Airlocks

Presented by Gordon Farquharson

August 2015
Agenda

Regulatory expectation

Different functional configurations

Good design practice

What often goes wrong

Qualification of airlock performance

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Regulatory expectation/guidance

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PIC/S Annex 1 guidance

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PIC/S Annex 3 guidance

PIC/S Annex 5 guidance

PIC/S Annex 10 guidance

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PIC/S Glossary

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WHO HVAC OSD supplementary Guidance
Airlocks

The Dp values are indicative – they aren’t a requirement

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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.

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 Biosafety levels: BL-1
Laboratory Special Practices Containment Laboratory
Practices Equipment Facility

Access limited Leak-proof container for None Easily cleaned

off-site decontamination
Daily and after-spill Hand wash
decontamination Pest control sink
Waste Screens in
decontaminated windows
No mouth pipette
Personal Wash
Minimise aerosols
Uniform

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 Biosafety levels: BL-2
Laboratory Special Practices Containment Laboratory
Practices Equipment Facility
Same as BL-1 Same as BL-1 except Biosafety Same as BL-1
Principal investigator limits cabinets (Class
Can also Autoclave for
I, II) if aerosols
perform BL-1 if access waste
Policies and procedures for or high number
isolated decontaminatio
access of organisms
n
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

Slide 10 © PharmOut 2015

Biosafety levels: BL-3
Laboratory Special Practices Containment Laboratory Facility
Practices Equipment
Same as BL-2 Same as BL-2 and: Biosafety Same as BL-2
Doors closed cabinets (Class Separated from
No entry
I, II, III) or building flow
under age 16 More limits on access
physical
Hazard sign required Airlock or gown room
Lesser containment
access
organisms in No open work devices
same Sink near door has no-
Clean-up when finished
laboratory contact faucet
Gowning
must follow Closed/sealed windows
decontamination
BL-3 Self-closing doors
Mask/respirator
Ducted exhaust
Special animal cages
BSC exhaust outdoors
HEPA on vacuum

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Biosafety levels: BL-4
Laboratroy Special Practices Containment Laboratory Facility
Practices Equipment

Same as BL-3 Double container Class III BSC Separate building or isolated
for waste zone
Decontaminate Class I or II Sealed internal shell, can be
everything but BSC using one decontaminated
product leaving the piece suit with Flooded floor drain traps
laboratory connected to waste
ventilation
Access tightly decontamination
controlled, locked HEPA on vents and drains
doors, logbook Minimize dust surfaces
Emergency Seamless bench tops
protocols
Dedicated central vacuum
Access in/out with HEPA at point of use
through shower Backflow prevention for
rooms process fluids
Doors self closing and
locking
Break resistant windows

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Biosafety levels: BL-4 cont…
Laboratory Special Practices Containment Laboratory Facility
Practices Equipment
Same as No street clothing, Class III BSC Double door autoclave or
special uniform dunk tank for
BL-3
Hazard signs Class I or II decontamination out
BSC using Heat decontamination for
Decontaminate liquid wastes
incoming materials, one piece
airlock access suit with Shower drain and toilet drain
ventilation disinfection
No spare materials,
clothing, animal Dedicated HVAC with DP
monitoring
Worker health
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

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Airlock functional configurations

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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.

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Cleanroom application for the control
of Dp and cleanliness
Doors closed

Corridor Grade D +

When all doors closed:

A/L C ++
• Door closed pressures
maintained.
• Corridor is Grade D.
• A/L must be at cleaner
Grade C.
Room Grade C +++ • Room is Grade C.

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Cleanroom application for the control
of Dp and cleanliness
Grade D Door open

Corridor Grade D +

When Grade D side door is open:

A/L D +
• A/L and Corridor pressures
equalise.
• Grade C room pressure is
maintained.
• A/L assumed to be Grade
D = Corridor.
Room Grade C +++
• Room maintains Grade C.

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Cleanroom application for the control
of Dp and cleanliness
Grade C Door open

Corridor Grade D +

When Grade C side door is open:

A/L C +++
• A/L and Room pressures
equalise.
• Grade C room pressure is
maintained.
• A/L assumed to be Grade
C = Room.
Room Grade C +++
• Room maintains Grade D.

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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

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Cascading pressure airlock

Clean Area + 30
+
P
aTypically, an
equal amount of
³ 15 Pa air is supplied to
and returned
from the airlock

-
Less Clean Corridor +15

0.05 in H2O = 12.5 Pascals

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

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Pressure Bubble Airlock
Contained
-15
- Clean Area

³.15 Pa
Clean conditioned
+ +15 air is used to
+ pressurize the
airlock.
³.15 Pa

-
Less Clean Corridor 0

0.05 in H2O = 12.5 Pascals

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

Slide 25 © PharmOut 2015

Pressure sink airlock

Contained
+ Clean Area +15

³15 Pa
All of the air that
- 0 infiltrates into the
- airlock and all of
the supply air is
³ 15 Pa exhausted

+
Less Clean Corridor
+15

0.05 in H2O = 12.5 Pascals

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

Slide 26 © PharmOut 2015

Potent Compound Airlock

+ Clean conditioned air is

used to pressurize the
airlock off of the corridor.
³15 Pa There is no return. All of
0 Potent Compound
Clean Area the air that infiltrates into
the airlock off the Potent
+ Compound
³.30 Pa Clean Area

+ +15
and all of the
- - - ³.15Pa supply air is
- exhausted

-15
.00 -
Less Clean Corridor

0.05 in H2O = 12.5 Pascals

A two-cell combination of the pressure bubble and pressure sink

airlocks
del Valle, Manuel A. PE “Design and Operation of Biotechnology: Design and Operation of
Biopharmaceutical Airlocks” CleanRooms February 2000

Slide 27 © 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

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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

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Airlock Good Design Practice

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Good airlock practice – Check list

 Describe the function:  Cleanliness levels:

• Cleaning / decontamination ; • Define levels.

gowning; etc. • Ventilation & air filtration
requirement.
Recovery
••Internal time.
furniture & equipment.

 Adequate space:

 Interlocks:
• Internal furniture & equipment.

Choose types:
 Pressurisation & • Electromechanical.
pressure control objectives. • Traffic lights.

 Leak tightness.  Time delays.

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Things that go wrong with airlocks

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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”.

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Qualification of airlock performance

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Airlock performance qualification (PQ)

To prove the function:

• 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.
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Thank you for your time.
Questions?

Gordon Farquharson
Executive Consultant

gordon.farquharson@pharmout.net
www.pharmout.net

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