A comprehensive review of facilities required for sterile pharmaceutical preparation.

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2. A comprehensive review of facilities required
for sterile pharmaceutical preparation.
Mohammad Imtiaz Halim BPH 130101003
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3. Contents
Introduction
Objective and Facility
Clean Room Purpose and Classification
Design of clean room
Gowning procedure
HVAC system process
 Components of HVAC and their functions
Air cleaning And Supply system
Performance of Air Filter
Laminar Air Flow Systems and types
Water Treatment process
Types of water supply
Water Quality Specifications
Conclusion 3

4. Introduction
“Sterile simply means there are no microorganisms that can
cause infection in the patient.”
“Sterile products refers to products that are going to be
administered directly into the bloodstream or body tissue”
Examples are:-
IV injections: Vancomycin, Doxorubicin.
IM injections: Lorazepam, Methotrexate.
SC injections: Insulin, Morphine.
Ophthalmic preparations: Atropine, Pilocarpine.
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5. Objective and Facility
To protect patients from harmful bacteria and other
pathogens
To prevent contamination and Cross contamination
To control drug stability
1.Clean Room
2.Gowning Procedure
3.HVAC System
4. HEPA Filter
5. Laminar Air Flow System
6.Water Treatment System
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6. What is Clean Room?
“A room in which the
concentration of airborne
particles, temperature,
humidity, and pressure is
controlled”.
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Fig: Clean room

7. Purposes of clean room
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Three Main Purposes of clean room are:-
1.The concentration of airborne particles is
controlled.
2.Constructed and used in a manner to minimize the
introduction, generation, and retention of particles
inside the room
3.Other parameters (Temperature, Humidity, and
Pressure) are controlled

8. Classification of clean room
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1.Classification of clean room according to ISO, Federal
Standard and EU GMP:

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Comparison among EU GMP, Federal Standard
and ISO classification:

10. Design of clean room:
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Fig: Design of clean Room

11. Design: Construction and materials
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12. Gowning procedure
The gowning procedure is
what garments are to be taken
off and put on.
Proper gowning order
0 Hair cover
0 Hood
0 Shoe covers
0 Coverall
0 Gloves
0 Face mask
0 Safety Glasses
Fig: Gowning
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13. Personal Hygiene
0 Hands and fingernails must be scrubbed thoroughly with the
disinfectant
0 Eyeglasses must be worn
0 Shoes must be covered or changed to approved clean room
footwear.
0 Approved clean room garments( Gown, hand gloves, mask, cap)
must be worn.
0 All hair is to be completely covered at all times.
0 Coveralls are not to be unzipped in the clean room.
0 No skin is to be exposed between the gloved hand and coveralls.
0 Cosmetics are not to be worn or applied in the clean room.
0 No jewelry is to be worn in the clean room.
0 Personal items such as keys, coins, cigarettes, matches, pencils,
handkerchiefs, - watches, tissues, and combs should not be carried
into the clean
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14. HVAC system
HVAC stands for Heating, ventilation, and air conditioning.
The system is used to provide heating and cooling services to
buildings.
Fig:HVAC System 14

15. HVAC system process and Function
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Heating is the process of generating heat to boil water,
generate steam, or air.
Ventilation is the process of changing or replacing air by
removing moisture, odors, smoke, heat, dust, airborne
bacteria, or carbon dioxide, and to replenish oxygen.
An air conditioning system that provides cooling and
humidity control for all or part of a building.
 Control airborne particles, dust, microorganisms.
 Maintain room pressure.
 Maintain relative humidity.
 Maintain temperature.
 Maintain proper air movement.

16. Parameter of HVAC System
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 Temperature: 22±2ºC
 Relative Humidity: RH within 35±5 % in all
manufacturing areas.
 Air Class: A, B, C & D
 Pressure Gradient: It should be maintain relatively
positive pressure.
 Air Quality: It should be Dust and Odor free.
 Sound level: It should be maintained within 20 db.

17. 0 Weather louvre
0 Silencer
0 Flow rate controller
0 Control damper
0 Heating unit
0 Cooling unit
Or dehumidifier
0 Humidifier
0 Filters
0 Ducts
Fig: Component of HVAC System17
Component of HVAC System

18.  Weather louvre:
To prevent insects, leaves, dirt and rain from entering.
 Silencer:
To reduce noise caused by air circulation.
 Flow rate controller:
Automated adjustment of volume of air.
 Control damper:
Fixed adjustment of volume of air.
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Different components of HVAC and their
functions

19.  Heating unit:
To heat the air to the proper temperature.
 Cooling unit /dehumidifier:
To cool the air to the required temperature or to remove moisture from
the air.
 Humidifier:
To bring the air to the proper humidity, if too low.
 Filters:
To eliminate particles of pre-determined dimensions and/or micro-
organisms.
 Ducts:
To transport the air.
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Different components of HVAC and their functions

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Flow Chart of HVAC System

21. A system that cleans smog, pollen, exhaust, smoke, and odors out
of the air. Cleans both interior circulated air and that coming
from the outside.
High efficiency particulate air
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.
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What is HEPA Filter?
Air cleaning And Supply system

22. 0 Ultra low penetration air
0 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.
0 Super Ultra Low Penetration Air
0 These filters have an efficiency of 99.9999% on the same
basis as ULPA.
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What is ULPA Filter?
What is SULPA Filter?

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Performance of Different Types of Air
Filter

24. 0 Laminar air flow systems are used for cleaning air in aseptic rooms.
0 In laminar air flow systems, clean air is obtained through HEPA filters
0 This air flows at a speed of 100 ft./min & sweeps dust particles making
entire room free of particulate matter
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Laminar Air Flow Systems
Types of Laminar Air Flow Systems
Laminar air flow systems are of 2 types
1. Downward flow systems
2. Horizontal flow systems

25. Downward flow systems
Fig: Downward flow systems
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 This system consists of false floor
& ceiling.
 The air is filtered through pre-
filters ,electrostatic filters and
HEPA filters in sequence.
 These 3 filters are placed in false
ceiling.
 From the false floor, a small
portion of filtered air is
recalculated in to false ceiling
through a recirculation duct.

26. Fig: Horizontal flow 26
 The air is filtered through pre
filters ,HEPA filters which are
placed in lateral walls.
 Air is recalculated through
punched plate wall or
recirculation duct.
 Achievement of complete
sterile conditions is not
possible because the airflow is
not focused on working area.
Horizontal flow systems

27. Fig: Water Treatment Plant
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Water Treatment System
Water treatment is any process that makes water more
acceptable for a specific use. The use may be drinking,
industrial water supply, irrigation, river flow maintenance
etc.

28. Importance of water Treatment System
 It removes all unnecessary bacteria and viruses from the water
which is hazardous for our health.
 It also helps to remove all unwanted chemicals and toxins from the
water which produce alpha radiation and leads to cancer and many
skin or digestive tract irritation.
 This water treatment facility helps in removing the heavy metals like
mercury, arsenic, lead from water which are very difficult to detect
and can cause long-term neurological impairments.
 This water treatment facility helps to improve the flavor and
appearance and remove unpleasant odor.
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29. Water treatment process
Raw water
Chlorination in over hade tank
Activated carbon filter
Buffer tank
(Reverse osmosis)
Pure water
Anode Cathode filter (deionization)
Distillation process (<0.2 u filter)
UV sterilizer
Purified water tank
User points
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Why Chlorination process is used to purify water?
H2O+Cl2 (at pH 7) ------- HCl + HOCl (main disinfectant)
Hypochlorous acid to destroy bacteria, to oxidize organic matter and
to neutralize the ammonia in water.
Why Activated carbon filter is used to purify water?
activated carbon filter is to remove contaminants and impurities,
using chemical adsorption. Active carbon filters are most effective at
removing chlorine, sediment, volatile organic compounds taste and
odor from water. They are not effective at removing minerals, salts,
and dissolved inorganic compounds.
Why filter Reverse osmosis process is used to purify water?
Reverse Osmosis (RO) is a water treatment process that
removes contaminants from water by using pressure to
force water molecules through a semipermeable
membrane. During this process, the contaminants are
filtered out and leaving clean water.
Different process to purify water

31. Why ion exchange process is used to purify water?
 ion-exchange is a process in which ions present in the water are replaced
by ions released by an ion-exchange resin
 There are two basic types of resins: cation-exchange and anion-exchange
resins.
 Cation exchange resins will release Hydrogen (H+) ions or other positively
charged ions in exchange for impurity cations present in the water.
 Anion exchange resins will release hydroxyl (OH-) ions or other negatively
charged ions in exchange for impurity anions present in the water.
Why Distillation process is used to purify water?
Distillation is the process of separating the component or substances from a
liquid mixture by selective evaporation and condensation by using stem.
Why is UV sterilizer used to purify water?
UV sterilizer is used to control infections by stopping the spread of
microorganisms from water. At certain wavelengths(260 nm–270 nm) UV is
mutagenic to bacteria, viruses and other microorganisms.
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32. Types of water supply in pharmaceutical preparation:
Purified Water is used as an excipient in the production of non-parenteral
preparations
It is used for cleaning of certain equipment’s and non-parenteral product-
contact components.
Purified Water must meet the requirements for ionic and organic chemical
purity and must be protected from microbial contamination.
Production process
1. Chlorination
2. Deionization
3. Reverse osmosis (RO)
4. Ultra Filtration
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33. Water for injection (WFI) is used as an excipient in the
production of parenteral and other preparations where
product endotoxin content must be controlled
It is used for cleaning of certain equipment and parenteral
product-contact components.
Water for injections should be prepared from drinking-water
(usually with further treatment) or purified water.
Production process
1. Chlorination
2. Deionization
3. Reverse osmosis (RO)
4. Ultra Filtration
5. Distillation process
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Water Quality Specifications for Pharmaceutical
Water
SI no Parameter Purified Water Water for
Injection
1 TOC 500 ppb 500 ppb
2 TDS 10 mg/ml 10 mg/ml
3 Conductivity 1.3 S/cm 1.1 S/cm
4 Nitrate 200 ppb 200 ppb
5 Chloride 500 ppb 500 ppb
6 Aerobic Bacteria 100 CFU/ml 10 CFU/ml
7 Bacterial Endotoxins NA NA
8 PH 5.0-7.0 5.0-7.0
9 Final purification process Any Distillation
,Reverse osmosis

35. Conclusion
0Sterile facility is required for Realizing the
crucial importance of quality, safety and efficacy
of sterile pharmaceutical preparations such as
eye drops, intravenous parenteral preparation.
0 There is an urgent need for better clean room
facilities, HVAC and Air supply system, water
supply system according to Whole concept of
WHO,ISO,FDA and GMP etc.
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THANK YOU