Shift in Burst Values for Seal Strength from Pre- to Post- Sterilization

Answer

Before discussing the rationale for this change there are a few questions that you may have
already addressed but are still ones that must be noted here. If there is a consistent trend that
data shows a drop in seal strength from pre- to post- EtO sterilization, it is an indicator that
something is occurring that may be unexpected and worthy of investigation.

• Is the material stressed enough during the sterilization cycle that seals may be creeping
  open but not to failure? If this is the case you may need to review what is happening in the process or in the materials used throughout the process, for example if breathable areas are blocked or too small to withstand pressure changes in ETO cycles, if seals are stressed by packing configuration or weight of the product.

• Is the material conditioned after sterilization before testing? Some products may react
  differently if not conditioned before testing.

• Are the tests performed on the same machine, same settings and, if not, have they been
  tested for repeatability? If different machines are used a separate criteria may need to be setup for each. Conversely, if the differences are clearly present from machine to machine, this can be used to better equate past results and be used in the rationale to eliminate post-testing. Either way, this will require some inter-laboratory study work to be done. Validation of test methods within your lab(s) is key to understanding differences.

• Is the same test method or technique used to burst the pouches? There are restrained and
  unrestrained methods that are used in the industry. The unrestrained version (documents referenced below) has several of its own approaches that appear in picture form within the document. There is also a restrained version (ASTM F2054) that uses plates that hold the package in place and prevent it from fully expanding. If the techniques used to
  implement the test differ (differences in the gap between restraining plates, for example)
  the result will be visible in the results.

• Can pre- and post- sterilization 1” tensile peel strength tests be run to see if the trend repeats? One way to determine if there is a problem is to see if the difference in results (or trend) repeats in a seal strength tensile peel test.

• Is the difference or variation in the post- sterilization testing just a reflection of lot-to-lot
  variability? If pre-tests from the same lot get compared to the post- tests and do not show
  a drop in results but show a difference to the spec, it may be normal lot-to-lot variation or it may identify a need to investigate the process. If compared to a specification that is tighter than historical data would demonstrate, it may point toward a need to re-assess the criteria.

Rationale for Current Specification:

Three established test procedures define methods for determining Burst and Creep test criteria,
and minimum specification values. Please review the following methods to determine if your
current criteria are in alignment with these standards:

• ASTM Test Method F1140-00 (2005) “Standard Test Methods for Internal Pressurization
  Failure Resistance of Unrestrained Packages for Medical Applications”

• SPMC Standard Test Method (FPA SPMC 003-96) “Burst and Creep Package Testing Using Internal Pressurization”

• ASTM Test Method F2054-00 (2005) “Standard Test Method for Burst Testing of Flexible Packaging Seals Using Internal Pressurization within Restraining Plates”

Post-sterile Inspection:

Once you have established that your test criterion meets the requirements of these standards, we
can address your post-sterile inspection question.

Since this appears to be an established practice that has been in place for a number of years, you
probably have enough statistical evidence to prove that if your packaging has met the required
pre-sterile test criteria, your seals, and the minimum specification is sufficient for the sterilization process and distribution. You may want to begin by compiling a significant amount of your pre-sterile test results. This should be a minimum of 30 values, and cover a minimum of 3 lots. The more data that you can compile will provide additional support for your rationale for suspending post-sterile inspection.

Next step would be to correlate your pre-sterile results with the post-sterile results. These results
should be examined over the same lots/time period you chose to compile for the pre-sterile analysis. Even if you had failing post-sterile burst/creep test data, (and the default criteria for release was a minimum seal width), it still supports your rationale – if these packages were released to the field, and no sterilization failures occurred in the field.

Of key importance is tying together these three pieces of information in order to create a rationale for the change you propose. The appropriate review and approvals would follow in accordance with your corporate change policy.