ISPE Great Lakes Chapter Meeting
28-29 April 2010
Kalamazoo, Michigan USA
Containment Basics “101”
Beth Brock, Consultant Engineer
Eli Lilly and Company
Learning Objectives
• At the conclusion of this session,
participants will be able to:
• Understand the basic terminology used in
“containment engineering.”
• Identify the stakeholders for containment.
• Understand fundamental concepts, such
as material migration and risk.
• Understand the containment hierarchy of
controls.
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ISPE Great Lakes Chapter Meeting
28-29 April 2010
Kalamazoo, Michigan USA
What is CONTAINMENT?
Containment: the
isolation of the raw
materials, and
subsequently the
finished goods, from
personnel, the
environment, and
adjacent products.
Containment
Product
People
Containment
Environment
Operation
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Containment Definitions
Emissions: Egress of a compound from the
designated containment system or other control volume.
Emissions may take the form of airborne, surface
residue, or powders contained in liquid.
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ISPE Great Lakes Chapter Meeting
28-29 April 2010
Kalamazoo, Michigan USA
Containment Definitions
Isolation: limiting compound migration to the people
and to the environment to below a defined threshold
will be taken to mean the product is isolated.
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Containment Definitions
Barrier: A device that protects product, people or the
environment by providing a physical impediment to
reduce levels of emissions and contamination.
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ISPE Great Lakes Chapter Meeting
28-29 April 2010
Kalamazoo, Michigan USA
Is this new?
NO!
•1897 – Downflow
bench Anthrax control
•1877 – Grinding Wheel LEV
•1726 – Wet grinding of flint
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History of Containment
nuclear
electronics
asbestos abatement
sterile chemical
medical
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ISPE Great Lakes Chapter Meeting
28-29 April 2010
Kalamazoo, Michigan USA
History
Containment as a Health and Safety issue.
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History
•The processing room becomes the
containment device.
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ISPE Great Lakes Chapter Meeting
28-29 April 2010
Kalamazoo, Michigan USA
History
Reliance on PPE increases.
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History
Containment of emissions at the source.
Pandora
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ISPE Great Lakes Chapter Meeting
28-29 April 2010
Kalamazoo, Michigan USA
Stakeholders – who cares about
containment?
• Health and Safety – protection of the workers.
• Prevent worker exposure.
• Quality – protection of the product (patient safety).
• Avoid cross-contamination
• Environmental – protection of the environment
• Prevent emissions to water, air, land surrounding the plant.
• Operations – prevent product loss and production
interruptions ($$$).
“Limits” are set differently for each of these
stakeholders …
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Next, Some Fundamental Concepts
•
•
•
•
Contain at the source
Containment challenge
Material migration
Measurement criteria for 3 differing
stakeholders
• Risk
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ISPE Great Lakes Chapter Meeting
28-29 April 2010
Kalamazoo, Michigan USA
Contain at the Source
A mill is in an isolated room with
uniflow ingress and egress, room
airlocks at entry and exit points,
pressurization cascades, HEPA
filtered HVAC system, gown /
degown / decontamination regimes,
and validated air monitoring
protocol.
•Emergency
Exit
Ongoing testing indicates “below the
threshold” outside the room airlock.
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Contain at the Source
The same mill now has a
glovebox around it. The
glovebox is provided with HEPA
filtered air, has appropriate
pressurization cascade, and is
double-gloved.
Ongoing testing indicates
“below the threshold” outside
the glovebox.
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ISPE Great Lakes Chapter Meeting
28-29 April 2010
Kalamazoo, Michigan USA
Contain at the Source
Again the same mill, now
with retrofitted housing and
gaskets, negative
pressurization within the
mill, and contained charge
and discharge.
Ongoing testing indicates
“below the threshold”
outside the mill.
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Containment Challenge
What filters more effectively:
A HEPA filter
or
Chicken wire?
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ISPE Great Lakes Chapter Meeting
28-29 April 2010
Kalamazoo, Michigan USA
Containment Challenge
What filters more effectively:
HEPA filter challenged with 10,000
0.3 µm particles?
or
Chicken wire challenged with 10,000
golf balls?
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Material Migration
Assume you have a quantity of lead
and an equal quantity of talc.
Which is more difficult to contain?
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ISPE Great Lakes Chapter Meeting
28-29 April 2010
Kalamazoo, Michigan USA
Material Migration
Assume you have an open conveying belt
transporting lead particles of 100 µm diameter,
and another open line conveying an equal mass
of talc particles of 1 µm diameter. You’re goal is
to control the emissions of each to the same
level.
Which line do you think will be a bigger
headache to contain?
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Material Migration
Particle Size
Settling Velocity (in still air)
0.01µm
3.5 inches/week
0.1µm
3.5 feet/week
0.3µm
2.5 feet/day
1 µm
10 inches/hour
5.0 µm
4 inches/minute
10 µm
1.2 feet/minute
50 µm
6 inches/second
100 µm
1.3 feet/second
200 µm
4 feet/second
1000 µm
20 feet/second
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ISPE Great Lakes Chapter Meeting
28-29 April 2010
Kalamazoo, Michigan USA
Material Migration
•Migration: many “vectors” or “pathways”
•Two major modes:
• Airborne.
• Dust or aerosolization of a liquid.
• Mechanical conveyance.
• Physical tracking.
• Liquid conveyance (e.g., as a solution).
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Measurement Criteria
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ISPE Great Lakes Chapter Meeting
28-29 April 2010
Kalamazoo, Michigan USA
Risk
Risk is a function of:
the likelihood of possible undesired
events, and
the magnitude (severity) of their
associated consequences.
In other words
how often and how bad?
Practically speaking, no such thing as “zero”!
Not zero emissions, not zero risk.
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Risk Assessment
• Regulators (e.g., FDA, EMA) initiatives
To
improve the regulatory and quality control systems
for pharmaceutical products, using a sciencebased, documented, risk management
approach.
• ICH Q9
• RiskMAPP
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ISPE Great Lakes Chapter Meeting
28-29 April 2010
Kalamazoo, Michigan USA
Containment Hierarchy
Address risk by
applying the
hierarchy of
controls
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Sourcecontainment
Hierarchy of containment technologies
Substitution / Elimination
Product modifications
Process modifications
Process Equipment modifications
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ISPE Great Lakes Chapter Meeting
28-29 April 2010
Kalamazoo, Michigan USA
Sourcecontainment
Engineering Controls
Hierarchy of containment technologies
Substitution
Product modifications
Process modifications
Process Equipment mod’s
Localized containment provisions
(gloveboxes, glovebags, different types
of exhaust mechanisms)
Facility provisions
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Sourcecontainment
Engineering Controls
Emissions Controls
Hierarchy of containment technologies
Substitution
Product modifications
Process modifications
Process Equipment mod’s
Localized containment provisions
Facility provisions
Procedural controls (and Training)
Administrative controls
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ISPE Great Lakes Chapter Meeting
28-29 April 2010
Kalamazoo, Michigan USA
Hierarchy of containment technologies
Substitution / Elimination
Product modifications
Process modifications
Equipment modifications
Localized containment
Facility provisions
Procedural controls
Administrative controls
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RiskMaPP Hierarchy of Control
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ISPE Great Lakes Chapter Meeting
28-29 April 2010
Kalamazoo, Michigan USA
Questions?
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Thank You!
Beth Brock, Consultant Engineer
Eli Lilly and Company
Lilly Corporate Center, DC 5611
Indianapolis, IN 46285
(317) 276-6870
[email protected]
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