Simplifying Downstream Processing for Complex Biologics
SPONSORED CONTENT: Downstream processing can be the cause of a bottleneck in manufacturing, particularly for complex biologics, leading to a need for simpler platform approaches, according to Kenneth Holbourn from FUJIFILM Biotechnologies.
As the bio/pharma industry increasingly diversifies into niche and complex modalities, the limitations of purification approaches currently used in downstream processing are becoming more apparent. Rather than continuing to use the one-off strategies, companies are demanding standardized, platform options to improve efficiencies.
To answer these demands, FUJIFILM Biotechnologies recently unveiled ShunzymeXTM — a precision purification technology that has been designed to harmonize the downstream workflow (1). In this technical interview, Kenneth Holbourn, Senior Director, Technical Project Leader Group at FUJIFILM Biotechnologies, discusses how ShunzymeX is relieving the downstream burden and allowing for flexibility.
Relieving Downstream Processing Burden
Q. Downstream processing for complex biologics is considered challenging and often the cause of a bottleneck in manufacturing. Are there any potential novel approaches of technologies that are offering companies relief in this area?
A. Yes, ShunzymeX is one of those solutions. ShunzymeX is our precision purification technology that helps to accelerate downstream processes. ShunzymeX is a novel, affinity-tag plus scarless protease approach. It allows for much of the microbial downstream processing to be standardized or ‘platformed’. This accelerates timelines and allows for a standard process and helps to simplify the more complex biologics.
Q. Could you discuss the inherent downstream processing challenges that are addressed by the ShunzymeX precision purification technology in more detail?
A. Some of the downstream processing challenges that are addressed by ShunzymeX include:
Microbial-expressed proteins that vary in size, structure, and sequence. Many lack suitable affinity resins, which can make downstream purification complex and highly customized.
No standardized/platform process — each microbial produced molecule behaves differently which can result in difficult process development work, leading to higher risk, timelines, etc. ShunzymeX provides a platformed process that simplifies and streamlines downstream processes.
Unwanted residues/non-specific activity — conventional affinity tags leave scars that can alter structure, function, and comparability. ShunzymeX uses a scarless protease approach, so this challenge is no longer an issue. Also, ShunzymeX was optimized for high specific activity.
Q. In large-scale downstream processing, protease activity can be sensitive to buffer conditions. What is the operational range of ShunzymeX in terms of pH, temperature, and conductivity, and how does it maintain its efficiency during extended residence times?
A. ShunzymeX works well at ambient conditions with a wide range of pH and buffer solutions. The lack of temperature requirement makes manufacturing easy. The reactions conditions were designed to align with the platform affinity purification step.
Q. Traditional microbial purification often struggles with low purity or yield due to the lack of robust affinity steps. Based on your data, what average percentage increase in step yield and purity are you seeing when comparing ShunzymeX to traditional multi-step non-affinity processes?
A. Using ShunzymeX we comfortably expect a > 80% purity after the initial capture step based on our work to date. This is a single step and avoids the need for multiple orthogonal steps and requires typically only a single polishing step after the tag removal.
Flexible Application and Compatibility
Q. Since the platform allows the use of off-the-shelf affinity resins, which specific tag systems are currently validated for the ShunzymeX workflow, and are there limitations on the size or folding of the target protein?
A. The current standard approach is based upon metal affinity tags. However, any tags are possible, in theory, as the approach is based on a unique linker and protease combination allowing flexibility as required.
Q. While the initial focus is on microbial-expressed proteins (leveraging the Paveway experience), is there a roadmap for applying ShunzymeX to mammalian (CHO) systems or advanced modalities like viral vectors?
A. Currently, ShunzymeX is applicable for use in E. coli and P. pastoris. In the future, yes, our roadmap includes using ShunzymeX with our mammalian expression system, ApolloX for non-mAb or non-FC affinity targets.
Q. Finally, is it possible to pair the ShunzymeX with automated platforms? If so, how does such combined equipment perform within automated cycles?
A. Yes. Feasibility screening and optimization of ShunzymeX platform is compatible with TECAN HTP systems for development.
Reference
FUJIFILM Biotechnologies. FUJIFILM Biotechnologies Unveils ShunzymeX Precision Purification Technology. Press Release, March 3, 2026.
About the Interviewee
Kenneth Holbourn serves as one of the Senior Directors in Process Development at the FUJIFILM Biotechnologies UK site, where he oversees a team of Technical Project Leaders to develop scalable and robust CGMP manufacturing processes for early and late phase therapies expressed in a range of mammalian and microbial hosts. Kenneth has over 15 years of process development experience within FUJIFILM Biotechnologies.
Prior to joining FUJIFILM Biotechnologies, Kenneth spent time in academia studying the structure of protein toxins. He holds a B.Sc. in Biochemistry from the University of St Andrews and a Ph.D. in Structural Biology from the University of Bath.
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