Lloyd Waxman and Vinod Vilivalam

June 18, 2014

Comparison of the Stability of Four Biologics Stored in Prefillable Syringes Made of Glass or Plastic

The use of proteins as therapeutics has focused attention on the need to maintain the stability of these labile molecules during both storage and shipment. The trend in the pharmaceutical industry has been to package therapeutic proteins in prefillable syringes made of glass. However, some biologics are not stable in glass syringes due to sensitivity to adhesives used in their manufacture and to tungsten oxides generated during needle placement.
Syringes made from the plastic Daikyo Crystal Zenith® (CZ) cyclic olefin polymer, in addition to being break resistant, have none of these issues. However, heretofore there have been no published studies that have compared the stability of biologics in syringes made from glass with ready to fill E-beam processed CZ syringes.

To investigate the stability of biologics maintained in 1mL long syringes made of CZ, four biotherapeutic proteins were stored at 5 and 25°C up to one year; two of these were also maintained at 40°C. The same proteins were also stored in syringes made of glass. Several methods were used to monitor aggregation and degradation of the test molecules including turbidity, size exclusion chromatography (SE-HPLC), reverse-phase chromatography (RP-HPLC), ion-exchange chromatography (IEX), and gel electrophoresis. This study focused on the data from the one year time point.

Conclusions

This study compared the stability of four structurally diverse biomolecules stored in 1mL long syringes made of glass or CZ for 1 year. All four proteins were stable at 5°C in syringes made of glass or E-beam processed CZ. Proteins A and B were also stable in both glass and CZ at 25°C. At 40°C, there was more aggregation in syringes made of glass than plastic. Proteins C and D aggregated at 25°C in both glass and CZ syringes. Turbidity was higher in CZ syringes, but recovery of soluble protein from syringes made of glass or CZ was the same. Using additional analytical techniques including IEX and electrophoresis, no significant differences were found whether the proteins were stored in CZ or glass syringes.

In a parallel study, autoclaved CZ syringes were compared with E-beam sterilized CZ syringes. There was no impact on protein stability at either 5°C or 25°C (data not shown). As a plastic, CZ has several advantages over glass including the ability to be molded into other syringe formats or cartridges for on-body injectors. A head-to-head comparison between glass and CZ can best determine the most suitable container closure system for a biotherapeutic protein.

Daikyo Crystal Zenith® is a registered trademark of Daikyo Seiko, Ltd.
Daikyo Crystal Zenith® technology is licensed from Daikyo Seiko, Ltd.