This document describes the development of a scalable upstream bioreactor process for lentiviral vector production using suspension cell culture. The goals were to design a manufacturing-friendly process that supports commercialization. A 50L bioreactor process was developed using a chemically-defined medium and HEK293T cells optimized for suspension growth. The process was demonstrated to be scalable through geometric similarity across bioreactor sizes from 3L to 2000L. This template process provides benefits like speed to patients, reliability, robustness, and efficiency for lentiviral vector manufacturing.
Process development guidance for AAV and lentivirus manufacturing based on co...MilliporeSigma
Access the interactive recording here: https://bit.ly/37nl3Ex
Webinar summary:
An efficient production platform is essential for successful commercial implementation of gene therapy programs. AAV and Lentivirus manufacturing process are often developed with compressed timelines, reduced process optimization and low product yields which can have significant effect on costs.
In this webinar, you will learn:
* How manufacturing costs are examined for adeno-associated virus and lentivirus production with several different for each vector
* That key process characteristics like production titer, production of empty viral particles, downstream product recovery, and the batching strategy can effect the overall manufacturing cost
* How holistic evaluation is an important tool during process development to help prioritize different approaches to improve viral vector production processes
Abstract:
An efficient production platform is essential for successful commercial implementation of gene therapy programs. Viral vector manufacturing processes are often developed under timelines which are considerably shorter than those for more mature biopharmaceuticals. Consequently, the level of process optimization is reduced and challenges related to low product yields are common. These factors, as well as the small batch sizes common for these processes, can have significant effect on manufacturing costs.
Production and purification of Viral vectors for gene and cell therapy appli...Dr. Priyabrata Pattnaik
Presentation at "2016 Osong BioExcellence - Renaissance in Immunotherapy" at South Korea, an event jointly hosted by Kbio Health and Merck on 6th October 2016.
Addressing the Challenge of Scalability in Viral VectorsMilliporeSigma
Watch this webinar here: https://bit.ly/3jlcEXH
Addressing the Challenge of Scalability in Viral Vectors
To meet the ever-increasing demands for cell and gene therapies, there is a need to shift away from expensive, labor-intensive cell culture and scale up systems. But this goal cannot be met without a robust production strategy based on clinical indication, population size and dosing requirements.
Early viral vector process development for cell and gene therapies is critical to assure a production strategy that supports commercial needs based on clinical indication, population size and dosing requirements. Most production processes today rely on labor-intensive and expensive adherent cell culture systems and scale out approaches. This webinar will highlight the importance of a scalable process that supports clinical through commercial needs. We will introduce a suspension-based process we have developed, including a HEK 293T cell line, chemically defined media, and optimized process conditions that results in higher yield, easier scalability, and lower production costs.
In this webinar, you will learn:
• Why suspension cell based processes are easier, faster, and more economical than adherent cell growth cultures
• Use of chemically defined medium for improved cellular growth, viral productivity, easier downstream purification and improved safety from adventitious agents
• Unraveling the complexities of the HEK293 and 293T cell lines
• The importance of planning for scalability and manufacturability from the earliest stages of process development
• How a scalable templated process can reduce time needed to move from product development to commercialization
Process Development for Cell Therapy and Viral Gene TherapyMerck Life Sciences
Today’s viral vector manufacturing processes remain challenging. Process development is a critical enabler to bring safe, effective, sustainable products to market to address patient needs. When done properly, it can reduce the timeline of the project and the cost of producing the therapeutic product.
The webinar discusses our strategies for developing lentivirus and adeno associated virus (AAV) and the impact these early decisions can have on commercial readiness.
Watch the interactive webinar now: https://bit.ly/2VplwQq
Employing Innovative Platform Manufacturing and Biosafety Testing for your Ge...MilliporeSigma
Watch the webinar here: https://event.on24.com/wcc/r/2003970/F5AFA4FE6C60AD00635D4D15BADB5D8E?partnerref=slideshare
As gene therapies and gene-modified cell therapies show increasing promise, the need for innovative and proficient viral vector manufacturing continues to grow. Concurrently, increased regulatory guidance governing the manufacturing and testing of viral vectors adds complexity and increases the timelines to successfully produce high-quality virus ready for clinical use.
This webinar will address how the implementation of both manufacturing templates and platform characterization and safety assays can increase the likelihood of success in process validation and reduce risk in the timeline to commercialization for your gene therapy product. Using adeno-associated virus (AAV) as a case study, we will demonstrate how our validated, templated process for production can reduce the need for qualification inherent in niche manufacturing workflows and anticipate forthcoming needs for process performance qualification. This webinar will also highlight benefits from a new, platform assay offering for characterization and safety testing of AAV. Because these assays are pre-qualified, they reduce the variability inherent in assay validation and subsequently the time needed to establish readiness for regulatory compliance.
While these developments increase the standardization across the manufacturing and testing workflows, they remain flexible to clients' needs and are created to be scalable and as future-proof as possible, allowing for adaptability as the regulatory landscape of gene therapies evolves.
In this webinar, you will learn:
● The unit operations in AAV manufacturing that are ideal for templating
● How the manufacturing workflow can be targeted to reduce variability in testing and improve readiness for commercial production
● How platform assays can ease the burden of assay qualification and improve overall commercialization timelines
Keeping the (Adventitious) Virus Out of the (Adeno-Associated) VirusMerck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/2VRylbi
How can you keep an adventitious virus from contaminating your gene therapy that is delivered by an adeno virus vector? As viral vector bioprocessing advances, regulatory requirements for viral safety will as well. Learn how to define your viral clearance strategy for AAV delivered gene therapies.
How do you define a strategy for viral clearance for a process that inherently aims at purifying a virus?
Gene delivery using AAV has received a boost from two major approvals and the nearly 300 programs in the clinic. Novel gene therapies using viral vectors enable companies to transform the lives of people living with certain rare and ultra-rare diseases where treatments are often not available currently. Amongst a multitude of challenges in viral vector bioprocessing, uncertainty in regulatory expectations is a major challenge to gene therapy developers. Regulatory requirements are evolving as the science and manufacturing matures with more stringent measures for viral safety assurance expected for future approvals.
Learn how to implement techniques for adventitious virus removal in your viral vector process; we will focus on strategies for viral clearance along your journey towards commercial readiness of AAV-based processes.
In this webinar, you will learn:
• AAV process flows and focus areas for viral safety
• Strategies for implementing viral clearance measures in bioprocessing
• Case studies and data driven approaches on log reduction values (LRV) in a viral vector process
• Best practices and evaluation roadmaps on conducting viral clearance studies
Presented by: Ratish Krishnan, Senior Strategy Consultant, Novel Modalities Bioprocessing
Abstract:
Cell and gene therapies, well recognized as the drug revolution for this decade, are booming in Asian countries. Several cell and gene therapeutic products launched successfully in Europe and the US. The commercialization of these therapies is a hot topic, while ensuring product safety, especially quality for the new modalities, raises challenges within the industry. As a globally leading biosafety testing provider, Merck is committed to optimizing and advancing innovation and development of biosafety testing. As your reliable partner in CMC consideration, our comprehensive solutions for cell and gene therapy biosafety testing enable regulatory compliance. This presentation will cover rationale and methodologies for cell and gene therapy product testing from Merck’s BioReliance® testing portfolio, as well as provide an overview of our testing capabilities and services.
Unveiling the Potential of your AAV Gene Therapy: Orthogonal methods to under...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3pCCjPF
Ensure your Adeno-Associated Virus (AAV) is safe throughout its entire drug development journey. Learn methods that will help you speed to clinic, potentially treating diseases sooner and with greater effectiveness.
The potential of gene therapies to cure previously untreatable diseases has spurred the development of novel drugs, including those based on Adeno-Associated Virus (AAV). As with all biopharmaceuticals, it is important to identify and monitor the critical quality attributes (CQAs) of these products to ensure their safety and efficacy.
In this webinar, we will present a range of orthogonal methods to understand and define the CQAs of AAV products. These include assays for the confirmation of capsid protein identity and quantity, as well as the characterization of important product-related impurities, such as aggregates. Together these methods represent a comprehensive analytical testing package to support the characterization and lot release of AAV products.
In this webinar, you will learn:
• How to identify and monitor the critical quality attributes (CQAs) of your AAV therapy
• What assays to utilize to confirm capsid protein identity and quantity
• Why you need look to product characterization to identify and remove important product-related impurities
Process development guidance for AAV and lentivirus manufacturing based on co...MilliporeSigma
Access the interactive recording here: https://bit.ly/37nl3Ex
Webinar summary:
An efficient production platform is essential for successful commercial implementation of gene therapy programs. AAV and Lentivirus manufacturing process are often developed with compressed timelines, reduced process optimization and low product yields which can have significant effect on costs.
In this webinar, you will learn:
* How manufacturing costs are examined for adeno-associated virus and lentivirus production with several different for each vector
* That key process characteristics like production titer, production of empty viral particles, downstream product recovery, and the batching strategy can effect the overall manufacturing cost
* How holistic evaluation is an important tool during process development to help prioritize different approaches to improve viral vector production processes
Abstract:
An efficient production platform is essential for successful commercial implementation of gene therapy programs. Viral vector manufacturing processes are often developed under timelines which are considerably shorter than those for more mature biopharmaceuticals. Consequently, the level of process optimization is reduced and challenges related to low product yields are common. These factors, as well as the small batch sizes common for these processes, can have significant effect on manufacturing costs.
Production and purification of Viral vectors for gene and cell therapy appli...Dr. Priyabrata Pattnaik
Presentation at "2016 Osong BioExcellence - Renaissance in Immunotherapy" at South Korea, an event jointly hosted by Kbio Health and Merck on 6th October 2016.
Addressing the Challenge of Scalability in Viral VectorsMilliporeSigma
Watch this webinar here: https://bit.ly/3jlcEXH
Addressing the Challenge of Scalability in Viral Vectors
To meet the ever-increasing demands for cell and gene therapies, there is a need to shift away from expensive, labor-intensive cell culture and scale up systems. But this goal cannot be met without a robust production strategy based on clinical indication, population size and dosing requirements.
Early viral vector process development for cell and gene therapies is critical to assure a production strategy that supports commercial needs based on clinical indication, population size and dosing requirements. Most production processes today rely on labor-intensive and expensive adherent cell culture systems and scale out approaches. This webinar will highlight the importance of a scalable process that supports clinical through commercial needs. We will introduce a suspension-based process we have developed, including a HEK 293T cell line, chemically defined media, and optimized process conditions that results in higher yield, easier scalability, and lower production costs.
In this webinar, you will learn:
• Why suspension cell based processes are easier, faster, and more economical than adherent cell growth cultures
• Use of chemically defined medium for improved cellular growth, viral productivity, easier downstream purification and improved safety from adventitious agents
• Unraveling the complexities of the HEK293 and 293T cell lines
• The importance of planning for scalability and manufacturability from the earliest stages of process development
• How a scalable templated process can reduce time needed to move from product development to commercialization
Process Development for Cell Therapy and Viral Gene TherapyMerck Life Sciences
Today’s viral vector manufacturing processes remain challenging. Process development is a critical enabler to bring safe, effective, sustainable products to market to address patient needs. When done properly, it can reduce the timeline of the project and the cost of producing the therapeutic product.
The webinar discusses our strategies for developing lentivirus and adeno associated virus (AAV) and the impact these early decisions can have on commercial readiness.
Watch the interactive webinar now: https://bit.ly/2VplwQq
Employing Innovative Platform Manufacturing and Biosafety Testing for your Ge...MilliporeSigma
Watch the webinar here: https://event.on24.com/wcc/r/2003970/F5AFA4FE6C60AD00635D4D15BADB5D8E?partnerref=slideshare
As gene therapies and gene-modified cell therapies show increasing promise, the need for innovative and proficient viral vector manufacturing continues to grow. Concurrently, increased regulatory guidance governing the manufacturing and testing of viral vectors adds complexity and increases the timelines to successfully produce high-quality virus ready for clinical use.
This webinar will address how the implementation of both manufacturing templates and platform characterization and safety assays can increase the likelihood of success in process validation and reduce risk in the timeline to commercialization for your gene therapy product. Using adeno-associated virus (AAV) as a case study, we will demonstrate how our validated, templated process for production can reduce the need for qualification inherent in niche manufacturing workflows and anticipate forthcoming needs for process performance qualification. This webinar will also highlight benefits from a new, platform assay offering for characterization and safety testing of AAV. Because these assays are pre-qualified, they reduce the variability inherent in assay validation and subsequently the time needed to establish readiness for regulatory compliance.
While these developments increase the standardization across the manufacturing and testing workflows, they remain flexible to clients' needs and are created to be scalable and as future-proof as possible, allowing for adaptability as the regulatory landscape of gene therapies evolves.
In this webinar, you will learn:
● The unit operations in AAV manufacturing that are ideal for templating
● How the manufacturing workflow can be targeted to reduce variability in testing and improve readiness for commercial production
● How platform assays can ease the burden of assay qualification and improve overall commercialization timelines
Keeping the (Adventitious) Virus Out of the (Adeno-Associated) VirusMerck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/2VRylbi
How can you keep an adventitious virus from contaminating your gene therapy that is delivered by an adeno virus vector? As viral vector bioprocessing advances, regulatory requirements for viral safety will as well. Learn how to define your viral clearance strategy for AAV delivered gene therapies.
How do you define a strategy for viral clearance for a process that inherently aims at purifying a virus?
Gene delivery using AAV has received a boost from two major approvals and the nearly 300 programs in the clinic. Novel gene therapies using viral vectors enable companies to transform the lives of people living with certain rare and ultra-rare diseases where treatments are often not available currently. Amongst a multitude of challenges in viral vector bioprocessing, uncertainty in regulatory expectations is a major challenge to gene therapy developers. Regulatory requirements are evolving as the science and manufacturing matures with more stringent measures for viral safety assurance expected for future approvals.
Learn how to implement techniques for adventitious virus removal in your viral vector process; we will focus on strategies for viral clearance along your journey towards commercial readiness of AAV-based processes.
In this webinar, you will learn:
• AAV process flows and focus areas for viral safety
• Strategies for implementing viral clearance measures in bioprocessing
• Case studies and data driven approaches on log reduction values (LRV) in a viral vector process
• Best practices and evaluation roadmaps on conducting viral clearance studies
Presented by: Ratish Krishnan, Senior Strategy Consultant, Novel Modalities Bioprocessing
Abstract:
Cell and gene therapies, well recognized as the drug revolution for this decade, are booming in Asian countries. Several cell and gene therapeutic products launched successfully in Europe and the US. The commercialization of these therapies is a hot topic, while ensuring product safety, especially quality for the new modalities, raises challenges within the industry. As a globally leading biosafety testing provider, Merck is committed to optimizing and advancing innovation and development of biosafety testing. As your reliable partner in CMC consideration, our comprehensive solutions for cell and gene therapy biosafety testing enable regulatory compliance. This presentation will cover rationale and methodologies for cell and gene therapy product testing from Merck’s BioReliance® testing portfolio, as well as provide an overview of our testing capabilities and services.
Unveiling the Potential of your AAV Gene Therapy: Orthogonal methods to under...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3pCCjPF
Ensure your Adeno-Associated Virus (AAV) is safe throughout its entire drug development journey. Learn methods that will help you speed to clinic, potentially treating diseases sooner and with greater effectiveness.
The potential of gene therapies to cure previously untreatable diseases has spurred the development of novel drugs, including those based on Adeno-Associated Virus (AAV). As with all biopharmaceuticals, it is important to identify and monitor the critical quality attributes (CQAs) of these products to ensure their safety and efficacy.
In this webinar, we will present a range of orthogonal methods to understand and define the CQAs of AAV products. These include assays for the confirmation of capsid protein identity and quantity, as well as the characterization of important product-related impurities, such as aggregates. Together these methods represent a comprehensive analytical testing package to support the characterization and lot release of AAV products.
In this webinar, you will learn:
• How to identify and monitor the critical quality attributes (CQAs) of your AAV therapy
• What assays to utilize to confirm capsid protein identity and quantity
• Why you need look to product characterization to identify and remove important product-related impurities
Does your cell line have a secret? Avoid surprises with characterizationMerck Life Sciences
Watch the recording of this webinar here: https://bit.ly/2Y05bV4
The first step to avoiding an unpleasant and costly contamination event is characterization of your cell banks.
Regardless of the biotech product, careful characterization of the cell banks used in its production is the first step in mitigating the risk of a contamination event. In fact, cell line characterization is an important component of the overall viral safety strategy for the product. We will describe the testing necessary to ensure cell banks are free from infectious and other adverse agents and that meets current regulatory expectations. Different levels of testing are performed for master, working, and end of production cell banks, and the differences in testing for each of these types of banks will be discussed.
In this webinar, you will learn:
• The types of tests that are needed to fully characterize your cell banks
• The best tests to use for your particular cell line
• Reasons why a viral contaminant may be missed
Sartorius is a well respected global solution provider within the biologics industry, especially for antibody and vaccine production. Our proven products and services are being diversified for upstream and downstream processing of cells and viruses for allogeneic and autologous advanced therapies.
Sartorius provides the cellular immunotherapy industry with a range of scalable single-use production technologies. Our portfolio supports viral vector transduction, cell expansion, and downstream processing steps including harvest, wash, and concentration of cells
Platform Technologies to Accelerate Novel Vaccine Development and ManufacturingMerck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3jmLYHu
State-of-the-art vaccine technologies are transforming vaccine development, and solutions for fast and reliable production are needed.
The vaccine industry has undergone a revolution in technology resulting in a variety of novel therapeutic platforms that accelerate development and significantly reduce the duration for process optimization and scale-up. However, challenges in maintaining efficacy and improving process robustness remain. In this presentation, we present a comparison of these novel technologies, discuss key considerations for manufacturing and share selected case studies for platforms such as virus-like-particles, viral vectors, plasmid DNA, and mRNA platform.
In this webinar, you will learn:
• Benefits of platform technologies in vaccine development
• Key considerations when deciding between platforms
• Vaccine pipeline analysis and selected case studies
Presented by:
David Loong, Ph.D, Senior Consultant, Novel Modalities Asia Pacific, Bioprocessing Strategy
Josephine Cheng, Senior Consultant, Core Modalities Asia Pacific, Bioprocessing Strategy
Scaling Strategies with Stirred Single-Use Bioreactors from Bench to Clinical...MilliporeSigma
This presentation introduces the general principles of scaling strategies with stirred single-use bioreactors, discusses key engineering parameters, and concludes with a case study of how these strategies are applied to Mobius® bioreactors from 2 liters to 2000 liters.
To learn more about this topic or collaborate with our technical experts, schedule an in-person or remote visit at our M Lab™ Collaboration Centers: www.emdmillipore.com/mlab
Streamlining Biopharmaceutical Cell Line Development - Reducing risk and decr...Merck Life Sciences
CHO cells with their unique characteristics, represent the major expression system within the biopharmaceutical industry. However, one of the major challenges in cell line development is to identify those rare, high-producing clones in a huge population of non-expressing or low-expressing cell lines. This leads to laborious and time consuming cell line development processes. This webinar will educate the audience about challenges faced with traditional expression systems and how the CHO cell line with the glutamine synthethase knock-out via Zinc Finger Nucleases provides benefits for fast and efficient cell line development as well as stable and high titer expression. We will explore additional cell line engineering targets that can be modified to engineer a cell line that mitigates risks and removes bottlenecks throughout the biopharmaceutical process.
In this webinar, you will learn:
• What are the benefits of using an optimized/engineered expression system?
• What can be done throughout the cell line development process to mitigate risks and remove bottlenecks?
• Applications of cell line engineering for further upstream biopharmaceutical enhancements.
Viral Based Gene Delivery System for Car-t Cell Engineering Creative-Biolabs
A brief introduction about lentiviral vector gene delivery system and its application in CAR-T cell construction. Creative Biolabs offers high quality lentivirus based CAR gene delivery service to help with your CAR-T cell development projects.
Validation of Tangential Flow Filtration in Biotech ProcessesMerck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3hUKfd7
The objective of validation of a unit operation is to demonstrate with a high degree of confidence that the process performs consistently. The present seminar will focus on the validation of the unit operation of TFF and will provide an overview of the regulatory landscape, the validation master plan, approaches to membrane re-use, cleaning validation, and best practices.
In this webinar, you will learn:
• Validation of TFF
• Validation master plan
• Membrane reuse and cleaning
• TFF scale down models
Speaker: Dr. Subhasis Banerjee,
Principal Technical Application Expert, Bioprocessing APAC
Membrane Chromatography Solutions for Single-Use, Intensified mAb PurificationMerck Life Sciences
Participate in the interactive webinar: http://bit.ly/NatrixChromMRK
Improve productivity, flexibility, and economics of mAb purification process with intensified, single-use membrane chromatography.
Explore our webinar library: www.merckmillipore.com/webinars
Characterization of monoclonal antibodies and Antibody drug conjugates by Sur...MilliporeSigma
Watch the presentation of this webinar: https://bit.ly/3Pjpjvr
Highlights of this webinar:
- Surface plasmon resonance as a powerful tool for biologic characterization including mAbs and ADCs.
- SPR allows rapid binding analysis in real time without using labels for SARS-CoV-2 receptor binding domain mutations.
- Kinetic data is indicative of possible neutralizing activity allowed assessment of neutralizing ability of therapeutic monoclonal antibodies.
- The application can provide preliminarily efficacy information and facilitated mAbs/ACDs candidate selection process
Detailed description:
Characterization of therapeutic monoclonal antibodies (mAbs) or Antibody drug conjugates (ADCs) is challenging due to their ability to bind to a variety of proteins via their Fc and Fab domains, giving rise to diverse biological functions associated with each domain. The Fc domain of mAbs interacts with Fc receptors with varying affinities, which can influence biological processes such as Complement-dependent cytotoxicity (CDC) and Antibody-dependent cellular cytotoxicity (ADCC), transcytosis, phagocytosis, and/or serum half-life.
An important characteristic of an antibody is its Fc effector function. Antibodies can be engineered to obtain desired binding of the Fc region to Fc receptors expressed on effector cells. Hence, it is crucial to evaluate the binding interaction of mAbs/ADC with Fc receptors in the early phase of drug development to understand the potential biological activity of the product in vivo.
Surface Plasmon Resonance (SPR) is a powerful technique to establish binding kinetics in real-time, label free, and high sensitivity with low sample consumption. Along with target antigen binding, it is crucial to evaluate the binding interaction of antibodies and ADCs with Fc receptors. Our SPR case studies investigated the impact on binding kinetics of ADCs with different linkers and the binding interactions of SARS-CoV-2 spike protein variants and evaluated the neutralizing ability of therapeutic mAbs. SPR characterisation can be facilitated in all stages of the product life cycle to ensure the quality and safety of mAbs and ADCs.
Viral clearance is a critical component of regulatory submissions as it helps demonstrate overall product safety . Laboratory scale-down models validate your downstream purification process for removal/inactivation of adventitious agents. The design of an effective viral clearance platform is essential for continual success. WuXi Advanced Therapies has the right experience for the nuanced world of viral clearance and a platform to drive higher log reduction values (LRV).
Vaccine Cell Bank and Virus Seed CharacterizationMilliporeSigma
In this webinar, you will learn:
- about the importance of characterising cell banks and virus seed stocks in order to meet worldwide regulatory requirements.
- the difference between guidance documents from different organizations worldwide
- new technologies for determining the identity of cell substrates and virus seed stocks
- detecting adventitious agent contamination
Straight to the Point: Reaching Clinical Stage Development with a CHOZN® Cell...Merck Life Sciences
Participate in the interactive webinar: http://bit.ly/CHOZNWebinar
In this case study, we will present how we support our clients thanks to advantages provided by the CHOZN® Cell Line, and a specific strategy for clone selection where semi-automation and pool selection are leveraged, to get upstream right first time.
Explore our webinar library: www.merckmillipore.com/webinars
Scalability of a Single-use Bioreactor Platform for Biopharmaceutical Manufac...KBI Biopharma
Increasing adoption of single-use technologies for bioprocessing along with higher titers from cell culture bioreactor processes has allowed clinical and even commercial manufacturing to be successfully performed in 2000 L-scale single-use bioreactors. Several biopharmaceutical manufacturers have successfully adopted single-use bioreactors for production. However, information about process scalability from glass bioreactors to 2000 L single-use bioreactors for different types of CHO cell lines is not widely available. Here we provide an overview of the key
differences between single-use and conventional stainless steel bioreactors, and highlight factors that are employed while scaling-up from small-scale glass bioreactors to 2000 L-scale single-use bioreactors. Several case studies focusing on process performance across scales into single-use bioreactors are provided. This analysis confirms that the 2000 L-scale single-use bioreactorsystem can be robustly employed for biopharmaceutical manufacturing.
Watch this webinar here: https://bit.ly/3jlcEXH
Addressing the Challenge of Scalability in Viral Vectors
To meet the ever-increasing demands for cell and gene therapies, there is a need to shift away from expensive, labor-intensive cell culture and scale up systems. But this goal cannot be met without a robust production strategy based on clinical indication, population size and dosing requirements.
Early viral vector process development for cell and gene therapies is critical to assure a production strategy that supports commercial needs based on clinical indication, population size and dosing requirements. Most production processes today rely on labor-intensive and expensive adherent cell culture systems and scale out approaches. This webinar will highlight the importance of a scalable process that supports clinical through commercial needs. We will introduce a suspension-based process we have developed, including a HEK 293T cell line, chemically defined media, and optimized process conditions that results in higher yield, easier scalability, and lower production costs.
In this webinar, you will learn:
• Why suspension cell based processes are easier, faster, and more economical than adherent cell growth cultures
• Use of chemically defined medium for improved cellular growth, viral productivity, easier downstream purification and improved safety from adventitious agents
• Unraveling the complexities of the HEK293 and 293T cell lines
• The importance of planning for scalability and manufacturability from the earliest stages of process development
• How a scalable templated process can reduce time needed to move from product development to commercialization
Scalability of Cell Culture Processes in Single-use Bioreactors using Differe...KBI Biopharma
Niket Bubna, Cameron T. Phillips, Sigma S. Mostafa and AbhinavA. Shukla. KBI Biopharma, Durham, NC
253rd ACS National Meeting & Exposition
April 2-6, 2017 • San Francisco, CA
#acsSanFran • www.acs.org/SanFran2017
Does your cell line have a secret? Avoid surprises with characterizationMerck Life Sciences
Watch the recording of this webinar here: https://bit.ly/2Y05bV4
The first step to avoiding an unpleasant and costly contamination event is characterization of your cell banks.
Regardless of the biotech product, careful characterization of the cell banks used in its production is the first step in mitigating the risk of a contamination event. In fact, cell line characterization is an important component of the overall viral safety strategy for the product. We will describe the testing necessary to ensure cell banks are free from infectious and other adverse agents and that meets current regulatory expectations. Different levels of testing are performed for master, working, and end of production cell banks, and the differences in testing for each of these types of banks will be discussed.
In this webinar, you will learn:
• The types of tests that are needed to fully characterize your cell banks
• The best tests to use for your particular cell line
• Reasons why a viral contaminant may be missed
Sartorius is a well respected global solution provider within the biologics industry, especially for antibody and vaccine production. Our proven products and services are being diversified for upstream and downstream processing of cells and viruses for allogeneic and autologous advanced therapies.
Sartorius provides the cellular immunotherapy industry with a range of scalable single-use production technologies. Our portfolio supports viral vector transduction, cell expansion, and downstream processing steps including harvest, wash, and concentration of cells
Platform Technologies to Accelerate Novel Vaccine Development and ManufacturingMerck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3jmLYHu
State-of-the-art vaccine technologies are transforming vaccine development, and solutions for fast and reliable production are needed.
The vaccine industry has undergone a revolution in technology resulting in a variety of novel therapeutic platforms that accelerate development and significantly reduce the duration for process optimization and scale-up. However, challenges in maintaining efficacy and improving process robustness remain. In this presentation, we present a comparison of these novel technologies, discuss key considerations for manufacturing and share selected case studies for platforms such as virus-like-particles, viral vectors, plasmid DNA, and mRNA platform.
In this webinar, you will learn:
• Benefits of platform technologies in vaccine development
• Key considerations when deciding between platforms
• Vaccine pipeline analysis and selected case studies
Presented by:
David Loong, Ph.D, Senior Consultant, Novel Modalities Asia Pacific, Bioprocessing Strategy
Josephine Cheng, Senior Consultant, Core Modalities Asia Pacific, Bioprocessing Strategy
Scaling Strategies with Stirred Single-Use Bioreactors from Bench to Clinical...MilliporeSigma
This presentation introduces the general principles of scaling strategies with stirred single-use bioreactors, discusses key engineering parameters, and concludes with a case study of how these strategies are applied to Mobius® bioreactors from 2 liters to 2000 liters.
To learn more about this topic or collaborate with our technical experts, schedule an in-person or remote visit at our M Lab™ Collaboration Centers: www.emdmillipore.com/mlab
Streamlining Biopharmaceutical Cell Line Development - Reducing risk and decr...Merck Life Sciences
CHO cells with their unique characteristics, represent the major expression system within the biopharmaceutical industry. However, one of the major challenges in cell line development is to identify those rare, high-producing clones in a huge population of non-expressing or low-expressing cell lines. This leads to laborious and time consuming cell line development processes. This webinar will educate the audience about challenges faced with traditional expression systems and how the CHO cell line with the glutamine synthethase knock-out via Zinc Finger Nucleases provides benefits for fast and efficient cell line development as well as stable and high titer expression. We will explore additional cell line engineering targets that can be modified to engineer a cell line that mitigates risks and removes bottlenecks throughout the biopharmaceutical process.
In this webinar, you will learn:
• What are the benefits of using an optimized/engineered expression system?
• What can be done throughout the cell line development process to mitigate risks and remove bottlenecks?
• Applications of cell line engineering for further upstream biopharmaceutical enhancements.
Viral Based Gene Delivery System for Car-t Cell Engineering Creative-Biolabs
A brief introduction about lentiviral vector gene delivery system and its application in CAR-T cell construction. Creative Biolabs offers high quality lentivirus based CAR gene delivery service to help with your CAR-T cell development projects.
Validation of Tangential Flow Filtration in Biotech ProcessesMerck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3hUKfd7
The objective of validation of a unit operation is to demonstrate with a high degree of confidence that the process performs consistently. The present seminar will focus on the validation of the unit operation of TFF and will provide an overview of the regulatory landscape, the validation master plan, approaches to membrane re-use, cleaning validation, and best practices.
In this webinar, you will learn:
• Validation of TFF
• Validation master plan
• Membrane reuse and cleaning
• TFF scale down models
Speaker: Dr. Subhasis Banerjee,
Principal Technical Application Expert, Bioprocessing APAC
Membrane Chromatography Solutions for Single-Use, Intensified mAb PurificationMerck Life Sciences
Participate in the interactive webinar: http://bit.ly/NatrixChromMRK
Improve productivity, flexibility, and economics of mAb purification process with intensified, single-use membrane chromatography.
Explore our webinar library: www.merckmillipore.com/webinars
Characterization of monoclonal antibodies and Antibody drug conjugates by Sur...MilliporeSigma
Watch the presentation of this webinar: https://bit.ly/3Pjpjvr
Highlights of this webinar:
- Surface plasmon resonance as a powerful tool for biologic characterization including mAbs and ADCs.
- SPR allows rapid binding analysis in real time without using labels for SARS-CoV-2 receptor binding domain mutations.
- Kinetic data is indicative of possible neutralizing activity allowed assessment of neutralizing ability of therapeutic monoclonal antibodies.
- The application can provide preliminarily efficacy information and facilitated mAbs/ACDs candidate selection process
Detailed description:
Characterization of therapeutic monoclonal antibodies (mAbs) or Antibody drug conjugates (ADCs) is challenging due to their ability to bind to a variety of proteins via their Fc and Fab domains, giving rise to diverse biological functions associated with each domain. The Fc domain of mAbs interacts with Fc receptors with varying affinities, which can influence biological processes such as Complement-dependent cytotoxicity (CDC) and Antibody-dependent cellular cytotoxicity (ADCC), transcytosis, phagocytosis, and/or serum half-life.
An important characteristic of an antibody is its Fc effector function. Antibodies can be engineered to obtain desired binding of the Fc region to Fc receptors expressed on effector cells. Hence, it is crucial to evaluate the binding interaction of mAbs/ADC with Fc receptors in the early phase of drug development to understand the potential biological activity of the product in vivo.
Surface Plasmon Resonance (SPR) is a powerful technique to establish binding kinetics in real-time, label free, and high sensitivity with low sample consumption. Along with target antigen binding, it is crucial to evaluate the binding interaction of antibodies and ADCs with Fc receptors. Our SPR case studies investigated the impact on binding kinetics of ADCs with different linkers and the binding interactions of SARS-CoV-2 spike protein variants and evaluated the neutralizing ability of therapeutic mAbs. SPR characterisation can be facilitated in all stages of the product life cycle to ensure the quality and safety of mAbs and ADCs.
Viral clearance is a critical component of regulatory submissions as it helps demonstrate overall product safety . Laboratory scale-down models validate your downstream purification process for removal/inactivation of adventitious agents. The design of an effective viral clearance platform is essential for continual success. WuXi Advanced Therapies has the right experience for the nuanced world of viral clearance and a platform to drive higher log reduction values (LRV).
Vaccine Cell Bank and Virus Seed CharacterizationMilliporeSigma
In this webinar, you will learn:
- about the importance of characterising cell banks and virus seed stocks in order to meet worldwide regulatory requirements.
- the difference between guidance documents from different organizations worldwide
- new technologies for determining the identity of cell substrates and virus seed stocks
- detecting adventitious agent contamination
Straight to the Point: Reaching Clinical Stage Development with a CHOZN® Cell...Merck Life Sciences
Participate in the interactive webinar: http://bit.ly/CHOZNWebinar
In this case study, we will present how we support our clients thanks to advantages provided by the CHOZN® Cell Line, and a specific strategy for clone selection where semi-automation and pool selection are leveraged, to get upstream right first time.
Explore our webinar library: www.merckmillipore.com/webinars
Scalability of a Single-use Bioreactor Platform for Biopharmaceutical Manufac...KBI Biopharma
Increasing adoption of single-use technologies for bioprocessing along with higher titers from cell culture bioreactor processes has allowed clinical and even commercial manufacturing to be successfully performed in 2000 L-scale single-use bioreactors. Several biopharmaceutical manufacturers have successfully adopted single-use bioreactors for production. However, information about process scalability from glass bioreactors to 2000 L single-use bioreactors for different types of CHO cell lines is not widely available. Here we provide an overview of the key
differences between single-use and conventional stainless steel bioreactors, and highlight factors that are employed while scaling-up from small-scale glass bioreactors to 2000 L-scale single-use bioreactors. Several case studies focusing on process performance across scales into single-use bioreactors are provided. This analysis confirms that the 2000 L-scale single-use bioreactorsystem can be robustly employed for biopharmaceutical manufacturing.
Watch this webinar here: https://bit.ly/3jlcEXH
Addressing the Challenge of Scalability in Viral Vectors
To meet the ever-increasing demands for cell and gene therapies, there is a need to shift away from expensive, labor-intensive cell culture and scale up systems. But this goal cannot be met without a robust production strategy based on clinical indication, population size and dosing requirements.
Early viral vector process development for cell and gene therapies is critical to assure a production strategy that supports commercial needs based on clinical indication, population size and dosing requirements. Most production processes today rely on labor-intensive and expensive adherent cell culture systems and scale out approaches. This webinar will highlight the importance of a scalable process that supports clinical through commercial needs. We will introduce a suspension-based process we have developed, including a HEK 293T cell line, chemically defined media, and optimized process conditions that results in higher yield, easier scalability, and lower production costs.
In this webinar, you will learn:
• Why suspension cell based processes are easier, faster, and more economical than adherent cell growth cultures
• Use of chemically defined medium for improved cellular growth, viral productivity, easier downstream purification and improved safety from adventitious agents
• Unraveling the complexities of the HEK293 and 293T cell lines
• The importance of planning for scalability and manufacturability from the earliest stages of process development
• How a scalable templated process can reduce time needed to move from product development to commercialization
Scalability of Cell Culture Processes in Single-use Bioreactors using Differe...KBI Biopharma
Niket Bubna, Cameron T. Phillips, Sigma S. Mostafa and AbhinavA. Shukla. KBI Biopharma, Durham, NC
253rd ACS National Meeting & Exposition
April 2-6, 2017 • San Francisco, CA
#acsSanFran • www.acs.org/SanFran2017
The demand for the fast and robust development of manufacturing cell lines is ever growing, with an increasing number of therapeutic proteins in development. To fulfill these needs, Celonic engineered the cell line kit CHOvolution™, which equips users with everything required for the development of mammalian cell lines and provides an integrated support system for assistance.
Webinar: Novel Perfusion Filter and Controller for N-1 ApplicationMerck Life Sciences
Participate in the interactive webinar now: http://bit.ly/SeedTrainPt2
The industry focus on process intensification is driving an increase in adoption of perfusion within the seed train. In an effort to deliver on the need for a robust solution we have developed a filter/controller duo that makes process intensification a reality!
Explore our webinar library: www.merckmillipore.com/webinars
Webinar: Novel Perfusion Filter and Controller for N-1 ApplicationMilliporeSigma
Participate in the interactive webinar now: http://bit.ly/SeedTrainPt2
The industry focus on process intensification is driving an increase in adoption of perfusion within the seed train. In an effort to deliver on the need for a robust solution we have developed a filter/controller duo that makes process intensification a reality!
Explore our webinar library: www.emdmillipore.com/webinars
The biopharmaceutical industry needs high-performance processing through the establishment of next-generation solutions to improve efficiency and effectiveness. The shift in the industry toward efficient monoclonal antibody (mAb) processing has necessitated the development of novel approaches.
In this webinar, you will learn:
• What benefits upstream process intensification brings to the manufactures addition to higher productivity
• Several scenarios with process modeling data to quantify financial benefits and value
• Perfused seed train process development data taken with our new Cellicon™ Solution and Cellvento® 4CHO-X expansion medium
Upstream process intensification can bring significant benefits to manufacturers in terms of smaller facilities, manufacturing flexibility, and reduction in footprint, with achieving significantly higher productivity. Several scenarios for Mab production become apparent with the implementation of perfusion-based operations, especially for the seed train. We will identify these scenarios with process modeling data to quantify their financial benefits and value. In addition, we will share perfused seed train process development data resulting from the use of our new Cellicon™ Solution and Cellvento® 4CHO-X expansion medium.
The biopharmaceutical industry needs high-performance processing through the establishment of next-generation solutions to improve efficiency and effectiveness. The shift in the industry toward efficient monoclonal antibody (mAb) processing has necessitated the development of novel approaches.
In this webinar, you will learn:
• What benefits upstream process intensification brings to the manufactures addition to higher productivity
• Several scenarios with process modeling data to quantify financial benefits and value
• Perfused seed train process development data taken with our new Cellicon™ Solution and Cellvento® 4CHO-X expansion medium
Upstream process intensification can bring significant benefits to manufacturers in terms of smaller facilities, manufacturing flexibility, and reduction in footprint, with achieving significantly higher productivity. Several scenarios for Mab production become apparent with the implementation of perfusion-based operations, especially for the seed train. We will identify these scenarios with process modeling data to quantify their financial benefits and value. In addition, we will share perfused seed train process development data resulting from the use of our new Cellicon™ Solution and Cellvento® 4CHO-X expansion medium.
Single-Use-Bioreactors-A-Comprehensive-Examination.
Single-use bioreactors (SUBs) have revolutionized biopharmaceutical production, offering advantages over traditional bioreactors.
Exploring Intensified Seed Train Through Advancements in Perfusion Processing...Merck Life Sciences
This poster explores key elements of bioreactor design and automation strategies that enable successful implementation of seed train intensification via perfusion:
- Sparger performance characterization
- Cell retention device connection
- Evaluation of the Hamiltion® Incyte viable cell density (or permittivity) sensor
- Cell culture case studies
To learn more about this topic or collaborate with our technical experts, schedule an in-person or remote visit at our M Lab™ Collaboration Centers: www.merckmillipore.com/mlab
Upstream Viral Safety – Protect your bioreactor with Virus FiltrationMilliporeSigma
This poster summarizes the performance of a filter specifically developed for virus removal from chemically defined cell culture media. The filter removes high levels of virus, mycoplasma and bacteria without impacting cell growth, antibody titer, or protein quality. The filter has robust performance over a broad range of conditions offering an effective, easy to implement solution for media treatment.
Developing a single use adenovirus-vectored vaccine process through public-pr...MilliporeSigma
This work highlights the importance of collaborations to accelerate vaccine process development and manufacturing under the constant pressure of emerging diseases and the growing need of global immunizations.
We are collaborating with the Jenner Institute of the University of Oxford to advance the development of a rapid, scalable and GMP compliant process for simian adenoviruses used as vector for vaccines such as Rabies and emerging threats like Zika and Ebola. This webinar will describe the transition from a labor and time intensive process development to one utilizing a maximum of disposable technologies such as single use bioreactors and filtration technologies, using the rabies vaccine as a first candidate. We will highlight the challenges and their corresponding solutions that in the end created a template that can be used for different types of adenoviral vectors-based vaccines manufacturing.
In this webinar, you will learn:
- The challenges of creating a rapid and scalable process for Adenovirus vector manufacturing.
- The solutions that overcame those challenges.
- How public-private collaborations can accelerate vaccine process development.
Developing a single use adenovirus-vectored vaccine process through public-pr...Merck Life Sciences
This work highlights the importance of collaborations to accelerate vaccine process development and manufacturing under the constant pressure of emerging diseases and the growing need of global immunizations.
We are collaborating with the Jenner Institute of the University of Oxford to advance the development of a rapid, scalable and GMP compliant process for simian adenoviruses used as vector for vaccines such as Rabies and emerging threats like Zika and Ebola. This webinar will describe the transition from a labor and time intensive process development to one utilizing a maximum of disposable technologies such as single use bioreactors and filtration technologies, using the rabies vaccine as a first candidate. We will highlight the challenges and their corresponding solutions that in the end created a template that can be used for different types of adenoviral vectors-based vaccines manufacturing.
In this webinar, you will learn:
- The challenges of creating a rapid and scalable process for Adenovirus vector manufacturing.
- The solutions that overcame those challenges.
- How public-private collaborations can accelerate vaccine process development.
Cellca is a leading provider of Cell Line Development Services allowing customers easy open access to a cost effective reliable technology platform consistently delivering well characterised stable research clones from DNA to Research Cell Bank (RCB) in 4 months with titres upwards of 3.0 g/L in an easily scalable fed batch process.
High Throughput Bioreactor Mimetic in Early and Late Stage Process DevelopmentKBI Biopharma
A presentation by KBI Scientist Shahid Rameez, Ph.D. at the American Chemical Society Annual Meeting– Biochemical Technology (BIOT) Division, New Orleans, LA
The Viscosity Reduction Platform: Viscosity-reducing excipients for improveme...Merck Life Sciences
Protein viscosity is a major challenge in preparing highly concentrated protein formulations suitable for subcutaneous injection. Recently, the Viscosity Reduction Platform (VRP) was introduced and its technical key features and benefits for formulations were discussed. However, highly viscous solutions do not only pose a challenge when administering a drug to a patient, they can also impose technical limitations in the manufacturing process.
This white paper evaluates the effect of the excipients in the Viscosity Reduction Platform on ultrafiltration processes used to produce a highly concentrated formulation of a monoclonal antibody (mAb). Two filtration methods are demonstrated in this work.
Find more information about the Viscosity Reduction Platform on our website: https://www.sigmaaldrich.com/products/pharma-and-biopharma-manufacturing/formulation/viscosity-reduction-platform
Use of Excipients in Downstream Processing to Improve Protein PurificationMerck Life Sciences
Excipients are used to improve the stability of protein-based therapeutics by protecting the protein against a range of stress conditions such as temperature changes, pH changes, or agitation. Similar stresses are applied to proteins during downstream purification. Shifts in pH during Protein A chromatography, subsequent incubations at low pH for virus inactivation, and changes in conductivity in ion exchange chromatography can lead to aggregation, fragmentation, or other chemical modifications of the therapeutic protein. Given the potential impact on the protein’s structural integrity, there is a need for approaches to reduce the risk presented by the conditions during downstream processing. For example, integration of a solution to prevent aggregation of proteins would be a more efficient strategy than implementing steps to remove multimeric forms.
This white paper highlights the results from a recent paper by Stange et. al., in which protein stabilizing excipients such as polyols, sugars, and polyethylene glycol (PEG4000) were used as buffer system additives. Effect of the excipients on elution patterns, stabilization of the monomer antibody, host-cell protein removal, virus inactivation rates and binding capacity of cation exchange chromatography were explored.
Exploring the protein stabilizing capability of surfactants against agitation...Merck Life Sciences
Agitation of therapeutic protein solutions during manufacturing, shipping and handling is one of the major initiators for protein aggregation and particle formation during the life history of a protein drug. Adsorption of protein molecules to liquid-air interfaces leads to the formation of highly concentrated protein surface films. The rupture of these protein films due to various mechanical processes can then result in the appearance of protein aggregates and particles in the bulk solution phase.
One technique to stabilize proteins against stress induced by liquid-air interfaces is the use of non-ionic surfactants. About 91% of antibody formulations commercially available in 2021 contained a surfactant. Polysorbate 20 and 80, composed of a hydrophilic polyoxyethylene sorbitan and hydrophobic fatty acid esters, made up the largest part being employed in 87% of said formulations.
Despite their frequent use in parenteral drug products, concerns have been raised for decades about the application of polysorbates as surfactants in biopharmaceutical formulations. Autoxidation of polysorbate, caused by residual peroxides in polysorbates, can damage the proteins and can further drive the oxidative degradation of polysorbate. Chemical and enzymatic hydrolysis of polysorbate may lead to the formation of free fatty acid particles, which may become visible; and both mechanisms eventually lead to the reduction in polysorbate concentration. Therefore, the purpose of the current study was to compare various molecules for their capabilities to reduced agitation-induced protein aggregation and particle formation; and furthermore, investigate their underlying protein stabilizing mechanisms.
The Viscosity Reduction Platform: Viscosity Reducing Excipients for Protein F...Merck Life Sciences
Protein viscosity is one of the major obstacles in preparing highly concentrated protein formulations suitable for subcutaneous injection.
This whitepaper examines how combining an amino acid with a second viscosity-reducing excipient circumvents adverse effects on protein stability and improves viscosity-reducing capacity.
To find more information about the Viscosity Reduction Platform, please visit our website: https://sigmaaldrich.com/products/pharma-and-biopharma-manufacturing/formulation/viscosity-reduction-platform
Characterization of monoclonal antibodies and Antibody drug conjugates by Sur...Merck Life Sciences
Watch the presentation of this webinar: https://bit.ly/3Pjpjvr
Highlights of this webinar:
- Surface plasmon resonance as a powerful tool for biologic characterization including mAbs and ADCs.
- SPR allows rapid binding analysis in real time without using labels for SARS-CoV-2 receptor binding domain mutations.
- Kinetic data is indicative of possible neutralizing activity allowed assessment of neutralizing ability of therapeutic monoclonal antibodies.
- The application can provide preliminarily efficacy information and facilitated mAbs/ACDs candidate selection process
Detailed description:
Characterization of therapeutic monoclonal antibodies (mAbs) or Antibody drug conjugates (ADCs) is challenging due to their ability to bind to a variety of proteins via their Fc and Fab domains, giving rise to diverse biological functions associated with each domain. The Fc domain of mAbs interacts with Fc receptors with varying affinities, which can influence biological processes such as Complement-dependent cytotoxicity (CDC) and Antibody-dependent cellular cytotoxicity (ADCC), transcytosis, phagocytosis, and/or serum half-life.
An important characteristic of an antibody is its Fc effector function. Antibodies can be engineered to obtain desired binding of the Fc region to Fc receptors expressed on effector cells. Hence, it is crucial to evaluate the binding interaction of mAbs/ADC with Fc receptors in the early phase of drug development to understand the potential biological activity of the product in vivo.
Surface Plasmon Resonance (SPR) is a powerful technique to establish binding kinetics in real-time, label free, and high sensitivity with low sample consumption. Along with target antigen binding, it is crucial to evaluate the binding interaction of antibodies and ADCs with Fc receptors. Our SPR case studies investigated the impact on binding kinetics of ADCs with different linkers and the binding interactions of SARS-CoV-2 spike protein variants and evaluated the neutralizing ability of therapeutic mAbs. SPR characterisation can be facilitated in all stages of the product life cycle to ensure the quality and safety of mAbs and ADCs.
The Role of BioPhorum Extractables Data in the Effective Adoption of Single-U...Merck Life Sciences
Regulatory expectation does require patient safety evaluations with supporting data for manufacturing components that directly come into contact with drug manufacturing process streams. Readily available extractables data can help manufacturers using singleuse technology to accelerate product qualifications, risk assessments and process optimization
This white paper guides you on how to save time and resources with supplier-provided single-use system extractables data and gives you an overview about the overall strategy for Extractables & Leachables. At the end you will find a case study.
Find more information about filters and single-use components on our website: https://www.sigmaaldrich.com/DE/en/services/product-services/emprove-program/emprove-filter-and-single-use-component-portfolio
Watch the recording of this presentation here: https://bit.ly/3zTOpe4
Detailed description:
SARS-CoV-2 showed us that technology supports us during our inspection activity even if on-site visits are not possible. Travel restrictions of various kinds will remain a risk in the future. The use of new technologies has shown that inspections and audits can be carried out despite these restrictions. We will focus on what possibilities the new technologies offer and take a look at the future of inspections and audits.
In this webinar, you will learn:
• Regulatory overview of remote audits
• The technologies needed to support the audit process
• What types of inspections are possible with the use of these technologies
• How audits may look in the future
Presented by:
Daniel Buescher, Product Manager - Digital Solutions
Moving your Gene Therapy from R&D to IND: How to navigate the Regulatory Land...Merck Life Sciences
Watch the recording of this presentation here: https://bit.ly/3SqOsoP
Novel therapies, including cell and gene therapies, continue to be central to innovation in healthcare and represent the fastest growing area of therapeutic medicine. As a consequence, the number of gene therapies undergoing clinical trials has increased significantly in the last five years.
Manufacturing processes for these novel therapeutics are very complex with a high risk of contamination. Regulatory agencies world-wide have responded by issuing guidance to outline their expectations for development and manufacture of cell and gene therapies. Currently, regulatory guidance is not harmonized globally and can often lead to confusion within industry and increased risk of non-compliance.
In this webinar, we'll answer:
• Which regulatory guidelines do you need to comply for your INDs?
• When do you start implementing GMPs and validated assays?
• How do you get your QC testing strategy ‘right the first time’?
• How do you ensure testing is not your rate limiting step for the IND submission?
Presented by:
Manjula Aysola, Senior Regulatory Consultant
Dr. Alison Armstrong, Sr. Director, Technical and Scientific Solutions
Identity testing by NGS as a means of risk mitigation for viral gene therapiesMerck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3RijkHC
Detailed description:
Imagine you’ve just completed a manufacturing run for your viral vector. Identity testing is performed to confirm the vector sequence. But when the results come back the data reveals unexpected sequence variants! With an appropriate risk mitigation testing strategy, this situation can be prevented.
The situation described above is not hypothetical, and happens more that you think, costing valuable time and resources.
Investigatory testing has shown that sequence variants present in starting materials (e.g. plasmids) are likely to make their way to the final product. Adequate identification of low-level variants with an appropriately sensitive method is critical in ensuring the quality of the final product. A risk-based testing strategy, in the context of identity, for viral vector manufacturing will be presented, focusing on key testing points. NGS assays for identity and variant detection will be highlighted due to their extremely sensitive nature compared to traditional approaches.
In this webinar, we'll explore:
• Regulatory requirements for identity testing
• NGS applications for identity testing as compared to traditional methods
• A case study on the impact of not establishing a proper risk-based testing strategy
Presented by: Bradley Hasson, Director of Lab Operations for NGS Services
Latest advancements of melt based 3D printing technologies for oral drug deli...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3A2WcH4
The application of polymer excipients in 3D printing manufacturing is usually limited due to the concerns of filament strength, high processing temperature and large scale manufacturing.
Latest technology developments are targeting a direct melt deposition to simplify the process and enable a constant and efficient process. Two different processing approaches will be presented:
The advanced melt drop deposition, where individual three dimensional geometries can be created by depostition of polymer droplets and the MED® 3D printing technology which allows by precise layer-by-layer deposition to produce objects with well-designed geometric structures.
In this webinar, you will learn:
• Latest advancements of melt based 3D printing approaches
• Application examples for the individual technologies
• Deep dive in the MED® 3D printing technology to design dedicated drug release profiles
Presented by:
Dr. Thomas Kipping, Head of Drug Carriers
Dr. Xianghao Zuo, Deputy Director of R&D, Triastek
CAR-T Manufacturing Innovations that Work - Automating Low Volume Processes a...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3NDNIKe
Automated, fit-for-purpose tools are essential in CAR-T processing to support sustainable manufacturing of clinical and market-approved cell therapy products. This webinar will discuss how the ekko™ Acoustic Cell Processing System uses acoustic technology as a touchless approach to manipulate cells, enabling a modular tool across the CAR-T manufacturing workflow. Typical performance of templated ekko™ System processes for DMSO washout of leukapheresis material, low volume and high cell concentrate for electroporation preparation, and harvest of expanded T cells will be reviewed.
This webinar will also give an early glimpse at the ekko™ Select System for unmatched T cell selection.
In this webinar, you will:
• Uncover how the ekko™ System supports the broad industrialization of cell therapy, with particular focus on how to achieve low volume, high concentrate cell product for critical transduction and transfection steps
• Discover how ekko™ System for wash and concentrate processes throughout the cell therapy workflow achieve high cell recovery, viability, and effective residual removal
• Preview to ekko™ Select, our cell therapy selection platform, to achieve unmatched ease-of-use with direct processing from leukopaks reducing the need for preparation steps
Presented by:
Benjamin Ross-Johnsrud, Acoustic Technology Expert
Robert Scott, Mechanical Engineer III
Viral safety of biologics: What's changing with the ICH Q5A revision?Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3t7X9tg
How does the ICH Q5A revision impact viral safety strategies for biologics?
Biologics continue to grow at a fast pace. Manufactured using cell lines of human or animal origin, these are at risk of viral contamination making safety strategies critical. A comprehensive risk mitigation strategy using multiple orthogonal measures is a regulatory expectation. ICH Q5A, the globally-harmonized guideline outlines the expectations. ICH Q5A is currently being revised to address recent scientific advancements including novel therapeutic modalities, new manufacturing paradigms, updates in viral clearance applications, and alternate detection technologies. We’ll discuss the expected changes and potential impact on viral safety strategies with case studies and examples.
In this webinar, you will learn about:
• The Importance of virus testing in biologics products
• Regulatory landscape, expectations for the Q5A revision
• What's new and changing
• Examples of alternate testing schedules, impact on viral clearance
Presented by:
Manjula Aysola, Senior Regulatory Consultant
Alison Armstrong, PhD, Sr. Director, Technical and Scientific Solutions
Improve Operational Efficiency by Over 30% with Product, Process, & Systems A...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3adaxWh
When implementing new automation systems, organizations must consider things like deployment time, user adoption, and costs.
They must also consider the cost of doing nothing – that is, what competitive advantage is lost in standing still? What time and quality is lost in repetitive, manual tasks rather than an automated, digital workflow? What operational efficiencies are lost?
In this webinar we examine how a product, process, and system agnostic automation platform can be deployed faster than traditional system specific software while bringing greater operational efficiencies (in many cases over 30% improvement).
To remain competitive in the market, biopharma manufacturers must adopt automation and digital technologies, but most plants still have island of automation consisting of independently functioning, standalone unit operations. This results in operational inefficiency, regulatory concerns, and a poor understanding of the process and product life cycle.
Taking the first, right step must include considering risks, costs, timelines, and technology alternatives. Traditional automation approaches tied to specific systems, processes, and products are, by their nature, limited; while an agnostic platform will address current biomanufacturing business challenges and ensure future readiness. With the right platform, a phased automation implementation can yield operational efficiency gains of up to 30% and improved product quality and regulatory compliance.
In this webinar, let's explore:
• Challenges of automation and digital technology adoption
• What a product, process, and system agnostic platform entails
• Applications and benefits of a process orchestration platform
• Ensuring future readiness with process orchestration
Presented by:
Braj Nandan Thakur, Global Product Manager - Automation
Insights from a Global Collaboration Accelerating Vaccine Development with an...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3Nbb5ug
Get insights and best practices from a multinational team establishing a platform for vaccine production. See how a long-term collaboration on a bench-scale process used to produce a Virus Like Particle (VLP) vaccine for SARS-CoV-2 was successfully converted to a robust GMP-compatible, scalable process.
The COVID-19 pandemic further emphasized the need for collaboration in the development of urgently needed vaccines and therapeutics. In this webinar, we take you behind the scenes of our collaboration with Technovax and Innovative Biotech in which a scalable VLP vaccine platform was optimized for use in a production facility in Nigeria in response to the need for local production of SARS-CoV-2 vaccines. The flexibility and robustness of the platform will enable its rapid deployment to support the West African pandemic readiness program. Initial development of the VLP process began in late 2019 and by March 2020, was already adapted for production of a SARS-CoV-2 vaccine.
In this webinar, you will learn:
• About building a priceless collaborative network with integrated solutions
• Virus-Like Particle Vaccines
• Process Development Overview and Challenges
• Pre-clinical Results and Next Steps
Presented by:
Jose M. Galarza, PhD,
President and Founder of TechnoVax
Naomi Baer,
Business development consultant, Emerging Biotech, BioProcess division
Youssef Gaabouri, Eng. ,
Associate Director, Head of Sales Middle East & Africa, BioProcess division
Risk-Based Qualification of X-Ray Sterilization for Single-Use SystemsMerck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3vQf0qv
In the single-use bioprocess industry, X-ray irradiation warrants consideration as an alternate sterilization technology. Using a risk-based qualification testing strategy is important when evaluating and implementing equivalent ionizing irradiation sterilization methods.
The urgent need for life-saving therapies as a result of the global pandemic has reinforced the criticality of flexibility in pharmaceutical manufacturing, including sterilization. The single-use bioprocess industry traditionally has employed gamma irradiation sterilization. X-ray irradiation is being considered as an additional sterilization technology for business and supply continuity. We will share a risk-based qualification testing strategy including Extractables and data generated to support comparability of gamma irradiation and X-ray irradiation as equivalent ionizing irradiation sterilization methods.
In this webinar, you will learn about:
• The comparison of gamma and X-ray irradiation sterilization
• A risk-based qualification test strategy
• Data evaluation of gamma versus X-ray sterilized single-use components
Presented by:
Monica Cardona,
Global Senior Program Manager
Paul Killian, Ph.D.,
R&D Director, Analytical Technologies
Rapid replication competent adenovirus (rRCA) detection: Accelerate your lot ...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3MJ4u9V
Testing for presence of replication competent adenovirus (RCA) is a key component to ensure patient safety and a requirement for all biologicals manufactured using adenoviral vectors. For many adenoviral-based products, the RCA assay is a rate-limiting assay for lot release.
Join this webinar to learn about a rapid RCA detection assay currently in development, which combines a 7-day culture assay with a highly sensitive molecular endpoint specific for RCA. The method can detect presence of as little as 1 RCA in adenoviral vector material at an approximate concentration of 5x107 - 2x108 vector particles (VP)/mL, making it a suitable method to meet regulatory requirements while accelerating your lot release timelines.
In this webinar, you will learn about:
• Regulatory framework for adenoviral vector products
• Considerations for lot release testing of adenoviral-based therapies
• Advantages of a rapid method for RCA testing on production lot material
Presented by:
Axel Fun, Ph.D.,
Principal Scientist
Alberto Santana, MBA,
Product Manager, Biologics Biosafety Testing
The High Intensity Sweeteners Neotame and Sucralose: 2 Ways to ace the Patien...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3vQyN7K
Bitter medicines are an important issue, especially for pediatric applications. As several APIs have bitter tasting components, high intensity sweeteners for taste optimization are of great interest. Join our webinar to discover our new sweetener toolbox enabling safe and stable formulations.
Mask bitter aftertaste for a sweeter pill to swallow! Patients’ compliance and the therapeutic benefit are supported by a pleasant taste of pharmaceutical formulations. With the high intensity sweeteners Neotame and Sucralose, you have efficient tools at hand which are superior to other sweeteners in many aspects:
• excellent sugar-like taste profile
• outstanding sweetness factors
• use effectiveness
• enhanced stability
We will present our new toolbox of two high performance sweeteners and focus on aspects of stability, safety, the application in various dosage forms, and market perception.
In this webinar, you will learn:
• How to optimize the patients' taste experience of your pharmaceuticals
• How sweeteners can be differentiated by their sensory profiles and features
• How our new product offering Neotame can be effectively used in your targeted formulations
Presented by:
Almut von der Brelie,
Senior Manager Strategic Marketing
Excipients for Solid Applications
The Developability Classification System (DCS): Enabling an Optimized Approac...Merck Life Sciences
This whitepaper by Dr. Daniel Joseph Price outlines how poorly soluble drug formulations can be designed using the developability classification system (DCS).
The DCS identifies the root cause of low solubility and enables lean, cost-effective and effective formulations to be developed.
#solubility #pharmaceuticalmanufacturing #oralsoliddosage #drugdevelopment
In this webinar, you will learn about:
The advantages of using advanced intermediates to develop ADC therapies
How to increase ADC solubility and efficiency
Fast, small-scale ADC library generation
Seamless supply chain with reduced complexity and regulatory support
The ADCore product line offers versatile intermediates that simplify the synthesis of common ADC payloads (dolastatins, maytansinoids, and PBDs) by greatly reducing the number of synthetic steps. This translates to savings in development and manufacturing costs and shorter timelines to the clinic. To address the poor solubility of many ADC payloads, ChetoSensar™ was developed to significantly increase the hydrophilicity of the drug linker, which has been shown to also substantially increase the efficacy of ADCs and broaden the therapeutic window.
Lastly, the ADC Express™ service leverages conjugation chemistry and analytical expertise to help design and quickly synthesize sets of potential ADC therapies suitable for screening to simplify candidate selection and get ADC therapies to market faster.
R3 Stem Cells and Kidney Repair A New Horizon in Nephrology.pptxR3 Stem Cell
R3 Stem Cells and Kidney Repair: A New Horizon in Nephrology" explores groundbreaking advancements in the use of R3 stem cells for kidney disease treatment. This insightful piece delves into the potential of these cells to regenerate damaged kidney tissue, offering new hope for patients and reshaping the future of nephrology.
The Importance of Community Nursing Care.pdfAD Healthcare
NDIS and Community 24/7 Nursing Care is a specific type of support that may be provided under the NDIS for individuals with complex medical needs who require ongoing nursing care in a community setting, such as their home or a supported accommodation facility.
Navigating Challenges: Mental Health, Legislation, and the Prison System in B...Guillermo Rivera
This conference will delve into the intricate intersections between mental health, legal frameworks, and the prison system in Bolivia. It aims to provide a comprehensive overview of the current challenges faced by mental health professionals working within the legislative and correctional landscapes. Topics of discussion will include the prevalence and impact of mental health issues among the incarcerated population, the effectiveness of existing mental health policies and legislation, and potential reforms to enhance the mental health support system within prisons.
CHAPTER 1 SEMESTER V - ROLE OF PEADIATRIC NURSE.pdfSachin Sharma
Pediatric nurses play a vital role in the health and well-being of children. Their responsibilities are wide-ranging, and their objectives can be categorized into several key areas:
1. Direct Patient Care:
Objective: Provide comprehensive and compassionate care to infants, children, and adolescents in various healthcare settings (hospitals, clinics, etc.).
This includes tasks like:
Monitoring vital signs and physical condition.
Administering medications and treatments.
Performing procedures as directed by doctors.
Assisting with daily living activities (bathing, feeding).
Providing emotional support and pain management.
2. Health Promotion and Education:
Objective: Promote healthy behaviors and educate children, families, and communities about preventive healthcare.
This includes tasks like:
Administering vaccinations.
Providing education on nutrition, hygiene, and development.
Offering breastfeeding and childbirth support.
Counseling families on safety and injury prevention.
3. Collaboration and Advocacy:
Objective: Collaborate effectively with doctors, social workers, therapists, and other healthcare professionals to ensure coordinated care for children.
Objective: Advocate for the rights and best interests of their patients, especially when children cannot speak for themselves.
This includes tasks like:
Communicating effectively with healthcare teams.
Identifying and addressing potential risks to child welfare.
Educating families about their child's condition and treatment options.
4. Professional Development and Research:
Objective: Stay up-to-date on the latest advancements in pediatric healthcare through continuing education and research.
Objective: Contribute to improving the quality of care for children by participating in research initiatives.
This includes tasks like:
Attending workshops and conferences on pediatric nursing.
Participating in clinical trials related to child health.
Implementing evidence-based practices into their daily routines.
By fulfilling these objectives, pediatric nurses play a crucial role in ensuring the optimal health and well-being of children throughout all stages of their development.
Global launch of the Healthy Ageing and Prevention Index 2nd wave – alongside...ILC- UK
The Healthy Ageing and Prevention Index is an online tool created by ILC that ranks countries on six metrics including, life span, health span, work span, income, environmental performance, and happiness. The Index helps us understand how well countries have adapted to longevity and inform decision makers on what must be done to maximise the economic benefits that comes with living well for longer.
Alongside the 77th World Health Assembly in Geneva on 28 May 2024, we launched the second version of our Index, allowing us to track progress and give new insights into what needs to be done to keep populations healthier for longer.
The speakers included:
Professor Orazio Schillaci, Minister of Health, Italy
Dr Hans Groth, Chairman of the Board, World Demographic & Ageing Forum
Professor Ilona Kickbusch, Founder and Chair, Global Health Centre, Geneva Graduate Institute and co-chair, World Health Summit Council
Dr Natasha Azzopardi Muscat, Director, Country Health Policies and Systems Division, World Health Organisation EURO
Dr Marta Lomazzi, Executive Manager, World Federation of Public Health Associations
Dr Shyam Bishen, Head, Centre for Health and Healthcare and Member of the Executive Committee, World Economic Forum
Dr Karin Tegmark Wisell, Director General, Public Health Agency of Sweden
Antibiotic Stewardship by Anushri Srivastava.pptxAnushriSrivastav
Stewardship is the act of taking good care of something.
Antimicrobial stewardship is a coordinated program that promotes the appropriate use of antimicrobials (including antibiotics), improves patient outcomes, reduces microbial resistance, and decreases the spread of infections caused by multidrug-resistant organisms.
WHO launched the Global Antimicrobial Resistance and Use Surveillance System (GLASS) in 2015 to fill knowledge gaps and inform strategies at all levels.
ACCORDING TO apic.org,
Antimicrobial stewardship is a coordinated program that promotes the appropriate use of antimicrobials (including antibiotics), improves patient outcomes, reduces microbial resistance, and decreases the spread of infections caused by multidrug-resistant organisms.
ACCORDING TO pewtrusts.org,
Antibiotic stewardship refers to efforts in doctors’ offices, hospitals, long term care facilities, and other health care settings to ensure that antibiotics are used only when necessary and appropriate
According to WHO,
Antimicrobial stewardship is a systematic approach to educate and support health care professionals to follow evidence-based guidelines for prescribing and administering antimicrobials
In 1996, John McGowan and Dale Gerding first applied the term antimicrobial stewardship, where they suggested a causal association between antimicrobial agent use and resistance. They also focused on the urgency of large-scale controlled trials of antimicrobial-use regulation employing sophisticated epidemiologic methods, molecular typing, and precise resistance mechanism analysis.
Antimicrobial Stewardship(AMS) refers to the optimal selection, dosing, and duration of antimicrobial treatment resulting in the best clinical outcome with minimal side effects to the patients and minimal impact on subsequent resistance.
According to the 2019 report, in the US, more than 2.8 million antibiotic-resistant infections occur each year, and more than 35000 people die. In addition to this, it also mentioned that 223,900 cases of Clostridoides difficile occurred in 2017, of which 12800 people died. The report did not include viruses or parasites
VISION
Being proactive
Supporting optimal animal and human health
Exploring ways to reduce overall use of antimicrobials
Using the drugs that prevent and treat disease by killing microscopic organisms in a responsible way
GOAL
to prevent the generation and spread of antimicrobial resistance (AMR). Doing so will preserve the effectiveness of these drugs in animals and humans for years to come.
being to preserve human and animal health and the effectiveness of antimicrobial medications.
to implement a multidisciplinary approach in assembling a stewardship team to include an infectious disease physician, a clinical pharmacist with infectious diseases training, infection preventionist, and a close collaboration with the staff in the clinical microbiology laboratory
to prevent antimicrobial overuse, misuse and abuse.
to minimize the developme
Explore our infographic on 'Essential Metrics for Palliative Care Management' which highlights key performance indicators crucial for enhancing the quality and efficiency of palliative care services.
This visual guide breaks down important metrics across four categories: Patient-Centered Metrics, Care Efficiency Metrics, Quality of Life Metrics, and Staff Metrics. Each section is designed to help healthcare professionals monitor and improve care delivery for patients facing serious illnesses. Understand how to implement these metrics in your palliative care practices for better outcomes and higher satisfaction levels.
India Clinical Trials Market: Industry Size and Growth Trends [2030] Analyzed...Kumar Satyam
According to TechSci Research report, "India Clinical Trials Market- By Region, Competition, Forecast & Opportunities, 2030F," the India Clinical Trials Market was valued at USD 2.05 billion in 2024 and is projected to grow at a compound annual growth rate (CAGR) of 8.64% through 2030. The market is driven by a variety of factors, making India an attractive destination for pharmaceutical companies and researchers. India's vast and diverse patient population, cost-effective operational environment, and a large pool of skilled medical professionals contribute significantly to the market's growth. Additionally, increasing government support in streamlining regulations and the growing prevalence of lifestyle diseases further propel the clinical trials market.
Growing Prevalence of Lifestyle Diseases
The rising incidence of lifestyle diseases such as diabetes, cardiovascular diseases, and cancer is a major trend driving the clinical trials market in India. These conditions necessitate the development and testing of new treatment methods, creating a robust demand for clinical trials. The increasing burden of these diseases highlights the need for innovative therapies and underscores the importance of India as a key player in global clinical research.
Defecation
Normal defecation begins with movement in the left colon, moving stool toward the anus. When stool reaches the rectum, the distention causes relaxation of the internal sphincter and an awareness of the need to defecate. At the time of defecation, the external sphincter relaxes, and abdominal muscles contract, increasing intrarectal pressure and forcing the stool out
The Valsalva maneuver exerts pressure to expel faeces through a voluntary contraction of the abdominal muscles while maintaining forced expiration against a closed airway. Patients with cardiovascular disease, glaucoma, increased intracranial pressure, or a new surgical wound are at greater risk for cardiac dysrhythmias and elevated blood pressure with the Valsalva maneuver and need to avoid straining to pass the stool.
Normal defecation is painless, resulting in passage of soft, formed stool
CONSTIPATION
Constipation is a symptom, not a disease. Improper diet, reduced fluid intake, lack of exercise, and certain medications can cause constipation. For example, patients receiving opiates for pain after surgery often require a stool softener or laxative to prevent constipation. The signs of constipation include infrequent bowel movements (less than every 3 days), difficulty passing stools, excessive straining, inability to defecate at will, and hard feaces
IMPACTION
Fecal impaction results from unrelieved constipation. It is a collection of hardened feces wedged in the rectum that a person cannot expel. In cases of severe impaction the mass extends up into the sigmoid colon.
DIARRHEA
Diarrhea is an increase in the number of stools and the passage of liquid, unformed feces. It is associated with disorders affecting digestion, absorption, and secretion in the GI tract. Intestinal contents pass through the small and large intestine too quickly to allow for the usual absorption of fluid and nutrients. Irritation within the colon results in increased mucus secretion. As a result, feces become watery, and the patient is unable to control the urge to defecate. Normally an anal bag is safe and effective in long-term treatment of patients with fecal incontinence at home, in hospice, or in the hospital. Fecal incontinence is expensive and a potentially dangerous condition in terms of contamination and risk of skin ulceration
HEMORRHOIDS
Hemorrhoids are dilated, engorged veins in the lining of the rectum. They are either external or internal.
FLATULENCE
As gas accumulates in the lumen of the intestines, the bowel wall stretches and distends (flatulence). It is a common cause of abdominal fullness, pain, and cramping. Normally intestinal gas escapes through the mouth (belching) or the anus (passing of flatus)
FECAL INCONTINENCE
Fecal incontinence is the inability to control passage of feces and gas from the anus. Incontinence harms a patient’s body image
PREPARATION AND GIVING OF LAXATIVESACCORDING TO POTTER AND PERRY,
An enema is the instillation of a solution into the rectum and sig
Empowering ACOs: Leveraging Quality Management Tools for MIPS and BeyondHealth Catalyst
Join us as we delve into the crucial realm of quality reporting for MSSP (Medicare Shared Savings Program) Accountable Care Organizations (ACOs).
In this session, we will explore how a robust quality management solution can empower your organization to meet regulatory requirements and improve processes for MIPS reporting and internal quality programs. Learn how our MeasureAble application enables compliance and fosters continuous improvement.
Deep Leg Vein Thrombosis (DVT): Meaning, Causes, Symptoms, Treatment, and Mor...The Lifesciences Magazine
Deep Leg Vein Thrombosis occurs when a blood clot forms in one or more of the deep veins in the legs. These clots can impede blood flow, leading to severe complications.
Deep Leg Vein Thrombosis (DVT): Meaning, Causes, Symptoms, Treatment, and Mor...
Developing a Scalable Upstream Bioreactor Process for Lentiviral Vector Production in Suspension
1. Eva Fong
February 25, 2021
Developing a scalable
upstream bioreactor
process for lentiviral
vector production in
suspension
2. 2
The life science business of
Merck KGaA, Darmstadt, Germany
operates as MilliporeSigma
in the U.S. and Canada.
Developing a Scalable Upstream Bioreactor Process for Lentiviral Vector Production in Suspension
3. 3
Agenda
Scale-up development of a suspension-based lentivirus
production process
The benefit of having a template manufacturing process
1
2
3
Designing a process that is manufacturing-friendly and supports
commercialization
The Importance of Scale in Viral Vector Manufacturing| 01.10.2020
Developing a Scalable Upstream Bioreactor Process for Lentiviral Vector Production in Suspension
5. in vivo and ex vivo Viral Gene Therapy
5
Gene Modified Cell
Therapy
Gene Delivery
Therapy
Oncolytic Virus
Therapy
Immunotherapy
Viral Gene Therapy
Gene Therapy
(broad definition)
Gene Therapy
(narrow definition)
e.g. AAV (in vivo)
e.g. Lentivirus
(ex vivo)
HSC
CAR-T, TCR-T
Developing a Scalable Upstream Bioreactor Process for Lentiviral Vector Production in Suspension
6. VirusExpress™ Lentiviral Production Platform
Key challenges in lentiviral production
6
Scale-out limitations
Serum-containing medium
Highly labor intensive
Open process
True scale-up
Chemically defined medium
Reduced labor
More closed process
Developing a Scalable Upstream Bioreactor Process for Lentiviral Vector Production in Suspension
7. VirusExpress Lentiviral Production Platform
1
2
3
EX-CELL® CD HEK293 Viral Vector
Medium
Chemically defined media for PEI transfection and
vector production.
VirusExpress 293T Lentiviral
Production Cells
293T clone optimized for suspension growth and
PEI based transient LV production. Growth and
virus production demonstrated in bioreactors up
to 40 L scale.
Lentiviral Production Process
Demonstrated scalable process from flasks to
50L.
7 Developing a Scalable Upstream Bioreactor Process for Lentiviral Vector Production in Suspension
8. Bench Scale Bioreactor Process Development
Experimental Approach
8
Phase 1 – Develop parameters for cell growth
Phase 2 – Develop parameters for virus production
Design of Experiment
Design
Data
Analysis
Execute
Defined process parameters
- pH, DO & Sparger Type and Agitation Rate
Understand process performance
3 L Mobius®
50L Mobius®
Proceed to scale-up development
Developing a Scalable Upstream Bioreactor Process for Lentiviral Vector Production in Suspension
9. Scaling – Geometric Similarity
Mobius® Single-use Bioreactor Family
9 Developing a Scalable Upstream Bioreactor Process for Lentiviral Vector Production in Suspension
Ratio
Working Volume : Total Volume 0.8 0.8 0.8 0.8 0.8
Impeller Diameter : Vessel Diam. 0.6 0.3 0.3 0.3 0.3
Vessel Height : Vessel Diameter 1.8:1 2.0:1 2.0:1 2.0:1 2.0:1
Liquid Height : Vessel Diameter 1.4:1 1.7:1 1.6:1 1.6:1 1.6:1
Dual sparger (open pipe/ micro) YES YES YES YES YES
Min – Max Working Volume (L) 1 – 2.4 10 – 50 40 – 200 200 - 1000 400 – 2000
2000 L
1000 L
200 L
50 L
3 L
H
D
Dimp
10. VirusExpress Lentiviral Production Platform
Bioreactor Scale-up Challenges
Many factors influence optimal cell growth, viability and viral vector production
• Mass transfer of gasses (kLa, vvm) Sufficient O2/Air delivery
• Mixing efficiency (Re) A higher Reynold’s number is an indication of turbulent flow
• Tip Speed (m/s) Influences mixing time and shear stress to cells
• Power per unit volume (P/V)* Influences mixing; based on impeller design and fluid density
* Common approach for bioreactor scale up includes determining an agitation rate that delivers equivalent energy dissipation rate or power
per unit volume (W/m3). Agitation rates for both growth and lentivirus production studies were determined using the power per unit volume
equation where (Po/V) = ρ*(N/60)^3*D^5*Np*Ni/V. The impeller design, fluid density, and agitation rate are considered in the equation.
10 Developing a Scalable Upstream Bioreactor Process for Lentiviral Vector Production in Suspension
11. Inoculate 50L
bioreactor for
N-1
Day
0
Volume-up to
N-stage
production
volume
Day
3
Transfection
Day
4
Monitor &
Sample
Day
5
Harvest
Day
6
Growth Lentivirus Production
Transfection
Our scale-up approach
Maintain the same power per unit volume
Linear scale-up of gasses
Linear scaling of transfection parameters (transfection cocktail to culture volume)
Utilize the same production vessel for cell expansion (N-1) and for production (N-stage)
Mimic the two phase approach utilized at bench scale; Phase 1 – optimize for cell growth, Phase 2 – optimize
for virus production
VirusExpress Lentiviral Production Platform
50 L Mobius Bioreactor LV Production Process Flow
11 Developing a Scalable Upstream Bioreactor Process for Lentiviral Vector Production in Suspension
12. Inoculate
50L
bioreactor
for N-1
D0
Volume-up to
N-stage
production
volume
D3 Monitor
D4-7
40
50
60
70
80
90
100
0
5
10
15
20
25
0.00 1.00 2.00 3.00 4.00 5.00 6.00 7.00 8.00
Viability
(%)
Viable
Cell
Density
(E6
cells/mL)
Culture Duration (Days)
50L BRX 500mL SF: N-1 stage Ctrl A 500mL SF: N-stage Ctrl A 500mL SF: N-1 stage Ctrl B 500mL SF: N-stage Ctrl B
Volume Up
• Cell growth at N-1 stage was able to achieve target VCD for transfection
• Peak VCD achieved on D7 was ~ 17x10^6 vc/mL
VirusExpress Lentiviral Production Platform
Scale-up Phase 1: Growth Optimization
12 Developing a Scalable Upstream Bioreactor Process for Lentiviral Vector Production in Suspension
13. ▪ Consistent growth profiles and achieved target cell density at time of transfection
▪ Target titer of ≥ 1e+07 TU/mL achieved for our confirmation runs
▪ Cell viabilities remained relatively high at time of harvest, ≥ 85%
VirusExpress Lentiviral Production Platform
Scale-up Phase 2: Virus Production
13 Developing a Scalable Upstream Bioreactor Process for Lentiviral Vector Production in Suspension
15. Developing Processes for Manufacturability
Manufacturing Considerations
15
Define Program Objectives
Target product profile (TPP)
Quality TPP
Planning for clinical & commercial supply
1
Development of Product
Design a process to meet quality requirements
Scalable
Robust
Efficiency
2
Developing a Scalable Upstream Bioreactor Process for Lentiviral Vector Production in Suspension
Continuous Improvement
Implementing changes with more process knowledge
3
16. Scalability
Developing Processes for Manufacturability
16 Developing a Scalable Upstream Bioreactor Process for Lentiviral Vector Production in Suspension
Ratio
Working Volume : Total Volume 0.8 0.8 0.8 0.8 0.8
Impeller Diameter : Vessel Diam. 0.6 0.3 0.3 0.3 0.3
Vessel Height : Vessel Diameter 1.8:1 2.0:1 2.0:1 2.0:1 2.0:1
Liquid Height : Vessel Diameter 1.4:1 1.7:1 1.6:1 1.6:1 1.6:1
Dual sparger (open pipe/ micro) YES YES YES YES YES
Min – Max Working Volume (L) 1 – 2.4 10 – 50 40 – 200 200 - 1000 400 – 2000
2000 L
1000 L
200 L
50 L
3 L
H
D
Dimp
17. Consistent process inputs and controls to ensure consistent product
Inputs
• VirusExpress HEK293T cells
• Chemically Defined Medium
• Transfection reagent
• Plasmids
• Consumables (Mobius Flexware)
Equipment
• Process parameter control
(Mobius Bioreactor
Control System)
• Automation
Outputs
• Quality Target Product
Profile
• Consistent quantity
Robustness
Developing Processes for Manufacturability
17 Developing a Scalable Upstream Bioreactor Process for Lentiviral Vector Production in Suspension
18. $0
$20,000
$40,000
$60,000
$80,000
$100,000
$120,000
T flask Mobius Bioreactor
50 L Lentivirus run
Labor Overhead Consumables + depreciation
Simplified operation
and a 57% cost
savings when using
suspension culture in a
Mobius bioreactor
Efficiency
Developing Processes for Manufacturability
18 Developing a Scalable Upstream Bioreactor Process for Lentiviral Vector Production in Suspension
20. The Benefits of Scalable Template Processes
Speed to Patient & Reliability
20 Developing a Scalable Upstream Bioreactor Process for Lentiviral Vector Production in Suspension