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

Area of Science:

• Biotechnology
• Virology
• Process Engineering

Background:

• Live virus production, like Coxsackievirus A21, faces significant viral titer decay.
• Optimal harvest timing is critical to maximize viral yield in bioprocesses.
• Existing time-based harvest strategies lack precision and lead to yield variability.

Purpose of the Study:

• To develop and validate novel process analytical technology (PAT) harvest triggers for optimizing live virus production.
• To improve batch-to-batch consistency and maximize viral titer at harvest.
• To compare the efficacy of PAT-based triggers against traditional time-based harvest methods.

Main Methods:

• A continuous viral product titer model was created using viable cell density, cell-specific viral productivity, and viral decay rates.
• Three online PAT harvest triggers were developed using dissolved oxygen (DO) and capacitance probes.
• Derived parameters included cell-specific oxygen uptake rate (OUR) and viable cell volume (VCV).

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.
• Time-based harvests yielded only 16% of peak titer under similar deviation conditions.

Conclusions:

• PAT-based harvest triggers offer superior control and consistency in live virus bioprocessing.
• These triggers enable robust optimization of viral yield, mitigating risks associated with decay and process variability.
• Implementation of DO, capacitance, and derived OUR offers a practical advancement for bioprocess harvest optimization.