Package and Product Integrity Blog

In continuation of our list from 2 weeks ago, here is the second part of a post highlighting common mistakes made by companies relating to their package validation. Package testing is a crucial component for medical device companies to have done properly to ensure that their packaging is validated for distribution to the market.

6. Having The Wrong Sample Size
The question of the ‘right’ sample size to use for testing is one of the most daunting to answer.  There are many factors that weigh into the determination of sample size.  The factors include; what type of test is it? (e.g. quantitative/variables or qualitative/attributes); what is the sample population? How many samples are available for testing? What are the economics? What are the risk factors?  (e.g. confidence intervals) .  Most often the sample size is too small and renders results that have no statistical significance.

7. Using the Wrong Package Type/Material
Using the wrong package type or material for the product is a package-product compatibility issue, which could have been avoided if pre-qualification of the packaging had occurred at an early stage.  Some of the typical observations that are prevalent include fracturing of thermoform trays as a result of using the wrong plastic material for the intended product (e.g.  Product mass is too great for the impact resistance of plastic).

This can be avoided for large, massive products, by using a high impact resistant plastic such as polycarbonate to reduce the possibility of fracturing during normal distribution and handling. The thermoform design is also critical to ensure that the product is held in place firmly so that a loose product is not jettisoned through the tray lid and fracturing of the plastic doesn’t occur from the inside-out.

8. Squeezing Oversized Pouches Into Cartons
Pinhole defects in pouches can be reduced by inserting the pouch into a carton without folding, wrinkling or creasing the ends.  Pinholes occur at the junctures of the creases and folds when they are vibrated causing the intersection to be ‘worked’ or fatigued at the juncture.   This effect is exacerbated by making complex folds of the pouch causing a very concentrated point of stress at the juncture of the materials.  This can be circumvented by using secondary packages (cartons/shelf boxes) that are large enough to allow for insertion of the pouch without folding.

This can be avoided for large, massive products, by using a high impact resistant plastic such as polycarbonate to reduce the possibility of fracturing during normal distribution and handling. The thermoform design is also critical to ensure that the product is held in place firmly so that a loose product is not jettisoned through the tray lid and fracturing of the plastic doesn’t occur from the inside-out.

9. Tyvek Separation Is Not Recognized As a False-Positive
One phenomenon that was discovered some years ago but only really came to light when medical device packages began to be integrity tested routinely using bubble and dye leak methods was ‘sheet separation of the porous web’ of Tyvek.

This ‘sheet separation’ can lead to a false-positive in the integrity test.  The false-positive occurs when the material is bent, folded, or ‘wrinkled’. Dupont has proven that this phenomenon does not change the sterile barrier performance of the material and that any leakage of air or dye solution is only along the transverse direction of the material and not between the Tyvek and poly material, as would be the case in an adhesive (seal) failure.  There is no loss of filtration capability when this occurs.  However, when performing these tests it is incumbent upon the tester to analyze the failure carefully.  In some cases, when there is a suspect ‘false-positive’, it may be necessary to look at it under high magnification to determine the cause of the leakage.

10. Accelerated Aging Is Performed At High Test Temperature
In ill conceived attempts to reduce costs and time, some manufacturers decide to accelerate the shelf life or expiration date studies to unrealistic and indefensible limits.  This is done by raising the test temperature to a level that causes packages to melt-down, warp, or change in other uncharacteristic behaviors.  In addition, temperatures over 65OC are indefensible based on the rationale which is typically used to justify accelerated aging protocols.

Accelerated aging is performed on packaged medical devices to document expiration dates for products.  Real time aging can be performed; however, products are often obsolete by the time a three year expiration date is validated.  FDA does not require expiration dating for products without components with a defined effective life such as batteries.  The European Directives imply that all sterile medical devices must have an expiration date.  Therefore documented evidence must exist to substantiate those claims.

Temperature selection for the accelerated aging study should avoid unrealistic failure conditions such as deformation due to melting.  This advice is sometimes ignored in the haste to bring products to market faster.

If you have experienced other issues with your package integrity or package testing, please feel free to share with us what the biggest challenges were.