Pharmaceutical Research

, Volume 27, Issue 11, pp 2402–2413 | Cite as

Leachables from Saline-Containing IV Bags Can Alter Therapeutic Protein Properties

  • Judy Y. Chang
  • Nina J. Xiao
  • Min Zhu
  • Jennifer Zhang
  • Ed Hoff
  • Stephen J. Russell
  • Viswanatham Katta
  • Steven J. ShireEmail author
Research Paper



To investigate the cause of the observed instability of dulanermin in 100 ml polyolefin (PO) infusion bags containing saline.


Diluted dulanermin in IV bags was collected and frozen prior to analysis by size exclusion chromatography. The UV absorption profiles of the IV bag solutions were characterized by using spectrophotometry. Inductively Coupled Plasma Mass Spectrometry (ICP-MS) measured the metal content. Leachables from IV bags were identified by LC-UV-high resolution MS/MS analysis.


An elevated loss of dulanermin monomers was observed only in 100 ml PO bags. These IV bag solutions have a compound that contains zinc and has absorbance at 320 nm. This compound was identified to be 2-Mercaptobenzothiazole, and its zinc salt and was found to come from the stopper used in the 100 ml PO bags. The manufacturer has subsequently corrected this problem by using non-latex components in the 100 ml PO IV bag.


End-users need to be aware that IV bags made from a particular polymer by the same manufacturer may contain components or use a manufacturing process that results in a different product. Analysis of samples after freezing and thawing proved to be useful in identifying potential incompatibility of dulanermin in the IV bags.


compatibility freeze and thawing dulanermin IV infusion bags leachables 



centralized intravenous additive service




Factor VIII


Inductively Coupled Plasma




Liquid Chromatography


Mass Spectrometry








polyvinyl chloride


sodium dodecyl sulfate





The authors wish to thank Heather Flores, Bruce Kabakoff and Sherry Martin-Moe for their support of this project.


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Judy Y. Chang
    • 1
  • Nina J. Xiao
    • 1
  • Min Zhu
    • 2
  • Jennifer Zhang
    • 2
  • Ed Hoff
    • 2
  • Stephen J. Russell
    • 3
  • Viswanatham Katta
    • 2
  • Steven J. Shire
    • 1
    Email author
  1. 1.Late Stage Pharmaceutical & Processing Development Genentech, Inc.San FranciscoUSA
  2. 2.Protein Analytical Chemistry, Genentech, Inc.San FranciscoUSA
  3. 3.Analytical Operations, Genentech, Inc.San FranciscoUSA

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