title: A strategy for the prevention of protein oxidation by drug product in polymer-based syringes.
abstract: Recently, new and advanced ideas have been presented on the value of polymer-based syringes for improved safety, better strength, reduced aggregation, and the prevention of drug degradation. In this report, our findings on drug degradation from protein oxidation will be presented and discussed. Commonly, dissolved oxygen is one of the factors for causing protein degradation. Due to the nature of higher gas permeability in polymer-based syringes, it was thought to be difficult to control the oxygen level during storage. However, this report demonstrates the appropriateness of combining the use of an oxygen absorber within the secondary packaging as a deoxygenated packaging system. In addition, this report suggests that another factor to enhance protein oxidization is related to radicals on the syringe barrel from sterilization by irradiation. We demonstrate that steam sterilization can minimize protein oxidization, as the protein filled in steam sterilized syringe is much more stable. In conclusion, the main oxidation pathway of a protein has been identified as dissolved oxygen and radical generation within a polymer container. Possible solutions are herewith presented for controlling oxidation by means of applying a deoxygenated packaging system as well as utilizing steam sterilization as a method of sterilization for prefillable polymer syringes.
  
  
  
  There have been many presentations and discussions about the risks associated with glass prefilled syringes. Advanced ideas are being presented on the value of polymer-based syringes for improved safety, better strength, reduced protein aggregation, and the prevention of drug degradation. Drug degradation based on protein oxidation is discussed in this report. Identification of the main factors causing this degradation and possible solutions available by using polymer-based syringes will be presented. The causes of protein oxidation have been identified as dissolved oxygen and radicals generated by the applied method of sterilization. The oxidation reaction created by dissolved oxygen within the drug product can be effectively inhibited by controlling the removal of the oxygen through the use of a deoxygenated packaging system. This packaging system can control the level or complete removal of oxygen from the primary container and the secondary packaging system. Protein oxidation induced by the formation of radicals from sterilization by irradiation is another critical aspect where it was thought that various sterilization methods were acceptable without loosing drug product quality. However, this report is first to demonstrate that gamma sterilized polymer-based syringes accelerated protein oxidation by radical generation; this effect can be prevented by means of steam sterilization.
authors.affiliation: Terumo Corporation, R&D Center, Kanagawa, Japan; Kouji2Nakamura@terumo.co.jp.
authors.forename: Koji
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Terumo Corporation, R&D Center, Kanagawa, Japan;
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Abe
authors.affiliation: Terumo Corporation, R&D Center, Kanagawa, Japan;
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kiminami
authors.affiliation: Terumo Corporation, R&D Center, Kanagawa, Japan;
authors.forename: Arisa
authors.initials: A
authors.lastname: Yamashita
authors.affiliation: Terumo Corporation, R&D Center, Kanagawa, Japan;
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Iwasaki
authors.affiliation: Terumo Corporation, R&D Center, Kanagawa, Japan;
authors.forename: Shigeru
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: Terumo Corporation, R&D Center, Kanagawa, Japan;
authors.forename: Keisuke
authors.initials: K
authors.lastname: Yoshino
authors.affiliation: Terumo Europe NV, Leuven, Belgium; and.
authors.forename: William
authors.initials: W
authors.lastname: Dierick
authors.affiliation: Terumo Medical Corporation, Somerset, NJ, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Constable
mesh_terms: D004349:Drug Packaging; D005720:Gamma Rays; D005898:Glass; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D019064:Product Packaging; D011506:Proteins / Q000737:chemistry*; D013227:Steam; D013242:Sterilization; D013594:Syringes
chemical_list: D011108:Polymers; D011506:Proteins; D013227:Steam; D010100:Oxygen
keywords: Autoclave; COP; Oxidation; Protein; Radicals; Steam sterilization; stability