Stopper Migration In Frozen Pre-Filled Syringes

By Jayasree M. Srinivasan, Ph. D.

Parenteral products offered in pre-filled syringes (PFS) provide distinct advantages for both patients and manufacturers. Compared to vial products, the PFS format simplifies administration, enhances dosing accuracy, and minimizes waste by requiring minimal to no overfill, with the container-closure system also serving as the delivery device (see Figure 1). However, because the closure system—specifically the plunger—is inherently mobile, it is essential to consider environmental factors that can affect product sterility during storage, transport, and handling prior to administration. Notably, fluctuations in temperature and pressure during transport, especially at higher elevations or in aircraft holds, can pose risks. Frozen products, in particular, may undergo rapid pressure changes when transferred into freezers.

This white paper introduces a semi-automated method for dynamically assessing plunger migration under controlled variations in temperature and pressure, utilizing computer vision tools. As an example of this method, the tools were employed to identify the key factors influencing the extent of plunger movement in a frozen PFS system.