Determining Breathable Area Of Sterilisation
For effective EtO sterilisation the packaging material
must be breathable to allow the high-humidity EtO gas
mixture to infiltrate the package. A partial vacuum is
drawn before and after the cycle to facilitate the
movement (in and out)of the EtO and moisture vapor.
If the package does not have sufficient permeability,
the process will be ineffective.
A packaging that allows a breathable barrier allows
sterilant to permeate during the sterilisation process
while prohibiting the penetration of microorganisms
during handling and storage, after sterilisation. The
total package porosity of a sterilisable pouch which is
dependent on the gas flow and surface area is a key for
sterilisation and aeration phases of ethylene oxide gas
sterilisation processes. The cycle and aeration times
decrease as the porosity increases. Hence a smaller
porous area is ample.
Determination of porous area requires knowledge of some
specific characteristics. Breathable surface area,
package volume, secondary and tertiary packaging, and
peel force are all factors that determine porosity
limitations. The worst case average porous area, the
volume of the package and the gas exchange rate for each
part of the EtO cycle at a minimum is needed for
determining the porosity. The end sterilisation testing
is also needed to qualify a package design. Product
families of worst-case design and cycles are helpful
defining the limitation of sterilisation testing, but
optimizing the porosity of a package for an EtO cycle is
a continuous process.
Packaging Failures: The Largest Source of
“Sterility Recalls” is a disturbing issue within the
healthcare industry. “The largest source of sterility
recalls [80% according to some sources] is packaging
failures. Packaging design has to match product
In the changing landscape of the healthcare industry,
one major change is the increase in more complex
i) Combination products, such as the pairing of a
delivery device and a pharmaceutical
ii) The growth of kits, and larger products made up of
more items connected together whereby reducing the
amount of manipulation and handling required by
iii) More microbiologic-centric products like skin
More complex products mean packaging/sterilization pros
must consider more complex material structures, and
understand that materials and products are likely to be
more sensitive to sterilization.
Another part of the changing healthcare landscape is
regulatory compliance. Major Factors Responsible for
Packaging Failure Recalls:
• Lack Of Technical Expertise: Technical talent require
thorough on-the-job training and expertise.
• Not Validated Packaging Processes
• Inappropriate Sealing
• Supplier Quality Issues
• Batch Sizes For Testing: Which may cover the issues
such as no. of batches of materials to be used,
sterilization stresses to be placed on packaging, etc.
Testing And Packaging Of Product With The Maximum Stress
It may be useful to test the product in the package,
even though testing just the packaging is a simpler,
less costly process.
Sterility assurance and packaging professionals need to
work together to make sure that the testing performed
will provide a safe and effective package.
Sterilization of Plastics
One of the greatest difficulties with sterilization of
medical devices is the range of plastics used in any
given device or kit. A simple device or kit may contain
up to 10 different plastics for a range of uses, e.g.
housings, tubing, connectors, valves, and seals. The
plastics used may be chosen for a variety of reasons
such as transparency, mechanical strength, or inertness
depending on the application. The difficulty is that
every plastic behaves in a different manner to the
various sterilization methods used. Manufacturers can
easily find that the completed device cannot be
effectively sterilized. If manufacturers make unwise
then it may be impossible to adequately sterilize the
The possible sterilization methods therefore need to be
considered as an integral and early part of the
materials selection process for all medical devices
using plastics. An additional complication in the
materials selection process is the multiplicity of
grades available, even for a nominally identical plastic
material. For example, PVC is available in several
different major materials families depending on the
production method, (e.g. suspension PVC, emulsion PVC
and mass polymerized PVC, and in tens of thousands of
different grades which will vary according to
plasticizers), fillers and other additives.
Using Steam For Sterilization
The use of steam for sterilization is fairly widespread;
however, steam is seldom used as a sterilization method
by the medical device industry. Most disposable plastic
devices are terminally sterilized by ethylene oxide (EtO)
or radiation. These processes provide low temperatures
that most plastics can tolerate. Steam, however, is the
most commonly used sterilization method in many
Despite its use of high temperatures, steam is a simple
and inexpensive sterilization method with many benefits.
It yields little waste (entropy is its only by-product).
It is also efficacious in terms of its ability to kill
With the growing complexity of medical device and drug
combinations, it is essential to consider steam. These
combination devices, such as drugs in syringes, drugs on
catheters, and drug-eluting stents, often require steam
sterilization because EtO cannot sterilize liquids and
irradiation breaks down many drug compounds.
Steam sterilization has long been used in hospitals as
well as in the pharmaceutical, aseptic processing, and
food industries. Its simplicity and low capital cost
make it an inexpensive, attractive, and viable
sterilization method. Typical steam sterilization
equipment costs less than one-third as much as an EtO
chamber system and controller. It costs less than
one-fourth as much as gamma or E-beam equipment and
Sterilization exposure times can range from as short as
3 minutes at 134°C to as long as 3 hours at 101°–111°C,
depending upon the bioburden. Hospitals use steam at
134°C for 3 minutes for flash sterilization in emergency
situations and 121°C for 15 minutes on a routine basis.
Packaging Combination Products (Medical Devices)
Packaging materials for combination devices must support
all regulatory and technical requirements that relate to
sterilized medical devices and pharmaceuticals. In
addition, the most notable combination products,
drug-eluting stents, are expensive and delicate items.
Their packaging systems must be protective, high
performance, and have almost zero defects to make
certain these sensitive products are efficacious in use.
Obviously, these products have higher value than a
syringe or an oral
tablet. For that reason, medical-device manufacturers
place stringent demands on combination-product-packaging
materials and systems.
One of the biggest challenge is providing the required
level of quality, which translates to reliability, ease
of use, and surpassing rigorous -Clifford Stoll
package specs. Quality also refers to zero failures,
especially zero defects in sterile barrier (sterility)
properties of the package.
One bad package could make a $2,000 drug-coated stent
unusable. Combination products are often used in
high-risk surgical procedures so it is critical that the
package provides absolute protection for the device. At
the same time, packaging materials must open easily so
the product can be aseptically removed.
How Different Sterilisation Methods Were Developed
During time of conflict and war, new sterilization
methods tend to be developed. EO sterilization was
developed after WWII for germ warfare. Radiation was
driven in part during the cold war as a means of using
unused source of radiation. In the terrorist anthrax
challenge, x-ray irradiation appears to be a practical
means of sterilizing / sanitizing pallets of mail
against anthrax, that other current methods couldn’t
complete adequately or in time. For the first time in
history we have xrays and the capability of sterilizing
bulk, dense mass and large volume of untreated
(contaminated) healthcare product in a matter of
minutes, just in time, without the additional handling
associated with unloading and loading.
The Importance of Keeping Premixed IV Bags Covered
in Their Plastic Overwraps.
The Institute for Safe Medication Practice (ISMP)
describes how the protective overwrap serves an
important purpose - to control the amount of water
vapour that escapes from an IV solution.
Once IV bags are removed from their overwraps and
exposed to room air, the rate of evaporation increases.
And over time, the drug’s concentration will increase
because the amount of drug in the bag stays the same
while amount of fluid decreases.
You can actually lose a large proportion of the liquid
in an IV bag this way. ISMP cites a case where half the
liquid in the bag was lost. In this case, a patient was
supposed to receive 40 mEq of potassium chloride in 100
mL over an hour, but the bag was empty in half an hour.
That’s because the overwrap had been removed from the
bag and over time, half of the water had evaporated,
leaving 40 mEq of potassium in just 50 mL of solution.
One solution may be to send them to the pharmacy, so
they can be sent to a unit where a patient is currently
receiving the solution and they can be used right away.
ISMP also cautions against writing an expiration date
directly on the bag, because volatile chemicals from the
ink may leach into the solution.