PCL is a leader in medical packaging engineering & testing due in large part to our experience working with a wide range of products and materials. We enjoy the opportunity of seeing what passes and what doesn’t, and using that information to help future clients with root cause analysis and design improvement. Recently we encountered a curious case of open seals with a failure mode not before seen at the lab. Though it was a challenging endeavor, we learned and grew from the investigation and were ultimately successful in identifying and recreating the root cause.
Here is the story.
Initially the client provided samples for Design Verification (DV) testing including environmental climate conditioning to ASTM D4332 and transportation simulation to ASTM D4169. The samples had been sterilized via an aggressive ETO cycle including a high pressure draw and 2x exposure. Then samples shipped to the lab via small parcel and arrived as twelve individual, large shipping boxes each containing five large thermoform trays sealed to Tyvek lids.
The climate conditioning and transportation simulation went off without a hitch. But upon visual inspection to ASTM F1886 afterwards, it was observed that 94% of trays contained open seals. Furthermore, the open seals did not leave any seal transfer to the flange of the tray despite being a coated Tyvek lid.
- Direction of the open seals was clearly from the inside-out
- Lack of seal transfer
- Consistent location of open seals on each tray – not random or sporadic
- Tray seals were known to be good upon initial sealing
Root Cause Investigation
The investigation began with a fishbone diagram to identify possible causes.
Like you’re probably thinking right now – check the seal validation! Lack of seal transfer must surely mean uneven seal gasket, improper placement of trays in the seal nest, or other sealing-related issue. Check, check, and check. The client performed a very robust seal validation – actually PCL authored the sealing validation protocols for Operational Qualification (OQ) and Process Qualification (PQ); and PCL performed the seal validation testing including seal strength ASTM F88 and dye leak ASTM F1929. And for the DV build, the engineers also visually inspected the tray seals to ASTM F1886 prior to boxing them. The seals were good initially.
Something more curious is happening.
Considering the open seals developed somewhere between shipping, sterilization, and transit simulation, we wanted to review system level stresses. Right away, the sterilization method was called into question. The samples were exposed 2x to a very strenuous validation cycle including a deep vacuum and fast ramp rate. To assess this, a set of samples were sealed and delivered to the lab non-sterile and were found to be in good condition! Possible success!
Next, the team provided samples that were sterilized via a production-equivalent sterilization process with shallower vacuum and more generous ramp rates. Again, samples were sent to the lab for inspection and found to be in good condition. Continued success!!
In good spirits, the client built a new round of DV samples, sterilized them via the production-equivalent process, and sent them to PCL for climate conditioning and transportation simulation. We processed that work in four days (this is typical with PCL’s commitment to keeping queue times at 24 hours or less) and then proceeded to visual inspections.
No luck. Open seals again. What in the curiosity is going on?
Now we questioned whether the dynamic forces of transportation could cause these open seals. Using leftover samples from the investigatory work on sterilization, we subjected non-sterile and production-equivalent-sterile samples to a heightened stress transportation simulation. This involved conducting the test severity at 1.5x Assurance Level 1:
- Higher drop heights for Schedule A Manual Handling
- Heavier target load for Schedule C Compression
- Extended vibration table time for Schedule F Loose Load and Schedule E Vehicle Vibration
The goal of the heightened stress transit simulation was to produce failures. We wanted to understand what the failure mode looks like if it were caused by transit. Following the heightened stress transit test, we were successful in producing open seals – but the results were inconsistent. The location of the open seals was more random, and the seals left seal transfer on the flange of the tray, unlike the original failures that were observed during DV.
Open Seal after Heightened Stress Transit Simulation – Note the Presence of Seal Transfer, and Direction of Open Seal is Outside - In
Not it. Very curious.
High Heat / High Humidity?
We’re feeling on to something. We know that aggressive sterilization cycles can cause this failure mode – which includes high heat and high humidity exposure. We also know that the full scale DV test includes climatic conditioning to ASTM D4332, which includes high heat and high humidity exposure; and wasn’t part of the prior root cause investigation study design. Could this be it?
To test this theory, we placed samples into our high performance climatic conditioning chambers and set the conditions to 70’c / 90% RH – both very extreme. After 3 hours we inspected the samples.
Success! We observed several open seals, from inside-out, and no seal transfer.
Condition of Seals After High Heat / High Humidity Exposure
The specific conditions of open seals, lack of seal transfer, and direction from inside-out was verified to be caused by high heat and high humidity. Those conditions are present during sterilization and transportation (specifically, environmental conditioning). With this information, where do we go from here?
Obviously, the tray needs to be sterilized – there’s no getting around this. We know that the production-equivalent ETO exposure does not produce the open seals on its own. Which is good. While humidity levels during sterilization can approach nearly 100%, the temperature (for this particular cycle is maintained around 40 – 45’C).
Environmental conditioning during transit is the true culprit. To avoid higher temperatures during distribution, a basic temperature indicator is being incorporated into the package. The temperature indicator will tell a user if temperatures have exceeded 50’c, in which case the instruction is to not use the product. This allows the validation to be performed to a modified ASTM D4332 exposure with the upper limit of 60’c reduced to 50’c.
While the processing conditions are challenging, they are certainly routine in the world of medical packaging and packaging validation. Furthermore, the overall package system design and materials of construction are also very common and don’t normally produce this result. So what gives?
This particular tray happens to be quite large and long – approximately 24” x 9” – which provides a large surface area and long segment of lidding. During thermal exposure, Tyvek can “shrink up” – even a little bit – which puts tension on the seals. Because the lidding is so large, this slight shrink-factor gets compounded which transfers more stress to the seals than what is common. Furthermore, the adhesive used to coat the lid is water based, which under the presence of high heat and high humidity can interact with moisture to weaken the bond to the tray flange. These two contributing factors, combined with the low-angle direction of peel, create the open seals with lack of seal transfer.
Curious? Not anymore!
This example highlights the need to conduct development / feasibility testing on your packaging system design before spending money on tooling and inventory. PCL has developed what we call our Design Diagnostics program which is aimed at challenging package-system designs during early stage development testing to build confidence in performance and understand opportunities for design improvement early. This critical step is key.
Contact PCL before your next project and learn how we can help you Speed to Market with Confidence.