Using Capacitance as a Process Analytical Technology (PAT) Tool to Improve Productivity and Reduce COGS in Bioprocesses

Capacitance as a Real-Time PAT Tool

Capacitance-based measurements use an alternating electric field to polarize viable cells. Only live cells with intact membranes contribute to the signal, meaning measurements directly reflect viable biomass, excluding debris, dead cells, or bubbles. As such, capacitance provides a true picture of cell health, growth trends, and bioprocess performance.

Improving Productivity in Fed-Batch Processes

Traditional feeding strategies rely on offline measurements taken every 24 hours. However, capacitance-based control allows for much more frequent monitoring and feed adjustments, as demonstrated by studies from Biogen and the National Research Council Canada (NRC).

One such strategy, feeding every four hours based on real-time capacitance data, led to a 21% increase in product titer due to improved nutrient management and reduced risk of depletion. Similarly, the NRC study demonstrated a 62.5% increase in titer compared to bolus feeding methods.

Enhancing Productivity in Viral Vector and Vaccine Production

In viral vector production, where the timing of harvest is critical, capacitance enables precise identification of the optimal harvest point. A study published in Biotechnology and Bioengineering reported that harvest consistently occurred approximately 39.6 hours after peak capacitance was observed, leading to a more than three-log increase in virus concentration. This enables significant scale-down, with equivalent output from 500 mL bioreactors compared to traditional 20 L setups—a 40-fold improvement in productivity.

Reducing COGS through Media Savings in Perfusion

Perfusion processes are inherently media-intensive, contributing to high COGS. Capacitance-controlled perfusion strategies optimize media usage through real-time control of cell-specific perfusion rates (CSPR). In one such study, capacitance-based perfusion control reduced media consumption by 30–40% in both 5 L and 250 L scales, while still supporting exponential cell growth every four hours.

Financial Impact and Return on Investment

Even modest productivity improvements can yield substantial financial benefits. A 1% increase in productivity in a 1,000 L fed-batch run (producing 3 kg of product at $1,000/dose) equates to an additional $300,000 per batch. Across 20 runs per year over 10 years, this could mean an additional $60 million in revenue, all without expanding bioreactor capacity.

When viewed in this context, the adoption of capacitance as a PAT tool becomes a strategic investment with the potential for high ROI, process stability, and regulatory confidence.

Join Our ISPE Webinar

To delve deeper into these findings and explore real-world data, join Aditya Bhat, PhD, and Eifion Loosley for the ISPE webinar:

Whether you’re exploring PAT tools or looking to scale efficiently while managing costs, this session will offer practical insights backed by data and case studies.