Balancing Sterile Barrier Packaging and Sterilization Requirements
pplied Sterilization Technologies, provided high-level overviews of ethylene oxide (EO), irradiation, and vaporized hydrogen peroxide (VHP) sterilization methods.
During the event, Elwell and McEvoy answered a number of attendee questions, and we asked them to expand upon those answers and address any additional questions we couldn’t include in the hour-long webinar. We encourage you to log on to the now-on-demand event for their presentation.
How can we mitigate risk when performing accelerated aging testing using sterilized samples?
Elwell: In any packaging verification study, it is important to understand the performance capabilities of your selected materials. It is also important to properly set up your test protocols per industry standards. You can reduce risk by performing higher-intensity feasibility testing prior to a verification study or by leveraging existing data. In some cases, it may be feasible to shorten the duration of accelerated aging conditioning by increasing temperature or changing Q10 levels (per ASTM F1980); however, a proper analysis must be performed since this may cause additional risk to both the packaging and device materials.
Is the maximum dose study also applied in E-beam sterilization?
McEvoy: Per ISO11137, the impact of maximum dose will be assessed in all three irradiation modalities: Gamma, E-beam, or X-ray.
Is coated Tyvek more compatible with extreme conditioning (2x EO sterilization + accelerated aging) more than uncoated Tyvek?
Elwell: While coated Tyvek does improve some aspects of a seal, both types of sterile barrier systems have been tested and proven to withstand extreme conditions.
Have you seen a greater effect on the packaging materials after being sterilized with Gamma versus E-Beam?
McEvoy: We have not observed anything specifically, since testing is conducted by our customers, and often we are not privy to the results and outcomes. To our knowledge, packaging materials tend not to be of primary concern here…it’s usually a material associated with the product itself.
If a product is sterilized in a two-tray system (a sealed tray inside a sealed tray), would the product still be considered sterile if the outer tray is opened?
Elwell: If appropriate verification and validation testing is performed, and the labeling of the inner tray meets the necessary requirements, the inner tray in this situation would be considered sterile as long as the sterile barrier is still intact.
Is seal creep a higher risk in Gamma irradiation or EO Sterilization when using a film to 1073B Tyvek Pouch?
Elwell: Seal creep is a higher risk with EO sterilization because it includes sterilization cycles with a combination of heat and vacuum while gamma irradiation does not. The risk can be mitigated if the recommendations discussed in the webinar are followed.
Is it appropriate to sterilize samples from a process qualification (OQ/PQ) before testing them?
Elwell: Typically, sterilization is not part of the OQ/PQ process since outputs from the OQ/PQ process are used for in process monitoring (unless you plan to perform in process monitoring using post sterilization samples in ongoing production). Activities after the packaging process (sterilization, distribution, storage, etc.) should be addressed through the design verification process and tied back into a minimum specification as identified by the OQ/PQ process. For more information, reference ISO 11607 part 1 and part 2.
Does printing directly on Tyvek impact the porosity of the sterile packaging?
Elwell: Printing on medical grade Tyvek is not anticipated to significantly impact the porosity of the substrate. Tyvek is a fibrous material. When ink is applied to Tyvek in a printing process, it is laid on the surface of the exposed fibers and does not typically “fill in” and block off the breathability of the material. To demonstrate this, Oliver Healthcare Packaging conducted a porosity study using a Gurley Hill porosity tester. Samples of Tyvek were printed on an offset process with a full lay down of ink (worst case scenario). Porosity was then measured in the printed area and compared to an adjacent area of unprinted Tyvek. Values were reported in Gurley seconds (number of seconds required for 100 cubic centimeters of air to pass through 1.0 square inch of the material). Results indicate the full lay down of ink has little impact on the porosity of the Tyvek. The study is available from Oliver Healthcare Packaging upon request.
What is considered sufficient seal strength?
Elwell: This has been an ongoing discussion in the industry. Please refer to our Developing a New Industry Standard for Seal Strength Testing webinar by Geoff Pavey, Oliver Technical Fellow.
Is there a recommended packaging design (e.g., flexible pouch design or rigid blister with top lid design) to use when the packaging will be subjected to E-Beam or Gamma radiation sterilization?
Elwell: Most of the materials we reviewed in the webinar are compatible with both E-beam and Gamma. For more information regarding compatibility, you can reference AAMI TIR 17 or watch the webinar recording. However, it is more likely that packaging design selection will be based on device requirements and end user needs.
For the validation of a new EO cycle, is it appropriate to evaluate a worst case to represent a packaging configuration family?
McEvoy: Generally speaking, it is feasible to perform sterilization validations per product family. However, every aspect of the packaging system and packaged device needs to be addressed. Some recommended factors to consider are density of packed product/pallet load, similarity of device design, packaging configuration and materials, pack out pattern, labeling, and IFU placement.
With the incorporation of electronics into medical devices, what are the best sterilization modalities?
McEvoy: Radiation can have an impact on sensitive electronic components. This would need to be assessed and (radiation) shielding/attenuation opportunities could be explored. VHP as a surface sterilization would be an effective method.
Is there a difference between a standard VHP and a VHP Plasma process for sterilization? (Or are these the same?)
McEvoy: A number of providers in healthcare sterilization and room decontamination offer variants of VHP solution, e.g., VHP combined with other chemicals or processes. Plasma is one such variant where the plasma is suspected to assist removal of sterilant in the aeration phase, which is necessary as VHP-plasma tend to use higher concentrations of sterilant than non-plasma VHP.
If I am lowering EO concentration and increasing the EO dwell time, do I need to repeat aging studies?
McEvoy: Adjusting these parameters will have an effect on EO product residuals, with a likely reduction due to lower concentration. Increase of dwell time will add more time to the overall process at a temperature elevated beyond ambient. The additional time would still have a process falling below the max times of the original process, and thus, likely to be an effect but should be reviewed and have risk assessed in the change management process.
Is there more risk to my packaging in an EO-CO2 mixture than EO-Nitrogen cycle?
McEvoy: We have no information/data of such an impact. Both CO2 and N2 are inert gases. EO:CO2 mixed gas processes are conducted over a wider pressure scale where a portion of the process is conducted above atmospheric pressure. Would need to assess the impact of that pressure differential.
What will be the predominant sterilization method for titanium / steel implants in 3 to 5 years?
McEvoy: Implants have enjoyed the benefits of radiation processing particularly with Gamma. Likely, over the coming years, X-ray will provide a beneficial alternative and necessary capacity: same penetration and bulk processing options without the reliance on cobalt radiation sources.
Does Nitrogen injection time play a crucial role in diluting process in EO sterilization? We can’t see this time on our report—is it important to place this time in the sterilization batch report?
McEvoy: The role of N2 is to assist in the dilution and removal of air. Air and EO form an explosive mixture. N2 is used to reduce the air concentration in the chamber to a level where an explosive atmosphere is not present upon the introduction of EO gas.