细胞系/菌株选择
细胞系/菌株选择
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.
▶ 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.
Application Data:
Ambr® 15 microcarrier
Ambr® 250 microcarrier
Ambr® 250 microcarrier poster
种子扩增
种子扩增
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 vaccinesA unique & robust film across the process ensuring excellent cell growthA closed process to lessen environmental risk to products and operatorsIntegration of a wide range of PAT including BioPAT® Viamass, BioPAT® Trace and BioPAT® SpectroA bag-integrated cell retention filter for intensified productionAdditional 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 cabinetA new generation of chemically defined (CD) and animal component free (ACF) cell culture media developed and tested with Sartorius bioreactorsApplication Data:
Single-Use, Stirred-Tank Bioreactors: Efficient Tools for Process Development and Characterization
▶ Adherent ProcessNeed
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 vaccinesA unique & robust film across the process ensuring excellent cell growthA closed process to lessen environmental risk to products and operatorsIntegration of a wide range of PAT including BioPAT® Viamass, BioPAT® Trace and BioPAT® SpectroA 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
病毒增殖
病毒增殖
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 growthIntegration of a wide range of PAT including BioPAT® Viamass, BioPAT® Trace and BioPAT® SpectroBuilt on Biosafety principles to reduce risk of leaksDirect scalability from Ambr® to STR for rapid process developmentCapable 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 ProcessNeed
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 growthIntegration of a wide range of PAT including BioPAT® Viamass, BioPAT® Trace and BioPAT® SpectroBuilt on Biosafety principles to reduce risk of leaksDirect scalability from Ambr® to STR, supporting microcarrier applications for rapid process developmentCapable 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:
Large pilot scale cultivation process study of adherent MDBK cells for porcine Influenza A virus propagation using a novel disposable stirred-tank bioreactorComparative study of bluetongue virus serotype 8 production on BHK-21 cells in a 50L Biostat® STR single-use bioreactors vs roller bottlesInactivated Enterovirus 71 Vaccine Produced by 200-L Scale Serum-Free Microcarrier Bioreactor System Provides Cross-Protective Efficacy in Human SCARB2 Transgenic Mouse.Process intensification for Peste des Petites Ruminants Virus vaccine productionControl and scale-up of a microcarrier-based viral vaccine process using BioPAT ® ViaMass for inline viable cell density measurement
澄清
澄清
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 filteredA low-shear clarification solution, retaining particles as a concentrated fluidized bed under a continuous flow of media or bufferEnsures containment of pathogenic viruses, compliant to Biosafety Level 2A 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 ProcessNeed
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 recoveryLowest filtration costs among polypropylene pre-filters on the marketAvailable as standard cartridges, in a closed capsule format, as filter transfer sets and in Maxicaps® MR formatFeaturing autoclavable capsules
Additional Solutions to Consider:
Ksep® single-use centrifuge to clarify shear sensitive and large viruses in a closed and pre-sterilized solutionClarification of Non-Enveloped Viruses▶ Suspension ProcessNeed
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 scalePre-assembled, closed Maxicaps® MR single-use skid integrating Sartopure® PP3 filters are available to ensure containment of filtration and clarification operationsApplication Data:
Poster: Clarification of Adenovirus serotype 5: Robust protection of downstream purification stepsPoster: Implementation of a Process-Scale Adenovirus Purification with a Single-Use Platform
▶ Adherent ProcessNeed
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 recoveryAvailable as standard cartridges, in a closed capsule format, as filter transfer sets and in Maxicaps® MR MR formatFeaturing 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
生物负载减低
生物负载减低
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 vaccinesAvailable in a large variety of prefilters and membranes, allowing full flexibility during process developmentWith 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 sizeThe 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 sizeApplication Data:
Clarification of Adenovirus serotype 5: Robust protection of downstream purification steps
浓缩/透析
浓缩/透析
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
病毒捕获层析
病毒捕获层析
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 recoveryFour ligands are available allowing purification of different types of viruses: Q, S, Sulfated Cellulose (SC) and PhenylEnsures containment and sterility through a closed autoclavable format up to 5L of membrane volume96-well plate format is available for high throughput screening experimentsAvailable 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 vaccinesSartobind® Sulfated Cellulose (SC) is a new membrane dedicated to the capture of heparin-binding viruses like InfluenzaApplication 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
精纯层析
精纯层析
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 capacityThe high flowrate allows for a smaller footprintFour ligands are available for contaminant removal: Q, STIC, S & PhenylEnsure 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 experimentsAvailable 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 chargesThe 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 designAdditional 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
灭活/裂解
灭活/裂解
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 mixingA 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 criticalSartorius’s validation services enable the verification of chemical compatibility and the extractable profile of the mixing step, a critical success factor during inactivation
浓缩/透析
浓缩/透析
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
除菌过滤
除菌过滤
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 assurancePoint-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 handlingThe 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 sizeSartocheck® 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