The rapidly growing interest for cell and gene therapies demands the development of robust, scalable, and cost-effective bioprocesses for viral vector production. For the production of lentiviral vector (LVV) at high titers, we have developed an inducible packaging system in suspension HEK293 cells from which we can also generate stable producer cell lines, in serum-free conditions. To evaluate the potential of this platform, we have generated a stable cell line that produces an LVV encoding a green fluorescent protein (GFP) and obtains 10E+07 to 10E+08 transduction units (TU)/mL at the 4 L, 10 L and 50 L scales. Functional LVV titers were maintained across all scales in bioreactors with different configurations and geometries indicating process robustness. Further, the addition of 10% feed increased the volumetric productivity by 3.5-fold in comparison to batch production, making our platform suitable for large-scale LVV production and showing a real potential for commercial manufacturing.
Category: <span>Biologics</span>
The FDA’s ICH Q9 quality risk management (QRM) guidance material is the foundation for understanding and evaluating patient risks associated with developing and manufacturing pharmaceuticals. This three-part paper describes approaches a team of subject matter experts (SMEs) can use for implementing two important applications of QRM. Part I provides a method for identifying and remediating threat risks that may affect the product’s quality or other important aspects of a manufacturing enterprise’s lifecycle, from product research and development to commercial manufacturing. The second QRM application covered in Part II manages patient risks by identifying, evaluating, and managing risks associated with process parameters (PP) on the product’s critical quality attributes (CQAs). The final paper, Part III, describes an approach for accepting or further mitigating the risks evaluated by the QRM exercise…