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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. Shire
Research Paper

ABSTRACT

Purpose

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

Methods

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.

Results

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.

Conclusions

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.

KEY WORDS

compatibility freeze and thawing dulanermin IV infusion bags leachables 

ABBREVIATIONS

CIVAS

centralized intravenous additive service

DEHP

di-2-ethylhexyl-phthalate

FVIII

Factor VIII

ICP

Inductively Coupled Plasma

IV

intravenous

LC

Liquid Chromatography

MS

Mass Spectrometry

PE

polyethylene

PO

polyolefin

PP

polypropylene

PVC

polyvinyl chloride

SDS

sodium dodecyl sulfate

UV

ultraviolet

Notes

ACKNOWLEDGMENTS

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
  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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