RT Journal Article
SR Electronic
T1 Root Cause Analysis of Tungsten-Induced Protein Aggregation in Pre-filled Syringes
JF PDA Journal of Pharmaceutical Science and Technology
JO PDA J Pharm Sci Technol
FD Parenteral Drug Association (PDA)
SP 11
OP 19
VO 64
IS 1
A1 Liu, Wei
A1 Swift, Rob
A1 Torraca, Gianni
A1 Nashed-Samuel, Yasser
A1 Wen, Zai-Qing
A1 Jiang, Yijia
A1 Vance, Aylin
A1 Mire-Sluis, Anthony
A1 Freund, Erwin
A1 Davis, Janice
A1 Narhi, Linda
YR 2010
UL http://journal.pda.org/content/64/1/11.abstract
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