Method to Predict Glass Vial Fogging in Lyophilized Drug Products

Glass fogging is a phenomenon occurring in lyophilized drug products and can be described as a thin product layer deposited on the inner surface of the glass container, in the area not covered by the lyo cake itself. It is often considered a cosmetic defect; however, the loss of container closure in...

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Bibliographic Details
Published in:	Journal of pharmaceutical sciences Vol. 109; no. 1; p. 323
Main Authors:	Langer, Carolin, Mahler, Hanns-Christian, Koulov, Atanas, Marti, Nicolas, Grigore, Cristina, Matter, Anja, Chalus, Pascal, Singh, Satish, Lemazurier, Thomas, Joerg, Susanne, Mathaes, Roman
Format:	Journal Article
Language:	English
Published:	United States 01-01-2020
Subjects:	Chemistry, Pharmaceutical Drug Compounding Drug Packaging - methods Drug Packaging - standards Freeze Drying Glass - chemistry Hydrophobic and Hydrophilic Interactions Models, Theoretical Pharmaceutical Preparations - chemistry Polysorbates - chemistry Serum Albumin, Bovine - chemistry Surface Properties Transition Temperature formulation process analytical technology (PAT) protein(s) lyophilization biopharmaceutical characterization protein formulation(s)
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Summary:	Glass fogging is a phenomenon occurring in lyophilized drug products and can be described as a thin product layer deposited on the inner surface of the glass container, in the area not covered by the lyo cake itself. It is often considered a cosmetic defect; however, the loss of container closure integrity is a potential consequence of the fogging's expansion to the vial neck region, making this a potential critical defect. Thus, a method for predicting the extent of vial fogging before the actual freeze-drying is of particular interest for the pharmaceutical industry. For that reason, we evaluated a simple method ("simulated fogging") applicable to drug product formulations in a specific container closure system. Two different vial types with different surface hydrophilicity were tested using 3 model protein formulations, comparing the simulated fogging test and the degree of fogging after actual lyophilization. The simulated fogging method could predict fogging and showed a correlation to fogging in lyophilized drug product glass vials. We observed that all formulations showed fogging in the hydrophilic vials. By contrast, hydrophobic vials prevented fogging, however, interestingly with remaining defects of so-called droplet formation. Other than extent of fogging, no additional differences of lyophilized cake properties or other product quality attributes were observed between products using the different glass vial types tested.
ISSN:	1520-6017
DOI:	10.1016/j.xphs.2019.08.024