New Methods to Assess the Performance of Prototype Form-Fill-Seal Packages

Medical Device & Diagnostic Industry Magazine
MDDI Article Index

An MD&DI January 1999 Column

PACKAGING

A study describes novel test procedures and equipment to detect packaging problems early in the development process.

The International Organization for Standardization (ISO) has defined a medical product as "the combination of both the medical device and/or additional components with the final package."¹ However, the realities of product development often leave development of the package itself until long after the rest of the product has been fully defined and, perhaps, is in limited production. When a project nears the end of the development period, major changes made to the device itself are difficult and costly, which forces all aspects of device/package compatibility and package performance to be achieved exclusively through package design modifications. A further problem in this typical development pattern is that when package development is finally undertaken, pressure to market the product soon is very high, thus encouraging the package development engineer to make package design decisions based on intuition rather than on scientific evidence from tests. Even in those instances when testing is done, the large number of products required for the standard packaging tests often leads to a product release before the tests are completed.

The package chosen for testing was that of the Insyte N catheter (Becton Dickinson; Sandy, UT), comprising an EVA/K-resin/EVA bottom web and coated Tyvek lid.

The net result of these problems in package development is often a compromised packaging system. Industry warranty results indicate that up to 40% of cases involving claims on medical supplies are the direct result of faulty packaging, and that these failures result in costs in excess of $8 billion in the United States alone—confirming that the system currently used for packaging design is a major problem.^2,3

The medical industry is particularly vulnerable to packaging failures. Some of the consequences of packaging failures have been identified as follows:

An improved product development system would include the development of a prototype package early in the overall process, simultaneously with the development of the prototype device. However, an impediment to this early package development has been the lack of reliable tests that can be performed on only a few samples, as would be required if the tests were done when only prototype devices and packages were available.

The purpose of the study presented in this article has been the development of tests—including the testing apparatus—that will allow for early development of medical packaging, so that problems can be noted early enough in the development sequence that real consideration can be given to modifying any negative device design aspects that could otherwise impair packaging performance.

The process of designing and testing a package has been defined as the following steps:

All of these stages were considered in the process of developing the tests outlined in this article. These criteria imply that we have made efforts to create tests that simulate actual conditions under which packages have been known to fail, or conditions that packages are likely to encounter that would result in failure.

The introduction of test methods that simulate actual package-failure conditions will be of benefit in two ways. First, prospective package configurations and materials can be placed under simulated failure conditions faced in the distribution environment. Depending on the results they achieve, they can be either accepted or rejected. If the latter occurs, improvements can be made to the package design until it is found acceptable. The second benefit is that the new test methods can be used in the early stages of the product's design, before production has started. This will allow the design of the package to take place concurrently with the design of the device, making the product design truly the combination of both the device and the package.

EXPERIMENTAL PROCEDURE

The obvious practical focus of this study suggests that the films and the packaging types examined should be limited to those having common application in commercial packaging equipment. Therefore, this study was restricted to the evaluation of testing on packages made using standard form-fill-seal machines and films made from the widely used EVA/K-resin/ EVA film (supplied by CT Film).

An important concept in the development of the tests is the identification of hazard elements that would be critical to the performance testing of packages and would be included in the procedures. Three critical hazard elements (package failure modes) were identified through discussions with medical device packaging personnel and through analysis of packages that had previously failed. These hazard elements are:

Flexing is a general term meant to apply to any change in the dimensions or shape of the film. For instance, the film can stretch, buckle, and twist as the package is flexed, compressed, and rotated during shipment or handling. On occasion, the forces on the package can cause the web to crease, thus creating areas of stress concentration that weaken the film and increase the possibility of cracks or pinholes forming in the film. Ship tests on typical finished products using procedures developed by the International Safe Transit Authority (ISTA) have confirmed the importance of film flexing as a hazard element.⁵ Twelve cases of medical devices containing 2400 products were tested, and 4 packages failed the ISTA testing. Examination of the failed packages indicated that pinholes had developed where creases had formed in the film. With the formation of these pinholes, the sterile barrier of the film was compromised.

Abrasion is one of the most common hazard elements because of the vibrations that occur during shipment. A common failure from vibration results from the interaction between some feature on the device (such as a rough surface, a protruding element, or a shelf) and the film. In a shipping test using ISTA procedures on 1200 products for which abrasion was thought to be a potential problem, 19 of the product packages failed from the effects of abrasion.

Shock causes package failure when the device is forced against and then penetrates the film. These shocks can come from such incidents as takeoffs and landings of planes, railcar switching, road potholes and speed bumps, and package drops. Upon the completion of ship testing, 1800 products were examined for shock-related failures, and 3 of the failures were found to have been caused by the shock from a sharp edge of the device puncturing the film.

NEW TESTS

Two new tests were created to investigate flex, abrasion, and shock hazard elements during the early phases of product and packaging design. When testing is done at an early stage of development, the final device shape will not have been established. Therefore, a "dummy device" must be created to simulate the likely shape of the final product. This dummy device should, as much as possible at this stage of development, contain those features most likely to have a strong impact on the package (e.g., sharp corners, protrusions, etc.).

The tests are designed for single packages. Good statistical analysis will usually require that multiple samples be tested, but only a few (just enough for good statistical evaluations) are generally required. The results should, of course, be averaged using normal statistical methods.

The creation of these new tests required careful definition of the environmental conditions under which they were conducted. The conditions (which are recounted in detail as each of the tests is described) were developed using standard, finished-product test practices as guides. These guide or reference test procedures were ASTM D 4169, Standard Practice for Performance Testing of Shipping Containers and Systems; ISTA Procedure 1A, Preshipment Test Procedures; and ASTM F 392, Standard Test Method for Flex Durability of Flexible Barrier Materials.

The intent of the present article is both to report the findings of the new tests and to encourage others to investigate the use of similar tests, so that some industry standardization might be achieved. Therefore, the authors will be pleased to make available machine part drawings, parts lists, schematics of the electrical circuits, and ladder logic schematics. The detailed procedures, written in a standard test-method format, are also available.⁶

Flex Test. This test is to allow the investigation of flexural crack durability of a single form-fill-seal package during the early stages of product development. In order to give a realistic simulation of the most likely flexural-type forces on a package, specifications were established for the new flex-test machine so that the apparatus could:

A schematic diagram of the flex-test machine is presented in Figure 1. Twisting and untwisting within a specified range is accomplished using a rotary actuator, which is attached to a sliding table in which the slide length can vary from 0 to 1 in. through the use of stop collars and a positioning bolt. A programmable logic controller (PLC) is used to control the cycling of the part through the twist, compression, untwist, and decompression steps. The PLC allows the sequence of commands to be programmed and executed in the proper order and within the required cycle time necessary for the test specifications. A counter permits the test administrator to observe the number of cycles completed.

Figure 1. Flex tester.

The test method has been titled "Testing Method for Flexural Crack Durability of a Single Form-Fill-Seal Package." In brief, the test procedures and conditions are as follows:

Abrasion and Shock Test. The abrasion and shock test was created to examine the interactive effects of abrasion and shock on a form-fill-seal package. A review of the hazard elements of abrasion and shock reveals that in many cases these two elements interact with one another. For example, a package that is traveling by truck and trailer will be exposed to road vibration in its journey to the end-user but, at the same time, will also be exposed to shocks from potholes, speed bumps, railroad crossings, etc. Because of the combined occurrence of these two elements in the distribution environment and the interactive effects they have on the package, they were combined into a single test to give a more accurate account of their joint action. A sketch of the abrasion-and-shock-test apparatus is provided in Figure 2.

Figure 2. Abrasion and shock tester.

In choosing the type of vibration to use in the test, two considerations were taken into account. First, what kind of vibrations were being used in standard test methods, which presumably reflected the vibrations encountered under actual shipping conditions? Second, what type of equipment corresponding to realistic vibrational situations could be purchased at relatively modest expense?

The current test methods, such as ASTM D 4728 and ISTA 2, use vibration profiles that plot forces (in G units) against frequency for various common shipping methods (e.g., truck, rail, or air). Typically, the forces will rise to a maximum at one or more frequencies that are characteristic for the particular type of shipping encountered. Therefore, to duplicate these tests, a vibratory table capable of many vibration frequencies would be needed. However, both equipment cost limitations and a recognition of the required level of test precision suggested that a vibration table with only single-frequency capabilities should be used. The frequency chosen—21 Hz—was within the peak range for all of the common transportation methods, thus ensuring that each method would be represented, although not necessarily at its maximum vibrational level. A package mounting accessory attached to the table allows packages of different sizes to be tested.

Besides undergoing vibration, the package is also subjected to shocks that would be typical of those encountered under various shipping conditions. Because the interaction between the device and the package is so critical in determining how the packaging film resists penetration by the device, it was decided that the level of shock impact should vary so that a wide range of package/device relationships could be accommodated. This variability was achieved by mounting the dummy device on a pneumatic cylinder with a load cell attached, so that the force of the dummy device on the film could be regulated and monitored by the test administrator. The purpose of the machine is to subject the package to vibrations and then to occasional shocks from having the dummy device rapidly pressed into the film.

This second test method has been titled "Testing Method for Abrasion and Shock Durability of a Formed Bottom Web of a Form-Fill-Seal Package." In brief, the test procedures and conditions are the following:

DATA ANALYSIS (RELIABILITY MODEL)

When a new package design has been created, one of the areas of interest lies in ascertaining when the package will fail—that is, in determining the reliability of the package. The reliability of a unit has been defined as "the probability that it will perform its intended purpose adequately for a given length of time under specified conditions."⁷ In the case of package testing, reliability studies are important for determining the probability of a package failing within the distribution environment at a given time.

All packaging will fail within the distribution environment if exposed to hazard elements for long enough. Prototype package testing requires determining the probability of failure at a given time, and under specified conditions, for a package that is known to work in the distribution environment. Given this information, new package designs can be tested under the same conditions, and probabilities of failure determined for the same time intervals. By comparing the failure probabilities of the prototype package to those of the known package design, a decision can be made on the reliability of the package. If the probability of failure of the prototype is lower than that of the known package, the prototype design can be accepted for continued development. However, if the probability of failure of the prototype is higher than that of the known package, the prototype design should be rejected and an alternative sought.

When modeling time to failure, it is important to choose the proper type of distribution to analyze the binary outcome variable (acceptable/pass or not acceptable/fail). For this study, the logistic distribution was chosen, because it is flexible and easy to use.⁸ Data collected from a known package can be analyzed using this distribution and future comparisons made to help determine whether a prototype package will survive the distribution environment.

The binary response of a package failing or not failing can be quantified using the logistic regression model:

(x) = exp(ß₀ + ß₁x) / [1 + exp(ß₀ + ß₁x)],

where (x) = E(Y/x).⁸ The quantity E(Y/x) is interpreted as the expected value Y, given the value of x. With the value of Y denoting the outcome variable (failure = 1, no failure = 0) and x denoting the independent variable (any given time from - to +), E(Y = 1/x) can be read as the probability of a failure occurring at x time. This analysis method will be applied to the results obtained from testing specific packages using the two tests developed in this study.

TEST PACKAGE DESIGN

The package chosen to be tested in the new performance tests was that used for Becton Dickinson's Insyte N catheter, one of the company's high-production-volume catheters. This product represents an ideal "safe" standard, since it has been on the market for many years and has not been known to have experienced any package failures caused by the distribution environment. The package, which measures approximately 6.66 in. long, 1.17 in. wide, and 0.52 in. deep, is made using an EVA/K-resin/EVA bottom web, with an 8-mil (0.008-in.) preformed thickness, and a coated Tyvek lid. Postforming wall thicknesses are approximately 3.5 mil (0.035 in.) in the flats and 2 mil (0.020 in.) in the corners at each end.

TEST RESULTS

Data collected from testing of the Insyte N package using the new flex test are given in Table I. Fifteen packaged products were divided into five lots, so that three specimens could be tested at each test period. The test procedures outlined earlier were used with the following test periods of minutes per cycle: 30/1290, 60/2580, 90/3870, 120/5160, and 150/6450. The integrity tests were performed using Becton Dickinson's QCGE-83 air and water seal leak test, with the number of failures also reported in Table I.

Table I. Specimen-integrity test results for flex test.

After obtaining the results of the integrity testing performed on the flex-test specimens, a logistic regression model was created to give probability of failures at the times tested. For the flex-test specimens, the logistic regression model is:

(t) = exp(–3.697 + 2.987 x t) / [1 + exp(–3.697 + 2.987) x t].

This model was created using the equation on page 134 and a standard statistical software package, and allows for the calculation of predicted probabilities of failure for the package at the different test periods used.⁹ The predicted probabilities of failure for the flex-test specimens at the different test periods are listed in Table II.

Table II. Probabilities of failure of flex-test specimens at given times.

The abrasion and shock test was performed on 18 Insyte N packages (the same product used in the flex test), following the procedures for this test presented earlier. The frequency of the vibration table was set at 21 ± 1 Hz, with a table amplitude of roughly 0.25 in.; cylinder stroke length was set at 0.050 in. The products were divided into six lots, with three specimens tested at each test period. Test periods were 30, 60, 90, 120, 180, and 240 minutes. After the abrasion and shock test was completed, each package was integrity tested using Becton Dickinson's QCGE-83 air and water seal leak test. Results of the abrasion and shock tests are given in Table III.

Table III. Specimen-integrity test results for abrasion and shock test.

Once the results of the integrity testing performed on the abrasion-and-shock-test specimens were obtained, a logistic regression model was created to predict the probability of failure at the times tested. For the abrasion-and-shock-test specimens, the logistic regression model is:

(t) = exp(–5.937 + 3.706 x t) /[1 + exp(–5.937 + 3.706) x t].

Again, this model was created using standard statistical software.⁹ The results are shown in Table IV.

Table IV. Probabilities of failure of the abrasion-and-shock-test specimens at given times.

An examination of the failures from both tests reveals that they were consistent with those found in packages that failed in the actual distribution environment. Packages tested in the flex-test apparatus failed because of pinholes formed in the areas where the material had been stressed by constant flexing and compressing, whereas packages tested with the abrasion and shock test failed because of pinholes and tears.