ABSTRACT
Therapeutic proteins such as monoclonal antibodies (mAbs) are exposed to ambient light conditions during manufacturing and handling processes, and the exposure time limits are generally determined by conducting relevant room temperature and room light (RT/RL) stability studies. In the case study presented here, a mAb drug product showed an unexpectedly higher level of protein aggregation during a formal RT/RL study conducted at a contract facility as compared to what had previously been seen during development studies. An investigation led to the finding that the RT/RL stability chamber was set up differently as compared to the one used for the internal studies. The UVA component of the light conditions used in the study was not representative of the conditions experienced by the drug product during normal manufacturing. During the investigation, three different light sources were evaluated for their UVA quotients along with the UV filtering effect of a plastic encasement. The mAb formulation showed a greater increase in aggregation when exposed to halophosphate and triphosphor-based cool white fluorescent (CWF) lights compared to a light emitting diode (LED) light. The plastic encasement on CWF lights significantly reduced the aggregation levels. Upon further assessment of additional mAb formulations, a similar trend was observed with sensitivity to the low level of UVA background emitted by the CWF lights. This study demonstrated that it is critical to understand UV levels at the sample handling level while setting up ambient light studies using CWF lights for biologic drug products. The use of non-representative light conditions (UV irradiance) can lead to unnecessary restrictions on the RL exposure allowance set for these products.