약독화 백신, 불활화 바이러스 백신

Selecting the optimum cell line or clone for the target virus relies on low-volume screening tools and fast analytics

Fully scalable HTPD tools, inline analytics are needed to quickly define the best operating conditions for cell expansion (media selection, process parameters optimization) and virus propagation (media, feed, multiplicity of infection, time of infection, harvest time, etc.)  

Many in industry are moving away from serum-containing media in favor of chemically defined (CD) media to support process safety and batch consistency,  

Ultimately, having an experienced partner capable of providing the characterization tools for the cell line is the way to select a stable and safe cell line with confidence

The flexibility and functionality of Ambr^® 15 & Ambr^® 250 can accelerate cell line selection and process optimization. Ambr^® is the only high-throughput cell culture system with scalable, multiparallel mini-bioreactors and automated functionality.

• Proven technology with all suspension cell lines
• Capable in all operation modes: batch, fed-batch, perfusion
• Integrated with a wide range of connectivity of inline analytics, including BioPAT^® Spectro  
• Available with MODDE^® software to facilitate DoE  

Additional Solutions to Consider:

• A new generation of chemically defined (CD) and animal component free (ACF) cell culture media developed and tested with Sartorius bioreactors
• With more than 70 experienced scientists in the US and Europe to conduct a full package of biosafety testing compliant with current regulations for viral-based vaccines, Sartorius is well positioned to support their customers from cell line and strain selection to commercial manufacturing.

Selecting the optimum cell line or clone for the target virus relies on low-volume screening tools and fast analytics

Fully scalable HTPD tools, inline analytics are needed to quickly define the best operating conditions for cell expansion (media selection, microcarrier selection, process parameters optimization) and virus propagation (media, feed, multiplicity of infection, time of infection, harvest time, etc.)  

In order to effectively evaluate adaptation of adherent cell line to suspension, there is a pressing need for low volume screening tools, fast analytics  

Many in industry are moving away from serum-containing media in favor of chemically defined (CD) media to support process safety and batch consistency

Ultimately, having an experienced partner capable of providing the characterization tools for the cell line is the way to select a stable and safe cell line with confidence

A new generation of Ambr^® 15 tailored to microcarriers applications and Ambr^® 250 vessels designed for microcarriers can accelerate cell line selection and process optimization. Ambr^® is the only high-throughput cell culture system with scalable, multiparallel mini-bioreactors, automated functionality and vessels developed for microcarriers.

• Proven technology with adherent cell lines
• Capable in batch and fed batch operation modes  
• Integrated with a wide range of connectivity of inline analytics, including BioPAT^® Spectro
• Available with MODDE^® software to facilitate DoE

Additional Solutions to Consider:

• New generation of chemically defined (CD) and animal component free (ACF) cell culture media developed and tested with Sartorius bioreactors
• With more than 70 experienced scientists in the US and Europe to conduct a full package of biosafety testing compliant with current regulations for viral-based vaccines, Sartorius is uniquely positioned to support their customers from cell line and strain selection to commercial manufacturing.

Adjusting the seed expansion step to production scale relies on fully scalable technologies from process development to manufacturing 

Intensifying processes are critical to reduce the seed train and decrease cost of production while achieving higher cell concentration  

The sterility of the seed train relies on a closed process from the shake flask through the rocking motion bioreactor  

Process Analytical Technologies can ensure the robustness and control of the seed train

Biostat^® RM, a fully GMP compliant, wave-mixed bioreactor, is an easy-to-use system for seed expansion offering the widest range of PAT in a Biosafety Level 2 environment  

• Industry-proven bioreactor for seed expansion of viral-based vaccines
• A unique & robust film across the process ensuring excellent cell growth
• A closed process to lessen environmental risk to products and operators
• Integration of a wide range of PAT including BioPAT^® Viamass, BioPAT^® Trace and BioPAT^® Spectro
• A bag-integrated cell retention filter for intensified production

Additional Solutions to Consider:

• Mycap^® CCX to grow cells in an incubator and passage between flasks without ever opening a flask and or going into a biosafety cabinet
• A new generation of chemically defined (CD) and animal component free (ACF) cell culture media developed and tested with Sartorius bioreactors

Adjusting the seed expansion step to production scale relies on fully scalable technologies from process development to manufacturing
 

Evaluation and implementation of the correct parameters and mixing conditions is critical to avoid cell detachment from the microcarriers and microcarriers breakage

 
The sterility of the seed train relies on a closed process from the shake flask through the rocking motion bioreactor

Process Analytical Technologies can ensure the robustness and control of the seed train

Biostat^® RM, a fully GMP compliant, wave-mixed bioreactor, is an easy-to-use system for seed expansion offering the widest range of PAT in a Biosafety Level 2 environment  

• Industry-proven bioreactor for seed expansion of viral-based vaccines
• A unique & robust film across the process ensuring excellent cell growth
• A closed process to lessen environmental risk to products and operators
• Integration of a wide range of PAT including BioPAT^® Viamass, BioPAT^® Trace and BioPAT^® Spectro
• A bag-integrated cell retention filter for intensified production

Additional Solutions to Consider:

• A new generation of chemically defined (CD) and animal component free (ACF) cell culture media developed and tested with Sartorius bioreactors

Fully scalable technologies, from process development to manufacturing, are needed to take virus propagation to production scale  

Achieving higher virus concentration while decreasing cost of production relies on process intensification

It is imperative to ensure containment and reduce contamination risk while working with infectious viral particles classified as Biosafety Level 2

Process Analytical Technologies in this environment are essential to enable robust processes and infection monitoring and control

Biostat STR^® is a single use bioreactor offering the widest range of PAT in a Biosafety Level 2 environment, making it the perfect match for viral production:

• A unique and robust film across the process ensuring excellent cell growth
• Integration of a wide range of PAT including BioPAT^® Viamass, BioPAT^® Trace and BioPAT^® Spectro
• Built on Biosafety principles to reduce risk of leaks
• Direct scalability from Ambr^® to STR for rapid process development
• Capable in all operation modes: batch, fed-batch, and perfusion

Additional Solutions to Consider:

• A new generation of chemically defined (CD) and animal component free (ACF) cell culture media developed and tested with Sartorius bioreactors

• Ambr^® 15 and 250 are the only high-throughput cell culture with scalable, multiparallel mini-bioreactors and automated functionality supporting viral-based vaccine application

• With more than 70 experienced scientists in the US and Europe to test the Master Virus Seed (MVS) in compliance with current regulations for viral vaccines, Sartorius is well positioned to support customers from cell line and strain selection to commercial manufacturing

Fully scalable technologies, from process development to manufacturing, are needed to take virus propagation to production scale  

Evaluation and implementation of the correct parameters and mixing conditions is critical to avoid cell detachment from the microcarriers and microcarriers breakage

It is imperative to ensure containment and reduce contamination risk while working with infectious viral particles classified as Biosafety Level 2

Process Analytical Technologies in this environment are essential to enable robust processes and infection monitoring and control

The Biostat STR^® is a single use bioreactor, offering the widest range of PAT in a Biosafety Level 2 environment, making it the perfect match for viral production:

• A unique and robust film across the process ensuring excellent cell growth
• Integration of a wide range of PAT including BioPAT^® Viamass, BioPAT^® Trace and BioPAT^® Spectro
• Built on Biosafety principles to reduce risk of leaks
• Direct scalability from Ambr^® to STR, supporting microcarrier applications for rapid process development
• Capable in all operation modes: batch, fed-batch, and perfusion 

Additional Solutions to Consider:

• A new generation of chemically defined (CD) and animal component free (ACF) cell culture media developed and tested with Sartorius bioreactors

• Ambr^® 15 and 250 are the only high-throughput cell culture with scalable, multiparallel mini-bioreactors, and automated functionality supporting adherent processes

• With more than 70 experienced scientists in the US and Europe to test the Master Virus Seed (MVS) in compliance with current regulations for viral vaccines, Sartorius is well positioned to support customers from cell line and strain selection to commercial manufacturing

Viral particles adsorb to depth filters, so it is critical to remove cells or cell debris while maintaining high product recovery

Viral particles are infectious, so containment during processing and disassembling is required to be compliant with Biosafety Level 2/3 requirements

Enveloped viruses that are larger than 0.2µm make sterile filtration impossible, so the only way to ensure process sterility and operator safety in those circumstances is through pre-sterilized and closed solutions

A high capacity clarification solution is needed to address the overall challenges of working with high cell density in a suspension process

Ksep^® single use centrifuge is the leading single-use centrifuge for clarification from low to high cell density.  

• Fully closed and pre-sterilized, ideal for viruses larger than 0.2µm that cannot be sterile filtered
• A low-shear clarification solution, retaining particles as a concentrated fluidized bed under a continuous flow of media or buffer
• Ensures containment of pathogenic viruses, compliant to Biosafety Level 2
• A solution adapted to high cell density applications

Additional Solutions to Consider:

• Sartoclear^® are depth filters with the highest capacity among Sartorius filters, enabling removal of small contaminants and DNA. Virus recovery must be tested by optimizing loading and rinsing conditions (pH and conductivity)

• Sartopure^® PP3 are low adsorption, high capacity pre-filters dedicated to non-intensified processes, providing high virus recovery. Available as standard cartridges, in a closed capsule format, as filter transfer sets and in Maxicaps^® MR format, from small to large scale

• Pre-assembled, closed Maxicaps^® MR single-use skid integrating Sartopure^® PP3 filters are available to ensure containment of filtration and clarification operations

Viral particles adsorb to depth filters, so it is critical to remove cells or cell debris while maintaining high product recovery

Viral particles are infectious, so containment during processing and disassembling is required to be compliant with Biosafety Level 2/3 requirements

Enveloped viruses that are larger than 0.2µm make sterile filtration impossible, so the only way to ensure process sterility in those circumstances is through pre-sterilized and closed solutions

A separation solution dedicated to microcarriers is required in order to remove cells growing on them 

Sartopure^® PP3 are high capacity pre-filters dedicated to non-intensified processes, providing the highest virus recovery

• Low-adsorption polypropylene depth filter leading to high virus recovery
• Lowest filtration costs among polypropylene pre-filters on the market
• Available as standard cartridges, in a closed capsule format, as filter transfer sets and in Maxicaps^® MR format
• Featuring autoclavable capsules

Additional Solutions to Consider:  

•  Ksep^® single-use centrifuge to clarify shear sensitive and large viruses in a closed and pre-sterilized solution

Viral particles adsorb to depth filters, so it is critical to remove cells or cell debris while maintaining high product recovery

Viruses are live particles, so containment during processing and disassembling is required to be in compliance with Biosafety Level 2/3 requirements

The significant number of contaminants released during cell lysis including DNA and host cell proteins (HCPs) leads to filter blockage, which can only be mitigated by a high capacity clarification solution  

A high capacity clarification solution also is needed to address the overall challenges of working with high cell density in a suspension process

Clarification is a challenging unit operation for suspension and lytic viral processes. A single step is often not sufficient and multiple technologies must be tested and combined, including flocculation, filter trains, and single-use centrifugation

A wide range of technical approaches can be optimized and sequenced to meet broad product requirements

Sartorius offers a range of filters to meet different needs:

• Sartoclear^® are depth filters with the highest capacity among Sartorius filters, enabling removal of small contaminants and DNA. Virus recovery must be tested by optimizing loading and rinsing conditions (pH and conductivity)
• Sartopure^® PP3 are low adsorption, high capacity pre-filters dedicated to non-intensified processes, providing high virus recovery. These filters are available as standard cartridges, in a closed capsule format, as filter transfer sets and in Maxicaps^® MR format, from small to large scale
• Pre-assembled, closed Maxicaps^® MR single-use skid integrating Sartopure^® PP3 filters are available to ensure containment of filtration and clarification operations

Viral particles adsorb to depth filters, so it is critical to remove cells or cell debris while maintaining high product recovery

Viral particles are infectious, so containment during processing and disassembling is required to be in compliance with Biosafety Level 2/3 requirements

The significant number of contaminants released during cell lysis including DNA and host cell proteins (HCPs) leads to filter blockage, which can only be mitigated by a high capacity clarification solution  

A separation solution dedicated to microcarriers is required in order to remove any cells growing on them 

Sartopure^® PP3 are high capacity pre-filters dedicated to non-intensified processes, providing the highest virus recovery

• Low-adsorption polypropylene depth filter leading to high virus recovery
• Available as standard cartridges, in a closed capsule format, as filter transfer sets and in Maxicaps^® MR MR format
• Featuring autoclavable capsules

Additional Solutions to Consider:

• Biostat STR^® SU bioreactors come with a deep tube configuration to facilitate microcarrier settling & removal

Viruses are large particles, and while most of them can be filtered through sterilizing grade filters (0.2µm), some cannot – if the virus is not filterable, it is important to evaluate 0.2µm (sterile filtration) as well as 0,45µm (bioburden reduction) and select fully closed and pre-sterilized technologies for the entire downstream process.

Viral particles tend to adsorb to filters, so it is important to use non-adsorptive membranes as an alternative to maximize recovery

Viral particles are infectious and must be processed in an environment compliant to Biosafety Level 2/3, so containment is critical

Maxicaps^® MR, a ready-to-use, pre-sterilized, pre-assembled and self-contained filtration device allows connection of up to nine capsules in parallel for large-scale filtration operations

• Ensuring containment during filtration of large volumes of viral-based vaccines
• Available in a large variety of prefilters and membranes, allowing full flexibility during process development
• With one inlet, one outlet and one venting filter to simplify implementation of closed single-use processes

Additional Solutions to Consider:

• The Sartopore^® 2 family provides the broadest range of PES membrane combinations that perfectly adapt to all types of products for lowest filtration costs, available with 0.2 or 0.45µm final membrane pore size
• The Sartobran^® family includes a well-proven range of low adsorption filters for high virus recovery – making it ideal in vaccine manufacturing for the filtration of viral- based vaccines – available with 0.2 and 0.45µm final membrane pore size

Viruses are large particles that are easy to separate from small contaminants. The optimization of the operating conditions should consider the benefit of contaminant removal (host cell proteins, DNA) which requires large molecular weight cut-off membrane cassettes and high throughput process development systems

Some viruses are larger than 0.2µm and cannot be sterile filtered, so those circumstances require closed & sterile environments

Prior to inactivation, viral particles are pathogenic, so containment is critical

The significant number of contaminants including DNA and host cell proteins in addition to virus can foul filter membranes prompting the need for low-adsorption membranes  

Enveloped viral particles are fragile and may be damaged by shear exposure, so low shear systems and optimal cassette designs need to be used.

Hydrosart^®, a state-of-the-art crossflow membrane designed for low adsorption of viruses has the benefit of resistance to chemicals, steam, heat and gamma-irradiation, allowing a wide range of operating conditions for viral-based vaccines

• Available with large molecular weight cut-off membrane dedicated to viral applications (up to 300kD)  
• Providing low adsorption, high flow rate and high product recovery
• Compatible with a wide range of chemicals for a broader spectrum of operations conditions and cleaning protocols
• Can be delivered gamma sterile, allowing closed, ready-to-use and sterile processing of large and/or live viruses that must be compliant to Biosafety Level 2
• Available in Sartocon^® ECO format for low-shear operations

 Additional Solutions to Consider:

• The scalable, GMP compliant Sartoflow^® Smart and Advanced systems for small scale development and production include low-shear pumps, ideal for viral applications
• Flexact^® Modular CF  is a single-use, fully closed automated system, including recirculation loop with single-use sensors and self-contained Hydrosart^® cassettes
• Ambr^® crossflow is a unique, small-scale, multi-parallel, automated system for screening of crossflow conditions with the lowest material quantities and recirculation volumes on the market

Viruses are large particles that cannot diffuse into chromatography beads, and can be trapped in small pores leading to low recovery during elution, requiring alternatives to traditional bead-based chromatography media  

Addressing an array of viruses requires a wide range of chromatography media and operating conditions with screening to ensure both highest capacity and highest recovery of viruses, so high throughput screening tools and a variety of chromatography ligands are needed

Some viruses are larger than 0.2µm and cannot be sterile filtered, so those circumstances require closed & sterile environments

Prior to inactivation, viral particles are pathogenic, so containment is critical

Sartobind^® 8mm chromatography membranes offer the widest range of ligands and a unique cassette scale-up solution up to 100L of membrane volume, ideal for virus purification in bind and elute mode

• Large pore structure allows direct access to ligands, leading to high capacity and high product recovery
• Four ligands are available allowing purification of different types of viruses: Q, S, Sulfated Cellulose (SC) and Phenyl
• Ensures containment and sterility through a closed autoclavable format up to 5L of membrane volume
• 96-well plate format is available for high throughput screening experiments
• Available in gamma-irradiated cassette format to unlock scale-up limitations of capsules

Additional Solutions to Consider:

• Sartobind^® Q is a well-proven membrane for the capture of a wide range of viruses and is already validated on existing viral-based vaccines
• Sartobind^® Sulfated Cellulose (SC) is a new membrane dedicated to the capture of heparin-binding viruses like Influenza

Viral processes can lead to cell lysis, releasing a significant number of contaminants including DNA that has to be removed in downstream processes without impact on the overall virus recovery – something that can be achieved through high recovery chromatographic solutions for polishing in flowthrough mode

Viruses are large particles that can be trapped in small pores, leading to low recovery during flowthrough operations, requiring alternatives to traditional bead-based chromatography media  

Addressing an array of viruses requires a wide range of chromatography media and operating conditions with screening to ensure both maximum levels of impurity removal and highest recovery of viruses, so high throughput screening tools and diverse chromatography ligands are needed.

Some viruses are larger than 0.2µm and cannot be sterile filtered, so those circumstances require closed & pre-sterilized systems

Prior to inactivation, viral particles are pathogenic, so containment is critical

Sartobind^® 4mm chromatography membranes offer the widest range of ligands and a unique cassette scale-up solution up to 100L of membrane volume, ideal for contaminant removal in flowthrough mode

• Large pore structure allows large impurities (e.g. DNA) to have direct access to ligands, leading to high capacity
• The high flowrate allows for a smaller footprint
• Four ligands are available for contaminant removal: Q, STIC, S & Phenyl
• Ensure containment and sterility through a closed autoclavable format up to jumbo capsule format (2.5L)
• 96-well plate format is available for high throughput screening experiments
• Available in gamma-irradiated cassette format to unlock scale-up limitations of capsules

Additional Solutions to Consider:

• Sartobind^® Q and STIC (Salt Tolerant Interaction Chromatography) anion exchangers are ligands that can be compared side by side for DNA removal, offering a complementary solution that takes into account process conditions and virus charges
• The Flexsafe^® Pro Mixer technology, the only single-use mixing solution with integrated sensors, accommodates both low-shear and rapid mixing applications in a fully closed design

In order to ensure the inactivation of every viral particle, having drop-free mixing, no dead volumes and no adsorption of chemicals is essential

Containment in this process is critical for two reasons: viral particles are pathogenic prior to inactivation and toxic chemicals are used during the inactivation process.

It is important to verify the compatibility of films with the structure and degradation profiles of the chemicals being used

Viral particles are fragile and may be damaged by shear exposure, so low shear mixing solutions are needed.

The Flexsafe^® Pro Mixer technology, the only single-use mixing solution with integrated sensors, accommodates both low-shear and rapid mixing applications in a fully closed design which enables viral inactivation while preserving the virus

• The only single use mixing solution with integrated sensors (pH, temperature, conductivity), allowing intelligent process monitoring  
• The fully closed design with the levitating impeller reduces the risk of shear degradation while allowing high performance mixing
• A flexible solution accommodating a wide range of mixing steps in both upstream and downstream processes

Additional Solutions to Consider:

• Sartorius offers a unique combination of post-installation supplier integrity test and point-of-use leak test for the highest assurance of integrity when containment and product sterility are critical
• Sartorius’s validation services enable the verification of chemical compatibility and the extractable profile of the mixing step, a critical success factor during inactivation 

Viruses are large particles that are easy to separate from small contaminants. The optimization of the operating conditions should consider the benefit of contaminant removal (host cell proteins, DNA) which requires large molecular weight cut-off membrane cassettes and high throughput process development systems

Some viruses are larger than 0.2µm and cannot be sterile filtered, so those circumstances require closed & sterile environments

Prior to inactivation, viral particles are pathogenic, so containment is critical

The significant number of contaminants including DNA and host cell proteins in addition to virus can foul filter membranes prompting the need for low-adsorption membranes  

Enveloped viral particles are fragile and may be damaged by shear exposure, so low shear systems and optimal cassette designs need to be used.

Hydrosart^®, a state-of-the-art crossflow membrane designed for low adsorption of viruses has the benefit of resistance to chemicals, steam, heat and gamma-irradiation, allowing a wide range of operating conditions for viral-based vaccines

• Available with large molecular weight cut-off membrane dedicated to viral applications (up to 300kD)  
• Providing low adsorption, high flow rate and high product recovery
• Compatible with a wide range of chemicals for a broader spectrum of operations conditions and cleaning protocols
• Can be delivered gamma sterile, allowing closed, ready-to-use and sterile processing of large and/or live viruses that must be compliant to Biosafety Level 2
• Available in Sartocon^® ECO format for low-shear operations

 Additional Solutions to Consider:

• The scalable, GMP compliant Sartoflow^® Smart and Advanced systems for small scale development and production include low-shear pumps, ideal for viral applications
• Flexact^® Modular CF  is a single-use, fully closed automated system, including recirculation loop with single-use sensors and self-contained Hydrosart^® cassettes
• Ambr^® crossflow is a unique, small-scale, multi-parallel, automated system for screening of crossflow conditions with the lowest material quantities and recirculation volumes on the market

Viruses are large particles, and while most of them can be filtered through sterilizing grade filters (0.2µm), some cannot. It is critical to evaluate 0.2µm (sterile filtration) as well as 0,45µm (bioburden reduction) and select fully closed and pre-sterilized technologies across the entire downstream process if a virus is not filterable

Viral particles adsorb to filters, so it is important to use non-adsorptive membranes as an alternative to maximize recovery

Viral particles are infectious so containment is critical

Helium supplier integrity test and point-of-use leak test with Sartocheck^® is the best risk mitigation strategy across the single-use bag portfolio, offering assurance of integrity when containment and product sterility are critical

• Helium test is a unique technology able to detect 2µm hole sizes correlated to liquid leaks and microbial ingress, increasing environmental, product and operator safety and providing integrity assurance
• Point-of-use leak test based on the well-established Sartocheck^® testing device reduces the risk of processing with leaking bags that may have been damaged during transportation and handling
• The only point-of-use integrity test for 2D bags correlated to microbial ingress, with a sensitivity of 10µm  

Additional Solutions to Consider:

• Sartopore^® Platinum is the ideal choice for final filling applications. The unique surface modification of the PES membrane provides lowest adsorption for high product yield and secure wetting for reliable integrity testing.
• The Sartobran^® family includes a well-proven range of low adsorption filters for high virus recovery – making it ideal in vaccine manufacturing for the filtration of viral based vaccines – available with 0.2 and 0.45µm final membrane pore size
• Sartocheck^® 5 is the benchmark for integrity testing of sterilizing grade filters. The unit is designed to provide industry leading data security and integrity, highest QRM standards for integrity testing in combination with intuitive use of the device

Selecting the optimum cell line or clone for the target virus relies on low-volume screening tools and fast analytics

Fully scalable HTPD tools, inline analytics are needed to quickly define the best operating conditions for cell expansion (media selection, process parameters optimization) and virus propagation (media, feed, multiplicity of infection, time of infection, harvest time, etc.)  

Many in industry are moving away from serum-containing media in favor of chemically defined (CD) media to support process safety and batch consistency,  

Ultimately, having an experienced partner capable of providing the characterization tools for the cell line is the way to select a stable and safe cell line with confidence

The flexibility and functionality of Ambr^® 15 & Ambr^® 250 can accelerate cell line selection and process optimization. Ambr^® is the only high-throughput cell culture system with scalable, multiparallel mini-bioreactors and automated functionality.

• Proven technology with all suspension cell lines
• Capable in all operation modes: batch, fed-batch, perfusion
• Integrated with a wide range of connectivity of inline analytics, including BioPAT^® Spectro  
• Available with MODDE^® software to facilitate DoE  

Additional Solutions to Consider:

• A new generation of chemically defined (CD) and animal component free (ACF) cell culture media developed and tested with Sartorius bioreactors
• With more than 70 experienced scientists in the US and Europe to conduct a full package of biosafety testing compliant with current regulations for viral-based vaccines, Sartorius is well positioned to support their customers from cell line and strain selection to commercial manufacturing.

Selecting the optimum cell line or clone for the target virus relies on low-volume screening tools and fast analytics

Fully scalable HTPD tools, inline analytics are needed to quickly define the best operating conditions for cell expansion (media selection, microcarrier selection, process parameters optimization) and virus propagation (media, feed, multiplicity of infection, time of infection, harvest time, etc.)  

In order to effectively evaluate adaptation of adherent cell line to suspension, there is a pressing need for low volume screening tools, fast analytics  

Many in industry are moving away from serum-containing media in favor of chemically defined (CD) media to support process safety and batch consistency

Ultimately, having an experienced partner capable of providing the characterization tools for the cell line is the way to select a stable and safe cell line with confidence

A new generation of Ambr^® 15 tailored to microcarriers applications and Ambr^® 250 vessels designed for microcarriers can accelerate cell line selection and process optimization. Ambr^® is the only high-throughput cell culture system with scalable, multiparallel mini-bioreactors, automated functionality and vessels developed for microcarriers.

• Proven technology with adherent cell lines
• Capable in batch and fed batch operation modes  
• Integrated with a wide range of connectivity of inline analytics, including BioPAT^® Spectro
• Available with MODDE^® software to facilitate DoE

Additional Solutions to Consider:

• New generation of chemically defined (CD) and animal component free (ACF) cell culture media developed and tested with Sartorius bioreactors
• With more than 70 experienced scientists in the US and Europe to conduct a full package of biosafety testing compliant with current regulations for viral-based vaccines, Sartorius is uniquely positioned to support their customers from cell line and strain selection to commercial manufacturing.

Adjusting the seed expansion step to production scale relies on fully scalable technologies from process development to manufacturing

Intensifying processes are critical to reduce the seed train and decrease cost of production while achieving higher cell concentration  

The sterility of the seed train relies on a closed process from the shake flask through the rocking motion bioreactor  
 
Only PAT toolsProcess Analytical Technologies can ensure the robustness and control of the seed train

Biostat^® RM, a fully GMP compliant, wave-mixed bioreactor, is an easy-to-use system for seed expansion offering the widest range of PAT in a Biosafety Level 2 environment  

• Industry-proven bioreactor for seed expansion of viral-based vaccines
• A unique & robust film across the process ensuring excellent cell growth
• A closed process to lessen environmental risk to products and operators
• Integration of a wide range of PAT including BioPAT^® Viamass, BioPAT^® Trace and BioPAT^® Spectro
• A bag-integrated cell retention filter for intensified production

Additional Solutions to Consider:

•  Mycap^® CCX to grow cells in an incubator and passage between flasks without ever opening a flask and or going into a biosafety cabinet
• A new generation of chemically defined (CD) and animal component free (ACF) cell culture media developed and tested with Sartorius bioreactors

Adjusting the seed expansion step to production scale relies on fully scalable technologies from process development to manufacturing
 

Evaluation and implementation of the correct parameters and mixing conditions is critical to avoid cell detachment from the microcarriers and microcarriers breakage

The sterility of the seed train relies on a closed process from the shake flask through the rocking motion bioreactor

Process Analytical Technologies can ensure the robustness and control of the seed train

Biostat^® RM,, a fully GMP compliant, wave-mixed bioreactor, is an easy-to-use system for seed expansion offering the widest range of PAT in a Biosafety Level 2 environment  

• Industry-proven bioreactor for seed expansion of viral-based vaccines
• A unique & robust film across the process ensuring excellent cell growth
• A closed process to lessen environmental risk to products and operators
• Integration of a wide range of PAT including BioPAT^® Viamass, BioPAT^® Trace and BioPAT^® Spectro
• A bag-integrated cell retention filter for intensified production

Additional Solutions to Consider:

• A new generation of chemically defined (CD) and animal component free (ACF) cell culture media developed and tested with Sartorius bioreactors

Fully scalable technologies, from process development to manufacturing, are needed to take virus propagation to production scale  

Achieving higher virus concentration while decreasing cost of production relies on process intensification

It is imperative to ensure containment and reduce contamination risk while working with infectious viral particles classified as Biosafety Level 2

Process Analytical Technologies in this environment are essential to enable robust processes and infection monitoring and control

Biostat STR^® is a single use bioreactor offering the widest range of PAT in a Biosafety Level 2 environment, making it the perfect match for viral production:

• A unique and robust film across the process ensuring excellent cell growth
• Integration of a wide range of PAT including BioPAT^® Viamass, BioPAT^® Trace and BioPAT^® Spectro
• Built on Biosafety principles to reduce risk of contamination and loss of product  
• Direct scalability from Ambr^® to STR for rapid process development
• Capable in all operation modes: batch, fed-batch, perfusion  

Additional Solutions to Consider:

• A new generation of chemically defined (CD) and animal component free (ACF) cell culture media developed and tested with Sartorius bioreactors
• Ambr^® 15 and 250 are the only high-throughput cell culture with scalable, multiparallel mini-bioreactors, automated functionality supporting viral-based vaccine application.
• With more than 70 experienced scientists in the US and Europe to conduct a full package of biosafety testing compliant with current regulations for viral-based vaccines, Sartorius is well positioned to support their customers from cell line and strain selection to commercial manufacturing.

Fully scalable technologies, from process development to manufacturing, are needed to take virus propagation to production scale 

It is imperative to ensure containment and reduce contamination risk while working with infectious viral particles classified as Biosafety Level 2

Evaluation and implementation of the correct parameters and mixing conditions is critical to avoid cell detachment from the microcarriers and microcarriers breakage

Process Analytical Technologies in this environment are essential to enable robust processes and infection monitoring and control

The Biostat STR^® is a single use bioreactor, offering the widest range of PAT in a Biosafety Level 2 environment, making it the perfect match for viral production:

• A unique and robust film across the process ensuring excellent cell growth
• Integration of a wide range of PAT including BioPAT^® Viamass, BioPAT^® Trace and BioPAT^® Spectro
• Built on Biosafety principles to reduce risk of contamination and loss of product  
• Direct scalability from Ambr^® to STR, supporting microcarrier applications for rapid process development
• Capable in all operation modes: batch, fed-batch, perfusion  

Additional Solutions to Consider:

• A new generation of chemically defined (CD) and animal component free (ACF) cell culture media developed and tested with Sartorius bioreactors
• Ambr^® 15 and 250 are the only high-throughput cell culture with scalable, multiparallel mini-bioreactors, automated functionality supporting viral-based vaccine application.
• With more than 70 experienced scientists in the US and Europe to conduct a full package of biosafety testing compliant with current regulations for viral-based vaccines, Sartorius is well positioned to support their customers from cell line and strain selection to commercial manufacturing.

Viral particles adsorb to depth filters, so it is critical to remove cells or cell debris while maintaining high product recovery

Attenuated viruses are live particles, so containment during processing and disassembling is required to be compliant with Biosafety Level 2/3 requirements

Enveloped viruses that are larger than 0.2µm make sterile filtration impossible, so the only way to ensure process sterility in those circumstances is through pre-sterilized and closed solutions

High capacity clarification solution is needed to address the overall challenges of working with high cell density in a suspension process

Enveloped viral particles are fragile may be damaged by shear exposure during clarification, so low shear solutions are essential to protect the infectious nature of the virus

Ksep^® single use centrifuge is the leading single-use centrifuge for clarification from low to high cell density.  

• Fully closed and pre-sterilized, ideal for viruses larger than 0.2µm that cannot be sterile filtered
• A low-shear clarification solution, retaining particles as a concentrated fluidized bed under a continuous flow of media or buffer
• Ensures containment of live viruses that must be compliant to Biosafety Level 2
• A solution adapted to high cell density applications

Additional Solutions to Consider:

• Sartoclear^® are depth filters with the highest capacity among Sartorius filters, enabling removal of small contaminants and DNA. Virus recovery must be tested by optimizing loading and rinsing conditions (pH and conductivity)
• Sartopure^® PP3 are low adsorption, high capacity pre-filters dedicated to non-intensified processes, providing high virus recovery. Available as standard cartridges, in a closed capsule format, as filter transfer sets and in Maxicaps^® MR format, from small to large scale
• Pre-assembled, closed Maxicaps^® MR single-use skid integrating Sartopure^® PP3 filters are available to ensure containment of filtration and clarification operations

Viral particles adsorb to depth filters, so it is critical to remove cells or cell debris while maintaining high product recovery

Attenuated viruses are live particles, so containment during processing and disassembling is required to be compliant with Biosafety Level 2/3 requirements

Enveloped viruses that are larger than 0.2µm make sterile filtration impossible, so the only way to ensure process sterility in those circumstances is through pre-sterilized and closed solutions

A separation solution dedicated to adherent processes is required in order to remove microcarriers  

Enveloped viral particles are fragile may be damaged by shear exposure during clarification, so low shear solutions are essential to protect the infectious nature of the virus

Sartopure^® PP3 are high capacity pre-filters dedicated to non-intensified processes, providing the highest virus recovery.

• Low-adsorption polypropylene depth filter leading to high virus recovery
• Available as standard cartridges, in a closed capsule format, as filter transfer sets and in Maxicaps^® MR

Additional Solutions to Consider:  

•  Ksep^® single-use centrifuge to clarify shear sensitive and large viruses in a closed and pre-sterilized solution

Viral particles adsorb to depth filters, so it is critical to remove cells or cell debris while maintaining high product recovery

Attenuated viruses are live particles, so containment during processing and disassembling is required to be in compliance with Biosafety Level 2/3 requirements

The significant number of contaminants released during cell lysis including DNA and host cell proteins (HCPs) leads to filter blockage, which can only be mitigated by a high capacity clarification solution  

High capacity clarification solution also is needed to address the overall challenges of working with high cell density in a suspension process

Clarification is a challenging unit operation for suspension and lytic viral processes. A single step is often not sufficient and multiple technologies must be tested and combined, including flocculation, filter trains, and single-use centrifugation

A wide range of technical approaches can be optimized and sequenced to meet broad product requirements

Sartorius offers a range of filters to meet different needs:

• Sartoclear^® are depth filters with the highest capacity among Sartorius filters, enabling removal of small contaminants and DNA. Virus recovery must be tested by optimizing loading and rinsing conditions (pH and conductivity)
• Sartopure^® PP3 are low adsorption, high capacity pre-filters dedicated to non-intensified processes, providing high virus recovery. Available as standard cartridges, in a closed capsule format, as filter transfer sets and in Maxicaps^® MR format, from small to large scale
• Pre-assembled, closed Maxicaps^® MR single-use skid integrating Sartopure^® PP3 filters are available to ensure containment of filtration and clarification operations

Viral particles adsorb to depth filters, so it is critical to remove cells or cell debris while maintaining high product recovery

Attenuated viruses are live particles, so containment during processing and disassembling is required to be in compliance with Biosafety Level 2/3 requirements

The significant number of contaminants released during cell lysis including DNA and host cell proteins (HCPs) leads to filter blockage, which can only be mitigated by a high capacity clarification solution  

A separation solution dedicated to adherent processes is required in order to remove microcarriers

Sartopure^® PP3 are high capacity pre-filters dedicated to non-intensified processes, providing the highest virus recovery

• Low-adsorption polypropylene depth filter leading to high virus recovery
• Available as standard cartridges, in a closed capsule format, as filter transfer sets and in Maxicaps^® MR

Additional Solutions to Consider:

• The Biostat STR^® SU bioreactors come with a deep tube configuration to facilitate microcarrier settling & removal

Viruses are large particles, and while most of them can be filtered through sterilizing grade filters (0.2µm), some cannot – if the virus is not filterable, it is important to 0,45µm (bioburden reduction) and select fully closed and pre-sterilized technologies for the entire downstream process.

Viral particles tend to adsorb to filters, so it is important to use non-adsorptive membranes as an alternative to maximize recovery

Attenuated viruses are live particles and must be processed in an environment compliant to Biosafety Level 2, so containment is critical

Maxicaps^® MR, a ready-to-use, pre-sterilized, pre-assembled and self-contained filtration device allows connection of up to nine capsules in parallel for large-scale filtration operations

• Ensuring containment during filtration of large volumes of viral-based vaccines
• Available in a large variety of prefilters and membranes, allowing full flexibility during process development
• With one inlet, one outlet and one venting filter to simplify implementation of closed single-use processes

Additional Solutions to Consider:

• The Sartopore^® 2 family provides the broadest range of PES membrane combinations that perfectly adapt to all types of products for lowest filtration costs, available with 0.2 or 0.45µm final membrane pore size
• The Sartobran^® family includes a well-proven range of low adsorption filters for high virus recovery – making it ideal in vaccine manufacturing for the filtration of viral- based vaccines – available with 0.2 and 0.45µm final membrane pore size

Viruses are large particles that cannot diffuse into chromatography beads, and can be trapped in small pores leading to low recovery during elution, requiring alternatives to traditional bead-based chromatography media  

Diversity of viruses requires a wide range of chromatography media and operating conditions with screening to ensure both highest capacity and highest recovery of infectious particle, so high throughput screening tools and a variety of chromatography ligands are needed

Some viruses are larger than 0.2µm and cannot be sterile filtered, so those circumstances require closed & sterile environments

Attenuated viruses are live particles that must be processed in an environment compliant to Biosafety Level 2, so containment is critical

Sartobind^® 8mm chromatography membranes offer the widest range of ligands and a unique cassette scale-up solution up to 100L of membrane volume, ideal for virus purification in bind-and-elute mode

• Large pore structure allows direct access to ligands, leading to high capacity and high product recovery
• Four ligands are available allowing purification of different types of viruses: Q, S, Sulfated Cellulose (SC) and Phenyl
• Ensures containment and sterility through a closed autoclavable format up to 5L of membrane volume
• 96-well plate format is available for high throughput screening experiments
• Available in gamma-irradiated cassette format to unlock scale-up limitations of capsules

Additional Solutions to Consider:

• Sartobind^® Q is a wellproven membrane for the capture of a wide range of viruses, already validated on existing viral-based vaccines
• Sartobind^® Sulfated Cellulose (SC), a new membrane dedicated to the capture of heparin-binding viruses like Influenza

Viral processes can lead to cell lysis, releasing a significant number of contaminants including DNA that has to be removed in downstream processes without impact on the overall virus recovery – something that can be achieved through high recovery chromatographic solutions for polishing in flowthrough mode

Viruses are large particles that cannot diffuse into chromatography beads, and can be trapped in small pores leading to low recovery during elution, requiring alternatives to traditional bead-based chromatography media  

Diversity of viruses requires a wide range of chromatography media and operating conditions with screening to ensure both highest capacity and highest recovery of infectious particle, so high throughput screening tools and diverse chromatography ligands are needed.

 Some viruses are larger than 0.2µm and cannot be sterile filtered, so those circumstances require closed & sterile environments

Attenuated viruses are live particles that must be processed in an environment compliant to Biosafety Level 2, so containment is critical

Sartobind^® 4mm chromatography membranes offer the widest range of ligands and a unique cassette scale-up solution up to 100L of membrane volume, ideal for contaminant removal in flowthrough mode

• Large pore structure allows large impurities (e.g. DNA) to have direct access to ligands, leading to high capacity
• The high flow-rate allows for a smaller footprint
• Four ligands are available for contaminant removal: Q, STIC, S & Phenyl
• Ensure containment and sterility through a closed autoclavable format up to jumbo capsule format (2.5L)
• 96-well plate format is available for high throughput screening experiments
• Available in gamma-irradiated cassette format to unlock scale-up limitations of capsules

Additional Solutions to Consider:

• Sartobind^® Q and STIC (Salt Tolerant Interaction Chromatography) anion exchangers are ligands that can be compared side by side for DNA removal, offering a complementary solution that takes into account process conditions and virus charges
• The Flexsafe^® Pro Mixer technology, the only single-use mixing solution with integrated sensors, accommodates both low-shear and rapid mixing applications, in a fully closed design

Viruses are large particles, and while most of them can be filtered through sterilizing grade filters (0.2µm), some cannot. It is critical to evaluate 0.2µm (sterile filtration) as well as 0,45µm (bioburden reduction) and select fully closed and pre-sterilized technologies across the entire downstream process if a virus is not filterable

Viral particles adsorb to filters, so it is important to use non-adsorptive membranes as an alternative to maximize recovery

Attenuated viruses are live particles that must be processes in an environment compliant to Biosafety Level 2, so containment is critical

Helium supplier integrity test and point-of-use leak test with Sartocheck^® is the best risk mitigation strategy across the single-use bag portfolio, offering assurance of integrity when containment and product sterility are critical

• Helium test is a unique technology able to detect 2µm hole sizes correlated to liquid leaks and microbial ingress, increasing environmental, product and operator safety and providing integrity assurance
• Point-of-use leak test based on the well-established Sartocheck^® testing device reduces the risk of processing with leaking bags that may have been damaged during transportation and handling
• The only point-of-use integrity test for 2D bags correlated to microbial ingress, with a sensitivity of 10µm  

Additional Solutions to Consider:

• Sartopore^® Platinum is the ideal choice for final filling applications. The unique surface modification of the PES membrane provides lowest adsorption for high product yield and secure wetting for reliable integrity testing.
• The Sartobran^® family includes a well-proven range of low adsorption filters for high virus recovery – making it ideal in vaccine manufacturing for the filtration of viral based vaccines – available with 0.2 and 0.45µm final membrane pore size
• Sartocheck^® 5 is the benchmark for integrity testing of sterilizing grade filters. The unit is designed to provide industry leading data security and integrity, highest QRM standards for integrity testing in combination with intuitive use of the device