Tungsten, prefilled syringes and protein aggregation

BIOT 15

Robert Swift, rswift@amgen.com1, Yasser Nashed-Samuel, snashed@amgen.com2, Wei Liu3, Linda Narhi4, and Janice Davis2. (1) Commercialization & Packaging, Amgen Inc, 1 Amgen Ctr Dr, Thousand Oaks, CA 91320, (2) Amgen Inc, One Amgen Ctr Dr, Thousand Oaks, CA 91320, (3) Drug Product and Device Development, Amgen, Thousand Oaks, CA 91320, (4) Global Cellular and Analytical Resources, Amgen Inc, One Amgen Center Dr, 30E1B, Thousand oaks, CA 91320
Amgen has learned recently that tungsten forming pins are used in the manufacture of glass pre-filled syringe barrels and that residual tungsten from the process can lead to protein aggregation in some therapeutic protein formulations. This paper discusses: 1) the source of tungsten in syringe manufacture, 2) how Amgen confirmed the link between aggregated proten and residual tungsten, 3) the effect of fill-finish processes on product exposure to tungsten, 4) development of methods to analyze residual tungsten in empty syringes, 5) the testing of drug products to determine sensitivity to tunsten, 6) the proposed aggregation mechanism, and 7) how this experience has changed Amgen's paradigm for managing relation supplier relationships.