bridging upstream and downstream bioprocessing
Backed by independent, peer-reviewed studies and proven in real-world applications, Sani Membranes’ Vibro® Membrane Filtration (VMF) technology helps partners achieve higher yields, lower costs, and robust process performance—no matter where they are on their bioprocessing journey.
the bioprocessing landscape
Upstream, Midstream and Downstream
Biomanufacturing is a highly integrated, multi-stage process that transforms living cells into purified, high-value bioproducts such as monoclonal antibodies (mAbs), recombinant proteins, and nucleic acids (e.g., mRNA). Each stage presents unique technical challenges and opportunities for innovation.
The biomanufacturing workflow is typically categorised into Upstream and Downstream processing. The intermediate steps, which involve the separation of biomass from the target product, may be classified as part of either Upstream or Downstream operations. However, it is increasingly common within the industry to refer to this segment as “Midstream” processing, recognising its distinct technical and operational considerations within the overall production continuum.
Upstream Processing
Seed Train Expansion and Cultivation
Upstream processing includes growing the organism from the cell bank through seed train steps to final cultivation and product expression in the production bioreactor.
Seed Train Expansion: For bacterial processes this is often limited to a few steps whereas for mammalian cell cultivation it may involve 4-5 individual steps with gradually more volume before reaching the production scale bioreactor. Process intensification involving high-density cultures, perfusion systems and advanced monitoring and control can reduce the number of steps required, and the time for the full production cycles considerably.
Bioreactor Operation: Cultivation of the production organism in controlled medium and environments. Several processing strategies are used, such as batch, fed-batch, or perfusion bioreactors. The process involves precise regulation of nutrients, pH, temperature, and agitation as well as dissolved oxygen for aerobic processes. The product expression may be controlled by manipulating the process conditions towards the end of batch and fed-batch processes, or maintained continuously throughout perfusion type processing.
Bleed stream productivity increase
Recovery of API from bleed stream.
- Continuous and sustainable yield optimization from perfusion process
- Fully comparable / compatible API quality
Seed train intensification
Cell retention device to improve upstream processing.
- Shorten seed trains
- Increased cell density
Perfusion stream processing
Cell retention device for perfusion processes.
- Improved product yield
- Sustainable long-term performance
Technical Considerations
Industry Trends
How Can VMF Improve Upstream Processing?
VMF supports robust and scalable cell retention technology for seed train intensification and perfusion, handling high cell densities with minimal fouling and gentle processing.
MIDstream Processing
Primary Recovery and Clarification
Midstream processing, often referred to as primary recovery, bridges the gap between cell cultivation and product purification. The main objectives are to efficiently separate cells and debris from the product-containing supernatant or lysate, and to prepare a clarified feed containing the target product for the downstream processing steps.
Key Steps:
Cell Harvest: Removal of cells from culture broth via centrifugation, depth filtration, or membrane-based microfiltration.
Cell Disruption (for intracellular products): Mechanical (e.g., high-pressure homogenisation), chemical, or enzymatic lysis to release target proteins or nucleic acids.
Clarification: Removal of cell debris, DNA, and colloidal impurities using depth filters, tangential flow filtration (TFF), or advanced membrane technologies.
Harvest clarification
Recovery of API from microbial and mammalian cell suspensions.
- Unique process control, low TMP & high API transmission
- High cell concentration, low cell damage
Clarified harvest intensification
Single-pass concentration of clarified harvest.
- Downstream intensification for improved capture step capacity
- Robust, continuous in-line process step
Perfusion stream processing
One process solution for combined harvest clarification and API concentration.
- Single operation to concentrated, clarified harvest
- Increased capture step capacity
- Inline clarified harvest concentration (MF in batch mode, coupled with SPVMF – inline concentration)
- Tandem solution MF and UF in batch mode, coupled, like MOC plant)
Combined cell harvest and recovery of intra-cellular API’s
One process technology for the recovery of intracellular API from bioreactor
- Harvest of cells for subsequent lysis step
- API recovery by clarification of cell lysate
Technical Considerations
Industry Trends
How Can VMF Improve Midstream Processing?
VMF excels in clarification and primary recovery, enabling extracellular product recovery with minimal cell damage as well as high-yield separation of cell debris for intracellular products, all using the very same technical solution.
downstream Processing
Downstream processing transforms the clarified product stream into a highly purified, formulated, and stable final product that meets regulatory and quality standards.
Key Steps:
Capture and Purification: Isolation and purification of the target molecule by several chromatography steps (e.g., Protein A, ion exchange, affinity, size exclusion).
Concentration and Buffer Exchange: Ultrafiltration/diafiltration (UF/DF) to concentrate the product and exchange buffers for adjustment of pH and ionic strength and securing product stability.
Polishing and Virus Removal: Removal of trace impurities, aggregates, viruses, and endotoxins to meet stringent purity requirements.
Formulation and Fill-Finish: Final formulation, sterile filtration, and aseptic filling into vials or syringes.
Concentration and Buffer Exchange
Gentle, low shear UF processing
- Efficient concentration, buffer exchange and diafiltration
- Processing at higher viscosities
- Batch or inline, continuous mode
- Low product impact, low energy consumption
Nano Lipid Particles Processing
Concentration, purification and buffer exchange of NLP suspension.
- Gentle, low shear impact technology
- Retaining size distribution of the NLP suspension
Technical Considerations
Industry Trends
How Can VMF Improve Downstream Processing?
VMF in batch operation or single-pass mode can be used as part of process intensification strategy for improved capacity of the first capture chromatography step, as well as for efficient ultrafiltration for concentration and buffer exchange.
Articles
Single-Pass TFF mAbs
Continuous processing of mAbs with groundbreaking Vibro® technology.
Single-Pass Tangential Flow Filtration (SPTFF) with Vibro® Membrane Filtration (VMF)
Single-Pass TFF mRNA
Outstanding mRNA concentration by Vibro technology.
Higher flux without compromising conversion rates.
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