Is ICH Q1B Fit for Purpose for Monoclonal Antibodies? Photostability Testing Conditions Versus Real-World Light Exposure

ICH Q1B sets a standardized photostability test for new drug substances and products, with a confirmatory exposure of at least 1.2 × 106 lux hours of visible light and 200 W·h/m2 of near-ultraviolet energy. It was finalized in 1996, when only two therapeutic monoclonal antibodies had been approved in the United States; the FDA approved its 100th in 2021. This review asks whether Q1B remains fit for purpose for this product class. We distinguish lack of real-world representativeness from lack of fitness for Q1B’s stated purpose of informing handling, packaging, and labeling. The confirmatory exposure greatly exceeds, and differs spectrally from manufacturing and clinical light, but that is by design. The weaknesses that matter are interpretive: little biologics-specific guidance on justifying alternative exposures, no recognition of excipient- and metal-mediated photochemistry that can vary between batches, and no antibody-specific direction on endpoints such as aggregation, charge variants, site-specific oxidation, and Fc receptor binding. The review covers antibody photochemistry, including IgG2- and IgG4-specific considerations; a quantitative comparison of test and real-world light; an orthogonal analytical toolbox; and formulation, container, and infusion-set mitigations. It also assesses the ICH Q1 draft guideline (Step 2b, April 2025), which recognizes that ambient light lies mainly above 400 nm and adds in-use stability, but retains the 1.2 × 106 lux hour confirmatory condition and does not address formulation-mediated photochemistry. A two-track framework is proposed that keeps the harmonized exposure for hazard identification and adds exposure-representative testing for risk assessment.