Evaluating Plunger Movement and Container Closure Integrity of Combination Products Under Simulated Air Shipment Conditions

Ensuring container closure integrity (CCI) is critical for maintaining the sterility and safety of sterile medicinal products, particularly during air transportation.

Leveraging regulatory guidance from ASTM D6653, ASTM D4169, and EU Annex 1, a plunger movement study was designed using vacuum chamber simulations to mimic high-altitude transport conditions.

Test specimens, conditioned per regulatory standards, included representative assembled packaging systems.

The methodology incorporated a tracer solution to visualize plunger movement, defined quantitatively as the displacement from initial to final stopper positions. Results were interpreted through the lens of qualitative pressure-differential effects and quantitative stopper movement, using ASTM D4169 to assess potential packaging failure or system compromise. In cases where unacceptable plunger movement was detected, root-cause analysis focused on air bubble control and component placement was recommended.

Findings reinforce the need for integrated product-package evaluations during development and the importance of plunger movement studies in maintaining CCI.