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Product-Specific Impact of Viscosity Modulating Formulation Excipients During Ultra-High Concentration
Danika Rodrigues1, Laura M Tanenbaum1, Renuka Thirumangalathu1
1BioTherapeutics Drug Product Development (BioTD DPD), Janssen Research and Development (Janssen R&D), Malvern, Pennsylvania 19355.
Journal of Pharmaceutical Sciences
|December 19, 2020
Summary
Classical excipients may not improve ultra-high concentration biologics. Their effectiveness on viscosity and stability differs significantly at concentrations above 150 mg/mL, requiring product-specific evaluation.
Area of Science:
- Biopharmaceutical Development
- Protein Formulation Science
Background:
- Developing ultra-high concentration biotherapeutics (>150 mg/mL) presents challenges in viscosity, processing, and stability.
- Traditional excipient evaluations are often performed at lower protein concentrations (<150 mg/mL).
Purpose of the Study:
- To investigate the efficacy of known viscosity and stability modulators at ultra-high protein concentrations.
- To determine if excipients effective at lower concentrations benefit ultra-high concentration formulations.
Main Methods:
- Evaluated arginine monohydrochloride, proline, and lysine monohydrochloride.
- Assessed effects on viscosity and concentratability of a monoclonal antibody (mAbN) formulation.
- Compared effects at high (>50-150 mg/mL) and ultra-high (>150 mg/mL) protein concentrations.
Main Results:
- Excipient effects on viscosity and concentratability varied between high and ultra-high protein concentrations.
- Classical excipients showed different modulation profiles at concentrations exceeding 150 mg/mL.
- The rate and extent of concentratability were impacted differently by excipients at varying concentrations.
Conclusions:
- Classical excipients may require re-evaluation at target concentrations for ultra-high concentration biologics.
- Product-specific assessment of excipients is crucial for developing stable and processable ultra-high concentration biotherapeutics.
- Understanding excipient behavior at ultra-high concentrations is key to successful biopharmaceutical development.
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