Determination of the Acceptable Ambient Light Exposure during Drug Product Manufacturing for Long-Term Stability of Monoclonal Antibodies

Abstract

Monoclonal antibodies (mAbs) are exposed to light during drug product (DP) manufacturing, and the acceptable levels of light exposure needs to be determined based on the impact on product quality. In this study, a mild and more representative light model consisting of ambient light instead of stress light as prescribed by ICH Q1B was used to evaluate the impact of light exposure on mAb DP quality. The immediate effect of ambient light exposure on protein DP quality was determined to be dependent on the amount of light exposure rather than light intensity (up to 5000 lux). The impact on quality of mAbs is product specific due to their differences in light sensitivity, in which mAb II shows larger increases in IEC basic variants and larger decreases in SEC monomer when compared to mAb I after 0.24 million lux hours of light exposure. The acceptable ambient light exposure for mAb II DP manufacturing was determined to be 0.13 million lux hours, in which no impact on product quality was observed after the short-term light exposure. Additionally, real-time storage (5 °C) of the DP after the prescribed ambient light exposure showed no impact to various product quality attributes. The light model used in this study is capable of determining the acceptable amount of ambient light exposure for mAbs, especially during DP manufacturing processes.

Visible Light Degradation of a Monoclonal Antibody in a High-Concentration Formulation: Characterization of a Tryptophan-Derived Chromophoric Photo-product by Comparison to Photo-degradation of N-Acetyl-l-tryptophan Amide

“…Importantly, Gurnani et al observed photo-degradation of Trp by visible light in the absence of photosensitizers. In addition, the photo-degradation of pharmaceutical proteins by visible light was reported in various publications. ,,, In their disclosure of intramolecular photo-sensitized cyclobutane formation from indoles, Zhu et al invoked a triplet state of the indole moiety, promoted by an electron-withdrawing substituent at the C2 position of the pyrrole ring. Theoretical calculations indicate that protonation of the indole ring system at C 3 and C 2 leads to an energy gap between ground and excited singlet states of 3.33–3.28 and 2.62 eV, respectively, associated with transitions around 373–378 and 474 nm, respectively .…”

Physicochemical Stability of Monoclonal Antibodies: A Review

“…They also showed that mAbs photostability depends on the overall amount of light exposure rather than light intensity. 112 Eventually, it is not to be forgotten that not only the mAb, but also the excipients in formulation may undergo light-induced degradation. Photodegradation of polysorbates occurs through autoxidation and can lead to the formation of peroxides that intensify oxidation processes.…”

“…Photodegradation of polysorbates occurs through autoxidation and can lead to the formation of peroxides that intensify oxidation processes. [112][113][114][115] Photo-oxidized histidine may crosslink with a nonoxidized histidine residue, forming a proteinbuffer adducts. 106 Concerns about photodegradation might however decrease because of the spread of light-emitting diode lighting.…”

Stress Factors in Protein Drug Product Manufacturing and Their Impact on Product Quality

“…Recent literature reports indicate that certain mAbs are sensitive to ambient light (characterized as both fluorescent lamps and dappled light through window sills observed in various laboratories). The impact of ambient light on proteins, while unusual, but is quite important to assess for various DP filling processes 108,109 and is directly proportional to the total light exposure (i.e., lux-hrs) as opposed to the light intensity alone (i. e., lux). Various mAb DPs have been shown to tolerate several thousand lux-hrs during typical DP processing, including visual inspection.…”