The landscape of monoclonal antibody (mAb) manufacturing is experiencing a significant transformation, with high-concentration formulations becoming increasingly prevalent in approved therapeutics. According to Antonio Pierno, senior manager of Scientific Laboratory Services at Cytiva, 76% of FDA-approved mAbs now feature high-concentration formulations, marking a notable shift in pharmaceutical development.
Market Trends and Therapeutic Evolution
The industry is witnessing a marked transition toward subcutaneous therapeutics, moving away from traditional intravenous administration. This shift is primarily driven by practical advantages, including patient self-administration capabilities and reduced time and costs associated with healthcare facility visits. These subcutaneous formulations necessitate high-concentration therapeutics due to volume constraints in injection delivery.
High-concentration biologics are characterized by final concentrations exceeding 100g/L, with some manufacturers pushing boundaries to achieve concentrations as high as 250g/L. This trend is partially fueled by the growing demand for biosimilar reformulation.
Notable High-Concentration Products
Several prominent high-concentration biologics have already established their presence in the market, including:
- Cosentyx (secukinumab) by Novartis, targeting IL-17A
- Xolair (omalizumab) from Genentech and Novartis
- Dupixent (dupilumab) by Sanofi/Regeneron Pharmaceuticals, targeting IL-4/IL-13
Manufacturing Challenges and Solutions
The primary challenges in high-concentration therapeutic manufacturing center around sterile filtration and tangential flow filtration (TFF). These processes can lead to:
- Increased product viscosity
- Extended processing times
- Formation of aggregates
- Higher unit volume costs
- Reduced processing efficiency
To address these challenges, industry experts emphasize the importance of optimizing TFF parameters and developing new cassette technologies to enhance recovery procedures. Membrane selection plays a crucial role in the successful manufacturing of high-concentration mAbs.
Future Developments
The industry is focusing on developing new sterile filters specifically designed for high-concentration mAbs, with the primary objectives being:
- Maximizing membrane area
- Enhancing filtration processes
- Maintaining product quality
- Reducing production costs
Success in this area requires a thorough understanding of high-concentration mAb characteristics, including viscosity and flux properties, through comprehensive preliminary studies. These developments are essential for meeting the growing demand for high-concentration therapeutic products while ensuring efficient and cost-effective manufacturing processes.
