6. CLEAN ROOM Presentation

7/30/2019 6. CLEAN ROOM Presentation

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PRESENTATI ON ON CLEAN ROOMAND

I TS PROTOCOLS

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WHAT I S CLEAN ROOM?

WHO ARE THE USERS OF CLEAN ROOM?

WHY CLEAN ROOMS ARE REQUI RED I N THE

PHARMACEUTI CAL I NDUSTRI ES?

WHAT I S THE DESI GN OF CLEAN ROOM

HOW THE CLEAN ROOMS ARE MAI NTAI NED?

CLEAN ROOMQUERRI ES?

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WHAT ARE THE PROTOCOLS TO ENTER I N TO CLEAN ROOM?

HOW THE CLEAN ROOMS ARE MAI NTAI NED?

WHAT QUALI TY OF AI R TO BE USED I N CLEAN ROOM?

WHAT QUALI TY OF WATER TO BE USED I N CLEAN ROOM?

CLEAN ROOM

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WHAT I S CLEAN ROOM

DEFI NI TI ON: Federal St andard 209 Defines a Clean Room

A Clean Room is an enclosed area employing cont rol over t he

part iculate matt er in air w it h t emperatur e, humidit y and pressure

cont rol as required. To meet t he requirements of a 'Clean Room' asdefined by t his standard, all Clean Rooms must not exceed a

part iculat e count as specified in t he air cleanliness class." This

st andard, fi rst i ssued in 1963, has been used in t he cur rent version

209B amendment 1 since 1976. I t is short ly t o be re-issued,

ent it led "Airbor ne Part iculat e Cleanliness Classes for Clean Rooms

and Clean Zones" .

CLEAN ROOM

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WHAT I S CLEAN ROOM

DEFI NI TI ON:

BS 5295 Defin it ion

"A Clean Room is a room w it h environmental control of part iculate

cont aminat ion, t emperatu re and hum idit y, constructed and used in

such a way as to m inim ize the int roduction, generation and

retention of part icles inside the room."

CLEAN ROOM

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I ndust ry Applicat ions

ELECTRONI CS Comput ers, TV-t ubes, Magnet ic Tapes

SEMI CONDUCTORS I nt egrat ed Cir cuit s

MI CROMECHANI CS Compact Disc Players, Mini ature Bearings, Gyroscopes

OPTI CS Lenses, Photographic Film, Laser Equipment

BI OTECHNOLOGY Ant ib iot ics, Gener ic Engineer ing

PHARMACY St erile Pharm aceut icals, St er ile Disposable

MEDI CAL DEVI CES Heart Valves, Card iac by-pass Syst ems

FOOD AND DRI NK Brewery Product ion, Unsterili zed Food and Drink s

HOSPI TALSI mm unodeficiency Therapy, I solation of ContagiousPatients, Operat ing Rooms

APPLI CATI ONS

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CLEAN ROOM

WHY CLEAN ROOMS ARE REQUI RED I N PHARMACEUTI CALI NDUSTRI ES ?

CLEAN ROMS ARE REQUI RED TO AVOI D THE SOURCE OF

CONTAMI NATI ONS.

TYPES OF CONTAMI NATI ONS

1. Part iculate: dust , makeup, skin, hair,

2. Chemical: oil, grease, perfum e,

3. Biological: bacteria, fungi,

4. Radiat ion (ul t raviolet l ight, )

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People (~ 75% )

Vent i lat ion (~ 15% )

Room structure (~ 5% )

Equipment (~ 5% )

SOURCES OF CONTAMI NATI ONS

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HOW TO CONTROL CONTAMI NATI ONS?

PERSONNEL CONTROL

* DRESS CODES

* Personal Hygiene

* GARMENTS/ GOWNI NG

Hair cover , Hood , Shoe covers ,Coverall, GlovesFace mask , Safety Glasses

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ENVI RONMENTAL CONTROL

* ENTERENCE AND EXI T CONTROL---

* SUPPLY OF MATERI AL AND TOOLS CONTROL

(Through Pass Box)

* ROUTI NE CLEAN ROOM CLEANI NG ANDMAI NTENANCE

Access

Cards

Air show er

w hile entering

CONTI NUED...

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GENERAL FEATURES OF CLEAN ROOM

Protocol for clean room provides general guidance andbasic aw areness

Successful clean room maintenance really relies onindividual users understanding, participation and selfdiscipline.

Everyone, whether faculty member, student user or staffengineer, is equally important to the success of theprotocol.

Trust , underst anding and shared r esponsibilit y among allusers ensures the success of every user.

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PRI NCI PLES OF CLEAN ROOM

Air is highly (HEPA) fil t ered (99.97% @ 0.3m)

Layout should minim ize part icle sources infi lt ered air st ream

Air flow should remove most part icles generatedby process

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HEPA - HI GH EFFI CI ENCY PARTI CULATE AI R FI LTER

ULPA Filt ers- ULTRA LOW PENETRATI ON AI R.

TYPES OF FI LTERS

EFFECT OF EFFI CI ENCY:

ULPA is more eff icient t han HEPA.

HEPA - 99.97% (To remove 0.3 micron part icles)

ULPA - 99.99% (To remove 0.1 micron part icles)

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HOW TO TEST THE EFFECI ENCY?

DOP TEST (PENETRATI ON TEST)

DOP - Di-oct yl-pt halat e

ADVANTAGE -

TO DETERMI NE % OF PARTI CLE PASSI NGTHROUGH FI LTERS

WHY I S THI S TEST PREFERRED?

DOP PARTI CLE SI ZE I S 0.2 MI CRON CONSI STANTLY.

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HOW SHOULD BE THE LAYOUT ..?

Production

Plant

Change

Room Toilets

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BUI LDI NG FI NI SHES

Not Acceptable Acceptable

PVA Paint Epoxy or Enamel paint

Window si l ls Window view panels

Exposed p ipes Smoot h sur f aces (Electro

polished)Horizont al pi pes &services Concealed services

Open f loor drains Hygienic drains

Floor cracks, f l aking

fl oor sur faces

Homog onous sealedf loors epoxy f inish or

welded vinyl

Cei l ing cracks & joint s Smooth sealed cei l ings

Exposed, open li gh tf i t t ings Flush l ight f i t t i ngs

Wooden fu rni tur e S/ Steel mi rr or f inished or

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FLOOR FI NI SHI NG

NOT ACCEPTABLE

Tiled Floor Epoxy Floor

RECCOMMENDED

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NOT ACCEPTABLE RECCOMMENDED11/ 21/ 2008 18KI RAN DESAI

Good WindowsPoor Window


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SERVI CE DI STRI BUTI ON

Accessibilit y for cleaning is not

there

Cleaning is easier

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Where ever it i s possible possible serv ices should be locat ed

behind w all panels.

Exposed serv ices & pipes are very diff icult t o clean, &

somet imes impossible t o clean.

Equipment such as Film Coaters should be enclosed so that

only t he fron t face is in the GMP area. This makes cleaning

much easier.

Make use of servi ce corridors behind equipment ( but must beunder negative pressure)

I nsulation of all the ut i l i t y l ines should be GI coated and

enamel paint ed.

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ALWAYS ROOM SHOULD BE WI TH POSI TI VE PRESSURES.

THE I NTERNAL PARTI CULATE GENERARTI ON TO BE CONTROLLED BY

EPOXY FLOORI NG

HARD SURFACED NON PORUS MATERI AL ( PVC PANELS)

EPOXY PAI NTED WALLS

GLASS BOARD CEI LI NGS

PROPER HVAC(HEATI NG VENTI LLATI ON AI R CONDI TI ONI NG)

PROPER DOOR CLOSURES

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Continued

BOTTOM CLOSURES

COVI NG ON WALLS AND FLOORS TO AVOI D ACCUMALATI ONOF DUST.

ENTRY FOR SPECI FI ED PERSON WI TH ACCESS CARDS

ALL THE ROOMS SHOULD HAVE FI RE ALARM SYSTEMS

CLEAN ROOM SHOULD HAVE TEMPERATURE ANDHUMI DI TY CONTROLLER SYSTEMS.

AI R LOCK SHOULD BE PROVI DED FOR ACCESSI NG TWOROOMS.

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AI R FLOW

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TYPES OF AI R FLOW

1. LAMI NAR AI RFLOW

2. TURBULENT AI RFLOW

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LAMI NAR AI R FLOW CLEAN ROOM

Laminar air f low is used w hen low airborne concentrat ions of

part icles or bacteria are required.

This air flow pattern is in one direction, usually horizontal or

vertical at a uniform speed of betw een 60 t o 90 ft / min. andth roughout t he ent ire space.

The air velocity is sufficient to remove relatively largepart icles before t hey sett le onto surf aces.

Any contaminant released into the air can therefore beimm ediat ely removed by this laminar f low of air, w hereas theturbulent air f low ventilated system relies on mixing anddilution t o remove cont amination.

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LAMI NAR AI R FLOW CLEAN ROOM

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Any obstructions wil l cause the laminar air f low to be

t urned into turbulent air f low around the obstr uctions.

Higher contamination concentrations will be established

in t he turbulent areas.

Air changes per unit of t ime are relat ed to t he volume ofthe room and are many times greater than thosesupplied to a t urbulent air f low Clean room.

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The general method of ventilation used in turbulent air f lowclean rooms is similar t o that found in bui ldings such as off ices,schools, malls, manufactur ing plant s, audit orium s, shops, et c.

The air is supplied by an air conditioning system throughdiff users in the ceiling.

However, a clean room differs from an ordinary vent ilated roomin three w ays. These are increased air supply, t he use of highefficiency filt ers and room pressurization .

The increased air supply is an important aspect of particlecontrol. A typical turbulent air f low clean room would have atleast 10 air changes per hour and lik ely to have betw een 20 and

60.

TURBULENT AI R FLOW

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TURBULANT AI R FLOW CLEAN ROOM

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TURBULANT AI R FLOW CLEAN ROOM

This additional air supply is mainly provided to dilute to anacceptable concentration the contamination produced in theroom.

High efficiency fi l t ers are used to f i l t er the supply air int o a cleanroom to ensure the removal of small particles. The high

efficiency filt ers used in clean rooms are installed at t he point ofair discharge into t he room.

Room pressurization is mainly provided to ensure that untreated

air does not pass fr om dir t ier adjacent areas int o t he clean room.

The clean room is positively pressurized with respect to thesedirtier areas. This is done by extracting less air from the roomthan is supplied to it .

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APPLI CATI ONS

LAMI NAR AI R FLOW

FORMULATI ON

STERI LE PLANTS

TURBULENT AI R FLOW

NON STERI LE PLANTS

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PARTI CLE CHARACTERI STI CS OF CLEAN ROOM

50 m icron part icles are visible

Average human hair is about 100 m icrons

Time t o fall 1 m eter in st il l air

33 seconds for 10 micron part icle

48 m inut es for 1 micron particle

Humans generate > 1x105 part icles perminute when mot ionless (f ully gowned)

Humans can generate > 1x106 particlesw hen w alking in t he clean room

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GUI DELI NES AND DESI GN PARAMETERS OF CLEAN ROOM

FUNDAMENTAL OF CLEAN ROOM DESI GN I S TO CONTROLTHE CONCENTRATI ON OF AI RBORNE PARTI CLES.

A PROPER HVAC SYSTEM I S CRI TI CAL PART OF CLEAN

ROOM DESI GN.

PARTI CULATE MATTER CAN BE CONTROLLED BY HEPAFI LTERS WI TH MI N EFFECI ENCY OF 99.97% TESTED ON0.3 MI CRON

NUMBER OF AI R CHANGES PER HOUR SHOULD BE I N THERAGE OF 10 TO 20 .

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CLASSI FI CATI ONS OF CLEAN ROOM

HOW ARE CLEAN ROOMS CLASSI FI ED?

CLEAN ROOMS ARE CLASSI FI ED BASED ON CLEANLI NESS OF AI R.

Federal St andard 209D Class Limit s

Federal St andard 209E Airborne Part iculat e CleanlinessClasses

Brit ish St andard 5295:1989

BR 525 Env ironm ent al Cleanl iness Classes

BS EN I SO St andard

STANDARDS OF CLEAN ROOM

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CLASS

MEASURED PARTICLE SIZE

(MICROMETERS)

0.1 0.2 0.3 0.5 5

1 35 7.5 3 1 NA

10 350 75 30 10 NA

100 NA 750 300 100 NA

1,000 NA NA NA 1,000 7

10,000 NA NA NA 10,000 70

100,000 NA NA NA 100,000 700

Federal Standard 209D Class Limit s

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Class Name Class Limits0.1m m 0.2m m 0.3m m 0.5m m 5m m

Volume Units Volume Units Volume Units Volume Units Volume Units

SI English (m^3) (ft^3) (m^3) (ft^3) (m^3) (ft^3) (m^3) (ft^3) (m^3) (ft^3)

M 1 350 9.91 75.7 2.14 30.9 0.875 10 0.283 -- --

M 1.5 1 1 240 35 265 7.5 106 3 35.3 1 -- --

M 2 3 500 99.1 757 21.4 309 8.75 100 2.83 -- --

M 2.5 10 12 400 350 2 650 75 1 060 30 353 10 -- --

M 3 35 000 991 7 570 214 3 090 87.5 1 000 28.3 -- --

M 3.5 100 -- -- 26 500 750 10 600 300 3 530 100 -- --

M 4 -- -- 75 700 2 140 30 900 875 10 000 283 -- --

M 4.5 1 000 -- -- -- -- -- -- 35 300 1 000 247 7

M 5 -- -- -- -- -- -- 100 000 2 830 618 17.5

M 5.5 10 000 -- -- -- -- -- -- 353 000 10 000 2 470 70

M 6 -- -- -- -- -- -- 1 000 000 28 300 6 180 175

M 6.5 100 000 -- -- -- -- -- -- 3 350 000 100 000 24 700 700

M 7 -- -- -- -- -- -- 10 000 000 283 000 61 800 1 750

Federal Standard 209E Airborne Particulate Cleanliness Classes

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BS 5295 ENVI RONMENTAL CLEANLI NESS CLASSES

Maximum permitted number of particles per m^3 (equal to,or greater than, stated size)

Maximumfloor area

per

sampling

position for

clean rooms(m^2)

Minimum pressuredifference*

Class of

environment

al cleanliness

0.3 m m 0.5 m m 5 m m 10 m m 25 m m Between

classified

areas andunclassifie

d areas(Pa)

Between

classified area

and adjacentareas of lower

classification(Pa)

C 100 35 0 NS NS 10 15 10

D 1 000 350 0 NS NS 10 15 10

E 10 000 3 500 0 NS NS 10 15 10

F NS 3 500 0 NS NS 25 15 10

G 100 000 35 000 200 0 NS 25 15 10

H NS 35 000 200 0 NS 25 15 10

J NS 350 000 2 000 450 0 25 15 10

K NS 3 500 000 20 000 4 500 500 50 15 10

L NS NS 200 000 45 00 5 000 50 10 10

M NS NS NS 450 000 50 000 50 10 NA

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I SO 209 airborne part iculate cleanliness classes for clean roomsand clean zones.

Numbers (N) Maximum concentration l imits (part icles /m^3 of ai r) for par ticles equal to and larger than the

considered sizes shown below

0.1m m* 0.2m m 0.3m m 0.5m m 1m m 5.0m m

ISO 1 10 2

ISO 2 100 24 10 4

ISO 3 1 000 237 102 35 8

ISO 4 10 000 2 370 1 020 352 83

ISO 5 100 000 23 700 10 200 3 520 832 29

ISO 6 1 000 000 237 000 102 000 35 200 8 320 293

ISO 7 352 000 83 200 2 930

ISO 8 3 520 000 832 000 29 300

ISO 9 35 200 000 8 320 000 293 000

* m m Micro Meter

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GRAPHI CAL REPRESENTATI ON OF AI RBORNE PARTI CLES

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GENERAL CLEAN ROOM REGULATI ONS

Below is a list of general regulat ions recomm ended as aminim um for t he successful operation of a clean room. Allprofessional cleaning personnel should be aware and followt hese regulations at all t imes.

All personal it ems such as keys, watches, rings, matches,

light ers and cigarett es should be stored in t he personal lockeroutside the gow ning room.

Valuable personal I t ems such as w allet s may be permi t t ed int he clean r oom provided t hey are NEVER removed fr om

beneath the clean room garm ents.

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CONTI NUED

NO eat ing, smoking or gum chew ing allow ed inside theclean room.

Only garm ents approved for t he clean room should bew orn when entering.

NO cosmet ics shall be w orn in t he clean room s. Thisincludes:

rouge, lipsti ck, eye shadow , eyebrow pencil, mascara,

eyeliner , false eye lashes, fingernail pol ish, hair spray,mousse, or t he heavy use of aerosols, aft er shaves and

perfumes.

Only approved clean room paper shall be allow ed in the

clean room.

Approved ball point pens shall be the only w rit ing t oolused.

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Use of paper or fabr ic tow els are prohibit ed. Use of hand dryersequipped w it h HEPA filt ers are suggest ed.

Gloves or fi nger coat s should not be allowed to t ouch any item or

surface t hat has not been t horough ly cleaned.

Only approved gloves, finger cots (pow der-f ree), pliers, t w eezersshould be used t o handle product . Finger pr int s can be a majorsource of cont aminat ion on some products.

Solvent cont act w it h t he bare skin should be avoided. They canremove skin oils and increase skin flaking.

CONTI NUED

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Approved skin lot ions or l anolin based soaps aresomet imes allow ed. These can r educe skin flaking.

All t ools, cont ainers and f ixt ures used in t he cleaning

process should be cleaned to t he same degree as theclean room surfaces. All of t hese it ems are a source ofcontamination.

NO tool should be allow ed to rest on t he surf ace of a benchor t able. I t should be place on a clean room w iper.

CONTI NUED.

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Only clean room approved w ipers are allow ed to be used.The w ipers must be approved for t he Class of clean roombeing cleaned.

ALL equipment , materials and containers intr oduced int o a

st erile facil it y m ust be subj ected t o stringent st eri l izationprior t o entrance.

NO ONE w ho is physically ill , especially w it h respirat ory orstomach di sorders, may ent er a sterile r oom. This is a good

practice in any clean room environment .

CONTI NUED.

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HVAC DESAI GN CONSI DERATI ONS

1. Temperature and Humidity

2. Pressurizat ion

3. Venti lat ion and Make Up Air

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Temperat ure and Humidit y

Most clean room require year-round cooling as a result of the fan

energy associated w it h high clean room airfl ow as w ell as t he heatgenerated by the process, people, and light ing w it hin t he facilit y.

Temperature control is required to provide stable conditions for

mat erials, instruments, and personnel comf ort .

Human comf ort requirements typically call for temperatu res in t herange of 72F to 75 F, since workers frequently wear clean roomgarments over st reet clothes.

Humidity control is necessary to prevent corrosion, condensationon w ork surfaces, eliminate st atic elect ricit y, and prov ide personnelcomfort.

The human comfort zone is generally in the range of 30% t o 70%relative humidity

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A clean room facil ity may consist of multiple rooms withdifferent requirements for contamination cont rol.

Rooms in a clean facility should be maintained at staticpressures higher than atmospheric to prevent infi ltration bywind.

Positive differential pressures should be maintained betweenthe rooms to ensure air f lows from the cleanest space to theleast clean space.

The only exception to using a positive differential pressure iswhen dealing with specific hazardous materials wheregovernmental agencies require the room to be at a negativepressure.

Pressurization

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HOW I S AI R PRESSURE MEASURED?

The pressure different ial over the doorw ay is measured w it ha portable magnahelic gauge or micro manometer

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Venti lati on and Make Up Air

Ventilation and makeup air volumes are dictated by the amountrequired to maintain indoor air quality, replace process exhaustand for building pressurization.

This provides assurance that carbon dioxide and oxygen remain in

balance, t hat formaldehyde and other vapors given off by buildingmaterials and furniture are diluted, and that air changes occurwith sufficient frequency to minimize the chance for highconcent ration of airborne pollutant s w ith in t he building.

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HOUSE KEEPI NG

Every user is responsible for k eeping t he clean room s clean.

Alw ays clean your w orkspace before leaving.

Dont leave or store it ems on or in equipment .

Do not set liqu ids on any equipm ent.

Properly store all materials before leaving t he clean room

Last one out should make sure t he room is in a safe idle mode.

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CHEMI CAL HANDLI NG IN CLEAN ROOMS

Chemical w ast e should be properly disposed of as

out lined by EHS systems.

No chemicals may be poured dow n t he drains Wast e cont ainers should be properly marked as such and

have a pink Hazardous Waste tag t ied to t hem at all

t imes.

I f you have quest ions about disposal cont act a st aff

member.

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VOI LATI ON OF RULES

First t ime

Warning

Report t o Advisor

Second t ime

Suspension of access

Report t o Advisor

Retraining may be required

Thir d Off ense

Suspension of access

Report t o Advisor

Access w ill not be renew ed until an accept able resolution is

reached betw een Advisor and Clean room Manager

Clean room Prot ocol re-t raining w ill be required.

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CLEAN ROOM

DOORS

FLUSHEDWI NDOWS

FALSE CEI LI NG

FLUSHED

LI GHTI NG

HVACSUPPLY

EPOXY FLOORI NG

COVI NG

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6. CLEAN ROOM Presentation