An Approach to Mitigate Particle Formation on the Dilution of a Monoclonal Antibody Drug Product in an IV Administration Fluid
| Autor: | Monica L. Adams, Rao V. Mantri, Songyan Zheng |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
medicine.drug_class
medicine.medical_treatment Chemistry Pharmaceutical Pharmaceutical Science Polysorbates 02 engineering and technology Monoclonal antibody 030226 pharmacology & pharmacy Excipients 03 medical and health sciences Surface-Active Agents 0302 clinical medicine Pulmonary surfactant Drug Stability medicine Infusions Intravenous Saline Clinical Trials as Topic Chromatography Chemistry Antibodies Monoclonal 021001 nanoscience & nanotechnology Dilution Pharmaceutical Solutions Compounding Drug product Particle Dose reduction 0210 nano-technology |
| Zdroj: | Journal of pharmaceutical sciences. 105(3) |
| ISSN: | 1520-6017 |
| Popis: | To support dose reduction, low dose of a monoclonal antibody (mAb) was required to be administered via IV infusion at a concentration of 0.1 mg/mL. To achieve the target protein concentration, the infusion solution was prepared by diluting the drug product containing 10-mg/mL mAb with normal saline, a 0.9% sodium chloride injection solution. However, particles were observed in the diluted solution. Particle formation must be avoided to administer the low dose using the existing drug product. To mitigate the particle formation, an unconventional compounding approach was used. With this approach, a stabilizing vehicle containing polysorbate-80 was added to saline before drug-product dilution to maintain suitable surfactant level to prevent precipitation of the mAb. In this way, use of the stabilizing vehicle to support low doses ensured suitable quality across a wider range of mAb concentrations, thereby allowing additional flexibility to the clinical trial. Such an approach may be useful for broader application in early-stage clinical trials where there is an uncertainty regarding doses or the need to revise to lower doses based on clinical observations or other drivers. |
| Databáze: | OpenAIRE |
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