High-performance polymers are used in a variety of medical applications: implants, surgical instruments, drug delivery systems, diagnostics and more. Selecting which polymers are best suited for a medical application is an essential part of the design process. Each material must support the end use application and withstand sterilization.
Many medical applications utilizing high-performance polymers require terminal sterilization of the device prior to its end use application. Some applications also require repeated cleaning and sterilization at the point of care. Device manufacturers must consider the sterilization modality during the design phase. Choosing the wrong materials could result in a longer, and costlier, design process.
What material compatibility issues do medical device manufacturers need to consider when evaluating different sterilization techniques, designing their products and packaging them?
Different medical polymers and device applications will require different sterilization methods. “Not all medical polymers are compatible with every type of sterilization,” explains Katie Schindler, Senior R&D Scientist, Mitsubishi Chemical Group, Americas.
Common sterilization options include:
It is essential to understand early in the design process how the medical polymers intended for a specific device application may react to the chosen sterilization modality.
Ethylene oxide sterilization is a critical sterilization method–used to sterilize approximately half of sterile medical devices, according to the CDC–often chosen for devices with moisture and heat sensitivity issues that preclude steam sterilization. Devices made with thermoplastic polyurethanes (TPUs), for example, typically cannot be steam sterilized; the heat and moisture can soften and degrade the material.
While ethylene oxide sterilization is common for devices made with TPUs, it may also be possible to utilize radiation-based sterilization methods for these devices. Device manufacturers have to consider how aromatic and aliphatic TPUs react. Aliphatic TPUs tend to be less sensitive to radiation-based sterilization while aromatic TPUs are prone to changing color.
Gamma irradiation can induce changes in the molecular structure and properties of certain polymers at its standard dose of 25 kGy. For example, medical devices that have silicone rubber components will have reduced elasticity following sterilization via gamma irradiation. Some polymers, such as PEEK and polyimide, are more resistant to the effects of gamma radiation than other polymers. In contrast, PTFE and POM are very sensitive and less suitable.
Given e-beam’s shorter processing time, it typically results in “less color change and embrittlement” compared to gamma irradiation, according to Medical Device and Diagnostic Industry. X-ray irradiation also has a shorter exposure time, which often translates into less impact on polymers.
VHP is considered compatible with many polymers, but some materials, such as nylon, have compatibility issues.
Given the moisture and high temperatures involved in steam sterilization, some materials may react poorly or degrade over time. For example, steam sterilization may negatively impact laryngoscope light transmission.
These are just some of the possible material and sterilization compatibility issues to consider when evaluating materials solutions. A designer must assess all the high-performance polymers within a device assembly to ensure that they support the end use case and are compatible with the chosen sterilization technique.
“Ultimately, the medical device manufacturer must validate the chosen sterilization method for each specific device and application,” says Schindler.
The sterilization method is not the only important factor to consider when choosing medical polymers for a device. It is also vital to consider the dose and dose rate, which refers to the amount of radiation (i.e., kGy) per unit of time (i.e., seconds or minutes).
Radiation-based sterilization methods like gamma, x-ray and e-beam have varying dose rates. For example, the dose rate for x-ray sterilization can be six times higher than that of gamma irradiation.
Different polymers respond differently to varying doses and dose rates. Materials need to be considered individually when defining the sterilization parameters.
Some polymers are compatible with a specific sterilization modality only up to a certain dose, after which discoloration may occur, or material properties may be affected at increased doses. For example, polymethylmethacrylate typically can tolerate up to 100 kGy, but it will usually yellow at 20 to 40 kGy, according to a Gamma Compatible Materials Reference Guide from Nordion.
Determining dose and dose rate for sterilization parameters is a delicate process. Radiation reacts with polymers by causing ionization, which leads to chain scission. A high dose rate can have reduced oxidative degradation but can also result in localized heating.
On the other hand, a low dose rate has the potential for higher oxidative degradation but may not have the extreme effects of localized heating. The dose and dose rate need to achieve the desired crosslinking level or sterility assurance level while minimizing any material degradation.
Validation and testing are critical for determining the long-term effects of sterilization on the materials throughout the shelf life and intended use of the product. Biocompatibility testing is a vital step in the process. Following terminal sterilization, device manufacturers need to conduct biocompatibility testing to ensure there are not any unforeseen residuals or byproducts.
Considering dose and dose rate and thorough testing ensures the efficacy and safety of the device.
In addition to materials selection, manufacturers must consider device design and its compatibility with sterilization methods.
Strict regulatory standards regarding sterilization are an essential guide for medical device design. AAMI TIR17, for example, guides health care manufacturers in the selection of polymeric and other materials used in health care products according to various sterilization modalities. Device manufacturers must also consider standards like ISO 11135 for ethylene oxide, ISO 11137 for radiation or ISO 17665 for steam.
Intricate medical devices with holes and crevices–think cannulated screws, catheters with internal channels and endoscopes–add another layer of complexity to sterilization considerations in the devices design process. For example, if ethylene oxide sterilization is utilized, the device design must ensure the ethylene oxide gas can be degassed from those small spaces.
Device design has the potential to limit sterilization options. Complex geometries, thin walls and multi-material assemblies can whittle down the list of compatible sterilization options. Dimensional stability of the device needs to be checked after sterilization, especially for steam sterilization where hydrolytic degradation may occur in moisture-sensitive polymers.
Device materials must be compatible with the chosen sterilization modality, but compatibility concerns do not end there. Device manufacturers also need to determine how different sterilization methods impact the packaging materials.
For example, devices sterilized with ethylene oxide need to have breathable packaging materials to allow gas penetration and outgassing. There is a potential for ethylene oxide residuals to remain on packaging materials.
For devices that can be steam sterilized, the packaging materials need to withstand high temperatures and moisture. Steam sterilization must achieve temperatures for a duration sufficient to kill microorganisms. For devices with multiple layers of packaging or temperature-sensitive packaging, steam sterilization may not be an option.
Regardless of the sterilization method, packaging must be durable, resist degradation and be able to maintain sterility during the intended shelf life of the device. Device manufacturers must account for penetration ability of the sterilant, prevention of microbial ingress, seal integrity, environmental stability, transportation stability and biocompatibility.
Multiple factors impact which high-performance polymers and sterilization techniques are best for a specific end use application. Considering these factors early in the design process is essential for ensuring device success.
Choosing the wrong device and packaging materials can result in a device incompatible with necessary sterilization techniques, resulting in risks to patient safety. Designers have access to peer-reviewed literature, device documentation, international standards, and historical data to help them select materials and sterilization methods, but the process remains a challenging one. Partnering with the right experts can help development engineers move forward with greater confidence.
“Raw material manufacturers and sterilization companies make excellent partners in providing material expertise to development engineers,” says Schindler. “Partnering with these suppliers early in the design process can help limit blind spots and avoid potentially costly changes later in the development process.”
Disclaimer: All statements, technical information, recommendations, and advice contained in this publication are presented in good faith and are, as a rule, based upon tests and such tests believed to be reliable and practical field experience. Mitsubishi Chemical Group – Advanced Materials Division of Mitsubishi Chemical Group and Mitsubishi Chemical Group does not guarantee the accuracy or completeness of this information and it is the customer’s responsibility to determine the suitability of Mitsubishi Chemical Group – Advanced Materials Division of Mitsubishi Chemical Group’s and Mitsubishi Chemical Group’s products in any given application.