ISPE Tampa Conference
22-25 February 2010
Tampa, Florida USA
ISOLATORS and EQUIPMENT
INTEGRATION
Loris Rinaldi
Learning Objectives
• At the conclusion of this session,
participants will be able to:
• Evaluate overall isolator performance.
• Recognize key aspects for equipment
integration into isolators.
• Address containment and cleanability
requirements for isolators.
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ISPE Tampa Conference
22-25 February 2010
Tampa, Florida USA
Containment
• Using an accurate pressure
control, the system must
guarantee an internal
pressure lower than the
external pressure
∆p = 50 ÷ 250 pascals
• In case of accident (leak,
glove leaks…) the system
must be able to maintain an
inward air flow, in order to
avoid the exit of any toxic
product (powder, liquid or
gaseous)
•The internal pressure must be
lower than the external pressure
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Aseptic
• Using an accurate pressure
control the system must
guarantee an internal
pressure higher than the
external pressure
∆p = 50 ÷ 250 pascals
• In case of accident (leak,
glove leaks…) the system
must be able to maintain an
outward air flow, in order to
avoid any contamination of
the internal environment by
non aseptic air
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•The internal pressure must be
higher than the external pressure
ISPE Tampa Conference
22-25 February 2010
Tampa, Florida USA
O2 and Moisture control
• Some products are sensitive to
any contact with O2 and/or
moisture. In those cases the
system must be purged with
Nitrogen or other inert gases
and it must be equipped with
sensors to evaluate the
environment before that any
activity starts.
• With high sensitive products
the system must be equipped
with a purification system in
order to reach very low levels
of O2 and moisture (few ppm)
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The internal environment must be
O2 and Moisture free
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Isolators for all types of applications
• Three main aspects to consider:
1) Environmental control
2) Equipment integration
3) Cleanability
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ISPE Tampa Conference
22-25 February 2010
Tampa, Florida USA
1) Environmental Control
- ISO 10648-2 leak tightness classes 1-4
- OEL/OEB
- Air Flows
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ISO 10648-2 leak tightness classes 1-4
Any Isolator should pass the Leak Test class 2 ISO 10648-2 !!!
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ISPE Tampa Conference
22-25 February 2010
Tampa, Florida USA
OEL/OEB
OEL
OEL Range
Design
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> 1000 µg/m3
General room ventilation. Conventional open
equipment with local exhaust ventilation (LEV)
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50 to 1000 µg/m3
Semi-closed to closed material transfers; laminar
flow / top-down flow, engineered LEV.
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20 to 50 µg/m3
Transfers using direct coupling & closed systems,
selected use of unidirectional air flow booths.
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1 to 20 µg/m3
Totally enclosed processes; transfers using direct
coupling; barrier/isolator technology.
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< 1 µg/m3
Isolator technology; remote operations, fully
automated.
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Unidirectional Air Flows
Air inlet
HEPA Filter
Air inlet
HEPA Filter
HEPA Filter
Air outlet
HEPA Filter
• 0.45 m/s 20% air
speed (1.48 ft/s 20%)
• Fastest “ambient
class” recovery time
• Excellent with powder
(in that case a topdown flow must be
adopted
• The huge amount of
air to be handled must
be taken into
consideration
Water Drain
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Side views
ISPE Tampa Conference
22-25 February 2010
Tampa, Florida USA
Turbulent Air Flows
• More than 20 air changes per
hour
• Higher “ambient class”
recovery time than with the
Unidirectional Flow, due to
the lowest volume of air used
• Excellent for transportable or
small size Isolators
• Excellent when an inert gas
(Nitrogen, Argon…) must be
used in alternative to the
normal Air
• Some areas can remain dirty
(non reached by the air flow)
Air inlet
Air outlet
HEPA
Filter
HEPA
Filter
Front view
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Air flows evaluation
• Turbulent flow
Isolator volume X number of air changes/hour
2 m3 x 20 air changes/ hour = 40 m3/hour
70.63 Cu ft x 20 air changes/ hour = 1,412 Cu ft /hour
• Unidirectional flow
(area covered by the flow) x (air speed) x (3600 number
of seconds in a hour)
2 m2 x 0.45 m/s x 3600s = 3,240 m3/hour
21.52 Sq ft x 1.48 ft/s x 3600s = 114,658 Cu ft/hour
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ISPE Tampa Conference
22-25 February 2010
Tampa, Florida USA
2) Equipment Integration
-
Mechanical Integration
Cables/Electrical connections
Gaskets/Seals
Technical Area
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Mechanical Integration
Different degrees of
complexity :
attention to all details!!
Removable platforms.
Rapid connectors for
liquids.
Electrical connectors for
high vacuum applications.
Remote electrical &
control panels.
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ISPE Tampa Conference
22-25 February 2010
Tampa, Florida USA
Mechanical Integration
MAIN EQUIPMENT
Ex. Micronizator (Jet-Mill):
high dusts residuals and
electrical sparks
Closed environment with
Nitrogen Atmosphere
All electrical motors placed
externally
Completely Washable System
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Mechanical Integration
UTILITY TYPE:
- Gas, Liquid,
- Electrical, Pneumatic
- Temperature, Pressure
- Aggressive Liquids,
Solvents/Acids
SUITABLE MATERIALS:
- PTFE, PVDF or Stainless Steel
Ergonomics and space constraints
require advanced design studies!!
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ISPE Tampa Conference
22-25 February 2010
Tampa, Florida USA
Mechanical Integration
MECHANICAL INTERFACES:
- Flange interface (Very important!!)
The equipment is ready to be
integrated into an isolator?
- The equipment manufacturer has
to guarantee that the equipment is
leak tight!!
- The overall leak tightness should
not be compromised!
Tests, LbM, Integration Expertise!!
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Mechanical Integration : Retrofit
• Working plane retrofit
• Electrical panel retrofit
• Lower Mechanical area retrofit
• Check all crevices, and
connections from upper working
plane to lower technical area,
mechanical connections:
Sealed? Washable?
No passage of material from top
to down: Pressurize Lower
Mechanical Area
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ISPE Tampa Conference
22-25 February 2010
Tampa, Florida USA
Mechanical Integration
Over all process, not only mechanical
but SW, One PLC and one HMI, I/O
Exchange, Safety Interlocks, all the
way to the stairs sheeting…
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Cables/Electrical connection
Electrical Connector for vacuum
applications avoid passage of air
(Ex. Fisher, Douglas EC, type of
connection)
Rapid connectors for liquids such as
Staubli (316L, with different gaskets
from NBR to PTFE)
All connections are a potential
source of Leakage.
High quality components should be
a must!!!
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ISPE Tampa Conference
22-25 February 2010
Tampa, Florida USA
Gaskets/Seals
• Static Gaskets Vs Pneumatic Gaskets
• EPDM Vs Silicon
• Custom Design Vs Standard
Cleanability and Leak tightness are
critically dependant on the gaskets!!
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3) Cleanability
- Surfaces: Isolator Design and
Manufacturing
- Valves and Piping
- Suitable Equipment for WIP
- Empirical tests for WIP Mock-up
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ISPE Tampa Conference
22-25 February 2010
Tampa, Florida USA
Surfaces: Isolator Design and Mfg.
• All of the internal angles should have a radius of curvature of
20mm to facilitate the cleaning and sterilization operations.
• All welds are ground, smoothed, and polished.
• All stainless steel components, welded using TIG method.
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www.comecer.com
Water Distribution System
•
VALVES:
Membrane/Diaphragm
Valves VS. Butterly or Ball
type
•
PIPING:
Stainless Steel With Full
Pentration Weldings VS.
Plastic piping
All components should be suitable
also for aseptic applications
Avoid potential bacteria
growth in the water
distribution system!!
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ISPE Tampa Conference
22-25 February 2010
Tampa, Florida USA
Draining System
• Sanitary Valve VS. Butterfly/Ball Type
• Slope: Correct inclination >1%
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Empirical tests for WIP Mock-up
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ISPE Tampa Conference
22-25 February 2010
Tampa, Florida USA
WIP Vs. CIP
•
•
•
The isolators can be dryed using hot
air(supplyed by a dedicated HVAC)
All circuits are self-drained
CIP? Fully automated recipes
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(washing + drying)
Capillary Effect to be
considered, increases
evaporation time, ex.:
screws, rivets...
Summary
• Efficient approach to Isolator project
requires particular attention to:
• Correct integration of equipment into Isolators to ensure
optimal containment.
• Right choice of connection components, mechanical
interfaces and gaskets to minimize the risk of leaks.
• WIP distribution systems details and components, to
ensure optimal drainage and cleanability and avoid cross
contamination and bacteria growth.
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ISPE Tampa Conference
22-25 February 2010
Tampa, Florida USA
Thank You!
Loris Rinaldi, Sales Manager Americas
COMECER
429 Lenox Ave
Miami FL 33139
(305) 606-6020
Lrinaldi@comecer.com
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