Virus-like Particles (VLPs) Vaccine Manufacturing

Optimize upstream productivity and clarification with reliable scale-up

The upstream production platform selected for manufacturing of VLPs must be optimized to meet productivity requirements. This optimization includes the clarification step which follows cell lysis for removal of cells and cell debris and ensures a robust harvest of particles. The upstream process is only successful, however, if it can be reliably scaled in order to meet anticipated market demand.

Achieve yield and efficiency goals with robust impurity removal

Nucleic acids from lysed cells are a common contaminant in VLP processes. The European Medicines Agency (EMA) and World Health Organization (WHO) allow 10 ng DNA per dose for parenteral vaccines and 100 µg DNA per dose for oral vaccines. Additionally, in order to minimize the risk of host cell nucleic acid oncogenicity, DNA size must be reduced to 100–200 base pairs in length.

Maximize downstream recovery

VLPs are commonly purified by ultracentrifugation. While this process is well established for small-scale production, it can be time consuming and poorly scalable. Purification methods such as ion-exchange chromatography can be used as an alternative. In certain processes, membrane adsorption and monolith technology can provide better dynamic binding capacity (DBC) than particle-based resins. Multimodal resins that employ both size exclusion and binding-based separation are another option.

Ensure patient safety with sterile filtration, formulation and final fill

To help ensure patient safety, the final VLP product must be sterile filtered using a 0.22 µm filter. Formulation of VLP-based vaccine can be achieved using single-use components; single-use bags containing formulation reagents can be connected to any mixer through sterile quick-connects. After compounding and formulation, the product can be aseptically transferred to single-use filling systems for final filling and vialing.