Systematic assessment of process analytical technologies for biologics

Area of Science:

• Biopharmaceutical Manufacturing
• Process Analytical Technology (PAT)
• Bioprocess Engineering

Background:

• Process Analytical Technology (PAT) is widely used in biotherapeutic development and manufacturing for its technological, economic, and regulatory benefits.
• PAT tools like chromatographic, spectroscopic, and mass spectrometric sensors are integrated for real-time process monitoring and control.
• A comprehensive business value assessment of PAT in biologics has been lacking.

Purpose of the Study:

• To evaluate PAT technologies based on technological and business attributes.
• To assess PAT tools for process understanding, control, high-throughput, implementation simplicity, lead time, and cost reduction.
• To provide guidance for prioritizing and steering PAT projects in biomanufacturing.

Main Methods:

• An industry-wide survey was conducted with subject matter experts to collect, assess, and rank various PAT tools.
• PAT technologies were evaluated based on predefined criteria for technological and business value.
• Insights were gathered from clinical and commercial biologics manufacturing experience.

Main Results:

• On-line liquid Chromatography (LC), in-line Raman, and gas analysis are highly valuable for upstream bioreactor operations.
• In-line variable path-length UV/VIS measurements (VPE), on-line LC, multiangle light scattering (MALS), and automated sampling show high business value in downstream Protein A purification and polishing.
• Specific PAT tools offer significant business value at different bioprocessing stages.

Conclusions:

• The study identifies key PAT tools with high business value for specific unit operations in biomanufacturing.
• Results aid practitioners in selecting and implementing PAT for improved bioprocess development and manufacturing.
• Prioritization of PAT projects can be enhanced by understanding their technological and business value.