3 Service work in t he cleanroom4 Lunch break5 Afternoon tea6 Work en ds7 Cleaners at work

Safety Zone

Time

Num

ber o

f par

ticles

Underlying Contamination


Air Flow Concepts VI

Measuring-Point No.

0

1

2

3

4

Measuring Location

Supply air in helical outlet

2,5 m from center of window-wall

0,5 m from center of window-wall, right corner

Lighting device without personDitto with working person

Center of room

Measuring Height in m

1,02,0

1,02,0

1,11,1

1,02,03,0

Particles= 0,5µ

21.300

19.10016.900

15.30012.900

52.00057.300

36.700117.10028.800

0

00

00

00

0<0

Particles= 5µ

1

11355

1729

1001.120

6311072

00

00

000

Measuring Particles in prescribed Cleanroom of Class 100,000 before Refit I

0 Class 10 000 not achieved < Class 100 000 not achieved

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Air Flow Concepts VII

Measuring-Point No.

5

6

7

8

9

Measuring Location

Waste air to cable conduit

0,5 m from No. 5 belowceiling

Brush machine, outlet-side

2 m in front of door to hallway

InspectionInspection with smoking(lunch break)

MeasuringHeight in m

1,02,0

2,02,0

Particles= 0,5µ

117.700

186.100

174.400

284.600318.500

84.830206.200

<

<

<

<<

0<

Particles= 5µ

14

54

106

3973

109119

0

0

0

00

Measuring Particles in prescribed Cleanroom of Class 100,000 before Refit II

0 Class 10 000 not achieved < Class 100 000 not achieved


Cleanroom Clothing

Particle Emission from Persons

Function of Cleanroom Clothing

Evaluation Criteria for Cleanroom Clothing

Recommended Cleanroom Clothing

Dressing according to Cleanroom Standards

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Particle Emission from Persons

300 100 55001000015000

5000050000

50000

50000

90000

35000

1800

1800

2500

45005000

9000

10000

17000

24000

120180

250300

400

600

900

1800

250400

500800

650

1000

2500

4000

Particle Emission per sParticle Size > 0,5µm

ClothingCleanroom Suit

One-Piece

Head, Mouth andNose covered Head covered

Street SuitTwo-Piece

Kind of Movement

Standing

SittingHead Movement

Arm Movement

Walking slowlyWalking fast

Moving Body

Moving alndstretching body

Body Movement

Comparison of ParticleEmissions from various Activities of Movement with Cleanroom Clothingor Street Suits


Particle emission from persons

Particle Counts for a Class 10.000 Cleanroom Suit

Exposed body parts,~10.000 particles

Wiping cloth,~9.356 particles

Cap, ~320 particlesMouth area, ~500 particles

Normal trousers, socks, shirt,underwear, ~20.000 particles

Cotton/polyester coat,~10.017 particles

Approximate number of particles: 50.892/ft3/min.1 shift = 8 h x 60 min. = 480 mins.85 persons per shift

3 shifts produce = 50.692/ft3/min. x 480 mins. x 85 persons x 3 shifts = 6.205 x 109 particles/ft3/24 h

Shoes, ~500 particles

20


Particle emission from persons

Exposed body parts,~2.000 particles

Wiping cloth,~1.574 particles

Cap, ~128 particlesFacemask, ~200 particles

100% Polyester-overall,~1.807 particles

Arm-length gloves,~112 particles

Knee-length boots,~228 particles

Approximate number of particles: 6.049/28,2l/min.1 shift = 8 h x 60 min. = 480 mins.85 persons per shift

3 shifts produce = 6.049/ft3/min. x 480 mins. x 85 persons x 3 shifts = 740.397.600 x particles/ft3/24 h

Particle Counts determined with Particle Counter: Class 100 Cleanroom Suit


Function of Cleanroom Clothing

Particle Barrier

functions as a barrier to the particles emitted by the human bodyas well as fibres and particles from undergarments

Physiological Aspects

wearing comfort

warmth and dampness emitted from garments

Protection for the Worker

resistance to penetration by fluids

resistance to chemicals and solvents

flame resistance

conductivity

21



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



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

22



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



Electrostatic Qualities

conductive fibres in the fabric

treated with anti-static's

23


Recommended Cleanroom Clothing for various Cleanroom Classes

1

10

100

1 000

10 000

100 000

CleanroomClass accordingto Fed.St. 209E

Cleanroom Clothing

SpecialUnderwear

Head Covering Shoes Gloves ChangeFrequency

overalls

overalls

overalls

overalls

overalls

white coat

yes

recommended

no

no

no

yes

full protective hood

cap



hoodbeard covering

hood or capbeard covering

long overboots

overshoes

long overboots

long overboots

overboots or

overshoes

overshoes

no powder or lint

as required

no powder or lint

no powder or lint

no powder or lint

as required

for every entry

daily

orevery 2 days

every 2 days

for every entry

daily

daily


Dressing according Cleanroom Protocol I

Remove street clothing Remove all additional items suchas watches, jewellery, rings, etc.

Put on head cover

Enter "controlled

area" Temporary gloves

1 2 3

4

5

24


Dressing according Cleanroom Protocol II

6 Carefully take out the blister-packed clothes

On the changing bench, take off clogs etc.

7 and move feet over the clean side

Put on full hood8 Put on mask 9 Take out new (cleaned) overalls

10


Dressing according Cleanroom Protocol III

11 Pull on overalls without letting them touch the floor

On the changing bench, take off clogs etc.

12

Take special care to put on gloves and overshoes without contamination

Pull overshoes up over overalls

14 Put on new gloves15Go to workplace in cleanroom

16

13

25


Dressing according to Cleanroom Protocol

~ 6 m~ 13 m

Cleanroom - Changing Area

Overpressure m

aintainedby locking both side

s

Wardrobe for coats

Clothes lockers

Shower

WC

WC

Used clothin g,wasteEmergency Exit

Put oncleanroom shoes

Wash basins

Laundryhandover

Cleanroom clothing

Cleanroom

Area

Outside A

rea

Airshower

Street ClothingC leaning ZoneClearoom Clothing

Bench


Dressing according to Cleanroom Protocol

2 31

Cleanroom Zone Cleaning Zone

26


Behaviour in the Cleanroom

Staff as a Source of Contamination

Selection Criteria for Cleanroom Staff

Behaviour according to Cleanroom Standards

Rules and Guidelines

Cleaning the Materials


Staff as Source of Contamination

100.000 Particles(contaminant emissions

= dustskin particles,hair,germs,viruses,smoke etc.)

Size: 0,001 micron to;1 micron = 1/1.000 mm

10 microns

*1x

50x

5x 10x

100x

25x

150x/300x

Emission of Particles

**

*

*

*

* *

27



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



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

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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



Inappropriate Behaviour

Fast walking causes turbulencesdue to low pressure points.

If installations and appliances are set horizontally to the air current, turbu-lence is created on the underside.

Seizing something quickly fromabove creates turbulences andcontamination outbursts.

29



All staff working at a Clean Workplace must be trained repeatedly in all aspects which are relevant to the work in question.

At the Clean Workplace only the required amount of staff should be present.

As far as possible, all monitoring and inspections should be carried out from the outside.

If inspectors, service staff or visitors enter the Clean Work-place, the same rules of behaviour apply as for permanent workers in this area.

The movement of people between the Clean Workplace and the surrounding areas should be kept to a minimum.

1. Training

2. Staff

3. Checks

4. Visitors

5. Moving about

13 "Do's" - Behaviour in the Cleanroom



It is not permitted to take food, cigarettes, jewellery and other personal items to the Clean Workplace.

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

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.

Care must be taken that the prescribed working clothes are worn in the Cleanroom in the correct way at all times.

6. Private items

7. Materials

8. Movements

9. Working clothes


30



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.)

Speaking, coughing and sneezing may never take place in the direction of the critical working area.

When temporarily not working or merely observing at the Clean Workplace, the staff must move as far away as possible from the critical area.

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.

10. Contacts

11. Communication

12. Jobs

13. Handling




Put on gloves Put on protective hood

31



Take out new overalls without contamination and pull on without letting them touch the floor



Pull overshoes up over overalls, put on new gloves and then go to workplace in the cleanroom

32



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



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

33



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



Cleaning of windows, walls, equipments and transport materials with moist one-way cloth

34


Designing Workplaces in accordance with Cleanroom Standards

Designing Workplaces

Storage and Transport of Materials

Airlocks for Materials



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

35



Fittings which allow flow to pass through

Outflow opposed to inflow

No areas for contamination to collectdue to non-air flow exposure

Dense flow around heat sources



Flow pattern with lateral outflow through wall Flow pattern with double floor outflow

36



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

Flow pattern with dividing screen (apron) with double floor outflow



Materials for Transport and Storage Containers

PE - Polyethylene

PFA - Polyfluoramide

PP - Polypropylene

PVC - Polyvenyl Chloride

PMMA - Polymethyl Methacrylate

AL - Auminium

37



Storage

open under laminar flow

dustproof boxes, containers

Handling

special tools

tweezers, forceps

vacuum grips

carrier



Transport

dustproof boxes, containers

transport cars with integrated super clean air supply

38


Airlocks for Materials

internal pallets

external pallets

take sample

dust removal,possible changeof pallets

feed belt

pallet loading point

to store

inward goods


Cleanroom Validation ProceduresPreliminary Considerations

Purpose of Cleanroom: GMP RequirementAll 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 Cleanroom1. 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 Sheet1. 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.

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Cleanroom Validation Procedures

Steps of Validation1. User Requirement Specification (URS) by User2. Cleanroom and Facility Design by Cleanroom Engineer3. Design Qualification (DQ) = Commissioning – Procurement4. Installation Qualification (IQ) = Commissioning – Installation and Testing5. Operation Qualification (OQ) = Commissioning – Certification6. Performance Qualification (PQ) = Compliance to Room Data Sheet7. Cleaning Validation

** DQ can be covered in normal design reviews


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

SpecificationsPurchase OrdersVendor Proposal DocumentsLayoutsP&ID/FlowsheetsContractor Strategy / Interfaces

Executed in Parallel with During Commissioning – Procurement

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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 CalibrationEquipment specifications, drawings, operation and maintenance manuals Installation check of Critical ComponentsCritical Component P&ID and Loop CheckTesting and Balancing ReportHEPA filter Integrity Testing Data Review

Executed in Parallel with During Commissioning – Installation


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 CalibrationTesting of Critical Alarms and Interlocks List of Critical Operating Parameters encompassed by Room Data SheetTesting for the Specifications detailed in the Room Data SheetStandard Operation Protocol for HVAC System ControlsCleanroom Operation Protocols for Cleanroom Operations

Executed in Parallel with During Commissioning – Testing, Balancing, Certification

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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 Cleanroomconditions.

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


Cleanroom Validation Procedures: Additional Considerations

Worst Case ScenariosIdentify critical operating parametersSet operational ranges for each critical parameterDesign worst case scenarios to test extremes of ranges

min/max temperatures and humidityprocess equipment operational contaminationpersonnel operational contaminationEquipment maintenance schedule

Operational ConsiderationsRecovery TimeCleaning ProceduresCleaning ValidationRe-testing, Re-Certification, and Re-Validation Schedule

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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 client’s 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.