Journal article
Container closure integrity testing-method development for freeze-dried products using laser-based headspace oxygen analysis
Technical University of Denmark1
Center for Energy Resources Engineering, Centers, Technical University of Denmark2
CERE – Center for Energy Ressources Engineering, Department of Chemical and Biochemical Engineering, Technical University of Denmark3
Department of Chemical and Biochemical Engineering, Technical University of Denmark4
Novo Nordisk Foundation5
The regulatory expectations introduced by the U.S. Food and Drug Administration in 1999, ICH Q5C, the revised draft of Annex 1, Eudralex volume 4 for consultation, and the recent update of USP general chapters 1207.1 and 1207.2 regarding container closure integrity (CCI) testing have created a need for further development of testing methods, although there are no universally accepted methods to test and evaluate the CCI of a biopharmaceutical drug product.
Each testing method and principle has merits and demerits. This paper will present a simple approach to be used in method validation of CCI testing based on headspace oxygen analysis for freeze-dried biopharmaceutical drug products in vials, as well as a method for testing and verifying positive control vials.
The model is based on Fick's law of diffusion and is empirically corrected to account for Knudsen diffusion in smaller defect sizes. The model considers storage conditions of the vials, allowing for testing of vials stored under anaerobic and near-sealing pressure conditions and different temperature conditions, as well as testing at different time points.
Using this approach based on headspace oxygen analysis, the minimum timeframe for leak detection is dependent on the volume of the object tested, but standard vial sizes have shown that leak sizes of 0.2 m can be detected within hours of vial stoppering with the model developed. CCI testing by headspace oxygen analysis using this approach can be done quickly and non-destructively.
This method can prove its effectiveness in demonstration of a protective critical barrier (CCI) for a biopharmaceutical drug product during real-time situations of manufacturing, transportation, registered storage conditions, etc. (life-cycle approach).
Language: | English |
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Year: | 2019 |
Pages: | 170-180 |
ISSN: | 19482124 and 10797440 |
Types: | Journal article |
DOI: | 10.5731/pdajpst.2018.008680 |
ORCIDs: | Fosbøl, Philip Loldrup |
Biological Products Container closure integrity testing Diffusion Drug Contamination Drug Packaging Drug Storage Freeze Drying Guidelines as Topic Laser-based headspace analysis Lasers Method development Modeling leak rate for artificial leaks in vials Models, Theoretical Oxygen Positive controls for container closure integrity studies Temperature Time Factors USP <1207> United States United States Food and Drug Administration Validation Studies as Topic