Evaluation of the impact of e-beam and X-ray irradiation conditions on radical generation in PE/EVOH/PE multilayer film

Sterilization of biopharmaceutical products has commonly employed gamma radiation from cobalt-60, a radioisotope with associated security and supply chain risks. Increased use of non-radioisotope alternative ionizing energy technologies, such as electron beam (e-beam) and X-rays, is promising but has been hindered by lack of thorough evaluation of the compatibility of these techniques with product materials. This study investigates radical generation in a polyethylene (PE)/ethylene-vinyl alcohol copolymer (EVOH)/PE multilayer film product (Sartorius Flexsafe® with the S80 film) under varying e-beam and X-ray irradiation conditions to address data gaps for these materials and technologies. Utilizing a full factorial design of experiments (DoE), we examined the effects of irradiation technology, dose level, dose rate, processing temperature, and ambient oxygen concentration on radical formation, as quantified by electron spin resonance (ESR). Our results indicate that the type of ionizing technology (e-beam vs. X-ray) does not significantly affect radical concentration generation in the materials. However, higher doses and lower temperatures were found to correlate with increased radical concentrations, while elevated oxygen levels effectively suppressed radicals through a presumed scavenging mechanism. For e-beam processing, a higher dose rate reduced radical accumulation, while the opposite trend was found for X-ray irradiation. Complementary Fourier-transform infrared spectroscopy (FTIR) and principal component analysis (PCA) revealed subtle oxidation differences of PE under specific irradiation conditions. • Electron beam and X-ray use increasing for sterilization of multilayer films • Ionizing energy generates reactive radicals measurable using ESR • Effects of source, dose, dose rate, temperature, and oxygen considered • Radiation source does not affect radical generation in PE/EVOH/PE • Design of experiment used to assess combined effects