title: Low Leachable Container System Consisting of a Polymer-Based Syringe with Chlorinated Isoprene Isobutene Rubber Plunger Stopper.
abstract: A 36 month leachable study on water for injection in direct contact within a polymer-based prefillable syringe consisting of a cyclo olefin polymer barrel, a chlorinated isoprene isobutene rubber plunger stopper, a polymer label attached on the barrel, and a secondary packaging was conducted at 25 ± 2 °C and 60 ± 5% relative humidity. Through the various comparison studies, no difference in the leachable amounts was observed between this polymer-based prefilled syringe and a glass bottle as a blank sample reference by 36 months. No influence on the leachables study outcome was noted from the printed label and/or label adhesive or from the secondary packaging. In an additional study, no acrylic acid used as the label adhesive leachable was detected by an extended storage for 45 months at 25 ± 2 °C and 60 ± 5% relative humidity as a worst case. To obtain more details, a comparison extractable study was conducted between a cyclo olefin polymer barrel and a glass barrel. In addition, chlorinated isoprene isobutene rubber and bromo isoprene isobutene rubber were compared. As a result, no remarkable difference was found in the organic extractables for syringe barrels. On the other hand, in the case of element extractable analysis, the values for the cyclo olefin polymer barrel were lower than that for the glass barrel. For the plunger stoppers, the chlorinated isoprene isobutene rubber applied in this study was showing a lower extractable profile as compared to the bromo isoprene isobutene rubber, both for organic and element extractables. In conclusion, the proposed polymer-based prefillable syringe system has great potential and represents a novel alternative that can achieve very low level extractable profiles and can bring additional value to the highly sensitive biotech drug market.
  
  
  
  A 36 month leachable study on water for injection in direct contact within a cyclo olefin polymer barrel and chlorinated isoprene isobutene rubber plunger stopper that has a polymer label attached to the barrel and is wrapped into a secondary packaging was conducted at 25 °C and 60% relative humidity. Through the various comparison studies, no difference in the leachable amounts was observed between polymer-based prefilled syringes and a glass bottle as a blank sample reference by 36 months. No influences on the leachables study outcome were noted from the secondary packaging. To obtain more details, a comparison extractable study was conducted between the cyclo olefin polymer and the glass barrel. In addition, chlorinated isoprene isobutene rubber and bromo isoprene isobutene rubber plunger stoppers were compared as well. As a result, no remarkable difference was found in the organic extractables for barrels. As for element extractable analysis, the values for the cyclo olefin polymer barrel were lower than that for the glass barrel. For the plunger stoppers, the chlorinated isoprene isobutene rubber applied in this study was showing a lower extractable profile as compared to the bromo isoprene isobutene rubber, both for organic and element extractables. In conclusion, the proposed polymer-based prefillable syringe system has great potential and represents a novel alternative that can achieve very low level extractable profiles and can bring additional value to the highly sensitive biotech drug market.
authors.affiliation: Terumo Corporation, R&D Center, Nakai-machi, Ashigarakami-gun, Kanagawa, Japan; and Hideaki_Kiminami@terumo.co.jp.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kiminami
authors.affiliation: Terumo Corporation, R&D Center, Nakai-machi, Ashigarakami-gun, Kanagawa, Japan; and.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Takeuchi
authors.affiliation: Terumo Corporation, R&D Center, Nakai-machi, Ashigarakami-gun, Kanagawa, Japan; and.
authors.forename: Koji
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Terumo Corporation, R&D Center, Nakai-machi, Ashigarakami-gun, Kanagawa, Japan; and.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Abe
authors.affiliation: Terumo Europe NV, Interleuvenlaan 40, 3001 Leuven, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Lauwers
authors.affiliation: Terumo Europe NV, Interleuvenlaan 40, 3001 Leuven, Belgium.
authors.forename: William
authors.initials: W
authors.lastname: Dierick
authors.affiliation: Terumo Corporation, R&D Center, Nakai-machi, Ashigarakami-gun, Kanagawa, Japan; and.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Yoshino
authors.affiliation: Terumo Corporation, R&D Center, Nakai-machi, Ashigarakami-gun, Kanagawa, Japan; and.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Suzuki
mesh_terms: D000179:Acrylates / Q000737:chemistry; D000475:Alkenes / Q000737:chemistry; D002070:Butadienes / Q000737:chemistry; D004340:Drug Contamination / Q000517:prevention & control; D004348:Drug Labeling; D004349:Drug Packaging; D005898:Glass / Q000737:chemistry; D045782:Hemiterpenes / Q000737:chemistry; D010420:Pentanes / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000592:standards; D011108:Polymers / Q000737:chemistry*; D012408:Rubber / Q000737:chemistry*; D013594:Syringes; D013997:Time Factors; D014867:Water / Q000737:chemistry
chemical_list: D000179:Acrylates; D000475:Alkenes; D002070:Butadienes; D045782:Hemiterpenes; D010420:Pentanes; D004364:Pharmaceutical Preparations; D011108:Polymers; D014867:Water; C005059:isoprene; D012408:Rubber; C036658:acrylic acid; C008176:isobutylene
keywords: Adhesive; Butyl rubber; Chlorinated isoprene isobutene rubber; Cyclo olefin polymer; Extractable; Label; Label printing; Leachable; Prefillable syringe; Prefilled; Secondary packaging; Stability