Minimizing batch-to-batch variability of a live virus vaccine by process analytical technologies

Area of Science:

• Biotechnology
• Virology
• Process Engineering

Background:

• Live virus bioprocesses, like those for Coxsackievirus A21, face significant viral titer decay.
• Optimal harvest timing is critical to maximize viral yield and ensure process efficiency.

Purpose of the Study:

• To develop and evaluate novel Process Analytical Technology (PAT) harvest triggers for optimizing live virus bioprocess harvests.
• To improve batch-to-batch consistency and maximize viral yield compared to traditional methods.

Main Methods:

• A continuous viral product titer model was created using viable cell density, cell-specific viral productivity, and decay rates.
• Three PAT harvest triggers were developed utilizing dissolved oxygen (DO) and capacitance probes, calculating cell-specific oxygen uptake rate (OUR).
• PAT triggers were compared against time-based harvests in experimental bioprocesses.

Main Results:

• PAT harvest triggers significantly reduced the standard deviation of harvest yield: 41% (DO), 56% (OUR), and 71% (capacitance) compared to time-based harvests.
• PAT triggers achieved >87% of peak viral titer even with process deviations, while time-based harvests yielded only 16%.

Conclusions:

• PAT-based harvest triggers offer superior control and consistency for live virus bioprocessing.
• These advanced triggers mitigate yield losses associated with viral decay and process variability, enhancing overall bioprocess performance.