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methods such as heat (steam and dry) sterilization and

several chemical and gas plasma methods represent a

very small share of the market. However, these other

methods offer efﬁciency, safety, and cost beneﬁts which

may make them attractive for particular segments of

device sterilization.

Ethylene Oxide (EtO) Sterilization. EtO gas is an effec-

tive sterilant that causes cell death by denaturating of the

proteins within it. The process does not cause discolora-

tion and embrittlement of the packaging. However, it

represents a major source of package stress and loss of

seal integrity (seal fatigue or sterilizer creep). The higher

stresses are induced by higher temperatures, pressures,

and humidity during sterilization. In addition, the EtO

residual level must be carefully monitored in order to

prevent patient harm. The key criteria for packaging

materials used in EtO sterilization are: porosity, hot

adhesive strength, moisture and EtO tolerance, and broad

product and chemical compatibility (9).

Radiation (Gamma and Electron Beam) Sterilization. Ra-

diation is used to break up a microorganism’s DNA

molecules so that it cannot multiply. It is a fast and

effective method for killing bacteria which leaves no toxic

residue after the process is complete, eliminating many of

the problems of EtO (heat, moisture, pressure, and che-

micals). Since radiation processes do not require gas

porous materials, all-plastic ﬁlm packaging is suitable

for this process. However, Tyvek

may be used in radia-

tion applications because of its other high-performance

characteristics, radiation resistance, and historic use.

Material compatibility is an issue since gamma radiation

may discolor or embrittle some polymers and some papers

may yellow. When using gamma radiation, packagers

need to focus on the effect of radiation on the package’s

properties, such as tensile strength, elastic modulus,

impact strength, elongation, and color.

Heat Sterilization. Heat sterilization is one of the oldest

techniques for killing bacteria. There are three types of

heat sterilization methods. One involves the use of moist

heat (high-pressure, saturated steam) as the sterilant; the

second employs an autoclave to heat liquid already inside

the package; and the third uses dry heat in an oven. The

energy from the heat causes the coagulation of proteins in

the cells, which, in turn, causes the microorganism’s

death. Steam under pressure is an effective sterilization

method; the equipment needed is available in a wide

range of sizes and prices, and there are no harmful

byproducts from the process, although the whole cycle

takes little time.

The major disadvantage is that it needs high tempera-

tures that will deform plastics such as poly(vinyl chloride),

polystyrene, polyethylene, and some synthetic fabrics.

Fortunately, there are plastic materials that can tolerate

varying levels of heat, these include nylon, polypropylene,

oriented polyester, polycarbonate, and some grades of

high-density polyethylene. Special precautions must be

taken with Tyvek

since it is composed of HDPE ﬁbers

that melt at approximately 2651F. If sterilizer conditions

are closely controlled between 2501F and 2551F, packages

containing Tyvek

may be safely steam-sterilized.

The key criteria for packaging materials used in steam

sterilization are (a) porosity (to allow the steam to pass

through the package and contact the device), (b) seals and

materials that can withstand high humidity at elevated

temperatures, (c) bacterial barrier, (d) reactivity (so that

product and package don’t interact), and (e) the cost-

effectiveness of proposed designs.

Packages that will sterilize devices via autoclave ster-

ilization must contain water inside the sterile barrier

system, have the barrier properties necessary to contain

that water and provide a bacterial barrier, be nonreactive

with the product, be able to withstand high humidity at

elevated temperatures, and be cost-effective.

In a dry heat sterilization process, a package is sub-

jected to controlled elevated temperatures (typically in

excees of 3001 F) for several hours. Silicone implants are

sterilized using this technique.

Gas Plasma Sterilization. Low-temperature gas plasma

(LTGP) provides an excellent alternative to EtO for ster-

ilizing devices that are heat-sensitive and not radiation-

stable. This is due, in large part, to its short sterilization

cycles, negligible environmental impacts, and lack of

aeration cycle (12). During this process ‘‘an aqueous

hydrogen peroxide solution boils in a heated vaporizer

and then ﬂows as a vapor into a sterilization chamber

containing a load of instruments at low pressure and low

temperature’’ (13).

LEGISLATION, REGULATION, AND TEST STANDARDS

The systems surrounding the production of medical de-

vices aim to maximize therapy safety and efﬁcacy while

minimizing cost. As a result, in most countries through-

out the world, professionals in the device industry must

demonstrate, with a high degree of conﬁdence, that the

products that they are producing are safe and effective.

However, this must be done in an economy where cost-

competitiveness is increasingly important and ballooning

healthcare costs are creating concerns.

The question becomes, How do you ensure safety and

efﬁcacy and remain affordable? The solution generally

involves using a scientiﬁc approach to design, production,

and testing by using data to draw conclusions about the

possibility of harm from a given device and/or lot. To do

this, a variety of test standards are employed as the device

and its packaging are developed.

Test Standards

The International Organization for Standardization (ISO).

The International Organization for Standardization (ISO)

has two standards regarding what type of information

should be gathered to ensure the packaging of terminally

sterilized medical devices performs as expected. The ﬁrst,

718 MEDICAL DEVICE PACKAGING

entitled ‘‘Packaging for Terminally Sterilized Medical

Devices—Part I: Requirements for Materials, Sterile Bar-

rier Systems, and Packaging,’’ ‘‘speciﬁes the basic attri-

butes required of materials and pre-formed systems

intended for use in packaging systems for terminally

sterilized medical devices while considering the wide

range of potential materials, medical devices, packaging

system designs and sterilization methods.’’ The second

document, ‘‘Packaging for Terminally Sterilized Medical

Devices—Part 2: Validation Requirements for Forming,

Sealing, and Assembly Processes,’’ describes the validation

process for forming, sealing, and assembly of the SBS.

Validation refers to the need to systematically gather data

through scientiﬁcally reliable means and interpret the

data to determine that a process is capable of yielding the

expected outcome.

Many organizations throughout the world have

adopted the ISO standards (ISO11607 parts I and II).

Among them are the Association for the Advancement of

Medical Instrumentation (AAMI) and the American Na-

tional Standards Institute (ANSI). AAMI went so far as to

produce a Technical Information Report (TIR 22:2007)

that provides guidance on implementing the ISO 11607

documents. Included in the TIR are the test methods

typically used to indicate compliance with the require-

ments in the ISO standards (14). In general, the ISO

documents indicate that:

. Package materials should be qualiﬁed.

. Packages should be tested.

. Processes should be validated.

These three things must be accomplished in order to

ensure that the product is protected, the system is

sterilized, and the sterility is maintained throughout

distribution. (15) The ‘‘ISO strategy was to develop a

single standard that addressed the required performance

attributes of medical packaging without establishing spe-

ciﬁc performance criteria’’ (14). The material qualiﬁcation,

package testing, and process validation dictated by the

ISO standards are all accomplished using data that are

collected using relevant standards from a variety of

organizations. See Table 3 for the types of tests that are

conducted under these broad categories (15).

The use of standardized tests to qualify materials, test

packages, and show evidence of controlled processes has

several beneﬁts. ‘‘Standardization of test methods allows

laboratories to reduce the number of speciﬁc methodolo-

gies while retaining the overall capability. In addition,

standardized test methods allow individual laboratories to

assess their own capabilities against the stated intra

laboratory variability’’ (14). The results provided from

standardized tests should be comparable to those sub-

mitted by others, or obtained at different points in time.

The United States. Devices manufactured or sold in the

United States are regulated by the U.S. Food and Drug

Administration (FDA). Within the FDA, the Center for

Devices and Radiological Health (CDRH) is responsible for

drafting the speciﬁc requirements for the design, manu-

facturing, and packaging of medical devices. Among the

key documents containing legislation and regulation of

medical devices are:

. The Federal, Food, Drug, and Cosmetic Act of 1938

. The Medical Device Amendments of 1976

. The Design Control Guidance for Medical Device

Manufacturers

Table 3. ISO Mandates. Types of tests conducted for material qualiﬁcation, package testing, and process validation

Categories Tests

Material

qualiﬁcation

Microbial barrier

Toxicity/biocompatibility/particulates

Physical and chemical properties, as dictated by product

requirements (extractables, retained solvents, etc.)

Barrier properties

Compatibility with the sterilization process

Compatibility with the forming and sealing process

Visibility and appearance

Requirements for shelf life

Package testing Package performance Distribution, handling, and storage

Integrity (microbial and physical)

Strength (burst, tensile, etc.)

Validation Installation Installed correctly? Operating as expected after

installation?

Operational What are the process control limits? What are the

actionable levels necessary in order to produce

product meeting predetermined requirements?

Performance Does the product, when produced under the expected

conditions of production, consistently meet the

predetermined requirements?

Source: Adapted from Miller (15).

MEDICAL DEVICE PACKAGING 719

. The Quality Systems Regulations (QSR), which are

located in 21CFR Part 820

The QSR document dictates the documented use of a

quality system and the veriﬁcation and/or validation of

the system’s ability to produce expected results. Documen-

tation to meet these objectives heavily relies on data

collected through standardized test methods. Test stan-

dards commonly used in the United States come from a

variety of organizations. These include: ASTM Interna-

tional, the United States Pharmacopeial Convention

(USP), the Technical Association of the Paper and Pulp

Industry (TAPPI), and the International Safe Transit

Association (ISTA). Standards that are frequently used

to develop, test, and monitor SBS are indicated in Table 4.

The European Union (EU). In the European Union (EU),

devices are regulated through a series of measures that

are part of the ‘‘New Approach Directives.’’ Directives

relating to medical devices include: the Medical Devices

Directive (MDD), the Active Implantable Medical

Devices Directive (AIMD), and the In vitro Diagnostics

Directive (IVDD). Compliance with the European Direc-

tives is signiﬁed through the use of a CE marking and

declaration of conformity.

The EU authorized the Committee for European Nor-

malization (CEN) to establish standards for compliance

with European Directives. Previously, this was EN 868-1,

‘‘Packaging Materials and Systems for Medical Devices

which Are to Be Sterilized—Part 1: General Requirements

and Test Methods,’’ this has since been replaced by the two

ISO standards previously discussed. A series of vertical

standards provide speciﬁc performance requirements and

test methods for materials typically used in the packaging

of medical devices (see Table 5).

CHALLENGES FACING THE MEDICAL DEVICE INDUSTRY

As indicated previously, the device industry invests heav-

ily in R&D and has historically been characterized by

innovation. That said, ‘‘traditional innovation is no longer

sufﬁcient to win in this competitive game’’ (4). The aging

of the population, escalating healthcare costs, rising ex-

pectations, problems within the supply chain, and ﬁerce

competition have created a climate where the designers of

medical devices and their packaging face a host of pres-

sures and considerations as they make design choices.

The Aging of the Population

It is estimated that by the year 2050, over 5% of the U.S.

population will be over the age of 85. The aging trend is

not limited to the United States, but is a global phenom-

enon that warrants the consideration of those that design

packaging for all types of products (see Figure 3).

Not only do aging consumers use medical products at a

higher per capita rate than the general population, they

are at risk from inappropriate product use for a variety of

reasons. They are likely to have various chronic disorders

that create the need to engage in multiple, complex

therapies on a daily basis. Further complicating things

is the fact that older consumers are also more likely to be

experiencing mental, physical, and perceptual declines

(see Figure 4).

This has prompted people like Patricia P. Barry, MD,

MPH, and Executive Director at the Merck Institute

of Aging, to issue a call to industry to begin thinking

differently. In The State of Aging and Health in America

(16), Barry indicated:

‘‘The demographic tidal wave is coming. Aging in the 21st

century, however, is more than just a matter of numbers. The

average 75-year-old has three chronic conditions and uses ﬁve

prescription drugs. Older consumers have different challenges

and medical needs than younger adults. Consequently, it is not

enough to be aware of the demographic imperative; we must

also be prepared for it’’ (16).

These trends have obvious ramiﬁcations for the de-

signers of devices that are sold over the counter; however,

this changing demographic also has impact for those that

are sold for institutional use; increasing life spans will tax

healthcare as we know it. As such, designs that catalyze

system-wide efﬁciencies will become paramount.

Medication Errors and Patient Noncompliance

It is well documented, both in human and ﬁnancial terms,

that medical errors are a major problem in healthcare

facilities throughout the world (17–19). At the turn of the

20th century, the Institute of Medicine (IOM) published

‘‘To err is human,’’ reporting that in between 44,000–

98,000 people in America die each year as the result of

medication errors. ‘‘Even when using the lower estimate,

deaths due to medical errors exceed the number attribu-

table to the 8th leading cause of death. More people die in

a given year as a result of medical errors than from motor

vehicle accidents (43,458), breast cancer (42,297), or AIDS

(16,516)’’ (20).

This comes at a signiﬁcant cost; estimates for U.S.

ﬁgures include the expense of additional care that is

necessitated by the errors, as well as lost income and

household productivity from resultant disability. These

have been estimated at US$ 17–29 billion annually. Esti-

mates for the cost of an adverse drug event (ADE) for each

patient range from US$ 2000–5000 (21).

These problems are certainly not limited to the United

States. Estimates from the United Kingdom indicate

that ‘‘about 10% of inpatient episodes result in errors of

some kind, about half [of which] are preventable’’ (17). A

study published by Vincent et al. suggested that of the

approximately 8 million hospital admissions that occur in

England each year, about 850,000 result in a patient

safety incident, costing the National Health Service

(NHS) approximately d2 billion in extra hospital days

(17, 22).

Issues of package and label design have been impli-

cated as a signiﬁcant part of the problem. The 2000 IOM

report, which made numerous recommendations for im-

proving the American healthcare system, stated that

‘‘drugs may be prone to error in use due to sound-alike

or look-alike names, unclear labeling or poorly designed

720 MEDICAL DEVICE PACKAGING

Table 4. Standards and tests used to develop, test, and monitor sterile barrier systems in the United States

Categories Standards/Tests

General ASTM International F2097: Standard guide for design and

evaluation of primary ﬂexible packaging for medical products

ASTM F99: Standard guide for writing a speciﬁcation for ﬂexible

barrier materials

ASTM F2559: Standard guide for writing a speciﬁcation for

sterilizable peel pouches

Material

qualiﬁcation

Microbial barrier ASTM F 1608: Standard test method for microbial ranking of

porous packaging materials (exposure chamber method)

ASTM F2638: Standard test method for using aerosol ﬁltration

for measuring the performance of porous packaging materials

as a surrogate microbial barrier.

Biocompatibility ISO 10993, Part 1: Biological evaluation of medical devices:

evaluation and testing

ASTM F2475: Standard guide for biocompatibility evaluation of

medical device packaging materials

USP o87W Biological reactivity testing, in vitro

USP o88W Biological reactivity testing, in vitro

USP o1031W Biocompatibility of materials used in drug

containers, medical device, and implants

Particulates ASTM D 2019: Standard test method for dirt in paper and

paperboard

TAPPI T-437: Dirt in paper and paperboard (TAPPI dirt chart)

AAMI TIR DP 01 Ed. 1 Particulates associated with vascular

medical devices (in progress)

ASTM D726: Standard test method for resistance of nonporous

paper to passage of air (Guriey test for low porosity)

Barrier (porous) TAPPI T 536: Resistance of paper to the passage of air (HP

method) (Gurley test method for medium porous materials)

TAPPI T460: Air resistance of paper (Gurley test method for

highly porous materials)

Barrier

(Nonporous)

ASTM F 2097: Standard guide for design and evaluation of

primary ﬂexible packaging for medical products (complete

listing of test methods at ASTM)

Durability ASTM F 2097: Standard guide for design and evaluation of

primary for medical products contains numbers for tests that

can be used to characterize puncture and tear resistance,

thickness, tensile, ﬂexural durability, basis weight, bond

strength, and aging

Processing ASTM D1894: Standard test method for static and kinetic

coefﬁcients of friction of plastic ﬁlm and sheeting

ASTM F 2029: Standard practices for making heat seals for

determination of heat sealability of ﬂexible webs measured by

seal strength

ASTM F 2217: Standard practice for coating/adhesive weight

determination

Visibility and

appearance

ASTM D1003: Haze ASTM D 2457: Gloss ASTM D 589: Opacity

ASTM D 5264: Standard test method for abrasion resistance of

printed materials by the Sutherland rub tester

ASTM F 2250: Standard practice for the evaluation of chemical

resistance of printed inks and coatings on ﬂexible packaging

materials

ASTM F 2252: Standard practice for evaluating ink or coating

adhesion to ﬂexible packaging materials using tape

Package testing Integrity ASTM F1886: Standard Test Method for Determining Integrity of

Seals for Medical Packaging by Visual Inspection

ASTM F1929: Standard Test Method for Detecting Seal Leaks in

Porous Medical Packaging by Dye Penetration

ASTM F 2391-05: Standard test method of measuring package

and seal integrity using helium as the tracer gas

ASTM F2338: Standard test method for nondestructive detection

of leaks in packages by vacuum decay method

(Continued)

MEDICAL DEVICE PACKAGING 721

packaging’’ (18). This was reiterated in the 2006 IOM

report, which indicated ‘‘drug information is communi-

cated through labeling and packaging, marketing prac-

tices and advertisements. Poorly designed materials

and inadequate representation of risks and beneﬁts to

providers and consumers have led to many errors’’ (19).

Other organizations have echoed these sentiments.

A study conducted by the United States Pharmacopeia

indicates, ‘‘USP investigators calculated that confusing

labeling or packaging of drug products contributed to

more than half of the incidents [of error]’’ (23).

Although there are systems in place for the voluntary

and mandatory reporting of adverse incidents associated

with medical devices, ‘‘they are limited by underreporting

Table 4. Continued

Categories Standards/Tests

ASTM F 2228: Standard test method for non destructive detection

of leaks in medical packaging which incorporates porous

barrier material by CO

tracer gas method

ASTM F 2227: Standard test method for non destructive detection

of leaks in non-sealed and empty medical packaging trays by

tracer gas method

ASTM F 2096: Standard test method for detecting gross leaks in

porous medical packaging by internal pressurization (bubble

test)

Strength ASTM F 2029: Standard practices for making heat seals for

determination of heat sealability of ﬂexible webs measured by

seal strength

ASTM F 88: Standard test method for seal strength of ﬂexible

barrier materials

ASTM F 2054: Standard test method for burst testing of ﬂexible

package seals using internal air pressurization within

restraining plates

Source: Adapted from Miller (15) and Larsen (36).

Table 5. Vertical European Standards for Medical Packaging EN 868 Series

Standard Title

EN 868-2: 1999 (Sterile

wrap)

Packaging materials and systems for medical devices which are to be sterilized, Part 2:

Sterilization wrap—Requirements and test methods

EN 868-3:1999 (Paper for

bags and pouches)

Packaging materials and systems for medical devices which are to be sterilized, Part 3:

Paper for use in the manufacture of paper bags (speciﬁed in EN 868-4) and in the

manufacture of pouches and reels (speciﬁed in EN 868-5)—Requirements and test

methods

EN 868-4:1999 (Paper

bags)

Packaging materials and systems for medical devices which are to be sterilized, Part 4:

Paper bags—Requirements and test methods

EN 868-5:1999 AC:2001

(Pouches)

Packaging materials and systems for medical devices which are to be sterilized, Part 5: Heat

and self-sealable pouches and reels of paper and plastic ﬁlm construction—Requirements

and test methods

EN 868-6:1999 (Paper for

packs)

Packaging materials and systems for medical devices which are to be sterilized, Part 6:

Paper for the manufacture of packs for medical use for sterilization by ethylene oxide or

irradiation—Requirements and test methods

EN 868-7:1999 (Adhesive

coated paper)

Packaging materials and systems for medical devices which are to be sterilized, Part 7:

Adhesive coated paper for the manufacture of heat sealable packs for medical use for

sterilization by ethylene oxide or irradiation—Requirements and test methods

EN 868-8:1999 (Reusable

sterilization containers

for steam sterilizers)

Packaging materials and systems for medical devices which are to be sterilized, Part 8: Re-

usable sterilization containers for steam sterilizers conforming to EN 285—Requirements

and test methods

EN 868-9:2000 (Uncoated

non-woven polyoleﬁn

materials, e.g., Tyvek)

Packaging materials and systems for medical devices which are to be sterilized, Part 9:

Uncoated nonwoven materials of poiyoleﬁnes for use in the manufacture of heat sealable

pouches, reels and lids—equirements and test methods

EN 868-10:2000

(Adhesive coated non-

woven polyoleﬁn

materials, e.g., Tyvek)

Packaging materials and systems for medical devices which are to be sterilized, Part 10:

Adhesive coated nonwoven materials of polyoleﬁnes for use in the manufacture of heat

sealable pouches, reels and lids—Requirements and test methods

722 MEDICAL DEVICE PACKAGING

and the absence of denominator data’’ (24). The diverse

array of devices, environments of use, and risks associated

with failures challenge the implementation of comprehen-

sive surveillance plans. The information that is available

suggests that adverse medical device events (AMDEs) are

an important patient safety issue that are presently

underreported; strategies for prevention and detection

need to be implemented, and it is likely that packaging

will play a role in these efforts.

Rising Nosocomial Infection Rates

The emergence of microbes that are resistant to cheap and

effective, ﬁrst-choice (or ‘‘ﬁrst-line’’) drugs presents one of

the most serious problems facing global healthcare. Bac-

terial infections that show the most evidence of resistant

microbes include: diarrheal diseases, respiratory tract

infections, meningitis, sexually transmitted infections,

and hospital acquired infections. Implicated microbes

include: penicillin-resistant Streptococcus pneumonia,

vancomycin-resistant enterococci, methicillin-resistant

Staphylococcus aureus, multi-resistant salmonellae, and

multi-resistant Mycobacterium tuberculosis (25).

Treatment failures lead to the requirement for second-

line therapies that can be more than 100 times expensive

than ﬁrst-line therapies. In countries where treatment

becomes cost prohibitive, the consequence is not only

the suffering and the potential death of the patient, but

also possible spread of the drug-resistant disease. ‘‘Most

alarming of all are diseases where resistance is developing

for virtually all currently available drugs, thus raising the

spectre of a post-antibiotic eraycurrent trends suggest

that some diseases will have no effective therapies within

the next ten years’’ (25).

Additionally, several concurrent trends conspire to aid

in the spread of infections. These include:

. The frequent need for hospital intervention of the

aging population.

. Increases in urbanization and overcrowding.

. A resurgence in certain diseases (e.g., tuberculosis

and malaria).

. Tremendous increases in global trade and travel.

. The AIDS epidemic, which gives rise to large num-

bers of immunocompromised patients that are sus-

ceptible to disease.

. Changes in the environment, which include pollu-

tion, environmental degradation, and changing wind

patterns. These impact both the incidence and dis-

tribution of disease across the globe (25).

Although device packagers have long understood the

need to maintain a sterile barrier throughout distribution,

at no time in history has sterile presentation of packaged

devices been more important. Designers must consider

how the design will assist the sterilization process (e.g.,

pore size on sterilization efﬁcacy), maintain the SBS

throughout distribution and handling, and facilitate asep-

tic presentation of package contents to the sterile ﬁeld.

As if the previously described challenges were not

enough to consider, issues associated with the supply

chain also create difﬁculties that should be considered

by designers.

Figure 3. Global aging. Percentage of people age 65 and over in selected countries for 2005 and projected 2025. [Source: U.S. Census

Bureau (37).]

Figure 4. Disability prevalence by age. Percent with speciﬁed level of disability. [Source: U.S. Census Bureau (37).]

MEDICAL DEVICE PACKAGING 723

Illicit Activities within the Supply Chain

Devices can be grouped into two broad categories with

regard to the supply chain: advanced devices and com-

modity-type medical surgical supplies. Advanced devices

are higher-priced, lower-volume, technologically sophisti-

cated diagnostic and therapeutic products. They are sold

mostly to hospitals, but to different customers within the

hospital supply chain: buying groups, distributors, and

providers. The manufacturers of commodity-type medical

surgical supplies have a more complicated supply chain;

products are frequently sold through a series of distribu-

tors, a multi-echelon global supply chain that, at present,

lacks transparency.

Even within the hospital, tracking therapies can be

difﬁcult. Complications of managing hospital inventories

include the fact that items to be tracked are varied. As

discussed previously, products are large and small, durable

and expendable, disposable and reprocessed, numerous

and few, and critical and noncritical to care. As such, the

relevant information varies from item to item. Further-

more, a ‘‘hospital’s size, geographic location, diversiﬁca-

tion, and various specializations all affect the nature

of its business and, hence, the requirements of its supply

chain. Likewise, each ward within a hospital is unique.

The number of products and demand of those products, for

example, varies greatly from an Emergency Room to a

Cardiac Cath Lab to an Intensive Care Unit’’ (26).

As such, tracing devices back to their components can

be difﬁcult in the current system. Compounding this

problem is the issue of arbitrage (both legal and illegal).

The healthcare industry, by its very nature, must balance

the tensions of innovation and access. The industry must

provide access to therapies for all people, but if it is to

continue to innovate, the costs associated with research

and development must also be recouped so that they can

be invested to develop future generations of lifesaving

products. The way that the industry generally deals with

the tension of access versus innovation is differential

pricing, selling at what the market will bear. For example,

OECD nations,* which can afford to pay more, generally

bear the majority of the cost for future innovations; areas

of the world that cannot afford this burden are sold

therapies at much lower prices. Markets can be segmented

along geographic borders, political borders, or buyer and

payer classes within countries (such as U.S. Medicare,

Medicaid, Veterans’ Affairs, Federal employees, or private

health plans).

However, one of the unfortunate side effects of differ-

ential pricing is that it makes the illegal arbitrage of

healthcare products possible. Economic arbitrage is the

opportunity to buy an asset at a low price and then

immediately sell it in another market for a higher price

(27). In instances where arbitrage involves intellectual

property and the product crosses an international border,

it is called parallel trade. Parallel trade involves ‘‘the act of

taking goods placed into circulation in one market, where

they are protected by a trademark, patent or copyright,

and shipping them to a second market without the author-

ization of the local owner of the intellectual property right’’

(28). Parallel trade may or may not be legal, depending on

the country’s intellectual property laws. Additionally, the

practice may be forbidden contractually, though this ap-

proach can run afoul of competition laws (27).

The problem of this global system of multiple hand-offs,

arbitrage, and opacity is that it presents opportunity for

those with illicit intentions. Criminals can participate in

the supply chain of surgical supplies in a variety of ways.

Tactics include:

. Buying medical supplies from ‘‘closed door’’ pharma-

cies and dispensaries of small institutions such as

nursing homes, hospices, and AIDS clinics at dis-

counted prices.

. Paying hospital or nursing home workers for devices

from their supplies.

. Offering cash to Medicaid patients in exchange for

their care items.

. Collaborating with corrupt company employees to

break into warehouses, or steal shipments from

loading docks.

. Stealing or purchasing devices that are intended for

charitable or low-income markets in order to divert

products to markets that will pay higher prices.

For those that are not willing to go to the effort that

illegal arbitrage takes, there is counterfeiting. ‘‘Counter-

feiting dispenses with the need to collect the product in

far-ﬂung locations, repackage it, and transporting [sic]

it back to the OECD markets. Counterfeiting can be

produced in market at very modest cost, more cheaply

than obtaining diversions in low-income countries’’ (27).

Counterfeiting of medical products (drug, device, and

biologic) is attractive to those with illicit intentions for a

variety of reasons, including:

. Lax penalties associated with the crime.

. The rise of technology which allows for easy produc-

tion of many medical products.

. Cottage industries that use unemployed, skilled

labor.

. The rise of internet sites where goods can be adver-

tised and sold.

An increase in the self-prescribing culture.

. Great

potential for proﬁt

(in part due to differential

pricing, in part due to the cost of genuine therapies).

. The nature of the industry; sick, and sometimes

desperate, people are open to exploitation.

. The globalization of the healthcare industry and free

trade, making the distribution of products easier.

Although the counterfeiting of drug products is more

widely investigated and reported, the number of counter-

feit medical devices is believed to have grown in recent

years and the potential ramiﬁcations are serious (29).

Both ﬁnished goods and device components have been

successfully faked. Glucose meters and test strips,

* Countries that are members of the Organisation for Economic

Co-operation and Development.

724 MEDICAL DEVICE PACKAGING

condoms, contact lenses, blood pressure meters, blood

bags, surgical mesh, stethoscopes, sphygmomanometers,

the components of X-ray machines, and even intra-aortic

pumps, to name a few, have been counterfeit in recent

years (30, 31).

As mentioned previously, manufacturers and even

regulators are looking to packaging as a component of

the solution to the problems associated with diversion and

counterfeiting.

Escalating Healthcare Costs

The previously discussed issues (aging populations

throughout the world, medication errors and patient non-

compliance, rising rates of infection, and devices delivered

by a supply chain that moves differentially priced thera-

pies in a world of arbitrage and counterfeits) have obvious

impacts. These issues, coupled with an ever-increasing

reliance on technologies that provide human sustenance

and comfort (i.e., complicated devices), are driving health-

care costs up the world over (32). ‘‘Health care costs are

rising worldwide at rates that alarm governments, busi-

ness and individuals’’y and have grown as a percentage

of GDP in most countries (33). This is happening in a

world where cost-competitiveness is increasingly impor-

tant and a reduction of ballooning healthcare costs is

recognized as a priority.

In turn, governments, providers, purchasing organiza-

tions, insurers, and patients are demanding better out-

comes for the dollars that they spend. Varying players

within the medical products’ supply chain are calling for

evidence-based medicine and comparative evidence upon

which decisions can be made. They desire the ability to

link speciﬁc devices to patient outcomes in order to max-

imize the impact of the healthcare dollar. Packaging has

the potential of playing a role in these efforts, because it

contains identifying marking of contents that can be fed

into patient records (and bills).

POTENTIAL SOLUTIONS

Automatic Identiﬁcation

The use of automatic identiﬁcation technologies (auto ID) to

carry and communicate standardized information about

medical devices is one approach that is being used to system

efﬁciencies and reduce cost. ‘‘Auto ID is the broad term given

to a host of technologies that are used to help machines

identify objects or persons’’ (34) and includes bar codes ,

radio-frequency identiﬁcation (RFID), and biometrics.

Proponents of implementing Auto ID in a standardized

fashion for the medical device industry indicate the fol-

lowing beneﬁts:

. Reductions in medication errors

. Facilitation of notiﬁcation and recalls

. Identiﬁcation of device incompatibilities

. Identiﬁcation of potential adverse effects (such as

allergic reactions)

. Deterrence of counterfeits

. Assistance in product authentication

. Data for evidence-based medicine

. Evidence for prosecution in the case of illicit activ-

ities (counterfeiting)

. Integration of product with electronic health records

(EHR) and Computerized Physician Order Entry

(CPOE) systems

. Improved inventory control

. Improved billing and reimbursement

. Improved post market surveillance (2).

The Rise of Combination Products

With increasing frequency, these challenges are being met

using (a) designs that are a convergence of devices, (b)

pharmaceutical and biologic products, or (c) customized

kits, and combination products. Combination products

are one way that device manufacturers can add value to

medical products. The market size of all combination

products in 2004 was estimated to be $6 billion and has

been projected to grow to $10 billion by 2009 (35). This

growth is largely due to the added convenience that these

products provide.

Products like insulin injector pens, metered dose in-

halers, transdermal patches, and preﬁlled syringes are

combination products that add convenience, saving end-

users time and effort. In these examples, two types of

therapy (a drug and a device) are combined into a single

product, and the device itself becomes a package for the

drug product. Customized kits, in which multiple products

are packaged into a single package, usually for a proce-

dure, are another example of combination products. Re-

gardless of whether the therapies are combined into a

single product, or multiple products packaged together,

things like shelf life, efﬁcacy, package testing, product

labeling, and regulation become more complicated. As

such, people that design packaging for combination pro-

ducts must consider not only the physical environment

(shocks, vibrations, and other aspects of dynamics), which

can

threaten the integrity

of the sterile barrier, but also

the ecospheric environment, which can render the drugs

that have been added unefﬁcaciously.

CONCLUSIONS

Because of the disparate array of medical devices,

thoroughly covering the packaging of medical devices

in a single book chapter is all but impossible. This article

is meant to serve as a guide to other resources for

the packagers of medical devices and also provide things

to consider during the design process (present and

future).

Acknowledgments: The authors gratefully acknowledge the ad-

vice, insights, and technical expertise of Dhuanne Dodrill.

Dhuanne was immensely helpful in providing writing much of

the technical information regarding materials, packages, and

sterilization processes.

MEDICAL DEVICE PACKAGING 725

BIBLIOGRAPHY

1. GHTF Study Group 1, ‘‘Information document concerning the

deﬁnition of the term ‘Medical Device,’’ 2005. ‘‘Available at

http://www.ghtf.org/sg1/sg1-ﬁnal.html (accessed July 1,

2008).

2. Eastern Research Group, ‘‘Unique identiﬁcation for Medical

Devices,’’ 2006, Food and Drug Administration. Available at

http://www.fda.gov/cdrh/ocd/udi/erg-report.pdf (accessed

April 4, 2008).

3. Research and Markets, ‘‘Medical Market Futures to 2011,’’

2007.

4. Capgemini, Medical Devices Industry: Growth Opportunities

and Cost Pressure’’ in The 3rd Annual World Health Care

Congress: Europe 2007, Barcelona, Spain, 2007. Available at

http://www.worldcongress.com/events/NW715/pdf/

thoughtLeadership/8-LS_MeddeviceIndustry.pdf (accessed

July 12, 2008).

5. US ‘‘Medical Device Industry Grows Rapidly’’, J. Clin. Eng.,

128, 2006.

6. GHTF Study Group 1, ‘‘Principles of Medical Devices Classi-

ﬁcation,’’ 2006. Available at http://www.ghtf.org/sg1/sg1-

ﬁnal.html (accessed July 1, 2008).

7. ISO/IEC Guide 51:1999, ‘‘Safety Aspects. Guidelines for Their

Inclusion in Standards,’’ International Organization for Stan-

dardization, 1999.

8. H. E. Lockhart, ‘‘A Paradigm for Packaging,’’ Packaging

Technol. Sci., 10, 237–252, 1997.

9. C. D. Marotta, ‘‘Packaging Materials,’’ in M. Sherman, ed.,

Medical Device Packaging Handbook, Marcel Dekker, New

York, 1998.

10. D. S. Barcan and H. F. Miller, ‘‘Package Validation’’ in M.

Sherman, ed., Medical Device Packaging Handbook, Marcel

Dekker, New York, 1998.

11. C. W. Bruch and R. R. Reich, ‘‘Package Sterilization Methods’’

in M. Sherman, ed., Medical Device Packaging Handbook,

Marcel Dekker, New York, 1998.

12. L. A. Feldman and H. K. Hui, ‘‘Compatibility of Medical

Devices and Materials with Low-temperature Hydrogen Per-

oxide Gas Plasma’’, Med. Device Diagn. Ind. Mag., 57–70,

1997.

13. B. M. Fryer and J. P. Kohler, ‘‘Parametric Release for Low-

Temperature Gas Plasma Sterilization’’, Med. Device Diagn.

Ind. Mag., 38–39, 2005.

14. M. Scholla, ‘‘Medical Packaging: Achieving a Single Global

Standard’’ in Medical Device and Diagnostics Industry, Jan-

uary 2004. Available at http://www.devicelink.com/mddi/

archive/04/01/007.html (accessed July 3, 2008).

15. H. Miller, Sterile Medical Device Packaging Regulations.

2006. Guest lecture for the Medical Packaging course at

Michigan State University.

16. Centers for Disease Control and Prevention and Merck

Institute of Aging and Health, ‘‘The State of Aging and Health

in America,’’ 2004. Available at http://www.cdc.gov/Aging/pdf/

State_of_Aging_and_Health_in_America_2004.pdf (accessed

June 11, 2008).

17. Department of Health, ‘‘Coding for Success: Simple Technol-

ogy for Safer Patient Safety,’’ 2007, London, UK. Available at

http://www.patientsafetyboard.org/DesktopModules/Docu-

ments/DocumentsView.aspx?tabID = 0&ItemID = 31895&

MId = 5204&wversion = Staging (accessed July 13, 2008).

18. Institute of Medicine, To Err is Human: Building a Safer

Health System. The National Academies Press, Washington,

DC, 2000.

19. Institute of Medicine, Preventing Medication Errors (prepu-

blication copy), The National Academies Press, Washington,

DC, 2006.

20. Healthcare Distribution Management Association, Medica-

tion Errors and Patient Safety: The Barcode Connection,

Reston, VA, 2004.

21. C. Vincent, G. Neale, and M. Woloshynowych, ‘‘Adverse

Events in British Hospitals: Preliminary Retrospective Record

Review,’’ Br. Med. J. 322, 517–519, 2001.

22. D. G. M. Vidt, ‘‘How Physicians Can Prevent Medication

Errors: Practical Strategies,’’ Cleveland Clini. J. Med. 64(7),

355–359, 1997.

23. M. Samore, R. Evans, A. Lassen, P. Gould, J. Lloyd, R. M.

Gardner, R. Abouzelof, C. Taylor, D. A. Woodbury, M. Wily,

and R. A. Bright, ‘‘Surveillance of Medical Device-Related

Hazards and Adverse Events in Hospitalized Patients,’’ J.

Am.

Med. Assoc. 291(3),

325–334, 2004.

24. World Health Organization, ‘‘Antimicrobial Resistance,’’

2002. Available at http://www.who.int/mediacentre/fact-

sheets/fs194/en/ (accessed June 17, 2008).

25. D. DeScioli, ‘‘Differentiating the Hospital Supply Chain for

Enhanced Performance,’’ Master’s degree in Logistics, Mas-

sachusetts Institute of Technology, Cambridge, MA, 2005.

26. K. Outterson, ‘‘Pharmaceutical Arbitrage: Balancing Access

and Innovation in International Prescription Drug Markets,’’

Yale J. Health Policy, Law, and Ethics, 5(1), 193–291, 2005.

27. M. Gansladt and K. Maskus, ‘‘Parallel Imports and the Pricing

of Pharmaceutical Products: Evidence from the European

Union,’’ 2004, The Research Institute of Industrial Economics,

Stockholm, Sweden. Available at http://www.naringslivsfors-

kning.se/Wﬁles/wp/WP622.pdf (accessed June 11, 2008).

28. G. Nighswonger, ‘‘Pursuing Counterfeit Medical Devices’’ in

Medical Device and Diagnostics Industry, January 2003.

Available at http://www.devicelink.com/mddi/archive/03/01/

021.html. (accessed June 12, 2008).

29. C. Bruderlin-Nelson, ‘‘Chinese Counterfeit Devices Elevate

Health Concerns’’ in IVD Technology, November/December

2007. Available at http://www.devicelink.com/ivdt/archive/07/

11/004.html (accessed June 12, 2008).

30. World Health Organization, ‘‘Medical Device Regulations:

Global Overview and Guiding Principles, 2003. Available

at http://www.who.int/medical_devices/publications/en/MD_

Regulations.pdf (accessed April 4, 2008).

31. C. Organ, ‘‘The Impact of Technology on Surgery,’’ Arch. Surg.

134(11), 1175–1177, 1999.

32. N. Smith, Aging Population Drives Rise in Global Healthcare

Costs,’’ News Ofﬁce press release, 2003, Massachusetts

Institute of Technology. Available at http://web.mit.edu/

newsofﬁce/2003/novartis-1001.html (accessed June 10, 2008).

33. ECRI, ‘‘Automatic Identiﬁcation of Medical Devices,’’ U.S.

Food and Drug Administration, 2005. Available at http://

www.fda.gov/cdrh/ocd/ecritask4.pdf (accessed June 10, 2008).

34. J. Solonika, ‘‘Convergent Medical Technologies: Local Im-

pacts, Global Opportunities,’’ YorkBiotech Inaugural Meet-

ing, 2005, Ontario, Canada.

35. C. Larsen and J. Spitzley, ‘‘Package Materials and Systems for

Sterile Medical Devices,’’ 2007. Guest lecture for the Medical

Packaging course at Michigan State University.

726 MEDICAL DEVICE PACKAGING

36. U.S. Census Bureau, International Data Base, August 2006

version. Available at www.census.gov/ipc/www/idbsum.html

(accessed June 5, 2007).

37. US Census Bureau, P70-61—American with Disabilities:

1994–1995 in Current Populations Reports—Household Eco-

nomic Studies, 1997, US Department of Commerce: Washing-

ton, DC, USA. 1-8. Available at http://www.census.gov/sipp/

p70-61.pdf (accessed July 14, 2008).

METAL CANS, FABRICATION

JEAN SILBEREIS

SLCC Can Consultants

La Tour de Peilz, Switzerland

The metal can is one of the oldest forms of packaging

preserved food for long periods. In the same way, it has

proven to be an adequate container for food stuffs, bev-

erages, and industrial products. Thousands of different

products of all kinds have been packed in metal cans. The

traditional method of manufacture is to start with a

rectangular sheet of tinplate or canstock that has special

surface treatments. Blanks, or bodies, are cut from the

sheets, ﬂexed and rolled into a cylinder, and then notched

and hooked so as to form a locked side seam, which results

in a longitudinal joint line bonding both the lateral cut

edges of the blank.

Bodies are beaded for increased resistance against

implosion of the can. More and more can bodies are necked

to use ends of reduced diameters or/and thinner and

more economical end stock, as well as to make cans

stackable.

Ends, i.e., the closures at the bottom and the top of

the cylindrical or any other geometrical section of the can

body, are tightly secured to the body by a double seam

(called so because they are made in two operations). Both

extremities of the can bodies are ﬂanged so as to create

the body hook, which engages with the end hook so as to

form a tight, compact, and interlocked closure. One end,

which is called the maker’s end, is ﬁtted by the can

manufacturer. The other, ﬁtted by the ﬁller or the packer

upon ﬁlling the ‘‘open top’’ can, is known as the packer’s

end.

Because the container is made from three separate

elements, it is known as a three-piece can. Its construction

had remained basically unchanged for more than 150

years. Advances have been made in engineering, automa-

tion, and speeding up of the original manual canmaking

processes. The metal input has been gradually and con-

stantly reduced through more sophisticated design geo-

metry and more recently by changing the methods of

making the side seam from tin/lead alloy soldering to

welding (see Figure 1).

Since the early 1970s, a different concept of canmaking

has gained acceptance in commercial production. In this,

the body and one of the ends, are formed in one entity from

a ﬂat circular blank by press forming technique (1). The

open top end is sealed with the usual packer’s end. It is

known as two-piece can. The methods of forming are

identiﬁed: drawing and ironing (D&I in the United States,

DWI in Europe) and draw and redraw (DRD) (2). D&I, for

instance, was used in World War I for making shell cases.

What distinguishes them in canmaking is the use of

ultrathin metal in high-speed production to yield outputs

counted in billions of cans per year.

CAN TYPES

All processes convert ﬂat sheet material into ﬁnished

cans, which are supplied with a loose end for the packer

or ﬁller, according to this basic scheme: prepare plate

matching the products to be packed, their ﬁlling

and processing conditions as well as market conditions

(climates, shelf lifes, presentation of cans, sanitary

regulations, etc.); make bodies and ends; apply ﬁnishes

(decorative or/and protective barriers). The order may

vary, depending on the process used. The manufacture of

three-piece and two-piece DRD cans starts with the

ﬁnishing step. Some cans are resprayed with a top coat

for increased corrosion resistance in a ﬁnal stage of

fabrication.

Coils are usually cut into sheets or scrolled strips

(technique Littell) if coil coated stock is used. Sheets are

coated on one or both sides and are decorated if appro-

priate. The coatings are called enamels in the United

States and lacquers in the United Kingdom. Decorations

are always protected by over-or ﬁnishing varnishes to

make them scratch proof and to add gloss. In case of

processed cans, decorative or barrier coats have to resist

the applied heat treatments in autoclaves.

If the starting point is a circular blank, as for DRD cans

or ends, then the cut edges of the sheets are scrolled for

economy of metal usage (Figure 2). Alternatively, pre-

coated coil stock may be fed directly into the cupping

press for blanking and drawing or into the multi-die end

stamping press. In the manufacture of two-piece D&I

cans, plain coil, as supplied from the mill, is the starting

point.

Figure 1. Three-piece can side seams (a) soldered; (b) cemented;

Conference, 1984.

METAL CANS, FABRICATION 727