Architecture and layout€¦ · Personnel & Material management objectives In order to produce an...

Architecture and layout

Gordon Farquharson

July 2017

© 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.

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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)…

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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.

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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.

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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

© PharmOut 2017

General Facility Requirements in the GMPs

• People

• Materials

• Process

Movement

• Walls

• Floors

Finishes• Drains

• Water

Utilities

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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

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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.

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Loose Fit Design Concepts Service Zone Concept Plan

Process

Area“B”

Unclassified Technical Support Area

Process Corridor “B”

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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.

© 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).

© 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

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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.

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11. Disinfect gloved hands.

12. Remove head covering and place in waste, open the sterile head gear and don.


14. Unwrap and don the aseptic area gown. (waste to waste box)


16. Unwrap and don the aseptic area booties.(waste to waste box)


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)

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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.

© 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

© 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


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


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


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

© PharmOut 2017

Thank you for your time.Questions?

Gordon Farquharson

[email protected]

www.pharmout.net

Executive Consultant

Architecture and layout€¦ · Personnel & Material management objectives In order to produce an...

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