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Regulatory Considerations and Revalidation Tests for Managing Change in Packaging Materials or Critical Supplies

In light of recent material changes within the medical device packaging industry, it is imperative manufacturers respond to triggers built into their change management process so they can (1) assess the impact a change in materials or processes has on new or old product packaging and (2) revalidate packaging following any changes to the materials or processes deemed at risk.

Medical device and drug manufacturers need to consider the regulatory requirements associated in managing these changes for packaging materials or critical supplies as well as preparing for and performing any revalidation that may be required.

Here we will show the regulatory considerations needed following a process or material change that can affect packaging and the revalidation tests that may be required.

Regulatory Considerations

  • Detect and Document the Change. Every manufacturer needs to have a way to detect changes in their critical supplies as part of managing the supply chain. Whether through a change agreement or an in-process test upon receipt of a supply, it needs to trigger a change management process.

Once detected it must go through the manufacturer’s change management system. This means updating the supplier file with the change notification received from the supplier.

  • Assess Risk and Impact of Product Change. Once the details of the change are known, then an assessment of the risk and impact on the product can be conducted – how it influences the processing, shelf life of packaging, permeability, etc. The goal is to assess the impact of the intended use of the product. Everyone, including regulatory and engineering experts, brainstorm together to get a comprehensive evaluation of the impact of the change.
  • Mitigation, Acceptance Verification, Validation. If there is an adverse impact to a medical device or drug product, it needs to be mitigated. Mitigation may include acceptance verification testing by bringing in new sample lots to ensure there is no impact to the process or product. Equivalency data provided by the material maker may help in determining the need for revalidation or acceptance testing.
  • Dissemination of Change Information to Personnel, Customers and Regulatory Authorities. Once determined and accepted, the applicable change information is disseminated to all parties who need to be aware of the change so documents can be updated as needed. Examples include purchase orders, procedures, supply specifications, regulatory submissions, and in-house regulatory files.
  • Change Management Documentation and Approvals. Implementation of change management processes should be well documented. Someone with the right authority to conduct the assessment also needs to conclude whether scoring, meeting a threshold, or whether action to assess the conclusion of each impact must be made. The important aspect is to remember someone needs to make the decision on whether the change has impact, and if it does not, document the rationale as to why there is no impact.

Ultimately, the objective is to be able to demonstrate to regulatory authorities that due diligence has been performed – awareness of the change is apparent, the impact and risk to product or process has been assessed, risks are mitigated (with an established plan to address the risk), the impact has been closed, and the loop is closed on implementation and documentation. At this point, the documentation should be filed onsite, and FDA submissions updated if needed. The manufacturer’s FDA reviewer may also be able to provide assistance in determining and ensuring all due diligence has been accomplished.

Revalidation Considerations
Once manufacturers have completed the regulatory considerations, they may find they need to reassess their packaging processes or materials. In such cases, there is a minimum of three categories that must be evaluated to validate packaging: Integrity, Strength and Microbial Barrier. The packaging standard (ISO 11607 Packaging for Terminally Sterilized Devices) indicates manufacturers choose one test from each category to evaluate their materials, sterile barrier systems or packaging systems.

A packaging matrix outlining the categories and test options manufacturers need to meet the requirements can be found here.


  • Bubble Emission Test – The bubble emission test is a ‘whole package’ integrity test. Immersing the test package in a surfactant fluid and inflating the package to a specific pressure conduct it. Bubbles originating from a single point indicate a failure in the packaging integrity. This test is used for porous and nonporous packaging.
  • Dye Migration Test – The dye migration test is conducted by injecting blue dye through the center of the package. The weight of the dye then presses against the seals of the packaging. If a seal is compromised, a visible blue channel is seen at the failed point in the seal. This test is currently not designed to test foil packages.


  • Seal Peel Test – The seal peel test evaluates the force required to open a package. It involves cutting a one-inch segment from the selected seal and placing it onto a tensile machine. The machine will then extend continuously measuring the strength required to pull it.
  • Burst Test – This test provides two pieces of information: it identifies the weakest seal on the package and provides the pressure needed to compromise or burst the seal. This test is especially important in assuring packaging can withstand the rigors of extreme altitudes such as regional elevation or air transit. Placing the package onto a probe and attaching it to the burst-testing machine to conduct the test. The air pressures will increase until it bursts.

In conjunction with the burst test, a creep test can be conducted. The creep test is similar to the burst test, but instead of increasing pressure until it bursts, the package is pressurized for an extended period of time. The set point for this test is 80 percent of its burst pressure. This test determines if the weak seal will slowly ‘creep’ to a burst.

Microbial Barrier

  • F1608 Microbial Ranking – This test provides a log reduction value of the organisms penetrating packaging material and can only be conducted on porous materials. The test involves taking a 47 mm disk of the porous material and exposing it to aerosolized organisms. The test then determines how many organisms were able to pass through the material. The result is a Log Reduction Value (LRV) that converts into an efficiency rating. For example, a 6.0 LRV equates to a 99.9999 percent efficiency rating.
  • Whole Package Aerosol Challenge – This test follows the concept outlined in the F1608 test, but instead of a material sample disk it tests the entire package. The test is conducted by taking a whole, sterilized package, hanging it in a chamber in the non-critical seal area and spraying the chamber with aerosolized indicator organisms. The organisms fall on the package. The package is then decontaminated after which the package is aseptically opened and the contents tested to determine if the indicator organism penetrated the packaging.

Anytime a change in materials or processes occur, medical device and drug manufacturers should immediately begin assessing the impact and risk that may exist with their product packaging. Once the assessment is made, it should be documented and provided to all those who need to know about the change, filed, and if needed, FDA submissions updated. It may be necessary to revalidate the packaging utilizing the tests mentioned.

The bottom line is that manufacturers need to put into place the triggers to start the management process resulting from changes with materials or supplies used in packaging. Regulatory agencies including FDA expect manufacturers to conduct their due diligence regarding any changes to their packaging.