Olaratumab is a recombinant human IgG1 monoclonal antibody that specifically binds to human platelet-derived growth factor receptor alpha (PDGFR-α). It was developed as an antineoplastic biological drug substance under the development code IMC-3G3. FDA identifies olaratumab as a human IgG1 monoclonal antibody with an approximate molecular weight of 154 kDa.
Olaratumab was the active substance in Lartruvo, an intravenous formulation that was previously authorized for use with doxorubicin in adults with advanced soft tissue sarcoma. The EMA marketing authorization for Lartruvo was subsequently revoked in July 2019 following regulatory review.
FDA's GSRS record confirms the CAS number, IgG1 classification, complete human sequence origin and an estimated molecular weight of approximately 147 kDa based on calculated molecular characteristics, while the FDA Lartruvo label gives approximately 154 kDa for the formulated antibody.
Olaratumab is a recombinant protein rather than a conventional low-molecular-weight chemical API. Consequently, its quality assessment relies on orthogonal physicochemical, biochemical and biological characterization, rather than conventional small-molecule tests such as melting point, specific rotation or HPLC assay alone.
The EMA assessment report states that olaratumab structure was elucidated using an extensive battery of physicochemical, biophysical and biological techniques and that product- and process-related impurities were characterized.
Olaratumab was developed as a targeted antineoplastic monoclonal antibody directed against PDGFR-α. Its mechanism involves binding to PDGFR-α and interfering with receptor-mediated signaling.
For pharmaceutical development, olaratumab can be characterized through:
The EMA active-substance assessment describes a control strategy based on the quality of clinical material, stability, manufacturing-process variability, analytical-method variability and ICH principles. Importantly, potency is determined using an assay based on the mechanism of action of olaratumab.
Because complete numerical active-substance release limits are not publicly disclosed in the EMA assessment report, conventional numerical specifications such as 98–102% HPLC assay or ≤1% total impurities should not be invented for this product.
Olaratumab as a biological drug substance should be handled under controlled conditions appropriate for a recombinant monoclonal antibody and according to the applicable approved specification and stability data.
The historical finished product, Lartruvo, was supplied as a sterile intravenous solution at 10 mg/mL, with a formulation pH of 5.2–5.8. These values apply to the finished drug product, not to isolated olaratumab active substance.
| 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% |
| pH (1% Solution) | 5.0 – 7.0 |
| Individual Impurity | NMT 0.5% |
| Total Impurities | NMT 2.0% |
| Water Content | NMT 1.0% |