The Pharmaceutical Capping Process-Correlation between Residual Seal Force, Torque Moment, and Flip-off Removal Force.

The majority of parenteral drug products are manufactured in glass vials with an elastomeric rubber stopper and a crimp cap. The vial sealing process is a critical process step during fill-and-finish operations, as it defines the seal quality of the final product. Different critical capping process parameters can affect rubber stopper defects, rubber stopper compression, container closure integrity, and also crimp cap quality. A sufficiently high force to remove the flip-off button prior to usage is required to ensure quality of the drug product unit by the flip-off button during storage, transportation, and until opening and use. Therefore, the final product is 100% visually inspected for lose or defective crimp caps, which is subjective as well as time- and labor-intensive. In this study, we sealed several container closure system configurations with different capping equipment settings (with corresponding residual seal force values) to investigate the torque moment required to turn the crimp cap. A correlation between torque moment and residual seal force has been established. The torque moment was found to be influenced by several parameters, including diameter of the vial head, type of rubber stopper (serum or lyophilized) and type of crimp cap (West(®) or Datwyler(®)). In addition, we measured the force required to remove the flip-off button of a sealed container closure system. The capping process had no influence on measured forces; however, it was possible to detect partially crimped vials. In conclusion, a controlled capping process with a defined target residual seal force range leads to a tight crimp cap on a sealed container closure system and can ensure product quality. LAY ABSTRACT: The majority of parenteral drug products are manufactured in a glass vials with an elastomeric rubber stopper and a crimp cap. The vial sealing process is a critical process step during fill-and-finish operations, as it defines the seal quality of the final product. An adequate force to remove the flip-off button prior to usage is required to ensure product quality during storage and transportation until use. In addition, the complete crimp cap needs to be fixed in a tight position on the vial. In this study, we investigated the torque moment required to turn the crimp cap and the force required to remove the flip-off button of container closure system sealed with different capping equipment process parameters (having different residual seal force values).

Leak testing in parenteral packaging: establishment of direct correlation between helium leak rate measurements and microbial ingress for two different leak types.

A direct test method using helium leak detection was developed to determine microbial ingress in parenteral vial/rubber closure systems. The purpose of this study was to establish a direct correlation between the helium leak rate and the presence of ingress when vials were submersed under pressure in a broth of bacteria. Results were obtained for two different types of leaks: microholes that have been laser-drilled into thin metal plates, and thin copper wire that was placed between the rubber closure and the glass vial's sealing surface. The results from the microholes showed that the helium leak rate was a function of the square of the hole diameter and fit well with theoretical calculations. The relationship with the wire gave a far more complex dependence and was not modeled theoretically. Comparison with the microbial challenge showed that for microholes a lower size limit was found to be 2 microm with a corresponding leak rate of 1.4 x 10(-3) mbarl/s. For the fine wire experiment the lower limit was 15-microm wire and a corresponding leak rate of 1.3 x 10(-5) mbarl/s. From these tests a safe, lower limit, leak rate was established.