ISPE Tampa Conference

22-25 February 2010

Tampa, Florida USA

Current Aseptic Processing Trends with the Use

of Isolators and RABS (Restricted Access
Barrier Systems)

Jack Lysfjord, Principal Consultant

Lysfjord Consulting LLC
952 546 2082
jlysfjord@q.com

Tampa, Florida
February 22-23, 2010

Learning Objectives
• At the conclusion of this session,
participants will be able to:
• Have a better understanding of Isolators
and RABS for Aseptic Processing
Fill/Finish Applications
• Understand Global and Regional Industry
Benchmarking Data and Trends Related
to the Use of Isolators and RABS

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Agenda

• Background - Diagrams
• Survey Data & Trends
• Q&A

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Conventional Clean Room

HEPA Filters

Filling
Class 100 Mechanism
(ISO 5)

Nozzle

Vial

Conveyor

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RABS (Passive)
Restricted Access Barrier System
HEPA Filters

• A barrier to prevent human 3-6" From

HEPAS
intervention.
• Air flow provided by ceiling Class 10,000 Class 100
Filling
Mechanism
(ISO 7) (ISO 5)
HEPAs to critical zone.
Nozzle
• Bottom of enclosure is
open for air outlet. Vial

• Glove ports and Transfer Conveyor

ports used for

manipulations and
commodity additions.
• Manual high level
disinfection.
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RABS (Active)
Restricted Access Barrier System
HEPA

• Similar to Passive RABS

but with integral HVAC

HEPA/HVAC air supply to HEPA Filters

critical zone.
Filling
Class
• Easiest way to have flow 10,000
(ISO 7)
Class 100
(ISO 5)
Mechanism

from critical area to room Nozzle

in case of open door Vial

intervention. Conveyor

• Manual high level

disinfection.

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Closed RABS

HEPA

• Similar to an isolator without

vapor biodecontamination. 


• Manual high level

disinfection. 

 !"#$






• Can be used for containment 

applications 



%&

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RABS needs

• Management Oversight
• A Quality System
• Proper surrounding room design
• ISO 5 Annex for Open Door routine interventions
• Proper Gowning
• Proper Training cGMP
• Initial high level disinfection with Sporicidal
agent
• Proper SOP for rare interventions allowed
• Properly Designed Equipment
• If interventions are allowed (Policy)
• Disinfection
• Line Clearance
• Documentation of event

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Isolators

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Isolator

HEPA

HEPA Filters

Class Filling
100,000 Mechanism
(ISO 8)

Nozzle

Vial
Conveyor

Air
Return

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Isolator for Containment

HEPA Filters Bag In

Bag Out

Baffle

Class CIP
Class 100 Filling
100,000
(ISO 5) Mechanism
(ISO 8)

Nozzle

Vial

Conveyor

Push Push HEPAS

Sterilizable
Drain for CIP

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Data & Trends

• Data is from Lysfjord Porter Surveys

• Isolator 1998, 2000, 2002, 2004, 2006
and 2008
• RABS 2005, 2007, 2009

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Filling Barriers Survey Summarys World Wide

Year 1998 2000 2002 2004 2005 2006 2007 2008 2009

Isolator 84 172 199 256 304 391

RABS 75 124 243

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Barrier Isolator Filling Line –

Deliveries by Year Total
Total

35

30

25

20

15

10

0
1985
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
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Barrier Isolator Filling Line - Cumulative

Deliveries
450
400
350
300
250
200
150
100
50
0
1985
1988
1989
1990
1991
1992
1993
1994
1995
1996

1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
1997
1998

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Barrier Isolator Filling Lines –

Deliveries by Year - Asia Only

Asia Total Responses 59

8
7
6
5
4
3
2
1
0
1985
1988

1989

1990
1991

1992
1993

1994

1995
1996

1997

1998
1999

2000
2001

2002

2003
2004

2005
2006

2007

2008
2009
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Barrier Isolator Filling Lines –

Deliveries by Year - Europe Only
Europe Total Responses 193

25

20

15

10

0
1985
1988
1989

1990
1991
1992

1993
1994
1995

1996
1997

1998
1999
2000

2001
2002
2003

2004
2005
2006

2007
2008
2009

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Barrier Isolator Filling Lines –

Deliveries by Year - North America Only

North America Total Responses 132

18
16
14
12
10
8
6
4
2
0
1985

1988

1989
1990

1991

1992

1993

1994

1995
1996

1997

1998

1999

2000
2001

2002

2003
2004

2005

2006
2007

2008

2009
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Number of RABS Units Delivered by Year Total

40

35

30

25

20

15

10

0
1990 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010

Asia Europe North America

• No year provided for 9 lines

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RABS Delivered by Year by Continent (39)

Asia
8

7
7

6
6

5
5

4 4
4

3 3
3

2 2 2
2

1
1

0
1990 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010

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RABS Delivered by Year by Continent (134)

Europe
25

21
20
20
18

15
15 14

10
7 7
6
5
5 4 4 4
3
2
1 1 1 1

0
1990 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010

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RABS Delivered by Year by Continent (61)

North America
12
11

10
10

8
8
7

6
5

4
4
3 3

2 2 2
2
1 1 1 1

0
1990 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010

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Types of RABS

Year Passive Active Closed Total

2005 16 25 17 58

2007 19 47 27 93

2009 51 121 64 236

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Philosophy for Using RABS

Doors:

Never Frequently
Year Opened Limited Open Open Total

2005 23 28 1 52

2007 26 45 6 77

2009 59 87 10 (6.4%) 156

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Barrier Isolator Filling Lines

Companies with Highest Usage
Compaies with more than 5

30

25

20

15

10

0
Sanofi Baxter Pfizer J&J GSK Novartis Taiyo Eli Lilly Nipropharma Apotex Merck

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Top Companies with RABS

2005 2007 2009

# of # of # of
Company RABS Company RABS Company RABS
Vetter Vetter
Pharma 10 Pharma 10 Pfizer 17
Vetter
Pfizer 7 Pfizer 10 Pharma 15

Aventis 5 GSK 7 GSK 12

GSK 4 Aventis 5 Merck 11

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Container Type Total

Vial Ampoule Syringe/ Ophthalmic IV Other Total
Cartridge

Isolator 201 48 98 20 25 20 399

08

RABS 155 19 53 13 2 4 246

09

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Container Type Asia

Vial Ampoule Syringe/ Ophthalmic IV Other Total
Cartridge

Isolator 25 13 8 6 9 1 62
08

RABS 20 2 8 7 3 40
09

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Container Type EU
Vial Ampoule Syringe/ Ophthalmic IV Other Total
Cartridge

Isolator 89 25 67 4 1 12 198
08

RABS 69 13 36 4 2 1 125
09

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Container Type NA
Vial Ampoule Syringe/ Ophthalmic IV Other Total
Cartridge

Isolator 84 7 18 8 14 5 136
08

RABS 47 4 9 2 62
09

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Reported Number of Lines vs. Maximum Line

Speed with Isolator
1-100 101- 201- 301- 401- 501- 601- 701- Total
200 300 400 500 600 700 800

Total 124 47 65 40 6 12 5 299

Asia 16 3 12 7 38

EU 39 30 36 27 3 8 5 148

NA 68 14 17 6 3 4 112

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Reported Number of Lines vs. Maximum Line

Speed with RABS
1-100 101- 201- 301- 401- 501- 601- 701- Total
200 300 400 500 600 700 800

Total 40 47 30 37 15 5 174

Asia 3 9 4 4 2 22

EU 21 28 18 27 7 4 105

NA 16 10 8 6 6 1 47

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Gloves

• 2nd Glove Used; ISO 89% Yes, RABS 98%

Yes
• Testing by Visual and Pressure Decay is
Predominant Test Both Iso and RABS
• Replacement up to 6 months with “As
Needed” most prevalent for ISO/RABS
• 1 Piece 46%, 2 Piece 54%*
• Smooth Sleeve 86%, Pleats 14%*
• * Isolator data only

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Containment

• Isolator, 90/214 Need Containment,

However 100% of Units Added in Last
2 Years!
• RABS, 22 Indicated a Containment
Need

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Do you Campaign Products (Isolator)

(run for multiple days)?

*
No 50 41% of total
Yes 71 59% of total
Total 121
*51% in 2006 data

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Campaign Products (longest run, Isolators)

25

20

15

10

0
2 3 4 5 6 7 8 10 14 28
# of Days

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Number of Days Line Campaigned RABS

12

11

10
10

1 1 1 1

2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

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Cumulative Deliveries
450
400
350
300 Isolators
RABS
250

200
150
100
50
0
1985

1987

1989

1991

1993

1995

1997

1999

2001

2003

2005

2007

2009
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Trends

• Both ISO and RABS Use Is Increasing

• ISO Rate is Increasing Slightly/Year
• RABS is Growing and Rapidly Increasing
• Syringe in Tubs Is Rapidly Increasing in EU Iso
• Containment Need is Increasing (100%) Iso
• 92% of Isolators Use H2O2 As a Biodecontaminant
• Campaigning Use and Duration Are Both
Increasing 28 days Iso, 20 days RABS

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Trends Continued

• Data Is Harder to Get, SPP COP in Japan

Helped Surveying Users for More Data
• RABS Problem; To Mount Sterile Stopper
Feed Components Aseptically! Trend in
EU (Bioquell), NA (Steris) and in Japan
(Airex, JGC and Shibuya) Is to H2O2 Room
with RABS and get 6 Log Reduction of
Bioburden on Stopper Feed Parts
• RABS Problem; Over 6% Are Opened
Frequently- Agency Issue!

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Trends Continued

• So Which Best? Isolator or RABS?

• It Depends, on Application Needs.
• Both are Tools That Work, IF Used
Properly.
• Keep Doors Closed on RABS.

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Summary

• We have reviewed options for aseptic

processing including isolators and
RABS.
• Data and trends were presented for
global and regional use of isolators
and RABS for aseptic processing.

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Thank You!

Jack Lysfjord, Principal Consultant

Lysfjord Consulting LLC
2711 Sylvan Road
Minnetonka, MN 55305
+1(952) 546-2082
jlysfjord@q.com

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