Pulsed light technology for surface decontamination in pharmaceutical environments: mechanisms, validation...

The recent revision of EU-GMP Annex 1 has intensified the demand for robust and reproducible surface decontamination technologies in pharmaceutical environments. Pulsed Light (PL) technology has emerged as a disruptive, chemical-free approach based on high-intensity, short-duration polychromatic pulses (200-1100 nm). Unlike conventional continuous UV treatments, PL-induced microbial inactivation results from a synergistic combination of photochemical, photophysical, and photothermal mechanisms, leading to irreversible damage to nucleic acids and cellular structures. Originally matured in the food industry, PL is increasingly attracting interest in aseptic processing as a sustainable alternative to chemical disinfectants and ionizing radiation. PL typically achieves Log Reduction Values of 4 to 6 without generating chemical residues. Its compact footprint and rapid cycle times make it particularly suitable for the flexible, small-batch manufacturing lines required for modern biopharmaceutical production. This review provides a critical overview of PL principles, inactivation kinetics, and industrial implementation. Emphasis is placed on the transition from time-based to energy-based validation strategies, introducing the D_fluence value as a key metric for process qualification. The critical role of biological indicators is discussed, addressing specific challenges such as shadowing effects, spore clumping, and the selection of worst-case surrogates. Beyond reviewing current knowledge, this work proposes a novel validation paradigm for photonic decontamination processes, integrating energy-based metrics, biological indicators, and Quality Risk Management principles to support regulatory qualification. Furthermore, it highlights the need for dedicated standardization pathways, including future ISO standards for photonic biological indicators and validation methodologies, to facilitate the broader regulatory acceptance of PL in pharmaceutical manufacturing.