Cleanroom Basics

A Presentation by

LAXMI SINGH KSHATRI

(04.12.2008)
 CLEAN ROOM
A room in which the concentration of airborne
particles is controlled, and which is constructed
and used in a manner to minimize the generation
ofparticles inside the room and in which other
relevant parameters, e.g., temperature, humidity
and pressure are controlled as necessary.
 CLEAN ROOM

It is maintained through supplying large

quantities of air that has been filtered with high
efficiency filters.(HEPA).
 CLEAN ROOM
This air used to
Dilute and remove the particles and

bacteria
Dispersed from personnel and machinery

with in the room

 Pressurize the room and ensure that no

dirty air flows into the clean air room
 CLEAN ROOM
Clean room is built with material that do not
generate particles and can be easily cleaned.

Clean room personnel use Proper clothing to

minimizes their ……
dispersion of
particles

Micro-organisms
 CLEAN ROOM
Clean rooms can also controlled by
followings…
Temperature

Humidity

Sound

Lighting

Vibration
THE NEED OF CLEANROOM

People and machinery and the building structure

generate contamination as..
1.Personnel Hygiene/movement/abnormal sound.
2.improper maintenance of machines.
3.Timely up gradation of building and areas.
CLEANROOM TECHNOLOGY

Cleanroom Operations
Monitoring the room conditions

Entry of people, machines and materials

Cleanroom disciplines to avoid

contaminating the product

Cleanroom garments including gloves,

masks, etc.
Cleanroom cleaning and cleaning

equipment
CLEANROOM CONSIDERATIONS
It is necessary to operate the cleanroom correctly
so that the manufactured products are not
contaminated. This requires
Entry of people

Entry of material

Garment selection

Cleanroom discipline

Cleaning of the room

….correctly carried out.

 Cleanroom Standards
The first standard written for cleanroom was
published by the American Air force on March
1961.

It was known as Technical Manual (T.O) 00-25-

203.

The concepts were

 Clean room design

Airborne particle standards

Entry procedures, clothing

Restriction of certain articles

Cleaning of materials

Procedure for cleaning the room

 Cleanroom Standards
The first Federal standard 209 was produced in the
year 1963.
 Conventional and unidirectional cleanrooms
were discussed.
 Measurement of particles of ≥0.5 µm by means
of optical particle counters was defined.

Why 0.5 µm?

“Art of achievable”
 At that time this was the smallest size that was
easily measured by optical particle counters.
 ISO Standard – 14644-1

The classification of the room be

carried out in
different occupancy states.
 As Built

 At-rest

 Operational
ISO Standard – 14644-1
As Built :
The condition where the installation is complete
with all services connected and functioning, but
with no production equipment materials or
personnel present

At Rest:
The condition where the installation is complete
with equipment installed and operating in a
manner agreed between the customer and
supplier, but with no personnel present.
ISO Standard – 14644-1
Operational:

The condition where the installation is

functioning
In the specified manner, with specified
number
of personnel present and working in
the manner agreed upon.
ISO Class 3 – Special Requirements
EU GGMP
 EU GGMP
Examples of cleanroom conditions required for
Different operations.
“Terminally Sterilized Products”
Grade A
 Filling of products, when unusually at risk.

Grade C
 Preparations of solutions, when unusually at

risk. Filling of products.

Grade D
 Preparation of solutions and components for

subsequent filling.
 EU GGMP
Examples of cleanroom conditions required for
Different operations.
“Aseptic Preparations”
Grade A
 Aseptic preparation and filling.

Grade C
 Preparation of solutions to be filtered.

Grade D
 Handling of components after washing.
 EU GGMP

Microbiological monitoring also required to

demonstrate the microbiological cleanliness of
the cleanroom during production.
 EU GGMP

 These are average values

 Individual settle plates may be exposed for less than 4 hours.

 Appropriate alert and action limits should be set for the results of particulate and
microbiological monitoring. If these limits are exceeded, operating procedures
should prescribe corrective action.
 US FDA
Guideline on Sterile Drug Products Produced
by Aseptic Processing.
 This document was published in 1987 by

USFDA.
 Revised on September 2004

 Critical Area
 Controlled Area
 US FDA
Critical Area:-
“one in which the sterilized dosage form,
containers, and closures are exposed to the
environment. Activities that are conducted in
this area include manipulations of these
sterilized materials/product prior to and during
filling/closing operations.”
 US FDA - Critical Area
 NMT 100 particles of 0.5µm per cubic foot
 Measured NMT 1 foot away from work site

 Upstream of the air flow

 Air should be supplied a the point of use as

HEPA filtered laminar air flow.
 Velocity 90 ± 20 feet per minute
 Not more than 1 colony forming unit per 10
cubic feet
 Should have positive pressure differential
relative to adjacent less clean areas
 A pressure differential of 0.05 inch of water is
acceptable.
 US FDA
Controlled Area:-
“An area in which it is important to control the
environment, is the area where un-sterilized
product, in-process materials, and container/
closures are prepared. This includes areas
where components are compounded, and
where components, in-process materials, drug
products and drug product contact surfaces of
equipment, containers, and closures, after final
rinse of such surfaces, are exposed to the plant
environment.”
US FDA- Controlled Area
 NMT 100000 particles of 0.5µm per cubic foot.
 NMT 25 colony forming units per 10 cubic
feet.
 Sufficient air flow.
 Positive pressure differential relative to
adjacent uncontrolled areas.
 20 air changes per hour

 Pressure differential of at least 0.05 inch of

water
 When doors are open, outward airflow should
be sufficient to minimize ingress of
contamination.
US FDA
Schedule M
Cleanroom contamination Classification
 Cleanroom Environmental Monitoring

Test Frequency

Particle Monitoring in air 6 monthly

HEPA Filter Integrity Testing Yearly
Air Changes Rate Calculation 6 Monthly
Air Pressure Differentials Daily
Temperature and Humidity Daily

Microbiological monitoring by Daily, and at decreased

settle plates and / or swabs in frequency in other
aseptic areas areas
 Thanks
LAXMI SINGH KSHATRI