Medical Device Link.

FLEXIBLE PACKAGING

Seal transfer is often used to assess a sterile barrier system. Photo courtesy Tolas Healthcare Packaging.

In 1997, a groundbreaking standard emerged that outlined the requirements to validate and prove the performance of sterile barrier packaging, materials, processes, and systems. ISO 11607: 1997, “Packaging for Terminally Sterilized Medical Devices,” created a common platform and language for qualifying materials and processes for sterile barrier packaging, for the first time in our industry’s history. The document was the result of the collaboration of numerous professionals working in the medical device packaging field. It compiled the full depth of their knowledge into one standard.

In accordance with the requirements for the periodic revision of a standard, the original document was revised and updated in 2003. In 2006, the standard was harmonized with EN 868-1, “Packaging Materials and Systems for Medical Devices Which Are to Be Sterilized.”

The 2006 revision of ISO 11607 was divided into two distinct sections: “Part 1: Requirements for Materials, Sterile Barrier Systems, and Packaging Systems,” and “Part 2: Validation Requirements for Forming, Sealing, and Assembly Processes.” Again, leaders in the medical device packaging industry worked together to provide additional clarity and precision to the myriad requirements for sterile barrier systems. The latest revision reflects the changes and advancements in both technology and regulations in the medical device industry.

To complement the release of the new standard, the AAMI guidance document, Technical Information Report (TIR) 22:2007, was updated. The Sterilization Packaging Manufacturers Council (SPMC), part of the Flexible Packaging Association, has distilled the complex requirements of the standard and the guidance document into a two-article series. This first part explores two critical areas: design inputs and the selection and evaluation of materials. Also interpreted is the complexity of three elements: sterile barrier system and protective packaging design (packaging system development), packaging process feasibility evaluation, and sterile barrier system design feasibility evaluation. In part two, to be published in the November 2007 issue, system elements of package and process validation are explained in three sections: validation of sterile barrier system manufacturing processes, final packaging system design validation, and revalidation.

DESIGN INPUTS

Starting the design process for the packaging system early in the development cycle of the device is key to project success. Such an approach provides opportunities to create a packaging system that enhances device functionality while maximizing economics. The first step is to determine the design inputs, those constraints that will shape the development process. Gathering design inputs should involve the product design, package development, manufacturing, regulatory, marketing, and sales departments, as well as the customer.

This collaborative process will consider the following nine drivers, as detailed in Annex D of AAMI TIR 22:2007:

Device Attributes. Physical characteristics of the device are pertinent to designing the best possible packaging system. They include size, weight or mass, center of gravity (used to determine best orientation), profile (shape), sharp edges or points, surface (rough, polished, coated), shelf life, and the ability to reconfigure (if desired to increase packaging options).

Device Protection. The device must be shielded from damage. At a minimum, device sensitivities or fragility levels should be understood and addressed sufficiently in relation to the following hazards: temperature, humidity, UV or visible light, oxygen (or other gases), shock, compression, and vibration.

Storage, Distribution, and Handling. The storage environments should be known. They may include those at the manufacturing site, distribution centers, and end-user facilities. For example, if the product is to be stored in an uncontrolled warehouse, temperature and/or humidity may require special packaging to protect temperature- or moisture-sensitive devices. Distribution environments should also be characterized to include modes of transportation such as ground, air, single parcel, etc. Handling should be understood, including method (manual or mechanical) and amount prior to device use.

Manufacturing. Capabilities are important to know when designing a packaging system. Can packaging be readily processed on existing equipment or will it require new equipment or outsourcing? Location(s), equipment, process validation requirements, and training needs must all be understood.

Sterilization. The sterilization process must be determined prior to designing the packaging system. The sterilization method may determine what materials and package types are suitable. For some applications, it may be required to design a packaging system that can be sterilized using more than one sterilization process or one that can be processed multiple times. (For an overview on sterilization procedures and how they influence design, see part two in the November issue.)

Marketing. Key factors that may influence the packaging system design include the customer or end-user, market distribution (domestic or international), requirements for multiple languages, and configurations needed, such as singles, multiples, or bulk. Product and brand identity must also be considered.

Budget. At a minimum, a budget should be known and measured against material costs, manufacturing, and the supply chain. Hidden costs such as setup charges, tooling charges, and design charges should be uncovered.

Customer. Who is going to use the device, open the sterile barrier system, and dispense it? Where is it to be used? Address ease of opening and ease of identification of the product, and any other pertinent details such as size or volume.

Regulatory. In addition to U.S. regulatory requirements, regional requirements may influence packaging ma­­t­­erial selections.

SELECTION AND EVALUATION OF MATERIALS

After establishing the design inputs, the next step will be to consider and evaluate material selection. Selection occurs concurrently with the design of the sterile barrier system and associated protective packaging. As stated in Annex E of AAMI TIR 22:2007, “Manufacturers of medical packaging can be a significant asset in determining suitable options.” Design inputs will help guide the appropriate choice.

Sterilization compatibility is critical to predetermine materials. EtO sterilization will differ from gamma sterilization or steam sterilization in terms of material options. For instance, if gamma sterilization is the chosen process, then radiation stability is key for packaging materials. Electron-beam sterilization may require careful consideration of product orientation and dose mapping. Steam sterilization may require highly heat-tolerant materials, whereas EtO sterilization would require a breathable-material component. Flexibility in sterilization may be needed, so some may need to select materials and packaging that can withstand two or more types of sterilization. Additionally it is always wise, when possible, to validate two or more cycles of sterilization in the event that resterilizing becomes necessary. All candidate materials should be tested poststerilization to ensure that material requirements are maintained.

In addition to sterilization compatibility, the following considerations found in ASTM F2097 should be taken into account:

Safety. Evaluation of materials according to safety needs may in­clude testing of extrac­tables, toxicity, retained solvents, heavy metals, and visual inspection for particulate.

Printing methods must be considered when selecting medical packaging materials. Photo courtesy Tolas Healthcare Packaging.

Barrier. From what does the device need to be protected? What materials provide the needed level of protection or exceed it? What does the packaging material need to do to control transmission of gases, water vapor, ul­tra­violet light, etc? Are combinations of materials needed to provide all the appropriate barriers? Material evaluation for breathable substrates may include testing for microbial barrier and porosity.

Durability. What does the packaging material need to do to physically protect the device? Will the device itself or the processing and distribution environment challenge material durability? Are punctures, abrasions, cutting, or flexing a concern?

Integrity and Seal Requirements. Will the packaging material(s) be capable of maintaining packaging integrity and preventing ingress of microorganisms or egress of contents? Will the packaging material(s) provide the desired seal strength?

Visibility and Appearance. Are certain visibility or appearance requirements part of the design criteria? Are there instructions that need to be read through the packaging materials? Is a glossy or matte finish desired?

Processing. Are specific material characteristics needed to ensure consistent and reliable production? Manufacturing conditions should be evaluated and materials tested for properties such as dimensional stability, thermal stability, coefficient of friction, sealability, and coat weight.

Printed Ink. Can the packaging materials be printed using the desired printing process and with the desired graphics? Will the printed ink on these materials be capable of providing physical and chemical resistance to degradation? Will printed materials hold up to exposure to sterilization conditions?

To properly select materials, one must consider all the key factors and then test accordingly. Use ASTM F2097, “Standard Guide for Design and Evaluation of Primary Packaging for Medical Products,” and AAMI TIR 22:2007 Annex E on selection, evaluation, and testing of packaging materials and sterile barrier systems for guidance in design and evaluation of primary packaging and also for selection of the appropriate test methods to evaluate the materials. ASTM F99, “Standard Guide for Writing a Specification for Flexible Barrier Materials,” is an excellent resource for properly specifying the packaging materials that are selected.

STERILE BARRIER SYSTEM AND PROTECTIVE PACKAGING DESIGN

As material selection is taking place, the design of the sterile barrier system and associated protective packaging should begin. Packaging development should follow a formal design control system. All activities should be documented, and care should be taken to address the previously identified design inputs.

A properly designed sterile barrier system will allow the device to be sterilized, will maintain sterility and device efficacy to the point of use or the expiry date, and will allow the device to be presented in an aseptic manner. The sterile barrier system can be of a type that requires only a closure seal upon loading the device (e.g., preformed tray and lid, preformed pouch, preformed sterilization bag, preformed header bag, or a reusable container); can be a self-contained device with a tortuous-path closure(s); or require complete fabrication of the sterile barrier system (e.g., form-fill-seal). The design inputs will help guide the appropriate choice.

Protective packaging is intended to do just as its name suggests: protect the sterile barrier system and its contents. It is desirable to prototype the packaging system to verify that the combination of the device, sterile barrier system, and protective packaging performs as intended. This process may be an iterative process, with improvements made as results from prototype testing are analyzed.

Finally, labeling must be considered. Labels can be preprinted directly onto packaging materials, or packaging materials can be printed in-line. Often a combination is used, with generic information preprinted and lot- and date-specific information printed at the time of packaging. Alternatively, labels can be affixed to the packaging system.

Before concluding packaging system development and beginning packaging process feasibility evaluations, the materials, dimensions, tolerances, geometry, and physical characteristics of the sterile barrier system, the protective packaging, and the labels should be specified and documented. Documents that will be useful in preparing these specifications for packaging materials are ASTM F99, and for preformed sterile barrier systems, ASTM F2559, “Standard Guide for Writing a Specification for Sterilizable Peel Pouches.”

PACKAGING PROCESS FEASIBILITY

Understanding the probable volume or rate of production for a new device is critical to designing the packaging process. This packaging process includes loading of the device and any accessories as well as sealing, and it usually includes packing in protective packaging. The rate of production will determine whether existing processes have the capacity or capability to meet the packaging needs of the new device.

If the capacity does not exist (and if the economic analysis determines it to be appropriate), it will be necessary to define, purchase, and install that capacity. The time required for this new equipment installation, validation, and operator training will be an important part of the project timeline. If utilizing existing equipment, the staffing needs of additional production will need to be considered. Any equipment modifications or new tooling will need to be obtained and validated.

Packaging system costs can be estimated after the components of the packaging system and the methods of packaging have been chosen. Packaging costs may be an important part of the total cost of the device.

Process parameters will need to be optimized at the required rate for each step of the process. After the process optimization is complete, prototype or trial runs of the entire packaging process can then be run.

STERILE BARRIER SYSTEM DESIGN FEASIBILITY

At this stage in package development, it is a good idea to evaluate the design of the packaging system. This evaluation should include real or simulated devices contained in the packaging system. Even though design feasibility is not a requirement of ISO 11607, reassurance in the design before investing significant resources in validation is valuable. The evaluation should be done in the form of an engineering study. An engineering study is a written test plan intended to screen the package against critical design inputs. Acceptance criteria for each performance test in the engineering study should include pass/fail conditions. Pass/fail criteria allow easy assessment of the results. They also offer a quick determination of whether the design should continue toward packaging system validation or be directed back to redesign. Design feasibility evaluation by means of performance testing of the packaging system provides needed confidence and direction early on in package development.

One of the goals of design feasibility evaluation is to reduce the risk of failure in the final packaging system design validation. Therefore, it may be advisable to consider the effects of worst-case manufacturing, sterilization, shipping configuration, distribution environment, and any other anticipated challenge to the design.

Package design performance testing should examine whether or not the package contained, protected, or adversely interacted with the device. Evaluations should also follow the package’s exposure to the simulated or actual distribution environment including intended sterilization processes. Common physical assessments to consider for evaluating device containment are package burst, creep, and peel-strength tests, which are all sterile barrier system strength tests. Integrity assessments for sterility maintenance often include visual inspection of the seal and dye penetration, or bubble emission tests. ASTM F2097 can provide helpful assistance in choosing the appropriate industry-standard test methods. This testing should incorporate validated test methods to ensure that the properties measured are repeatable and reproducible.

The sterile barrier system interaction with the device should be assessed. Biocompatibility should be evaluated in accordance with ASTM F2475. Other interactions between the sterile barrier system and device can be observed through a visual assessment.

CONCLUSION

To successfully complete any project, one must begin with a clear definition of the inputs and the materials needed. The design of a complex sterile barrier packaging system is no different. If proper attention is given to material selection and evaluation, the likelihood of successfully developing a sterile barrier system and a packaging system that meet functional and economic acceptance criteria will be greatly enhanced.

At this stage in the process, package design inputs have been defined, materials selected and evaluated, the package design chosen, and the feasibility of the entire design has been examined. With the proper attention to detail, the use of quality tools and test methods, and design control systems, the sterile barrier packaging system should be properly documented and ready for validation.

In part two, we will examine the characteristics for the validation of sterile barrier system manufacturing processes, final packaging system design validation, and revalidation.

The authors are all members of the Sterilization Packaging Manufacturers Council (SPMC) Technical Committee, as well as of ASTM, IOPP, and AAMI WG7 on Packaging. The SPMC is composed of manufacturers of sterilizable flexible packaging and materials. These companies work voluntarily as FPA-SPMC members to develop test methods and guidance documents for the sterilization of flexible packaging for medical devices. SPMC member companies include Alcan Packaging, Amcor Flexibles Healthcare, Beacon Converters Inc., Oliver Medical, Perfecseal, Rollprint Packaging Products Inc., Technipaq Inc., and TOLAS Health Care Packaging. The SPMC is part of the Flexible Packaging Association. Visit the SPMC Web site for more information: www.sterilizationpackaging.org.