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HVAC | Slide 1 of 26 May 2006
Heating, Ventilation and Air-Conditioning (HVAC)
Part 1 (a):Introduction and overview
Supplementary Training Modules onGood Manufacturing Practice
WHO Technical Report Series,No. 937, 2006. Annex 2
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HVAC | Slide 2 of 26 May 2006
HVAC
Objectives
To understand:
The need for HVAC systems (Part 1a)
The role of HVAC in protection:
Product
Personnel Environment
The role of HVAC in dust control (Part 1b)
HVAC system design and its components (Part 2)
Commissioning, qualification and maintenance (Part 3)
1, 2
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HVAC | Slide 3 of 26 May 2006
HVAC
Introduction and Scope
HVAC systems can have an impact on product quality
It can provide comfortable conditions for operators
The impact on premises and prevention of contamination and
cross-contamination to be considered at the design stage
Temperature, relative humidity control where appropriate
Supplement to basic GMP text 1, 2
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Factors contributing toquality products
Starting materials
Personnel
Procedures
Validated processes
Equipment
Premises
Environment
Packing materials
HVAC
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HVAC | Slide 5 of 26 May 2006
The manufacturing environment is critical for product
quality. Factors to be considered include:1. Light
2. Temperature
3. Relative humidity
4. Air movement
5. Microbial contamination
6. Particulate contamination
Uncontrolled environment can lead to product degradation
product contamination (including cross-contamination)
loss of product and profit
HVAC
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HVAC | Slide 6 of 26 May 2006
What is contamination?
It is "the undesired introduction of impurities (chemical/ microbial/
foreign matter into or on to starting material or intermediate
during sampling, production, packaging or repackaging".
Impurities could include products or substances other than the
product manufactured, foreign products, particulate matter, micro-
organisms, endotoxins (degraded microorganisms), etc.
HVAC
Glossary
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What is Cross-contamination?"Contamination of a starting material, intermediate product, orfinished product with another starting material or productduring production".
Cross-contamination can result from, e.g.
1. Poorly designed, operated or maintained air-handling systemsand dust extraction systems
2. Inadequate procedures for, and movement of personnel,materials and equipment
3. Insufficiently cleaned equipment
HVAC
Glossary,4.1.11
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Contamination
Contaminantfrom
Environment
Operators
Contaminantfrom
Equipment
CrossContamination
Product
fromEnvironment
Operators
Product
fromEquipment
Cross-Contamination
HVAC
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HVAC | Slide 9 of 26 May 2006
Cross-contamination can be minimized by, e.g.
1. Personnel procedures
2.Adequate premises
3. Use of closed production systems
4.Adequate, validated cleaning procedures
5.Appropriate levels of protection of product
6. Correct air pressure cascade
HVAC
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HVAC | Slide 10 of 26 May 2006
HVAC
The guideline further focuses on three concepts ofthe system:
Product protection
Contamination
Cross-contamination
Environmental conditions
Personnel protection
Prevent contact
Comfort conditions
Environment protection 2
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HVAC
Protection: Product and personnel
Areas where materials and products are exposed, should beclassified as "clean areas"
Achievement of clean area classification depends on factors suchas:
Building finishes and structure Air filtration Air change rate Room pressure Temperature Relative humidity
Material and personnel flow
Outside environment Occupancy and type of product
4.1.1 - 4.1.3
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HVAC
Air filtration and air change rate should ensure attainment of
classification
Air change rate is dependent on factors, e.g.
Level of protection required
Quality and filtration of supply air
Particulates generated
Room configuration
Containment effect
Room heat load
Room pressure
Air change rate normally varies between 6 20 air changes
per hour
4.1.4 - 4.1.6
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HVAC
The classification should beachieved in the state as
specified (1):
"As built"
Bare room, without equipment or
personnel
4.1.7 - 4.1.8
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HVAC
The classification should beachieved in the state as
specified (2):
"At rest"
Equipment may be operating, but
no operators present
4.1.9
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HVAC
The classification should beachieved in the state as
specified (3):
"In operation" Normal production process with
equipment and personnel,
Clean up time validated
normally in the order of 20minutes
4.1.10
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HVAC | Slide 16 of 26 May 2006
HVAC
Control of contaminants
External contaminants removed through effective filtration
Internal contaminants controlled through dilution and flushing,
or displacement airflow
Airborne particulates and level of filtration considered critical
4.1.12 - 4.1.15
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Therapeutic risks
ManufacturingEnvironment
requirements
Clean
roomClassA
/B
CleanroomClas
sC
Cleanrm.ClassD
Others
HVAC
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HVAC
Level of protection and air cleanliness determinedaccording to:
Product to be manufactured
Process to be used
Product susceptibility to degradation
4.1.16
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Parameters influencing Levels of Protection
Number of particles in the air, number of microorganisms in theair or on surfaces
Number of air changes for each room
Air velocity and airflow pattern
Filters (type, position)
Air pressure differentials between rooms
Temperature, relative humidity
HVAC
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Tools to help achieve the desired Level ofProtection
Air HandlingSystem
Production Room
With
Defined
Requirements
SupplyAir
OutletAir
HVAC
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HVAC | Slide 21 of 26 May 2006
Tools to help achieve the desired Level of Protection (2)
Air-handling system can be the main tool for reaching requiredparameters
May not be sufficient as such
Need for additional measures such as appropriate gowning (type of clothing, proper changing
rooms)
validated sanitation
adequate transfer procedures for materials and personnel
HVAC
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Cleanroom Classdefined by
Critical Parameters
Air HandlingSystem
Additional Measures
Tools to help achieve the desired Level of Protection (2)
HVAC
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Examples of Levels of Protection
Types of Clean room classes
WHO, EC, PIC/S: A, B, C, D
US FDA: Critical and controlled
ISPE: Level 1, 2 or 3
ISO: Class 5, 6, 7 or 8
HVAC
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Particles / m3
0.5mUS 209D
non-metric
US 209E1992
metric
EC cGMPAnnex I
1997
GermanyVDI 2083
1990
UKBS 5295
1989
JapanJIS B 9920
1989
ISO 14644-1
1
3,5 0 2 2
10 M 1
35 1 M 1.5 1 3 3
100 M 2
353 10 M 2.5 2 4 4
1.000 M 3
3.530 100 M 3.5 A, BA= unidirectional
B= turbulent
3 E or F 5 5
10.000 M 4
35.300 1.000 M 4.5 4 G or H 6 6
100.000 M 5
353.000 10.000 M 5.5 C 5 J 7 7
1.000.000 M 6
3.530.000 100.000 M 6.5 D 6 K 8 8
10.000.000 M 7
Comparing International Cleanroom Classifications
HVAC
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HVAC
Examples of levels of protection 4.1.16
Example of areaConditionLevel
Area with normal housekeeping, e.g.
warehouse
GeneralLevel 1
Area where steps are taken to protect
exposed material/product, e.g. dispensing
ProtectedLevel 2
Area with defined, controlled, monitored
environmental conditions to preventcontamination and degradation
ControlledLevel 3
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All operationswithin a pharmaceutical facilility should becorrelated to well-defined clean room classes, and can beincluded in a hygiene concept.
Example:
etc.
XFilling for aseptic process
XFilling for terminal sterilisation
XDepyrogenisation of containers
XXXPreparation of solutions for aseptic filling
XPreparation of solution for terminal sterilisation
XWashing of containers
DCBACleanroom Class
HVAC