Effect of ambient light on IgG1 monoclonal antibodies during drug product processing and development

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• 作者：Alavattam Sreedhara^a ; ^{sreedhaa@gene.com" class="auth_mail" title="E-mail the corresponding author} ; Jian Yin^b ; Michael Joyce^a ; Kimberly Lau^a ; Aaron T. Wecksler^c ; Galahad Deperalta^c ; Li Yi^a ; Y. John Wang^a ; Bruce Kabakoff^b ; Ravuri S.K. Kishore^d
• 关键词：ACN ; acetonitrile ; DTT ; dithiothreitol ; FS ; fluorescence ; His ; l-Histidine ; ICH ; International Conference on Harmonization ; mAb ; monoclonal antibody ; Met ; l-Methionine ; Phe ; Phenylalanine ; TFA ; trifluoroacetic acid ; Trp ; l-Tryptophan ; Tyr ; l-Tyrosine
• 刊名：European Journal of Pharmaceutics and Biopharmaceutics
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：100
• 期：Complete
• 页码：38-46
• 全文大小：1165 K

文摘

Photostability studies are standard stress testing conducted during drug product development of various pharmaceutical compounds, including small molecules and proteins. These studies as recommended by ICH Q1B are carried out using no less than 1.2 × 10⁶ lux-hours in the visible region and no less than 200 W h/m² in UV light. However, normal drug product processing is carried out under fluorescent lamps that emit white light almost exclusively in the >400 nm region with a small UV quotient. We term these as ambient or mild light conditions. We tested several IgG1 monoclonal antibodies (mAbs 1–5) under these ambient light conditions and compared them to the ICH light conditions. All the mAbs were significantly degraded under the ICH light but several mAbs (mAbs 3–5) were processed without impacting any product quality attributes under ambient or mild light conditions. Interestingly we observed site-specific Trp oxidation in mAb1, while higher aggregation and color change were observed for mAb2 under mild light conditions. The recommended ICH light conditions have a high UV component and hence may not help to rank order photosensitivity under normal protein DP processing conditions.