Value of a negative cervical smear

Abstract

Certain types of glass vials used as primary containers for liquid formulations of biopharmaceutical drug products have been observed with glass flake like delamination or 9lamellae9 under certain conditions during storage. The cause of this delamination is in part related to the glass surface defects, which renders the vials susceptible to flaking, and are formed during the high temperature melting and annealing used for vial fabrication and shaping. Current European Pharmacopoeia (Ph. Eur.) method to assess glass vial quality utilizes acid titration of vial extract pools to determine hydrolytic resistance or alkalinity. Four alternative techniques with improved throughput, convenience, and/or comprehension were examined by subjecting seven lots of vials to analysis by all techniques. The first three new techniques of conductivity, flame photometry, and inductively coupled plasma mass spectrometry (ICP-MS) measured the same sample pools as acid titration. All three showed good correlation with alkalinity; conductivity (R2=0.9951), flame photometry sodium (R2=0.9895), and several elements by ICP-MS [(sodium (R2=0.9869), boron (R2=0.9796), silicon (R2=0.9426), total (R2=0.9639)]. The fourth technique processed the vials under conditions that promote delamination, termed the Accelerated Lamellae Formation (ALF), and then inspected those vials visually for lamellae. The visual inspection results without the lot with different processing condition correlated well with alkalinity (R2=0.9474). Due to vial processing differences affecting alkalinity measurements and delamination propensity differently, ratio of silicon and sodium measurements from ICP-MS was the most informative technique to assess overall vial quality and vial propensity for lamellae formation. The other techniques of conductivity, flame photometry, and ALF condition may still be suitable for routine screening of vial lots produced under consistent processes.