pt05 - hvac system design
DESCRIPTION
HVAC System DesignTRANSCRIPT
HVAC Systems and the Pharmaceutical Manufacturing Environment Radisson SAS Hotel, Amsterdam 2008
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HVAC Systems and the Pharmaceutical Manufacturing Environment
HVAC Systems and the Pharmaceutical Manufacturing Environment
Part 05: HVAC System DesignPart 05: HVAC System Design
David Dickinson, DD Validation Services Ltd.David Dickinson, DD Validation Services Ltd.
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Part 05/a - HVAC Design ConsiderationsPart 05/a - HVAC Design Considerations
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HVAC - Principal FunctionHVAC - Principal Function
• Normally, principal function is to control the number of particles within the manufacturing facility environment
• As you move towards aseptic conditions– Ability of the HVAC system to control particulate levels
becomes more and more critical– For Grade B areas, immediately adjacent to Grade A (ISO 5)
aseptic filling areas, design for particle control is essential– The fundamentals of clean room design are to control the
concentration of airborne particles– To design a facility and HVAC system such that particles are
controlled to the correct level• Must understand particle generation mechanisms how these can
be minimised.
• Normally, principal function is to control the number of particles within the manufacturing facility environment
• As you move towards aseptic conditions– Ability of the HVAC system to control particulate levels
becomes more and more critical– For Grade B areas, immediately adjacent to Grade A (ISO 5)
aseptic filling areas, design for particle control is essential– The fundamentals of clean room design are to control the
concentration of airborne particles– To design a facility and HVAC system such that particles are
controlled to the correct level• Must understand particle generation mechanisms how these can
be minimised.
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Particle GenerationParticle Generation
• The particulate matter can come from three sources: – The air supply– Internal particle generation– Infiltration from adjacent spaces
• To control these airborne particles, all three sources need to be considered.
• The particulate matter can come from three sources: – The air supply– Internal particle generation– Infiltration from adjacent spaces
• To control these airborne particles, all three sources need to be considered.
Air SupplyAir SupplyInfiltrationInfiltration
Internal GenerationInternal Generation
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Supply Air ControlsSupply Air Controls
• Supply air particle control is relatively easy– Use of HEPA (high-efficiency particulate air) filters
• HEPA Filter Efficiency Comparison– EU14
• Remove 99.995% of particles of the size of 0.15 to 0.3 µmfrom the air
• If there are 350,000/m3 particles of ≥ 0.5µm in the air supply to the filter (Grade C):
– Room air supply would have LESS than 18 particles (≥ 0.5µm) per m3 (Grade A specification is 3,500)
• Considered almost particulate-free!!!!!!!
– EU13 would give 180 particles– EU12 would give 1,800 particles.
• Supply air particle control is relatively easy– Use of HEPA (high-efficiency particulate air) filters
• HEPA Filter Efficiency Comparison– EU14
• Remove 99.995% of particles of the size of 0.15 to 0.3 µmfrom the air
• If there are 350,000/m3 particles of ≥ 0.5µm in the air supply to the filter (Grade C):
– Room air supply would have LESS than 18 particles (≥ 0.5µm) per m3 (Grade A specification is 3,500)
• Considered almost particulate-free!!!!!!!
– EU13 would give 180 particles– EU12 would give 1,800 particles.
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Internal Particle GenerationInternal Particle Generation
• Internal generation consists of particles from:– Building elements:
• Walls• Floors• Ceilings, etc.
– Equipment:• Conveyors• Moving parts
– Operators - MOST IMPORTANT!!!
• Internal generation consists of particles from:– Building elements:
• Walls• Floors• Ceilings, etc.
– Equipment:• Conveyors• Moving parts
– Operators - MOST IMPORTANT!!!
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Internal Particle Control – Buildings and Equipment
Internal Particle Control – Buildings and Equipment
• Particles from building– Minimized using hard-surfaced, non-porous
materials such as polyvinyl panels, epoxy painted walls, and glass board ceilings
• Equipment– Best design– Use of correct materials– Proper containment of machinery - outside of clean
space where possible– Use of additional filters, e.g. point of use filters on
utilities such as compressed air.
• Particles from building– Minimized using hard-surfaced, non-porous
materials such as polyvinyl panels, epoxy painted walls, and glass board ceilings
• Equipment– Best design– Use of correct materials– Proper containment of machinery - outside of clean
space where possible– Use of additional filters, e.g. point of use filters on
utilities such as compressed air.
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Control of Particle Generation by Operators
Control of Particle Generation by Operators
• Operators are the main source of internal particle generation in a cleanroom– Thousands of dead cells are shed from the human
body every minute• Without protection - contribute millions of particulate counts into
a clean room
• Particle generation by operators restricted by– Proper gowning– Minimising activity
• Level and standard of garments and room finishes required - driven by the particle specification of the room
• Best gowned clean room operators will still generate numerous particles per minute to the local environment:– Approx. 700,000 particles of 0.5 µm or larger per
minute
• Operators are the main source of internal particle generation in a cleanroom– Thousands of dead cells are shed from the human
body every minute• Without protection - contribute millions of particulate counts into
a clean room
• Particle generation by operators restricted by– Proper gowning– Minimising activity
• Level and standard of garments and room finishes required - driven by the particle specification of the room
• Best gowned clean room operators will still generate numerous particles per minute to the local environment:– Approx. 700,000 particles of 0.5 µm or larger per
minute
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Particle Infiltration Control [1]Particle Infiltration Control [1]
• Particles from adjacent spaces – relatively easy to control– If the adjacent area is less clean than the clean room of
concern• Particle infiltration can be minimized by controlling the airflow
direction, so that air flows from the clean room to its adjacentspace
• Accomplished by ensuring the room is operated at a greater pressure to the adjacent (less clean) space/room
• Need to ensure a degree of leakage to encourage correct air flow direction when doors are ajar/open.
• Particles from adjacent spaces – relatively easy to control– If the adjacent area is less clean than the clean room of
concern• Particle infiltration can be minimized by controlling the airflow
direction, so that air flows from the clean room to its adjacentspace
• Accomplished by ensuring the room is operated at a greater pressure to the adjacent (less clean) space/room
• Need to ensure a degree of leakage to encourage correct air flow direction when doors are ajar/open.
E E BB CC DD
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Particle Infiltration Control [2]Particle Infiltration Control [2]
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Room Particle Level ControlRoom Particle Level Control
• All rooms will have a level of internal particle generation– Without control, particle levels will simply carry on
increasing• For clean rooms
– Particle levels controlled by effective replacement of particle laden air with ‘clean’ air
– 3 factors that dictate this rate of clean-up are:• Amount of air supplied to the room [1]• The size of the room [2]• Effectiveness of ‘clean’ air distribution
– Factors 1 and 2 will give you the air change rate.
• All rooms will have a level of internal particle generation– Without control, particle levels will simply carry on
increasing• For clean rooms
– Particle levels controlled by effective replacement of particle laden air with ‘clean’ air
– 3 factors that dictate this rate of clean-up are:• Amount of air supplied to the room [1]• The size of the room [2]• Effectiveness of ‘clean’ air distribution
– Factors 1 and 2 will give you the air change rate.
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Recovery Period versus Air Change Rates [1]
Recovery Period versus Air Change Rates [1]
• HVAC systems are quite often designed around a particular particle recovery period required– This may be the deciding criterion for the air change rate
• The following slide shows the relationship between particle recovery rate and air change rates– Calculations involve two major assumptions
• Perfect mixing of supply and room air• Supply air contains essentially zero particles of the size used as
the basis of calculation
• Generally, the higher the classification/specification of the environment, the greater the recovery rate required.
• HVAC systems are quite often designed around a particular particle recovery period required– This may be the deciding criterion for the air change rate
• The following slide shows the relationship between particle recovery rate and air change rates– Calculations involve two major assumptions
• Perfect mixing of supply and room air• Supply air contains essentially zero particles of the size used as
the basis of calculation
• Generally, the higher the classification/specification of the environment, the greater the recovery rate required.
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Recovery Period versus Air Change Rates [2]
Recovery Period versus Air Change Rates [2]
Recovery Period versus Air Change Rate
1
10
100
1000
10000
100000
1000000
10000000
0 10 20 30 40 50 60 70 80 90
Time (minutes)
Part
icul
e C
once
ntra
tion
(log
scal
e)
10 ACH
20 ACH
30 ACH
40 ACH
• The drawing shows how by assuming a simple exponential decay the recovery period changes greatly with air change rate
• To recover from Class 10,000 to Class 100, with 20 air changes per hour, takes approximately 14 minutes, with 30 air changes per hour it takes approximately 9 minutes.
• The drawing shows how by assuming a simple exponential decay the recovery period changes greatly with air change rate
• To recover from Class 10,000 to Class 100, with 20 air changes per hour, takes approximately 14 minutes, with 30 air changes per hour it takes approximately 9 minutes.
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Particle Generation and Room Air Change Rates [1]
Particle Generation and Room Air Change Rates [1]
• Very Best Case (assumes instantaneous mixing of air within the total room volume):– For a 10m x 10m x 3m room and 4 clean room operators (using
particle generation rate of 700,000 particles of 0.5 µm or larger per minute per operator):
• Particle generation rate within entire room = approx. 10,000 (0.5 µm or larger) per m3 per minute
• To maintain entire room at Grade B “in operation” limit of 350,000 particles (≥ 0.5 µm per m3) – requires an air change rate of approximately 2 (10,000 x 60 /350,000)
• Very Best Case (assumes instantaneous mixing of air within the total room volume):– For a 10m x 10m x 3m room and 4 clean room operators (using
particle generation rate of 700,000 particles of 0.5 µm or larger per minute per operator):
• Particle generation rate within entire room = approx. 10,000 (0.5 µm or larger) per m3 per minute
• To maintain entire room at Grade B “in operation” limit of 350,000 particles (≥ 0.5 µm per m3) – requires an air change rate of approximately 2 (10,000 x 60 /350,000)
10m
3m
10m
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Particle Generation and Room Air Change Rates [2]
Particle Generation and Room Air Change Rates [2]
• More realistic estimate (assumes all particles transmitted to local 8 m3 air space around an operator)– Particle generation rate will be 700,000/8 = approx. 90,000
particles of 0.5 µm or larger per m3 per minute– To maintain this area at Grade B “in operation” limit of 350,000
particles of ≥ 0.5 µm per m3 – requires air change rate of approximately 15 (90,000 x 60/350,000)
– To maintain at 100,000 particles requires an air change rate of 54
• More realistic estimate (assumes all particles transmitted to local 8 m3 air space around an operator)– Particle generation rate will be 700,000/8 = approx. 90,000
particles of 0.5 µm or larger per m3 per minute– To maintain this area at Grade B “in operation” limit of 350,000
particles of ≥ 0.5 µm per m3 – requires air change rate of approximately 15 (90,000 x 60/350,000)
– To maintain at 100,000 particles requires an air change rate of 54
10m
3m
10m
2m
2m2m
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Effective Air DistributionEffective Air Distribution
• We have seen that particle generation from operators is controlled by continuously removing particles from the area– Effectively ‘flushing’ with filtered air
– The rate of particle reduction is proportional to air supplied and the size of the room (air change rates)
– Effective air distribution is essential to ensure all areas are ‘flushed’ at the desired rate
– Following slide depicts what can happen if you get it wrong!!!
• We have seen that particle generation from operators is controlled by continuously removing particles from the area– Effectively ‘flushing’ with filtered air
– The rate of particle reduction is proportional to air supplied and the size of the room (air change rates)
– Effective air distribution is essential to ensure all areas are ‘flushed’ at the desired rate
– Following slide depicts what can happen if you get it wrong!!!
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Ineffective Air DistributionIneffective Air Distribution
Clean RoomClean Room
Terminal Supply HEPA Filters
Terminal Supply HEPA Filters
Clean Room• 30 Air changes/hour by design• Only 2/3 of room with adequate air distribution.
Clean Room• 30 Air changes/hour by design• Only 2/3 of room with adequate air distribution.
Zero – Air ChangesZero – Air Changes
45 – Air Changes
ExtractionExtraction
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Part 05/b - Processes & How They ImpactPart 05/b - Processes & How They Impact
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Introduction [1]Introduction [1]
• HVAC is often overlooked in the initial planning stages• Contractors with little exposure to, or understanding of,
pharmaceutical product manufacturing requirements, are often involved in the design of HVAC systems
• The main difference between Commercial & Pharmaceutical areas of construction is in the performance expected of the systems
• Pharma products, in particular those that are required to be sterile, present a risk to patient health, if not manufactured to an exacting standard within a closely controlled environment
• HVAC system design influences architectural layout with regards to items such as airlock positions, doorways and lobbies.
• HVAC is often overlooked in the initial planning stages• Contractors with little exposure to, or understanding of,
pharmaceutical product manufacturing requirements, are often involved in the design of HVAC systems
• The main difference between Commercial & Pharmaceutical areas of construction is in the performance expected of the systems
• Pharma products, in particular those that are required to be sterile, present a risk to patient health, if not manufactured to an exacting standard within a closely controlled environment
• HVAC system design influences architectural layout with regards to items such as airlock positions, doorways and lobbies.
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Introduction [2]Introduction [2]
• Pharmaceutical HVAC– Careful control over the production environment, in
terms of cleanliness, sterility, containment –biological or product, equipment stability and comfort criteria
• Commercial HVAC– Primarily targeted to achieve human comfort
conditions only, temperature and possibly humidity, but over a much wider tolerance range
• HVAC can not be designed independently of the facility and the process– Manufacturing Process, equipment and facility
layout, finish, fittings and fixtures are equally important
• Facility and HVAC must be designed in tandem in order to achieve the desired end result.
• Pharmaceutical HVAC– Careful control over the production environment, in
terms of cleanliness, sterility, containment –biological or product, equipment stability and comfort criteria
• Commercial HVAC– Primarily targeted to achieve human comfort
conditions only, temperature and possibly humidity, but over a much wider tolerance range
• HVAC can not be designed independently of the facility and the process– Manufacturing Process, equipment and facility
layout, finish, fittings and fixtures are equally important
• Facility and HVAC must be designed in tandem in order to achieve the desired end result.
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HVAC Design DriversHVAC Design Drivers
• Major Drivers– Product
• Type• Hazards• Properties• Number of products
– Process• Equipment• Exposure (closed/open)
– Cost• How much money do you have to
spend?– Time
• When do you need the system?– Available space.
• Major Drivers– Product
• Type• Hazards• Properties• Number of products
– Process• Equipment• Exposure (closed/open)
– Cost• How much money do you have to
spend?– Time
• When do you need the system?– Available space.
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• HVAC system requirements are closely related to the product(s) and process(es) involved– Nature of product / process
• Sterility – non sterile or sterile products?• Aseptically manufactured or terminally sterilised?• Penicillin, cephalosporins – require dedicated HVAC and
facility
– Closed Processes• Physical segregation of the product from the environment• Less emphasis on the HVAC system!
• HVAC system requirements are closely related to the product(s) and process(es) involved– Nature of product / process
• Sterility – non sterile or sterile products?• Aseptically manufactured or terminally sterilised?• Penicillin, cephalosporins – require dedicated HVAC and
facility
– Closed Processes• Physical segregation of the product from the environment• Less emphasis on the HVAC system!
Understanding the Product & Process [1]
Understanding the Product & Process [1]
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Understanding the Product & Process [2]
Understanding the Product & Process [2]
• Open Processes– Product exposed to the atmosphere and to surfaces– Facility / HVAC design / operation will have a greater
CGMP impact:• Critical for aseptic manufacturing areas• Critical for dusty multi-product non-sterile manufacturing
facilities:– Airflow direction important
– Degree of impact determined by both type of process and nature of product.
• Open Processes– Product exposed to the atmosphere and to surfaces– Facility / HVAC design / operation will have a greater
CGMP impact:• Critical for aseptic manufacturing areas• Critical for dusty multi-product non-sterile manufacturing
facilities:– Airflow direction important
– Degree of impact determined by both type of process and nature of product.
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Understanding the Product & Process [3]
Understanding the Product & Process [3]
• Product properties will also dictate HVAC system requirements (especially open processes)– Sensitivity - Temperature / relative
humidity– Level of operator protection– Dusty or non-dusty
• Company / regulatory rules and guidelines (CGMPs) will also drive requirements.
• Product properties will also dictate HVAC system requirements (especially open processes)– Sensitivity - Temperature / relative
humidity– Level of operator protection– Dusty or non-dusty
• Company / regulatory rules and guidelines (CGMPs) will also drive requirements.
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Part 05/c - HVAC ConfigurationPart 05/c - HVAC Configuration
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Design Considerations [1]Design Considerations [1]
PRODUCTPROTECTION
PERSONNELPROTECTION
ENVIRONMENTPROTECTION
Cross-contaminationControl
Correct temper-temperature & humidity
Prevent contact with fumes
Acceptable comfort conditions
Avoid fume discharge
Avoid effluent discharge
SYSTEMS
SYSTEM VALIDATION
Contamination(Control)
Avoid dust discharge
GMP MANUFACTURINGENVIRONMENT
Prevent contact with dust
3 Key Areas of Consideration – CGMP HVAC Systems3 Key Areas of Consideration – CGMP HVAC Systems
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Design Considerations [2]Design Considerations [2]
• HVAC design requirements will significantly influence capital and operating costs. Key areas:– Air change rates
• Increased equipment capacities + additional space
– Differential pressure regime• Drive facility costs
– Filtration• More expensive filter media• Higher fan ratings• Testing
……………………..continued on next slide
• HVAC design requirements will significantly influence capital and operating costs. Key areas:– Air change rates
• Increased equipment capacities + additional space
– Differential pressure regime• Drive facility costs
– Filtration• More expensive filter media• Higher fan ratings• Testing
……………………..continued on next slide
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Design Considerations [3]Design Considerations [3]
• Key Areas (continued)– Use of standard equipment
• Filters• Avoid bespoke items• Maintenance• Lead times
– Independent monitoring system• increased capital cost• Improved compliance• Do you want to validate a Building Management System (BMS)?
……………………..continued on next slide
• Key Areas (continued)– Use of standard equipment
• Filters• Avoid bespoke items• Maintenance• Lead times
– Independent monitoring system• increased capital cost• Improved compliance• Do you want to validate a Building Management System (BMS)?
……………………..continued on next slide
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Design Considerations [4]Design Considerations [4]
• Key areas (continued)– Design for ease of maintenance
• Access– Savings in plant space could lead to maintenance costs
beyond original benefit– Air recirculation (ratio of fresh to recycled air)
• Increase in fresh air percentage leads to an increase in conditioning elements capacity
– Challenge to filter longevity» ……………………..continued on next slide
• Key areas (continued)– Design for ease of maintenance
• Access– Savings in plant space could lead to maintenance costs
beyond original benefit– Air recirculation (ratio of fresh to recycled air)
• Increase in fresh air percentage leads to an increase in conditioning elements capacity
– Challenge to filter longevity» ……………………..continued on next slide
Quick access housing gives complete accessibility to the wheel and inside of the fan housing Quick access housing gives complete accessibility to the wheel and inside of the fan housing
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Design Considerations [5]Design Considerations [5]
• Key areas (continued)– Barrier technology
• Grade A isolator requires grade D background• Can adversely effect production rate• Isolators are high capital costs
– Extent of room or process specific conditioning requirements
• Dehumidifcation in one room rather than the whole suite• Temperature and RH control range
– Extraction• Local independent extraction system
• Key areas (continued)– Barrier technology
• Grade A isolator requires grade D background• Can adversely effect production rate• Isolators are high capital costs
– Extent of room or process specific conditioning requirements
• Dehumidifcation in one room rather than the whole suite• Temperature and RH control range
– Extraction• Local independent extraction system
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HVAC Design ReviewHVAC Design Review
• Essential that design is regularly and properly reviewed – BY THE RIGHT PEOPLE
• The level of design review undertaken will depend on– System Impact– Level of complexity / novelty.
• Essential that design is regularly and properly reviewed –– BY THE RIGHT PEOPLE
• The level of design review undertaken will depend on– System Impact– Level of complexity / novelty.
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System Impact Versus System Complexity / Novelty
System Impact Versus System Complexity / Novelty
NONENONENONE
INDIRECTINDIRECT
DIRECTDIRECTDIRECT
LOWLOW HIGHHIGH
System ImpactSystem System ImpactImpact
Complexity / NoveltyComplexity / Complexity / NoveltyNovelty
DESIGN REVIEWDESIGN REVIEW
STRUCTURED DESIGN REVIEWSTRUCTURED DESIGN REVIEW
STRUCTURED DESIGN REVIEW + FMEASTRUCTURED DESIGN REVIEW + FMEA
Car ParkCar ParkSite Electrical SupplySite Electrical Supply
Chilled WaterChilled Water
Chart RecorderChart Recorder
Product HVAC (non-sterile)Product HVAC (non-sterile)
Purified Water SystemPurified Water System
Familiar AutoclaveFamiliar AutoclaveNew Autoclave
Sterile facility HVAC
New Autoclave
Sterile facility HVAC
Structured Design Review • Systematic method of reviewing and documenting the design covering: component
criticality, system impact, system boundaries, user requirements, critical process parameters, CGMP etc.)
Structured Design Review • Systematic method of reviewing and documenting the design covering: component
criticality, system impact, system boundaries, user requirements, critical process parameters, CGMP etc.)
.
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Part 05/d - Control & Maintenance of the Variable Parameters
Part 05/d - Control & Maintenance of the Variable Parameters
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Room Air-Change RatesRoom Air-Change Rates
• Room air change rates – primarily used together with filtration to control particulates– Particle clean-up rate
• Dependant on the supply air volume and room volume– Example: Room (10x10x3m) - 20 air changes per
hour:• Requires air supply flow = 6,000m3hr-1 or 100m3min-1
• Air extraction rate (+ leakage) will be used to control differential pressure – see later.
• Room air change rates – primarily used together with filtration to control particulates– Particle clean-up rate
• Dependant on the supply air volume and room volume– Example: Room (10x10x3m) - 20 air changes per
hour:• Requires air supply flow = 6,000m3hr-1 or 100m3min-1
• Air extraction rate (+ leakage) will be used to control differential pressure – see later.
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Differential Pressure (DP) [1]Differential Pressure (DP) [1]
• Normally steps of at least 10Pa required – normally tolerance of ± 2 to 3Pa– Any less and control is difficult
• Trying to hold levels of +1 to +5Pa is next to impossible– Set point needs to be 2 to 3Pa above required level to
ensure substantial compliance• General industry limits
– 15Pa minimum required between unclassified and classified areas
– 10Pa minimum between rooms of different classifications
• Belts and braces – increments of 15 Pa throughout– Beware this can lead to excessive pressures
• Consider use of negative sink air locks
• Normally steps of at least 10Pa required – normally tolerance of ± 2 to 3Pa– Any less and control is difficult
• Trying to hold levels of +1 to +5Pa is next to impossible– Set point needs to be 2 to 3Pa above required level to
ensure substantial compliance• General industry limits
– 15Pa minimum required between unclassified and classified areas
– 10Pa minimum between rooms of different classifications
• Belts and braces – increments of 15 Pa throughout– Beware this can lead to excessive pressures
• Consider use of negative sink air locks
Change Room+30Pa
Corridor+45Pa
Change+60Pa
Primary changelobby+15Pa
Manufacturing+75Pa
0 (reference)
DP = 15Pa
DP = 15Pa
DP = 15Pa
DP = 15Pa
DP = 15Pa
Primary function: Prevent infiltration of particles from one area to another
Primary function: Prevent infiltration of particles from one area to another
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Differential Pressure (DP) [2]Differential Pressure (DP) [2]
• Room pressurisation is achieved by changing the ratio of supply air to extracted air– Room pressure should be neutral (atmospheric pressure) if
supply rate = extraction rate– Room pressure positive if supply rate > extraction rate– Room pressure negative if extraction rate > supply rate
• Easy to achieve + ve pressure in a well sealed room– What about air flow from room to room when doors are
opened?• A level of designed leakage whilst doors are closed required to
provide correct airflow when doors are opened.
• Room pressurisation is achieved by changing the ratio of supply air to extracted air– Room pressure should be neutral (atmospheric pressure) if
supply rate = extraction rate– Room pressure positive if supply rate > extraction rate– Room pressure negative if extraction rate > supply rate
• Easy to achieve + ve pressure in a well sealed room– What about air flow from room to room when doors are
opened?• A level of designed leakage whilst doors are closed required to
provide correct airflow when doors are opened.
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Differential Pressure (DP) [3]Differential Pressure (DP) [3]
• DP Control– Passive
• Achieved by adjusting and fixing the return (extracted) air flow rate against a fixed supply
• Difference between them provides room pressure and small air flow from room to room when doors are opened
…………………………continued on next slide
• DP Control– Passive
• Achieved by adjusting and fixing the return (extracted) air flow rate against a fixed supply
• Difference between them provides room pressure and small air flow from room to room when doors are opened
…………………………continued on next slide
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Differential Pressure (DP) [4]Differential Pressure (DP) [4]
• DP Control (continued)– Passive + Pressure Control Dampers
(Flaps)• Pressure dampers often mounted in
partitions above the door– Allow certain amount of air to pass through
with doors closed– As door is opened the flap closes and allows
more air to pass through door opening– Useful in air balancing
» Factory set on design DP» Air balancing between supply and extract
doesn’t need to be so precise…………………………continued on next slide
• DP Control (continued)– Passive + Pressure Control Dampers
(Flaps)• Pressure dampers often mounted in
partitions above the door– Allow certain amount of air to pass through
with doors closed– As door is opened the flap closes and allows
more air to pass through door opening– Useful in air balancing
» Factory set on design DP» Air balancing between supply and extract
doesn’t need to be so precise…………………………continued on next slide
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Differential Pressure (DP) [5]Differential Pressure (DP) [5]
• DP Control (continued)– Active
• DPs monitored continuously and return air dampers and fan (inverters) modulated to off-set changes in DP
• Doesn’t work across an open door– Some systems can increase room supply to a preset
maximum to protect the open doorway• Require independent controls of high quality with rapid
response– Expensive– Slow response systems will result in unstable facility
pressure control…………………………continued on next slide
• DP Control (continued)– Active
• DPs monitored continuously and return air dampers and fan (inverters) modulated to off-set changes in DP
• Doesn’t work across an open door– Some systems can increase room supply to a preset
maximum to protect the open doorway• Require independent controls of high quality with rapid
response– Expensive– Slow response systems will result in unstable facility
pressure control…………………………continued on next slide
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Differential Pressure (DP) [6]Differential Pressure (DP) [6]
• DP Measurement– Magnehelic gauges
• Very common• Simple and inexpensive• They do have their drawbacks
– Difficult to make all gauges visible to manufacturing area
» All manufacturing room interface DPsshould be readable from manufacturing room
– Often find all facility DP gauges on a single panel
» Should be visible from the facility» Not located in an access corridor
– Easy to miss out-of-compliance conditions• Some have 4 to 20mA transmitters to allow
remote monitoring…………….continued on next slide
• DP Measurement– Magnehelic gauges
• Very common• Simple and inexpensive• They do have their drawbacks
– Difficult to make all gauges visible to manufacturing area
» All manufacturing room interface DPsshould be readable from manufacturing room
– Often find all facility DP gauges on a single panel
» Should be visible from the facility» Not located in an access corridor
– Easy to miss out-of-compliance conditions• Some have 4 to 20mA transmitters to allow
remote monitoring…………….continued on next slide
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Differential Pressure (DP) [7]Differential Pressure (DP) [7]
• DP Measurement Continued– Electronic continuous monitoring
• Differential pressure transmitters• Data acquisition systems• Local readouts• Remote readouts• All parameters constantly monitored
– Monitored against alarms– Local and remote alarms– Event log
• Secure saving of data (21 CFR Part11)
• DP Measurement Continued– Electronic continuous monitoring
• Differential pressure transmitters• Data acquisition systems• Local readouts• Remote readouts• All parameters constantly monitored
– Monitored against alarms– Local and remote alarms– Event log
• Secure saving of data (21 CFR Part11)
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Maintaining Air-flow [1]Maintaining Air-flow [1]
• Without a level of flow control, air supply flow rates from the AHU and terminal room supplies would decay:– Related to filter life – level of filter exhaustion– As a filter become ‘dirty’
• Resistance to flow increases• Pressure drop across it increases as flow is maintained• Supply pressure must be increased to maintain flow
• Without a level of flow control– Critical parameters will go out of specification with time
• e.g. room air-change rates and flow velocities
• Without a level of flow control, air supply flow rates from the AHU and terminal room supplies would decay:– Related to filter life – level of filter exhaustion– As a filter become ‘dirty’
• Resistance to flow increases• Pressure drop across it increases as flow is maintained• Supply pressure must be increased to maintain flow
• Without a level of flow control– Critical parameters will go out of specification with time
• e.g. room air-change rates and flow velocities
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Maintaining Air-flow [2]Maintaining Air-flow [2]
• Total air-flow from the AHU– Normally controlled by increasing the fan
speed to compensate for the greater resistance to flow from the filters – inverter on fan motorVariable Speed Drive (VSD)
• Regulated from flow measurement in supply
• Air-flow to zones (numerous HEPA filters, e.g rooms) or individual HEPAscan be maintained using:– Constant flow devices– Active control using induct flow
measurement and motorised control dampers
• Total air-flow from the AHU– Normally controlled by increasing the fan
speed to compensate for the greater resistance to flow from the filters – inverter on fan motorVariable Speed Drive (VSD)
• Regulated from flow measurement in supply
• Air-flow to zones (numerous HEPA filters, e.g rooms) or individual HEPAscan be maintained using:– Constant flow devices– Active control using induct flow
measurement and motorised control dampers
Multi-point airflow monitorMulti-point airflow monitor
Motorised zone damperMotorised zone damper
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Maintaining Air-flow [3]Maintaining Air-flow [3]
• Adjustable venturi type constant flow device• Adjustable venturi type constant flow device
As the flow decreases, the venturi action reduces the force on the regulator and the spring expands. This moves the regulator outwards allowing more air to pass and so maintaining flow
As the flow decreases, the venturi action reduces the force on the regulator and the spring expands. This moves the regulator outwards allowing more air to pass and so maintaining flow
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Maintaining Air-flow [4]Maintaining Air-flow [4]
• Constant flow devices– Located supply ducting to zones (banks of HEPA filters)– Normally assumed terminal HEPA filters will become
exhausted at a similar rate (similar air flow rate to each)• AHU will ensure total flow is constant• Zone constant flow devices will ensure room supply
flow is constant• Helps maintain control of critical parameters:
– Room air change rates– Pressure regimes– Particle levels.
• Constant flow devices– Located supply ducting to zones (banks of HEPA filters)– Normally assumed terminal HEPA filters will become
exhausted at a similar rate (similar air flow rate to each)• AHU will ensure total flow is constant• Zone constant flow devices will ensure room supply
flow is constant• Helps maintain control of critical parameters:
– Room air change rates– Pressure regimes– Particle levels.
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Fan Filter Units (FFU)Fan Filter Units (FFU)
• Fan-Powered Units– Self-powered air filter modules have become a
popular substitute for terminal air filtration units because of their flexibility and ease of installation
• Self-adjusting filter units automatically change speeds as external static pressures fluctuate.
• Fan-Powered Units– Self-powered air filter modules have become a
popular substitute for terminal air filtration units because of their flexibility and ease of installation
• Self-adjusting filter units automatically change speeds as external static pressures fluctuate.
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Multiple FFUsMultiple FFUs
Supply PlenumSupply Plenum
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NotesNotes
• More recently, FFUs have taken a cost conscious direction with the inclusion of built-in intelligence. These new “smart” FFUsoffer a number of new benefits. First, they are powered by DC, which reduces energy consumption by as much as 50%. Second, their fan motors can be monitored and adjusted individually, in groups, or all at one time using a computerized control interface. By controlling the rpm of the fan motor and hence the airflow ofthe FFU, the operator has complete control over the systems at all times.
• Some of these new DC/EC (electronically commutated) motors have a built-in smart chip that detects changes in resistance to airflow through the filter and increases the rpm of the motor tomaintain airflow at the original settings. Due to the longevity of most HEPAs and ULPAs in the cleanroom, however, this feature is becoming less attractive because the payback cycle is too long to be economically justified. Moreover, this type of motor is not as electrically efficient as others currently on the market.
• More recently, FFUs have taken a cost conscious direction with the inclusion of built-in intelligence. These new “smart” FFUsoffer a number of new benefits. First, they are powered by DC, which reduces energy consumption by as much as 50%. Second, their fan motors can be monitored and adjusted individually, in groups, or all at one time using a computerized control interface. By controlling the rpm of the fan motor and hence the airflow ofthe FFU, the operator has complete control over the systems at all times.
• Some of these new DC/EC (electronically commutated) motors have a built-in smart chip that detects changes in resistance to airflow through the filter and increases the rpm of the motor tomaintain airflow at the original settings. Due to the longevity of most HEPAs and ULPAs in the cleanroom, however, this feature is becoming less attractive because the payback cycle is too long to be economically justified. Moreover, this type of motor is not as electrically efficient as others currently on the market.
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Airflow [1]Airflow [1]
• Airflow can be used to protect both the product and the operator
• Airflow direction can be controlled by a number of mechanisms (continued on next slide):– Flow from filters to extract – governed by:
• Position of supply and extract points• Size of supply / extract grille• Speed (flow) of supply
– Laminar air flow:» Maintained across a critical work area at a velocity of 0.36 - 0.54
m/s» Can protect the product and the operator
• Principle mechanism for ensuring adequate air sweeps / distribution within rooms.
• Airflow can be used to protect both the product and the operator
• Airflow direction can be controlled by a number of mechanisms (continued on next slide):– Flow from filters to extract – governed by:
• Position of supply and extract points• Size of supply / extract grille• Speed (flow) of supply
– Laminar air flow:» Maintained across a critical work area at a velocity of 0.36 - 0.54
m/s» Can protect the product and the operator
• Principle mechanism for ensuring adequate air sweeps / distribution within rooms.
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Airflow [2]Airflow [2]
• Airflow direction can be controlled by a number of mechanisms (continued):– Air flow from room to room
• Positioning of supply and extraction points– Supply points in one room/corridor and extraction points in
another room (see later example)– Protects product from cross-contamination– Protect operators working in adjacent areas from hazards
posed by ‘dusty’ operations• Differential pressure regime and designed leakage
– Air flows from higher pressure to lower pressure– Help prevent cross-contamination– Help prevent adverse air flow (lower classification to higher
classification.
• Airflow direction can be controlled by a number of mechanisms (continued):– Air flow from room to room
• Positioning of supply and extraction points– Supply points in one room/corridor and extraction points in
another room (see later example)– Protects product from cross-contamination– Protect operators working in adjacent areas from hazards
posed by ‘dusty’ operations• Differential pressure regime and designed leakage
– Air flows from higher pressure to lower pressure– Help prevent cross-contamination– Help prevent adverse air flow (lower classification to higher
classification.
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Room Airflow PatternsRoom Airflow Patterns
AHUTerminal filtersTerminal filters
1
Turbulent
3
Turbulent
2
Uni-directional
ExtractionExtraction
Room Air-FlowsRoom Air-Flows
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Turbulent and Unidirectional Flow
Turbulent and Unidirectional Flow
Turbulent dilution of dirty air
0.45 m/s
Unidirectional / laminardisplacement of dirty air
Unidirectional / laminardisplacement of dirty air
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NotesNotes
• The air speed in the uni-directional flow is defined by the WHO at:
– 0.45 m/s for horizontal units– 0.30 m/s for vertical units (most commonly used)
• It is important to know that the WHO definition(*) for the air speed differs from those of other guidelines.
• For the air exhaust, in case of a vertical unit, a low return is more favourable, as the air is better distributed in the room.
• Objects in the room can significantly disturb the flow of air, and even block it, so that there might be pockets without air circulation.
• During the 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, in which case adjustments to the layout or to the air handling systems must be made.
• (*) WHO Expert Committee on Specifications for Pharmaceutical Preparations. Thirty-second Report. Geneva, World Health Organization, 1992: 59-60 (Technical Report Series, No. 823). Annex 1, 17.3.
• The air speed in the uni-directional flow is defined by the WHO at:
– 0.45 m/s for horizontal units– 0.30 m/s for vertical units (most commonly used)
• It is important to know that the WHO definition(*) for the air speed differs from those of other guidelines.
• For the air exhaust, in case of a vertical unit, a low return is more favourable, as the air is better distributed in the room.
• Objects in the room can significantly disturb the flow of air, and even block it, so that there might be pockets without air circulation.
• During the 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, in which case adjustments to the layout or to the air handling systems must be made.
• (*) WHO Expert Committee on Specifications for Pharmaceutical Preparations. Thirty-second Report. Geneva, World Health Organization, 1992: 59-60 (Technical Report Series, No. 823). Annex 1, 17.3.
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Cabin/ boothCabin/ boothWorkbench (vertical)Workbench (vertical) CeilingCeiling
Laminar Flow DevicesLaminar Flow Devices
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Safety CabinetsSafety Cabinets
Class II Biological Safety Cabinet – Product + Operator ProtectionClass II Biological Safety Cabinet – Product + Operator Protection
A = Operator accessB = Transparent ScreenC = Exhaust HEPAD = Supply HEPA (laminar flow)E = Supply and Exhaust AirF = Fan (supply + exhaust)
A = Operator accessB = Transparent ScreenC = Exhaust HEPAD = Supply HEPA (laminar flow)E = Supply and Exhaust AirF = Fan (supply + exhaust)
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NotesNotes
• Uni-directional (laminar) flow units exist mostly as vertical, but also as horizontal, units.
• Often, we are just dealing 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 the ceiling of a room and also connected to the central air conditioning system.
• Due to the 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. Surfaces covered by them should be reduced to a minimum.
• Only the product 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.
• Uni-directional (laminar) flow units exist mostly as vertical, but also as horizontal, units.
• Often, we are just dealing 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 the ceiling of a room and also connected to the central air conditioning system.
• Due to the 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. Surfaces covered by them should be reduced to a minimum.
• Only the product 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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Unidirectional Flow Entire Room
Unidirectional Flow Entire Room
SUPPLY FANSUPPLY FANSUPPLY FANSUPPLY FAN
HEPA FILTERHEPA FILTER
Return PlenumReturn Plenum
Supply PlenumSupply Plenum
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Simple Cross-contamination Control [1]Simple Cross-contamination Control [1]
PROCESS ROOMPROCESS ROOM
PROCESS ROOMPROCESS ROOM
CORRIDORCORRIDOR
VentVent
Extraction Grille – to extraction system (may include dust filters)
Extraction Grille – to extraction system (may include dust filters)
Ceiling Mounted Air Supply GrilleCeiling Mounted Air Supply Grille Air flowAir flow
Cross-contamination control – Supply and extraction mechanismCross-contamination control – Supply and extraction mechanism
Not ideally suited for microbiological controlled environmentsNot ideally suited for microbiological controlled environments
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Simple Cross-contamination Control [2]Simple Cross-contamination Control [2]
Process Room – Door ClosedProcess Room – Door Closed
ExtractExtractGravity DamperGravity Damper
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Simple Cross-contamination Control [3]Simple Cross-contamination Control [3]
Process Room – Door OpenProcess Room – Door Open
Damper flaps closeDamper flaps close
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Dusty ProcessesDusty Processes
• Best place to remove dust is at source• Once dispersed into a room, it becomes more difficult
to remove• Wherever the dust is extracted it has to be dealt with
• Best place to remove dust is at source• Once dispersed into a room, it becomes more difficult
to remove• Wherever the dust is extracted it has to be dealt with
• Baghouse unit connected to various Pharmaceutical operations, such as tablet presses, mixing operations, weighing and encapsulation machines
• Exhaust air is run through a secondary HEPA filter and then a portion of the exhaust air is run back into the air conditioning system.
• Baghouse unit connected to various Pharmaceutical operations, such as tablet presses, mixing operations, weighing and encapsulation machines
• Exhaust air is run through a secondary HEPA filter and then a portion of the exhaust air is run back into the air conditioning system.
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Cross-Contamination Control –Differential Pressure
Cross-Contamination Control –Differential Pressure
0
Process Room 1Process Room 1
Process Room 2Process Room 2
Material Out Air LockMaterial Out Air Lock
MaterialsEntry
Changing RoomChanging Room
Process RoomAccess Air -Lock
Process RoomAccess Air -Lock
+ +
++
+
+
+
KEYKEY= Reference (bordering rooms)= Reference (bordering rooms)o
Low Level Extraction Grille – to extraction system (may include dust filters)
Low Level Extraction Grille – to extraction system (may include dust filters)
Ceiling Mounted Air Supply Grille - via terminal HEPA filter
Ceiling Mounted Air Supply Grille - via terminal HEPA filter
= Air Flow Direction= Air Flow Direction
+ += Pressure of 30 Pa
above reference(1 Pascal = 1 N/m2)
= Pressure of 30 Pa above reference(1 Pascal = 1 N/m2)
+ = Pressure of 15 Pa above reference= Pressure of 15 Pa above reference
Not suitable for aseptic operations Not suitable for aseptic operations
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Product Protection – Differential Pressure
Product Protection – Differential Pressure
Process Room 1Process Room 1
Process Room 2Process Room 2
Material Out Air LockMaterial Out Air Lock
MaterialsEntryMaterialsEntry
Changing RoomChanging Room
Process RoomAccess Air -Lock
Process RoomAccess Air -Lock
KEYKEY
o
Reference (bordering rooms)Reference (bordering rooms)o
Ceiling Mounted Air Supply Grille - via terminal HEPA filter
Ceiling Mounted Air Supply Grille - via terminal HEPA filter
Low Level Extraction Grille – to extraction system (may include dust filters)
Low Level Extraction Grille – to extraction system (may include dust filters)
++
+
+ Pressure of 15 Pa above referencePressure of 15 Pa above reference
+ + + + Pressure of 30 Pa above referencePressure of 30 Pa above reference
Air Flow DirectionAir Flow Direction
+++ +++
+++ Pressure of 55 Pa above referencePressure of 55 Pa above reference
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Nested Manufacturing ZonesNested Manufacturing Zones
External AreasStreet, Offices, Restaurant
Transition ZoneBrings people, materials etc. from external areas to the
manufacturing areas in a controlled mannerClean Area
Provides protective envelope to minimise challenge to critical area
Critical Processing Areae.g. Point of Fill
ChangePeople Change Raw Materials
Com-pounding
RemoveOuters
RemoveOuters
Containers / Closures
Sterilise
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Notes on Nested Zone DiagramNotes on Nested Zone Diagram
• Product out not illustrated on the diagram• The diagram shows the increasing protection as you
move towards the product exposure area. In a manufacturing facility air pressures will be such to ensure a cascade of flow from the critical area outward.
• The level of personnel entry and general activity will decrease considerably as you move towards the core of the conceptual diagram
• In a sterile area the zones would have the following classifications:
• Critical area – Class 100, Grade B, ISO 5 - in operation• Clean area – Class 10,000, Grade C, ISO 7 – in
operation• Transition – General Pharmaceutical or ISO 8 (Grade D)
• Product out not illustrated on the diagram• The diagram shows the increasing protection as you
move towards the product exposure area. In a manufacturing facility air pressures will be such to ensure a cascade of flow from the critical area outward.
• The level of personnel entry and general activity will decrease considerably as you move towards the core of the conceptual diagram
• In a sterile area the zones would have the following classifications:
• Critical area – Class 100, Grade B, ISO 5 - in operation• Clean area – Class 10,000, Grade C, ISO 7 – in
operation• Transition – General Pharmaceutical or ISO 8 (Grade D)
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Example Aseptic Filling Facility
Example Aseptic Filling Facility
Final Washing / Sterilising TunnelFinal Washing /
Sterilising Tunnel
45 Pa45 Pa
60Pa60Pa 75Pa75Pa
75Pa75Pa
30Pa30Pa
30Pa30Pa
Cooling RoomCooling Room
Aseptic Processing Room
Aseptic Processing Room
Changing RoomChanging Room
AirlockAirlock
AutoclaveAutoclave
Autoclave loading RoomAutoclave loading Room
Component preparationComponent preparation
Packing HallPacking Hall
Critical AreaCritical Area
Critical AreaCritical AreaGrade AGrade A
Grade AGrade A
Critical AreaCritical AreaGrade AGrade A
Grade BGrade B
Grade BGrade B
Grade BGrade B
Grade DGrade D
Grade DGrade D
Grade CGrade C
Grade BGrade B
Grade CGrade C Solution Preparation AreaSolution Preparation Area
30Pa30Pa
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Part 05/e - Control & InstrumentationPart 05/e - Control & Instrumentation
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Building Management System (BMS) [1]
Building Management System (BMS) [1]
• HVAC control is usually effected by a BMS:– Normally some type of PC based supervisory
application software– PC linked to local area controllers– Local controllers (Modular Building Controllers –
MBC) linked to field instruments and devices• Temperature, pressure, relative humidity, flow instruments• Tachometers• Motorised dampers• Fan speed controllers• Control valves to services• Motor control centres (MCC).
• HVAC control is usually effected by a BMS:– Normally some type of PC based supervisory
application software– PC linked to local area controllers– Local controllers (Modular Building Controllers –
MBC) linked to field instruments and devices• Temperature, pressure, relative humidity, flow instruments• Tachometers• Motorised dampers• Fan speed controllers• Control valves to services• Motor control centres (MCC).
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BMS [2]BMS [2]
• BMS (continued)– Similar to SCADA system– Graphic interface (HMI)– Normally used by engineers rather than operators– Main functions:
• Monitor, control and trend conditions – area + AHU• Monitors controls and trends equipment performance• Filter performance monitoring• Maintains air flow to each area:
– Not all control differential pressures in areas• Alarms and associated trends.
• BMS (continued)– Similar to SCADA system– Graphic interface (HMI)– Normally used by engineers rather than operators– Main functions:
• Monitor, control and trend conditions – area + AHU• Monitors controls and trends equipment performance• Filter performance monitoring• Maintains air flow to each area:
– Not all control differential pressures in areas• Alarms and associated trends.
SCADA – Supervisory control and data acquisitionHMI – Human machine interface
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BMS [3]BMS [3]
Management Level NetworkManagement Level Network
Building Level Network (BLN) :Building Level Network (BLN) :
Clients:Engineering InterfaceClients:Engineering Interface
Floor Level NetworkFloor Level Network
BMS ServerBMS Server
Field devicesField devicesField instrumentsField instruments MCCsMCCs
Modular Building ControllersModular Building Controllers
Closed / Open NetworkClosed / Open Network
BMS SchematicBMS Schematic
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BMS – Facility Control SensorsBMS – Facility Control Sensors
Laboratory Animal Facilities Laboratory Animal Facilities
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Control And InstrumentationControl And Instrumentation
• Care required when specifying temperatures and relative humidity requirements for products– Measuring humidity during development work and
applying a specification for manufacturing based on this, without adequate experimentation
• Can cause major design and control issues – Do not over specify parameters
– The tighter the control, the more accurate the instrumentation and the more expensive the HVAC and control system
• Also remember a 1 degree change in temperature will alter the RH by ~ 2.5% without changing the absolute moisture content.
• Care required when specifying temperatures and relative humidity requirements for products– Measuring humidity during development work and
applying a specification for manufacturing based on this, without adequate experimentation
• Can cause major design and control issues – Do not over specify parameters
– The tighter the control, the more accurate the instrumentation and the more expensive the HVAC and control system
• Also remember a 1 degree change in temperature will alter the RH by ~ 2.5% without changing the absolute moisture content.
HVAC Systems and the Pharmaceutical Manufacturing Environment Radisson SAS Hotel, Amsterdam 2008
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End of PresentationEnd of Presentation
Any further questions?Any further questions?