ISOLATION TECHNOLOGIES

Different solutions for different needs

February 2017
 SUMMARY

• ORABS- CRABS – ISOLATORS

• Isolated filling lines for aseptic and/or toxic processes
• Actual technical solutions
• VHP decontamination cycles
• Isolator for sterility test
• Isolator for dispensing
• Glove leak tester

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 OPEN PASSIVE RABS

A RABS (Reduced Access Barrier System) is used to increase the product protection
from external contaminations.
Its is a system that uses the laminar flow, already available in the clean room, to
create a barrier around the production area.
• What it allows:
• Product protection

• Access to the aseptic area through gloves

• Installation on existing machines

• What it does not allow:

• Operator protection

• Automatic or semiautomatic WIP (Wash-In-Place)

• Automatic decontamination cycles (VHP)

• Access Control

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 OPEN PASSIVE RABS

To grant a production area in Class A, the system must be installed in a cleanroom

classified as B

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 OPEN PASSIVE RABS

 Air flow

Clean room LAF filters

Filtered air from the production

room LAF

Class A

RABS walls / windows

Air exhaust to the production room

Class B surrounding

Machine basement

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 OPEN ACTIVE RABS

Same features as the passive RABS, but it is equipped with a dedicated AHU (Air
Handling Unit). The AHU allows a better pressure control inside the RABS.

• What it allows:
• Increased product protection due to a more reliable air flow control

• Access to the aseptic area through gloves

• Installation on existing machines

• What it does not allow:

• Operator protection

• Automatic or semiautomatic WIP (Wash-In-Place)

• Automatic decontamination cycles (VHP)

• Access Control

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OPEN ACTIVE RABS

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 OPEN ACTIVE RABS

 Air flow

Clean room filters (for LAF or Turbulent ventilation)

Air IN from
production room
dedicated LAF filters

Class A

RABS walls / windows

Air exhaust to the production room

Class B surrounding

Machine basement

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 CLOSED RABS

Reliable solution for production lines for slightly potent components, the installation
will be in a conventional Class B area.
• What it allows:
• Product protection
• Operator protection: NON measurable/quantifiable due to a NON
measurable/quantifiable leak rate (OEL/OEB level can NOT be guaranteed)
• Access to the aseptic area through gloves

• Access Control (doors can be interlocked)

• Air recirculation, to reduce HVAC costs

• Automatic or semiautomatic WIP (Wash-In-Place)

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 CLOSED RABS

• What it does not allow:

• Automatic decontamination cycles (VHP)

• It can NOT be installed on existing machines

• Main technical characteristics:

• Walls / structure in stainless steel with rounded corners (24mm radius) for
better cleaning

• Inflatable gaskets

• Windows / doors in tempered glass

• Dedicated and integrated AHU (Air Handling Unit)

• Dedicated HVAC

• WIP circuit

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 CLOSED RABS

 Air flow

Clean room filters (for LAF or Turbulent ventilation)

Air IN from
production room or from
a dedicated HVAC dedicated LAF filters

Class A
RABS walls / windows

Air exhaust to the production room

Class B surrounding

Machine basement

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CLOSED RABS

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 ISOLATORS

State of the art solution, providing the highest and most reliable machine
configuration to grant:

• Highest SAL (Sterility Assurance Level)

• Highest Operator Protection

• Highest Automated Operations

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 ISOLATORS

• What it allows:
• Product protection (SAL 10-6)
• Measurable/quantifiable operator protection, due to a
measurable/quantifiable leak rate
• Access to the aseptic area through gloves

• Access Control (doors can be interlocked)

• Air recirculation, to reduce HVAC costs

• Automatic or semiautomatic WIP (Wash-In-Place)

• Automatic sanitization with VHP

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 ISOLATORS

• What it does not allow:

• It can NOT be installed on existing machines

• Main technical characteristics:

• Walls / structure in stainless steel with rounded corners (24mm radius) for
better cleaning
• Inflatable gaskets

• Windows / doors in tempered glass

• Dedicated and integrated AHU (Air Handling Unit)

• Dedicated HVAC

• WIP circuit
• VHP distribution circuit an dedicated sensors to control the VHP cycles
(VHP, T, RH%)

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 AVAILABLE TECHNICAL SOLUTIONS

• 6 walls design

• No gaskets between
Isolator and machine
basement

• No more maintenance
(long term higher leak
tightness)

• Perfectly clean

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 AVAILABLE TECHNICAL SOLUTIONS

• 6 walls design

Perfect integration Isolator-Machine

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 AVAILABLE TECHNICAL SOLUTIONS

• Single wall principle

• Air return through dedicated ducts and not through cavity wall or windows, all
ducts are located in the opposite area as to the operator

• Easy to clean solution, and easy to validate a WIP cycle

• Easy to maintain, higher visibility, easy to change gloves, etc.

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 AVAILABLE TECHNICAL SOLUTIONS

• Why and When: WIP (Wash in Place)

• It is suggested when toxic products are manipulated

• A WIP cycle drastically reduces the risk for operators

(manufacturing/maintenance)

• Enhancing product quality avoiding cross-contamination

• Frequency of WIP in according to internal SOP (safety/quality)

• It allows a better decontamination of all air ducts

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 AVAILABLE TECHNICAL SOLUTIONS

• Integrates WIP (Wash in Place)

Automatic washing
with spray balls

Manual washing Time according to the

with spray guns size and number of
sections of the isolator
and to the amount of
Manual drying water available per
with spray guns minute

Automatic drying
with forced ventilation

X min

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 AVAILABLE TECHNICAL SOLUTIONS

• Integrated WIP (Wash in Place)

• Energetic washing and rinsing cycles, in order to mechanically remove all

contamination
• All machines must be IP67
• All sections must be sloped, in order to facilitate water drainage

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 AVAILABLE TECHNICAL SOLUTIONS

• Easy HEPA Filters replacement

• Filter replacement procedure performed form outside the isolator and not from
inside
• Procedure protected by password, authorized by supervisor only and tracked

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 AVAILABLE TECHNICAL SOLUTIONS

• Easy HEPA Filters replacement

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 AVAILABLE TECHNICAL SOLUTIONS

• Engineered Air Ventilation Circuit

• Must grant:
• The unidirectional Air Flow required in the production zone
• A correct number of air exchanges per hour
• The required temperature and relative humidity

• Must allow:
• Dynamic and fast pressure control
• Fine adjustment of required air parameters
• All pipes and ducts must be washable, in order to be decontaminated
• Energy saving, recycling up to 80% of the used air

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 AVAILABLE TECHNICAL SOLUTIONS

• Engineered Air Ventilation Circuit

VHP PLC
VHP
(slave) HVAC New AIR
Generator
Dedicated
to VHP
Conditioned AIR
New AIR
20%
AIR to be HVAC
Recycled
Isolated
80%
filling line
AIR to be
Air extraction
Exhausted
AIR to be unit
20%
exhausted
or recycled
Isolator PLC (Master) HVAC PLC (slave)

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 AVAILABLE TECHNICAL SOLUTIONS

• Rapid Transfer Port

• It allows IN/OUT from the isolator

respecting the containment and aseptic
levels

• Used for:
• Stoppers
• Alu-caps
• Petri plates
• Tools, change parts, etc.

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 AVAILABLE TECHNICAL SOLUTIONS

• Rapid Transfer Port

• Available in different sizes

• Possibility to connect bins

(made of polyethylene or
stainless steel) or bags,
with pre-washed and
pre-sterilized stoppers or
Alu-caps available from
major brands

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 AVAILABLE TECHNICAL SOLUTIONS

• Separation between
sections

• Each section can be

isolated from others by
easily installing a
dedicated cover

• It is made of PTFE, easy to

clean and decontaminate

• It is locked using an
inflatable gasket, and its
presence is monitored
with a sensor

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 AVAILABLE TECHNICAL SOLUTIONS

• Pressure cascade

• A difference of pressure between sections helps us to concentrate major

contamination in the capping area, where also some aluminum powder is
generated during the capping process

• Each section should have an independent pressure control, able to

maintain the correct ΔP, in relation with the adjacent sections

• Pressure inside the filling area should be always higher than the external
room, also during phase changes (decontamination to ventilation, to production,
etc.)

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 AVAILABLE TECHNICAL SOLUTIONS

• Pressure cascade
Xtrema + ALU400 + 2 CLU

Accumulation Accumulation
Table Table
+60Pa +50Pa

Vials Filling Freeze Dryers

Cooling and Loading and Unloading
Zone Capping
Stoppering 1&2
+30Pa +40Pa
+50Pa +50Pa

Mouse hole 0Pa Production room

+25Pa

Possibility to fill liquid products while the FD are lyophilizing

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 AVAILABLE TECHNICAL SOLUTIONS
• Pressure cascade
Xtrema + ALU400 + 2 CLU Accumulation Filling
Table and
+30Pa Stoppering
+60Pa

Vials
Cooling
Zone
+30Pa Freeze Dryers
Loading and Unloading
1&2
Production room +50Pa
+25Pa

Mouse hole 0Pa Capping

+40Pa

NO possibility to fill liquid products while the FD are lyophilizing

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 AVAILABLE TECHNICAL SOLUTIONS
Vials Production room
Cooling +15Pa
• Pressure cascade
Zone
Sterifill FSC +40Pa

Accumulation
Table
+55Pa

Filling
and
Stoppering
+60Pa
Mouse hole
0Pa

Capping
+45Pa

Production room
+25Pa

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 AVAILABLE TECHNICAL SOLUTIONS

• Filters, with bag-in/bag-out

• Filters are located in a

technical area above the
production room

• Filters are located between

the false ceiling and the roof
in the same production room

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 LATEST VHP CYCLE RESULTS
RT + Xtrema

Parameters PQ1 PQ2 PQ3

Register (31/03/2015) (01/04/2015) (02/04/2015)

T: 22,6 °C and UR%: 19,0

Environmental test conditions T: 23,0 °C and UR%: 13,0 % T: 23,0 °C and UR%: 19,0 %
%
Conditioning Phase Dosing
14.5 g/min 14.5 g/min 14.5 g/min
rate [g/mins]
Decontamination Phase
8.3 g/min 8.3 g/min 8.3 g/min
Dosing rate [g/mins]
Duration of Dehumidification
30 min; 180 m3/h 33 min; 180 m3/h 31 min; 180 m3/h
Phase [mins]
Duration of the Conditioning
11min; 130 m3/h 11min; 130 m3/h 11min; 130 m3/h
Phase [mins]
Duration of the
Decontamination Phase 50 min; 130 m3/h 50 min; 130 m3/h 50 min; 130 m3/h
[mins]

Duration of the Aeration Phase 1h:13 min (1.0 ppm) 1h:16 min (1.0 ppm) 1h:08 min (1.0 ppm)

Total length of the cycle 2h: 46 min (1.0 ppm) 2h: 50 min (1.0 ppm) 2h: 39 min (1.0 ppm)

Without catalyzers on the recirculation system

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 LATEST VHP CYCLE RESULTS
PQ1 (31/03/2015)- 2h:46 min (1.0 ppm)

1 ppm

PQ2 (01/04/2015) - 2h:50 min (1.0 ppm)

1 ppm

PQ3 (02/04/2015) - 2h: 39 min (1 ppm)

1 ppm

Without catalyzers on the recirculation system 35

 LATEST VHP CYCLE RESULTS
RT + Sterifill Smart FSC

Parameters I Run II Run III Run

Register (19/05/2015) (19/05/2015) (20/05/2015)

T: 22,0 °C and UR%: 53,0

Start Conditions T: 23,0 °C and UR%: 52,4% T: 20,5 °C and UR%: 55,0 %
%
Conditioning Phase Dosing
7,5g/min 7,5g/min 7,5g/min
rate [g/mins]
Decontamination Phase
7.5 g/min 7.5 g/min 7.5 g/min
Dosing rate [g/mins]

Duration of Dehumidification
28 min; 400 m3/h 30 min; 400 m3/h 18 min; 400 m3/h
Phase [mins]

Duration of the Conditioning

36min; 120 m3/h 36min; 120 m3/h 36min; 120 m3/h
Phase [mins]
Duration of the
Decontamination Phase 10 min; 120 m3/h 10 min; 120 m3/h 10 min; 120 m3/h
[mins]

Duration of the Aeration Phase 57 min (1.0 ppm) 80 min (1.0 ppm) 78 min (1.0 ppm)

2h:26 min (1.0 ppm) 2h:36 min (1.0 ppm) 2h:22 min (1.0 ppm)
Total cycle length
2h:51 min (0.5 ppm) 3h:03 min (0.5 ppm) 2h:56 min (0.5 ppm)

Without catalyzers on the recirculation system

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 STERILITY TEST ISOLATOR

• Stand alone isolator

• Used to perform Sterility Test on

samples

• Internally it grants a class A

environment

• Fully automated by a Siemens

S7-3xx PLC + 7” HMI

• Fully decontaminated with a

dedicated VHP cycle by an
integrated VHP generator

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 STERILITY TEST ISOLATOR

• Pre chamber that allows a fast

decontamination cycle of the material
that must be introduced in the test
chamber such as:
• Sample to be tested
• Ready to use filtration devices
• Culture media
• Rinsing water

• Decontamination time: approx. 45’

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 STERILITY TEST ISOLATOR

• Main test chamber used to

perform filtration processed on
samples

• Filtration pumps made by

Sartorius or Millipore can be
integrated (special models for
installation in isolators)

• Shelves and hooks are available

in order to optimize the process
flow

• Decontamination time: approx.

90’

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 DISPENSING ISOLATOR

• Normally used to weight and dispense toxic powders in order to prepare the right
powder mix to be sent to the tablet press or capsule filler machine.

• Composed by:
• Pre chamber to enter and exit with bags, boxes, bottles, etc.
• Main chamber to perform weigh, mix and dispense powders in NON aseptic
condition

• Turbulent air flow

• HEPA H14 inlet & outlet filters
• Fully PLC controlled
• Washable with water and/or detergents
• High containment valves are normally used to receive/discharge active products
(API)

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DISPENSING ISOLATOR

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 GLOVE LEAK TESTER

from ANNEX 1:
Monitoring should be carried out routinely and should include frequent leak
testing of the isolator and glove/sleeve system.
Therefore, a glove leak tester should be present in any installation where gloves are
present.

AGLTS: Automatic Glove leak

testing System
It is the most advanced and fully
automatic GMP compliant glove
integrity testing system for
isolators and RABS in the
pharmaceutical industry,
developed according to the
Positive Pressure Decay Method
according to the international
standard ISO 14644-7 Annex
E.5.

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 GLOVE LEAK TESTER

• Control PC integrated in the

recharging cart or remote

• Glove tester battery operated,

wireless communication with the
control PC

• Glove tester with integrated air

pump: NO need of additional air
supply

• RFID glove flange recognition

• Unlimited number of glove tester

controlled by the same PC

• Additional access points

available in order to increase
the communication area

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