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Airlocks
Presented by Gordon Farquharson
August 2015
Slide 2 © PharmOut 2015
Agenda
Regulatory expectation
Different functional configurations
Good design practice
What often goes wrong
Qualification of airlock performance
Slide 3 © PharmOut 2015
Regulatory expectation/guidance
Slide 4 © PharmOut 2015
PIC/S Annex 1 guidance
Slide 5 © PharmOut 2015
PIC/S Annex 3 guidance
PIC/S Annex 5 guidance
PIC/S Annex 10 guidance
Slide 6 © PharmOut 2015
PIC/S Glossary
Slide 7 © PharmOut 2015
WHO HVAC OSD supplementary Guidance Airlocks
The Dp values are indicative – they aren’t a requirement
Slide 8 © PharmOut 2015
Biosafety Regulations
• For the containment of human & animal pathogens.
• There are different regulations in each nation, but the principles are all similar.
• Facility design impact:
– Conflict – Containing Hazards vs Protecting Processes
-ve pressure vs +ve pressure
Let’s look at the essential features of the biosafety regulations.
Slide 9 © PharmOut 2015
Biosafety levels: BL-1
Laboratory Practices
Special Practices Containment Equipment
Laboratory Facility
Access limited
Daily and after-spill decontamination
Wastedecontaminated
No mouth pipette
Personal Wash
Minimise aerosols
Uniform
Leak-proof container for off-site decontamination
Pest control
None Easily cleaned
Hand wash sink
Screens in windows
Slide 10 © PharmOut 2015
Biosafety levels: BL-2
Laboratory Practices
Special Practices Containment Equipment
Laboratory Facility
Same as BL-1
Can also perform BL-1 if isolated
Same as BL-1 except
Principal investigator limits access
Policies and procedures for access
Hazard warning sign if special procedures
Special gowning for laboratory
No spare animals in laboratory
Avoid skin cross contamination
Waste decontamination
Limited use of syringes
Report spills to NIH
Worker blood samples
Biosafety manual
Biosafety cabinets (Class I, II) if aerosols or high number of organisms
Same as BL-1
Autoclave for waste decontamination
Slide 11 © PharmOut 2015
Biosafety levels: BL-3
Laboratory Practices
Special Practices Containment Equipment
Laboratory Facility
Same as BL-2
No entry under age 16
Lesser organisms in same laboratory must follow BL-3
Same as BL-2 and:
Doors closed
More limits on access
Hazard sign required
No open work
Clean-up when finished
Gowning decontamination
Mask/respirator
Special animal cages
HEPA on vacuum
Biosafetycabinets (Class I, II, III) or physical containment devices
Same as BL-2
Separated from building flow
Airlock or gown room access
Sink near door has no-contact faucet
Closed/sealed windows
Self-closing doors
Ducted exhaust
BSC exhaust outdoors
Slide 12 © PharmOut 2015
Biosafety levels: BL-4
LaboratroyPractices
Special Practices Containment Equipment
Laboratory Facility
Same as BL-3 Double container for waste
Decontaminate everything but product leaving the laboratory
Access tightly controlled, locked doors, logbook
Emergency protocols
Access in/out through shower rooms
Class III BSC
Class I or II BSC using one piece suit with ventilation
Separate building or isolated zone
Sealed internal shell, can be decontaminated
Flooded floor drain traps connected to waste decontamination
HEPA on vents and drains
Minimize dust surfaces
Seamless bench tops
Dedicated central vacuum with HEPA at point of use
Backflow prevention for process fluids
Doors self closing and locking
Break resistant windows
Slide 13 © PharmOut 2015
Biosafety levels: BL-4 cont…
Laboratory Practices
Special Practices Containment Equipment
Laboratory Facility
Same as BL-3
No street clothing, special uniform
Hazard signs
Decontaminate incoming materials, airlock access
No spare materials, clothing, animal
Worker health monitoring
Class III BSC
Class I or II BSC using one piece suit with ventilation
Double door autoclave or dunk tank for decontamination out
Heat decontamination for liquid wastes
Shower drain and toilet drain disinfection
Dedicated HVAC with DP monitoring
HEPA exhaust
Class III BSC exhaust to outdoors through HEPA
One-piece suit, suit-up area
Chemical shower for suit decontamination, redundant HEPA exhaust
Slide 14 © PharmOut 2015
Slide 15 © PharmOut 2015
Slide 16 © PharmOut 2015
Slide 17 © PharmOut 2015
Slide 18 © PharmOut 2015
Airlock functional configurations
Slide 19 © PharmOut 2015
Objective of airlocks
Before we look at different conceptual options, we need to understand some basics:
• To maintain room differential pressure as personnel and/or materials enter or leave.
• To maintain cleanliness differentials.
• To provide an intermediate zone between rooms to implement a status change:
– Gowning / Un-gowning of personal. Personnel changing rooms are special kinds of airlock.
– Cleaning / Decontamination of materiel surfaces.
Slide 20 © PharmOut 2015
Cleanroom application for the control of Dp and cleanliness
Corridor Grade D +
A/L C ++
Room Grade C +++
When all doors closed:
• Door closed pressures maintained.
• Corridor is Grade D.
• A/L must be at cleaner Grade C.
• Room is Grade C.
Doors closed
Slide 21 © PharmOut 2015
Cleanroom application for the control of Dp and cleanliness
Corridor Grade D +
A/L D +
Room Grade C +++
When Grade D side door is open:
• A/L and Corridor pressures equalise.
• Grade C room pressure is maintained.
• A/L assumed to be Grade D = Corridor.
• Room maintains Grade C.
Grade D Door open
Slide 22 © PharmOut 2015
Cleanroom application for the control of Dp and cleanliness
Corridor Grade D +
A/L C +++
Room Grade C +++
When Grade C side door is open:
• A/L and Room pressures equalise.
• Grade C room pressure is maintained.
• A/L assumed to be Grade C = Room.
• Room maintains Grade D.
Grade C Door open
Slide 23 © PharmOut 2015
What are the different types of Airlock used in the Pharma world?
• Cascading Pressure Airlock• Pressure Bubble Airlock• Pressure Sink Airlock• Potent Compound Airlock
del Valle, Manuel A. PE “Design and Operation of Biotechnology: Design and Operation of Biopharmaceutical Airlocks” CleanRooms February 2000
Slide 24 © PharmOut 2015
Cascading pressure airlock
Pressurized air cascades from a clean to a less clean adjacent area
del Valle, Manuel A. PE “Design and Operation of Biotechnology: Design and Operation of Biopharmaceutical Airlocks” CleanRooms February 2000
Less Clean Corridor
Clean Area
³ 15 Pa
+
-
Typically, an
equal amount of
air is supplied to
and returned
from the airlock
+ 30
+15
0.05 in H2O = 12.5 Pascals
P
a
Slide 25 © PharmOut 2015
Pressure Bubble Airlock
Cleaned conditioned air is used to pressurize the airlock. This air dissipates through the airlock doors to adjacent areas.
del Valle, Manuel A. PE “Design and Operation of Biotechnology: Design and Operation of Biopharmaceutical Airlocks” CleanRooms February 2000
Less Clean Corridor
Contained Clean Area -
-
³.15 Pa
³.15 Pa
+
+
Clean conditioned
air is used to
pressurize the airlock.
+15
-15
0
0.05 in H2O = 12.5 Pascals
Slide 26 © PharmOut 2015
Pressure sink airlock
Negative pressure is maintained relative to the adjacent areas and all of the air entering the room is exhausted.
del Valle, Manuel A. PE “Design and Operation of Biotechnology: Design and Operation of Biopharmaceutical Airlocks” CleanRooms February 2000
Less Clean Corridor
Contained Clean Area +
+
³15 Pa
³ 15 Pa
-
-
All of the air that
infiltrates into the
airlock and all of
the supply air is exhausted
0
+15
+15
0.05 in H2O = 12.5 Pascals
Slide 27 © PharmOut 2015
Potent Compound Airlock
A two-cell combination of the pressure bubble and pressure sink airlocksdel Valle, Manuel A. PE “Design and Operation of Biotechnology: Design and Operation of Biopharmaceutical Airlocks” CleanRooms February 2000
Less Clean Corridor
Potent Compound Clean Area
- -
³15 Pa
-
+
³.15Pa
+
-
³.30 Pa
+ -
0
-15
+15
.00
Clean conditioned air is
used to pressurize the
airlock off of the corridor.
There is no return. All of
the air that infiltrates into
the airlock off the Potent Compound
Clean Area
and all of the
supply air is
exhausted
0.05 in H2O = 12.5 Pascals
Slide 28 © PharmOut 2015
Estimation of leakage
Important for any HVAC pressurisation design
• Designer must estimate the known leakage rate
• Designer must allow for any unknown leakage rates
• Doors should be the main leakage path
• Leakage rate through small gaps can be determined from:
– Q = 0.827 x A x (DP)0.5
– Where:
› Q = leakage rate m3/sec
› A = leakage area m2
› and, DP = differential pressure between spaces Pa
Slide 29 © PharmOut 2015
Estimation of leakage around door cracks
Door Size Leakage (Iitre/s) at Differential Pressure (Pa)
5 10 15 20 25 30 35 40 45
Single 24 35 42 49 55 60 65 69 73
Double 53 74 91 105 118 129 140 149 158
Slide 30 © PharmOut 2015
Airlock Good Design Practice
Slide 31 © PharmOut 2015
Good airlock practice – Check list
Describe the function:
• Cleaning / decontamination ; gowning; etc.
Adequate space:
• Internal furniture & equipment.
Pressurisation &
pressure control objectives.
Leak tightness.
• Internal furniture & equipment.
Cleanliness levels:
• Define levels.
• Ventilation & air filtration requirement.
• Recovery time.
Interlocks:
Choose types:
• Electromechanical.
• Traffic lights.
Time delays.
Slide 32 © PharmOut 2015
Things that go wrong with airlocks
Slide 33 © PharmOut 2015
Common airlock problems
• Door leakage prevents adequate room pressure maintenance.
• Internal space too small.
• Recovery time not adequately characterised.
• Changing / Gowning rooms:
– Inadequate space.
– Process not well defined.
– Inadequate segregation of different phases of change process.
› Separation of entry & exit (Spatial or Temporal)
− Failure to comply with Annex 1 “final part of change room should be the same grade as the space accessed”.
Slide 34 © PharmOut 2015
Qualification of airlock performance
Slide 35 © PharmOut 2015
Airlock performance qualification (PQ)
• Confirm supply & return airflow volume.
• Test pressure stability:
1. Open each door in turn, and confirm that the overall critical room/zone pressure regime remains within specification (some small changes should be anticipated because the leakage path resistance for the higher pressure room is reduced when individual doors are open.
2. Open individual doors to different airlocks to mimic normal simultaneous use worst-case situations.
• Cleanliness classification
A. At rest
B. Operational
• Recovery time to qualify interlock time delays.
To prove the function:
Slide 36 © PharmOut 2015
Thank you for your time.Questions?
Gordon Farquharson
Executive Consultant
www.pharmout.net