The document discusses aseptic pharmaceutical manufacturing, emphasizing the importance of clean rooms, HVAC systems, and various engineering controls to minimize contamination of sterile products. It details the design and classification of clean rooms, the functions of HVAC systems, types of air conditioning systems, and components involved, including air handling units and ducting materials. Additionally, it outlines the characteristics and maintenance of HVAC systems to ensure proper temperature, humidity control, and air quality in pharmaceutical environments.

1. ASEPTIC PHARMACEUTICAL
MANUFACTURING

2. Content
Clean room
HVAC system
Validating of clean room
Cleaning and sterilization of
containers and closures
Pyrogen and depyrogenation
Filling and sealing of sterile
products
Clean in place (CIP) and sterilize in
place (SIP) system,
Manufacturing of SVP and LVP

3. •Aseptic technique refers to the sum total of methods
and manipulations required to minimize the
contamination of compounded sterile products and is
of paramount importance when preparing such
preparations.

4. Clean rooms
• Clean rooms are areas specially constructed and
maintained to reduce the probability of environmental
contamination of sterile products during the manufacturing
process. Engineering controls to reduce the potential for
airborne contamination include airflow through high-effi
ciency particulate- air (HEPA) filters, use of horizontal flow
clean benches, vertical flow clean benches, biological safety
cabinets, and barrier isolators. Clean rooms are traditionally
designed in multicompartments or partitioned work areas
for aseptic processing (Figure 17-1).

5. Clean
room
layout

6. Clean rooms
1. Ante-area provides a clean area for personal cleaning and for donning
personal protective equipment such as hair covers, gloves, gowns, or full
clean room attire. Supplies are removed from shipping cartons and
decontaminated with a disinfecting agent. The area should provide at least
an International Organization for Standardization (ISO) class 8 or better
work environment.
2. Buffer area contains the work surfaces for the staging of supplies and
equipment used in CSP preparation. It should provide at least an ISO class 7
work environment. They contain no sinks or drains and be free of objects
that shed particles (cardboard, paper, cotton, etc.). Traffic flow in and out is
minimized and restricted to qualified compounding personnel. buffer area
should

7. Clean rooms
• Primary engineering control is the room that provides the ISO class 5
environment for CSP preparation.
• Direct compounding area is the critical area with the primary engineering
control where compounding is performed and critical sites are exposed to
HEPA-filtered air.
• HEPA filters are used to cleanse the air entering the room. These filters
remove all airborne particles 0.3 mm or larger, with an efficiency of 99.97%.
The reference standards for HEPA-filtered rooms have changed to a metric-
based system (Table 17-3). HEPA-filtered rooms are classified as ISO class 3
through 8. An ISO class 8 room contains no more than 3,520,000 particles
of 0.5 m or larger per cubic meter of air.

8. Clean rooms
• Positive-pressure airflow is used to prevent contaminated air from
flowing into the clean room. To achieve this, the air pressure inside the
clean room must be greater than the pressure outside the room, so that
when a door or window to the clean room is opened, the airflow is
outward.
• Counters in the clean room are made of stainless steel or other
nonporous, easily cleaned material.
• Walls, floors, and ceilings do not have cracks or crevices and have
rounded should also be nonporous and washable to enable regular
disinfection. If walls or floors are painted, epoxy paint is used. corners. All
surfaces

9. Clean room Classification

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INTRODUCTION
HVAC stands for Heating Ventilating and Air-conditioning system.
HEATING:
Heating is provided by heaters. Heaters are appliances whose purpose is to generate heat for the
building. This can be done via central heating or by direct heating system.
VENTILATION:
 Ventilating or ventilation (the V in HVAC) is the process of exchanging or replacing air in any space to
provide high indoor air quality which involves temperature control, oxygen replenishment, and
removal of moisture, odors, smoke, heat, dust, airborne bacteria, carbon dioxide, and other gases.
Ventilation removes unpleasant smells and excessive moisture, introduces outside air, keeps interior
building air circulating, and prevents stagnation of the interior air.
Ventilation includes both the exchange of air to the outside as well as circulation of air within the
building. It is one of the most important factors for maintaining acceptable indoor air quality in
buildings.

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INTRODUCTION
Air-Conditioning:
An air conditioning system provides cooling and humidity control for all or part of
a building. Air conditioned buildings often have sealed windows, because open
windows would work against the system intended to maintain constant indoor air
conditions.
Dehumidification (air drying) in an air conditioning system is provided by the
evaporator. Since the evaporator operates at a temperature below the dew point,
moisture in the air condenses on the evaporator coil tubes. This moisture is
collected at the bottom of the evaporator in a pan and removed by piping to a
central drain or onto the ground outside.

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FUNCTIONS OF HVAC
To Control Temperature.
To Control Humidity.
To Develop Differential Pressure.
To Prevent Cross Contamination.
To Maintain proper Air Movement.

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TYPES OF HVAC
There are two types of Air-
Conditioning system.
1.Ducted
2.Non Ducted
Ducted
It includes,
Chilled Water System
 Dx System (Direct Expansion)
Non Ducted
It includes
1. Window System
2. Split system

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TYPES OF HVAC
Ducted System:
Chilled water system
In chilled water system the refrigeration system in chiller is used to first chill the water, which is then
used to chill the air used for cooling the rooms or spaces.
Technically speaking, water can be classified as a refrigerant
Chilled water system is indirect method of cooling the air.
A typical chiller uses the process of refrigeration to chill water in a chiller barrel. This water is pumped
through chilled water piping to the building AHU where it will pass through a coil.
 Air is passed over this coil and the heat exchange process takes place. The heat in the air is absorbed
into the coils and then into the water.
The water is pumped back to the chiller to have the heat removed. It then makes the trip back to the
building AHU and the coils.

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TYPES OF HVAC
Chilled water system:
Chiller
Many chillers have cooling towers where the heat removed in the chiller barrel is
transferred to another barrel.
It is the condenser barrel where the refrigerant is condensed and sent back to the
evaporator barrel to remove the heat. The process is in reverse in the condenser
barrel. The water absorbs heat from the refrigerant and allows it to condense.
The water is then transferred to a cooling tower where the heat in this water is
removed to the atmosphere.
Once the heat is removed from the water it is pumped back to the chiller barrel
to absorb more heat from the refrigerant.

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TYPES OF HVAC
Ducted System:
Direct Expansion (DX Type)
In the DX system the air used for cooling the room or space is directly passed over the cooling coil of
the refrigeration plant.
DX is direct type of cooling air.
In the direct expansion or DX types of air conditioning plants the air used for cooling space is directly
chilled by the refrigerant in the cooling coil of the air handling unit (AHU).
Since the air is cooled directly by the refrigerant, the cooling efficiency of the DX plants is higher.
However, it is not always feasible to carry the refrigerant piping to the large distances hence, direct
expansion or the DX type of central air conditioning system is usually used for cooling the small
buildings or the rooms on the single floor.

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TYPES OF HVAC
Non Ducted System:
Window system
 Window system is the most commonly used air conditioner for single rooms.
 In this air conditioner all the components, namely the compressor, condenser, expansion valve
or coil, evaporator and cooling coil are enclosed in a single box.
 This unit is fitted in a slot made in the wall of the room, or more commonly a window.
Split System
The split air conditioner comprises of two parts,
i. Outdoor unit
ii. Indoor unit
 The outdoor unit, fitted outside the room contain components like the compressor, condenser
and expansion valve.
 The indoor unit comprises the evaporator or cooling coil and the cooling fan.

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COMPONENTS OF HVAC
A. Air Handling Unit (AHU)
The definition of air handling unit from ANSI/AHRI Standard 430-2009 states that it is "A factory-made
encased assembly consisting of a fan or fans and other necessary equipment to perform one or more of
the functions of circulating, cleaning, heating, cooling, humidifying, dehumidifying and mixing of air.
An air handler is usually a large metal box containing a blower, heating or cooling elements, filter racks
or chambers, sound attenuators, and dampers. Air handlers usually connect to a ductwork ventilation
system that distributes the conditioned air through the building and returns it to the AHU.
(AHU) are the lungs of any HVAC system.
An air handling unit is a device used to regulate and circulate air as part of the heating, ventilation and
air conditioning system.
The AHU takes in outside air, reconditions (filtered and either heated or cooled) it and supplies it as
fresh air to the air conditioned room.
Air handler that conditions 100% outside air, and no recirculated air, is known as a makeup air unit
(MAU).

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AIR HANDLING UNIT(AHU)

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COMPONENTS OF AIR HANDLING UNIT
1.Housing.
The housing that contains all the other components of an AHU is usually make of metal, some are painted
to prevent corrosion.
In sections where the fans and the coil are located,1-2 inches of polyurethane foam or PU is used to insulate
them to prevent the condensation on the panel.
2.Mixing Box.
Mixing box has air inlets that are attached to the dampers.
This is the place where the outside fresh air and the return air are mixed to provide the correct proportion
of air to be distributed to the space that is to be conditioned.
3.FILTERS:
Filters are typically placed first in the AHU in order to keep all the downstream components clean.
Coarse-grade Panel filters or Pre filters are placed in front of a fine-grade Bag filters and then come "final"
filtration medium (HEPA).
The panel filter is cheaper to replace and maintain, and thus protects the more expensive bag filters.

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COMPONENTS OF AHU
Filter Classification
Following types of filters are used.
1. Standard Filters
2. Aerosol Filters
1. Standard Filters
It include following
i. Coarse Filters
ii. Medium Filters
iii. Fine filters
i. Coarse Filters G1,G2,G3,G4
It includes
a. Mesh Filters (Aluminum Washable)
b. Pre Filters/Panel Filters/Primary
Filters
ii. Medium Filters M5,M6
iii. Fine Filters F7,F8,F9
it includes
Bag Filters/Secondary Filters

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PRE FILTER & BAG FILTER

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COMPONENTS OF AHU
Filter Classification
2. Aerosol Filters:
It includes,
i. Efficient Particulate Air Filters (EPA) E10,E11,E12
ii. High Efficient Particulate Air Filters (HEPA) H13,H14
iii. Ultra Low Particulate Air Filters (ULPA) U15,U16,U17

25. 25
COMPONENTS OF AHU

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COMPONENTS OF AHU

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CLASSIFICATION OF FILTERS

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CLASSIFICATION OF FILTERS

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CLASSIFICATION OF FILTERS

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CLASSIFICATION OF FILTERS

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CLASSIFICATION OF FILTERS

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COMPONENTS OF AIR HANDLING UNIT
4.COOLING COILS
 Cooling coils are used to cool and dehumidify the air.
 There are two methods to cool air in cooling coils.
i. Chilled water system
in this air in coil is cooled by circulating chilled water.Use of
Chiller.
ii. Direct Expansion (Dx Type)
 In this air is cooled directly by refrigerants which circulate
in the coil.
 Both DX & chilled water cooling coils are available for use
depending on the system design. These coils are arranged
in rows with different fin spacing.
 Aluminum fins and copper tubes are used in the design of
the coils. The corrosion resistance hydrophilic fins are also
used due to its lower cost and lower resistance to the air
velocity.
5.HEATING COILS
Heating Coils are used to heat the air.
 Are of 2 types
i. In Direct heat exchangers.
Air is heated by the hot water which circulate in coils. Use of Boiler.
ii. Direct heat exchanger
Air is heated directly by electric heaters or gas heaters.

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COOLING & HEATING COILS

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COMPONENT OF AHU
6.Dehumidifier
 If dehumidification is required, then the cooling coil is employed to over-cool so that the dew point is reached and condensation occurs.
 A heater coil placed after the cooling coil re-heats the air (therefore known as a re-heat coil) to the desired supply temperature. This
process has the effect of reducing the relative humidity level of the supply air.
7.Humidifiers
 During winter, the humidity level of the air can be low hence causing discomfort to the occupants/working.
 The humidity of the air is increased by using the humidifiers. Here are the commonly used humidifiers:
i. Spray Type
 Has a header and spray nozzles that spray water with a pressure of 15 psi or more.
ii. Steam Pan Type
It has a pan and a heating coil to heat up the water of the pan. The evaporation of water caused by the heating will increase the humidity
level of the surrounding air.
iii. Steam Grid Type
It has tiny holes on the pipe to distribute the steam that flows through it. In this case, the water that is heated up to produce the steam to
be supplied to the grid is conditioned to prevent odor being discharged to the room.

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COMPONENTS OF AHU
8: Air Blower/Fan
Centrifugal fan is used to circulate the air to the various parts of the sections in the building. The typical
types of fan available are Backward Inclined, Backward Curved, Forward Curved and Airfoil. The selection
of the fan will depend on the air volume
Air handlers typically have a large squirrel cage blower or fan driven by eleectric motor to move the air.
The blower may operate at a single speed, offer a variety of set speeds, or be driven by a variable-
frequency drive to allow a wide range of air flow rates.
The use of variable air volume (VAV) system is becoming more popular as the volume of the air being
discharged can be varied depending on the load condition. If the load is high, the fan speed will be higher
and if the load is lower, the speed of the fan will be lower.
The blowers in an air handler can create substantial vibration and the large area of the duct system
would transmit this noise and vibration to the occupants of the building. To avoid this, vibration isolators
(flexible sections) are normally inserted into the duct immediately before and after the air handler and
often also between the fan compartment and the rest of the AHU.

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AIR BLOWER/FAN OF AHU

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COMPONENTS OF HVAC
B. DUCTING SYSTEM

Ducts are passages used in heating, ventilation, and air conditioning (HVAC) to deliver and
remove air.

The needed airflows include, for example, supply air, return air, and exhaust air.
TYPES OF DUCTS:
Following are types of ducts
SAD = (Supply Air Duct)
It supplies air from AHU to the required area to be conditioned. This air is treated air & contains
all the desired qualities as provided by the air conditioning system.
RAD =(Return Air Duct)
It supplies air from conditioned area back to the AHU for retreatment and recirculation or fully
exhaust in the air.
FAD = (Fresh Air Duct)
It supplies ambient/fresh air to the AHU from the outside atmosphere. This air is supplied to the
AHU inlet from the outside atmosphere after being initially treated/filtered.

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DUCTING SYSTEM

39. 39
COMPONENTS OF HVAC
DUCT SHAPES
i. Rectangular Duct
ii. Circular Duct
iii. Square Duct
iv. Spiral Duct
DUCTING MATERIALS
Following type of materials are used
i. Galvanized iron
 Low Cost & Easy Fabrication.
ii. Aluminum Sheet Metal
 It is used for light weight & resistance to moisture application.

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COMPONENTS OF HVAC
iii. Fiber Glass Duct
 Low velocity application only otherwise heavy vibration will generate.
iv. Thick Black Mid Steel
This sheet are used for exhaust duct.
v. High Corrosion Resistance Application
 Marine galvanized steel sheets with heavy deposition of zinc (not less than
270gms/sq.m) for internal ducting & stainless steel grade 316L for external ducting.
vi. PUF (polyurethane foam)
 These Ducts are flexible & do not require insulation as PUF is an insulation
material. But it is costly & may generate toxic gases in case of fire.

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COMPONENTS OF HVAC
CLAIFICATION OF DUCTS
i. Low Pressure Duct Work
Velocity <600mpm & static pressure 5cm of H20 gauge.
No specified requirements of class of cleanliness.
Space do not require specific +ve pressure.
ii. Medium Pressure Duct Work
Velocity <600mpm & static pressure 5-15cm of H20 gauge.
 Specified class of cleanliness often incorporates deburring (exclude) of coil, absolute filters, supply, Return, Exhaust & Fresh air ducts.
Clean room application require Medium pressure duct work because heavy pressure lose take place through high efficiency filters.
Care to be taken to seal all duct joints to prevent leakage. Joint should be soldered or sealed with good quality sealant.
Sheet used should be free from flaking or any such defects as this likely to add eroded metal particles to the conditioned air.
iii. High Pressure Duct Work
Velocity >600mpm & static pressure 15cm of H20 gauge.
For specified class or marine applications.
Pressure drop in supply Air Ducting: 10-15cm of H20 gauge.
Pressure drop in Return Air Ducting: 5-10cm of H20 gauge. circular (or) spiral ducting (machine fabricated) is recommended as the helically
wound longitudinal joints provide adequate mechanical strength.

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COMPONENTS OF HVAC
C. Grille/Register/Diffuser
GRILLE:
 A fixed opening through which air passes. Typically used for return air applications.
 A grill is used on the return side to protect the system from objects entering the intake. As a grill is often used on the return side, it must be free
of a damper to ensure the unrestricted flow of air back to the central system
REGISTER:
 A grille equipped with a damper which supplies conditioned air. Typically used for supply air applications.
DIFFUSER:
 An air flow device designed to discharge conditioned air in a specific direction, path, or pattern.
 Used for supply air applications.
 The main role a diffuser plays is spreading the air around a given space to increase the impact area of the air.
 A diffuser also allows air to be comfortably spread, as opposed to pouring directly out of a duct onto the space below it. The diffuser is beneficial for noise
reduction.
 Diffuser can come in many shapes (square, rectangle, linear or round), the most popular and recognizable style is the large round diffuser.
MATERIAL OF CONSTRUCTION:
i. Aluminum
ii. Mild steel
iii. Stainless steel
iv. Plastic

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COMPONENTS OF HVAC
Types of Grille:
There are following types of grilles,
i. Egg grate grille
ii. Bar grille
iii. Transfer grille
Types of Diffusers:
iv. Louvre bladed diffuser
v. Straight bladed diffuser
vi. Linear slot diffuser
vii. Swirl diffuser
viii.Floor outlet diffuser
ix. Jet diffuser
x. Punkah diffuser
xi. Barrel diffuser
xii. Perforated diffuser
xiii.Plain face diffuser

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COMPONENTS OF HVAC