In part four of this series on CCIT, two commonly used methods – Residual Seal Force and Laser Diffraction – will be reviewed.
Parenteral Vial Capping and Residual Seal Force Testing
Residual seal force testing of parenteral vials is often performed in conjunction with helium leak testing or vacuum decay testing. Residual seal force is not a leak test, but is an indirect measure of the compressive force exerted by the stopper on the vial’s land surface. A slow, constant rate of strain is applied to the top of a capped vial and the resistance to compression is monitored and reported. The appropriate amount of compressive force is required to ensure a quality seal. Vials capped at an insufficient force may leak from the sealing surface. On the other hand, vials capped at an excessive force may experience cracking and bulging, also risking the integrity of the closure system. When used in conjunction with leak test methods such as helium mass spectrometry or vacuum decay, an optimal range of residual seal force values may be determined that correlate to a reduced risk of leakage resulting from improper capping force.
This type of testing is of value to clients aiming to establish optimal sealing parameters or those who wish to implement a sampling procedure during product production.
Laser-Based Headspace Analysis
Gas headspace analysis via laser-based analysis techniques provides a quantitative, nondestructive measure of oxygen content, nitrogen content, water vapor content, or low internal pressure in a nonporous, rigid or non-rigid package headspace.
A near-infrared diode laser light is passed through the gas headspace region of the sealed package. Light absorption, measured using frequency-modulated spectroscopy, is indicative of gas concentration and pressure. Gas headspace analysis, as a function of time, provides a quantitative measure of the total leakage rate of the test sample.
This technology is especially applicable when verifying the integrity of packages that must maintain a specific gas headspace content such as low oxygen, low water vapor, and/or low pressure. For testing, packages only need be either transparent or semi-transparent material, either amber or colorless; test samples require a minimum headspace volume and headspace path length. Vials, syringes, cartridges and bottles are all amenable to this approach.