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 

Seed Expansion

Virus Propagation

Clarification

Bioburden Reduction 

Concentration / Diafiltration

Virus Capture Chromatography

Polishing Chromatography

Inactivation / Split

Concentration / Diafiltration

Sterile Filtration

Other Technologies

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


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


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

Application Data:

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 

Seed Expansion

Virus Propagation

Clarification

Bioburden Reduction 

Concentration / Diafiltration

Virus Capture Chromatography

Polishing Chromatography

Concentration / Diafiltration

Sterile Filtration

Other Technologies

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


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


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

Application Data:

Contact a Vaccine Specialist