PHARMACEUTICAL

CLEAN ROOM
 What is a Clean room?
• “Federal Standard 209E” defines a clean room as
a room in which the concentration of airborne
particles is controlled to specified limits.

• “British Standard” defines a clean room as a room

with control of particulate contamination,
constructed and used in such a way as to minimize
the introduction, generation and retention of
particles inside the room and in which the
temperature, humidity, airflow patterns, air motion
and pressure are controlled
 Principles Of The Clean Environment

• Air is highly (HEPA)

filtered (99.97% @
0.3μm)
• Layout should minimize
particle sources in
filtered air stream

• Air flow should remove

most particles generated
by process
 TYPES OF CONTAMINATION

• Particulate
Dust, skin, hair, makeup…
• Chemical
Oil, grease, metal ions, perfume…
• Biological
Bacteria, fungi, rodents
• Radiation
Ultraviolet light…
CONTAMINATION SOURCES

• People ~75%
• Ventilation ~15%
• Room Structure ~5%
• Equipment ~5%
CONTAMINATION CONTROL
•Environmental Control
•Personnel Control •Entrance and exit
•Dress code •Materials and supplies
•Personal Hygiene •Cleaning and maintenance
•Gowning •Atmospheric (HVAC &
Microbial monitoring)
 PERSONAL HYGIENE
• Shower each day before entry
• Control Dermatitis & Dandruff
• Do not smoke before or after entry
• No chewing gum or tobacco
• No Cosmetics , Jewellery or wrist watches should be worn
• Leave all personal items in changing room
(wallets,keys,comb etc.)
• Avoid coughing and sneezing if unavoidable leave the clean
room
• Do not move vigorously(Brisk movements shed large
particles from body movement)
There are Two Standards today Firstly,
Federal Standard 209
In 2001, ISO
14644-1 replaced Federal
Standard 209E on basis of clean Room classification
Federal Standard 209E ISO 14644-1
They measured 0.5µm But ISO 14644-1
and larger standard take account
even smaller particles
ranging from
0.1µm to 0.5µm
per cubic meter of air
Classified based on
that range
Classification Of Clean Room ISO 14644-1

Classified based on amount of micron particles in

one cubic meter of air
Classification Of Air & Micro-organism
As Per WHO Guidelines
 CLASSIFICATION AS PER EU cGMP

For examples in Blister packing

Temp 21c
Humidity 60-40%
Pressure 15pa
Schedule M

Schedule M: Contains various regulations for manufacturing,

premises, waste disposal and equipment for pharm units in India
 Gowning

• Proper gowning order

– Hair cover
– Hood
– Shoe covers
– Coverall
– Gloves
– Face mask
– Safety Glasses
• Cotton garments shed
fibers. Hence, not used
AIR HANDLING SYSTEM:
• Requirements –
 Temp should be 15-25 °C.
 Atleast 20 air changes should be there per
hr.
 Cleanliness requirements i.e. class 100.
 Relative humidity 45-55 %.
 Pressure differential between 2 area
should be 0.05-0.1 inch water gauge.
Hvac systems in clean room http://pune.All.Biz
 HEPA & UEPA
HIGH EFFICIENCY PARTICULATE AIR (HEPA):
They are box type depth filters used for air filtration.
These filters are made up of glass fibers.
Efficiency of HEPA filters are 99.97% against 0.3 μm particles.
Testing for HEPA filters:
Hot DOP test (efficiency testing), Cold DOP test (integrity testing)
, Air flow resistance test
ULTRA LOW PENETRATION AIR (ULPA):
Most ULPA filters are replaceable extended media dry filters that
have a minimum particle collection efficiency of 99.9997 % efficient
for particles greater than or equal to 0.12-micron in size.
 AIRFLOW DISTRIBUTION AND CONTROL
• Unidirectional:(sometimes referred as laminar flow)
is an airflow pattern in which essentially the entire
body of air within a confined area moves with
uniform velocity and in single direction with generally
parallel airstreams. Clean rooms; class 100 and
below have unidirectional airflow pattern. Laminar air
flow ----120 FPM
• Non-unidirectional: airflow is not unidirectional by
having a varying velocity, multiple pass circulation or
nonparallel flow direction. Conventional flow clean
rooms (class 1000 & 10000) have non-unidirectional
or mixed air flow patterns.
• Mixed patterns : combine some of each flow type.
 Entry & Exit
• Enter and exit quickly.
• Only one person may enter at a time.
• Each user must use their own access card.
• Pass from the gowning area to the clean area slowly
to reduce migration of particles between areas.

Some specific requirements

• Restricted no. of people in aseptic area.
• Drug sensitivity tests should be carried out for
employees working in critical area.
• Medical check-ups of people works in critical area
should be more frequent than other employees.
 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

 Reference
• Current Good Manufacturing For pharmaceuticals; Manohar A. Potdar;
Page no:70-73.
• Pharmaceutical Quality Assurance, Manohar A. Potdar , Nirali
Prakashan; Page no:13.1-13.10
• Comparison of Quality Requirements for Sterile Product Manufacture as
Per Indian GMP and USFDA ;Yogita P, N Vishal Gupta, Natasha NS,
Ashwini Nageen L, R Sudeendra Bhat; Research Journal of
Pharmaceutical, Biological and Chemical Sciences; Jan 2012 volume
3(1): 225-236.
• www.fda.gov