Architecture and layout Gordon Farquharson July 2017
Architecture and layout
Gordon Farquharson
July 2017
Slide 2 © PharmOut 2017
Learning Objectives
1. Understand importance of layout design
2. Understand importance of thinking about this at the outset
and the link between equipment and delivery of product
CQAs
3. Explain people and product impact, flows etc.
Slide 3 © PharmOut 2017
Equipment and Facility Design
The facility layout and configuration must be an integrated design that satisfies process and equipment layout requirements, and satisfies the cGMP objectives (hence it is necessary to select equipment prior to the design process)…
Slide 4 © PharmOut 2017
Mitigate unacceptable product risk by good design
In the context of facility design, risk management is a process that evaluates where the product is at risk (risk assessment), and deploys mitigation measures to reduce the risk to an acceptable level.
Typical risks are:
• contamination of product;
• cross-contamination;
• and mix-ups.
Slide 5 © PharmOut 2017
Risk depends upon certain process attributes
These are all fundamental to the design of a facility:
• Open aseptic processing in a traditional cleanroom environment.
• Open aseptic processing in an Isolator.
• Closed aseptic processing.
• Open processing (bio-burden control) for terminally sterilized products.
Slide 6 © PharmOut 2017
Barrier Technology
The term Barrier Technology includes:
• RABS (Restricted access barrier systems).
• Isolators.
−Open isolators.
−Closed isolators.
• RABS require Grade B surrounding room.
• Isolators require:
– Minimum Grade D room for EU.
– Grade C equivalent Room for US compliance (& TGA).
See the more detailed RABS & Isolator presentation
Slide 7 © PharmOut 2017
General Facility Requirements in the GMPs
• People
• Materials
• Process
Movement
• Walls
• Floors
Finishes• Drains
• Water
Utilities
Slide 8 © PharmOut 2017
Personnel & Material management objectives
In order to produce an acceptable sterile product, the design must achieve the following:
➢ Control of contamination ingress➢ Prevent contamination spread (dissemination)➢ Manage personnel movements and changing regimes➢ Manage material flows to prevent errors and mix-ups
Slide 9 © PharmOut 2017
Some other design considerations
Classified areas need storage space for:
• Work-in-progress (WIP) (don’t use the corridors).
• Clean/sterile equipment.
Consider a means of isolating filling rooms from classified corridors, and providing a secondary means of entry so that a room can be isolated for unplanned or longer term maintenance or process modification.
Slide 10 © PharmOut 2017
Loose Fit Design Concepts Service Zone Concept Plan
Process
Area“B”
Unclassified Technical Support Area
Process Corridor “B”
Slide 11 © PharmOut 2017
Floor drains – GMP requirements
Sinks and drains should be prohibited in grade A/B areas used for aseptic manufacture.
In other areas air breaks should be fitted between the machine or sink and the drains (to prevent suck-back in the event of a process fault).
Floor drains in lower grade clean rooms should be fitted with traps or water seals to prevent back flow.
Ensure disinfection of drains is part of microbiological control.
Slide 12 © PharmOut 2017
Changing / Gowning Rooms
Change rooms are specialized airlocks and should minimize or prevent the introduction of contaminants to the clean area.
1. Separate ingress/egress for aseptic operations, if possible
• Can separate by time (temporal) or space (spatial)
2. Gowning rooms need a clear progression from “less clean” “more clean”; and back again on exit. (define it
as a process).
3. Need provisions for personnel monitoring.
4. Need space for garment storage (clean & dirty).
5. Final stage of gowning room should be same classification as area it opens into (GMP Annex 1 requirement).
Slide 13 © PharmOut 2017
Aseptic Changing Room
Over
shoe
10
12
14
16
Wrap
wasteDisinfect
mirror
waste
Disp
waste
Garment
out
disinfect
30
29 28
2726
24
25
23
2219
18
20
8,11,13,15,17,21
96,7
5
3,4
1,2
Aseptic
Processing
Area
Possible
additional
Airlock
Entry/Exit from Grade D or
Controlled/Unclassified
Airflow direction
Slide 14 © PharmOut 2017
Changing is a critical process
1. Factory shoe removal (putting in locker)
2. Factory clothes removal (putting in locker)
3. Sit on the bench, taking the overshoe and head wear
4. Putting on the overshoe and head wear, turn on the bench
5. Hand washing or disinfection.
6. Collect the shoes for aseptic area
7. Take off overshoes, putting into waste box, don the aseptic area shoes.
8. Disinfect hands.
9. Collect the latex glove (1), putting on and disinfect gloved hand.
10. Collect aseptic area garments and place them on the bench.
Slide 15 © PharmOut 2017
Changing is a critical process
11. Disinfect gloved hands.
12. Remove head covering and place in waste, open the sterile head gear and don.
13. Disinfect gloved hands.
14. Unwrap and don the aseptic area gown. (waste to waste box)
15. Disinfect gloved hands.
16. Unwrap and don the aseptic area booties.(waste to waste box)
17. Disinfect gloved hands.
18. Turn on the bench and stand up.
19. Check dress in mirror.
20. Remove latex glove (1) (waste to waste box) Don latex glove (2), putting on (waste to waste box)
Slide 16 © PharmOut 2017
Changing is a critical process
21. Disinfect gloved hands.
22. Enter aseptic processing area
23. Exit from aseptic area
24. Remove aseptic area clothing.
25. Remove aseptic area shoes and place in locker.
26. Place reusable garments in hamper for garments to be laundered
27. Waste receptacle for disposable garments
28. Waste receptacle for disposable garments
29. Don the factory clothing.
30. Don factory shoes.
31. Return to the general factory areas.
Slide 17 © PharmOut 2017
The Design Sequence (Steps)
1
• Product requirements
• Process requirements
2
• Prepare process flow diagram
• Prepare an accommodation schedule
3
• Prepare a conceptual association diagram
• Develop the layout – usually there will be options to explore
Slide 18 © PharmOut 2017
Simple Process Flow Diagram
Slide 19 © PharmOut 2017
Finished
Goods to
Warehouse
Roof
Level
First
Floor
Level
Second
Floor
Level
Building Services Distribution Zone and Technical Space
Materials
Receipt.
Load/
Unload BayRaw
Materials
Receipt
Raw
Materials
and
Glassware
Warehouse
Q.C.
Samplin
g
Vial Wash Vial Capping
Check Weigher
Palletising Manual Case Packing
Automated Printed
Cartoning and leaflet insertion
Glassware/
Components
Airlock
Transfer
Sterilising/Depyrogenation Tunnel
Vial Washing Machine Vial filler and Stopper insert Vial Over Cap
Component
Preparation
Component
Transfer
Building Services Distribution Zone and Technical Space
Airlock
Transfer
Ground
Floor
Level
First
Floor
Level
Autoclave
Stopper Washing
Machine
Stopper/Caps and
equip’t Sterilisation
Automatic
Inspection
Leak Detector
(Grade C)
(Grade C)
(Grade C) (Grade A/B) (Grade B)
(Grade D)
(Grade D)
(Socially
Clean)
Thermoform Plastic
Raw
Materials
Airlock
Transfer
(Grade C)
Waste Materials
return
Filtration
of Solution
Compounding Vessel
Freeze Drier
Plantroom(Unclassified)
Sterile solution
transferred to
filling line in
mobile vessel
(Grade A/B)
Vial Filling/Stopper
Freeze Drier
Loading(Grade A/B)
(Grade C)
Autoclave
Loading(Grade C)
Autoclave
Component
Transfer
Reject
Material
Store
Transfer Filled Vials
to Leak Detection
and Auto-Inspection
Transfer Inspected Vials to Warehouse
for Quarantine and Packaging Release
Q.C. Released Vials transfer to
Packaging
Secondary Packaging Hall
Liquid Aseptic Vials
Liquid Terminally Sterilised Vials
Lyophilised Vials
Leak detected and inspected vials for quarantine
Secondary packaged vials
Secondary packaged Components
Component transfer
Active/Excipient transfer
Legend
Ground
Floor
Level
Ground
Floor
Level
Solution
Compounding
Area
(Grade C)(Grade C)
Dispensary
(D.F.B.)
Finished
Goods to
Warehouse
Finished
Goods to
Warehouse
Roof
Level
First
Floor
Level
Second
Floor
Level
Building Services Distribution Zone and Technical Space
Materials
Receipt.
Load/
Unload BayRaw
Materials
Receipt
Raw
Materials
and
Glassware
Warehouse
Q.C.
Samplin
g
Vial Wash Vial Capping
Check Weigher
Palletising Manual Case Packing
Automated Printed
Cartoning and leaflet insertion
Glassware/
Components
Airlock
Transfer
Sterilising/Depyrogenation Tunnel
Vial Washing Machine Vial filler and Stopper insert Vial Over Cap
Component
Preparation
Component
Transfer
Building Services Distribution Zone and Technical Space
Airlock
Transfer
Ground
Floor
Level
First
Floor
Level
Autoclave
Stopper Washing
Machine
Stopper/Caps and
equip’t Sterilisation
Automatic
Inspection
Leak Detector
(Grade C)
(Grade C)
(Grade C) (Grade A/B) (Grade B)
(Grade D)
(Grade D)
(Socially
Clean)
Thermoform Plastic
Raw
Materials
Airlock
Transfer
(Grade C)
Waste Materials
return
Filtration
of Solution
Compounding Vessel
Freeze Drier
Plantroom(Unclassified)
Sterile solution
transferred to
filling line in
mobile vessel
(Grade A/B)
Vial Filling/Stopper
Freeze Drier
Loading(Grade A/B)
(Grade C)
Autoclave
Loading(Grade C)
Autoclave
Component
Transfer
Reject
Material
Store
Reject
Material
Store
Transfer Filled Vials
to Leak Detection
and Auto-Inspection
Transfer Inspected Vials to Warehouse
for Quarantine and Packaging Release
Q.C. Released Vials transfer to
Packaging
Secondary Packaging Hall
Liquid Aseptic Vials
Liquid Terminally Sterilised Vials
Lyophilised Vials
Leak detected and inspected vials for quarantine
Secondary packaged vials
Secondary packaged Components
Component transfer
Active/Excipient transfer
Legend
Ground
Floor
Level
Ground
Floor
Level
Solution
Compounding
Area
(Grade C)(Grade C)
Dispensary
(D.F.B.)
Sterile Manufacturing Pictogram
Slide 20 © PharmOut 2017
Accommodation association diagram
Slide 21 © PharmOut 2017
Sterile Manufacturing, Layout
Slide 22 © PharmOut 2017
U-shape Filling Line
Slide 23 © PharmOut 2017
Linear Filling Line
Slide 24 © PharmOut 2017
Thank you for your time.Questions?
Gordon Farquharson
www.pharmout.net
Executive Consultant