ISPE Great Lakes Chapter Meeting
28-29 April 2010
Kalamazoo, Michigan USA
Containment Technologies:
Applying the Hierarchy
Beth Brock, Consultant Engineer
Eli Lilly and Company
Learning Objective
Identify containment technologies and their position on the “containment hierarchy.”
Substitution or Elimination
Product modifications
Process modifications
Process equipment modifications
Localized containment
Facility provisions
Procedural controls
Administrative controls
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ISPE Great Lakes Chapter Meeting
28-29 April 2010
Kalamazoo, Michigan USA
Substitution or Elimination
• Always involves early discussions with development!
• Substitution of less hazardous chemicals, or even a less hazardous phase or concentration of the chemical (e.g., liquid vs. solid).
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Product Modification
• Also involves early discussions with development!
• Particle size
• Delivery method
• Packaging choices
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ISPE Great Lakes Chapter Meeting
28-29 April 2010
Kalamazoo, Michigan USA
Product Modification – Particle Size
Before discussion with formulation chemist.
After discussion with
Formulation chemist.
Particle Size Settling Velocity (still air)
0.01µm
0.1µm
0.3µm
3.5 inches/week
3.5 feet/week
2.5 feet/day
1.0µm
5. µm
10. µm
50. µm
100. µm
200. µm
1,000. µm
10. inches/hour
4. inches/minute
1.2 feet/minute
6. inches/second
1.3 feet/second
4. feet/second
20. feet/second
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Process Modification
• Also involves early discussions with development! (there’s a theme here…)
• Technology platform selection
• Choose technologies more suited to
CLOSED processing (e.g., roller compaction versus high shear wet granulation).
• Eliminate riskier steps if possible (e.g., milling, sieving) – are they absolutely necessary?
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ISPE Great Lakes Chapter Meeting
28-29 April 2010
Kalamazoo, Michigan USA
Process Modification (Technology Choice)
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Process Modification (better?)
Low containment.
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High containment.
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ISPE Great Lakes Chapter Meeting
28-29 April 2010
Kalamazoo, Michigan USA
Process Equipment Modification
• BEST: Purchase equipment made to be operated in a fully contained and closed manner.
• Retrofit equipment or attach components such as split butterfly valves, etc.
• Don’t forget sampling, cleaning, and maintenance!
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Process Equipment Modification
Fette Tablet Press
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Milling
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ISPE Great Lakes Chapter Meeting
28-29 April 2010
Kalamazoo, Michigan USA
Process Equipment Modification:
Discharge glovebox – Agitated Filter Dryer
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Local Containment Provisions
AFTER you’ve done all you can with the equipment itself . . .
• Enclose the process in an isolator, glovebox, glovebag, etc.
• Don’t forget ergonomics!
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ISPE Great Lakes Chapter Meeting
28-29 April 2010
Kalamazoo, Michigan USA
Local Containment Provisions
Barrier-based (glovebox, glovebag)
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Local Containment Provisions
Air-based
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ISPE Great Lakes Chapter Meeting
28-29 April 2010
Kalamazoo, Michigan USA
Glovebox examples
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Charging & Discharging Solutions
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ISPE Great Lakes Chapter Meeting
28-29 April 2010
Kalamazoo, Michigan USA
Dispensing Systems
Pack-Off Isolator
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ISPE Great Lakes Chapter Meeting
28-29 April 2010
Kalamazoo, Michigan USA
Glovebags and Flexible Enclosures
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Drum transfer system
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ISPE Great Lakes Chapter Meeting
28-29 April 2010
Kalamazoo, Michigan USA
Glovebag solution for filter change
Piping penetrations through specially designed flange connection.
Special grooved ring for attaching glovebag.
Bag-in and bag-out sleeves for clean/dirty filters.
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“Closed” Restricted Access Barrier
System (RABS) serves dual purposes
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ISPE Great Lakes Chapter Meeting
28-29 April 2010
Kalamazoo, Michigan USA
Walk-in unidirectional flow booth
Add screens or other barriers to provide more protection.
Very technique dependent.
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Real time Data: unidirectional flow booth
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ISPE Great Lakes Chapter Meeting
28-29 April 2010
Kalamazoo, Michigan USA
Facility Containment Provisions
• Architectural layout
• Product, material, and personnel flows
• Pressure zones
• Dust collection systems
• Facility cleaning provisions, cleanability of surfaces
• Gown/degown areas, showers, etc.
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Facility Provisions
Airlock
Traffic flows:
• people
• product
• equipment
• waste
Architectural separations
Support areas:
•degowning
•decontamination
•clean storage
HVAC & filtration
Emergency exit
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ISPE Great Lakes Chapter Meeting
28-29 April 2010
Kalamazoo, Michigan USA
Facility Provisions
Air locks | Area housing bag house / dust collector
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Dust Collector
Engineering Control Capabilities and
Estimated Cost Ranges
Engineering Control
Walk-in fume hood, set in place (no utilities)
Laminar flow booth, horizontal (installed & started up)
Downflow booth (installed & started up)
Downflow booth w/ screen
Flexible intermediate bulk container (FIBC)
Split butterfly valve (SBV), 316 stainless
Continuous liner: system installed (sized for180 lit drum)
/
300 mm liner, consumable cost
Single chamber glovebox
SBV w/ purge capability, 316 SS
Glovebox isolator around continuous liner
Glovebox w/ Rapid Transfer Port (RTP)
Multi-chamber glovebox w/ RTP or enhanced SBV
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Capability
(µg/m 3 )
< 5000
< 500
< 100
< 25
< 20
< 10
< 10
< 1
< 0.5
< 0.1
< 0.05
< 0.01
Estimated
Cost
$30k-40k
$75k – 300k
$300k – 400k
$300k – 430k
$75-150
$12k – 16k
$7k / $250
$75k-200k
$55k – 60k
$90k / 220k
$90k / 210k
$150k – 250k
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ISPE Great Lakes Chapter Meeting
28-29 April 2010
Kalamazoo, Michigan USA
Procedural and Administrative Controls
• Proper procedures required for ALL containment solutions!
• Administrative Controls
• Reduce the containment challenge (e.g., by reducing quantities in area).
• Restrict access to areas or set time limits on tasks.
• Personal Protective Equipment
• Alone, is the LAST RESORT!
• May be required in addition to other containment provisions.
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Recap
What technologies can you see here?
What hierarchy tiers are apparent, and what others are likely in use?
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ISPE Great Lakes Chapter Meeting
28-29 April 2010
Kalamazoo, Michigan USA
Conclusions
• Many options available.
• Do a RISK ASSESSMENT to determine your most likely areas of concern – concentrate on them first.
• Involve the operators!
• Work from the “inside out” – start with the product/material, then the primary equipment, then on to the room/facility.
• Consider cleaning, maintenance, and sampling when designing and selecting your system!
• DOCUMENT YOUR RATIONALE AND DESIGN
DECISIONS! Inspectors will look for this . . .
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Questions?
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ISPE Great Lakes Chapter Meeting
28-29 April 2010
Kalamazoo, Michigan USA
Beth Brock, Consultant Engineer
Eli Lilly and Company
Lilly Corporate Center, DC 5611
Indianapolis, IN 46285
(317) 276-6870 bethbrock@lilly.com
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