Supplementary Training Modules on Good Manufacturing Practice Heating, Ventilation and AirConditioning (HVAC)

Part 1 (b): Introduction and overview

WHO Technical Report Series, No. 937, 2006. Annex 2
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Objectives
To continue from Part 1(a), now focus on:  Air filtration  The role of HVAC in dust control  HVAC system design and its components (part 2)  Commissioning, qualification and maintenance (part 3)

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Air Filtration
 Degree of filtration is important to prevent contamination  Type of filters to be used dependent on the quality of ambient air, return air and air change rates  Manufacturer to determine, select and prove appropriate filters for use considering level of ambient air contamination, national requirements, product specific requirements

4.2.1, 4.2.3

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Levels of protection and recommended filtration
Level of protection
Level 1 Level 2 and 3

Recommended filtration
Primary filters, e.g. EN779 G4* Production area with 100% outside air: Primary plus secondary filter (e.g. EN779 G4 plus F8 filters) Production area with recirculated plus ambient air with a risk of cross-contamination: Primary plus secondary plus tertiary filter (e.g. EN779 G4 plus F8 plus EN1822 H13 filters)
4.2.1

Level 2 and 3

*Filter class should be referenced to the standard test method

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Contamination should be prevented through appropriate:
 Materials for components and construction  Design and appropriate access to dampers, filters and other components  Personnel operations  Airflow direction  Air distribution component design and installation and location  Type of diffusers (non-induction type recommended)  Air exhaust (normally from a low level)
4.2.4 4.2.10

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Airflow patterns
Filtered air entering a production room or covering a process can be
 

turbulent, or unidirectional (laminar) GMP aspect economical aspect

Other technologies: barrier technology/isolator technology.

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Airflow patterns
Turbulent
dilution of dirty air

Unidirectional/laminar
displacement of dirty air

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Airflow patterns
Prefilter

AHU

Main filter

Turbulent
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Unidirectional

Turbulent

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Airflow patterns (4)
Workbench (vertical) Cabin/booth Ceiling

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Unidirectional airflow (UDAF):
Provided where needed over product or material to prevent contamination, or to protect operator

UDAF in weighing areas

 The aim is to provide dust containment  Airflow velocity should not affect balance  Position of material, balance, operator determined and validated no obstruction of airflow or risk
4.3.1 4.3.10

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Annex 5, 7.

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Annex 5, 7.

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Infiltration
 Facilities normally under positive pressure to the outside  Prevent infiltration of unfiltered, contaminated air from outside  Some cases - negative pressure (e.g. penicillin manufacture). Special precautions to be taken
4.4.1 4.4.4

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Cross-contamination
 General aspects and concepts  Displacement concept low pressure differential, high airflow  Pressure differential concept high pressure differential, low airflow  Physical barrier concept
4.5

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General aspects
 Multiproduct OSD manufacturing, prevent movement of dust between areas where different products are processed  Directional air movement and pressure cascade can be helpful dust containment  Normally, corridor at higher pressure than cubicles, cubicles at higher pressure than atmosphere
4.5.1 4.5.3

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Containment concepts
 Pressure cascade regime influenced by:
Product and product group, e.g. highly potent products (in some cases, pressure cascade regime negative to atmosphere) Processing methods

 Building structure should be considered including airtight ceilings and walls, close fitting doors, sealed light fittings
4.5.4 4.5.9

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Displacement concept
 Air supplied to the corridor, through the doors (grilles) to the cubicles  Air extracted at the back of the cubicle  Velocity high enough to prevent turbulence in doorway  Requires large air quantities (Not preferred method)
4.5.10 4.5.12

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Pressure differential concept
 Concept can include high pressure differential, low airflow, and airlocks in the design  Airlock types include: Cascade, sink and bubble type  Sufficient pressure differential required to ensure containment and prevent flow reversal but not so high as to create turbulence  Consider effect of other items such as equipment and extraction systems in cubicles  Operating limits and tolerances
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4.5.13 4.5.18, 4.5.22

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Pressure differential concept (2)
 Calibrated monitoring devices, set to alarm system  Monitoring and recording of results  Doors open to higher pressure  Dust extraction system design
Interlocked with air-handling system No airflow between rooms linked to same system Room pressure imbalance 4.5.19 4.5.26
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Pressure cascade solids Protection from cross-contamination
R oom 1
15P a

R oom 2
15P a

R oom 3
15P a

Air Lock

Air Lock Air Loc k

E

30P a

0P a

Pa ssa ge

15P a

N ot : D i ecton of door openi r atve t r e r i ng el i o oom pr sur es e

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Physical barrier concept
 In some cases, impervious barriers are used to prevent cross-contamination  Spot ventilation  Capture hoods

4.5.27 4.5.28

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Temperature and relative humidity (RH)
 Controlled, monitored and recorded where relevant  Materials and product requirements, operator comfort  Minimum and maximum limits  Premises design appropriate, e.g. low humidity areas, well sealed and airlocks where necessary  HVAC design also prevent moisture migration
4.6.1. 4.6.6

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Temperature and relative humidity (RH) (2)
 Remove moisture, or add moisture as necessary  Dehumidification
Refrigerated dehumidifiers with cooling media Chemical dehumidifiers

 Humidifiers should not be sources of contamination

Use of pure steam or clean steam No chemicals added to boiler system if these can have a detrimental effect on product (e.g. some corrosion inhibitors/chelating agents)
4.6.7. 4.6.11
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Temperature and relative humidity (RH) (3)
Humidification systems: Design should be such that the system does not become the source of contamination:  No accumulation of condensate  Avoid evaporative systems, atomizers, water-mist sprays  Suitable duct material, insulation of cold surfaces  Air filters not immediately downstream of humidifiers  Chemical driers used if not sources of contamination
4.6.12. 4.6.18
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Dust Control
 Dust and vapour removed at source  Point of use extraction fixed points or movable hood plus general directional airflow in room  Ensure sufficient transfer velocity to prevent dust settling in ducting  Risk analysis airflow direction, hazards, operator
5.1. 5.7

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Dust Control (2)
 Normally air supplied through ceiling diffusers, and air extracted from low level aids flushing effect  Extraction of vapours consider density of vapour  Handling harmful products additional steps needed
e.g. barrier technology, glove boxes totally enclosed garments with air-breathing systems

 Fresh air rate supply

comfort, odour and fume removal, leakage, pressure control, etc.
5.8. 5.14

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Protection of the environment (Exhaust air dust)
 Exhaust air from equipment and some areas of production carry heavy loads of dust (e.g. FBD, coating, weighing)  Filtration needed to prevent ambient contamination  Not highly potent material
EN779 F9 filter recommended

 Harmful substances (e.g. hormones)

EN1822 H12 (HEPA) filter recommended In some cases two banks of HEPA filters Safe change filter housings ("bag-in bag-out" filters)
6.1.1 6.1.5
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Protection of the environment (Exhaust air dust) (2)
 Filter banks provided with pressure differential indication gauges  Limits indicated, results monitored at regular intervals
Manual, Building Management Systems, Building Automated Systems, System Control and Data Acquisition systems

 Automated systems provided with alarm or similar system to indicate OOS

6.1.6 6.1.10

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Protection of the environment (Exhaust air dust) (3)
 Reverse pulse dust collectors
Should be equipped with cartridge filters with compressed air lance, Continuous operation no interruption of airflow

 Dust collectors with mechanical shakers

Used in a manner not to become source of contamination Switched off at times resulting in loss of airflow, and disruption of pressure cascade

 Wet scrubbers
Use suitable drainage system for dust slurry
6.1.11 6.1.15

 Determine exhaust air quality to verify filtration efficiency

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Protection of the environment (Fume removal)
 Appropriate design, installation, and operation of fume, dust, effluent control  Wet scrubbers
Added chemicals for increased adsorption efficiency

 Deep bed scrubbers

Activated carbon or chemical adsorption granular media Specific to type of effluent Type and volume prepared
6.2.1 6.2.5

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