3. PURPOSE OF CLEAN PROTOCOL
Promote Successful Cleanroom Operations
Ensure Safety in the Clean Environment
Provide Operational Conditions that Meet Process
& User Needs
3
4. WHAT IS A CLEAN ROOM?
A clean environment designed to reduce the
contamination of processes and materials. This is
accomplished by removing or reducing contamination
sources.
“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.
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5. 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
5
Clean room
11. 11
Sr. no U.S. Federal
209 E
MHRA/TGA ISO
Standards
1 Class 100 A & B 5
2 Class 10,000 C 7
3 Class
1,00,000
D 8
Comparison of various grades described in
various guidelines
12. TYPES OF CONTAMINATION
Particulate
Dust, skin, hair, makeup…
Chemical
Oil, grease, metal ions, perfume…
Biological
Bacteria, fungi, rodents???
Radiation
Ultraviolet light…
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13. CONTAMINATION SOURCES
People ~75%
Ventilation ~15%
Room Structure ~5%
Equipment ~5%
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CONTAMINATION CONTROL
•Personnel Control
•Dress code
•Personal Hygiene
•Gowning
•Environmental Control
•Entrance and exit
•Materials and supplies
•Cleaning and maintenance
•Atmospheric (HVAC &
Microbial monitoring)
14. 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)
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15. GOWNING
Proper gowning order
Hair cover
Hood
Shoe covers
Coverall
Gloves
Face mask
Safety Glasses
Cotton garments shed
fibers. Hence, not used
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Decron (polyster)
16. HVAC SYSTEM
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
guage.
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17. 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. 17
18. 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. 18
20. 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.
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.
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Some specific requirements
21. CLEAN ROOM ENVIRONMENT
MONITORING
Test Frequency
I. Particle Monitoring in air--------------6 monthly
II. HEPA Filter Integrity Testing---------Yearly
III. Air Changes Rate Calculation-------6 Monthly
IV. Air Pressure Differentials--------------Daily
V. Temperature and Humidity------------Daily
VI. Microbiological monitoring by---------Daily, and at
decreased
settle plates and / or swabs in frequency in
other
aseptic areas areas
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22. CONCLUSION
The main purpose of building a cleanroom suite is
to provide a vital element in the assurance of
product quality according to whole concept of good
pharmaceutical manufacturing operation.
The resultant facility should prevent contamination
of the product, and should be seen to be doing so
by the incorporation of effective monitoring devices.
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23. REFERENCES
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
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