title: Effect of ambient light on IgG1 monoclonal antibodies during drug product processing and development.
abstract: 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× 10(6)lux-hours in the visible region and no less than 200Wh/m(2) in UV light. However, normal drug product processing is carried out under fluorescent lamps that emit white light almost exclusively in the >400nm 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.
authors.affiliation: Late Stage Pharmaceutical Development, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA. Electronic address: sreedhaa@gene.com.
authors.forename: Alavattam
authors.initials: A
authors.lastname: Sreedhara
authors.affiliation: Early Stage Pharmaceutical Development, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Yin
authors.affiliation: Late Stage Pharmaceutical Development, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Joyce
authors.affiliation: Late Stage Pharmaceutical Development, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Lau
authors.affiliation: Protein Analytical Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: Aaron T
authors.initials: AT
authors.lastname: Wecksler
authors.affiliation: Protein Analytical Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: Galahad
authors.initials: G
authors.lastname: Deperalta
authors.affiliation: Late Stage Pharmaceutical Development, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Yi
authors.affiliation: Late Stage Pharmaceutical Development, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: John Wang
authors.affiliation: Early Stage Pharmaceutical Development, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Kabakoff
authors.affiliation: Late Stage Pharmaceutical and Processing Development, F. Hoffmann-La Roche Ltd., CH-4070 Basel, Switzerland.
authors.forename: Ravuri S K
authors.initials: RS
authors.lastname: Kishore
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000528:radiation effects*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D055808:Drug Discovery / Q000379:methods; D004355:Drug Stability; D007074:Immunoglobulin G / Q000737:chemistry* / Q000528:radiation effects*; D008027:Light / Q000009:adverse effects*; D010084:Oxidation-Reduction
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G
keywords: Ambient light; Drug product processing; HunterLab; Mild light; Photodegradation; Photooxidation; Photostability; Relevant stress