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The benefits of producing single-use devices come with a significant number of requirements for orthopedic companies. They must understand verification, validation and testing requirements to ensure sterile devices can endure the stresses of storage, distribution and delivery.
The recent standards ISO 11607-1 and ISO 11607-2 address testing methods for materials, preformed sterile barrier systems, sterile barrier systems and packaging systems that must maintain the integrity of terminally sterilized medical devices until the point of use.
Several experts we spoke with provided insights on what device makers must do to comply with parts 1 and 2 of ISO 11607. They also discussed the best methods for packaging sterilized orthopedic devices.
Prioritized From the Start
Packaging is often a secondary concern for orthopedic manufacturers, according to NovaSterilis CEO Tony Eisenhut. “That’s unfortunate because it leads to suboptimal solutions,” he said. “It can also result in significant reengineering and additional testing of packaged devices, which drives up production costs and delays time to market.”
Eisenhut said smart orthopedic companies work with knowledgeable packaging suppliers and consultants early in the product design process. “Companies that prioritize packaging compliance run into far fewer issues and redesigns,” he said. “Collaborating with sterilization partners is a valuable exercise that minimizes the risk of late-stage project failures.”
Companies should select a compatible packaging solution that suits the lifespan of the products they’re developing, said David Opie, Ph.D., Senior Vice President of Research and Development at Noxilizer.
“Considering the packaging requirements imposed by the device, sterilization method, shipping requirements and shelf-life is essential for avoiding delays late in product development,” he said. “Selecting a packaging solution that is compatible with traditional (ethylene oxide) and alternative sterilization methods (nitrogen dioxide) provides supply chain flexibility.”
Jody Birks serves as the RA/NPI Manager at Eagle Medical in California. She has over two decades of experience in medical device contract manufacturing and sterilization. “Packaging service providers can be a valuable resource,” she said. “They have deep connections with multiple packaging suppliers and documented records of quality from each one.”
Birks advised orthopedic manufacturers to prioritize the design, materials and performance of device packaging to comply with ISO 11607-1 guidance. “Determine the materials that will protect the device physically, chemically and microbially,” she said. “Packaging materials must be compatible with the sterilization process and labeling system. Usability must also be considered.”
Birks noted that having access to multiple suppliers streamlines product design and packaging. “With the infrastructure for cleaning, assembly, packaging, labeling and sterilization in place, speed to market accelerates,” she said.
Some orthopedic manufacturers have begun adopting pre-validated packaging solutions, Birks acknowledged, while highlighting their drawbacks. “Current pre-validated materials have been tested to maintain shelf-life integrity for a predetermined amount of time using a validated sealing process,” she said. “All other stages of packaging design, packaging performance and end-user testing must still be performed.”
Validating the Process
Dr. Opie highlighted the importance of stability testing, which is noted in Section 8.3 of ISO 11607. “Stability testing uses real-time aging to show that the sterile barrier system maintains integrity until the time the product is used,” he said. “Accelerated aging data can often be used until real-time aging results are available.”
Stability testing is essential, regardless of the type of sterilization process used for a device. Some key attributes of stability testing are tensile strength, elongation, puncture and tear resistance, barrier properties, product sterility and the physical appearance of the packaging.
Specific methods for testing the physical properties of packaging material and the integrity of the sterile barrier system are provided in AAMI/ISO TIR 16775, a guidance document for the application of the requirements contained in parts 1 and 2 of ISO 11607.
A packaging system must be validated by subjecting it to handling, distribution and storage tests. “Stability testing must show that the sterile barrier system maintains integrity over time,” Birks said. “New emphasis has been placed on human factors. A documented evaluation of the ability of sterile contents to be aseptically presented must be performed.”
Birks cautioned that a significant planning period is required for orthopedic manufacturers that conduct stability tests for packaging. “ISO 11607-1 requires that companies conduct real-time aging tests,” she explained. “Real-time aging sampling should begin within three months of accelerated aging tests and before the launch of products to be compliant with the standard.”
Aging samples must be based on three key factors: risk, feature/performance and safety. “Sampling is helpful when it provides failure information that informs the design, process and manufacturing of specific components in a device or its packaging,” Birks said.
Orthopedic companies should rely on ISO 11607 to guide the validation of the packaging process. Dr. Opie said this includes having an installation qualification (IQ) for the equipment used to package medical devices; an operation qualification (OQ) to assess the upper and lower limits that produce the sterile barrier system that meets predetermined specifications; and a performance qualification (PQ) that demonstrates the sterile barrier system consistently meets predetermined requirements under selected operating conditions.
Dr. Opie added that validating the packaging process requires a sampling plan that shows predetermined acceptance criteria are met. “This plan should reflect the risk policy of the device manufacturer,” he said. “And it should be based on a statistically valid and documented rationale.”
Selecting a sample size that provides statistically significant data is key for validating the packaging of sterile devices. Considering the type of data that will be collected — variable or attribute — is also important. Variable data involves measuring a specific value; attribute data involves noting pass/fail results.
Dr. Opie said that TIR 16775 suggests using fewer samples when obtaining variable data, which is preferable to attribute data. “For this reason, selecting tests that provide variable data can reduce costs for a device manufacturer,” he said. “The sampling plan developed for validating a packaging process can be used to establish the routine sampling plan for production lots.”
Orthopedic manufacturers should adopt a “whole process” perspective to validate the packaging method, suggested Dr. Opie. Consider factors such as lot sizes, annual production volumes and risk assessments, which are outlined in AAMI/ISO TIR 16775.
The guidance document provides latitude for supporting a validation rationale based on factors such as the number of packages in a lot, the way the lot is produced and defined, the type of data recorded for a test method, variability of the measurements (standard deviation) in a test method, the level of risk that is acceptable by the device manufacturer, and costs associated with the sampling plan and testing.
Documented Proof
Dr. Opie suggested that orthopedic companies create tables with columns that note sub-clauses of ISO 11607 and the corresponding means of compliance. “This matrix ensures compliance with all elements of the standard and provides a guide for companies to follow,” Dr. Opie said.
For example, section 5 of ISO 11607-1 provides general performance requirements for materials, adhesive coatings, preformed sterile barrier systems and other packaging systems.
“A packaging manufacturer could use the compliance matrix approach to review this section of the standard line by line, identify the sub-clauses that apply to their packaging and document compliance of each packaging material,” Dr. Opie said.
Drilling down to the details involved in validating the intricate packaging of single-use devices has increased in importance as orthopedic devices have become more complex and more companies adopt the approach. Dr. Opie said, “Documenting the compliance of packaging materials to general performance requirements makes selecting an effective solution easier for device manufacturers.”
