For terminally sterilized medical devices for compliance to ISO 11607, Packaging for Terminally Sterilized Medical Devices, it is required to evaluate any changes that may impact sterile barrier integrity and determine whether a revalidation is required. So your focus should be on continuously evaluating material, process, and device changes that could negatively impact sterile barrier integrity and establishing a revalidation plan if such changes can be rationalized as impacting sterile barrier integrity. If no changes have occurred in materials, processes, or device, then it may be prudent to consider a 5-year revalidation plan in conjunction with any major shifts in regulatory policy and testing methodologies.

Seal strength and burst strength values are performance-based requirements, that is, the minimum burst or seal strength should be whatever required to meet your real world experience and required performance standard. That said, in an analytical world you would have to quantify the maximum force you would expect to be placed on your seals during their life cycle—distribution, handling (bundling, dropping), shipping, point of use, etc.  I suspect that this is not practical for you.

I cannot comment if your current burst strength specification is reasonable or sufficient for your magazine application. As pouches or sachets typically have destructive or nonpeelable seals, my gut reaction is that these are reasonably sufficiently strong seals when placed in a dynamic environment.

For sterile medical packaging, where maintaining seal integrity throughout the product or package shelf life is imperative, there is a performance-based test within ASTM D 4169, “Performance Testing of Shipping Containers and Systems” (www.astm.org to buy standard) to simulate a high altitude, low pressure situation (air shipment) that could cause nonporous packages to experience a seal breach. That is when the pressure outside the package is lower than the atmospheric pressure inside (packages sealed at sea level or a few thousand feet above sea level, which then experience high altitudes during air travel), the package will blow or puff up, stressing the seals and film.

Again, this is not a specification-driven test, but rather, a performance-based test, which may provide some increased confidence on the seal strength of your pouch package during distribution and shipping.

Your thoughts around contacting suppliers for their experience with customers in a similar application makes sense, too.

I cannot comment if the 18 PSI line pressure is appropriate, per se, for your pouch integrity tests. I can, however, direct to several industry standard tests for whole package integrity evaluation.

The positive pressurization of packages for leak detection such as the testing performed per ASTM F 2096 “Detecting Gross Leaks in Medical Packaging by Internal Pressurization (Bubble Leak Test)” has as part of the procedure a calibration step, which is essentially conducted by making a known defect in the pouch with a calibrated wire of calibrated diameter and slowly increasing the pressure until the know defect begins to leak.  The pressure level at which the known defect begins to leak is the test pressure. It is different for every package of every different type of geometry and size, hence no pressurization standard. If your package fails or bursts at or about the required test pressure then the test method may be inappropriate for that package design (assuming that seal strength is sufficient for maintaining physical integrity, as determined by other means) and you need to select a different test method, possibly a vacuum leak test.

According to ASTM F2097 “Standard Guide for Design and Evaluation of Primary Flexible Packaging for Medical Products”  under Package Integrity (the ASTM test methods for Package Integrity), perhaps trying a vacuum leak test such as ASTM D 3078 “Determination of Leak in Flexible Packaging by Bubble Emission” may be a viable alternative to prevent bursting of the new pouch.

I hope this information is useful, essentially there is no absolute minimum pressurization standard, other than the necessary test pressure as determined through those test methods utilizing positive pressure and having a test pressure “calibration” step.

I’ll take the answer from ISO 11607-1:2006, “Packaging for Terminally Sterilized Medical Devices—Part 1: Requirements for materials, sterile barrier systems and packaging systems,” Section 6-Design and Development Requirements for packaging systems, 6.1.4. It states the sterile barrier system shall maintain sterility until the point of use or until the expiry date. And 6.1.5 Maintenance of sterile barrier integrity may be used to demonstrate maintenance of sterility.

A device sterility protocol is executed at time zero to demonstrate that your selected package design, selected sterilization method, and dosage result in a sterile device per your predetermined requirements. As ISO 11607 allows that–6.1.5 Maintenance of sterile barrier integrity may be used to demonstrate maintenance of sterility–an accelerated and real-time aging study whereby package strength and integrity are evaluated at the your desired label expiry dating and shelf-life claim, there is no requirement for performing a device sterility evaluation at any aging interval. The zero time sterility validation addresses the device sterility per package design, sterilization method and dosage.

An Accelerated Aging or Shelf Life Study for the package per ASTM F 1980 with a corresponding Real-Time Aging Study (real-time aging is the requirement) will suffice for demonstration of package sterility. The Package Accelerated and Real-Time Aging Studies provide the requisite data to demonstrate that the selected package design can provide a physical integrity barrier for the device. If physical package integrity is demonstrated over the real-time claimed shelf life, then sterility inside the package is presumed.

If by “air integrity” failures you mean noncompliance to whole package integrity tests such as ASTM F 2096, “Detecting Gross Leaks in Medical Packaging by Internal Pressurization (Bubble Test) then the AQL level is accept on zero failures. Sterile barrier integrity, as measured via physical integrity, is a critical defect and no integrity failures are permissible. Additionally, sterile barrier system package validations should have as part of the protocol, a statistical rationale for the selected sample size. Regardless of the sample size the physical integrity acceptance criterion is zero defects. Another note to consider is that each individual medical device manufacturer should have a risk assessment on file for their manufactured products. There are no industry standards for risk, however, breach of sterile barrier integrity is universally considered a critical defect, relative to AQL levels.

I am making an assumption here, but if you are referring to integrity failures found as part of a set of manufacturing release criteria and if a defect is found, then a typical QA response is to determine root cause and examine packages produced prior and after the date of manufacture to determine the cause and extent of the failures, and make all prudent and required corrective actions.

Are you referring to air permeance through your porous Paper substrate?   As you have a porous substrate—Paper, there is a normative reference (hard requirement) for resistance of impermeable materials to the passage of air (Annex C) of ISO 11607. Impermeable materials for sterile barrier systems shall be tested for air permeance in accordance with ISO 5636-5. Test criterion: After not less than 1 hours, there shall be no visible movement of the cylinder, within the tolerance of +1 mm.

If I have misunderstood your question, please provide additional clarifying information.

I don’t have an authoritative answer to your question as I do not have experience with this specific issue. I would suggest that you and/or your client will have direct this question back to the foam manufacturer and likely back to the plastic resin manufacturer who produces the resin beads out of which the foam is manufactured.  You will first need to identify what type of resin is used in the foam-polyurethane, polyether, polyethylene, etc,  there exists a large array of polymers used in packaging foam manufacturing. Also, you call it foam, could it be more of an bio-based foam, using a plant based product? Another consideration: You mention that your device is an electronic device–could they have stored it in an antistatic or static dissipative foam to minimize ESD(electro-static discharge) problems? I do not know what chemical or chemicals are used in the creation of antistatic or static dissipative foams but perhaps this issue could be explored and the antistat agent evaluated for its potential reaction with gold. Regarding antistatic foams, the 2 typical foams with antistatic agents are polyethylene and polyurethane.  he foams are typically tinted pink to identify them as an antistatic foam component.

Consider the following for developing a protocol for executing a time or labor study for a thermal shipper:

1. Develop a protocol or work instruction and seek review and approval from a few key stakeholders.  Those with industrial engineering experience, manufacturing, cost accounting, quality engineering (product integrity) and package engineering responsibilities.

2.  Make sure all of the packaging personnel are trained.  Review/reread (if needed) the SOP.

3. Identify and inventory fixed assets such as freezer size and conditioning capabilities. This will impact the time for preconditioning as well as identify if any special assets will be required (such as a dedicated freezing and/or refrigerating capabilities). Determine your projected conditioning time and throughput based on your thermal package design.

4.  Have all of the components readily available, this includes applicable labeling. If gel packs or dry ice will be used, ensure that they’ve been preconditioned as required and specified.

5.  Establish a mini production line that mimics the actual or proposed production setup. Consider whether an operator is performing the packout from beginning to end. Consider that they may be taking gloves on and off, doing transactions on a computer, and possibly generating labels.

6.  Test in “live” conditions. For example, if they’re in an uncontrolled warehouse in Minneapolis in the winter or Phoenix in the summer, replicate those conditions. This includes not only the ambient temperature and humidity but manufacturing conditions such as an automated line or other processing steps that will be part of the production process.

7.  Evaluate several personnel, or a good representative population from the potential operator “pool.” This may point out those who are really good and efficient and those who require more training. You generate a bell curve of performance and determine how to optimize or maintain performance excellence.

8.  Perform the evaluation, several times, over the course of a rolling 12 months to determine variations over time and/or possibly adjust the labor standard.  You can set the standard at time “X,” however, a few more data points may compel you to more accurately adjust the labor standard.

Creating a region of heat sealed Tyvek where that sealed region has become “transparent” or “Transparentizing Tyvek” is characterized as an oversealed area or region of Tyvek.  Excerpted from ASTM F 1886-98:

“X1.4. Oversealed Areas–A combination of too much heat, pressure, or dwell time may cause oversealing to the point that it may cause packaging componenets to melt and become brittle and susceptible to cracking. When Tyvek sppunbonded polyolefin or a similar porous material is one of the substrates, this condition often is seen as a transparent or translucent seal where the material fibers are fused. This may become evident through an evaluation for pinholes or cracks along the seal. Another result of oversealing may be a spotty or incomplete looking seal, where, in this case, the heat seal adhesive is overheated an flows into the porous fiber structure of the material.”

The functional effect of oversealing Tyvek is to create potentially weakened transitional regions within the Tyvek structure.  That is, a potentially weakened region is formed in the transition area between the sealed and non-sealed areas of the Tyvek structure.  The transition area between sealed and unsealed region can be weakened, brittle and more prone to physical integrity compromises resulting from the fusing and embrittlement of the Tyvek structure.  Of course, any physically compromised area of a sterile barrier package increases the risk level for loss of physical package integrity which compromises sterile barrier integrity.

Oversealing is not a positive attribute and should be avoided by means of good sealing process development and sealing process control.  A Design of Experiments is a useful tool in developing sealing parameters which avoid oversealing your Tyvek structure.

I am not aware of any industry accepted procedures or best demonstrated practices for measuring finished packages internal vacuum or pressure.  I contacted Mr. Heinz Wolf, general manager, at PTI Industries, Packaging Technologies and Inspection, for some suggested measurement insight, as they are leaders in non destructive leak testing  Depending on your starting package vacuum, their nondestructive leak testing equipment can be utilized to derive an internal package vacuum by observing the pressure value on their equipment at the moment that the evacuated package starts to “expand” as additional vacuum is pulled on the already evacuated package.

The greatest vacuum that can be applied to the evacuated package is absolute vacuum at 29.93 in Hg. If your packages are very close to absolute vacuum (resulting from your vacuum sealing process) then no method is viable for determining internal package vacuum as insufficient pressure differential exists in order to measure vacuum.

 This method requires PTI Industries equipment or similar equipment with sophisticated pressure transducer systems for accurate pressure and negative pressure generation and measurement.

If your foil pouch seal strength is yielding a steep peel strength curve, perhaps you can consider whole package, in-process BURST testing to monitor your sealing process output. Although there is no demonstrable correlation between burst and peel strength the objective would be to develop control limits on your pouch burst strength values and routinely measure and monitor your seal integrity through burst testing data.

You can create control charts for your burst testing values for your package and establish upper and lower control limits based on your sealer operational capabilities and validated sealing parameters. Burst testing can discern a breach in the seal integrity. Furthermore, once you establish upper and lower control limits from your control charting activities, you can use your routine burst values to determine when you are trending outside your control limits and further evaluate the seal quality and integrity of the pouch to ensure you are producing acceptable seals.

I would recommend performing restrained burst testing and use a defined restraining fixture and defined headspace between pouch and fixture when performing the test to provide as much test method consistency as possible.