Heating Ventilation and Air Conditioning (HVAC) Part 3: Design, qualification and maintenance Air...

HeatingVentilation andAir Conditioning (HVAC)

Part 3: Design, qualification and maintenance

Air Handling Systems

Supplementary Training Modules on GMP

Module 3, Part 3: Qualification and maintenance Slide 1 of 27WHO - EDM

Module 3, Part 3: Design, qualification and maintenance Slide 2 of 27WHO - EDM

Air Handling SystemsCharacteristics of air handling systems

In the following slides, we will study alternatives in air handling systems

Turbulent or uni-directional airflows Filter position Air re-circulation vs fresh air Return air systems (positions) Overpressure requirements



Uni-directional / laminar

displacement of dirty air

Turbulent

dilution of dirty air

0,30 m/s

Annex 1, 17.3

Air flow patterns (1)




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

turbulent uni-directional (laminar)

GMP aspect economical aspect

New technologies: barrier technology/isolator technology.

Annex 1, 17.3, 17.4



PrefilterAir flow patterns

(3)

AHU

Main filter

Uni-directional TurbulentTurbulent

1 2 3

Annex 1, 17.3



Workbench (vertical) Cabin/ booth Ceiling



Air Handling SystemsPositioning of

filters (1)

Filter in terminal position AHU mounted final filter

Production Room

+

Production Room

HEPA Filter

HEPA Filter



Prefilter

AHU

Main filter

1 2 3

Low level exhausts

Ceiling exhausts

Positioning of filters (2)



AHUPrefilter

Final filter

21

Positioning of filters (3)



Air re-circulation

The filtered air entering a production room can be

100% exhausted or a proportion re-circulated

GMP aspect economical reasons

Annex 1, 15.10, 17.24


Air Handling SystemsVentilation with 100% fresh air (no air re-

circulation)

Annex 1, 17.24

W

Washer (optional)

Central Air Handling Unit

Production Rooms

Exhaust Unit


Air Handling SystemsVentilation with re-circulated air + make-

up air

Central Air Handling Unit

Return air

Exhaust Unit



Definition of Conditions

air

as built

air air

at rest in operation



Qualification / Validation issues

A good design is essential, but it has to be complemented by:

Qualification of air handling systems Process validation Maintenance and periodic re-qualification Adequate documentation


Air Handling SystemsQualification (OQ, PQ)

(1)

Test

Differential pressure on filters

Turbulent / mixed airflow

Description Uni-directional airflow / LAF

Room differential pressure

Airflow velocity / uniformity

Airflow volume / rate

Parallelism

Air flow pattern

2 2

N/A 2, 3

2, 3 Optional

2 2

2 N/A

2 3

1 := As built (ideally used to perform IQ)

2 = At rest (ideally used to perform OQ)

3 = Operational (ideally used to perform PQ)

IQ tests are not mentioned on this slide

Annex 1, 17. 4



Qualification (OQ, PQ) (2)

Test Turbulent /

mixed airflow Description

Uni-directional airflow / LAF

Recovery time

Room classification (airborne particle)

Temperature, humidity

N/A 2

2 2,3

N/A 2,3

1 := As built (ideally used to perform IQ)

2 = At rest (ideally used to perform OQ)

3 = Operational (ideally used to perform PQ)

Annex 1, 17. 4

IQ tests are not mentioned on this slide



ACTION LIMIT

ALERT LIMITALERT LIMIT

ACTION LIMIT

Operating Range - Validated Acceptance Criteria

Normal Operating Range

Design Condition

Microbiological validation1. Definition of alert / action limits as a function of

cleanliness zone1. Identification and marking of sampling points

2. Definition of transport, storage, and incubation conditions

Ask the question: “What are the alert and action Limits and what procedures are followed if these points are exceeded?”



air

Sampling point

Cleanroom monitoring program (1)

Cleanrooms should be monitored for micro-organisms and particles



Cleanroom monitoring program (2)

Routine monitoring program as part of quality assurance

Additional monitoring and triggers

1. Shutdown 2. Replacement of filter elements3. Maintenance of air handling systems4. Exceeding of established limits

Annex 1, 17.37



Cleanroom maintenance program (1)

Schedule of Tests to Demonstrate Continuing Compliance

Test Parameter Class Maximum TimeInterval

Test Procedure

A, B<= ISO 5

6 Months ISO 14644 -1 Annex AParticle Count Test

C, D> ISO 5

12 Months ISO 14644 -1 Annex A

Air Pressure Difference All Classes 12 Months ISO 14644 -1 Annex B5

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



Cleanroom maintenance program (2)

Schedule of Additional Optional Tests

Test Parameter Class Maximum TimeInterval

Test Procedure

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



1. Description of installation and functions2. Specification of the requirements3. Operating procedures4. Instructions for performance control5. Maintenance instructions and records6. Maintenance records7. Training of personnel (program and records)

Documentation requirements



1. Verification of design documentation, including description of installation and functions specification of the requirements

2. Operating procedures3. Maintenance instructions4. Maintenance records5. Training logs6. Environmental records 7. Discussion on actions if OOS values8. Walking around the plant

Inspecting the air handling plant



Air handling systems:

1. Play a major role in the quality of pharmaceuticals2. Must be designed properly, by professionals3. Must be treated as a critical system

Conclusion



This series of explanations will now be followed by:

Group discussion, with a simple exercise Short test

Further proceedings


Air Handling SystemsGroup Session

Service Room

Warehouse

A/ Lock 1

Air Lock 2

Air Shower

SamplingRooom Service Corridor

(contains Vacuum & RO water supply)

Weighing Tablet 1 Tablet 2 Liquids Mix Softgel CapsulePacking

EmergencyExit

Clean Corridor

Equipment Wash

Air Lock 3

Sterile eyedropsdispensing

& aceptic filling

2 Stagepersonnelentry foreyedrops

MaleChange 2

MaleChange 1

FemaleChange 1

FemaleChange 2

PackedGoods

Quarantine

Air Lock 4

Primary & SecondaryPacking


Air Handling SystemsGroup Session – modified

layout

SecondaryPacking

30Pa

0Pa

20Pa 30Pa

0Pa0Pa

10Pa

10Pa 10Pa

20Pa20Pa

40Pa

50Pa

60Pa

50Pa

40Pa

15Pa

15Pa

PrimaryPacking

Change

MAL 3

Air Lock

30Pa

PostStaging

30Pa

30Pa

0Pa

15Pa15Pa

20Pa

20Pa

30Pa

20Pa

0Pa

10Pa

Service RoomAir Lock 4

PackedGoods

Quarantine

FemaleChange 2

FemaleChange 1

MaleChange 1

MaleChange 2

PAL

Sterile eyedropsdispensing

& asceptic filling

MAL 4Equipment Wash

Clean CorridorEmergency

Exit

Softgel CapsulePackingLiquids MixTablet 2Tablet 1

WeighBooth

(contains Vacuum & RO water supply)Service Corridor

SamplingRooom

Air Shower

MAL 2

MAL1

Warehouse

MAL = Material Air Lock

PAL = Personnel Air Lock

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