Clean Room

PRESENTATION ON CLEAN ROOM
AND
ITS PROTOCOLS
11/21/2008 KIRAN DESAI 1

CLEAN ROOM
QUERRIES…………?
 WHAT IS CLEAN ROOM?
 WHO ARE THE USERS OF CLEAN ROOM?
 WHY CLEAN ROOMS ARE REQUIRED IN THE
PHARMACEUTICAL INDUSTRIES?
 WHAT IS THE DESIGN OF CLEAN ROOM
 HOW THE CLEAN ROOMS ARE MAINTAINED?

CLEAN ROOM
 WHAT ARE THE PROTOCOLS TO ENTER IN TO CLEAN ROOM?
 HOW THE CLEAN ROOMS ARE MAINTAINED?
 WHAT QUALITY OF AIR TO BE USED IN CLEAN ROOM?
 WHAT QUALITY OF WATER TO BE USED IN CLEAN ROOM?

CLEAN ROOM
WHAT IS CLEAN ROOM
DEFINITION:
• Federal Standard 209 Defines a Clean Room
A Clean Room is an enclosed area employing control over the
particulate matter in air with temperature, humidity and pressure
control as required. To meet the requirements of a 'Clean Room' as
defined by this standard, all Clean Rooms must not exceed a
particulate count as specified in the air cleanliness class." This
standard, first issued in 1963, has been used in the current version
209B amendment 1 since 1976. It is shortly to be re-issued,
entitled "Airborne Particulate Cleanliness Classes for Clean Rooms
and Clean Zones".

CLEAN ROOM
WHAT IS CLEAN ROOM
DEFINITION:
BS 5295 Definition
"A Clean Room is a room with environmental control of particulate
contamination, temperature and humidity, constructed and used in
such a way as to minimize the introduction, generation and
retention of particles inside the room."

APPLICATIONS
Industry Applications
ELECTRONICS Computers, TV-tubes, Magnetic Tapes
SEMICONDUCTORS Integrated Circuits
MICROMECHANICS Compact Disc Players, Miniature Bearings, Gyroscopes
OPTICS Lenses, Photographic Film, Laser Equipment
BIOTECHNOLOGY Antibiotics, Generic Engineering
PHARMACY Sterile Pharmaceuticals, Sterile Disposable
MEDICAL DEVICES Heart Valves, Cardiac by-pass Systems
FOOD AND DRINK Brewery Production, Unsterilized Food and Drinks

Immunodeficiency Therapy, Isolation of Contagious
HOSPITALS Patients, Operating Rooms

CLEAN ROOM
WHY CLEAN ROOMS ARE REQUIRED IN PHARMACEUTICAL
INDUSTRIES ?
CLEAN ROMS ARE REQUIRED TO AVOID THE SOURCE OF

CONTAMINATIONS.
TYPES OF CONTAMINATIONS
1. Particulate: dust, makeup, skin, hair, …
2. Chemical: oil, grease, perfume, …
3. Biological: bacteria, fungi, …
4. Radiation (ultraviolet light, …)

SOURCES OF CONTAMINATIONS
 People (~ 75%)
 Ventilation (~ 15%)
 Room structure (~ 5%)
 Equipment (~ 5%)

HOW TO CONTROL CONTAMINATIONS?
 PERSONNEL CONTROL
* DRESS CODES
* Personal Hygiene
* GARMENTS/GOWNING
Hair cover , Hood , Shoe covers ,
Coverall, Gloves
Face mask , Safety Glasses

CONTINUED...
 ENVIRONMENTAL CONTROL
Access
Cards
* ENTERENCE AND EXIT CONTROL---
Air shower
while entering
* SUPPLY OF MATERIAL AND TOOLS CONTROL

(Through Pass Box)
* ROUTINE CLEAN ROOM CLEANING AND

MAINTENANCE

GENERAL FEATURES OF CLEAN ROOM
 Protocol for clean room provides general guidance and

basic awareness
 Successful clean room maintenance really relies on

individual user’s understanding, participation and self
discipline.
 Everyone, whether faculty member, student user or staff

engineer, is equally important to the success of the
protocol.
 Trust, understanding and shared responsibility among all

users ensures the success of every user.

PRINCIPLES OF CLEAN ROOM
•Air is highly (HEPA) filtered (99.97% @ 0.3m)
•Layout should minimize particle sources in

filtered air stream
•Air flow should remove most particles generated

by process

TYPES OF FILTERS
HEPA - HIGH EFFICIENCY PARTICULATE AIR FILTER
ULPA Filters- ULTRA LOW PENETRATION AIR.
EFFECT OF EFFICIENCY:
ULPA is more efficient than HEPA.
HEPA - 99.97% (To remove 0.3 micron particles)
ULPA - 99.99% (To remove 0.1 micron particles)

HOW TO TEST THE EFFECIENCY?
DOP TEST (PENETRATION TEST)
DOP - Di-octyl-pthalate
ADVANTAGE -
TO DETERMINE % OF PARTICLE PASSING

THROUGH FILTERS
WHY IS THIS TEST PREFERRED?
DOP PARTICLE SIZE IS 0.2 MICRON CONSISTANTLY.

HOW SHOULD BE THE LAYOUT ………………..?
Production
Plant
Change
Room Toilets

BUILDING FINISHES
Not Acceptable Acceptable
PVA Paint Epoxy or Enamel paint
Window sills Window view panels
Exposed pipes Smooth surfaces (Electro

polished)
Horizontal pipes & Concealed services
services
Open floor drains Hygienic drains
Floor cracks, flaking Homogonous sealed

floor surfaces floors – epoxy finish or
welded vinyl
Ceiling cracks & joints Smooth sealed ceilings
Exposed, open light Flush light fittings
fittings
Wooden furniture S/Steel mirror finished or
11/21/2008
Melamine furniture
KIRAN DESAI 16
FLOOR FINISHING…………
Tiled Floor Epoxy Floor
NOT ACCEPTABLE RECCOMMENDED

Poor Window
Good Windows
NOT ACCEPTABLE RECCOMMENDED

SERVICE DISTRIBUTION
Cleaning is easier
Accessibility for cleaning is not

there
 Where ever it is possible possible services should be located
behind wall panels.
 Exposed services & pipes are very difficult to clean, &
sometimes impossible to clean.
 Equipment such as Film Coaters should be enclosed so that
only the front face is in the GMP area. This makes cleaning
much easier.
 Make use of service corridors behind equipment (but must be
under negative pressure)
 Insulation of all the utility lines should be GI coated and
enamel painted.

ALWAYS ROOM SHOULD BE WITH POSITIVE PRESSURES.
THE INTERNAL PARTICULATE GENERARTION TO BE CONTROLLED BY
 EPOXY FLOORING
 HARD SURFACED NON PORUS MATERIAL (PVC PANELS)
 EPOXY PAINTED WALLS
 GLASS BOARD CEILINGS
 PROPER HVAC
(HEATING VENTILLATION AIR CONDITIONING)
PROPER DOOR CLOSURES

Continued………
 BOTTOM CLOSURES
 COVING ON WALLS AND FLOORS TO AVOID ACCUMALATION

OF DUST.
 ENTRY FOR SPECIFIED PERSON WITH ACCESS CARDS
 ALL THE ROOMS SHOULD HAVE FIRE ALARM SYSTEMS
 CLEAN ROOM SHOULD HAVE TEMPERATURE AND

HUMIDITY CONTROLLER SYSTEMS.
 AIR LOCK SHOULD BE PROVIDED FOR ACCESSING TWO

ROOMS.

AIR FLOW

TYPES OF AIR FLOW
1. LAMINAR AIRFLOW
2. TURBULENT AIRFLOW

LAMINAR AIR FLOW CLEAN ROOM
 Laminar air flow is used when low airborne concentrations of

particles or bacteria are required.
 This air flow pattern is in one direction, usually horizontal or

vertical at a uniform speed of between 60 to 90 ft/min. and
throughout the entire space.
 The air velocity is sufficient to remove relatively large

particles before they settle onto surfaces.
 Any contaminant released into the air can therefore be

immediately removed by this laminar flow of air, whereas the
turbulent air flow ventilated system relies on mixing and
dilution to remove contamination.

LAMINAR AIR FLOW CLEAN ROOM

 Any obstructions will cause the laminar air flow to be
turned into turbulent air flow around the obstructions.
 Higher contamination concentrations will be established

in the turbulent areas.
 Air changes per unit of time are related to the volume of

the room and are many times greater than those
supplied to a turbulent air flow Clean room.

TURBULENT AIR FLOW
 The general method of ventilation used in turbulent air flow

clean rooms is similar to that found in buildings such as offices,
schools, malls, manufacturing plants, auditoriums, shops, etc.
 The air is supplied by an air conditioning system through

diffusers in the ceiling.
 However, a clean room differs from an ordinary ventilated room

in three ways. These are increased air supply, the use of high
efficiency filters and room pressurization.
 The increased air supply is an important aspect of particle

control. A typical turbulent air flow clean room would have at
least 10 air changes per hour and likely to have between 20 and
60.

TURBULANT AIR FLOW CLEAN ROOM

TURBULANT AIR FLOW CLEAN ROOM
 This additional air supply is mainly provided to dilute to an

acceptable concentration the contamination produced in the
room.
 High efficiency filters are used to filter the supply air into a clean
room to ensure the removal of small particles. The high
efficiency filters used in clean rooms are installed at the point of
air discharge into the room.
 Room pressurization is mainly provided to ensure that untreated

air does not pass from dirtier adjacent areas into the clean room.
The clean room is positively pressurized with respect to these
dirtier areas. This is done by extracting less air from the room
than is supplied to it.

APPLICATIONS
LAMINAR AIR FLOW
 FORMULATION
 STERILE PLANTS
TURBULENT AIR FLOW
 NON STERILE PLANTS

PARTICLE CHARACTERISTICS OF CLEAN ROOM
 50 micron particles are visible
 Average human hair is about 100 microns
 Time to fall 1 meter in still air
• 33 seconds for 10 micron particle
• 48 minutes for 1 micron particle
 Humans generate >1x105 particles per

minute when motionless (fully gowned)
 Humans can generate >1x106 particles

when walking in the clean room
GUIDELINES AND DESIGN PARAMETERS OF CLEAN ROOM
 FUNDAMENTAL OF CLEAN ROOM DESIGN IS TO CONTROL

THE CONCENTRATION OF AIRBORNE PARTICLES.
 A PROPER HVAC SYSTEM IS CRITICAL PART OF CLEAN

ROOM DESIGN.
 PARTICULATE MATTER CAN BE CONTROLLED BY HEPA

FILTERS WITH MIN EFFECIENCY OF 99.97% TESTED ON
0.3 MICRON
 NUMBER OF AIR CHANGES PER HOUR SHOULD BE IN THE

RAGE OF 10 TO 20.

CLASSIFICATIONS OF CLEAN ROOM
• HOW ARE CLEAN ROOMS CLASSIFIED?

CLEAN ROOMS ARE CLASSIFIED BASED ON CLEANLINESS OF AIR.
STANDARDS OF CLEAN ROOM
• Federal Standard 209D Class Limits

• Federal Standard 209E Airborne Particulate Cleanliness
Classes
• British Standard 5295:1989
• BR 525 Environmental Cleanliness Classes
• BS EN ISO Standard

Federal Standard 209D Class Limits
MEASURED PARTICLE SIZE

CLASS (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 209E Airborne Particulate Cleanliness Classes
Class Name Class Limits

0.1m 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)
M1 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 -- --
M2 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 -- --
M3 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 -- --
M4 -- -- 75 700 2 140 30 900 875 10 000 283 -- --
M 4.5 1 000 -- -- -- -- -- -- 35 300 1 000 247 7
M5 -- -- -- -- -- -- 100 000 2 830 618 17.5
M 5.5 10 000 -- -- -- -- -- -- 353 000 10 000 2 470 70
M6 -- -- -- -- -- -- 1 000 000 28 300 6 180 175
M 6.5 100 000 -- -- -- -- -- -- 3 350 000 100 000 24 700 700
M7 -- -- -- -- -- -- 10 000 000 283 000 61 800 1 750

BS 5295 ENVIRONMENTAL CLEANLINESS CLASSES
Maximum permitted number of particles per m^3 (equal to, Maximum Minimum pressure
or greater than, stated size) floor area difference*
per
sampling
position for
clean rooms
(m^2)
Class of 0.3 m m 0.5 m m 5mm 10 m m 25 m m Between Between
environment classified classified area
al cleanliness areas and and adjacent
unclassifie areas of lower
d areas classification
(Pa) (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

ISO 209 airborne particulate cleanliness classes for clean rooms
and clean zones.
Numbers (N) Maximum concentration limits (particles/m^3 of air) for particles 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
GRAPHICAL REPRESENTATION OF AIRBORNE PARTICLES

GENERAL CLEAN ROOM REGULATIONS
Below is a list of general regulations recommended as a

minimum for the successful operation of a clean room. All
professional cleaning personnel should be aware and follow
these regulations at all times.
• All personal items such as keys, watches, rings, matches,

lighters and cigarettes should be stored in the personal locker
outside the gowning room.
• Valuable personal Items such as wallets may be permitted in

the clean room provided they are NEVER removed from
beneath the clean room garments.

CONTINUED………
• NO eating, smoking or gum chewing allowed inside the

clean room.
• Only garments approved for the clean room should be

worn when entering.
• NO cosmetics shall be worn in the clean rooms. This

includes:
• rouge, lipstick, eye shadow, eyebrow pencil, mascara,
eyeliner, false eye lashes, fingernail polish, hair spray,
mousse, or the heavy use of aerosols, after shaves and
perfumes.
• Only approved clean room paper shall be allowed in the

clean room.
• Approved ball point pens shall be the only writing tool

used.
CONTINUED………
• Use of paper or fabric towels are prohibited. Use of hand dryers

equipped with HEPA filters are suggested.
• Gloves or finger coats should not be allowed to touch any item or

surface that has not been thoroughly cleaned.
• Only approved gloves, finger cots (powder-free), pliers, tweezers

should be used to handle product. Finger prints can be a major
source of contamination on some products.
• Solvent contact with the bare skin should be avoided. They can
remove skin oils and increase skin flaking.

CONTINUED……….
• Approved skin lotions or lanolin based soaps are

sometimes allowed. These can reduce skin flaking.
• All tools, containers and fixtures used in the cleaning

process should be cleaned to the same degree as the
clean room surfaces. All of these items are a source of
contamination.
• NO tool should be allowed to rest on the surface of a bench

or table. It should be place on a clean room wiper.

CONTINUED……….
• Only clean room approved wipers are allowed to be used.

The wipers must be approved for the Class of clean room
being cleaned.
• ALL equipment, materials and containers introduced into a

sterile facility must be subjected to stringent sterilization
prior to entrance.
• NO ONE who is physically ill, especially with respiratory or

stomach disorders, may enter a sterile room. This is a good
practice in any clean room environment.

HVAC DESAIGN CONSIDERATIONS
1. Temperature and Humidity
2. Pressurization
3. Ventilation and Make Up Air

Temperature and Humidity
 Most clean room require year-round cooling as a result of the fan

energy associated with high clean room airflow as well as the heat
generated by the process, people, and lighting within the facility.
 Temperature control is required to provide stable conditions for

materials, instruments, and personnel comfort.
 Human comfort requirements typically call for temperatures in the

range of 72F to 75 F, since workers frequently wear clean room
garments over street clothes.
 Humidity control is necessary to prevent corrosion, condensation

on work surfaces, eliminate static electricity, and provide personnel
comfort.
 The human comfort zone is generally in the range of 30% to 70%

relative humidity
Pressurization
 A clean room facility may consist of multiple rooms with

different requirements for contamination control.
 Rooms in a clean facility should be maintained at static

pressures higher than atmospheric to prevent infiltration by
wind.
 Positive differential pressures should be maintained between

the rooms to ensure air flows from the cleanest space to the
least clean space.
 The only exception to using a positive differential pressure is

when dealing with specific hazardous materials where
governmental agencies require the room to be at a negative
pressure.

HOW IS AIR PRESSURE MEASURED?
The pressure differential over the doorway is measured with

a portable magnahelic gauge or micro manometer

Ventilation and Make Up Air
 Ventilation and makeup air volumes are dictated by the amount

required to maintain indoor air quality, replace process exhaust
and for building pressurization.
 This provides assurance that carbon dioxide and oxygen remain in

balance, that formaldehyde and other vapors given off by building
materials and furniture are diluted, and that air changes occur
with sufficient frequency to minimize the chance for high
concentration of airborne pollutants within the building.

HOUSE KEEPING
Every user is responsible for keeping the clean rooms clean.
Always clean your workspace before leaving.
Don’t leave or store items on or in equipment.
Do not set liquids on any equipment.
Properly store all materials before leaving the clean room
Last one out should make sure the room is in a safe idle mode.

CHEMICAL HANDLING IN CLEAN ROOMS
 Chemical waste should be properly disposed of as

outlined by EHS systems.
 No chemicals may be poured down the drains
 Waste containers should be properly marked as such and
have a pink Hazardous Waste tag tied to them at all
times.
 If you have questions about disposal contact a staff
member.

VOILATION OF RULES
First time
 Warning
 Report to Advisor
Second time
 Suspension of access
 Retraining may be required
Third Offense
 Suspension of access
 Access will not be renewed until an acceptable resolution is
reached between Advisor and Clean room Manager
 Clean room Protocol re-training will be required.
HVAC
SUPPLY
CLEAN ROOM FLUSHED
DOORS LIGHTING FALSE CEILING
FLUSHED
WINDOWS
EPOXY FLOORING
COVING

Clean Room

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PRESENTATION ON CLEAN ROOM

11/21/2008 KIRAN DESAI 1

 WHAT IS CLEAN ROOM?

 WHO ARE THE USERS OF CLEAN ROOM?

 WHY CLEAN ROOMS ARE REQUIRED IN THE

 WHAT IS THE DESIGN OF CLEAN ROOM

 HOW THE CLEAN ROOMS ARE MAINTAINED?

11/21/2008 KIRAN DESAI 2

 WHAT ARE THE PROTOCOLS TO ENTER IN TO CLEAN ROOM?

 HOW THE CLEAN ROOMS ARE MAINTAINED?

 WHAT QUALITY OF AIR TO BE USED IN CLEAN ROOM?

 WHAT QUALITY OF WATER TO BE USED IN CLEAN ROOM?

11/21/2008 KIRAN DESAI 3

11/21/2008 KIRAN DESAI 4

11/21/2008 KIRAN DESAI 5

SEMICONDUCTORS Integrated Circuits

MICROMECHANICS Compact Disc Players, Miniature Bearings, Gyroscopes

OPTICS Lenses, Photographic Film, Laser Equipment

BIOTECHNOLOGY Antibiotics, Generic Engineering

PHARMACY Sterile Pharmaceuticals, Sterile Disposable

MEDICAL DEVICES Heart Valves, Cardiac by-pass Systems

FOOD AND DRINK Brewery Production, Unsterilized Food and Drinks

11/21/2008 KIRAN DESAI 6

CLEAN ROMS ARE REQUIRED TO AVOID THE SOURCE OF

1. Particulate: dust, makeup, skin, hair, …

2. Chemical: oil, grease, perfume, …

3. Biological: bacteria, fungi, …

4. Radiation (ultraviolet light, …)

11/21/2008 KIRAN DESAI 7

 Room structure (~ 5%)

11/21/2008 KIRAN DESAI 8

11/21/2008 KIRAN DESAI 9

* SUPPLY OF MATERIAL AND TOOLS CONTROL

* ROUTINE CLEAN ROOM CLEANING AND

11/21/2008 KIRAN DESAI 10

 Protocol for clean room provides general guidance and

 Successful clean room maintenance really relies on

 Everyone, whether faculty member, student user or staff

 Trust, understanding and shared responsibility among all

11/21/2008 KIRAN DESAI 11

•Air is highly (HEPA) filtered (99.97% @ 0.3m)

•Layout should minimize particle sources in

•Air flow should remove most particles generated

11/21/2008 KIRAN DESAI 12

HEPA - HIGH EFFICIENCY PARTICULATE AIR FILTER

ULPA Filters- ULTRA LOW PENETRATION AIR.

ULPA is more efficient than HEPA.

HEPA - 99.97% (To remove 0.3 micron particles)

ULPA - 99.99% (To remove 0.1 micron particles)

11/21/2008 KIRAN DESAI 13

DOP TEST (PENETRATION TEST)

TO DETERMINE % OF PARTICLE PASSING

WHY IS THIS TEST PREFERRED?

DOP PARTICLE SIZE IS 0.2 MICRON CONSISTANTLY.

11/21/2008 KIRAN DESAI 14

11/21/2008 KIRAN DESAI 15

Not Acceptable Acceptable

PVA Paint Epoxy or Enamel paint

Window sills Window view panels

Exposed pipes Smooth surfaces (Electro

Floor cracks, flaking Homogonous sealed

Tiled Floor Epoxy Floor

NOT ACCEPTABLE RECCOMMENDED

11/21/2008 KIRAN DESAI 17