Ravulizumab is a recombinant humanized monoclonal antibody designed to inhibit the terminal complement pathway by selectively binding to complement component C5. It is engineered with an IgG2/4 heavy-chain constant region and a human kappa light-chain constant region. The molecule is produced using Chinese hamster ovary (CHO) cells and has an approximate molecular weight of 148 kDa.
Ravulizumab is marketed as ravulizumab-cwvz and is the active substance in ULTOMIRIS. Current regulatory information covers its use in paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), generalized myasthenia gravis (gMG) and aquaporin-4-antibody-positive neuromyelitis optica spectrum disorder (NMOSD).
Ravulizumab is a large biological molecule rather than a conventional synthetic small-molecule API. Its quality evaluation therefore relies on orthogonal analytical characterization, including molecular identity, protein concentration, purity, aggregation, charge heterogeneity, glycosylation, potency and process-related impurities. EMA's assessment confirms characterization of the antibody's glycosylation, charge variants, aggregates and biological activity.
| Parameter | Value |
|---|---|
| CAS | 1803171-55-2 |
| UNII | C3VX249T6L |
| Molecular type | Recombinant monoclonal antibody |
| Isotype | IgG2/4-kappa |
| Heavy chains | 2 × 448 amino acids |
| Light chains | 2 × 214 amino acids |
| Molecular weight | Approximately 148 kDa |
| Expression system | CHO cells |
| Target | Complement C5 |
| Mechanism | Inhibition of terminal complement activation |
FDA documentation confirms the antibody architecture and approximately 148 kDa molecular weight.
Ravulizumab is used as a complement inhibitor in several complement-mediated disorders. Current EMA information lists indications including PNH, aHUS, anti-AChR-antibody-positive generalized myasthenia gravis and AQP4-antibody-positive NMOSD.
Ravulizumab requires biologic-specific analytical characterization rather than a standard small-molecule HPLC assay. Important quality attributes include:
EMA reports characterization of ravulizumab biological activity, C5 binding, FcRn binding, glycosylation, aggregates and charge variants.
Ravulizumab active substance requires validated biologic storage conditions. The finished ULTOMIRIS formulation is supplied as a preservative-free sterile solution in single-dose glass vials. Current FDA labeling lists 300 mg/30 mL, 300 mg/3 mL and 1,100 mg/11 mL IV presentations.
Typical documentation for a Ravulizumab biological API can include:
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 0.5% |
| Residue on Ignition | NMT 0.1% |
| Individual Impurity | NMT 0.10% |
| Total Impurities | NMT 0.50% |
| Water Content | NMT 1.0% |