A parenteral vial system consists of a vial, a stopper and an overseal. Container/closure integrity of this parenteral vial system is achieved primarily by the proper deformation of the rubber stopper. Deformation is achieved by compressing the stopper against the sealing surface of the vial finish. Once compressed, the stopper is held in place by crimping an aluminum ferrule or seal around the components. In deforming the rubber stopper, the viscous flow of the elastomer fills and seals the voids between the sealing surfaces of the vial finish and the stopper flange. The elastomeric property of the rubber, which is the tendency of the elastomer to revert to its original shape while being held it in the deformed state, creates a force (strain) that effectively maintains the created seal. Although the compression of the stopper plug created by the interference fit between the plug and the inside diameter of the neck of the vial may also create a seal, it is the vertical force from the compression of the stopper flange against the top of the vial finish that creates the primary and more reliable seal. By correlating RSF to stopper compression and CCI testing during packaging development RSF may be used as a predictor of container closure seal integrity (Orosz, Guazzo 2010)*. This work clearly shows that an appropriate amount of stopper compression creates effective container closure integrity where leak rates of less than 10-7 Pa m3/s can be achieved even on glass vials with “large” surface defects. Therefore, the primary function of a sealing operation is the deformation of the rubber stopper by compression; secondary is the crimping mechanism to hold that compressed stopper in place.

It is important to understand that Residual Seal Force is not a constant value. The change in RSF can be illustrated graphically utilizing the degenerative Maxwell Curve. Changes in RSF are the result of stress relaxation and the compression set of the elastomer. Over time, as indicated by the curve, the elastomeric stress continues to very slowly decline due to the rheological characteristics of the rubber until a relative plateau is reached. A specific RSF value is meaningless unless its location on the curve is known since the changes in stress are not linear. This degeneration and its effects on RSF need to be understood for each elastomeric formulation and stopper design. The physical and mechanical properties of the closure are determined by the rubber formulation and the stopper dimensions. These properties include durometer (relative hardness), compression set and modulus of elongation. Thus the stress relaxation curve and residual seal force may vary with each different rubber formulation. Processing and storage parameters, particularly temperature, may also influence this curve. By correlating RSF values with the compression of the rubber stopper and the corresponding leak rates, the measurement of RSF can be used to effectively evaluate proper and continued sealing of the vial system. FDA in its Guidance for Industry Container and Closure System Integrity Testing in Lieu of Sterility Testing as a Component of the Stability Protocol for Sterile Products recognizes the usefulness of properly validated seal force testing. Most importantly, RSF is useful in the establishment, validation and control of capping machine settings.

*Orosz and D Guazzo, “Leak Detection and Product Risk Assessment’ presented at PDA Meeting, Mar 2010, Orlando, FL