In this study, the oxidation of methionine is used as a proxy to model the gamma radiation-induced changes in single-use bags; these changes lead to the formation of acids, radicals, and hydroperoxides. The mechanisms of formation of these reactive species and of methionine oxidation are discussed. With the help of reaction kinetics, the optimal conditions for the use of these single-use bags minimizing the impact of radical chemistry are highlighted. Biopharmaceutical bags gamma irradiated from 0 kGy to 260 kGy and aged from 0 to 36 months were filled with a methionine solution to follow the oxidation of the methionine. The methionine sulfoxide was measured with HPLC after different storage times (0, 3, 10, 14, 17, and 21 days). Three main results were analyzed through a design of experiments: the oxidative induction time, the methionine sulfoxide formation rate, and the maximum methionine sulfoxide concentration detected. A key aspect of the study is that it highlights that methionine is oxidized not necessarily directly by hydro(gen) peroxide but throughperacid, and likely peracetic acid. The answers to the design of experiments were considered to obtain the desirability domain for the optimization of the conditions of use for the single-use bags limiting the oxidation of methionine as well as the release of reactive species thereof.