中国国际医疗器械设计与制造技术展览会(Medtec China)2021

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December 7-9 2022 | Suzhou lnternational Expo Centre B1-E1

EO Optimization and Potential Effects on Sterile Barrier Packaging

2022-03-18

Ethylene oxide (EO) is the most common medical device sterilization modality. About 50 percent of sterile medical devices on the market are sterilized with EO. EO optimization is on the forefront of many medical device manufacturers’ minds. The benefits of their efforts to optimize EO can include: continued safe usage of EO, lower EO-residuals in products, allows for reduction in required aeration times resulting in improved customer supply chain efficiencies, may reduce cycle time resulting in additional capacity for manufacturers, and further reducing fugitive emissions to enhance health and safety.

Manufacturers must thoughtfully assess the impact of any changes to a validated process, either through paper justification, testing, or both. When a sterilization process is changed, the impact on the sterilization validation comes to mind, but other aspects may be impacted—for example, sterile-barrier packaging.

EO-optimization efforts fall into three categories: cycle changes, cycle-monitoring changes, and product and packaging changes. This article will focus on how these changes can affect the manufacturer’s packaging validation and help to more thoughtfully address the impact, either through paper justification or additional package testing.

Cycle Changes
EO sterilization cycles have four key parameters: gas concentration, humidity, temperature, and time. Changes made to any of these to optimize the cycle will impact the sterilization validation, but only some will affect packaging.

Most commercial cycles specify 500–700 mg/L EO concentrations but some recent studies show sterilization can be achieved with EO concentrations as low as 250 mg/L. Lower EO concentrations would likely have less impact on material changes resulting from EO exposure, which should not pose additional risk to packaging or product materials. Lower EO concentrations in the sterilization cycle can yield lower EO residuals, requiring less aeration time and improved patient safety. One point to remember: lower EO concentrations may require longer exposure phases to achieve sterility.

EO sterilization is commonly performed at 50° to 60°C temperatures. Increasing the temperature 5°–10°C increases reaction rate, shortening cycle time. When temperature is increased, evaluate materials to ensure the new temperature is still sufficiently below all packaging and product materials’ glass transition point (Tg); otherwise, the heat may cause unwanted damage.

Increasing the vacuum or adding additional vacuum pulses can increase gas penetration into and out of the product and packaging configuration. Increasing the EO penetration rate can decrease overall cycle time. However, increasing vacuum draw or adding additional cycle pulses can add more stress to packaging seals and may cause seal creep or rupture. Evaluate packaging to ensure sufficient breathability in the package, in order to handle increased vacuum without damaging the seals.

Many manufacturers have validated both a full and partial chamber (min/max load) configuration. Running only full chambers is another way to reduce EO utilization. EO cycles are typically designed to inject EO to a certain chamber pressure. Processing in partially full chambers may result in a higher amount of EO absorbed per pallet compared to a maximized chamber load. Only sterilizing chambers with max-load conditions can reduce the overall amount of EO used because fewer cycles will be needed to sterilize the same volume of product.

Cycle Monitoring Changes
Changes to how the sterilization process is monitored can reduce cycle times and EO consumption. No cycle-optimization tools in this category should affect packaging validation but will require additional sterilization validation testing.

The process challenge device (PCD) is the monitoring control for the sterilization cycle. PCDs consist of a biological indicator (BI) encased in a barrier to control EO-gas penetration rate and, consequently, the time to kill spores on the BI. The longer the gas takes to penetrate the barrier, the more conservative (harder to sterilize) the PCD will be. During the validation process, a PCD more resistant to sterilization than the natural bioburden is selected. The PCD is generally more challenging to sterilize than the device, providing an extra layer of safety. Sometimes, either to increase that safety margin or allow more product adoption into the cycle later, an overly conservative PCD is selected. Cycle times are based on requirements to kill or inactivate the PCD but the time to kill all organisms on the product can be substantially less. Selecting a PCD that is less conservative and more representative of the product bioburden could reduce cycle times and EO consumption.

Most manufacturer’s EO cycles are based on the “overkill” approach. A six-log reduction is demonstrated by killing all the spores on the BI in the PCD during a half cycle. The half-cycle time is doubled for a 12-log reduction, which is the routine production sterilization cycle. Most devices have far less bioburden than 106, so changing from an overkill approach to a recognized alternate method—such as a bioburden-based method—could reduce the cycle time similar to selecting an easier to sterilize PCD. The BI/bioburden approach requires more initial validation testing to characterize the device’s natural bioburden and more process monitoring to ensure the bioburden remains similar (in both numbers and types of organisms) but often results in shorter sterilization cycles that use less EO.

Using liquid inoculum vs. paper-carrier BIs during validation can impact overall cycle times. Paper carriers potentially obstruct gas pathways, slowing EO penetration into the device interior. This artificially inflates the device’s estimated resistance and leads to selecting a PCD that is harder to sterilize, leading to longer cycle times.

Product & Packaging Changes
EO optimization is a great time to thoughtfully review packaging and assess if alterations could or must be made to improve EO penetration. Paper-based products like cardboard and multi-page instructions for use (IFU) absorb EO. Higher EO concentrations will be required to compensate for EO absorbed if the load has significant amounts of paper. Reducing the amount of paper in an IFU or using an electronic IFU can reduce the amount of EO needed to penetrate the product.

Changes to protective packaging could also be made to reduce paper-based content in the sterilization load. This could be done by increasing the number of devices per shipper, removing carton boxes or protective cardboard inserts, or reducing the amount of cardboard in the shipper (e.g., by using a thinner box). Protective packaging is often over-engineered to ensure it won’t fail during extreme use. Edge of failure testing to ensure protective packaging is sufficiently protective without being over-engineered can save packaging material and sterilization costs over the long run.

Increasing the packaging material breathability will increase EO penetration as well. To accomplish this, increase the porous material’s surface area in the package (move or resize labels on porous material), change to a material with a higher porosity, or remove extra layers of protective packaging.

Stretch wrap is often used to secure the load to the pallet but is an additional EO penetration barrier. Consider changing to banding or netting, which secures the pallet without adding an extra barrier to the EO gas. Pallets can be reconfigured to include a chimney, allowing EO to access the center of the pallet easily, increasing penetration rate to the center of the pallet load.

Removing gas-path restrictions in the product will increase EO penetration. This could be as simple as opening stopcocks, separating caps, or partially disassembling the device before packaging. Product changes could alter how the product interacts with the packaging and will probably require additional packaging testing.

Conclusion
EO sterilization is critical to ensure a sufficient supply of sterile medical devices for the world. EO optimization is intended to ensure EO sterilization is available to the medical device industry for years while meeting global gas emission requirements.

Traditional EO sterilization cycles have multiple layers of overkill built into cycle development. The hardest-to-sterilize organism is used for validation studies, the number of organisms is substantially higher than the device’s natural bioburden, and the PCD to establish and monitor the cycle is harder to sterilize than the actual device. It is possible to reduce these extra layers of safety/overkill and still achieve the same sterility-assurance level, posing no additional risk to patient safety.

While many of these potential changes as part of EO optimization efforts will have no negative impact on packaging and can easily be addressed through a paper justification, there are some instances where packaging could be affected and additional packaging testing will be required. These include, but are not limited to, adding vacuum pulses or increasing vacuum draw, reducing protective packaging (less cardboard, down-gauging packaging materials, or removing layers), removing gas-path restrictions (changing device to allow better penetration), increasing temperature, and increasing breathable-surface area.

EO optimization efforts are a great time to reevaluate packaging and assess if changes could be made to reduce packaging materials and improve sterilization. Though packaging changes may necessitate additional packaging-validation testing, possible material cost savings over time may outweigh initial costs to implement and validate packaging changes.

If you are currently in the process of optimizing your EO cycles or are ready to start, the sterilization experts at Sterigenics can assist with EO-optimization efforts, and the packaging experts at Nelson Labs can assist with packaging justifications.

Article source: Medical Product Sourcing