Oligonucleotide manufacturing is a complex process that demands precision, efficiency, and stringent quality control. As the demand for oligonucleotides increases in therapeutics, diagnostics, and research applications, manufacturers must optimize production while maintaining high product integrity and safety. One of the critical steps in this process is the transition from cleavage and deprotection (C&D) to ultrafiltration/diafiltration (UF/DF). Traditional manufacturing setups often require separate units for these steps, leading to inefficiencies, increased handling, and higher contamination risks. The THESYS^® C&D/TFF system addresses these challenges by integrating both operations into a single, patent-pending automated platform, thereby streamlining workflows and enhancing overall manufacturing efficiency.

Technical & Design Aspects

The THESYS C&D/TFF system was designed to overcome key challenges in oligonucleotide manufacturing. By integrating C&D and UF/DF, the system significantly reduces product handling and transport between different equipment and plant areas. This consolidation minimizes exposure to reagents and media, enhancing both operator and product safety. Additionally, the system is designed to function within a classified hazardous area, eliminating unnecessary transfers that could compromise product integrity.

Compared to traditional setups with separate units, the integrated system offers the same level of efficiency and safety while delivering key cost savings. Ownership and maintenance costs are lowered, as manufacturers only need to manage a single asset instead of two. IT communication and asset management are also simplified, further reducing operational complexity.

Cutting-Edge Innovations in System Design

A key innovation behind the THESYS C&D/TFF system is its ability to control the exothermic addition of TEA-3HF using a recirculation heat exchanger. This technology ensures precise temperature management, preventing thermal fluctuations that could affect product quality. Additionally, inline quenching at the transition point between C&D and UF/DF optimizes processing efficiency and eliminates unnecessary stabilization steps.

The system’s geometry is designed to maximize product recovery, ensuring complete capture once the final UF/DF step is completed.

Optimized Processing Time and Space Utilization

By integrating C&D and UF/DF into a single, streamlined system, manufacturers eliminate unnecessary stabilization and transport steps, reducing processing time. This innovation enables the quick succession of unit operations followed by immediate purification, minimizing downtime and enhancing throughput.

The system’s integrated dual-use tank further enhances efficiency by eliminating the need for a separate tank. The tank, incorporated within the skid, allows for seamless communication with sensors, easy cleaning, and efficient management as part of the system. Traditional setups require an additional external tank, adding to the equipment footprint. By incorporating the tank into the system frame, the THESYS C&D/TFF system conserves valuable space while streamlining cleaning and maintenance. For manufacturers who require an external tank, the system’s software and piping design accommodate external integration without compromising functionality.

OCELOT^® System Control: Unparalleled Automation and Flexibility

The system is powered by OCELOT System Control software, which provides an intuitive interface and seamless integration with various plant systems and equipment. Its application-specific features ensure ease of use and greater flexibility in process control.

Ergonomic Design for Enhanced Usability

Designed with user accessibility in mind, the TFF filter cart is engineered for easy sliding in and out, making filter connection and replacement hassle-free. Additionally, all calibration instruments and maintenance components are within reach at the periphery of the frame, streamlining system upkeep.

Seamless Adoption and Ongoing Support

Customers adopting the THESYS C&D/TFF system benefit from comprehensive training, which is integrated into both Factory Acceptance Testing (FAT) at AKBA and Site Acceptance Testing (SAT) upon installation. This hands-on support ensures smooth system implementation and operation.

The Future of Automation in Oligonucleotide Synthesis

As oligonucleotide synthesis advances, automation will continue to enhance both flow-through solid-phase synthesis and alternative methods. The THESYS C&D/TFF System represents a pivotal step in optimizing existing processes, ensuring more reliable, repeatable, and efficient synthesis at all production stages.

By addressing key industry challenges and leveraging innovative automation, the THESYS C&D/TFF System is poised to redefine efficiency, safety, and process control in oligonucleotide manufacturing.

Conclusion

The THESYS C&D/TFF system marks a significant advancement in oligonucleotide manufacturing by integrating C&D and UF/DF into a single, automated platform. This innovative system minimizes process inefficiencies, enhances product control, and reduces operational costs. With its cutting-edge design, advanced software, and ergonomic features, it sets a new benchmark for streamlined oligonucleotide production, enabling manufacturers to achieve higher productivity and quality with greater ease.

To learn more, please see THESYS C&D/TFF system