Functions of AHU

1. Heating
2. Cooling
3. Humidification
4. Dehumidification
5. Filtration

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 1-Dehumidifier
(a) Desiccant type Dehumidifier
Desiccants are used which can adsorb
moisture, as a result quantity of
moisture in air will decrease.
Passing air through desiccant again
and again, will get moisture free air.
Fan passes moisture-laden air
through desiccant which adsorbs
moisture from air making it moisture
free.
Desiccant becomes inactive due to
adsorption of moisture.
Desiccant can be again reactivated by
passing hot air through it. 4
 (b) Refrigeration type Dehumidifier
 Refrigerants: Substances that are circulated in a
closed refrigeration system to transfer heat.
Examples: Trichloro Monofluro Methane, Dichloro
Difluro Methane, Monochloro Trifluro Methane
 Compressor: Circulates refrigerants through a
closed system.
 Condenser: Receives hot, high-pressure refrigerants
from compressor and converts it into liquid
refrigerants.
 Evaporator: Liquid refrigerant is vaporized at lower
pressure in evaporator.
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 The content ability of air is temperature dependent.
 Hot air can contain more moisture than cool air.
 Refrigeration type dehumidifier can decrease the
temperature of air.
 As a result air will be first saturated and then excess
water will be separated from air.
WORKING
 Refrigerants are used in refrigerant type
dehumidifier.
 These refrigerants are evaporated in the evaporator.
 Heat is taken by the refrigerants as a latent heat for
this conversion.
 As a result the evaporation coils become very cool. 6
 In contact with the evaporating coil, air also
becomes very cool.
 As cool air can contain less moisture, the
excess water will be separated from the air.
 When the unit is started, fan begins to pull
moisture-laden air across the evaporating
coils making the air cool & moisture free.
 Then moisture free air is passed through the
condenser, where the air becomes hot due
to the latent heat of condensation of
refrigerants in the condenser.

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1.Compressor propels the fan & flow of the
refrigerant.
2.Fan draws humid air into the dehumidifier via an air
inlet.
3.Humid air is met with a series of very cold
coils (basically, a refrigerator). There water from the
air is condensed on the cold coils.
4.Drip tray gathers the water in the water tank and
remove water from the dehumidifier’s water tank.
5.Now dry cold air will run over hot coils to warm up
(basically, a heater).
6.Same fan that absorbs the humid air into the
dehumidifier will now propel the dry air out. 9
 2 Temperature Control
1. Air Cooler 2. Air Heater
Components
 Refrigerants: Substances that are circulated in a closed
refrigeration system to transfer heat; Trichloro
Monofluro Methane, Dichloro Difluro Methane,
Monochloro Trifluro Methane.
 Compressor: Circulates refrigerants through a closed
system.
 Condenser: receives hot, high-pressure refrigerants
from the compressor and converts it into liquid
refrigerants.
 Evaporator: liquid refrigerant is vaporized at lower
pressure in evaporator. 10
 Refrigerants are used in air cooler.
 These refrigerants are evaporated in the evaporator.
 Heat is taken by the refrigerants as a latent heat for this
conversion.
 As a result the evaporation coils become very cool.
 In contact with the evaporating coil, air also becomes
very cool.
 This cool air is distributed in the room.
 Condenser receives hot, high-pressure refrigerants from
compressor & converts it into liquid refrigerants.
 Heat is released from the refrigerant at this conversion.
 Air from out side the room is passed across the
condenser to transfer heat.
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 When the unit is started, the fan begins to pull hot air
of the room across the evaporating coils making the
air cool and this cool air is distributed in the room.
 At the same time fan passes the out side air across the
condenser and keep it cool by removing heat from the
condenser.

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 Hot water coils are designed to meet a variety of
heating applications.

 Chilled water coil are used for applications including

comfort cooling, dehumidification, process cooling,
and more.

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 3 Filters
 Filtration efficacy depends on several mechanisms, and
results in a rough filter classification.
 Commonly used classification, with current abbreviations
G= Gross, F= Fine, H=High, U= Ultra.
 Filters are certified by suppliers (challenge/efficiency
test), but may often not be properly installed or can be
damaged.
 Leak tests, showing leakage of air through filter itself or
through its frame, therefore, have to be performed.
 Integrity tests are usually only carried out on the Aerosol
filters (HEPA & ULPA).
 Integrity or penetration testing is performed to detect
leaks from filter media, filter frame & seal.
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 Challenge is a poly-dispersed aerosol usually
composed of particles ranging in size from one to
three microns.
 Test is done in place and the filter face is scanned
with a photometer probe; the measured downstream
leakage is taken as a percentage of the upstream
challenge.
 Integrity tests should be carried out with filters
installed in the system and should be carried out by
an independent body (not the filter supplier).

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 The efficiency test, on the
other hand, is used to
determine filter's rating.
 This test uses a mono-
dispersed aerosol of 0.3
micron size particles,
relates to filter media, and
usually requires specialized
equipment.
 Downstream readings
represent an average over
the entire filter surface.
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 HEPA Filters
 High Efficiency Particulate Air f
ilters are replaceable extended
-media dry-type filters in a ri
gid frame having a minimum p
article collective efficiency of;
1. 99.97 percent for a 0.3 micro
n particle (Standard grade)
2.99.90 percent for a 0.3 micro
n particle (Low grade)
3. 99.99 percent for a 0.3 micro
n particle (high grade)

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 Efficiency Testing of HEPA Filters
 HEPA filters generally tested for efficiency at
the filter manufacturing site using a
thermally generated dioctylphalate (DOP)
aerosol
 Challenge is a homogeneous, monodispersed
aerosol with a particle size of 0.3
micrometers
 Penetration of DOP through filter should not
exceed .03% (Note: 100% -.03% = 99.97%
efficiency)
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 Integrity Testing of HEPA Filters
 Similar test used for the verification of filter integrity
(leak testing or pinhole detection)
 Includes cold DOP, DEHS, Emery 3000 POA leak test
 Test differs from efficiency test in complexity of aerosol
generator & portability of photometer employed
 In Cold DOP, Aerosol generator used to produce a
polydispersed aerosol containing a range of particles
(0.1-3 micron) that is introduced upstream of the filter
bank while in operation
 Downstream side of filter is scanned with optical
measuring device, usually a light scattering photometer
 If pinhole leaks are present, particles pass through filter
and are detected by optical device
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 ULPA (Ultra Low Penetration Air) filter
 A filter with a higher efficiency than a HEPA filter.
 It has a DOP efficiency of 99.999% and 12 in. (304.8
mm.) deep version has a clean pressure drop of 273.6 Pa
when operating at a face velocity of 250 fpm (1.27 m/s).
 Ultra Low Penetration Air filters are extended media dr
y filters in a rigid frame that have a minimum particle c
ollection efficiency of 99.999 percent for particles gr
eater than or equal to 0.12 micron in size.
 This filter has helped meet the requirement for cleaner
air in facilities needed for the manufacture of
microelectronics.
 It is identified by the generic name ULPA (Ultra Low
Particulate Air) filter. 25
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Characteristics of air handling systems
1. Air Flow Patterns (Turbulent or
uni-directional airflows)
2. Filter position
3. Air re-circulation vs fresh air
4. Return air systems (positions)
5. Overpressure requirements

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 1- Air flow patterns
 There are 2 ways to supply air
to a room or equipment:
1. Turbulent air flow
2. Uni-directional flow, often
called laminar flow.
 The air speed in the uni-
directional flow is defined by
the WHO at;
a)0.45 m/s for horizontal units
b)0.30 m/s for vertical units
(most commonly used)
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 For air exhaust, in case of a vertical unit, a low return
is more favourable, as air is better distributed in the
room.
 Objects in the room can significantly disturb flow of
air, and even block it, so that there might be pockets
without air circulation.
 During qualification phase, the air flow is visualized
if possible, and air samples are taken in different
points, to make sure that there are no such pockets
 Otherwise case adjustments to the layout or to the air
handling systems must be made.

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 Filtered air entering a production room or covering a
process can be;
1. Turbulent
2.Uni-directional
 Two aspects have to be considered:
a)GMP aspect: uni-directional air (laminar) installations
give a better protection, because of the displacement
effect rather than the dilution effect.
b)Economical aspect: turbulent air installations are
cheaper, as less air has to be treated.
3.New technologies: barrier technology/isolator
technology. 32
 For certain operations, namely in class A, a “Laminar
flow” must be used.
 Such installations can give false impression of
security, purpose of such installations is that there
should be, whenever possible, no human
interventions under them during the process.
 If interventions have to occur, they should be
performed in a well-documented way, recorded and
evaluated for possible damage to the products.
 Use of barrier technology systems (isolator
technology) is highly recommended in cases of
operations in class A, or for sterility testing
operations. 33
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 Uni-directional (laminar) flow units exist mostly as
vertical, but also as horizontal, units.
 Often, we deal with LF workbenches (mainly used in
sterility testing) or LF cabins/booths, routinely used in
production, for instance on top of a filling machine.
 In some cases, the units can be integrated into ceiling
of a room & also connected to central air conditioning
system.

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 Due to high air velocity, it is important to have objects
with good aerodynamical properties under the
laminar flow. If not, turbulences and, therefore,
particles are unavoidable.
 Laminar flow units are comparatively expensive so
surfaces covered by them should be reduced to a
minimum.
 Only products in a critical production phase, and not
the personnel, should be under laminar flow (aseptic
filling, sterile blending, etc.).
 Manual interventions should be restricted to a
minimum, and should be recorded and evaluated for
possible consequences.
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 2- Positioning of filters
 Filters are seen both in central air handling units
(AHU) and terminally mounted at the
production rooms.
 Filtered air entering a production room can be
coming from;
1. Air-handling unit, equipped with pre-filtration &
main (HEPA) filter, but at some distance from
that room (left drawing).
2.Air-handling unit, equipped with pre-filtration in
AHU, and an additional filter (HEPA) situated
immediately on the air outlet (right drawing).
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 In many cases, there are only filters in the AHU.
 For injectables & sterile forms, it is recommended that
they be placed in terminal position, though there is a
growing tendency to have terminal filters in all rooms
where open products are handled.
 It is recommended that classes A & B (ISO 4, 5 & 6)
have terminal HEPA filters.

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 There are advantages and disadvantages of terminal or
non-terminal filters, generally terminal positioning
1. Is more expensive
2. Provides a better protection (any problem arising
from the ducts is eliminated)
3. Preferred method in cleanroom classes with high
requirements.
 Filters can be in different positions, considering the
central AHU and the rooms.
 Slide A shows an HVAC installation feeding 3 rooms,
each one with terminal filters, all filters protected by a
remote pre-filter.
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 Slide A
a) Room 1 has
turbulent air flow,
with low level
exhaust.
b) Room 2 has a uni-
directional (laminar)
air flow over largest
part of the surface,
hence large number
of filters.
c) Room 3 has a
turbulent air flow,
with ceiling exhaust. 40
 Slide B
 Slide B shows an HVAC
installation feeding two
rooms, each without
terminal filters, but with
remote final filters
protected by a pre-filter.
a)Room 1 has a turbulent air
flow, with low level
exhaust.
b)Room 2 has a turbulent air
flow, with ceiling exhaust.
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 If there is no filter in terminal position, it
should be ascertained that there are no
elements between the main filter and the air
outlets which could add contamination.
 No elements such as fans, heating/cooling
batteries, should be situated downstream of
the final filter.

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 3- Air re-circulation & 4-Return Air
 The filtered air entering a production room
can be 100% exhausted or a proportion re-
circulated.
a)GMP aspect
b)Economical reasons
1)Eliminated at 100% (exhaust air)
2)Proportion re-circulated
 Re-circulated air must be filtered, at an
efficiency rate which is such that cross-
contamination can be excluded.
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 In case of re-circulation, every possible measure
of protection must be taken to ensure that air
coming from a production unit and loaded with
product particles does not flow to other
production units, thereby contaminating them.
 It makes sense to re-circulate air for reasons of
energy conservation, but there can be a
contradiction between pharmaceutical
requirements and energy conservation.
 There are also cases, in which air re-circulation is
prohibited, for example if solvents are used or
cytotoxic products are manufactured.
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Ventilation with 100% fresh air
 Below Fig. illustrates a typical 100% fresh air setup,
where a central unit distributes fresh, treated air to
different production rooms.
 Exhaust air is collected in a central duct, treated
(filtered or washed) and eliminated.
 Degree of exhaust air filtration will depend on
contaminants in exhaust air & also on environmental
regulations.

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Ventilation with Re-circulated air + Make-up air
 Below fig. illustrates typical re-circulated air setup,
where a central unit distributes a mixture of fresh and
re-circulated air to different production rooms.
 Part of exhaust air is collected in a central duct, treated
(filtered) & exhausted. Rest is re-circulated (dotted line).
 With control dampers, proportions of fresh and re-
circulated air can be adjusted.

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 Summary For AHU
 Air must be exchanged at intervals & filtered, fresh or
recycled air introduced free from contaminants.
 Spun glass, cloth or shredded polyethylene filter used as
prefilters (single/multiple).
 To remove finer particles of debris & microorganisms in
submicron range, HEPA filters are used.
 Defined as at least 99.97% efficient in removing particles of
0.3µm or larger.
 Composed of glass fibers & fibers or electrostatic
precipitators & provide air virtually free from foreign
matter.
 Air cleaning systems wash air with a disinfectant & at the
same time controls humidity.
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 Blowers installed in the ventilation system upstream to
filters so that all dirt producing devices are ahead of
filters.
 Clean air distributed in such away that it flows to
maximum security rooms at greatest volume flow rate,
thus a positive pressure is developed in these areas.
 Unclean air is thus prevented from entering aseptic
area through cracks, temporarily opened doors & other
openings.
 Pressure is reduced successively to draw the air from
maximum security area to less critical areas and then
return to filtration system.
 At the intake about 25% of fresh air is introduced for
comfort and needs of personnel.
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 New air control system is based on laminar flow
principles which have improved environmental
control & only means to get a Class 100 room.
 HEPA-Filtered air is blown evenly on the workbench
or area.
 Airflow be uniform in velocity & direction throughout
an area, and is exhausted from opposite side.
 Air velocity 90-100 ± 20 ft/min.
 Contamination is swept away with airflow but any
downstream contamination through supplies,
personnel or equipment carried to critical area.
 Vertical flow has less risk so preferred for most critical
areas.
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Requirement for Personnel PROCESSING
i. Non professional & 1. Preparation of WFI
require guidance. 2. Storage and distribution
ii. Neat, orderly, 3. Cleaning equipment &
reliable, alert, containers
active. 4. Rinsing new containers
iii. Good health. 5. Cleaning rubber and
plastic components
iv. Properly clothed.
6. Sterilization of equipment
v. While entering &
7. Compounding of product
leaving follow
proper procedures. 8. Filtration of solution
9. Filling
10. Packaging 53
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 Liquid Filling
 Repetitive forcing a measured volume of liquid through the
orifice of a delivery tube designed to enter the constricted
opening of the container.
 Size depends on opening in container, viscosity and density of
liquid & speed of delivery.
 Be of maximum possible diameter & must freely deliver liquid
deep enough to permit air to escape without forcing liquid out
into neck or out of container.
 Excessive delivery force cause splashing or foaming.
 Retraction device is present in most filling machines as part of
machine to retract the drop which normally hangs at tip of the
tube after delivery.
 Operating factors can affect precision which is not a big
problem for low potency large volume solutions but serious for
high potency low volume solutions.
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V

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 Filling of Solids
 More difficult b/c of slow and
irregular flow (more
tolerance allowed).
 Large opening containers
used, even then filling slow
as compared to liquid.
 Individual manual weighing.
 Mechanical weighing can be
done in case of free flowing
powders.

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 Problems associated with automatic filling are;
i. Stratification due to variable size.
ii.Development of electrostatic charge.
iii.Air pockets.
iv.Uneven flow due to clumping.
 All result in uneven filling.
 Can be minimized by making size uniform and
use of electric current to neutralize the charge.

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 Sealing
 In aseptic area done adjacent to filling machine.
 Retention of contents & assurance of not being
opened.
 Ampoule closed by melting portion of the glass of
neck to form bead-seals (tip-seals) or pull-seals.
 Tip-seals are made by melting sufficient glass at
the tip of ampoule neck to form a bead of glass &
close the opening.
 Pull-seals are made by heating neck of rotating
ampoule below the tip, & pull the tip away to form
a small twisted capillary just prior to being closed
by melting.
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 PROCEDURE
 Feed the Ampoules to an inclined charging hopper
from Sterilized S.S boxes.
 Ampoules are passed continuously through rotating
feeding wheel, which transfers the Ampoules to
Ampoule conveyor by the Charging hopper.
 Ampoule conveyor carries the Ampoules vertically at
an angle.
 Pass the nitrogen (Inert Gas) into the empty
Ampoules.
 Volume to be filled passes through the pumps, by
positive displacement through the valve, filling tubes
and filling needles, finally into the Ampoules.

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 Pass nitrogen (Inert Gas) into the Filled Ampoules.
 The filled Ampoules are moved to sealing station.
 In sealing station the Ampoules necks are pre-
heated and the pre-heated necks are gripped by the
draw-off tongs and sealed.
 Make sure that the sealing has been done before
the Inert gas can diffuse to the outside.
 Collect the sealed Ampoules in the collection
hopper with proper labeling.

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