Monitoring of Peroxide in Gamma Irradiated EVA Multilayer Film Using Methionine Probe

Area of Science:

• Materials Science
• Chemical Engineering
• Biotechnology

Background:

• Single-use bags in biopharmaceutical manufacturing are susceptible to changes from gamma irradiation.
• Gamma irradiation can induce the formation of reactive species like acids, radicals, and hydroperoxides within these bags.
• Understanding these changes is crucial for maintaining product integrity and safety.

Purpose of the Study:

• To model gamma radiation-induced changes in single-use bags using methionine oxidation as a proxy.
• To investigate the mechanisms of reactive species formation and methionine oxidation.
• To determine optimal conditions for single-use bag utilization, minimizing radical chemistry impact.

Main Methods:

• Methionine solution was used to assess oxidation in gamma-irradiated (0-260 kGy) and aged (0-36 months) biopharmaceutical bags.
• Methionine sulfoxide levels were quantified using High-Performance Liquid Chromatography (HPLC) over various storage times.
• A design of experiments approach analyzed oxidative induction time, methionine sulfoxide formation rate, and maximum concentration.

Main Results:

• Methionine oxidation is primarily driven by peracids, particularly peracetic acid, rather than directly by hydro(gen) peroxide.
• Key parameters like oxidative induction time, formation rate, and maximum concentration of methionine sulfoxide were quantified.
• The study identified specific conditions that influence the extent of methionine oxidation.

Conclusions:

• Optimizing the conditions for single-use bag use can significantly limit methionine oxidation and the release of reactive species.
• Reaction kinetics and design of experiments provide a framework for defining a desirability domain for bag usage.
• This research contributes to ensuring the quality and safety of biopharmaceuticals manufactured using single-use systems.