ARE YOU STUCK WITH A PROCESS THAT CAN’T CHANGE?

Consider Single-Use Powder Containment for Easy, Secure, Flexible Manufacturing

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THE TREND TOWARD LEAN, AGILE MANUFACTURING

In the past decade, both pharmaceutical and

biopharmaceutical manufacturing have seen a rapid

migration from traditional manufacturing schemes 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.

• Multiproduct manufacturing lines designed for

short runs and fast product changeover.

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.

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 or moved. Furthermore, it adds another

layer of complexity to moving or modifying the enclosed

equipment it protects or isolates.

• Increased 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 10-, 15- or even 20-year operating lives

producing a single API. Typically, these plants have

dedicated equipment lined up by chemical process,

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 spacesuits 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 multilayered

polymer films and DoverPac® containment systems.

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 workflow? Do you worry that someday 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.

PRESSURE TESTING CONDUCTED TO VERIFY DOVERPAC PRODUCT INTEGRITY

Consider Single-Use Powder Containment for Easy, Secure, Flexible Manufacturing 4 / 5

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 from 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 multilayered polymer ArmorFlex films

developed by ILC Dover for its flexible containment

systems, for instance, are based on the most advanced

polymer production 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 five-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 PRACTICAL ONLY FOR RETROFITS.

True, in its early applications, flexible containment was

primarily selected for retrofit applications, where existing

equipment was being retasked 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.

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 handling 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.

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.

THREE FLEXIBLE CONTAINMENT MYTHS

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.

TRAY-DRYER FLEXIBLE CONTAINMENT ENCLOSURE

FLEXIBLE CONTAINMENT ENGINEERED TO PROVIDE ERGONOMIC INTERFACE TO GRANULATOR

Consider Single-Use Powder Containment for Easy, Secure, Flexible Manufacturing 6 / 7

FLEXIBLE CONTAINMENT INSTALLATION AND USE

To maintain their integrity, flexible containment systems must be set up properly. And that requires care on the part of

the people 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, as

they are used once and replaced. And their inherent resilience and toughness ensure the normal manipulation needed to

uninstall and install flexible film barriers will not result in failures in the film.

And to ensure proper containment during intraplant material transport and interplant 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 handled

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 been complemented by

fittings, flanges, crimp-sealing systems, stands and support

structures designed specifically for use with multilayer

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.

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.

ILC DOVER’S PROVEN CRIMPING SYSTEMS ENSURE A CLEAN AND SECURE SEPARATION EVERY TIME

CONTAINMENT INTEGRITY1

1 Based on surrogate-monitoring testing conducted by Kasai Consulting, Pharmatek’s facilities in San Diego, California, achieved the nanogram containment values shown.

2 Measured at operator breathing zone; 8-hour time-weighted average.

ILC DOVER ENCLOSURE SYSTEM

TEST MATERIAL

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)

FLEXIBLE ENCLOSURE TO FULLY SUPPORT LAB-SCALE GRANULATOR OPERATION For more information on products and services,

email customer_service@ilcdover.com,

or call +1.302.335.3911 or toll-free

+1.800.631.9567 (US & CAN).

MILL CONTAINMENT SYSTEM SUPPORTS CHARGING AND DISCHARGING

One Moonwalker RoadFrederica, DE 19946 USA

+1.302.335.3911+1.800.631.9567

customer_service@ilcdover.com

www.ilcdover.com

Since 1947, ILC Dover has built a global reputation for out-of-the-box thinking

that makes the seemingly impossible possible. Our engineered solutions solve our

customers’ most complex challenges through the creative and efficient application

of flexible materials often integrated with advanced equipment and hardware.

We look beyond the boundaries of convention to help customers see what could

be, and discover the extraordinary possibilities within everyday things. We are a

diverse company serving many markets. We are dreamers, engineers, scientists and

pragmatists — all dedicated to outperforming tradition to better mankind.

We apply our vast knowledge of materials, soft goods, film-based solutions and

design to move the world forward, from advancing spacesuits for astronauts to

developing solutions for NASA Mars missions to engineering lighter-than-air

vehicles here on Earth. We continue to pioneer the use of flexible containment

solutions to support advanced pharmaceutical and biopharmaceutical

manufacturing, and we’re revolutionizing the packaging and extraction of bulk

liquids to enhance customer profitability and sustainability.

Additionally, we create quick-deploy systems that protect cities and critical

infrastructure from floods, and design and manufacture advanced respirators to

protect against a range of chemical and biological threats.

Every day, everything we do brings new solutions to light. Are you ready to take

your vision beyond boundaries? Let’s talk.

MK

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