Individuals responsible for medical packaging system design and validation are required to provide a safe and effective packaging system that can deliver the enclosed product to the end-user without incurring defect or risk to patient safety.
For manufacturers of terminally sterilized medical devices, compliance to ISO 11607:2006 - “Packaging for Terminally sterilized medical devices” ---Part 1 and Part 2 is a requirement. A published tool to guide and assist you in compliance with ISO 11607 is ISO/TS 16775. ISO/TS 16775 is published by ISO for compliance assistance. It is an informative document, not normative and does not include requirements, only guidance.
The focus of this article is to provide those responsible for medical device packaging system design with some key best practices and insights for the design and development of the medical packaging system. We do not address Part 2, equipment and process validation.
The following seven essentials are not comprehensive however, if they are ignored, a successful package design is at risk or delayed in the ever-critical time to market.
Packaging Essential #1: Packaging design requirements
It is imperative to define the packaging system to produce a successful package design. The packaging engineer/designer must collaborate with project team members to create a packaging design requirements document which provides a clear expectation of the function, limitations, special features, aesthetics, product/company branding, cost limitations, size limitations, sterilization method, labeling requirements, hospital/clinic storage requirements, case count and possible adverse conditions of use and/or distribution and storage. Do not limit your consultation to your Marketing and product development representative. Valuable and detailed input can be obtained from the clinical team member, the end user, such as the clinical nurse, the O.R. technician, the Cath Lab technician, and the physician. Also, consult your field sales representative for insight into competitive products. Plan a trip to a local clinical site to see first-hand the environment in which your packaged device will be deployed. Pre-arrange a visit and you will find a warm reception from the clinical staff as people love to provide their opinions.
Packaging Essential #2: Packaging System Hazard Analysis
The goal of a thorough packaging system hazard analysis is to eliminate all high-severity hazards and reduce as many medium and low severity hazards as possible1. Two prime high severity hazards are breach of the sterile barrier (for sterile barrier package) and damage to the medical device which is not easily detectable and may impact the safe and effective use of the device. Annex A (medical devices) and Annex B (in vitro diagnostics) of ISO 14971 provide a set of questions to help illicit the identification of hazards. The package/device system can be reviewed by several analysis techniques, including top-down and bottom-up approaches.2 A typical bottom-up approach is an FMEA, failure modes and effects analysis. An FMEA facilitates focus on a specific component or element, e.g. a sterile barrier system. A typical top-down approach is an FTA, fault tree analysis. You start with an undesired consequence, such as breach of the sterile barrier, and then identify the initiating and contributing events that must occur to produce it3.
In summary, perform a packaging system hazard analysis early on after the package design requirements have been established and then move through the next few essential activities of defining the clinical storage, handling, and use environments as well as the distribution and handling environments so that you can begin the valuable activity of prototyping the packaging system design.
Packaging Essential #3:
Evaluation of similar or competing devices
The value of evaluating similar or competing devices may appear to be obvious but is not rigorously put into practice. Identify your key competitors and/or comparable devices and get yourself out into the clinical setting and determine what your target customer’s love and hate about these packages. Inquire about every facet of the packaging design and request your customers to prioritize their top 3 requirements for the package.
Labeling for product identification, directions for use, barcoding and inventory management requirements
Examination of existing storage systems for integration
Ease of use of package/device
Package size as it relates to storage and use
Packaging materials utilized (primary, secondary, tertiary packaging systems)
Is it imperative that the package is see-through and why?
Does the primary sterile barrier package impede removal and aseptic technique?
Does a coiled device present a significant hurdle to good clinical application because the device has taken an unacceptable “set”?
Does the package facilitate one-handed opening and removal?
You will not have the time or resources to gather a statistically significant data set on these package design considerations but the value of a first-hand experience in the clinical setting including a dialogue with the clinical staff on their input and the reasons for their opinions will prove invaluable towards a successful package design. As a packaging design professional, you will be able to quickly discern what will or will not work based on first hand clinical input.
Packaging Essential #4:
Clinical application of the Sterile Medical Device
In Packaging Essential #3, you researched how your packaging system would be stored and staged for use on your patients. In Packaging Essential #4, you gather information on the direct use of your sterile medical device on the patient and the specific role your packaging system plays in the safe and effective use of the medical device. An extremely valuable experience for the packaging designer is to witness a like or identical clinical procedure with the devices. You will experience firsthand how the technicians, nurses and doctors access and if necessary utilize the package design to successfully execute the procedure.
Packaging Essential #5:
Distribution, storage and handling of the medical device
Today’s increasingly complex medical devices require the package designer to perform a thorough investigation of the anticipated distribution, storage and handling conditions of their medical device. Clinical trial packages require focused attention as frequently shipping, storage and handling activities contain exceptions such as prolonged storage at temperature extremes at small clinical settings. Devices are occasionally carried in luggage by members of the project team to the clinical site. Perhaps the device is temperature sensitive and requires thermal insulation, what is the temperature profile of the seasonal shipping event as well as the device temperature and humidity stability range. For air shipments, does altitude and corresponding pressure differentials create a problem for maintenance of package integrity (seals)? Seek out and discuss these issues with project team members responsible for the execution of the clinical trial (as applicable) or your shipping and logistics team for a flowchart of the distribution channel of your medical device. At this stage in your project, you are now ready to prototype your package system design.
Packaging Essential #6: Prototype the packaging system
Medical device prototype packages can be used to evaluate the performance of the product/package prior to the commitment of the validation. Prototyping packages can incorporate multiple design options that will allow you the opportunity to evaluate the performance of different designs without going into production. Parallel path development of multiple design options will help prevent the dreaded ‘starting over at the beginning’ if an unexpected packaging design flaw presents itself.
To develop a medical device packaging prototype, you must first understand the package design input requirements. These are the requirements to which the package must perform. Understanding the design input requirements is critical in the development of a medical device packaging prototype. Basic package design input requirements include; new or redesign packaging, product characteristics & hazards, device classification, sterilization method, shelf life requirements, atmospheric hazards, aseptic transfer, materials, materials compatibility, visual appearance, mechanics, manufacturing processes, performance testing, and sustainability. Brought together, the packaging prototype is an indispensable tool to be used to determine which design options will work, and help determine which design options will not.
When developing a medical device packaging prototype, there are two primary types of sources for your packaging prototype. One is the packaging design and prototyping firm. These firms specialize in designing packaging prototypes. Packaging design and prototyping firms offer an unbiased approach. This is advantageous in that you will not be obligated to a specific material combination, and the complete
packaging system is developed by one source. Typically, costs from the packaging design and prototype firm is structured on an individual unit or low quantity basis. The other primary source for the medical device packaging prototype is the materials manufacturer. The materials manufacturer is an expert with their materials. The prototype will typically be to the exact specifications of the manufactured materials. The packaging material supplier is usually able to offer packaging prototypes at little or no cost, based on the stipulation that there is a degree of confidence in securing the production materials business.
Medical device packaging prototyping is a specialized and precise discipline. A package failure recognized at the validation stage is as unacceptable as a failure in the operating room. When done right, the medical device packaging prototype can be the difference in the success or failure of a medical device.
Packaging Essential #7: Package System Performance Testing
A design process is always iterative. After you sort and filter through the input on your package system prototype, modify your package system design such that these top 3 issues can be successfully addressed:
Package can be effectively sterilized via the designated method (including materials sterilization compatibility).
Package does not render the device useless or a risk to patient safety.
Package/device can be assembled with a time standard (rough) acceptable to your manufacturing team.
You have now sourced sufficient input to develop a package system that you can run through package performance testing and seal integrity testing to refine your package system design for maintenance of sterile barrier integrity and deliver a safe and effective medical device.
For a terminally sterilized medical device, you will be pursuing compliance to ISO 11607-1:2006. This article does not present an outline for compliance to this document however; these activities support the compliance requirements specified with ISO 11607-1:2006.
For appropriate test methods to evaluate the performance of your packaging system prototype, reference Annex B within ISO 11607-1:2006.
It is important to secure actual medical devices or simulated devices to be included in this package performance testing. Inclusion of the medical device or simulated or like device will provide input towards determining the hazards of shipping and handling on the safety and efficacy of the device and device/package system. Assemble the device/package system and sterilize the test units with the production sterilization process. Consider challenging the packaging system to bring forth design weaknesses. Evaluate and correct the design as necessary.
Suggested Test Methods
Conditioning of packaging materials, packages - ASTM D4332
Performance testing - ASTM D4169 Practice for performance testing of shipping containers, ISTA 1, 2, 3 Series - International Safe Transit Association Pre-Shipment Test Procedures
Package Integrity (porous packages) - ASTM F1929 - Standard test method for detecting seal leaks in porous medical packaging by dye penetration.
Package Integrity (internal pressurization) - ASTM F2096—Standard test method for detecting gross leaks in porous medical packaging by internal pressurization (bubble test).
Seal Strength - ASTM F88 - Standard test method for seal strength of flexible barrier materials.
Visual Inspection - ASTM F1886 - Standard test method for determining integrity of seals for medical packaging by visual inspection.
Medical device evaluation--- Return the devices to your product development partner for their evaluation and input.
Analysis of Test Results
You have now executed a feasibility, package system performance test or a notebook study. The test results from the package integrity tests, seal strength and device evaluation and performance will support the completion of the risk assessment portion of the risk management process.
Findings such as physical breaches to the sterile barrier materials (films, pouches, trays), compromised seal integrity (open seals, channels) and damaged or compromised medical devices will require a package system design modification to eliminate the failures as well as possible modification to the medical device to eliminate the package failures and/or device failures. Package performance testing will be repeated with the modified package system to evaluate the improvements.
Following these 7 packaging essentials effectively and efficiently supports the required compliance to ISO 14971& 14971/A1, Application of Risk Management to Medical Devices regarding executing a risk assessment and provides valuable input towards compliance to ISO 11607-1:2006 relative to package sterile barrier integrity and medical device functionality through the hazards of handling, distribution and storage. The competitive advantage for the medical device manufacturer of executing these suggested 7 essentials is a successful medical package design.
Engage early in the medical device development process
Gather package design input from multiple relevant sources
Prototype your package system design
Performance test your prototype package design (with device or simulated device)
Evaluate package integrity and medical device performance
Iterate as required to eliminate high severity hazards and minimize medium to low hazards.
1 Ozog H, “Risk Management in Medical Device Design, “Medical Device and Diagnostic Industry, October: 112, 1997.
2 Ozog H, “Risk Management in Medical Device Design, “Medical Device and Diagnostic Industry, October: 112, 1997.
3 Ozog H, “Risk Management in Medical Device Design, “Medical Device and Diagnostic Industry, October: 112, 1997.
ISO 11607-1:2006 Packaging for Terminally sterilized medical devices---Part 1
ISO 14971 & 14971/A1, Application of Risk Management to Medical Devices
ASTM D4332 Conditioning of packaging materials, packages
ASTM D4169 Practice for performance testing of shipping containers
ISTA 1, 2, 3 Series—International Safe Transit Association Pre-Shipment Test Procedures
ASTM F 1929—Standard test method for detecting seal leaks in porous medical packaging by dye penetration
ASTM F2096—Standard test method for detecting gross leaks in porous medical packaging by internal pressurization (bubble test)
ASTM F88—Standard test method for seal strength of flexible barrier materials
ASTM F1886—Standard test method for determining integrity of seals for medical packaging by visual inspection
ISO/TS 16775—Packaging for Terminally Sterilized Medical Devices—Guidance on the application of ISO 11607-1 and -2.
Karen K. Greene, CPP is Vice President, Client Solutions Western Region, Network Packaging Partners and President, Life Pack Labs. You can contact her at firstname.lastname@example.org or visit her contributor page.