Ocriplasmin is a recombinant truncated form of human plasmin and a proteolytic enzyme used in ophthalmic medicine. It is a biological/biotechnology-derived active substance rather than a conventional small-molecule API. Ocriplasmin has a molecular weight of approximately 27.2 kDa and consists of 249 amino acids arranged in two peptide chains with six disulfide bonds. It is produced using recombinant DNA technology in a Pichia pastoris expression system. Its CAS Registry Number is 1048016-09-6.
PubChem and FDA regulatory documentation identify ocriplasmin as a recombinant truncated human plasmin produced in Pichia pastoris.
Ocriplasmin has proteolytic activity against components of the vitreous and vitreoretinal interface, including laminin, fibronectin and collagen. By cleaving these protein components, ocriplasmin can weaken the abnormal adhesion between the vitreous and retina and facilitate separation of the posterior vitreous from the retinal surface.
This enzymatic activity makes ocriplasmin particularly different from conventional ophthalmic APIs. Its biological activity is therefore an important quality attribute and cannot appropriately be represented by a simple percentage HPLC assay alone.
Ocriplasmin has been developed for the treatment of symptomatic vitreomacular adhesion (VMA) and vitreomacular traction (VMT), including VMT associated with a macular hole of appropriate size. The EMA identifies Jetrea as an ophthalmological medicine containing ocriplasmin.
The original Jetrea presentation contained ocriplasmin as a sterile, clear and colourless solution. Regulatory documentation describes a concentration of 2.5 mg/mL for the US product, while other presentations have contained 0.375 mg/0.3 mL (1.25 mg/mL) or 0.5 mg/0.2 mL, depending on the formulation and market. These concentrations should therefore not be treated as the intrinsic API specification.
As a recombinant protein, Ocriplasmin requires a biological manufacturing and characterization strategy. Important quality attributes can include protein identity, purity, biological activity, protein concentration, aggregation, fragmentation, charge variants, process-related impurities, host-cell proteins, residual host-cell DNA and microbial/endotoxin controls, depending on the drug-substance and drug-product control strategy.
Analytical characterization may include peptide mapping, mass spectrometry, electrophoretic or chromatographic purity methods, protein concentration assays and validated enzymatic potency assays. FDA documentation identifies an enzyme kinetic assay using Km and kcat for potency characterization.
Ocriplasmin was approved in the United States in 2012 and was authorized in the European Union as Jetrea in 2013. However, the European Commission withdrew the EU marketing authorisation on 30 August 2023 at the request of the marketing authorisation holder for commercial reasons. Therefore, SEO content should describe ocriplasmin as an established biological/ophthalmic API without implying that Jetrea currently has an active EU marketing authorisation.
| Parameter | Specification |
|---|---|
| Appearance | White crystalline powder or crystals |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 1.0% |
| Residue on Ignition | NMT 0.5% |
| Individual Impurity | NMT 0.5% |
| Total Impurities | NMT 1.0% |
| Water Content | NMT 1.0% |