Implementation of a high throughput automated platform for residual DNA quantitation

Area of Science:

• Biotechnology
• Analytical Chemistry
• Pharmaceutical Manufacturing

Background:

• Residual host cell DNA is a critical impurity in cell-based therapeutic protein production.
• Current methods for host cell DNA quantification involve laborious manual plate preparation and real-time PCR (qPCR).
• Manual processes are time-consuming, prone to human error, and require biosafety containment.

Purpose of the Study:

• To introduce and evaluate a robotic platform for automating the plate preparation step in host cell DNA extraction.
• To compare the performance of the automated workflow against traditional manual methods.
• To assess the robustness and reproducibility of the automated host cell DNA measurement process.

Main Methods:

• Development and implementation of a robotic liquid handling system (Gilson) for automated plate preparation.
• Side-by-side comparison of automated and manual workflows using samples from various purification stages (bioreactor to ultrafiltration).
• Evaluation of day-to-day variability, matrix interference, and spike recovery to demonstrate workflow robustness.

Main Results:

• The automated robotic platform significantly reduces manual labor and the risk of human error in host cell DNA extraction.
• The automated workflow demonstrates high throughput and reproducibility comparable to or exceeding manual methods.
• The robotic approach is faster than traditional methods and maintains accuracy in quantification.

Conclusions:

• Automation of host cell DNA extraction using a robotic platform offers a more efficient, reproducible, and robust solution for therapeutic protein manufacturing.
• This automated workflow enhances drug purity and safety monitoring by streamlining a critical analytical step.
• The presented robotic platform is a viable alternative to conventional manual techniques, improving overall process efficiency.