Characterization of Protein Aggregating Tungstates: Electrospray Mass Spectrometry Analysis of Extracts from Prefilled Syringes and from Tungsten Pins Used in the Manufacture of Syringes.

UNLABELLED

Glass prefilled syringes are increasingly becoming a container of choice for storing and administering therapeutic protein products to patients. Tungsten leaching from a PFS is known to induce protein particle formation, and the source was traced to the tungsten pins used in the manufacturing process of the syringe barrels. Study of the tungstates present in extracts from both tungsten pins used in the syringe manufacturing process and from single syringes from various suppliers was undertaken. Electrospray mass spectrometry was chosen as a technique with the sensitivity to characterize tungstates at levels (∼1 ppm of elemental tungsten) observed in single syringes. Extraction solvents were chosen to simulate the range (pH 4.0-7.0) typically used for therapeutic protein formulation. A commercial product formulation buffer was also used as an extraction solution to characterize tungstate species used for tungsten spiking studies of protein. All pin and syringe extracts from various manufacturers were similar in regards to containing stable Na/K containing lacunary polytungstate (W11O39) species, which were the main species present in syringe extracts and are different than the metatungstate (W12O39) species identified in commercially available sodium polytungstate and as the main species in pin extracts. These stable Na/K containing polytungstates species present in pin and syringe extracts are likely formed during the glass manufacturing process at >400 °C and may have the capability to subsequently form larger polytungstate complexes.

LAY ABSTRACT

Glass prefilled syringes are a type of container used for storing and administering biotechnology medicines to patients. The manufacturing process for the syringes may lead to very low levels of the metal tungsten being present in the syringes, and thus in the medicine stored in the syringes. The presence of tungsten in certain biotechnology medicines has been shown to cause changes to the medicine. Understanding something that can cause a medicine to change is an important part of producing safe and effective medicines for patients. The study described in this article sought to increase understanding by characterizing the form of tungsten observed in syringes from a number of vendors. Study of the tungsten present in syringes from four vendors indicates the same form of tungsten is observed regardless of the vendor. The study also found that the form of tungsten differed from that expected.