Packaging for medical devices play a key role in safely delivering specialized treatment to patients. Most single-use, sterilized medical devices can be opened with a high degree of confidence that it has remained sterile throughout storage, handling, and transportation.

What makes packaging doubly important is that regulatory authorities recognize the critical nature of sterile barrier or primary package by considering them components or accessories to the medical device. This implies that packaging is almost as important as the device itself. And it is. If a package does not keep, for instance, a pacemaker sterile, patients will be put at risk.

The design and development of packaging has rightfully come under closer scrutiny by international and domestic regulatory agencies. This scrutiny has placed a great deal of emphasis on standardizing package development. Some standardization comes in the form of the international standard ISO 11607: Packaging for terminally sterilized medical devices.

As critical as packaging is, some companies occasionally don't take it seriously. They'll consider it late in the design cycle, cut corners, or use inappropriate materials. Here are ten common mistakes companies make when developing and validating packaging systems for terminally sterilized (inside a closed package) medical devices.

The ten

The most common defect in medical packaging is loss of sterile integrity from fractured thermoforms along with pinholes, slits, cuts, and tears in pouch packages. These defects come from handling (or mishandling), vibrations during transportation, storage, and impacts caused by dropping.

Tears are usually caused during manufacturing or assembly, or while inserting pouches into cartons. Even “Information for Use” booklets can be hazardous because their sharp edges or staples can snag the packaging.

Sterile-barrier systems formerly called primary packages, and protective packages, formerly referred to as shipping containers, may provide the solution to package defects from handling and shipping. The two part system reduces the risks of puncturing, tearing, and fracturing the primary package.

Cutting too many corners

Most people in manufacturing are unaware of the need to test their packaging, or even that the ISO 11607 standard exists and is used by the FDA and European Community. So they try to validate the packaging “on the cheap” without using sound, scientific practices. In their haste to get a product to market, companies risk non-compliance with regulations, or worse yet, unknowingly let suspect devices reach patients.

The time to properly validate a full-package system depends on the product's shelf life and its expiration date. For example, it usually takes three to six months to go from package concept to final qualification for a one-year shelf life. The validation schedule should also allow for unexpected events, such as finding pin holes in the packaging after a test. Of course, this halts the validation.

Package validation should be on a parallel path with product development, so the product and package finish together. This is possible using prototype products for package compatibility and testing. When products have a longer shelf life, package development should be extended by about 45 days for each year of shelf life.

The package and product are not prequalified for compatibility

A common package-development mistake skips the preliminary evaluation and just dives into package validation. Cutting corners to trim time is short sighted and usually backfires by extending development schedules and increasing over-all validation costs because some part of the package fails. That means retests.

A few common prequalification tests that should be used to detect potential design and manufacturing problems include seal strength and integrity tests on manufactured packages. A seal test, for instance, measures the force needed to open a seal.

Such tests point out potential deficiencies in manufacturing and may indicate the production line needs corrective action. This should be done far in advance of testing package performance, such as for transportation, sterilization, or handling. Prequalification tests should also be the basis for establishing targets for process quality control.

Another test used to prequalify package-product compatibility is dynamic testing associated with transportation and handling. A shaker table reproduces the frequencies and amplitudes the shipping container is likely to experience and for a prescribed duration.

Most sterile medical-device packages do not typically lose sterility simply sitting on a shelf. Failures often stem from events in manufacturing, during shipping to the sterilization facility, or during distribution. Therefore, proposed packages should always undergo a prequalification to isolate potential hazards and determine the package response to each of those hazards.

Ignoring the worst-case scenario

It's often difficult to determine which shipping configuration to validate. Should you test just one product in one package? Or four products in a box?

To determine the worst-case scenario, it is necessary to determine the most common shipping configuration before validating the package. In this way, other package configurations of the same or similar products may be covered by one validation.

A few ISO 11607 guidelines work to device manufacturers' benefit. For example, a provision allows validating families of packaged products rather than individual configurations.

No time to develop protocols

Before working on a validation, write a protocol. It provides a blueprint for how testing will be done, including its purpose, scope, responsibilities, parameters, production equipment and settings, and acceptance test criteria.

Validation qualifies the materials and processes that make the complete package. If one process is not right, the entire system breaks down and the manufacturer risks harm to patients.

The wrong sample size

How many packages must be tested? Finding the right one is a daunting task because many factors determine it. For example, what type of test will be done? Quantitative tests provide values while qualitative tests report pass-fail or go, no-go results.

Other questions to answer include: What is the sample population? How many samples are available for testing? What are the costs? What are the risks? (e.g. confidence intervals). Sample sizes are usually too small and produce results that have no statistical significance.

Selecting an inappropriate material or package

A packaging prequalification would have guided package designers to an appropriate material or package. The problem shows up as fractured thermoform trays because product weight is too great for the impact resistance of the material.

Large or massive products should use high impact-resistant plastics such as polycarbonate to reduce the possibility of fracturing during distribution and handling. The design of the thermoform tray is also critical to ensure it will firmly hold the product so nothing jettisons through the tray lid.

Squeezing oversized pouches into cartons

Pinholes in pouches can be reduced by inserting the pouch into a carton without folding, wrinkling, or creasing the ends. Pinholes may form at creases and folds after sufficient vibration. This effect is exacerbated by folding the package in a complex manner that concentrates stress. The problem is solved by simply using secondary packages (cartons or shelf boxes) large enough to hold the unfolded pouch.

Misidentifying Tyvek separation as a failure

The phenomenon of sheet separation of Tyvek's porous web was discovered some years ago during a routine integrity test of a medical-device package. The test used bubble and dye-leak methods.

Sheet separation during an integrity test can falsely indicate an apparent failure, a false-positive. This happens after bending, folding, or wrinkling Tyvek. Dupont has proven that this phenomenon does not change the material's sterile barrier performance. Any leakage of air or dye solution is only along the transverse direction of the material, not between the Tyvek and poly material, as would be the case in an adhesive or sealing failure.

Consequently, the tester must carefully analyze such apparent failures. In some cases, suspect false-positives may call for a closer look under magnification.

Accelerating too fast

Accelerated aging performed at temperatures too high

Manufacturers occasionally accelerate shelf life and expiration-date studies to unrealistic and indefensible limits. This ill-conceived attempt to reduce time and costs is done by raising test temperatures to levels that melt, warp, or produce changes that are uncharacteristic behaviors. Temperatures over 55°C, for example, are indefensible based on the rationale typically used to justify accelerated-aging protocols.

Accelerated aging is usually performed on packaged medical devices to document expiration dates. Companies can perform real-time aging on products, but results are often obsolete by the time the test validates a three year expiration date. The FDA does not require expiration dating for products that don't have components with defined effective lives, such as batteries. European Directives imply that all sterile medical devices must have expiration dates. Therefore documented evidence must substantiate such claims.

Temperature selections for accelerated aging studies should avoid unrealistic failure conditions such as deformation due to melting. This obvious advice is sometimes ignored in the rush to bring products to market.