Characterization of filter extractables by proton NMR spectroscopy: studies on intact filters with process buffers.
Studies were conducted to characterize potential extractables from sterilizing grade filters. The focus of this report is the 0.22 micron Durapore (hydrophilic modified PVDF) filter which is used throughout our recovery processes. The objectives of this study are (1) to identify potential filter extractables from the hydrophilic PVDF filters; (2) to show that NMR spectroscopy may be used to detect filter extractables in the presence of product and excipients; and (3) to establish levels of filter extractables obtained by extraction with a variety of buffers. The data show that the primary source of filter extractables is the hydrophilic modification of the PVDF membrane surface. Extractables from the modified hydrophilic PVDF filter include propylene glycol (PG) and soluble oligomers of the hydroxypropyl acrylate and cross-linker. Propylene glycol, arising from the hydrolysis of the hydroxypropyl acrylate, appears to be the primary extractable in buffers above pH 11. Since the 1H-NMR method can easily detect the methyl proton signals of PG, an NMR assay was developed to detect PG in the presence of buffer excipients and final product. Propylene glycol can be used as a marker for the extractables from Durapore hydrophilic PVDF filters. Although numerous buffers were used to generate extractables from the PVDF filter, significant extractables (PG and soluble oligomers) were found only in high pH extraction buffers. As a result of this finding, only a limited number of new buffers or new PVDF filters will require testing for future validation studies. Process validation studies have shown that neither PG nor soluble oligomers are at levels that impact the quality or safety of the product.
Kao
Y H
YH
Genentech, Inc., South San Francisco, CA 94080, USA. yhk@gene.com
Bender
J
J
Hagewiesche
A
A
Wong
P
P
Huang
Y
Y
Vanderlaan
M
M
D002021:Buffers; D004345:Drug Industry; D005079:Excipients; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D013242:Sterilization / Q000295:instrumentation*; D014462:Ultrafiltration
D002021:Buffers; D005079:Excipients