Serving Package Testing with Better Science
As test equipment promotes higher accuracy, research progresses on defining acceptable hole size.
By David Vaczek
Testing methodologies for innovative equipment have promised ease of use and more-precise results for establishing integrity and seal-strength values of medical device and drug packaging. Some newer solutions accomplish several testing methods in one machine. In supporting R&D applications and package validation, models are offered with computer-supported analysis and results documentation.
Mocon's new Lippke 4000 and 4500 models employ positive pressure for leak and seal strength measurement on flexible and rigid packages.
Recent package testers from Mocon (Minneapolis), for example, offer enhanced features for destructive package testing. Mocon has gained numerous customers for its automated blue dye test method for blister packages. The Lippke VC 1380 benchtop leak and seal-strength analyzer avoids blister handling and user exposure to the dye, says Steve Bunnell, Mocon’s national sales and marketing manager.
A slight vacuum is pulled in a bowl containing the dye into which the blister has been submerged. Dye shoots through the package when the vacuum is released, leaving trails of blue dye and bubbles where leaks are present, Bunnell says.
For leak and seal-strength measurement, Mocon is launching the Lippke 4000 and 4500 package test systems, from its Neuwied, Germany, Lippke division. Flexible and rigid packages are tested using positive pressure. The Model 4000 supports easy operation for testing off of the production line. Featuring a high-flow option for testing porous packages, the units will test to a more-precise level than Mocon’s Lippke 2500 SL model, says Bunnell.
The Pac Check package integrity analyzer introduced last year pulls a vacuum inside the package for measuring leak-hole size and absolute aggregate-hole size. The three-in-one tester also analyzes oxygen headspace and package volume as other variables affecting product shelf life. In calculating aggregate-hole size, the analyzer correlates measured pressure and flow with material thickness or seam length entered in by the operator, detecting holes and channel leaks from 20 µm in diameter. AccuLeak technology used in the Pac Check Models 820 and 840 is “far more accurate” than positive-pressure decay leak testing, besides providing the aggregate-hole size measurement, Bunnell adds.
Solutions have emerged that support nondestructive testing, allowing normal packaging to be returned to the line. Waste is eliminated, which is of particular concern when higher-priced functional medical devices are tested in their packaging.
For meeting AAMI/ANSI/ISO 11607:2006 package testing requirements for medical devices, ASTM has defined several standard methods for nondestructive testing.
TM Electronics (Boylston, MA) offers the TME Solution-C testers for nondestructive leak testing of sealed flexible packages, as well as induction-welded seals on pharmaceutical bottles. For nondestructive leak testing, Uson (Houston) features its Qualipak line of vacuum chamber–style units for in-line audit testing of flexible packages and rigid containers.
Many of these newer units feature advantages such as rapid test completion, minimal required operator skill levels, and pass-fail results that require minimal operator interpretation. Test results derive from quantitative measurement, without the subjectivity inherent in visual inspection used in bubble immersion and dye-penetration testing.
These nondestructive technologies have made inroads as replacements for or as supplements to established destructive testing methods. But the cost of the equipment is a drawback for many companies.
Karen Greene, technical director, DDL (Eden Prairie, MN; Costa Mesa, CA), says that newer testing equipment provides “more precise, more finite analyses” of package characteristics, but is often too expensive or is limited in the applications for which it can be used.
“The technology can be a substantial capital investment for smaller-sized companies and start-ups as well as for larger companies that desire to proliferate this technology across global manufacturing facilities,” says Greene, a former senior manager, package engineering, with Edwards Life Sciences (Irvine, CA).
Also, “in my experience, the test equipment has limited package design application,” such as for addressing larger-sized devices and packages, Greene adds.
The VeriPak Model 325 from Packaging Technologies & Inspection provides nondestructive vacuum-decay leak testing for rigid, nonporous packages such as vials and bottles.
“Though there are limitations to the widespread application of these nondestructive technologies, they are viable options for precision leak detection. It is reasonable to assume that the technology will continue to improve its applicability,” Greene says.
For nondestructive integrity testing of packaging that incorporates porous barrier materials, Mocon offers the Pac Guard Model 500. The device tests trays for holes and channels using CO2 tracer gas, following ASTM standard F2228-02. The typical sensitivity of the $40,000 unit is 100 µm for channels and leaks in the seals and 50 µm for pinholes and leaks in the trays, says Bunnell.
“Companies face having to justify any changes to their SOPs with FDA. Nondestructive test methods are always going to be higher priced, and it is often more than people are willing to pay. As a replacement for visual inspection methods, newer technology has to meet [a] firm’s investment requirements,” Bunnell says.
Uson’s Qualipak units range in cost from $13,000 to $16,000. “We have found that once customers purchase the testers, they will buy multiple units. The hard part is finding someone who will champion the introduction of the technology,” says Martin Bryant, sales and marketing director.
ASTM standard F2338-05 describes a nondestructive leak testing method using vacuum-decay technology for a variety of package configurations. VeriPac Models 225 and 325 vacuum-decay inspection systems from Packaging Technologies & Inspection (PTI; Tuckahoe, NY) were used in developing the standard’s precision and bias documentation. Approved in 2003 by ASTM committee F02, the Standard Test Method for Nondestructive Detection of Leaks in Packages by Vacuum Decay Method was updated in 2005 to include testing of flexible nonporous packages.
“The only package not described in the standard is a fully porous package,” says Dana Guazzo, PhD, president, RxPax LLC, a pharmaceutical package development consultant firm (Bridgewater, NJ). Guazzo served as the independent laboratory coordinator for the precision and bias studies performed to support ASTM F2338-05.
The test method’s advantages include that it can be performed quickly without the complications of human intervention and the cost of package destruction. Packages can be tested 100% on-line, or pulled off-line for sampling, Guazzo says.
“Because this test is completely non-destructive, tests can be repeated on the same product sample. Many more packages can be evaluated, giving you more confidence in your process,” says Guazzo.
For testing nonporous rigid packages, the test can detect hole defects down to 5 µm in diameter. PTI tested induction-sealed high-density polyethylene screw-cap bottles in which microscopically validated defects were created in the induction seal located under the screw cap. For testing trays sealed with porous lidding, a flexible bladder covers the porous lid to mask gas flow, after which a vacuum is created to a predetermined level. Pressure change resulting from any leaks is measured with a pressure transducer. Holes in tray or cup walls of at least 100 µm are detected, and seal-area channel defects made using wires of 125 µm in diameter are found.
“Based on published FDA recall notices, seal-area defects result in the greatest number of product recalls because of package integrity failure for medical device packages such as lidded trays or pouches,” Guazzo says.
Package quality is accepted or rejected, based on the quantitative measurement of the chamber pressure change over time. A volumetric airflow meter calibrated to a NIST leak rate standard can be used with the system for verifying the sensitivity of the test, she adds.
“PTI models (in this testing method) provide results that are more reliable and repeatable than methods that depend on the ingress and detection of liquids such as dye leak tests, because there is no human intervention or subjectivity involved,” says Heinz Wolf, general manager, PTI.
“Tracer-gas detection methods have the potential to be more sensitive than vacuum decay. However, for packages with relatively large leaks, trace gas may be lost prior to leak testing, resulting in false ‘no leak’ results. Vacuum decay can detect both very large leaks and leaks down to a single-digit-micron defect hole size,” Wolf says.
PTI offers the ASTM-approved vacuum-decay technology for non-destructive testing of seal integrity and cavity leaks in blisters, with the VeriPac 225/BLV. The unit features an integrated vision system providing a screen display of the location of defective blister cavities with test results. A new user interface allows the operator to quickly change to a different test format in environments running multiple blister styles.
“For process control applications, the VeriPac 225/BLV provides easily validatable results without the sample preparation and subjectivity required in methods such as bubble testing,” says Wolf.
A PATH TO MICROBIAL TESTING
Ondrea Kassarjian, quality manager, Lansmont Corp. (Monterey, CA), was hired recently to expand the scope of Lansmont’s primary packaging testing services. “Nondestructive test methods are very desirable for packaged product worth thousands of dollars. But these solutions are not always perfect. Airborne ultrasound is an interesting and promising technology. I have had false negatives with vacuum decay, where a package with a defect has passed the test. For identifying gross defects, visual inspection is a commonly used method,” she says.
Package testing companies such as DDL and Nelson Laboratories Inc. (Salt Lake City) employ a phalanx of standard test methods for whole package integrity leak testing and seal-strength testing. Nelson Labs offers microbial barrier challenge testing for whole packages and for specific porous materials following ASTM F1608.
DDL tests and validates packaging for medical devices and pharmaceuticals following ISO, ASTM, and ISTA standards, and ICH and USP guidelines, says Greene.
“Test methods for whole package and seal integrity, package stability, and quantification and qualification of seal strength demonstrate that the package provides a sterile barrier for the product, through rigorous testing that challenges the package for specific environmental conditions,” Greene says.
DDL also provides thermal package testing, environmental conditioning, and simulated distribution/package performance testing.
Greene says the revised ISO 11607 standard provides a more comprehensive list of suggested or informative test methods for evaluating the performance of the packaging materials for the sterile barrier system. The only normative, or required, standard is ISO 5636-5 (ISO 11607 Part 1, Annex C) that calls for demonstrating the resistance of impermeable materials to the passage of air. Greene notes that this air-permeation testing is typically performed either by the material converter or the medical device company.
For package stability testing employing accelerated aging, DDL follows ASTM 1980, for which a revision was recently endorsed by committee F02 (F1980-07). “The revision specifies the use of more realistic humidity levels based on the equivalent moisture content in air as compared to 23°C and 50% RH for a selected elevated temperature for accelerated aging. This revised approach avoids the potential unnatural physical changes to materials such as delamination of water-based laminates and coextrusions,” Greene says.
DDL is a sponsor of the project spearheaded by the Michigan State School of Packaging to define the impact of hole size on microbial contamination and provide a new method for whole package microbial barrier testing. Project results promise to yield several commercial advantages, says Greene.
“While there are numerous physical tests, a need still exists for a standardized full-package microbial-challenge test that overcomes the problems of earlier microbial challenge methods, such as lack of method standardization and variable test results. A standard microbial test will provide an additional tool for validating a package and provides the microbial contamination reference,” says Greene.
Physical test methods will benefit from the project’s work to quantify the minimum hole size that will compromise package sterility and find out “when is a hole really a problem.” The hole size and package conditions will be standardized, allowing testers to standardize and validate test methodologies to identify leaks no smaller than the defined hole size, she says.
“The objective is not package perfection; it is maintenance of sterility. It is not reasonable to fail a package because of holes or breaches that have no sterility consequence,” says Greene.
The Michigan State working group has published results on the whole package microbial method (online at the Journal of Testing and Evaluation, May 23, 2007, issue, Paper ID JTE 100869). The test aseptically introduces agar growth medium into a sterile package, after which trays are challenged with microbes. Testing performed by the project to date has demonstrated that 10-µm and 100-µm holes have the potential to allow microbial penetration in nonporous lidded trays.
The next phase will examine the impact of secondary packaging on microbe ingress. “We are working on the design of experiment. Different variables will be considered, [but] the secondary packaging will be the focus,” she says.
“People are concerned about testing sensitivity, but in reality, we don’t know what the critical hole size is yet. [And] other factors besides hole size come into play, such as pressure differential and microbe motility,” Kassarjian says. In other words, as testing technology drives for testing uniformity, higher accuracy, and better science, it will be useful to establish what the testing should be looking for.