High-tungsten content clinical lots A and B, and experimentally heat-stressed HX575 contain increased HX575 aggregate levels
| HX575 batches . | Clinical batches . | Experimental batches . | |||
|---|---|---|---|---|---|
| Lot A (260108) . | Lot B (270108) . | Heat-stressed HX575* . | Nonstressed HX575 . | Low-tungsten HX575 . | |
| Monomers, % | 96.9 | 97.8 | 92.1 | 100.0 | 100.0 |
| Sum of higher-order aggregates and dimers, %† | 3.1 | 2.2 | 7.9 | Not detectable | Not detectable |
| Dimers | 1.5 | 1.1 | 6.6 | Not detectable | Not detectable |
| Aggregates | 1.6 | 1.1 | 1.3 | Not detectable | Not detectable |
| Covalent aggregation, %‡ | 0.3 | 0.2 | 5.8 | Not detectable | Not detectable |
| HX575 content, μg/mL | 81.5 | 82.2 | 84.0 | 84.0 | 87.6 |
| Tungsten quantification, ppm§ | 2.4 | 2.9 | 0.6 | 0.6 | 0.06 |
| Neutralizing antibodies | Yes | Yes | N/A | N/A | N/A |
| PRCA | No | Yes (P1)12 | N/A | N/A | N/A |
| HX575 batches . | Clinical batches . | Experimental batches . | |||
|---|---|---|---|---|---|
| Lot A (260108) . | Lot B (270108) . | Heat-stressed HX575* . | Nonstressed HX575 . | Low-tungsten HX575 . | |
| Monomers, % | 96.9 | 97.8 | 92.1 | 100.0 | 100.0 |
| Sum of higher-order aggregates and dimers, %† | 3.1 | 2.2 | 7.9 | Not detectable | Not detectable |
| Dimers | 1.5 | 1.1 | 6.6 | Not detectable | Not detectable |
| Aggregates | 1.6 | 1.1 | 1.3 | Not detectable | Not detectable |
| Covalent aggregation, %‡ | 0.3 | 0.2 | 5.8 | Not detectable | Not detectable |
| HX575 content, μg/mL | 81.5 | 82.2 | 84.0 | 84.0 | 87.6 |
| Tungsten quantification, ppm§ | 2.4 | 2.9 | 0.6 | 0.6 | 0.06 |
| Neutralizing antibodies | Yes | Yes | N/A | N/A | N/A |
| PRCA | No | Yes (P1)12 | N/A | N/A | N/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.