Test & measurement
RAMAN INTERFACE TO HIGH- THROUGHPUT DEVELOPMENT Recent advances have expanded Raman analysis to the smallest bioreactor setups and large-scale single-use bioreactors (SUBs). One such innovation is the union between Endress+Hauser Raman analyzers equipped with Rxn-46 bioprocess probe technology and the BioPAT Spectro platform by Sartorius. This integrated solution offers an ideal interface to high-throughput development through single-use clinical and commercial manufacturing. The Rxn-46 probe, adapted to fit Sartorius’s BioPAT Spectro platform, utilises the same probe design for Ambr 15, Ambr 250 and Biostat STR bioreactors. The integration allows for the rapid generation of Raman data to build robust, scalable models. Providing fast, reliable and accurate measurement of key bioprocess variables has never been easier.
INTEGRATION INTO SINGLE-USE SYSTEMS
Another recent revolution is the ability to offer Raman technology pre-installed into single-use bioreactor and mixing bags. Integrated single- use Raman probe connections eliminate contamination risks associated with end-user probe sterilisation and aseptic insertion. Endress+Hauser stands out by offering one of the only multi-attribute sensors available for different types of bioprocessing containers and from multiple single-use vendors. The Raman optic system for single use comprises a disposable fitting and a reusable non-contact optic. The disposable wetted part aligns with industry standards and is sold directly to single-use vendors. There, it undergoes gamma sterilisation and is delivered as a sterile, ready-to-use component of the SUB or mixing bag. This approach enhances ease of use, reduces cleaning and maintenance requirements, and minimises contamination risk without compromising performance.
VERSATILE IMMERSION OPTIC SYSTEMS FOR BENCHTOP BIOREACTORS Expanding on its single-use technology, Endress+Hauser has also introduced a bio multi optic and sleeve option for benchtop scale bioreactors. This versatile system streamlines the user’s workflow, reduces contamination risk, is maintenance-free and enables integration into benchtop-style single-use bioreactors. Connection with the Raman analyzer and probe is achieved via a specially designed multi-use optic that fits into a disposable sleeve. The disposable bio sleeve eliminates the need for specialised Raman lenses and probe components to endure frequent sterilisations and sample exposures, addressing issues associated with long- term reusability of process contact components. While suitable for gamma sterilisation and single use, the stability of the bio sleeve also allows for multiple autoclave cycles. The bio
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multi optic and sleeve system enables biopharmaceutical companies to maintain sterility and spectral quality while reducing set-up and cleaning burdens.
UNIQUE CHALLENGES IN DOWNSTREAM UNIT OPERATIONS
Downstream operations encompass buffer preparation, clarification, chromatography, ultrafiltration/diafiltration (UF/DF), viral inactivation, polishing, formulation stability and more. While upstream applications have seen widespread adoption of Raman technology, downstream unit operations each face unique challenges and therefore have been slower to adopt PAT solutions. Previous technological challenges that have impeded efficiency improvements for downstream applications include reliance on extractive analytical methods for composition measurement, slow response times, insufficient nominal ranges, background interference, accuracy issues, lack of stability and a lack of specificity to quality attributes. The increasing complexity of purification steps due to intensified upstream processes has also highlighted the need for innovative solutions in downstream bioprocessing.
INNOVATIONS BRINGING RAMAN TO DOWNSTREAM Recognising the unmet needs in downstream processing, Endress+Hauser recently launched the Raman flow assembly to fill the lab- and pilot- scale flow cell system void. This offering is optimised specifically for downstream flow paths, utilising signal amplification coupled with low noise technology for faster results. The Raman flow assembly is a specialised Raman tool designed for biopharmaceutical labs and process development in the purification and perfusion spaces, with the potential to scale up to cGMP manufacturing. The Raman flow assembly consists of a micro flow cell and associated micro flow bench connected to a Raman probe and analyzer. The system meets the speed demands of downstream by optimising Raman collection for low-turbidity, low-volume samples. The micro flow cell is a streamlined piece of wetted hardware that can be cleaned and sterilised for reuse or discarded after each use, offering flexibility to the user. The non-wetted flow bench generates Raman signal- to-noise enhancement, crucial for fast measurements at low concentrations. With the Raman flow assembly, biopharmaceutical manufacturers have an opportunity to embrace Raman spectroscopy to achieve real-time monitoring, rapid process optimisation and process control for chromatography and other downstream unit operations.
NEW CALIBRATION AND VERIFICATION TECHNOLOGY As Raman spectroscopy gains prominence in both upstream and downstream bioprocessing, the need for efficient calibration and verification
becomes paramount. Endress+Hauser recently introduced a new suite of convenient calibration and verification kits that encompass all the necessary hardware to streamline calibration and verification for their multi optic (and single-use optic), Rxn-46 probe and
Raman flow assembly (with others to come). The modular hardware in the kits was designed to enable quick instrument standardisation for minimal downtime. The kits require no external power, allowing for easy field deployment. Another efficiency element is that the process-contact part of the Raman probe, optic or flow cell is no longer required for calibration and verification steps, which drastically simplifies the workflow and reduces risk.
CONCLUSION Raman spectroscopy, once a novel technology, is now a well-established tool with vast potential to continue to reshape the life sciences industry. Highly automated processes, combined with real- time monitoring of quality parameters and meticulous risk management, are becoming increasingly prevalent. As the borders of Raman’s capabilities continue to expand, biopharmaceutical manufacturers are embracing it to successfully boost process efficiencies and yields. Finding a trusted partner in Raman technology is crucial for biopharmaceutical companies seeking to navigate the ongoing complexities of upstream and downstream bioprocessing. Endress+Hauser, with its extensive process automation experience and commitment to advancing Raman technology, stands out as a pioneer in the field. Its portfolio of robust and comprehensive Raman systems, as well as its tailored global service and support offerings, exemplify the company’s commitment to meeting the industry-specific requirements of its customers. The shift towards single-use technology in bioprocessing is undeniable, and Endress+Hauser’s advancements in single-use systems, coupled with its dedication to quality and versatility, position it as a key player in shaping the future of biopharmaceutical manufacturing. The integration of Endress+Hauser’s Raman technology into high-throughput platforms like BioPAT Spectro and its newly launched bio multi optic and sleeve system further demonstrates the flexibility of its technology to meet evolving industry needs in upstream processes. In addition, Endress+Hauser’s introduction of the Raman flow assembly adeptly addresses many downstream application concerns, and in doing so expands the broader potential of Raman spectroscopy in that arena. As biopharmaceutical companies continue to embrace the benefits of Raman technology, collaboration with a reliable partner like Endress+Hauser becomes indispensable, ensuring the successful integration of Raman spectroscopy for enhanced process control, quality assurance and, ultimately, improved patient outcomes.
Endress+Hauser
www.endress.com August 2024 Instrumentation Monthly
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