Table 1.

High-tungsten content clinical lots A and B, and experimentally heat-stressed HX575 contain increased HX575 aggregate levels

HX575 batchesClinical batchesExperimental batches
Lot A (260108)Lot B (270108)Heat-stressed HX575*Nonstressed HX575Low-tungsten HX575
Monomers, %96.997.892.1100.0100.0
Sum of higher-order aggregates and dimers, %3.12.27.9Not detectableNot detectable
 Dimers1.51.16.6Not detectableNot detectable
 Aggregates1.61.11.3Not detectableNot detectable
Covalent aggregation, %‡0.30.25.8Not detectableNot detectable
HX575 content, μg/mL81.582.284.084.087.6
Tungsten quantification, ppm§2.42.90.60.60.06
Neutralizing antibodiesYesYesN/AN/AN/A
PRCANoYes (P1)12N/AN/AN/A
  • HX575 batch values obtained after pooling of screened syringes with high aggregation levels. See supplemental Text 1 for further details.

  • N/A, not applicable.

  • *Heat-stressed HX575 was obtained by incubation at 54°C for 3 days.

  • †Determined by size exclusion chromatography: sum of higher-order aggregates and dimers.

  • ‡Determined by C4-high performance liquid chromatography (C4 RP-HPLC): covalent aggregation. Approximately 10% of the total aggregation determined by size exclusion chromatography was of covalent nature.

  • §Determined by inductively coupled plasma mass spectrometry.