Medical Device Packaging Testing Case Study

Research Scope

The authors conducted a comprehensive study to evaluate the performance of flexible blister packaging made from DuPont™ Tyvek® 2FS™, Tyvek® 40L, and two commonly used medical papers (greater than 80 grams medical dialysis paper and 60 grams direct-seal medical dialysis paper) formed – filled – heat sealed (FFS). Approximately 2,800 packages were tested in two phases of the study.

In the first phase of the study, the thermal sealing process window range for all four blister packaging material combinations was defined, and the optimal process parameters for producing the four types of packaging were determined. All four material combinations met the specified requirements (minimum heat seal strength, seal integrity, peel performance, and visual inspection requirements), but there were some differences in heat seal strength performance. The white paper covering the first phase of the study was published in October 2018.

After completing the basic assessment, flexible blisters were processed according to the defined nominal process parameters and used to package selected medical devices (blood transfusion devices), followed by sterilization (double-cycle ethylene oxide sterilization or gamma radiation sterilization). Packaging testing was conducted by an independent and certified laboratory according to the standards listed in ISO 11607.

Figure 1. Sample of packaging for blood transfusion devices

Integrity and strength tests of the packaging were conducted before and after sterilization; environmental standard condition simulations and subsequent pallet simulation transport tests (Sequence A); as well as humid environmental condition simulations and subsequent carton simulation transport tests (Sequence B). The purpose of Sequence B was to assess whether high humidity conditions could negatively affect packaging materials and heat seals, potentially increasing the risk of sterility breaches. Standard statistical methods were applied to define the sample size.

Packaging Integrity

The packaging integrity report indicated that three of the four tested blister material combinations failed the tests. Several blisters made from medical paper (greater than 80 grams medical dialysis paper and 60 grams direct-seal medical dialysis paper) exhibited bubble leakage tests (ASTM F2096) after standard environmental simulation (Sequence A) and transport tests under humid environmental conditions (Sequence B). One blister made from Tyvek® 40L reported a failure after Sequence B testing, while all blisters made from Tyvek® 2FS™ passed.

The integrity test results indicated that increasing the weight of the paper does not necessarily reduce the risk of packaging failure. Moisture or humid environmental conditions negatively affect the integrity of the packaging after transport, especially for cellulose-based materials. (The integrity test failures for the above blisters occurred only after gamma radiation sterilization and transport testing.)

Figure 2. Example of integrity failure in medical paper blister packaging

All samples of the four blister material combinations passed the dye penetration test, confirming the integrity of all blister heat seals.

Visual Inspection

Visual inspection of the color stability and heat seal quality of the packaging materials. Among the four tested blister material combinations, two types of medical paper showed varying degrees of yellowing after gamma radiation sterilization. This indicates that gamma radiation negatively affects the appearance of the paper, likely related to the degradation of cellulose or other components. Blisters made from Tyvek® 40L or Tyvek® 2FS™ showed no noticeable discoloration.

Figure 3. Color changes in medical paper blister packaging after sterilization

According to ASTM F1886 testing method, all blister packaging heat seals were inspected before and after sterilization, with no abnormalities reported.

Packaging Strength Analysis

The heat seal strength results (ASTM F88) of each blister material combination were verified to determine whether sterilization (ethylene oxide or gamma irradiation) and humid environmental simulations, as well as subsequent transport tests, affected the data trends.

Heat seal strengths for Tyvek® 40L and Tyvek® 2FS™ blisters ranged between 3 N / 15 mm and 4 N / 15 mm, showing normal variability, and the heat seal strength remained stable after sterilization under each condition.

Heat seal strength for blisters made from greater than 80 grams medical dialysis paper was at the same level but exhibited a wider range of variability, with further increases in variability observed after sterilization and under humid conditions during subsequent transport tests.

Compared to other blister material combinations, the heat seal strength of the 60 grams direct-seal medical dialysis paper blisters was the lowest (approximately 2 N / 15 mm). This affected the data trends.

Verification analysis of burst strength results (ASTM F2054) for each blister material combination was performed to determine whether sterilization (gamma radiation sterilization) and/or humid environmental conditions and subsequent transport tests could potentially affect data trends.

Compared to other blister material combinations, Tyvek® 2FS™ blister packaging exhibited the highest burst strength, while the 60 grams direct-seal medical dialysis paper blister had the lowest burst strength. All blister material combinations, except for Tyvek® 40L blisters, showed a reduction in burst strength after sterilization and humid environmental simulations, as well as subsequent transport tests.

Burst Testing

During transport, pressure changes due to altitude and temperature variations may increase the risk of sterility breaches in the packaging. Experiments based on the modified burst strength testing of ASTM F1140 demonstrated that high permeability positively impacts the burst strength of the packaging.

This experiment clearly demonstrated the benefits of high permeability packaging, such as those made from Tyvek® 40L, which reduced the risk of package rupture during transport and handling.

Conclusion

Based on the results of Phase 2 of the study, it can be concluded that a risk-based packaging performance testing plan (e.g., including humid environmental simulations before transport tests) is essential to ensure that all device packaging meets requirements, such as compliance with the new MDR and ISO 11607 standards. Test conditions should be selected based on risk assessments that consider all potential challenges throughout the lifecycle of the device and packaging, from manufacturing to use. It is crucial to consider all aspects of risk, such as transport or extreme environmental conditions and/or sterilization methods and doses, to determine appropriate packaging materials and designs. It is strongly recommended to conduct pre-screening tests before starting any validation work to avoid costly re-validation and commercialization delays.

Authors: Nicole Kaller, Laetitia Clerc, Zhu Xueyan, Qin Lei,

DuPont (China) R&D Management Co., Ltd.

Medical Device Packaging Testing, Simulation Transport Testing

National Customer Service Phone: 4008180021

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