PT  - JOURNAL ARTICLE
AU  - Liu, Wei
AU  - Swift, Rob
AU  - Torraca, Gianni
AU  - Nashed-Samuel, Yasser
AU  - Wen, Zai-Qing
AU  - Jiang, Yijia
AU  - Vance, Aylin
AU  - Mire-Sluis, Anthony
AU  - Freund, Erwin
AU  - Davis, Janice
AU  - Narhi, Linda
TI  - Root Cause Analysis of Tungsten-Induced Protein Aggregation in Pre-filled Syringes
DP  - 2010 Jan 01
TA  - PDA Journal of Pharmaceutical Science and Technology
PG  - 11--19
VI  - 64
IP  - 1
4099  - http://journal.pda.org/content/64/1/11.short
4100  - http://journal.pda.org/content/64/1/11.full
SO  - PDA J Pharm Sci Technol2010 Jan 01; 64
AB  - Particles isolated from a pre-filled syringe containing a protein-based solution were identified as aggregated protein and tungsten. The origin of the tungsten was traced to the tungsten pins used in the supplier's syringe barrel forming process. A tungsten recovery study showed that the vacuum stopper placement process has a significant impact on the total amount of tungsten in solutions. The air gap formed in the syringe funnel area (rich in residual tungsten) becomes accessible to solutions when the vacuum is pulled. Leachable tungsten deposits that were not removed by the supplier's wash process are concentrated in this small area. Extraction procedures used to measure residual tungsten in empty syringes would under-report the tungsten quantity unless the funnel area is wetted during the extraction. Improved syringe barrel forming and washing processes at the supplier have lowered the residual tungsten content and significantly reduced the risk of protein aggregate formation. This experience demonstrates that packaging component manufacturing processes, which are outside the direct control of drug manufacturers, can have an impact on the drug product quality. Thus close technical communication with suppliers of product contact components plays an important role in making a successful biotherapeutic.© PDA, Inc. 2010