are you stuck with a process that can’t change? consider...
TRANSCRIPT
Are you stuck with a process that can’t change?
Consider Single-Use Powder Containment for Easy, Secure, Flexible Manufacturing
Single-use Powder Containment for Easy, Secure, Flexible Manufacturing
Can you easily modify containment schemes and switch equipment
to suit a changeover to a new drug product? If the new drug product
doesn’t require containment, can you easily and inexpensively
remove the existing containment system so it doesn’t disrupt
the new work flow? Do you worry that some day a failure in
your containment system cleaning procedures might lead to
cross-contamination and all the financial and health-safety risks
that come with it?
If any of these questions trouble you, you should learn more about
flexible containment.
The trend toward lean, agile manufacturing
In the past decade, both pharmaceutical and biopharmaceutical
manufacturing have seen a rapid migration from traditional
manufacturing schemas to lean, agile or flexible manufacturing.
The changes have affected not only organizational dynamics and
structural philosophies within the industry, but also the details of
manufacturing approaches and the equipment required to remain
competitive.
The trends representing the most significant changes are these:
• Development of distributed manufacturing, whereby drugs are
made in facilities close to user populations. These plants focus
on smaller production runs of a broader array of pharmaceuticals
and biopharmaceuticals tailored to the health issues and genetics
of the surrounding regional populations.
• Increased use of contract manufacturing partners by large,
integrated firms
• Multi-product manufacturing lines, designed for short runs and
fast product changeover
• Increasing emphasis on cost management as the route to profit
• Continuing quality and patient-safety concerns within a stringent
regulatory environment and litigious atmosphere
In the United States, particularly, changes in the regulatory
environment effectively shortened the patent-protected
commercial phase of most drugs’ life cycles, which in turn has
exacerbated or accelerated these trends, if it didn’t actually spur
their creation.
The implications for containment
A decade ago, before these trends became prevalent, most API
manufacturing was carried out by large, integrated companies that
controlled the product from initial research characterization to final
packaging and shipping to user locations globally.
In that paradigm, manufacturing plants were most often designed
for ten-, fifteen- or even twenty-year operating lives producing
a single API. Typically, these plants have dedicated equipment
lined up by chemical process, facilitating a seamless flow of API
from one piece of equipment to the next. When a new drug was
developed and launched, a new plant was designed and built,
irrespective of the utilization rate of existing plants.
DoverPac® system being SMEPAC-tested to establish containment performance
2
Where containment was required, it was typically provided by
cabinets, barriers and fittings made of a combination of Type 316
stainless steel and glass, with occasional flexible sleeves and
gloves for manual manipulation within the containment. Rigid
containment and rigid packaging were the norm. And for the
long-run manufacturing plant, it was the most efficient and cost-
effective method.
However, as the flexible manufacturing trend continued to morph
away from the traditional model, the old, rigid containment
scheme began to reveal serious weaknesses.
Manufacturing has become much more flexible; stainless steel-
and-glass containment has not. Once built, it is not easily modified
nor moved. Furthermore, it adds another layer of complexity to
moving or modifying the enclosed equipment it protects
or isolates.
Enter flexible (single-use) containment
As far back as the late ’90s, during the early move to agile
manufacturing, the need arose for containment systems that were
more adaptable and efficient than rigid systems were at that time.
ILC Dover was among the early developers of flexible systems. Its
solution combined its polymer film and fabric technology with the
joining expertise it developed while creating the most challenging
of flexible barriers—the space suits used by all U.S. astronauts
from the Apollo missions onward.
With that technology as the foundation, the company explored
polymer formulations that would withstand the rigors of a
manufacturing environment, remain impervious to chemical
degradation in the face of most common solvents, and yet be
inexpensive enough to make single-use containment economically
viable.
The result: ILC Dover’s ArmorFlex® Series multi-layered polymer
films and DoverPac containment systems.
Three flexible containment myths
While the technology used in developing flexible containment
systems represents some of the most advanced available and
performance has been established in literally thousands of
successful installations with years of data as proof, certain myths
persist.
Myth #1: You’re
paying a lot of
money for a “bag”
It’s natural enough.
Nearly everyone
has had a plastic
grocery bag rip
through under the
load of a simple
carton of milk or a
box of detergent. Associate a flexible containment vessel with that
experience, and it would seem hard to justify the price.
However, flexible containment systems could hardly be
considered such a simplistic “plastic bag,” and a careful
evaluation will show the true value and impressive performance
characteristics of flexible systems.
Just as an automotive airbag’s system elements—its g-sensors,
pyrotechnics and venting systems—elevate it far above a simple
“burlap sack,” the stainless steel grooved canisters, precision
o-rings, 316SS supporting clamps and proven crimping system
for separating and sealing flexible polymeric enclosures raise a
flexible pharmaceutical containment system far above the humble
“plastic bag.”
Furthermore, the multi-layered polymer ArmorFlex® films
developed by ILC Dover for its flexible containment systems, for
instance, are based on the most advanced polymer production
Pressure testing conducted to verify DoverPac®product integrity
3
Now, agile manufacturing dictates that production lines be
flexible, capable of being switched quickly to different drug
products, able to run smaller batches profitably with maximum
versatility in handlwing incoming raw materials, and process
material transfers, equipment isolation and end-product packaging.
Rigid systems provide exactly the wrong kind of containment for
current manufacturing schemes. Once in place, they’re difficult and
expensive to remove, adding another layer of complexity to the
production of drug products that don’t require containment.
Flexible containment systems, on the other hand, offer just the
right mix of economy, agility and performance. They can be
designed from inception for easy installation and removal, so
containment is available when needed and not in the way when it
isn’t.
If life-cycle costs are calculated and flexible containment’s ability to
provide the competitive edge in plant configurations is considered,
it becomes obvious flexible containment can bring increased
profitability to new plant construction as well as to retrofit applications.
technology available. The films are regularly tested and proved
to meet or exceed the requirements of virtually all applicable
standards and regulatory compliance requirements.
These include:
• FDA 21 CFR
• 2002/72/EC
• EP 3.1.3 for food
• USP <661> physiochemical tests for plastics
• USP <88> Class VI (7-day implant)
• USP <87> biological reactivity, in vitro
Moreover, several ArmorFlex films provide permanent static
dissipative properties and pass Chilworth incendivity tests, and all
offer a 5-year shelf life. Tensile strength is in the range of 6,500 psi,
minimum, and tear strength is approximately 470 ppi.
DoverPac films are also tested for specific solvent resistance against
a broad array of chemicals used in pharmaceutical production.
The net result is a film that, when used to form a plastic container,
does not rip or split under load, forms a leak-free barrier and does
not leach contaminants into the contents it holds.
Moreover, films like ILC ArmorFlex can be quickly and ergonomically
designed into a virtually limitless variety of system configurations
to provide robust containment for any process.
Myth #2: Flexible containment is only practical for retrofits
True, in its early applications, flexible containment was primarily
selected for retrofit applications, where existing equipment was
being re-tasked to produce a new drug with new containment
requirements. With its much lower first cost and easier installation,
a flexible system was often much more economical than trying to
modify an existing rigid (316SS and glass) system or build a new
one for short-term use.
Single-use Powder Containment for Easy, Secure, Flexible Manufacturing
Tray dryer flexible containment enclosure
4
Myth #3: Bags can’t possibly
provide sufficient containment
This is perhaps the most
egregious of the flexible
containment myths. While all
flexible containment system
manufacturers may not be able
to substantiate the containment
integrity and performance of
their systems, ILC Dover has
successfully documented the integrity of its films and containment
systems down to the nanogram level.
Flexible containment installation and use
To maintain their
integrity, flexible
containment sys-
tems must be set
up properly. And
that requires care
on the part of the
persons doing the
set-up work. However,
the procedures are
straightforward.
With basic training
typically provided
by the flexible
containment system
supplier, the average
workers employed in
pharmaceutical and
biopharmaceutical manufacturing have shown they can master the
procedures quickly.
Moreover, unlike rigid containment equipment,
flexible containment systems require no
complex cleaning procedures, but are
used once and replaced. And their inherent
resilience and toughness assure the normal
manipulation needed to uninstall and install
flexible film barriers will not result in failures
in the film.
And to assure proper containment during
intra-plant material transport and inter-plant
shipping, ILC Dover has developed an
extremely effective, easy-to-use, proprietary
crimping system for containment closure.
Flexible containment—product options
Today, virtually any containment scenario
can be effected using flexible systems.
Not only have a wide range of films been
developed that provide a selection of physical
strength, chemical resistance and permanent
antistatic properties, but they also have Flexible drum transfer system designed to provide complete isolation during drum opening, conveying to charging position and drum removal. Note the ease with which this charging station could be added to or removed from the process operation.
Containment Integrity1
ILC DoverEnclosure System
TestMaterial
OBZ-TWA2
(µg/m3)Comment(No. of Operators)
Granulator Lactose 0.0026–0.0027 Operation (2)
Granulator Lactose 0.0027–0.0331 Cleaning (2)
Drying Oven Lactose 0.0026–0.0028 Operation (2)
Drying Oven Lactose 0.0026–0.0037 Cleaning (3)
1 Based on surrogate-monitoring testing conducted by Kasai Consulting, Pharmatek’s
facilities in San Diego, CA, achieved the nanogram containment values shown.2 Measured at operator breathing zone; 8-hour time-weighted average.
Mill Containment System supports charging and discharging.
5
Flexible containment engineered to provide ergonomic interface to granulator
been complemented by fittings, flanges, crimp-sealing systems,
stands and support structures designed specifically for use with
multi-layer flexible membranes.
Where needed, complete flexible rooms can be quickly erected
within a facility, and drum transfer and reactor charging systems
can be added to handle incoming ingredients or to safely move
materials from one plant area to another to allow maximum
flexibility in the arrangement of process equipment within a given
building footprint.
Dispensing to weight can be achieved by including a scale under
the pallet that holds the receiving DoverPac or other vessel.
Easy scalability is also a consideration in designing containment
systems. Flexible containment systems designed for laboratory-
scale processes can be quickly scaled to process-level equipment.
Flexible containment systems can be designed to handle a wide
variety of containment duties in laboratory or production scale,
including:
• Blender enclosures
• Tablet presses and coaters
• Mill containment systems
• Material transfer
• Dispensing to weight
• Drum transfer systems for reactor charging
• Final packaging
• Media and buffer preparation
• Lypholization
Moreover, the relatively low cost of flexible containment barriers
means making ergonomic adjustments in the field after installation
is economically feasible. For instance, say a set of gloved sleeves
is integrated into a barrier sidewall, but proves to be six inches
too high to be comfortable for most workers in the plant. Revising
its location on the next barrier is achieved simply by adjusting
the CAD drawings and fabrication instructions before its manufacture.
Trying to make such adjustments with rigid systems would be
prohibitively expensive.
Flexible Enclosure to fully support lab scale granulator operation
Single-use Powder Containment for Easy, Secure, Flexible Manufacturing
ILC Dover’s proven crimping systems assure a clean and secure separation every time.
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Recap—flexible containment’s place in lean, agile
manufacturing
With the competitive pressures you face, whether you are involved
in pharmaceutical or biopharmaceutical operations, adopting flexible
containment schemes means increasing profit. But importantly,
you address the profit eating factors such as minimizing cross-
contamination that ensures patient safety and maximizing containment
that ensures operator safety.
The alternative is to install a rigid containment system that will
eventually become a monument to a product you no longer make.
ABOUT ILC DOVER ILC Dover is a world leader in the innovative design and production
of engineered products employing high-performance flexible materials.
Since 1947, ILC has provided engineered solutions to complex
customer problems. Known for the production of space suits
for NASA, we leverage our vast materials, engineering, process,
and design experience to create high performance systems for
a wide range of industries. For more information about ILC Dover,
call 1-800-631-9567 or visit www.ilcdover.com
Contact Information
For information on products and services:
Visit www.ilcdover.com
E-mail: [email protected]
General:
Tel: +1 (302) 335-3911
Fax: +1 (302) 335-0762
Sales & Customer Service
Tel: +1 (302) 335-3922 ext. 506 or
1-(800) 631-9567 (US Toll Free)
7
One Moonwalker Road
Frederica, DE USA 19446-2080
(302) 335-3911
(800) 631-9567
www.ilcdover.com
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