scale-x structured fixed-bed bioreactor  (Univercells)

Journal: Vaccine

Article Title: Sabin inactivated polio vaccine upstream process development using fixed-bed bioreactor technology

doi: 10.1016/j.vaccine.2025.126950

Figure Lengend Snippet: Overview of the scale-X fixed-bed bioreactor and NevoLine Polio prototype. A) The scale-X bioreactor technology uses a structured fixed-bed matrix composed of two immobilization layers, alternated with a single spacer layer for flow distribution. The fixed-bed is enclosed in a bioreactor vessel with integrated process control and recirculation using an impeller. B) The NevoLine prototype developed for the sIPV process, composed of 3 isolators respectively containing upstream, downstream and inactivation process steps.

Article Snippet: Univercells Technologies has developed the scale-X structured fixed-bed bioreactor, which encloses a spiral-wound fixed-bed matrix composed of two immobilization layers, alternated with a single-spacer layer for proper media flow ( A).

Techniques: Control

Journal: Vaccine

Article Title: Sabin inactivated polio vaccine upstream process development using fixed-bed bioreactor technology

doi: 10.1016/j.vaccine.2025.126950

Figure Lengend Snippet: Cell densities and cell growth in fixed-bed bioreactors. (A) Comparison of the cell density of WHO Vero 10–87 cell line in three 2.4 m 2 structured fixed-bed bioreactors (from 2 separate laboratories in different locations belonging to different companies) and two 4 m 2 unstructured fixed-bed bioreactors over time. The cell density was determined from picked fibers of the fixed bed. The target cell density of 1.5 × 10 5 cells/cm 2 is indicated with a dotted line. (B) The structured fixed-beds of two 2.4 m 2 bioreactors were dissected to analyze the distribution of cell growth across the fixed-bed surface with a radial dissection (0, 8, 17 mm) and across the height of the 10 cm fixed-bed (top, middle, bottom). Data are represented as mean ± standard deviation. (C) Vero cell density over time was assessed using fiber picking for 36 independent runs on 2.4m 2 fixed-bed bioreactors. The target cell density of 1.5 × 10 5 cells/cm 2 is indicated with a dotted line. (D) Glucose (blue) and lactate (green) concentrations over time of Vero cells on the structured fixed-bed bioreactors. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Article Snippet: Univercells Technologies has developed the scale-X structured fixed-bed bioreactor, which encloses a spiral-wound fixed-bed matrix composed of two immobilization layers, alternated with a single-spacer layer for proper media flow ( A).

Techniques: Comparison, Dissection, Standard Deviation

Journal: Vaccine

Article Title: Sabin inactivated polio vaccine upstream process development using fixed-bed bioreactor technology

doi: 10.1016/j.vaccine.2025.126950

Figure Lengend Snippet: Implementation of TFF for footprint reduction of the sIPV process ( n = 4 biological replicates per virus serotype with n = 3 technical replicates for fiber picking each). (A) Vero cell densities were determined through fiber picking before media replacement and infection with PV strains on day 5. The target cell density of 1.5 × 10 5 cells/cm 2 is indicated with a dotted line. (B) Population doubling times (PDTs) of Vero cells cultured in the 2.4 m 2 fixed-bed bioreactor or T-flasks. Data is represented with min-to-max floating bars with the mean. To reach the target of 1.5 × 10 5 cells/cm 2 on day 5 from 6000 cells/cm 2 seed a PDT of ≤25.8 h is required and depicted with a dotted line. (C & D) Glucose and lactate levels in the culture medium over time. The time of the media replacement and viral infection (day 5) is indicated with a dotted line. (E) Scheme describing the process of media replacement in perfusion mode after viral infection (infection medium), and subsequent continuous viral harvest using without (left panel) and with TFF (right panel, red box) for manufacturing footprint reduction. During the TFF, the (easily decontaminated) permeate is discharged and the harvest is concentrated in the harvest bottle. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Article Snippet: Univercells Technologies has developed the scale-X structured fixed-bed bioreactor, which encloses a spiral-wound fixed-bed matrix composed of two immobilization layers, alternated with a single-spacer layer for proper media flow ( A).

Techniques: Virus, Infection, Cell Culture

Journal: Vaccine

Article Title: Sabin inactivated polio vaccine upstream process development using fixed-bed bioreactor technology

doi: 10.1016/j.vaccine.2025.126950

Figure Lengend Snippet: Scale-up of the TFF sPV process to 30 m 2 . (A) Vero cell density over time at 2.4 m 2 and 30 m 2 fixed bed measured with fiber picking (2.4 m 2 ) or modeled based on the biomass glucose yield from glucose levels in the culture medium (30 m 2 ). The target cell density of 1.5 × 10 5 cells/cm 2 is indicated with a dotted line. (B) Vero cell growth over time in 30 m 2 and 150 m 2 fixed-bed bioreactors was measured by fiber-picking and calculated based on medium glucose levels. Data obtained in laboratory A. The target cell density of 1.5 × 10 5 cells/cm 2 is indicated with a dotted line. (C) Comparison of Vero cell density over time at 150 m 2 fixed bed, data from laboratory A vs B.

Article Snippet: Univercells Technologies has developed the scale-X structured fixed-bed bioreactor, which encloses a spiral-wound fixed-bed matrix composed of two immobilization layers, alternated with a single-spacer layer for proper media flow ( A).

Techniques: Comparison

Journal: Vaccine

Article Title: Sabin inactivated polio vaccine upstream process development using fixed-bed bioreactor technology

doi: 10.1016/j.vaccine.2025.126950

Figure Lengend Snippet: D-antigen productivity and infectious virus titers in a 30 m 2 fixed-bed bioreactor (FBR) for three Sabin poliovirus types and proof-of-principle for scaled-up production of sPV-3 using a 150 m 2 FBR in a containment isolator. (A) D-antigen productivity per surface area in DU/cm 2 in the bioreactor harvest of the fixed-bed bioreactor for sPV-1 (at 30 m 2 scale), sPV-2 (at 30 m 2 scale) and sPV-3 (n = 3 at 30 m 2 scale, and n = 1 at 150 m 2 scale), respectively. For comparison, estimations regarding the reference process (for sPV-2 and sPV-3) and for literature data (for sPV-1, sPV-2 and sPV-3), both using 3 g/L Cytodex 1, were based on assuming the available surface area at 4400 cm 2 /g microcarriers . (B) Infectious virus particles concentration in log 10 TCID 50 /mL in the fixed-bed bioreactor harvest for sPV-1 (at 30 m 2 scale), sPV-2 (at 30 m 2 scale) and sPV-3 (n = 3 at 30 m 2 scale, and n = 1 at 150 m 2 scale), respectively. Error bars indicate standard deviation.

Article Snippet: Univercells Technologies has developed the scale-X structured fixed-bed bioreactor, which encloses a spiral-wound fixed-bed matrix composed of two immobilization layers, alternated with a single-spacer layer for proper media flow ( A).

Techniques: Virus, Comparison, Concentration Assay, Standard Deviation

Journal: Human Vaccines & Immunotherapeutics

Article Title: Innovations in cell culture-based influenza vaccine manufacturing – from static cultures to high cell density cultivations

doi: 10.1080/21645515.2024.2373521

Figure Lengend Snippet: Technological advancements in cell culture-based influenza virus production processes using MDCK cells. Traditional egg-based processes were available since the 1940s (red arrow). Starting from the initial isolation of MDCK cells from the kidney of a healthy cocker spaniel by Madin and Darby in 1958, various options for cell culture-based production were established. Advances in medium development and the adaptation of MDCK cells to suspension growth have opened the possibility for establishment of more efficient and intensified processes. For perfusion processes relying on suspension cell lines, a bioreactor system is coupled to a cell retention device that can either be membrane-based or an inclined settler (gravity) or acoustic filter. Since the turn of the millennium, MDCK cell-based processes were licensed for the production of human influenza vaccines (blue arrows). BR: bioreactor; CSTR: continuous stirred tank reactor.

Article Snippet: Recent developments such as single-use fixed-bed bioreactor systems (scale-X, Univercells or iCELLis, Pall) allow to overcome several of the previously described limitations of static cultures.

Techniques: Cell Culture, Virus, Isolation, Suspension, Membrane, Vaccines

Journal: Human Vaccines & Immunotherapeutics

Article Title: Innovations in cell culture-based influenza vaccine manufacturing – from static cultures to high cell density cultivations

doi: 10.1080/21645515.2024.2373521

Figure Lengend Snippet: Comparison of available cultivation systems for influenza vaccine manufacturing in adherent or suspension cells. STR: stirred-tank bioreactor; OSB: orbitally shaken bioreactor (single use); Wave bioreactor (single-use); semi-perfusion in shake flask; ATF: alternating tangential flow filtration; TFF: tangential flow filtration; TFDF: tangential flow depth filtration; AS: acoustic settler; IS: inclined settler; HFBR: hollow-fiber bioreactor; semi-continuous: two-stage semi-continuous shake flask cultivation system; CSTR: two-stage continuous stirred-tank bioreactor cultivation system.

Article Snippet: Recent developments such as single-use fixed-bed bioreactor systems (scale-X, Univercells or iCELLis, Pall) allow to overcome several of the previously described limitations of static cultures.

Techniques: Comparison, Suspension, Filtration

Journal: Biotechnology Reports

Article Title: Development and Scale-up of rVSV-SARS-CoV-2 Vaccine Process Using Single Use Bioreactor

doi: 10.1016/j.btre.2023.e00782

Figure Lengend Snippet: a. Comparison of production of rVSV-SARS-CoV-2 at various infection conditions, with temperatures ranging from 32°C to 37°C and pH of either 7.0 or 7.3 in 3 L bioreactors. N = 1 for all conditions except 32°C, pH 7.3 and 32°C, pH 7.0 which have n = 2. Virus production titers measured by µPlaque (PFU/mL) are plotted against days post infection (DPI). Data represents means by condition, with at least 2 independent samples per bioreactor ± 1 standard deviation. b . Linear model specifying optimal infection pH and temperature during virus production phase and harvest time. The model predicts that the optimal infection parameters are a pH of 7.0, a temperature of 34°C, and a harvest time of approximately 2.5 days post-infection.

Article Snippet: Other alternative systems to roller bottles and cell factories are fixed-bed or packed-bed systems such as the iCELLis® bioreactor (Pall) [ , , ], Fibra-Cel® disks (Eppendorf) , and the scale-X™ bioreactor (Univercells) [ , ].

Techniques: Infection, Standard Deviation

Journal: Biotechnology Reports

Article Title: Development and Scale-up of rVSV-SARS-CoV-2 Vaccine Process Using Single Use Bioreactor

doi: 10.1016/j.btre.2023.e00782

Figure Lengend Snippet: Comparison of production of rVSV-SARS-CoV-2 at two different temperature and pH combinations: 34°C/pH 7.0 (n = 1) and 37°C/pH 7.3 (n = 1) in 50 L bioreactors. Virus production titers measured by Plaque (PFU/mL) are plotted against days post infection (DPI). Data represents the means of at least 3 independent samples per bioreactor ± 1 standard deviation.

Article Snippet: Other alternative systems to roller bottles and cell factories are fixed-bed or packed-bed systems such as the iCELLis® bioreactor (Pall) [ , , ], Fibra-Cel® disks (Eppendorf) , and the scale-X™ bioreactor (Univercells) [ , ].

Techniques: Infection, Standard Deviation

Journal: Biotechnology Reports

Article Title: Development and Scale-up of rVSV-SARS-CoV-2 Vaccine Process Using Single Use Bioreactor

doi: 10.1016/j.btre.2023.e00782

Figure Lengend Snippet: a . Comparison of Vero cell growth in 50 L (n = 4), 500 L (n = 2) and 2000 L (n = 1) bioreactors. Cell growth expressed as vc/mL is plotted against days post cell inoculation (DPCI). Data represents means by scale, with at least 4 independent samples per bioreactor ± 1 standard deviation. b . Production of rVSV-SARS-CoV-2 in 50 L (n = 4), 500 L (n = 2) and 2000 L (n = 1) bioreactors. Virus production titers measured by Plaque (PFU/mL) are plotted against days post infection (DPI). Data represents means by scale, with at least 3 independent samples per bioreactor ± 1 standard deviation.

Article Snippet: Other alternative systems to roller bottles and cell factories are fixed-bed or packed-bed systems such as the iCELLis® bioreactor (Pall) [ , , ], Fibra-Cel® disks (Eppendorf) , and the scale-X™ bioreactor (Univercells) [ , ].

Techniques: Standard Deviation, Infection

Journal: Biotechnology Reports

Article Title: Development and Scale-up of rVSV-SARS-CoV-2 Vaccine Process Using Single Use Bioreactor

doi: 10.1016/j.btre.2023.e00782

Figure Lengend Snippet: a . Comparison of viable cell density for 1 g/L (n = 1), 2 g/L (n = 2), and 3 g/L (n = 2) Cytodex 1 in 2 L bioreactors. Cell growth expressed as vc/mL is plotted against days post cell inoculation (DPCI). Data represents means by condition, with at least 2 independent samples per bioreactor ± 1 standard deviation. b . Comparison of µPlaque titers for 1 g/L (n = 1), 2 g/L (n = 2), and 3 g/L (n = 2) Cytodex 1 in 2 L bioreactors. Virus production titers measured by µPlaque (PFU/mL) are plotted against days post infection (DPI). Data represents means by condition, with at least 2 independent samples per bioreactor ± 1 standard deviation.

Article Snippet: Other alternative systems to roller bottles and cell factories are fixed-bed or packed-bed systems such as the iCELLis® bioreactor (Pall) [ , , ], Fibra-Cel® disks (Eppendorf) , and the scale-X™ bioreactor (Univercells) [ , ].

Techniques: Standard Deviation, Infection

Journal: Biotechnology Reports

Article Title: Development and Scale-up of rVSV-SARS-CoV-2 Vaccine Process Using Single Use Bioreactor

doi: 10.1016/j.btre.2023.e00782

Figure Lengend Snippet: a . Vero cells growth in 50 L bioreactors with 1 g/L Cytodex 1 with MX (n = 1), 2 g/L Cytodex 1 (n = 1), and 1 g/L Cytodex 1 without MX (n = 1). Cell growth expressed as vc/mL is plotted against days post cell inoculation (DPCI). Data represents the means of at least 4 independent samples per bioreactor ± 1 standard deviation. b . Production of rVSV-SARS-CoV-2 in 50 L bioreactors with 1 g/L Cytodex 1 with MX (n = 1), 2 g/L Cytodex 1 (n = 1), and 1 g/L Cytodex 1 without MX (n = 1). Virus production titers measured by Plaque (PFU/mL) are plotted against days post infection (DPI). Data represents the means of at least 3 independent samples per bioreactor ± 1 standard deviation.

Article Snippet: Other alternative systems to roller bottles and cell factories are fixed-bed or packed-bed systems such as the iCELLis® bioreactor (Pall) [ , , ], Fibra-Cel® disks (Eppendorf) , and the scale-X™ bioreactor (Univercells) [ , ].

Techniques: Standard Deviation, Infection

Journal: Biotechnology Reports

Article Title: Development and Scale-up of rVSV-SARS-CoV-2 Vaccine Process Using Single Use Bioreactor

doi: 10.1016/j.btre.2023.e00782

Figure Lengend Snippet: L-glutamine (A), glucose (B) and lactate (C) concentrations in 50 L bioreactors with 1 g/L Cytodex 1 with MX (n = 1), 2 g/L Cytodex 1 (n = 1), and 1 g/L Cytodex 1 without MX (n = 1). Metabolite concentrations measured by Nova Bioprofile Flex 2 are plotted against days post cell inoculation (DPCI). Data represents one sample reading per bioreactor.

Article Snippet: Other alternative systems to roller bottles and cell factories are fixed-bed or packed-bed systems such as the iCELLis® bioreactor (Pall) [ , , ], Fibra-Cel® disks (Eppendorf) , and the scale-X™ bioreactor (Univercells) [ , ].

Techniques:

Journal: Biotechnology Reports

Article Title: Development and Scale-up of rVSV-SARS-CoV-2 Vaccine Process Using Single Use Bioreactor

doi: 10.1016/j.btre.2023.e00782

Figure Lengend Snippet: a . Head-to-head comparison of Vero cell growth in 3 L bioreactors between with MX (n = 3) and without MX (n = 3) conditions. Cell growth expressed as vc/mL is plotted against days post cell inoculation (DPCI). Data represents the means by condition, with at least 2 independent samples per bioreactor ± 1 standard deviation. b . Production of rVSV-SARS-CoV-2 with (n = 3) or without MX (n = 3) in 3 L bioreactors as measured by µPlaque. Virus production titers measured by µPlaque (PFU/mL) are plotted against days post infection (DPI). Data represents means by condition, with at least 2 independent samples per bioreactor ± 1 standard deviation.

Article Snippet: Other alternative systems to roller bottles and cell factories are fixed-bed or packed-bed systems such as the iCELLis® bioreactor (Pall) [ , , ], Fibra-Cel® disks (Eppendorf) , and the scale-X™ bioreactor (Univercells) [ , ].

Techniques: Standard Deviation, Infection

Journal: Frontiers in Bioengineering and Biotechnology

Article Title: Application of bioreactor technology for cell culture-based viral vaccine production: Present status and future prospects

doi: 10.3389/fbioe.2022.921755

Figure Lengend Snippet: Overview the upstream culture process of viral vaccines. (A) Development and scale-up of a cell culture bioreactor. The left plot shows a small-scale bioreactor, which can contain cell lines, microcarriers, virus vectors, and viruses. The right plot shows an engineering grade bioreactor that can be produced on a large scale at one time. (B) Virus produced by cell lines in a bioreactor. The types of viruses produced by cell culture in a bioreactor mentioned in this review, including SARS-CoV-2, Influenza Virus, Tropical Virus, Enterovirus, and Rabies Virus. (C) Vaccine production based on large-scale virus culture. Bioreactors are mainly used to produce inactivated vaccines, live attenuated vaccines, and several subtypes of vaccines (including protein subunit vaccines, virus-like particles vaccines, and replicating viral vector vaccines).

Article Snippet: For the application of in vitro gene therapy, because of a lack of medium-sized bioreactors in the iCELLis series, which might be more suitable for in vitro therapy, Univercells has launched the competitive fixed-bed bioreactor scale-X biological series ( ).

Techniques: Vaccines, Cell Culture, Virus, Produced, Plasmid Preparation

Journal: Frontiers in Bioengineering and Biotechnology

Article Title: Application of bioreactor technology for cell culture-based viral vaccine production: Present status and future prospects

doi: 10.3389/fbioe.2022.921755

Figure Lengend Snippet: Types of cell culture bioreactors and biosafety risks.

Article Snippet: For the application of in vitro gene therapy, because of a lack of medium-sized bioreactors in the iCELLis series, which might be more suitable for in vitro therapy, Univercells has launched the competitive fixed-bed bioreactor scale-X biological series ( ).

Techniques: Cell Culture, Shear, Infection, Suspension, Recombinant, Expressing, Virus

Journal: Frontiers in Bioengineering and Biotechnology

Article Title: Application of bioreactor technology for cell culture-based viral vaccine production: Present status and future prospects

doi: 10.3389/fbioe.2022.921755

Figure Lengend Snippet: Process definition in bioreactor and its result influence in celluar environment. (A) Bioreactors can preset important parameter values through four strategies (pH Control Srategy, dO2 Control Strategy, Temperature Control strategy, pressure control strategy). The output of the process includes physical and chemical parameters such as pH, solubility of different gases, temperature, osmotic pressure, shear force and so on. Different process definitions have a great influence on the cellular environment. (B) Different celluar environment will lead to different growth states of cells. Good cell state and higher cell concentration can produce more virus titers. But the replication and release of the virus can also lead to cell death. Meanwhile, the accumulation of waste from cell metabolism will affect the celluar environment. The state of the cellular environment ultimately determines the formation and quality of the product.

Article Snippet: For the application of in vitro gene therapy, because of a lack of medium-sized bioreactors in the iCELLis series, which might be more suitable for in vitro therapy, Univercells has launched the competitive fixed-bed bioreactor scale-X biological series ( ).

Techniques: Control, Solubility, Shear, Concentration Assay, Virus