Airlocks - PharmOut · or high number of organisms Same as BL-1 ... Potent Compound Airlock ... • Cleanliness classification A. At rest B. Operational

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


Regulatory expectation/guidance


PIC/S Annex 1 guidance






PIC/S Glossary


WHO HVAC OSD supplementary Guidance Airlocks

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


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.


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





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





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



LaboratroyPractices


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


Biosafety levels: BL-4 cont…



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






Airlock functional configurations


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.


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



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



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


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


Cascading pressure airlock

Pressurized air cascades from a clean to a less clean adjacent area


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


Pressure Bubble Airlock

Cleaned conditioned air is used to pressurize the airlock. This air dissipates through the airlock doors to adjacent areas.


Less Clean Corridor

Contained Clean Area -

-

³.15 Pa

³.15 Pa

+

+

Clean conditioned

air is used to

pressurize the airlock.

+15

-15

0



Pressure sink airlock

Negative pressure is maintained relative to the adjacent areas and all of the air entering the room is exhausted.


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



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



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


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


Airlock Good Design Practice


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.


Things that go wrong with airlocks


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”.


Qualification of airlock performance


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:


Thank you for your time.Questions?

Gordon Farquharson

[email protected]

Executive Consultant

www.pharmout.net

Documents

Airlocks - PharmOut · or high number of organisms Same as BL-1 ... Potent Compound Airlock ... • Cleanliness classification A. At rest B. Operational