Air Handling Systm in Pharmaceutical Manufacturing Pharm R.A. Binitie

AIR HANDLING SYSTEM IN
PHARMACEUTICAL
MANUFACTURING
A presentation By
Pharm R.A.BINITIE
Assistant Director
Drug Evaluation and Research Directorate
NAFDAC
24-Jan-18 1
PHARMACEUTICAL MANUFACTURING
OUTLINE
• INTRODUCTION
• OBJECTIVES
• REGULATORY IMPERATIVE
• APPLICATIONS
• HVAC SYSTEM
• PRODUCT PROTECTION
• CONCLUSION
• REFERENCES
24-Jan-18 2
INTRODUCTION (I)
• Air handling system plays a major role in the quality of
pharmaceutical product manufacturing( all types).
• It is the technology of indoor and manufacturing space
environmental control and or comfort
• It regarded as one of the most important utility in drug
product manufacturing (a critical system)
• The manufacturing environment or space is very critical to
product quality and is premised / dependent on the air
handling system which controls the level of containment (
pressurization)and cleanliness( room classification)
24-Jan-18 3
INTRODUCTION (II)
• The uncontrolled environment can lead to product
degradation, loss of product, and economic issue-profit ,
product contamination/cross contamination
• The manufacturing environment is critical for products and
considers these factors(GMP environment) :light , temp,
humidity, air movement, microbial contamination, particulate
contamination,
• Air handling system to satisfy GMP/regulatory requirements
must be suitably designed, installed, qualified/Validated,
monitored and maintained by professionals ( GEP)
24-Jan-18 4
OBJECTIVES
• To understand the need for air handling system in the
pharmaceutical industry
• The technical requirements for air handling system
• Different types of air handling system
• Qualification and validation of HVAC system
• Monitoring and maintenance
24-Jan-18 5
WHY AIR HANDLING SYSTEM IN PHARMACEUTICAL
MANUFACTURING
• Needed to condition and provide the ideal GMP environment

or air space cleanliness needed for the various
pharmaceutical processes and controls in manufacturing .
• A critical factor of Quality Assurance for pharmaceutical
products( Clean areas/space for manufacturing)
• Issue of personnel comfort, satisfaction and safety
• As a means of containment control ( airborne
particulate)and prevent Contamination and cross
contamination
• Avoid product rejection
Contamination only mentioned in the presentation

24-Jan-18 6
REGULATORY IMPERATIVES
• NAFDAC cGMP Regulatory Guidelines for Pharmaceutical
Products 2106 – entrenches/prescribes Air handling system in
manufacturing; viz
Sections 3.20 : Production areas
Section 3.22 : Dust Controls
Section 3.25 : Storage of equipment air requirement
Section 3.26 : Air Supply to manufacturing space
and laboratory operations.
Section: laboratory design(for microbiology section)
Section 3.28: storage area for materials
Section 3.42-3.46 : HVAC system
section 4.3a-d: Qualification & Validation ( equipment and
utilities) etc
24-Jan-18
Other sections not included on this slide 7
APPLICATIONS OF AIR HANDLING SYSTEM
An ideal cGMP environment for manufacturing (HVAC system) should provide:
• Product protection:
protect from contamination , cross contamination, prevent contamination
by operatives, correct conditions of humidity and temperature.
• Personnel protection:
prevent contact with dust, prevent contact with fumes, good comfort
condition
• Environment protection:
No dust discharge, no fumes discharge, no effluent discharge
• Preservation of materials and equipment
Handling, holding and storage
• Maintenance of animals and equipment
• The GMP environment is only possible with an Air Handling System
24-Jan-18 8
WHAT IS AIR HANDLING SYSTEM
• Air handling system is regard as HVAC and refers to Systems

which are mechanical arrangements that treats outside air to
produce cleaned (from dust and microbes) conditioned air (
temperature and humidity) which is circulated or re-circulated for
use in controlled and critical areas within the pharmaceutical
manufacturing space
• OR
• Can be simply said to be a utility system used to provide air
ventilation, heating, cooling and air conditioning services to a
building or a pharmaceutical space for drug manufacturing
• The Acronym HVAC means: H= Heating, V= Ventilation; A= Air; C=

Conditioning
24-Jan-18 9
24-Jan-18 10
HVAC SYSTEM
• HVAC system comprises of Air Handling Unit ( AHU)
connected to a ductwork ventilation system that distributes
the conditioned air through the building and returns it to the
air handler(AHU).
• Air Handling Unit (AHU) is a device used to condition and
circluate air as a part of HVAC. It is usually a large metal box
containing a blower, heating or cooling elements, filter racks
or chambers, sound attenuators and dampers
24-Jan-18 11
INSIDE AN AIR HANDLING UNIT
24-Jan-18 12
SCHEMATIC OF AIR HANDLING UNIT (AHU)
AHU SECTION
24-Jan-18 13
AIR HANDLING SYSTEM/HVAC COMPONENTS
• Ducting ( for delivery of controlled air)
• Fan component
• Vibration isolator (flex joint)
• Heating and /or coiling coil
• Filter compartment ( houses pre and post filters)
• HEPA Filter
• Mixed (re-circulated + outside ) air duct
• Louvers ( Weather)
• Damper ( fixed adjustment of volume of air)
• Dehumidifiers
• Flow rate controller
• Humidity, Temperature, Pressure sensors, alarms and audit log
system
•24-Jan-18
Dust extractors 14
24-Jan-18 15
TYPICAL INSTALLATION OF AHU UNIT (VISUAL)
24-Jan-18 16
HVAC MAIN SUBSYSTEMS
Exhaust air treatment
Fresh air treatment

(make-up air) Terminal air treatment
+
at production room level
Production Room
Central air handling unit
24-Jan-18 17
OVERVIEW OF HVAC COMPONENTS
Silence Flow rate controller Fan Filter
r
Weather louvre Control damper
+
Prefilter Humidifier Terminal filter
Cooling Production Room

coil
with
Heating
droplet
coil
separator
24-Jan-18 18
Air-handling unit
AHU with fan

Control damper for airflow Variable Speed
Controller
Adsorber wheel
Humid room air Filter Pressure
Gauges
Regeneration air Humid room air
Air heater
24-Jan-18 19
CHARACTERISTICS OF AIR HANDLING SYSTEM/HVAC
• Turbulent air flow ( air flow pattern)
• Unidirectional airflow ( air flow pattern)
• Filter position ( Terminal Position, air recirculation
system)
• Fresh air (100%)/Once through / external air
• Air re-circulation
• Return air systems (positions low wall air return)
• Overpressure requirements
• Local extraction system( deduster, canister)
24-Jan-18 20
FUNCTIONS OF AIR HANDLING SYSTEM (HVAC)
• Control airborne particulate , dust and micro-organisms
through air filtration using HEPA filters
• Maintains room pressures ( in areas that must remain cleaner
that surrounding areas (+ve)
• Reduces contamination by air flow from cleaner areas toward
adjoining space through doors, , ceiling openings ( reduces
chances of contamination)
• Maintains space moisture RH(by cooling to due point
temperature and using desiccant dehumidifiers)
• Maintains space temperature ( can affect product directly or
indirectly)
All to minimise and prevent contamination and cross contamination

24-Jan-18 21
WHAT CAN AIR HANDLING SYSTEM NOT DO
• Cannot clean up contaminated surfaces, room or equipment
• Do not compensate for workers who do not follow
procedures
24-Jan-18 22
QUALITIES AND ATTRIBUTES OF A GOOD HVAC SYSTEM
• Suitably designed, installed, Qualified / validated and
maintained (GEP) to meet GMP requirements for the intended
purpose
• Reliable and economical to run
• Supported by appropriate documentation (lay outs, SOPs,
reports of commissioning, qualification and validation,
monitoring and maintenance records etc
24-Jan-18 23
CLEAN AIR SUPPLY CONCEPTS
There are two basic concepts of clean air delivery for
pharmaceutical production:
• Full Fresh air or Make up air
• Recirculation or Return air
All to provide the need conditioned clean air for intended
clean room required for manufacturing areas.
What is clean area/ room/space?
• A closed room supplied with filtered ( purified air ) in which
the particulate and microbial contamination load is below
specified level. And is used in such a way to minimise
introduction, generation and retention of contaminants
24-Jan-18 24
CLEAN AREA/ROOM CONSIDERATIONS
• All pharmaceutical facilities belong to one/ certain or other class of
clean rooms
• Facility classification are based on clean air supply that matches the
requirement for manufacturing process/product
• Clean rooms classification differs for sterile and non sterile and can
be classified as such:
 Non sterile operations/controlled or non aseptic
 Sterile operation/critical areas/aseptic applications
 Examples of clean room requirements for some product lines: eg
tablets class D (10,000)
topical and oral liquids belong to class C(10,000)
sterile preparations/injectable – class A or B(100)
24-Jan-18 25
CLEAN AREA CLASSIFICATION CONSIDERATIONS
• Clean Room Classification defined in the state of “as
built”, “at rest ,” or “in-operation”
• Clean rooms are also Categorized by way of which supply
air is distributed :
 Generally two air configuration: Unidirectional -UDAF
(Laminar) LAF or RLAF) . This achieved by Vertical down
displacement of room air or by horizontal laminar flow)
– defined air velocity
 Or Non –Unidirectional air flow
• EU classification is based on alphabet system A,B,C,D;
FDA numerical eg class 100; 1000; 10,000; and 100,000
24-Jan-18 26
CLEAN ROON CLASIFICATION CONSIDERATIONS
• WHO & EC,EU, PIC/S, TGA: classes A,B, C, D
• USFDA : critical and Controlled
• ISE: level1,2,or 3
• INSERT PICTURE OR SLIDE of

classification??????
24-Jan-18 27
DEFINITIONS OF ROOM CONDITION
as built at rest in operation
air air air
24-Jan-18 28
AIR FILTRATION AND CONTROL OF CONTAMINANTS
• External Air contaminants are removed by filtration
• Internal contaminants are controlled by dilution and flushing or by
displacement air flow
• Airborne particulates and level of filtration are considered critical
in Air Handling system
• The filtered air entering a production room can be derivable from
 100% fresh air/external air or
 a proportion re-circulated ( Mixed with external/fresh air)
 New technologies: barrier technology/isolator technology
24-Jan-18 29
AIR HANDLING SYSTEM IN PHARMACEUTICAL
MANUFACTURING
Types of Air encountered in HVAC system: fresh air, supply air, recirculated and exhaust
air
Air types
Fresh air
(make-up + Exhaust
Supply air
air)
air
Production Room
Return air
(recirculated)
24-Jan-18 30
FRESH AIR ( 100%)/ONCE THROUGH SYSTEM (1)
• Applicable to factory dealing with toxic products
• Low risk of cross contamination
• Provides
• The exhaust air filtration depends on the degree of contaminants
and local environmental regulations
• Offers abundant oxygen rich fresh air for dilution of contaminants
• Air leakage between the supply and exhaust air should be
prevented, supply air pressure should be higher that the exhaust air
pressure
• Exhaust fan may be located remote from the AHU making ducting
simpler
24-Jan-18 31
FRESH AIR ( 100%)/ONCE THROUGH SYSTEM (2)
• Usually more expensive to run ( heating and cooling
demand)
• High filter loading resulting in frequent filters
replacement
• Additional requirement for air treatment(scrubber,
dust collectors)
• Applicable in laboratory hood, API plant handling
highly inflammable materials, oral solid dosage plant(
OSD) where potent /product/materials are exposed.
24-Jan-18 32
VENTILATION WITH 100% FRESH AIR (no air re-circulation)
Washer (optional)
Exhaust Unit
Central Air Handling Unit
24-Jan-18 33
24-Jan-18 34
RECIRCULATION SYSTEM (1)
• A proportion or % of re-circulated air mixed with
fresh air/external air
• Requires installation of HEPA filters in the supply
air stream to remove contaminants which may be
placed terminally or in AHU ( H13 HEPA filter
recommended)
• Single product facility may not require HEPA
• Not suitable for fumes or dust from highly toxic
processes
24-Jan-18 35
• RECIRCULATION SYSTEM (2)
• Proportioning of fresh (external air) to re-circulated air
can be fixed or variable air volumes( temperature and
no of operatives, )
• Less air filter loading –lower maintenance cost (
variable air flow)
• Energy saving/cost
• Complex design and high level of automation
• Chances of cross contamination from system failures
• Applicable for OSD manufacturing , sterile operations,
Final bulk APIs
24-Jan-18 36
VENTILATION WITH RECIRCULATED AIR + MAKE UP AIR
Exhaust Unit
Central Air Handling Unit
Return air
24-Jan-18 37
AIR FLOW PATTERN (1)
• The air flow pattern is used to control the
internal contaminant by dilution or
displacement flow
• May be unidirectional or turbulent flow
• Turbulent can cause particulate settled on the
ground to be re-entrained in the air.
• Vertical down flow is the preferred (
displacement flow)
24-Jan-18 38
AIR FLOW PATTERN (2)
• Usually class 100 (must have unidirectional ( laminar) with
100% HEPA Coverage on the ceiling or wall and return on
opposite side
• Class 1000 and above are generally non unidirectional with
supply air outlet at the ceiling and return at the floor level
• Return grill – positioned low down , not near a door
opening into an adjacent lower pressure room ( to prevent
reverse air leakage to the high pressure room during door
opening
• Return risers should be fitted with manually operated
dampers
24-Jan-18 39
AIR FLOW PATTERN
Turbulent Uni-directional / laminar

displacement of dirty air
dilution of dirty air
0,30 m/s
24-Jan-18 40
PHARMACEUTICALMANUFACTURING
AIR FLOW PATTERN (II)
Prefilter
AHU
Main filter
Ceiling
exhausts
1 2 3
Low level exhausts
24-Jan-18 41
AIR FLOW PATTERN (III)
Workbench (vertical) Cabin/ booth Ceiling
24-Jan-18 42
POSITIONING OF FILTERS
• The required cleanliness or purity of air can be achieved with effective
cleaning of the external air or recirculated air through correctly
designed and installed filters to meet the specifications or
requirements for intended activity or manufacturing operation.
• Filter location can be in the AHU, terminal …………….????
• filters are of various types , specifications and classes
TYPES OF AIR FLTERS
 Ultra Low Particulate Air filter( ULPA)
 High Efficiency particulate air filter( HEPA)
 Packed towers
 Membrane filter cartridges
 Hydrophobic filters
24-Jan-18 43
SPECIFICATIONS FOR FILTERS
• Simple MERV (1-16), pre filters (10, 20, 50µ efficiency
80-90% , secondary filters(5µ: efficiency up to 99%),
HEPA filters (0.3µ: efficiency upto 99.99
CLASSES OF FILTERS
• Coarse (Dp < 10µ , G1-G4, Fine ( 1.0µ <Dp <10µ : F5 –
F9); HEPA( H10-H14) &ULPA(U15-U16) both of Dp <
1.0µ)
Filter efficiency testing should be linked to the standard
test methods ( different test methods could give
different results for same filter)
24-Jan-18 44
FILTERS
24-Jan-18 45
HEPA FILTER
24-Jan-18 46
POSITIONING OR LOCATION OF FILTER IN AHU (1)
TERMINAL ( AHU OR 47
ROOM SUPPLY VENT
POSITIONING OF HEPA FILTERS (2)
AHU mounted final filter Filter in terminal position

HEPA Filter
Production Room Production Room
HEPA Filter
24-Jan-18 48
POSITIONING OF FILTERS (3)
Prefilter
AHU
Main filter
Ceiling
exhausts
1 2 3
24-Jan-18 49
POSITIONING OF FILTERS (4)
Final filter
AHU
Prefilter
1 2
24-Jan-18 50
VALIDATION AND HVAC SYSTEM
• An HVAC system is viewed as a process using outside air as a
raw material and producing conditioned air. The conditioned
air comes in contact with the product and hence has a direct
impact on the quality of the product
• Such system being a part of the facility in which
manufacturing occurs must be qualified and validated.
24-Jan-18 51
QAULIFICATION/ VALIDATION ISSUES
A good design is essential, but it has to be complemented by:
• Qualification of air handling systems (USR, DQ, IQ, OQ,).
• Process validation ( process performance qualification PPQ-
encompassing the facility, utility and equipment
• Operation &Continuous process Verification ( establish
environmental monitoring program, data collection trend
analysis, define action and alert limits).
• Maintenance and periodic re-qualification
• Adequate documentation
USR & DQ concept should be based on data from process(target

critical environmental parameters), Quality (regulatory &
quality principles-impact on product), Operation and
maintenance
24-Jan-18 52
WHAT TO QUALIFY/VALIDATE
• The mechanical system( the installations and operations; and
the controls
• The air distribution system (installation, adequacy, safety
issues, air flow pattern, filter integrity test)
• The condition prevailing in the rooms( temperature and
humidity, air changes, air velocity, relative pressurization –
differential pressure across filter F6. F9, H13, classification if
applicable)
• Particulate and microbial validation
• Alarms and audit log features
• Time scheduling of AHU ????????
24-Jan-18 53
Qualification (OQ, PQ) (1)
Uni-directional Turbulent /
Test Description
airflow / LAF mixed airflow
Differential pressure on filters 2 2

1 := As built (ideally used to perform IQ)
Room differential pressure N/A 2, 3 2 = At rest (ideally used to perform OQ)
Airflow velocity / uniformity 2, 3 Optional 3 = Operational (ideally used to perform
PQ)
Airflow volume / rate 2 2
Parallelism 2 N/A
Air flow pattern ( Smoke test) 2 3
IQ tests are not mentioned on this slide
24-Jan-18 54
Qualification (OQ, PQ) (2)
Uni-directional Turbulent /
Test Description
airflow / LAF mixed airflow
Recovery time N/A 2 1 := As built (ideally used to perform IQ)

Room classification (airborne 2 = At rest (ideally used to perform OQ)
2 2,3
particle)
3 = Operational (ideally used to perform
Temperature, humidity N/A 2,3 PQ)
24-Jan-18 55
WHAT TO MONITOR
• Temperature
• Humidity
• Pressure (pressure differential)
• Particulate
• Microbial or Biological load
24-Jan-18 56
WHERE TO MONITOR
• All production areas ( including corridors and airlock)
• Storage areas for product, intermediates and raw materials(
especially if affected by environmental conditions, in critical
areas near the doors, ceiling)
• Clean rooms an laminar flow hoods
• Critical surfaces
• Environmentally controlled rooms and chambers
• Freezers, refrigerators, incubators
24-Jan-18 57
CRITERIA
• Set criteria from product requirements( temp sensitivity,
microbial contents for sterile areas, regulatory, compendia
standards, literature and industry experience etc
HOW TO MONITOR
• Various specified instruments, equipment and materials for
monitoring are in use – eg pressure Magnehelic gauges
(method should be specific)
ALERT AND ACTION LIMITS
• Define alert and action limits –use of historical data to
calculate the standard deviation and apply 3standard
deviations around the mean as action limit and 2 standard
deviation as alert limit
24-Jan-18 58
EXPECTATIONS
• Data trends towards deviations
• Repeat occurrences ( problematic issue)
• Data pattern
• Any changes / differences from what you have been observing
in the past
24-Jan-18 59
POSSIBLE PROBLEMS THAT CAN OCCUR
Problem with controller : blockage
Control damper: Poorly adjusted , bad pressure
differential system
Humidifier : Bad water/steam quality poor drainage
Cooling battery : No elimination of condensed
water/poor drainage
Filters: Incorrect retention rate/damage/badly installed
Duct:- Inappropriate material internal insulator leakage
24-Jan-18 60
DEFINING ALERT AND ACTION LIMITS
1. Definition of alert / action limits as a function of cleanliness zone.

2. Identification and marking of sampling points
3. Definition of transport, storage, and incubation conditions
ACTION LIMIT ACTION LIMIT
ALERT LIMIT ALERT LIMIT
Design Condition
Normal Operating Range
Operating Range - Validated Acceptance Criteria
24-Jan-18 61
AIRHANDLING SYSTEM IN
CLEAN ROOM MONITORING (1)
Clean rooms should be monitored for
microorganisms and particles
air
Sampling point
24-Jan-18 62
CLEAN ROOM MONITORING (2)
• There should be routine monitoring program as part
quality assurance
• Additional monitoring and triggers
 Shutdown
 Replacement of filter elements
 Maintenance of air handling systems
 Exceeding of established limits)
24-Jan-18 63
CLEAN ROOM OPERATIONS/ ACTIVITIES

• All operations within a pharmaceutical facility should be correlated to
well defined clean room classes and can be included in a hygiene
concept
Cleanroom Class A B C D
Washing of containers X
Preparation of solution for terminal sterilization X
Preparation of solutions for aseptic filling X X X
Depyrogenisation of containers X
Filling for terminal sterilization X
Filling for aseptic process X

etc.
24-Jan-18 64
CLEAN ROOM MAINTENANCE
PROGRAM (1)
Schedule of Tests to Demonstrate Continuing Compliance
Test Parameter Class Maximum Time Test Procedure

Interval
Particle Count Test A, B 6 Months ISO 14644 -1 Annex A
<= ISO 5
C, D 12 Months ISO 14644 -1 Annex A
> ISO 5
Air Pressure Difference All Classes 12 Months ISO 14644 -1 Annex B5
Air Flow All Classes 12 Months ISO 14644 -1 Annex B4
24-Jan-18 65
CLEAN ROOM MAINTENANCE
PROGRAM (2)
Schedule of Additional Optional Tests
Test Parameter Class Maximum Time Test Procedure

Interval
Installed Filter Leakage All Classes 24 Months ISO 14644-1 Annex B6
Containment Leakage All Classes 24 Months ISO 14644-1 Annex B4
Recovery All Classes 24 Months ISO 14644-1 Annex B13
Air Flow Visualisation All Classes 24 Months ISO 14644-1 Annex B7
24-Jan-18 66
HVAC PARAMETER MONITORING AND FREQUENCY
Serial PARAMETER FREQUENCY
No
1 HEPA Filter Integrity ( Annual / Yearly ( 12
DOP testing) monthly)
2 Air Change rate Every 6 months(
biennially)
3 Air pressure Daily
differential
4 Microbial load ( settle Daily
plate & Swabs)
5 Temperature Daily
6 Humidity ( Relative Daily

24-Jan-18 Humidity) 67
DOCUMENTATION REQUIREMENT FOR AIR HANDLING SYSTEM
• Description of installation and functions
• Specification of the requirements ( Engineering and MOC)
• Operating procedures (SOP)
• Instructions for performance control (switch on and off)
• Maintenance instructions and Maintenance records
• Training of personnel (program and records)
• O& M manual (operation and maintenance manual)
• Test and balance ( TAB) reports/ Commissioning
• Engineering drawings ( mechanical drawings, architectural
drawings
• Log records for monitoring and data
24-Jan-18 68
CONECRNS FOR PRODUCT PROTECTION IN MANUFACTURING (1):
Include contamination/cross contamination of products that could
result from:
• Non reliable and poorly designed air handling s/ dust extraction
system
• Poor operation and no maintenance
• Inadequate procedures for equipment and personnel
• Improperly cleaned equipment
24-Jan-18 69
CONECRNS FOR PRODUCT PROTECTION IN MANUFACTURING (2)
Product protection can be archived through controls:
 filtration of particulates from incoming air to remove external
contaminants and
 Air dilution and displacement to control internal contaminants/
local extraction (point of use)
 Local air supply or extraction eg isolators and barrier systems
 Maintaining sufficient air supply velocity and volume to flush
unwanted dust from work areas.
 Air lock system used to limit or minimise migration of contaminants
 Airlock system can be cascade, bubble or sink type
 Pressurizing helps to prevent cross contamination between areas,
ingress of materials from outside, separate areas of different
cleanliness
24-Jan-18 70
SOME DESIGN FEATURES OF AIR HADNDLING SYSTEM
• Airlocks
• Pressurization
• Supply air diffuser
• Gauges, alarm and warning system
24-Jan-18 71
AIRLOCK SYSTEM (1)
• Small room with controlled air flow acting as barrier between spaces,
minimises volume of contaminated air that is introduced into the cleaner
area when door is opened
• Air lock should open and close fast( minimise time of contamination
• No simultaneous opening of booth doors
• High air change rate and smaller airlock ensure faster recovery time
• Three types : cascade, sink and bubble airlock. Airlock should open to the
higher pressure side
Cascade :
• High pressure on one side of the airlock and low pressure on the other
side. They are very common.
• Outward for sterile operations and inward d for toxic or hazardous
materials
• Pressure differential range from 10-15pa and is measured across the
airlock and not the single doors
• Used in dispensary layout must be designed to be adequate for purpose
24-Jan-18 72
AIRLOCK SYSTEM (2)
Sink
Low pressure inside the air lock and high pressure on both outer sides
Usually designed 5-8pa below the smaller of the two classes pressure
Designed for dirty operation like gowning, decontamination/exit
Used when there are requirements for both area and classification
and product containment
Bubble
High pressure inside and low pressure on both outer sides
Used for clean operations like gowning and Material entry airlock
Used when there are requirements for both area and product
containment
24-Jan-18 73
THREE TYPES OF AIRLOCK IN USE IN PHARMACEUTICAL INDUSTRY
24-Jan-18 74
PRESSURIZATION
• Pressure gradient maintained between adjacent rooms
• Net airflow from aseptic to the non aseptic areas
• Air flow from high pressure to low pressure zone
• Pressure between two room is pressured differential
measured
• Air locks are used when there is requirement for pressure
demarcations.
• Alarms for pressure drops and failures required
24-Jan-18 75
DIFFUSERS
• Used to create air supply pattern in the room
• Types include induction diffusers, perforated plate diffuser,
swirl diffusers
• Caution should be preclude non usage of high induction
diffusers in clean areas because of induction of air, instead
non induction type should be used so as to maximise
flushing effects
24-Jan-18 76
AIR HANDLING SYSTEM IN PHARMACEUTICAL
MANUFACTURING
Swirl Type air diffusors with
terminal filters
1
2
3
4
1. Filter
2. Tightening frame
3. Registered outlet
4. Screw fixation for
register
24-Jan-18 77
HIGH INDUCTION
DIFFUSOR
High induction Low induction

office type diffusor swirl diffusor
(avoid) (preferred)
24-Jan-18 78
REGULATION OF ROOM PRESSURE – pressure differentials
concept
Room pressure
Room pressure indication panel gauges
Room pressure
indication panel could
also be electronic type
24-Jan-18 79
AIR HANDLING SYSTEM AND
INSPECTING THE AIR HANDLING PLANT
1. Verification of design documentation,

including
 description of installation and functions
 specification of the requirements
2. Operating procedures
3. Maintenance instructions
4. Maintenance records
5. Training logs
6. Environmental records
7. Discussion on actions if OOS values
8. Walking around the plant
24-Jan-18 80
HOW MANY HVAC SHOULD BE USED
• HVAC are of simple or small unit ( Modular) or Large Single
Unit ( Central Unit)
• The use of multiple small units ( modular) improves
reliability ( impossible for all units to fail)
• Air balancing is easier with multiple small units
• They require smaller distribution ductwork and is easier to
route through ceiling void
• It is easier to make modification to parts and upgrade as
compared to large single units ( Central unit)
• Allows for easier separation of areas within multi-products
concurrent manufacturing facility or plant
24-Jan-18 81
CONCLUSION
Air Handling System plays a critical role in the
wheel of factors contributing to product quality in
pharmaceutical manufacturing by providing the
specific set of room space conditions needed to
make quality product. It must be properly
designed, installed , validated by professionals, ,
monitored and maintained as a part of
continuous validation/revalidation of the citical
system.
24-Jan-18 82
REFERNCES
• NAFDAC GMP Guidelines for Pharmaceutical products
2016
• HVAC Design for Pharmaceutical Products, A. Bhatia
• WHO Technical Report Series No.937, 2006, Annex 2
• GMP and Quality Assurance of TB products, Kuala
Lumpur, by Majia Hietava
• HVAC ; Gamal Amer, Premier Compliance services
limited
• HVAC Basics; Vishal Katyar
24-Jan-18 83
THANK YOU
THANK YOU
THANK YOU
24-Jan-18 84
CASE STUDY 1
A multiproduct OSD pharmaceutical company
with a central HVAC system of recirulated air has
just commenced operation in Nigeria and one of
the product being manufactured in the facility is
misoprostol. It was noticed that air supply to
production was by induction system and during a
production section water was observed to be
dripping from the false ceiling void along the
HVAC duct .
What do think are a stake in this situation?- Outline
24-Jan-18 85
CASE STUDY 2
• Outline the interventions you would take for
a multiproduct manufacturing plant that has
been having issues of down time with their air
Handling System, which resulted in microbial
load exceeding limits and eventual adoption
of AHU scheduling( shutdown at weekends).
24-Jan-18 86

Air Handling Systm in Pharmaceutical Manufacturing Pharm R.A. Binitie

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Air Handling Systm in Pharmaceutical Manufacturing Pharm R.A. Binitie

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AIR HANDLING SYSTEM IN

• Needed to condition and provide the ideal GMP environment

Contamination only mentioned in the presentation

• The GMP environment is only possible with an Air Handling System

• Air handling system is regard as HVAC and refers to Systems

• The Acronym HVAC means: H= Heating, V= Ventilation; A= Air; C=

Fresh air treatment

Weather louvre Control damper

Cooling Production Room

AHU with fan

Regeneration air Humid room air

All to minimise and prevent contamination and cross contamination

• INSERT PICTURE OR SLIDE of

as built at rest in operation

air air air

 New technologies: barrier technology/isolator technology

Central Air Handling Unit

Central Air Handling Unit

Turbulent Uni-directional / laminar

Low level exhausts

AHU mounted final filter Filter in terminal position

Production Room Production Room

USR & DQ concept should be based on data from process(target

Differential pressure on filters 2 2

IQ tests are not mentioned on this slide

Recovery time N/A 2 1 := As built (ideally used to perform IQ)

1. Definition of alert / action limits as a function of cleanliness zone.

ALERT LIMIT ALERT LIMIT

Normal Operating Range

Operating Range - Validated Acceptance Criteria

CLEAN ROOM OPERATIONS/ ACTIVITIES

Preparation of solution for terminal sterilization X

Preparation of solutions for aseptic filling X X X

Filling for terminal sterilization X

Filling for aseptic process X

Schedule of Tests to Demonstrate Continuing Compliance

Test Parameter Class Maximum Time Test Procedure

Air Flow All Classes 12 Months ISO 14644 -1 Annex B4

Schedule of Additional Optional Tests

Test Parameter Class Maximum Time Test Procedure

Containment Leakage All Classes 24 Months ISO 14644-1 Annex B4

Recovery All Classes 24 Months ISO 14644-1 Annex B13

Air Flow Visualisation All Classes 24 Months ISO 14644-1 Annex B7

6 Humidity ( Relative Daily

High induction Low induction

1. Verification of design documentation,

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