Drotrecogin alfa is a recombinant form of human activated protein C that was developed as a biological pharmaceutical product for the treatment of severe sepsis. It belongs to the class of recombinant anticoagulant and anti-inflammatory biological agents.
Drotrecogin alfa is a recombinant human activated protein C produced using recombinant DNA technology. Activated protein C participates in the regulation of coagulation and inflammatory pathways.
The product was formerly marketed as drotrecogin alfa (activated) under the brand name Xigris. It was subsequently withdrawn from the market after clinical evidence failed to confirm a mortality benefit in patients with severe sepsis.
Drotrecogin alfa is a recombinant biological active pharmaceutical ingredient rather than a conventional small-molecule chemical API. Its development involved recombinant protein manufacturing and extensive biological and physicochemical characterization.
Activated protein C has anticoagulant, anti-inflammatory and potentially cytoprotective effects. It inactivates activated coagulation factors Va and VIIIa, thereby reducing thrombin generation and influencing coagulation pathways.
Drotrecogin alfa was developed for the treatment of adult patients with severe sepsis and a high risk of death.
However, the product was withdrawn from worldwide markets after subsequent clinical evidence did not demonstrate the expected clinical benefit.
Drotrecogin alfa is a recombinant human protein with a molecular structure related to naturally occurring activated protein C. As a biological product, its characterization involves protein identity, purity, biological activity, aggregation, glycosylation and other critical quality attributes.
Manufacturing of recombinant protein APIs requires controlled biological production processes and specialized purification and analytical characterization. Relevant quality attributes can include identity, purity, potency, aggregation, host-cell protein, residual DNA, endotoxin and sterility-related parameters, depending on the stage and intended use of the material.
| Parameter | Specification |
|---|---|
| Appearance | White to off-white crystalline powder |
| Identification | Conforms to USP identification tests |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 1.0% |
| Residue on Ignition | NMT 0.5% |
| Heavy Metals | NMT 10 ppm |
| pH (1% Solution) | 2.0 – 4.0 |
| Individual Impurity | NMT 0.5% |
| Total Impurities | NMT 2.0% |
| Water Content | NMT 1.0% |
| Melting Point | 150°C – 154°C |