Leachables from saline-containing IV bags can alter therapeutic protein properties.
OBJECTIVE
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.
Chang
Judy Y
JY
Late Stage Pharmaceutical & Processing Development Genentech, Inc., 1 DNA Way South, San Francisco, California 94080, USA.
Xiao
Nina J
NJ
Zhu
Min
M
Zhang
Jennifer
J
Hoff
Ed
E
Russell
Stephen J
SJ
Katta
Viswanatham
V
Shire
Steven J
SJ
D002851:Chromatography, High Pressure Liquid; D007262:Infusions, Intravenous; D013058:Mass Spectrometry / Q000379:methods; D011506:Proteins / Q000008:administration & dosage*; D012965:Sodium Chloride; D013056:Spectrophotometry, Ultraviolet
D011506:Proteins; D012965:Sodium Chloride