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Bring chromatographic clarification into your AAV purification process 

Discover how Solventum has developed a model endonuclease-free AAV lysate clarification step. 

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Target your clarification step to upgrade your process

Medical Research Laboratory: Portrait of Female Scientist Working on Computer, Analysing DNA, Virus

Adeno-associated viruses (AAV) are a leading platform for the delivery of gene therapies.  

However, the use of endonuclease treatment of AAV lysate for clarification can cost as much as $100,000 USD per 500-L batch.1,2 Eliminating the endonuclease step while maintaining quality and yield could improve process efficiency and reduce the cost of clarification. Process development may also be able to go from discovery to production more quickly by employing a streamlined approach with reliable solutions in sizes that match each development stage. 

As you strive to bring accessible treatments to fruition, consider how an innovative clarification solution can deliver the DNA reduction and AAV recovery you need. 

 

 

References

1 Garima Thakur, Sheldon Mink, Hanne Bak, and Andrew D. Tustian, “Improving process efficiency to reduce cost-of-goods per dose in manufacturing of recombinant AAVs,” Cell & Gene Therapy Insights, 10, no.3 (2024): 479-499, DOI: 10.18609/cgti.2024.061. https://www.insights.bio/cell-and-gene-therapy-insights/journal/article/3192/Improving-process-efficiency-to-reduce-cost-of-goods-per-dose-in-manufacturing-of-recombinant-AAVs


2 Garima Thakur, Sheldon Mink, Hanne Bak, and Andrew D. Tustian, “Single-use chromatographic clarification to eliminate endonuclease treatment in production of recombinant adeno-associated viral vectors,” Separation and Purification Technology, 2024, 128557, DOI: 10.1016/j.seppur.2024.128557. Single-use chromatographic clarification to eliminate endonuclease treatment in production of recombinant adeno-associated viral vectors - ScienceDirect

 

Endonuclease-free AAV clarification in a model system

Case study results suggest that an efficient, endonuclease-free process may be achieved with the 3M™ Harvest RC Chromatographic Clarifier.


Designed as an efficient option to increase monoclonal antibody (mAb) yields while intensifying the upstream process, the 3M Harvest RC chromatographic clarifier is the next generation in harvest and clarification technology. In mAb clarification processes, it can replace primary and secondary clarification, and guard membrane stages.  


Applying this technology to AAV processes, the 3M Harvest RC chromatographic clarifier was studied to compare its use with and without endonuclease treatment. Results from the case study include: 

  • Comparable AAV recovery (>90%) and turbidity reduction (>95%) with or without endonuclease treatment 
  • DNA concentrations (>94% reduction) and characteristics in clarified lysates were comparable irrespective of endonuclease use 
  • Overall predicted lower cost per batch in the endonuclease-free process 
  • Similar AAV recovery and DNA reduction across the range of Harvest RC chromatographic clarifier product sizes evaluated in the case study 
3M™ Harvest RC family with 3M™ Harvest RC Chromatographic Clarifier BT500. 3M™ Harvest RC is the next generation in harvest and clarification technology for high cell density cultures. This solution is designed as an efficient option to increase monoclonal antibody (mAb) yields while simplifying the upstream process by replacing the centrifuge and/or depth filtration unit operations.

Average AAV recovery yield >90% in a recent case study across a range of product sizes without endonuclease treatment

From discovery through each development stage, you rely on consistent performance. Study results with 3M™ Harvest RC Chromatographic Clarifier showed similarly high average AAV recovery yield at each product scale (bars) and across numerous process runs (dots) — with no endonuclease treatment of the lysate. 

Average host cell DNA reduction ≥94% in a recent case study across a range of product sizes

At each stage of development, you need high-performance DNA reduction without endonuclease. In endonuclease-free AAV5 lysate process runs, each size of the 3M™ Harvest RC Chromatographic Clarifier achieved 94% or higher reduction in DNA — and >99% in the largest sizes evaluated.

Depth filtration solutions for AAV clarification

AAV lysate clarification can also be achieved with depth filtration.  This clarification solution remains an important option for many biopharmaceutical processes — and Solventum has the depth filtration solutions you need. 

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School of Purification: Start learning today

Developed by our global experts, passionate about innovative approaches to biopharmaceutical separation and purification, School of Purification provides resources to help you and your team ramp up quickly. These free webinars and on-demand learning resources cover overcoming bottlenecks, optimizing efficiency, current trends, and future possibilities.

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