Abstract

High Voltage Leak Detection: Impact on the quality of biopharmaceuticals: Container Closure Integrity testing of sterile dosage forms via high voltage

High Voltage Leak Detection (HVLD) is a highly efficient and well-established deterministic method to control Container Closure Integrity (CCI). The method is mainly used as an in-line 100 % controlling method in pharmaceutical manufacturing. Within the here presented case study, the possible negative influence of HVLD on parenteral protein solutions is examined and discussed. As a primary step, the inspection of parenteral protein solutions via HVLD was comprehensively analyzed and potential thermodynamic risks of the method were assessed. Other than the direct influence of the high voltage on the product, previous publications suggested oxidation of the product due to ozone generation in the headspace of the tested container. In order to directly quantify the amount of oxidative stress being applied to the active ingredient, the oxidation level of amino acid side chains was measured using a protein carbonyl colorimetric assay. In this study it could be shown that CCI examination via HVLD was found to have no critical oxidative effect on the two tested drug products. Hereby for each product two vial formats with different head space volumes were exposed to the HVLD device. Even extensive exposure to the HVLD device by 10-fold runs showed no signs of effect on different product solutions. The increase in temperature of ≤ 1 K influenced by the HVLD was negligible regarding the protein activity. Combining these results with the thermodynamic process analysis, HVLD can safely be assumed to have no degradation potential on parenteral protein solutions within the tested parameters.

Correspondence:

Dr. Tobias Posset, Sandhofer Str. 116, 68305 Mannheim, Germany; e-mail: tobias.posset@roche.com