Critical Process Parameters of Capping Equipment used in GMP DP manufacturing

Roman Mathaes; Hanns-Christian Mahler; Yves Roggo; Joerg Huwyler; Juergen Eder; Kamila Fritsch; Tobias Posset; Silke Mohl; Alexander Streubel

doi:10.5731/pdajpst.2015.005918

Abstract

Capping equipment used in good manufacturing practice (GMP) manufacturing feature different designs and a variety of adjustable process parameters. The overall capping result is a complex interplay of the different capping process parameters and is insufficiently described in literature. It remains poorly studied how the different capping equipment designs and capping equipment process parameters (e.g. pre- compression force, capping plate height, turntable rotating speed) contribute to the final residual seal force (RSF) of a sealed container closure system (CCS) and its relation to CCI and other Drug Product (DP) quality parameters. Stopper compression measured by computer tomography correlated to residual seal force measurements. In our studies, we used different container closure system (CSS) configurations from different GMP DP fill&finish facilities to investigate the influence of differences in primary packaging, i.e. vial size and rubber stopper design on the capping process and the capped drug product. In addition, we compared two large scale GMP manufacturing capping equipment and different capping equipment settings and their impact on product quality and integrity, as determined by residual seal force. The capping plate to plunger distance had a major influence on the obtained RSF values of a sealed vial, whereas the capping pre-compression force and the turntable rotation speed showed only a minor influence on the RSF of a sealed vial. Capping process parameters could not easily be transferred from capping equipment of different manufacturers. Yet, the RSF tester did provide a valuable tool to compare capping performance of different capping equipment. No vial showed any leakage greater than 10-8 mbarl/s as measured by a helium mass spectrometry system, suggesting that CCI was warranted in the RSF range tested for the tested CCSs.

Received July 28, 2015.
Accepted November 5, 2015.

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