Biologics molecules need special handling during drug substance and drug product manufacturing, usage, and storage. Extra care is needed as biologics molecules are sensitive to external stresses, including temperature excursions, shear and interfacial stress, and light exposure. All proteins are known to be photosensitive, especially to UV light in the 200 – 400 nm range. [1] The amino acids, including tryptophan (Trp), tyrosine (Tyr), phenylalanine (Phe), histidine (His) and disulfide bonds, are the primary targets of photo-degradation in proteins. [1], [2], [3] Photo-induced degradation of proteins can occur at any point during drug substance and drug product manufacturing and up to final delivery to the patient. [4], [5] During this entire process, the biologics drug product is exposed to different types of lights from various sources, including metal halide, fluorescent, and LED lamps. Depending on the length of exposures, the UV component of light can significantly affect the degree of degradation and final quality of a biologics drug. Photostability studies are performed as a part of stress stability as per ICH Q1B guidelines, where biologics products are exposed to CWF light (400 - 800 nm) and UVA light (315 - 400 nm) with a minimum exposure of 1.2 million lux-hours under visible light and 200 Wh/m2 of UV light. [6] These exposure guidelines are not a true representation of biologics photostability at ambient light conditions. Therefore, it is necessary to understand this risk by conducting RT/RL studies to determine light exposure limits during drug manufacture.

The RT/RL studies are generally conducted under CWF lights with temperature and humidity controlled at 25°C/ 60% RH. Recent research has shown that these fluorescent lamps have a UVA quotient in the range of 315-400 nm. [7] Sreedhara et al. made similar observations for fluorescent lamps in laboratories as well as GMP processing areas emitting UV irradiance ranging from 0.05 to 0.3 W/m2. [2] They also observed that the CWF lamps covered with a plastic canopy decreased UV irradiance by approximately 5-fold without affecting the light intensity in the visible region. The studies reported a significant increase in the aggregation of monoclonal antibody (mAb) evaluated using these lights. Cheng et al. recently reported that when exposed to LED light, mAb exhibits wavelength-dependent light sensitivity. [8] The study showed that the mAb exposed to blue light (400 - 500 nm) LED generated more aggregates than mAb exposed to to red light (620 - 750 nm) or CWF light.

The studies reported in the literature mostly revolve around exposure to either UV light alone or a combination of UV and CWF light. [9], [10], [11], [12] While only a few studies published in the literature have discussed the CWF light with UVA leakage, [2], [9] there are no reports on the type of CWF lights and their spectral power distribution (SPD) in the UVA region and their impact on mAb stability. Therefore, it is important to understand the CWF lights in more detail for their SPD in the UV-visible range and how light fixtures (plastic canopy) used for diffusion affect this SPD and its impact on the stability of biologics formulations. In this manuscript, we investigated the unexpected finding observed during the RT/RL study of a mAb formulation. The effect of minor UV leakage from different CWF lights on mAbs aggregation and the impact of plastic encasement on the reduction of UV transmission were studied. In addition, we also evaluated different mAbs in their respective formulations for their light sensitivity under CWF light with and without encasement. The result from this study showed that each mAb molecule has different light sensitivity, with UVA irradiance from CWF light being the major contributor towards photosensitivity, with some mAbs being sensitive even under the blue region of the visible light spectrum.