Validating Test Methods

ISO 11607, TIR 22, and ASTM all help manufacturers understand their package testing responsibilities.

by Daphne Allen
Editor

Test-a-Pack Systems is introducing the F100-3000 Non-Destructive Leak Tester, a bench-top unit that can identify holes as small as 10 microns. Jim Zynda reports that up to eight nonporous packages can be tested simultaneously. Chambers may be customized upon request to handle higher package quantities.

Any medical device package test that is used to support conformance with ANSI/AAMI/ISO 11607, Packaging for Terminally Sterilized Medical Devices—Part 1 and Part 2:2006, must be validated. While not a new concept, test method validation continues to challenge packaging professionals throughout the industry.

According to section 4.4.1 of ISO 11607, “all test methods used to show compliance with this part of ISO 11607 shall be validated and documented.” AAMI Technical Information Report (TIR) 22:2007, reiterates the point in 5.2.1: “All test methods must be validated.” ISO 11607 and TIR 22 then point users to Annex B’s list of “suitable test methods.”

So are the methods of Annex B all you need?

“If you follow ISO 11607, an FDA consensus document, and use the test methods in the annex, you don’t have to create your own rationale as to why another test is appropriate,” explains Jackie Daly Johnson, president of Beacon Converters (Saddle Brook, NJ) and cochair of the AAMI Sterilization Packaging Working Group, which developed TIR 22. “You don’t have to reinvent the wheel every time.”

Many of the methods listed in the annex have been recognized by FDA as consensus standards. But just because a method is listed in the annex or recognized by FDA does not mean that it will work for every medical device manufacturer and for every medical device package. Determining the appropriateness of a particular method—and validating that method for a given package and in a given lab—is the responsibility of each medical device manufacturer.

YOUR RISK, YOUR RESPONSIBILITY

It may seem contradictory, but FDA regulations do give medical device packagers some freedom. “The beauty of FDA [regulation] is that it is up to you to pick a position and justify it,” says Laura Bix, PhD, assistant professor, Michigan State University School of Packaging. “But you’ve got to be able to defend that position. There is a degree of uncertainty, so the choices you make depend upon the risks you want to assume. If you cannot defend your position, it could mean that you are not correct.”

Companies, though, may look for a less risky course of action. And that course may keep them on a path well traveled.

“Companies are looking for something in black and white,” explains Ondrea Kassarjian, training programs manager for Lansmont Corp. (Monterey, CA). For some, black and white may mean following standards tested by peers and recognized by FDA.

Sidebars: ASTM F88 and F1886 Testing Plus Sealing All in One Machine Taking in Oxygen Tests Validate Every SBS Test, advises SPMC

Explains one of Bix’s graduate students, Raghav Prashant Sundar: “As a graduate student engaged in active research, I feel that it always helps to keep pace with ASTM and ISO standards. Doing so enables us to use standardized test methods in our research projects. On a personal note, I have always felt very comfortable while talking to someone about research projects when the test methods used are based on a standard. I always seem to have a strange sense of self confidence while presenting research findings or proposals when they are based on a standard rather than some in-house method.”

UNIVERSAL UTILITY?

Alas, there is safety in numbers. If a test method has been tested for reproducibility and repeatability in several different settings, and it proves to be so, the method can be standardized. But does that mean the method is more reliable and more likely to reveal your package’s potential defects? To answer that question, you must validate that you can perform and repeat the method in your laboratory accurately with the precision necessary to identify defects particular to your package.

“Only consensus methods with precision and bias [P&B] statements are cited in TIR 22, which makes those methods easier to validate,” says Johnson. “Users compare their own facility tests—their own lab’s variability—to the P&B statements published in the test methods.”

Explains TIR 22 in 5.2.1.1: “Test methods that have been subjected to rigorous inter-laboratory studies may be preferred since the repeatability and reproducibility have been determined. When incorporating these methods into a specific laboratory it is important to demonstrate the accuracy and repeatability of the method are at least as good as the reproducibility from inter-laboratory studies.”

Says Michael L. Troedel, president of Troedel & Associates Inc. (Lake Villa, IL). “I believe the publishing of ISO 11607 Parts 1 and 2, TIR 22, and FDA recognition of physical test methods for package integrity have all led to an increased awareness of the need to validate and test medical device packaging. Furthermore, most people are just now finally becoming aware of the need to document the repeatability and reproducibility of their test methods to ensure their data being generated is valid.”

TIR 22 does say that other tests may be used. Reads 5.2.1.2: “Test methods developed independently or from the scientific literature may be used. However it is important to determine if the test method meets the required sensitivity and that the accuracy and repeatability meet predetermined criteria.”

A table of often-used ASTM methods for strength and integrity testing, by Ondrea Kassarjian, training programs manager for Lansmont Corp. (click image to enlarge)

ASTM F2097, “Standard Guide for Design and Evaluation of Primary Flexible Packaging for Medical Products,” can serve as another source of support for medical device packagers. “It complements TIR 22, presenting things a different way, such as in charts. The similarity is not coincidental—the ASTM document was written first and was very useful as a compendium in writing the guidance in TIR 22,” says Johnson.

Hal Miller, principal of PACE Solutions LLC and cochair of ASTM Committee F02 (Flexible Barrier Packaging), says that the committee is preparing a compilation of flexible barrier packaging design standards that will provide the user with all the most commonly used standards referenced in F2097. “This guide references specific individual test methods, their descriptions, and their applicability for testing, research and development, or compliance based on the characteristics of the specific product to be packaged. The design and evaluation guide is organized into several categories for evaluating flexible barrier packages and packaging materials. Each category has specific material or package properties or functions to be evaluated. The organization of the compilation follows this same structure with the standards included.” The compilation will be published in both book and CD form, and the committee hopes to have it available in the spring.

Adds Troedel: “The compendium, as currently planned, will include medical device test methods from multiple sources. It will be all inclusive and cover topics such as safety properties, barrier properties, durability, package integrity and seal strength, visibility and appearance, processing properties, transportation simulation, guides, conditioning, and definitions.”

ASTM committees play a crucial role in easing decision-making in the industry. “Through ASTM, we try to create test methods that people can utilize,” says Steve Franks, executive vice president of T.M. Electronics. He reports that ASTM Committee F02 is working to establish a new method, designated WK19529, “Nondestructive Pressure or Vacuum Decay Leak Test for Sealed Products or Packages.” Says Franks: “An interlaboratory study should be underway in the next six months.”

Another new test method is ASTM F2714-08, “Standard Test Method for Oxygen Headspace Analysis of Packages Using Fluorescent Decay.” Mocon Inc. (Minneapolis) will be participating in round-robin tests to provide correlation data with the method, reports Ed Emerson, business development, Mocon.

READY, SET . . . VALIDATE

As “off-the-shelf” as the methods in Annex B of ISO 11607 seem to be, though, if a medical device manufacturer has chosen to use a listed method, there is still work to do. “I often hear a potential user say, ‘I will just use it,” when considering a method,” say Franks. “But the reality is that the method and equipment all need to be validated with a company’s own systems and with its own operators. They have to validate that the whole process of using the method is reliable in their lab and ultimately ensures that the package being tested meets its performance requirements.”

Concludes Franks: “The wonderful thing about packaging is that there are no two packages that are alike, so no two testing programs will be alike.”

Validate Every SBS Test, advises SPMC

The Sterilization Packaging Manufacturers Council of the Flexible Packaging Association has been addressing questions about test method validation and other issues pertaining to sterile barrier systems after speaking in the 2008 PMP News Webcast, “Understanding the Nuances of ISO 11607.” To view the archived Webcast, visit www.devicelink.com/pmpn/iso11607.

A recent question posed to the group inquired about how far test method validation should extend:

Most medical device manufacturers perform in-process and/or final inspection of sterile barrier packaging seals. Do the requirements for test method validation (reproducibility, repeatability, sensitivity, etc.) apply only to test methods used to validate sterile barrier packaging, or do they also apply to tests performed as part of in-process and final inspection during routine production?

SPMC Response:

All test methods that are used to obtain data that support sterile barrier system conformance to ISO 11607 must be validated. Conformance to ISO 11607 includes ISO 11607-2, validation requirements for forming, sealing, and assembly processes. As “routine production” would be in accordance with the validated processes, the tests performed during in-process and final inspection during routine production would most likely have been performed or specified during the validation as well. Therefore, they should be validated.

Demystifying Medical Device Package Validation

Answers to frequently asked questions help guide manufacturers through the validation process.

Scott Levy Packaging Engineer DDL Inc.

Many medical device manufacturers struggle daily with what they need to do to set up package shelf-life validation and what it takes to satisfy regulatory requirements for sterile medical packaging.
Using the ISO 11607 standard as a reference guide, this article will demystify the validation process for manufacturers by answering 10 common questions.

What is validation?

According to FDA, validation is documented evidence providing assurance that a specific process will produce a product that meets predetermined requirements and quality attributes.

Why should I validate my package?

Medical device manufacturers are required to obtain 510(k) approval on each medical device package. According to the ISO 11607 standard, the manufacturer “must ensure the product and package system combine to create a total product that performs efficiently, safely, and effectively in the hands of the user.”

What is the ISO 11607 standard?

According to Section 1.1.3 of the standard, “The intent of this international standard is to provide designers and manufacturers of medical devices with a framework of laboratory tests and evaluations that can be used to qualify the overall performance of the package used to protect the device components during handling, distribution, and storage.”
ISO 11607 considers the following attributes: selection of material, design of the package, process validation, and final package validation.

What must I do prior to the validation process?

Before a final package shelf-life validation can be put together, specific questions need to be answered.

• What types of packages are we
validating?
• What type of expiration date do we want?
• What is the overall package
configuration?
• Which strength and integrity methods do I use?
• What are the glass-transition, melt, and heat-distortion temperatures of the package and product?

Which kind of testing methodologies are implemented?

Package Strength. In order to produce acceptable packages on a daily basis and throughout a determined shelf-life validation, it is important to evaluate the strength characteristic. Not only does the strength characteristic play a key role in a shelf-life validation, it lets medical device manufacturers determine on a daily basis that their process for sealing packages is consistent with their predetermined specification set in the process validation.

There seems to be some confusion in the medical device industry regarding the strength of a package versus the integrity of a package. Package strength concerns the force required to separate two components of the package. It could be the force to separate two flexible components of a pouch or a flexible lid and a thermoform tray. These forces may be measured in pounds per inch width, as in the seal/peel test, or in pounds per square inch, as in the burst-test method.

Alone, these tests of package strength do not necessarily prove the integrity of the entire package. In fact, the seal width that was actually measured may be within the strength specification but may have a channel leak that could breach the package and negate integrity.

The main culprit for poor package strength is the sealing parameters. If a proper process validation of the sealer is not performed, the medical device manufacturer can expect failure. Some typical package-strength testing includes ASTM F88-00, package strength testing by seal peel testing, and ASTM F-1140-00, package strength testing by burst testing.

Package Integrity. To maintain the sterility of an enclosed product until it reaches its point of end use, the packaging must provide a microbial barrier in the poststerilization environment. The manufacturer must demonstrate that, under the rigors of distribution, storage, handling, and aging, sterile- package integrity is maintained at least for the claimed shelf life of the medical device. The microbial barrier properties of the package materials and design must be evaluated after exposure to the environmental and dynamic stresses expected for the finished package. Several methods may be used to satisfy these requirements. They involve evaluating the material performance itself and the whole, finished package as produced on the packaging line.

Packages may lose their integrity as a result of the dynamic-related events that occur during processing and distribution. Physical test methods may be used to validate that the package integrity has been maintained throughout the package’s processing, expected shelf life, and handling. Testing includes ASTM F1929-98, package leak testing by dye penetration; ASTM F2096-02, package leak testing by bubble emission; and ASTM D3079-02 and ASTM D4991-94, package leak testing by vacuum.

What is the accelerated-aging rationale?

Accelerated aging is performed on packaged medical devices to document shelf-life and expiration times for products. Real-time aging can be performed; however, products are often obsolete by the time a three-year expiration date is validated.

Accelerated aging is based on a thermodynamic temperature coefficient formulated by van’t Hof that states, “For every 10°C rise in temperature, the rate of chemical reaction will double.” However, this formula was based on rate kinetics of a single chemical reaction, not on packages with various kinds of materials. So, the direct extrapolation of this theory to the aging of packaging materials must be used with caution. But the industry and FDA believe the theory is useful in defining and justifying accelerated- aging test programs.

How is accelerated aging performed?

The temperature that avoids unrealistic failure conditions, such as deformation due to melting, should determine temperature selection for the accelerated aging study. Real-time aging must be performed in conjunction with any accelerated-aging study to correlate the results found during accelerated aging.

In order to perform accelerated aging, the following information is required:

• Volume of material (the size of the individual packages that will be placed inside the environment chamber).
• Test temperature (the temperature at which the chamber will be set).
• Expiration date (the desired shelf life of the product/package system).
• Ambient temperature (the temperature at which the product will most likely be stored).
• Aging factor (2.0 is the most common).

The main test methodology used for accelerated aging: ASTM F1980-02.

How are packages tested for shipping and distribution endurance?

Manufacturers must evaluate the packages’ ability to adequately protect the medical device through the handling and distribution environment. Damage, such as material puncture, abrasion, or seal failure, may result from the dynamic events to which packages are subjected.

Tests performed include ASTM D4169 test sequence and various ISTA procedures. All of these test procedures address three common variables for ship testing: shock/drop testing, vibration testing, compression testing.

Why should I develop a test protocol?

Since documentation is key to the sterile medical packaging validation process, developing a protocol is essential for satisfying the ISO 11607 requirement.

What happens after testing is complete?

A final test report must be generated to document the test results, corrective actions, or other issues found during the validation process.

Make sure you allow adequate time to perform a thorough package evaluation validation. The time taken to complete the validation can vary from one to nine months. You should expect to spend $5000–$15,000 on a package shelf-life system validation, depending on the experience and expertise of the packaging engineers.

Remember that the ISO 11607 test standard is only a framework. The final objective of developing a safe and effective package system can be achieved by taking many different paths.

Developing a Master Plan for Complex Validation Projects

An overview of validation can show FDA that a process is under control.

by Erik Swain, Senior Editor

When validating a complex healthcare packaging line, a master plan can be an essential tool. Not only is it a valuable internal resource, but a correctly prepared plan can help win FDA's confidence that the process in question is under control.

Mark Celeste, validation project leader at O'Neal Inc. (Raleigh, NC), addressed the master plan's importance at a seminar sponsored by the Institute of Packaging Professionals' (IoPP; Herndon, VA) Eastern Equipment Committee Conference, held March 9 in Secaucus, NJ, as well as during an interview with Pharmaceutical & Medical Packaging News.

The master plan is not the same thing as the validation protocol. The master plan is an overview of the process to be used to validate the project. The validation protocol is the specific set of test procedures and acceptance criteria for each system being validated. The master plan is much less detailed, although the information included in the two should be consistent. Celeste says the master plan requires senior management's approval—the absence of which can cause serious doubts in the minds of FDA inspectors as to the company's commitment to the project. "The overall objective is to set out the philosophy for how you will handle the project," Celeste says. If there is no indication that senior management agrees with the objective, then the philosophy loses credibility with FDA, and so may the entire project.

THE PLAN'S CONTENTS

According to Celeste, the master plan should include the following:

• A discussion of the scope of the project.

• A physical description of the equipment.

• A rationale for each validation decision. Explain which machines are being validated and which machines are not, and explain the reasons for each decision. Celeste's advice is to validate what is defined as critical, and not to validate what is defined as noncritical, as long as the rationale justifying each decision is documented and the decisions are consistent with current practices. For the strict purposes of validation, a critical item, he says, is something that "directly affects the quality of the product being produced." That includes anything that contacts the product and anything that can cause a corrective action (such as computer systems). Some items are ambiguous. In these cases, a company must make policy decisions and attempt to maintain consistency. A lack of consistency may demonstrate a need to revisit the criticality of the system involved. It is normal to reevaluate what is critical and what is not critical, but once a decision to change a definition is made, the reasons must be documented.

• A methodology for each validation. Product qualifications document the performance of the processing and packaging equipment. Process qualifications can be used to document performances of continuous processes or of utility systems. For example, Celeste says, if a line is to run three packages for 15 products, the full product performance qualification may not have to be conducted for 15 different products for the complete line. For a drug, product performance qualifications might be conducted on each of the 15 different tablet fills, while the qualifications for the capper might be done on just the different cap-bottle combinations. A corresponding analysis of the different aspects of packaging for a medical device might be instituted, but how so would depend on the specific product.

• Identities and responsibilities of each member of the validation team.

• General acceptance criteria. Matrices are a good tool to use here. Do not describe the criteria in detail—that is for the protocol.

• Any related programs that have been conducted, such as calibration and lab testing. "List the sort of programs that will in fact support the project," Celeste says. "Many [engineers] use the finished product testing from the labs."

• A schedule tied into construction or installation schedules.

Not only should upper management have access to this document, but so should every member of the validation team and anyone who is developing the protocols, Celeste says.

The master plan may also be revised as required. Each change must be logged and explained as to why the change was made. Previous revisions of the plan should be kept on file for reference.

Sample table of contents for a master plan for a packaging line. Source: O'Neal Inc.

1. Table of Contents 2. Approval Page 3. Project Introduction 4. Scope 5. Definitions 5.1 Critical Items 5.2 Noncritical Items 6. Facility Considerations 7. Utility, Process, and Descriptions 7.1 Utility Systems 7.2 Equipment 8. Document Requirements 9. Required Protocol Matrix 10. Standard Operating Procedure Matrix 11. Support Programs 12. Responsibilities 12.1 Master Plan 12.2 Validation Protocols—Prior to Execution 12.3 Validation Protocols—Postexecution 13. Schedule 14. Acceptance Criteria

ASKED FOR BY FDA

While the master plan may not be specifically noted in any FDA regulations, its use has become common practice in the industry. "It is usually one of the first things FDA asks for" during an inspection, Celeste says. "Therefore, it can serve to limit their digging into other things. If you demonstrate you have followed the master plan, that shows preparedness and control. Without one, I would expect them to start digging from there."

It may not be necessary for simple validations, such as for a single machine. In those cases, the information that would go into a master plan may be able to be covered in the change control documents, Celeste says.

Planning can help in other ways, Celeste says. If a company has its validation people present when the machine is installed, the tests can also double as the installation qualification and the operational qualification, saving money.

FOCUS ON RESULTS

Some companies may choose to focus on specific products during validation, while others on an overall process—it will depend upon what the line is running.

But, Celeste says, what is most important is showing that "the specific products and process you're running meet predetermined acceptance criteria," which is part of a predetermined test protocol.

If the actual results do not match the predetermined criteria, "you must investigate what happened, come to a conclusion, and determine how much it affects the validation effort," Celeste says.

A serious problem likely signals a problem that should have been corrected before validation got under way, not a problem in the validation process. "In process validation, you shouldn't be solving problems," he says. "Troubleshooting should be done during development and technology transfer. It should be completed before FDA comes in—or else you must present what you've got and say how you plan to correct it."

CONCLUSION

Validation is likely to be a topic of any FDA inspection or audit. As with any system, it is important to demonstrate that the validation process is under control. A master plan is an excellent way to demonstrate that that is the case for your system.

"If a master plan is well laid out—if you describe what you're doing and the protocols are consistent with it—then FDA has more confidence that you have control over what you're doing," Celeste says. "It is definitely a document to take very seriously."

Validation of the Thermal Modeling Process for Cold-Chain Shippers

One company shows a strong parallel between phase change simulations and actual data.

By Richard M. Formato, Cold Chain Technologies Inc., and Iftekhar Ahmed, Maya HTT Ltd.

In “Bringing Cold Chain Shippers to Market Faster with Thermal Modeling” (Pharmaceutical & Medical Packaging News, May 2008), we discussed Cold Chain Technologies’ (CCT) use of predictive thermal modeling to simulate multiple design scenarios to arrive at an optimal configuration before making prototypes and conducting chamber testing. A computer program used during the modeling process lets the user pass through a number of required steps, including analysis selection, geometry creation, element selection, boundary condition application, and program execution.

As this modeling process makes certain approximations and assumptions, model validation must occur before the process can be confidently utilized over CCT’s full array of products. This article discusses the thermal modeling validation process that is being undertaken by CCT to accomplish this task, along with some of its initial results.

Thermal Modeling Validation Method

To successfully simulate thermal packaging, modeling (and validation) of the complete transient thermal response must be completed. This validation process includes, but is not limited to, the following coupled areas:

• Phase change of refrigerant(transient).

• Free convection in shipper (transient).

• Conduction in shipper (transient).

• Payload geometry approximations.

• Material properties of shipper components.

By validating each of the above areas separately, the complete thermal package can be simulated with much more certainty. In general, the validation process consists of the following steps:

• Design and execution of experiment (data generation).

• Develop simulation to model experiment.

• Run simulation and generate results.

• Compare actual data versus simulation.

• Repeat above steps until data and simulation agree within desired tolerance.

Validation of Refrigerant Phase Change

Figure 1: 316F Foam Brick (back to back) Phase Change Experimental Setup. In this experiment, two CCT water-based foam bricks (CCT 316F, 7 × 5 × 1 in.) were placed back-to-back with three TCs in between them. (click image to enlarge)

Phase Change Experiment. A robust modeling process needs accurate simulations of phase change in thermal shippers. The phase change validation process began by designing a simple, controlled experiment to model the phase change process in a similar way to what actually occurs during shipping. In one experiment, two CCT water-based foam bricks (CCT 316F, 7 × 5 × 1 in.) were placed back-to-back, with three thermocouples (TCs) in between them, and secured together. This approach eliminates the need to insert the TCs directly into the frozen bricks, and makes exact TC geometric location easy to control. The taped brick assembly was placed into an environmental chamber at –20ºC, and once all three TCs verified that the bricks were completely frozen, the assembly was suspended in a temperature-controlled (ambient, 22ºC) chamber with the configuration and direction of gravity as shown in Figure 1.

The thermal response of the brick assembly, including phase change, was measured via TC, at the locations shown in Figure 1, namely: a) 1 in. from the bottom left corner, b) the absolute geometric center, and c) the midpoint between the geometric center and the top edge. The data were collected, and temperature versus time graphs were constructed for each of the three TCs and the chamber (ambient).

Phase Change Simulation and Comparison of Results. The brick geometry was generated via solid modeling software and input into the analysis program, along with the thermal properties—density, specific heat, and thermal conductivity—of solid ice. To account for phase change from solid ice to liquid water, thermal conductivity and specific heat variation with temperature were input into the program, along with the corresponding latent heat of fusion. The brick geometry was meshed using solid elements. The air surrounding the brick was assigned room temperature properties and meshed using fluid elements (perfect thermal contact was assumed between the two bricks).

Table 1: The location of each thermocoupling shown in Figure 1 can be referenced here. (click image to enlarge)

A 3-D transient thermal model, including both conduction and free convection was then executed. To replicate the above testing conditions, an initial condition of –20ºC was assigned to the entire solid brick volume, and an initial air temperature of 22ºC was assigned to the brick surroundings. The transient model was run for 14 hours, saving data every hour. Variations of fluid volume, brick mesh size, and solver time step were completed to determine a satisfactory trade off between accuracy and solve time. The results of the simulation, and the corresponding actual data for the three TC locations “A”, “B”, and “C” are shown in Figures 2a, 2b, and 2c, respectively.

As shown in the figures, the agreement between the actual TC data and the simulation results is reasonably good. The ramp rate from –20º to 0ºC and the phase change time for each TC location are close to actual data. As the phase change time is of critical importance, these initial results are certainly promising.

Figure 2a: Foam Brick Phase Change Data vs. Simulation for TC location “A.” The agreement between the actual TC data and the simulation shows the phase change time for each TC location are close to actual data. (click image to enlarge)

Figure 2b: Foam Brick Phase Change Data vs. Simulation for TC location “B.” Here, and in Figure 2a, the values of the simulations at the end of phase change are higher than actual data, but the trends appear correct. (click image to enlarge)

Figure 2c: Foam Brick Phase Change Data vs. Simulation for TC location “C.” Here the shape of the simulated phase change curve at the end of phase change is not accurate compared to actual data. (click image to enlarge)

To improve upon the simulation, however, deviations with actual data must be analyzed and corrected via compounding. In TC locations A and B, for example, the values of the simulations at the end of phase change are higher than actual data, but the trends appear to be correct. In location C the shape of the simulated phase change curve at the end of phase change does not match the actual data. These deviations can be explained by considering the material properties input into the analysis program. Specifically, the variation in specific heat with temperature was input into the program as a “step” function (one value for solid that is switched to a different value for liquid).

In reality, the specific heat versus temperature will be smooth, showing much more of a curve. As such, the shape of the transient simulation curve will tend to “mirror” the specific heat versus temperature curve input into the program. Specific heat versus temperature data are being generated at CCT, as part of the model validation process, and will be used during future simulation runs to further compound and validate the model.

Validation of Free Convection, Conduction, Payload Geometry, and Material Properties

Experiments, similar to refrigerant phase change described above, are being designed to extend the validation process to:

• Free convection.

• Conduction.

• Payload geometry.

• Material properties.

Free convection and conduction experiments will involve the use of simple geometry, known boundary conditions and initial conditions via thermal chamber, and continually improved material properties. Steady-state analysis will be used whenever possible. Payload geometry experiments will be completed and followed by simulation to determine the relative importance of free convection and conduction. The overall goal is to find how much detail is needed for solid modeling of the product load to obtain satisfactory results. Material property determination will include all key transient thermal characteristics—thermal conductivity, specific heat, and density—for the range of components used at CCT such as shippers, refrigerants, corrugate, and dunnage. It should be noted, too, that the above phase change validation process did incorporate free convection, even though that was not the focus of the validation work. This fact provides additional evidence for the robustness of the thermal modeling techniques being used by CCT.

Comparison of simulation results and actual chamber test data has shown that CCT now has the capability to reliably model phase change of its refrigerants in a stagnant air (free convection) environment. Additional phase change model compounding will be completed as material properties (for example, specific heat versus temperature) are further developed. In addition, this validation process can, and will be, extended to other key areas for shipper simulation, including free convection, conduction, payload geometry, and material properties. Once simulation of each of these individual areas has been completed, validation of total representative shipper solutions will follow.

Isolator Technology for Vial Filling

Greater experience spells shorter time to commercial production. Turnkey isolators can now be validated within 18 months of delivery.

Jenevieve Blair Polin, Contributing Editor

At least two to three dozen isolator systems have been approved to date for commercial production of pharmaceutical products, and many more systems are in validation. At least as many are in these stages for biological products. This technology has changed the industry, both for those who are using it and for their competitors still doing aseptic filling in traditional cleanrooms.

STERILITY ASSURANCE AND COST SAVINGS

The greatest lure of isolator technology is the promise of greater sterility assurance. "Trying to save money was not part of our criteria," stresses Greg Zimmerman, a process engineer for Eli Lilly & Co. (Indianapolis). "We were looking for improved sterility assurance, getting the operator further away from the product path or critical zone."

John Barnes, manager of engineering for filling and packaging at Aventis Pasteur (Swiftwater, PA), also cites greater sterility assurance as the primary draw of isolators. "We sterilize the inside of our isolator such that our alert limit at most sites would be one colony forming unit, and we rarely get any hits. So we know that the inside of that isolator is ultraclean," he says. "Some of our products do not get sterile filtered from the bulk tank to the line, so having them in the cleanest possible environment for filling is a real plus."

"FDA looks for sound aseptic processing line design as well as maintenance and control procedures to support the design," stresses Richard Friedman, compliance officer for FDA's Center for Drug Evaluation and Research (CDER). "As long as the line is designed in a manner to prevent contamination and it's meeting CGMPs, a company doesn't necessarily have to use an isolator in order to attain the required level of sterility assurance." Traditional cleanrooms, however, are notoriously expensive to operate and hard to control. Product recalls for lack of sterility have increased. Many large pharmaceutical companies that have received warning letters from FDA regarding their traditional aseptic processing lines are making the transition to barrier isolators.

While the initial cost of a barrier isolation system is greater than that of a filling line without the isolator, operating costs are less. With greater sterility assurance, less product is wasted because of contamination. The possibility of a product recall because of lack of sterility is a cost that must be factored in for traditional cleanrooms. The overall footprint of the aseptic processing area is reduced, gowning is reduced or eliminated, the volume of air to be handled by HVAC systems is reduced, and, where appropriate, room classifications may be lowered.

Adds FDA's Friedman: "Instead of having to dismantle the line, sterilize, and aseptically assemble, firms are now able to do multiple-day campaigns, which offer another tremendous cost savings. The findings of industry when they talk about the economic benefits are that they are able to increase throughput and that they're making money on the isolator not long after they've installed and begun to run it."

Aventis Pasteur hopes to reap such additional cost savings from operational improvements. "We have plans for next year to validate the isolator to run as many as three or four days in a row without resterilization. When we get to that point, we'll start to see additional real economic advantages," Barnes predicts.

Some have proposed that having the highly automated equipment inside the isolator do more of the tasks requires fewer highly skilled personnel. "I don't agree with that," argues Jack P. Lysfjord, vice president, technology, Bosch Packaging Technology (Minneapolis). "I think the industry has downsized to the point where they are barely able to keep up with today's technology and current cleanrooms. If you throw in the complexity of a system that has its own clean environment, sterilization system, control systems, automation machinery, and microbiology requirements, as well as maintenance and general business operations, it's a more complex challenge for those who manage that operation. Maybe the actual operators themselves don't have to be as highly skilled, but they have to have some knowledge of microbiology, maybe more than what they had as a cleanroom operator."

"It's difficult to get and keep really qualified operators," says Aventis's Barnes. "One of the drawbacks to a system like that is that there are a lot of things that you can do procedurally that may cause you to lose the batch, lose sterility on either the bulk or the isolator, and throw you back hours or even a day or so. So we've worked hard to build and maintain a good, consistent crew."

BIOLOGICAL PRODUCTS

With many vaccines currently in development or in production—such as those for HIV, hepatitis C, and smallpox—protecting operators is a big concern. "These vaccines can be very dangerous to the operator," points out Oliver Bausch, vice president of Bausch + Stroebel Machine Company, Inc. (Clinton, CT). "The isolator provides greater safeguards than a conventional cleanroom."

Some unit-dose packages present an additional source of risk to operators. "We see a lot of manufacturers going toward disposable syringes, which they can market as ready-to-use products. The needle in the syringe adds an additional source of risk," Bausch says. Risk can be better controlled with isolators that provide greater separation of people and product.

The sensitivity of vaccines also makes isolators particularly invaluable. "It is more and more often the requirement to have low residual-oxygen levels within the product, or within the container together with the product," says Bausch. "With isolators, this can be better controlled, up to a level where you run the whole isolator with a nitrogen atmosphere."

Aventis Pasteur is filling 90% of its flu vaccine on an isolator line this year. Theirs is a MAFS (Mini Aseptic Filling System) unit from Bosch, running 225 to 250 10-dose vials a minute.

"There's pretty much a mandate to get the preservative out of all vaccines," Barnes adds. "Once the preservative is gone, it will be even more of an advantage to manufacture the vaccine in such an ultraclean environment."

VALIDATION

One hesitation some pharmaceu-tical manufacturers have regarding use of isolators is the fear of the seemingly never-ending validation process. Barnes says engineers at a major U.S.-based pharmaceutical manufacturer recently told him they have an isolator line that took five years to validate and never did go into commercial production. This fear of prolonged validation, however, may be based more on the experience of these hardy pioneers in this technology than on current capabilities.

Validation streamlined. "At the beginning of isolator technology, people were doing a lot of environmental monitoring," points out Patrice Cloué, director of corporate technology, La Calhène (Rush City, MN). "The trend now is to do less because it was getting very difficult to validate and now people focus on the essential. There were some data that were redundant and disturbing the validation." Particle content or air velocity, for example, he adds, are measured at one point instead of at several points within the isolator now. La Calhène provides not only isolators with integrated HVAC systems and transfer systems for getting components into the isolator, but also an extensive line of monitoring equipment.

Timeline Shortening. While early models required time-consuming custom engineering, today standardized commercial production models, such as Bosch's MAFS unit, are available for vial filling. Bosch manufactures the complete MAFS unit: the isolator, the filling system, and the air-handling units, and it has recently launched the next-generation FLM system. "That gives customers some economies of scale," Lysfjord explains. "They're working with fewer vendors, and we offer more-predictable delivery and shorter lead times." Lysfjord estimates time from order date to delivery for a MAFS unit is now at 12 months and startup through validation is at 18 months, which rivals that for traditional cleanroom-based aseptic filling installations.

"This is a very encouraging piece of information to hear, because really the lone drawback has now been essentially eliminated," Friedman says. "Isolators are getting approved; it's as simple as that. And the reason they're getting approved is because they're generally very good systems, and we've been seeing excellent results. FDA also works with these firms carefully to resolve any issues that occasionally come up in a preapproval inspection, and approval has followed rapidly thereafter."

Barnes suggests that newcomers to isolator technology consider hiring a validation group, such as Advanced Barrier Concepts. These veterans, he says, will "help with design, certainly help with validation. They'll hold your hand through the whole process."

Guidance Still Lacking. Much of the murkiness about validation requirements would be eliminated if the long-awaited revision of the aseptic processing guidelines—last revised in 1987, when barrier isolation was in its infancy—were finally made public. "At the end of September we posted a preliminary concept paper to the Internet that has all the technical commentary as a preview," FDA's Friedman says. "Following an advisory committee meeting, we will soon issue a formal guidance for public comment." (See www.fda.gov/cder/dmpq/ for more information.)

CUSTOMIZATION

Like Bosch has done with the MAFS unit, Bausch + Stroebel has also streamlined its process by standardization. Its FFV 6024/8024 vial-filling machine with a linear, continuous-motion feed interfaces with an isolator Model RRI (manufactured by Metal and Plastique, Staringen, Germany). "If the customer starts with a new facility," Bausch explains, "we can propose an ideal layout with minimal customization for a vial-filling line." If the equipment must fit into an existing facility, the vendors will customize it and make the work flow in the required direction.

The issue of component entry is key to isolator success. "Figuring out how to get things in and out of the isolator is one of the biggest challenges," Zimmerman says. Lilly uses a Getinge stopper processing system that interfaces with an RTP (Rapid Transfer Port) system. The stoppers are loaded into the system, where they can be washed, siliconized, sterilized, and dried. The system then docks with the isolator itself. This custom-engineered system was the progenitor of a similar system that is now commercially available.

The experience of B. Braun (Irvine, CA) demonstrates that it is possible to validate an isolator line and successfully launch commercial production of one of the greatest challenges: a novel drug-delivery system that is difficult to package, containing incompatible components that must be kept separate. The Duplex drug delivery system is a two-chambered bag. One chamber containing powdered antibiotic is separated by a peelable seal from the other chamber, which contains the liquid diluent that will be used for reconstitution. (See "Alternatives to PVC for IV Bags," PMP News, April 2002, for more details on this bag.) In this drug delivery system, B. Braun currently offers cefazolin and plans ultimately to offer a range of cephalosporins. These drugs are unstable as liquids at room temperature.

Manmohan Sihra, director of technical services for B. Braun, describes these challenges. "Knowing how difficult it is to automate a flexible container, I was better prepared to face the challenge of automation of this technology," he says. "And automation is the key to success with isolation technology. We had to develop the technology from scratch to engineer not only the empty container but also the isolators. You can well imagine the problems with the sensitivity of the powder. You can't have moisture with the powder, which is a highly moisture-sensitive drug. We have been able by design to accomplish all those things: to maintain a very-low-moisture atmosphere for powder filling and to immediately fill the liquid next to it in a series of isolators. We have developed automation to handle this flexible container through this series of isolators to do these operations." B. Braun uses an isolator made by Bioquell (Andover, UK) with filling equipment from IMA (Bologna, Italy).

FUTURE GROWTH

Another area of increasing demand and interest is isolation systems for aseptic potent filling applications that generally involve integrated freeze dryers as well, says Bill Friedheim, technical sales representative, Carlisle Life Sciences (New Lisbon, WI). "Due to the potency of new products in pharmaceutical development for fill/finishing, it is now absolutely essential to use isolators for containment (protection of operators) while still ensuring increased sterility assurance levels," says Friedheim.

"Furthermore, most new systems have been requiring the ability to fill and transfer vials to freeze dryers in an inert, low oxygen level atmosphere (as low as 0.25% oxygen). This requirement, along with solvent filling, leaves customers little choice other than isolation technology."

Many in the industry predict that isolators will one day be the norm for aseptic pharmaceutical filling. "One major U.S.-based pharmaceutical company has essentially mandated that any and all new filling systems that it builds and installs are going to be in isolators," says Aventis's Barnes. "That's its interpretation of where FDA is going with all this. The company feels that once the environmental data start rolling in on how clean the process of filling in isolators is, eventually FDA is going to expect isolators."

Still, despite pressures for greater sterility assurance, there appears to be a dampened demand for barrier isolator systems. Lysfjord, together with Michael Porter from Merck, has surveyed vendors and users of barrier isolators every other year since 1998. The results of this latest survey, which will be published in an upcoming issue of Pharmaceutical Engineering, show a definite downturn. Lysfjord speculates this may have to do with scarce personnel resources. "People are realizing that it takes maybe more time and energy to validate systems that are more complex, which an isolator is. And, with the issues that they're having with FDA warning letters, they're tucking their horns in on technology. They don't have resources to devote to that."

"I personally think this downturn is only a temporary reaction following the big first initial push for isolators," says Bausch. "A lot of people took a more conservative approach again, choosing rather to go with the conventional line. In the long run, however, that's going to be not the right direction."

Those who have the technology, however, are sold on it. "We're actually retrofitting our isolator with a time pressure filling system and configuring it to fill our adsorbed products," says Aventis Pasteur's Barnes. One adsorbed product is the Tripedia DPT vaccine. Because it is adsorbed with aluminum phospate, it must be kept in suspension continuously for a consistent fill. "So we're going to put more products on this isolator, and we're also considering putting an isolator in a new facility that we're working on right now," Barnes

Process Validation Responsibilities

The purpose of validating sterile barrier packaging systems is to ensure package and device integrity. All seals, regardless of who makes them, are equally important.

When utilizing preformed sterile barrier systems, the responsibility for validation of the sterile barrier system sealing process for pouches, header, and other bags is split between the sterilization packaging manufacturer and the device packager. The sterilization packaging manufacturer will validate the process of making the seals
present on the preformed sterile barrier system. The device packager will validate the process of making the closure seals.

In a form-fill-seal process, all the seals of sterile barrier systems are formed at the medical device packager. Therefore, the validation responsibility lies solely with the medical device manufacturer. For further guidance on validation considerations, review ISO 11607-2.

Test Method Validation

Meeting the test method validation requirements of ISO 11607 has often been mistaken as simply using ASTM or other published test methods. Because of the confusion, TIR 22:2007 Annex B was created to give further guidance. Using industry standards often provides the user with a head start on test method validation, but it is not required; in-house test methods may be validated as well.

When using a test method that has been through an interlaboratory study (ILS) with a precision and bias statement, such as some ASTM test methods, most of the initial validation work has been done. Since repeatability and reproducibility evaluations are supplied in the precision statement, what remains is to perform an internal repeatability study to show comparable results to the ILS. This needs to be done using same or similar materials in the ILS. This repeatability study is not intended to replicate values, but replicate similar variability. For integrity tests, the level of sensitivity is also required. If the same level of sensitivity is not required for an application, a rationale must be documented as to why. For further guidance on performing repeatability studies refer to ASTM E 691 Standard Practice for conducting an ILS to determine the precision of a test method.

In-house and other test methods that have not been subject to an ILS have to demonstrate that they are measuring the property intended, that the sensitivity and accuracy are sufficient, and that repeatability can be determined. Validation can be accomplished by consideration and examination of the following:

• Precision. Repeatability (one lab or apparatus) and reproducibility (multiple labs or multiple apparatus) is again required. For further guidance, E691 Conduction an Inter-laboratory Study to Determine Precision of a Test Method.
• Sensitivity. The detection limit of a test method needs to be determined for integrity tests.

For further guidance, refer to ASTM E1488 Standard Guide for Statistical Procedures, E2282 Standard Guide for Defining the Test Results of a Test Method, ASTM E177 Standard terms of the Precision and Bias in ASTM Test Methods, and E456 Standard Terminology Related to Quality and Statistics.

Finally, it is important to recognize that many methods are not tests but are standard means to condition samples for tests. Such methods are performed prior to testing and therefore are not required to be validated. Some conditioning methods that are sometimes mistakenly thought to be test methods are accelerated aging and distribution simulations.

Finding the Right Validation Package

Enlist your equipment provider to help you ensure quality and repeatability from your packaging process.

By Wil Caraballo, Technical Manager
Multivac Inc. (Kansas City, MO)

For pharmaceutical and medical device manufacturers, process validation is required under the Good Manufacturing Practices (GMP) regulations 21 CFR Parts 210 and 211 and 21 CFR Part 820, respectively. Within the regulations, there are several areas of manufacturing that process engineers must address to comply with these standards. Validating packaging machinery processes is crucial for compliance.

Because current standards provide only a framework, it behooves companies to employ equipment with a validation package that surpasses these guidelines. Packaging process validation refers to the documented evidence that certifies the machine has been designed to perform a repeatable process. It also defines the machine’s reactions under a variety of different circumstances.

By selecting machinery that offers a comprehensive validation package, process engineers can streamline the installation process, ensure package quality, and sustain manufacturing best practices for the life of the system. Following are a few items to consider when selecting a validation package for a new packaging process.

THIRD-PARTY CERTIFICATION

It is extremely important to work with suppliers that are able to produce machinery that is certified by third parties. These certifications often represent a higher standard of quality and can help to ensure best manufacturing practices. The following certifications apply to all types of packaging machinery:

• ISO (International Organization for Standardization) 9000-14000.

• CE Standards.

• GS Standards.

• UL Approval.

• CSA Approval.

• TUV.

Certificates with expiration dates and brief descriptions of these standards should be included in the documentation portion of the validation package. The types of certifications that are most appropriate depend on the application, so it is imperative to address this issue in the initial stages of selecting your packaging machinery supplier.

EQUIPMENT COMPONENT VALIDATION

Validation of packaging machinery components is another step toward ensuring that quality packages will be produced on a repeatable basis. Documentation can be provided on all components of a packaging system, including the machine’s software installation and handling, operating systems, error testing logs, temperature controls, tolerances of sensors, and electrical standards. The features on packaging machinery that should be validated depend on the application and the system. Working closely with your packaging machinery manufacturer to validate the appropriate components is a key element for quality assurance and FDA compliance.

CALIBRATION DOCUMENTATION

All new packaging machines need to be calibrated before they are incorporated into a production line. As specified by FDA, packaging machinery manufacturers may not calibrate a machine for a customer. There are companies that will calibrate your system, but this task is often given to the process or packaging engineer. Therefore, partnering with a packaging machinery manufacturer that provides comprehensive instructions for calibrating the machine can greatly expedite installation.

Generally, instructions should consist of a step-by-step process for retooling critical application components and a list of instruments that were used during the factory’s calibration process. Each instrument must identify the model and serial number, and a certificate of instrumentation must be supplied that includes dates and application-specific tips for streamlining the process. These documents are also necessary for maintenance, as they allow technicians to quickly troubleshoot any machine-calibration issues that may occur throughout the life of the system.

QUALITY CONTROL SAFEGUARDS

Quality control safeguards refer to the machine’s ability to track the quality of a package as it moves through the equipment and to generate a predetermined response should it be compromised. For instance, the machine could mark the package by printing error on the top, or it could shut down entirely. With an automated system, the machine could put the package into a reject bin to ensure that it is not distributed. These responses can be determined by the customer and are outlined in the machine’s validation package documentation.

The quality process differs from system to system. For automated packaging machinery, many manufacturers have incorporated sensors into its systems to ensure that all the machine’s components are consistently operating within predetermined, acceptable ranges. Types of automated systems that use sensors include tray sealers, rollstock machines, or any other piece of equipment that can be configured with an autoloader or autopacker. Some of the functions these sensors regulate are:

• Forming and sealing pressures.

• Clean separation of two packages by the knife.

• Security of the contents within the package.

• Bar code accuracy.

Machines that offer these sensors receive documentation that certifies that the sensors are working properly.

The process for ensuring package quality on chamber machines differs from that of automated systems. Validation of the seal bar is critical with chamber systems. The performance of a seal bar influences the seal time, pressure, and temperature. However, confirming temperature accuracy can be the most-challenging task.

CONCLUSION

There are several components of a packaging machine’s validation package that can help pharmaceutical and medical companies ensure compliance and expedite installation. Identifying packaging machinery manufacturers that have established validation programs, yet offer the expertise to customize a machine to your specific business needs, will help to ensure manufacturing best practices.

Can Validation Be Exciting? Frankly, it can't. But the results can be.

by Jim Wagner, Contributing Editor

Validation may not be the most glamorous job in the world, but it is very important to packaging engineers. The Institute of Packaging Professionals (IoPP) discovered just how important when it held a seminar on validation last year with the help of Pharmaceutical & Medical Packaging News. IoPP was pleasantly surprised when the seminar sold out. It succeeded partly because FDA's David Pulham was speaking, partly because some heavy hitters were on the program, and partly because few packaging departments are overstaffed with validation experts.

IoPP got the message. In the time since the seminar, it has formed a new group called the Validation Technical Committee to help members with validation. The committee is worth a look because it could become a valuable resource for information about the validation process. It also wants to do something about the lack of guidelines for validating packaging machinery.

Spearheaded by Tom MacMurray and Steve Drucker of Warner Lambert and Howard Leary of Luciano Packaging Technologies, the committee plans to establish validation guidelines and publish them through IoPP. While FDA would be unable to endorse or approve the guidelines, it could monitor them as it did the U.S. standard for the International Organization for Standardization (ISO) medical device packaging requirements. If a problem or a question came up during validation, FDA could refer to the guidelines for answers.

Work is already under way. During the committee's first meeting, groups were established to take the first steps.

First, guidelines will be written for specific types of packaging machines. The guidelines will outline the minimum validation requirements for qualifying each machine component, including how each component is to be documented. The guidelines will also spell out which parameters are to be measured and qualified.

The validation guidelines may also indicate which machines would have to be validated for regulatory purposes. It's a question that nags validation protocols and slows them down. Is it necessary to validate every labeler? Yes. But is it necessary to validate every powered conveyor and accumulator? It depends. That's what the Validation Technical Committee hopes to sort out.

Finally, the guidelines would set up standard practices for integrity testing of different types of packages. The practices would satisfy validation for a package's function. As it stands, every company has its own way of testing package integrity. If the committee succeeds, testing protocols would reference a standard. Plus, FDA would know what to expect, which could ultimately speed up product approvals.

During last year's validation seminar, FDA's Pulham was asked about protocols for validating a cartoner. A motor had burned out, the man explained, and he wanted to know whether the machine would have to be revalidated if the motor were replaced by the same model. Pulham listened to the details, paused, and replied, "Why are you validating a cartoner?"

That's the $10,000 question. FDA may not consider cartoners, palletizers, and case packers critical equipment, yet manufacturers may spend countless hours validating them anyway. The validation committee will help eliminate unnecessary validation by specifying what's critical. It will make validation easier and, ultimately, more of a tool along the same lines as statistical quality control. Now if only someone can make statistics appealing.

For more information, contact Howard Leary at Luciano Packaging Technologies (Somerville, NJ) at 908/722-3222.

Don’t Be Afraid to Reduce Risk and Redundancy

“Standardization is our friend.” Beth Staub, vice president of quality and regulatory affairs of Stryker Corp., offered these words of advice at HealthPack during her opening keynote. Focusing her talk on “lessons learned,” Staub outlined Stryker’s ongoing companywide reorganization of its packaging functions and the importance of a common packaging philosophy.

Stryker manufactures thousands of SKUs that consist of high-value products in small lots. “Orthopedic products are like shoes—there are several sizes,” Staub told the audience. With seven company divisions divided into 22 sites, “everyone did things their own way.”

When Stryker decided to move to a common corporate quality system, it found that “packaging was the greatest source of commonality,” she explained. But “we saw issues with packaging that could have been avoided.”

Staub consulted with medical packaging industry veterans Curt Larsen and John Spitzley of Spartan Design Group. “They suggested drafting ‘should-be templates and protocols’ that could be used by all sites,” she recounts. “They helped us see that a packaging system is a three-legged stool dependent upon manufacturing/process validation, package design, and stability testing.”

Staub summed up some of the key packaging lessons that Stryker learned as follows:

• A common packaging vocabulary is key. For instance, the term validation is overused and misused.

• Old habits die hard. For instance, it is not necessary to age packaging with a product, regardless of how aging was conducted in the past. Less testing is supported by guidance. But it takes confidence to eliminate testing.

• Even the best packaging engineer needs a statistician. Everyone wants to know, “How many samples do I test?” But one size—i.e., one sample size—does not fit all. A common risk-based approach is necessary for audits to go smoothly.

• Standardization is our friend. It reduces risk and redundant improvement activity, and we won’t have to do the same work over and over again.

• Remember the customer, especially when it comes to opening and waste issues.

• Design controls for packaging should mirror those for medical devices. Packaging is getting the same regulatory scrutiny as products.

• Expertise and oversight are needed. Avoid grandfathering, waivers, concessions, or deviations from procedures.

Staub found that her colleagues welcomed standardization. “I don’t have to figure it out by myself,” she heard, almost as a sigh of relief. Standardization minimizes costs and risks, she added.

Working at developing common packaging approaches for two years now, Stryker’s path forward is to solidify minimum requirements and develop common vocabulary and quality systems. Best practices will be shared through templates. “A harmonized common approach is the right way to go,” she said.

On behalf of PMP News, I asked Staub after her keynote whether anyone was afraid to make these changes because doing so could have been seen as an admission of problems that required recalls. “Everyone was meeting requirements,” she answered. “We took a harmonized approach to developing a safety net for the future. If we had found problems, we would have recalled products.”

PMP News will be sharing more articles on HealthPack 2009, including the exclusive and ever-popular nurses’ survey and panel discussion which gave attendees eye-opening feedback on packaging, in its upcoming April issue as well as in future blogs and newsletters. Check back at www.pmpnews.com/blog shortly!

For details on HealthPack 2010, which will be held March 2-4, 2010, in San Antonio and will feature even more input from nurses, visit www.healthpack.net.