Methionine oxidation is used as a proxy to model the gamma radiation induced changes in single-use bags. These changes can be the formation of acids, radicals and hydroperoxides due to the irradiation of the multilayer film the single use bag is made from. Biopharmaceutical multilayer polyethylene bags irradiated from 0 to 260 kGy and aged from 0 to 36 months were filled with a methionine solution to follow the oxidation of methionine. Methionine sulfoxide was measured using high performance liquid chromatography after 21 days of storage. The maximum methionine sulfoxide concentration detected after 21 days of storage was analyzed through a design of experiments. The results 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.