Virus Based Vaccines

Attenuated and Inactivated Virus Based Vaccines

Viral vaccines include inactivated viral vaccines and live-attenuated viral vaccines. Both rely on a traditional approach i.e.; the disease-causing virus is identified, produced in a bioreactor, and purified. This type of strategy has been used for many diseases with success, and most of the current vaccines against viral diseases use this strategy. This approach, however, does have its challenges:

Ensuring the capacity of a virus to be produced in a bioreactor
Identifying the right host cell
Designing a process tailored to each disease
Complying with the requirements of production at a high biosafety level to protect operators and the environment

We, at Sartorius, understand the needs of vaccine developers and producers working with viral vaccines and have developed a dedicated toolbox of solutions.

Inactivated Viral Vaccine

Inactivated viral vaccines represent a significant part of the vaccine market, influenza and polio chief among them. In addition to new vaccine developments, process transfers, capacity expansions and continuous improvement can lead to positive disruption in this space with technologies that make safer and more productive processes possible, helping to decrease overall costs.

We invite you to discover the Sartorius toolbox of technologies, dedicated to the production and purification of inactivated viral vaccines. As you explore our generic process overviews for enveloped viruses, such as SARS-CoV-2, non-enveloped viruses and specific viruses such as influenza and polio, you can click on each step to reveal the challenges that manufacturers face when working with inactivated viral vaccines – and discover how Sartorius offers unique solutions to meet those needs. You will also find relevant literature on available technologies for the process steps.

Contact a Vaccine Specialist

Generic Inactivated Virus

Cell Line / Strain Selection

Selecting cell lines and strains that produce commercially acceptable yields can be difficult and labor-intensive. Proper high throughput development tools — or a capable partner who has access to those tools — allow operators to confidently select a stable and safe cell line.

▶ Suspension Process

Need	Solution
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.

Need

Solution

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.

▶ Adherent Process

Need	Solution
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.

Need

Solution

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.

Application Data:

Ambr^® 15 microcarrier

Ambr^® 250 microcarrier

Ambr^® 250 microcarrier poster

Seed Expansion

Seed expansion from cell bank to production bioreactor must be successfully achieved before the virus propagation in the production bioreactor. The latest innovations use process intensification to reduce the seed train and ensure the highest possible process consistency while Process Analytical Technologies enable full process control.

▶ Suspension Process

Need	Solution
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 , 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

Need

Solution

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 , 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

Application Data:

Single-Use, Stirred-Tank Bioreactors: Efficient Tools for Process Development and Characterization

▶ Adherent Process

Need	Solution
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 , 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

Need

Solution

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 , 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

Virus Propagation

Robust virus propagation in vaccine development relies on scalability from process development to production scale manufacturing while ensuring containment in a Biosafety Level 2/3 environment. The use of Process Analytical Technologies in viral-based vaccine applications enables process controls and monitoring to achieve a higher virus concentration.

▶ Suspension Process

Need	Solution
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 , 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

Need

Solution

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 , 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

▶ Adherent Process

Need	Solution
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 , 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

Need

Solution

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 , 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

Application data:

Clarification

Clarification of vaccines is a critical step that has a significant impact on product recovery and subsequent downstream purification. The main challenge of virus clarification is to recover a high yield of viral particles while efficiently removing cell debris, large aggregates and insoluble contaminants.

Clarification of Enveloped Viruses

▶ Suspension Process

Need	Solution
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

Need

Solution

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

▶ Adherent Process

Need	Solution
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

Need

Solution

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

Clarification of Non-Enveloped Viruses

▶ Suspension Process

Need	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

Need

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

Application Data:

Poster: Clarification of Adenovirus serotype 5: Robust protection of downstream purification steps
Poster: Implementation of a Process-Scale Adenovirus Purification with a Single-Use Platform

▶ Adherent Process

Need	Solution
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

Need

Solution

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

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

Application data:

Comparative study of bluetongue virus serotype 8 production on BHK-21 cells in a 50L Biostat^® STR single-use bioreactors vs roller bottles

Bioburden Reduction

Bioburden reduction relies on membrane filtration of the clarified viral vaccine in order to protect the subsequent Downstream Unit Operations. A large range of membrane types and potential combinations create options to achieve the highest throughput while maintaining the highest recovery.

Need	Solution
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 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

Need

Solution

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 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

Application Data:

Clarification of Adenovirus serotype 5: Robust protection of downstream purification steps

Concentration / Diafiltration

Concentration of viruses, contaminant removal and buffer exchange steps are essential steps in all viral vaccine processing, but these steps can be especially challenging when working with shear-sensitive viruses. The latest innovations combine low-shear operations and fully closed processing to allow the highest recovery with full containment – creating an ideal environment for viral vaccine manufacturing.

Need	Solution
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

Need

Solution

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

Virus Capture Chromatography

Virus capture is a critical step in the Downstream process, removing the majority of contaminants while concentrating the virus. Innovative chromatography membrane formats eliminate barriers to scalability and allow implementation of high capacity membranes at very large scale.

Need	Solution
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

Need

Solution

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

Application data:

Optimizing Adenovirus Purification Processes Using Sartobind^® Q and STIC PA anion exchange membranes

Poster: Implementation of a Process-Scale Adenovirus Purification with a Single-Use Platform

Membrane Chromatography Cassettes for Bind & Elute Applications of Viruses and Large Proteins

Polishing Chromatography

A second step of chromatography for polishing might be required to remove remaining contaminants, such as DNA and HCP. Membrane adsorbers allow the easy implementation of this secondary chromatography step in a fully contained format.

Need	Solution
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

Need

Solution

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

Additional Data:

Optimizing Adenovirus Purification Processes Using Sartobind^® Q and STIC PA anion exchange membranes

Poster: Implementation of a Process-Scale Adenovirus Purification with a Single-Use Platform

Rational Development of Two Flowthrough Purification Strategies for Adenovirus Type 5 and Retro Virus-Like Particles

Inactivation / Split

Inactivation of the virus is critical to ensure safety for patients. Inactivation is achieved by exposing viruses to chemical agents, such as formalin and beta-propiolactone. State-of-the-art single use mixing solutions offer a robust inactivation, while ensuring containment for operator safety.

Need	Solution
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

Need

Solution

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

Concentration / Diafiltration

Need	Solution
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

Need

Solution

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.

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

Sterile Filtration

The final sterile filtration step is critical to prevent microbial contamination and ensure patient safety. Innovative risk mitigation strategies ensure safety of the complete solution, from sterile filtration to storage in single-use bags.

Need	Solution
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 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

Need

Solution

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 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

Other Technologies

Viral Quantification

Viral quantification, meaning the measurement of viral particle concentration in a defined volume, is invaluable information that’s needed as close to in real-time as possible when developing a vaccine. Existing techniques all have limitations, so employing complementary novel technologies are necessary to ensure rapid and precise quantification.

Need	Solution
Virus infectivity tests can take days or weeks to get results – rapid detection analytics are needed to address that critical issue ELISA and PCR methods are faster than infectivity tests, but there is a higher incidence of error variability since they measure virus building blocks and derive total titers from these numbers, leading to a need for alternative, reliable analytics Situations often demand ready-to-use analytics, but ELISA and PCR need development and validation time to ensure method robustness A lot of virus samples are generated during process development and manufacturing of viral based vaccines, highlighting the need for an easier workflow allowing rapid quantification of virus samples	The Virus Counter^® Platform, a unique and rapid virus quantification method, is the only system able to directly quantify assembled viruses (protein and nucleic acids) for real-time insight Real-time quantification for process monitoring and production optimization can deliver a single sample measurement in three minutes Total viral particle quantification High-specificity and universal ready-to-use quantification reagents The Combo Dye^® reagent enables measurement of all enveloped viruses The Virotag^® (antibody-based reagent) enables measurement of specific viruses Software-assisted system operation and data analysis limits the risk of variability

Need

Solution

Virus infectivity tests can take days or weeks to get results – rapid detection analytics are needed to address that critical issue

ELISA and PCR methods are faster than infectivity tests, but there is a higher incidence of error variability since they measure virus building blocks and derive total titers from these numbers, leading to a need for alternative, reliable analytics

Situations often demand ready-to-use analytics, but ELISA and PCR need development and validation time to ensure method robustness

A lot of virus samples are generated during process development and manufacturing of viral based vaccines, highlighting the need for an easier workflow allowing rapid quantification of virus samples

The Virus Counter^® Platform, a unique and rapid virus quantification method, is the only system able to directly quantify assembled viruses (protein and nucleic acids) for real-time insight

Real-time quantification for process monitoring and production optimization can deliver a single sample measurement in three minutes
Total viral particle quantification
High-specificity and universal ready-to-use quantification reagents
The Combo Dye^® reagent enables measurement of all enveloped viruses
The Virotag^® (antibody-based reagent) enables measurement of specific viruses
Software-assisted system operation and data analysis limits the risk of variability

Data Analytics

Advanced chemometric methods such as Design of Experiments (DOE) and Multivariate Data Analysis (MVDA) give broad visibility into data, ultimately leading to greater process reliability and robustness in addition to cost savings.

Need	Solution
Quality by Design (QbD) relies on DoE to understand critical process parameters, which is dependent on implementing many experiments – a tool that can help design and plan experiments alleviates the burden Process Analytical Technologies generate a lot of data that is difficult to analyze, resulting in significant demand for a tool to evaluate historical data in order to identify correlations, do troubleshooting and gain process understanding Most of vaccine developers and manufacturers are not statisticians and rely on user-friendly interfaces and software	The Umetrics^® suite includes three user-friendly and intuitive software solutions designed for process developers and manufacturers to support data analytics through unique data visualization, extensive wizard functionality and customizable plots to maximize usability and versatility MODDE^® is an advanced, high-quality DOE solution designed for ease of use. The benefit of DOE is to gain knowledge and estimate the best operating conditions of a process or product, and with MODDE^® ^® the graphical interface and analytics support make it easy to interpret results with complete confidence SIMCA^® Multivariate Data Analysis (MVDA) software is used for scale and batch-to-batch comparison investigations. SIMCA^® transforms data into visual information for easy interpretation, enabling decisions and actions to be taken rapidly and with confidence. SIMCA^® helps to analyze process variations, identify critical parameters and predict final product quality. An overview of the process status can be obtained in a few clicks SIMCA^® online is a highly efficient software for real-time multivariate statistical process monitoring & control. SIMCA^®-online provides a complete set of interactive and visual monitoring tools to production teams, to ensure that batch and continuous operations run smoothly These software solutions are fully integrated in most Sartorius systems and are available as stand-alone programs

Need

Solution

Quality by Design (QbD) relies on DoE to understand critical process parameters, which is dependent on implementing many experiments – a tool that can help design and plan experiments alleviates the burden

Process Analytical Technologies generate a lot of data that is difficult to analyze, resulting in significant demand for a tool to evaluate historical data in order to identify correlations, do troubleshooting and gain process understanding

Most of vaccine developers and manufacturers are not statisticians and rely on user-friendly interfaces and software

The Umetrics^® suite includes three user-friendly and intuitive software solutions designed for process developers and manufacturers to support data analytics through unique data visualization, extensive wizard functionality and customizable plots to maximize usability and versatility

MODDE^® is an advanced, high-quality DOE solution designed for ease of use. The benefit of DOE is to gain knowledge and estimate the best operating conditions of a process or product, and with MODDE^® ^® the graphical interface and analytics support make it easy to interpret results with complete confidence
SIMCA^® Multivariate Data Analysis (MVDA) software is used for scale and batch-to-batch comparison investigations. SIMCA^® transforms data into visual information for easy interpretation, enabling decisions and actions to be taken rapidly and with confidence. SIMCA^® helps to analyze process variations, identify critical parameters and predict final product quality. An overview of the process status can be obtained in a few clicks
SIMCA^® online is a highly efficient software for real-time multivariate statistical process monitoring & control. SIMCA^®-online provides a complete set of interactive and visual monitoring tools to production teams, to ensure that batch and continuous operations run smoothly

These software solutions are fully integrated in most Sartorius systems and are available as stand-alone programs

Process Analytical Technologies

The increasing development of single-use technologies with integrated single-use sensors, has not only enabled real-time data gathering and analysis, it has resulted in process efficiencies, reduced risk of contamination, improved operator safety and overall titer improvements.

Need	Solution
Vaccine manufacturers want to better understand and control their processes, which are very complex and highly regulated, but to do so requires real-time measurement of critical process parameters to allow process monitoring, set-point control (feed control and bleed control), event time point predictions (harvest and infection) and timely identification of process deviations A range of PAT sensors would be required to effectively apply QbD principles and ensure consistency in product quality and quantity, quickly identifying and correcting process deviations to reduce the risk of lost batches The ability to integrate PAT into single-use systems would mitigate risk of spillages and contamination during sampling	BioPAT^® toolbox, an expending range of fully qualified single-use sensors, are integrated across the Sartorius portfolio making Sartorius the market leader for PAT Available in process development and manufacturing technologies for full process understanding, monitoring and control Data analysis is straightforward thanks to the full integration in the Sartorius products & technologies BioPAT^® Viamass for inline monitoring of viable cell density and automated cell bleed control BioPAT^® Trace for online monitoring of glucose and lactate and automated feed control BioPAT^® Xgas for inline monitoring of CO2 and 02 BioPAT^® Spectro platform for Raman spectroscopy integration in Ambr^® and STR bioreactor systems for non-invasive, inline measurement of multiple analytes

Need

Solution

Vaccine manufacturers want to better understand and control their processes, which are very complex and highly regulated, but to do so requires real-time measurement of critical process parameters to allow process monitoring, set-point control (feed control and bleed control), event time point predictions (harvest and infection) and timely identification of process deviations

A range of PAT sensors would be required to effectively apply QbD principles and ensure consistency in product quality and quantity, quickly identifying and correcting process deviations to reduce the risk of lost batches

The ability to integrate PAT into single-use systems would mitigate risk of spillages and contamination during sampling

BioPAT^® toolbox, an expending range of fully qualified single-use sensors, are integrated across the Sartorius portfolio making Sartorius the market leader for PAT

Available in process development and manufacturing technologies for full process understanding, monitoring and control
Data analysis is straightforward thanks to the full integration in the Sartorius products & technologies
BioPAT^® Viamass for inline monitoring of viable cell density and automated cell bleed control
BioPAT^® Trace for online monitoring of glucose and lactate and automated feed control
BioPAT^® Xgas for inline monitoring of CO2 and 02
BioPAT^® Spectro platform for Raman spectroscopy integration in Ambr^® and STR bioreactor systems for non-invasive, inline measurement of multiple analytes

Application Data:

Control and scale-up of a microcarrier-based viral vaccine process using BioPAT ^® ViaMass for inline viable cell density measurement

Live-Attenuated Viral Vaccine

As a result of advances in the fields of molecular biology and genetic engineering, a new generation of live-attenuated viral vaccines is emerging. Vaccines for viruses such as influenza, as well as newer applications such as dengue or respiratory syncytial virus (RSV) are part of this promising pipeline. As is often the case with areas experiencing rapid advancement, innovative technologies are required to keep step with new processes to continuously improve upon safety and productivity.

We invite you to discover the Sartorius toolbox of technologies, dedicated to the production and purification of live-attenuated viral vaccines. As you explore our generic process overviews for enveloped viruses, such as SARS-CoV-2, non-enveloped viruses and specific viruses such as dengue and RSV, you can click on each step to reveal the challenges that manufacturers face when working with live-attenuated viral vaccines – and discover how Sartorius offers unique solutions to meet those needs. You will also find relevant literature on available technologies for the process steps.

Contact a Vaccine Specialist

Generic Attenuated Virus

Cell Line / Strain Selection

▶ Suspension Process

Need	Solution
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.

Need

Solution

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

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.

▶ Adherent Process

Need	Solution
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.

Need

Solution

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

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

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.

Application Data:

Seed Expansion

▶ Suspension Process

Need	Solution
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 , 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

Need

Solution

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 , 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

Application Data:

Garcia L, Mourino M, Urniza A, Juanola S. BioProcess J, 2019; 18.
Evaluation of a Single-Use Benchtop Process Development System to Optimize Cell Growth and Scale-Up of Veterinary Vaccine Production

▶ Adherent Process

Need	Solution
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

Need

Solution

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

Application Data:

Single-Use, Stirred-Tank Bioreactors: Efficient Tools for Process Development and Characterization

Virus Propagation

▶ Suspension Process

Need	Solution
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 , 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.

Need

Solution

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 , 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.

▶ Adherent Process

Need	Solution
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 , 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.

Need

Solution

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 , 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.

Application data:

Clarification

Clarification of Enveloped Viruses

▶ Suspension Process

Need	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 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

Need

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 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

▶ Adherent Process

Need	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 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

Need

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 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

Clarification of Non-Enveloped Viruses

▶ Suspension Process

Need	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

Need

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

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

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

▶ Adherent Process

Need	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 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

Need

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

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

Application data:

Comparative study of bluetongue virus serotype 8 production on BHK-21 cells in a 50L Biostat^® STR single-use bioreactors vs roller bottles

Bioburden Reduction

Need	Solution
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 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

Need

Solution

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 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

Concentration / Diafiltration

Need	Solution
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 Attenuated viruses are live particles that must be processed in an environment compliant to Biosafety Level 2, 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

Need

Solution

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

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

Virus Capture Chromatography

Need	Solution
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

Need

Solution

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

Application data:

Polishing Chromatography

Need	Solution
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

Need

Solution

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

Concentration / Diafiltration

Need	Solution
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 Attenuated viruses are live particles that must be processed in an environment compliant to Biosafety Level 2, 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

Need

Solution

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

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

Sterile Filtration

Need	Solution
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 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

Need

Solution

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 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 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

Other Technologies

Viral Quantification

Need	Solution
Virus infectivity tests can take days or weeks to get results – rapid detection analytics are needed to address that critical issue ELISA and PCR methods are faster than infectivity tests, but there is a higher incidence of error variability since they measure virus building blocks and derive total titers from these numbers, leading to a need for alternative, reliable analytics Situations often demand ready-to-use analytics, but ELISA and PCR need development and validation time to ensure method robustness A lot of virus samples are generated during process development and manufacturing of viral based vaccines, highlighting the need for an easier workflow allowing rapid quantification of virus samples	The Virus Counter^® Platform, a unique and rapid virus quantification method, is the only system able to directly quantify assembled viruses (protein and nucleic acids) for real-time insight Real-time quantification for process monitoring and production optimization can deliver a single sample measurement in three minutes Total viral particle quantification High-specificity and universal ready-to-use quantification reagents The Combo Dye^® reagent enables measurement of all enveloped viruses The Virotag^® (antibody-based reagent) enables measurement of specific viruses Software-assisted system operation and data analysis limits the risk of variability

Need

Solution

Virus infectivity tests can take days or weeks to get results – rapid detection analytics are needed to address that critical issue

Situations often demand ready-to-use analytics, but ELISA and PCR need development and validation time to ensure method robustness

A lot of virus samples are generated during process development and manufacturing of viral based vaccines, highlighting the need for an easier workflow allowing rapid quantification of virus samples

The Virus Counter^® Platform, a unique and rapid virus quantification method, is the only system able to directly quantify assembled viruses (protein and nucleic acids) for real-time insight

Real-time quantification for process monitoring and production optimization can deliver a single sample measurement in three minutes
Total viral particle quantification
High-specificity and universal ready-to-use quantification reagents
The Combo Dye^® reagent enables measurement of all enveloped viruses
The Virotag^® (antibody-based reagent) enables measurement of specific viruses
Software-assisted system operation and data analysis limits the risk of variability

Data Analytics

Need	Solution
Quality by Design (QbD) relies on DoE to understand critical process parameters, which is dependent on implementing many experiments – a tool that can help design and plan experiments alleviates the burden Process Analytical Technologies generate a lot of data that is difficult to analyze, resulting in significant demand for a tool to evaluate historical data in order to identify correlations, do troubleshooting and gain process understanding Most of vaccine developers and manufacturers are not statisticians and rely on user-friendly interfaces and software	The Umetrics^® suite includes three user-friendly and intuitive software solutions designed for process developers and manufacturers to support data analytics through unique data visualization, extensive wizard functionality and customizable plots to maximize usability and versatility MODDE^® is an advanced, high-quality DOE solution designed for ease of use. The benefit of DOE is to gain knowledge and estimate the best operating conditions of a process or product, and with MODDE^® ^® the graphical interface and analytics support make it easy to interpret results with complete confidence SIMCA^® Multivariate Data Analysis (MVDA) software is used for scale and batch-to-batch comparison investigations. SIMCA^® transforms data into visual information for easy interpretation, enabling decisions and actions to be taken rapidly and with confidence. SIMCA^® helps to analyze process variations, identify critical parameters and predict final product quality. An overview of the process status can be obtained in a few clicks SIMCA^® online is a highly efficient software for real-time multivariate statistical process monitoring & control. SIMCA^®-online provides a complete set of interactive and visual monitoring tools to production teams, to ensure that batch and continuous operations run smoothly These software solutions are fully integrated in most Sartorius systems and are available as stand-alone programs

Need

Solution

Most of vaccine developers and manufacturers are not statisticians and rely on user-friendly interfaces and software

MODDE^® is an advanced, high-quality DOE solution designed for ease of use. The benefit of DOE is to gain knowledge and estimate the best operating conditions of a process or product, and with MODDE^® ^® the graphical interface and analytics support make it easy to interpret results with complete confidence
SIMCA^® Multivariate Data Analysis (MVDA) software is used for scale and batch-to-batch comparison investigations. SIMCA^® transforms data into visual information for easy interpretation, enabling decisions and actions to be taken rapidly and with confidence. SIMCA^® helps to analyze process variations, identify critical parameters and predict final product quality. An overview of the process status can be obtained in a few clicks
SIMCA^® online is a highly efficient software for real-time multivariate statistical process monitoring & control. SIMCA^®-online provides a complete set of interactive and visual monitoring tools to production teams, to ensure that batch and continuous operations run smoothly

These software solutions are fully integrated in most Sartorius systems and are available as stand-alone programs

Process Analytical Technologies

Need	Solution
Vaccine manufacturers want to better understand and control their processes, which are very complex and highly regulated, but to do so requires real-time measurement of critical process parameters to allow process monitoring, set-point control (feed control and bleed control), event time point predictions (harvest and infection) and timely identification of process deviations A range of PAT sensors would be required to effectively apply QbD principles and ensure consistency in product quality and quantity, quickly identifying and correcting process deviations to reduce the risk of lost batches The ability to integrate PAT into single-use systems would mitigate risk of spillages and contamination during sampling	BioPAT^® toolbox, an expending range of fully qualified single-use sensors, are integrated across the Sartorius portfolio making Sartorius the market leader for PAT Available in process development and manufacturing technologies for full process understanding, monitoring and control Data analysis is straightforward thanks to the full integration in the Sartorius products & technologies BioPAT^® Viamass for inline monitoring of viable cell density and automated cell bleed control BioPAT^® Trace for online monitoring of glucose and lactate and automated feed control BioPAT^® Xgas for inline monitoring of CO2 and 02 BioPAT^® Spectro platform for Raman spectroscopy integration in Ambr^® and STR bioreactor systems for non-invasive, inline measurement of multiple analytes

Need

Solution

The ability to integrate PAT into single-use systems would mitigate risk of spillages and contamination during sampling

BioPAT^® toolbox, an expending range of fully qualified single-use sensors, are integrated across the Sartorius portfolio making Sartorius the market leader for PAT

Available in process development and manufacturing technologies for full process understanding, monitoring and control
Data analysis is straightforward thanks to the full integration in the Sartorius products & technologies
BioPAT^® Viamass for inline monitoring of viable cell density and automated cell bleed control
BioPAT^® Trace for online monitoring of glucose and lactate and automated feed control
BioPAT^® Xgas for inline monitoring of CO2 and 02
BioPAT^® Spectro platform for Raman spectroscopy integration in Ambr^® and STR bioreactor systems for non-invasive, inline measurement of multiple analytes

Application Data:

Control and scale-up of a microcarrier-based viral vaccine process using BioPAT ^® ViaMass for inline viable cell density measurement

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