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
Production and purification of Viral vectors for gene and cell therapy appli...Dr. Priyabrata Pattnaik
The cell and gene therapy market is growing rapidly and is projected to reach $10 billion in 5 years. There are three main segments: gene therapy, stem cell therapy, and cell immunotherapy. Gene therapy uses viral vectors like lentivirus or adenovirus to deliver nucleic acids. The production of viral vectors like AAV involves growing HEK 293 cells in bioreactors, transfecting them with plasmids, harvesting and purifying the virus through clarification, filtration, and chromatography. CAR-T cell therapy is also discussed as an example of cell immunotherapy, which uses lentivirus to modify patient T-cells that are then reintroduced to the patient.
An Integrated Approach to Ensure Viral Vector and Gene Therapy Commercial Rea...MilliporeSigma
This document discusses an integrated approach to ensuring viral vector and gene therapy commercial readiness. It covers four main topics: 1) the current state and future perspectives of viral vectors, 2) scalability and reproducibility in viral vector manufacturing, 3) testing and quality considerations, and 4) regulatory approval and commercial readiness. The current demand for clinical and commercial doses of viral vectors is increasing. Ensuring scalable, reproducible manufacturing processes and comprehensive testing and quality measures is critical for regulatory approval and commercialization.
Viral Risk Mitigation Strategies: Key Considerations in the Prevention and De...Merck Life Sciences
This document discusses strategies for preventing and detecting viral contamination in biologic manufacturing processes. It outlines sources of viral contamination including raw materials, facilities, and personnel. A multi-tiered approach is recommended involving screening raw materials and cell banks, in-process testing, and confirming downstream processes can clear viruses. Detection methods like in vitro and in vivo assays have limitations and next generation sequencing is presented as a powerful new tool to detect unknown viruses. Upstream prevention focuses on raw material control through pretreatment or virus-resistant cell lines while downstream processes aim to clear any contamination through viral inactivation or filtration steps. A holistic biosafety strategy applying prevention, detection, and removal approaches at all stages is emphasized.
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
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.
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
Tech transfer and Scale-up - Tips and tricks from a Biodevelopment centerMilliporeSigma
Technology transfer could be considered as the corner stone of biodevelopment activities, as it is required each time people want to switch from a lab or a facility to another. It is expected to be handled in a methodical manner, following regulatory requirements, in order to ensure patients safety. Difficulties often come from differences between sending and receiving entities, where equipment, level of resources, internal culture, can be different. In case of failure, the cost can be huge for a drug maker.
This presentation will cover points to consider for successful tech transfers, and includes lessons learned from real cases.
In this webinar, you will learn:
● How to design a bioreactor model in order to scale up a process.
● How to build a team and tech transfer a process.
● How to accurately assess the success of a tech transfer.
Production and purification of Viral vectors for gene and cell therapy appli...Dr. Priyabrata Pattnaik
The cell and gene therapy market is growing rapidly and is projected to reach $10 billion in 5 years. There are three main segments: gene therapy, stem cell therapy, and cell immunotherapy. Gene therapy uses viral vectors like lentivirus or adenovirus to deliver nucleic acids. The production of viral vectors like AAV involves growing HEK 293 cells in bioreactors, transfecting them with plasmids, harvesting and purifying the virus through clarification, filtration, and chromatography. CAR-T cell therapy is also discussed as an example of cell immunotherapy, which uses lentivirus to modify patient T-cells that are then reintroduced to the patient.
An Integrated Approach to Ensure Viral Vector and Gene Therapy Commercial Rea...MilliporeSigma
This document discusses an integrated approach to ensuring viral vector and gene therapy commercial readiness. It covers four main topics: 1) the current state and future perspectives of viral vectors, 2) scalability and reproducibility in viral vector manufacturing, 3) testing and quality considerations, and 4) regulatory approval and commercial readiness. The current demand for clinical and commercial doses of viral vectors is increasing. Ensuring scalable, reproducible manufacturing processes and comprehensive testing and quality measures is critical for regulatory approval and commercialization.
Viral Risk Mitigation Strategies: Key Considerations in the Prevention and De...Merck Life Sciences
This document discusses strategies for preventing and detecting viral contamination in biologic manufacturing processes. It outlines sources of viral contamination including raw materials, facilities, and personnel. A multi-tiered approach is recommended involving screening raw materials and cell banks, in-process testing, and confirming downstream processes can clear viruses. Detection methods like in vitro and in vivo assays have limitations and next generation sequencing is presented as a powerful new tool to detect unknown viruses. Upstream prevention focuses on raw material control through pretreatment or virus-resistant cell lines while downstream processes aim to clear any contamination through viral inactivation or filtration steps. A holistic biosafety strategy applying prevention, detection, and removal approaches at all stages is emphasized.
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
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.
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
Tech transfer and Scale-up - Tips and tricks from a Biodevelopment centerMilliporeSigma
Technology transfer could be considered as the corner stone of biodevelopment activities, as it is required each time people want to switch from a lab or a facility to another. It is expected to be handled in a methodical manner, following regulatory requirements, in order to ensure patients safety. Difficulties often come from differences between sending and receiving entities, where equipment, level of resources, internal culture, can be different. In case of failure, the cost can be huge for a drug maker.
This presentation will cover points to consider for successful tech transfers, and includes lessons learned from real cases.
In this webinar, you will learn:
● How to design a bioreactor model in order to scale up a process.
● How to build a team and tech transfer a process.
● How to accurately assess the success of a tech transfer.
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
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
Getting Biopharmaceutical Production Processes Right the First TimeKBI Biopharma
Strategies for rapid acceleration of cell line, upstream and downstream process development. A presentation by Ying Huang, Ph.D., Associate Director of Cell Line Development at KBI Biopharma. Presented at World Orphan Drug Congress. Washington DC. (2014)
Biosafety in Gene Therapy: Applying the latest regulatory guidance for RCL te...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/33WUiqE
Ensuring the safety and quality of your lentiviral vector is of the utmost importance. Attend this webinar to learn about testing strategies to monitor replication competent lentivirus. You will also hear about recent changes in regulatory guidance with regards to sample types and volumes tested.
The use of lentivirus vectors to produce groundbreaking gene therapies is on the rise. Ensuring the biosafety and quality of these vectors is achieved through a multi-tiered testing approach.
For lentivirus-based therapies, generation of replication competent particles is a potential risk. While improvements in design and manufacturing have decreased the probability of producing replication competent viruses, regulatory agencies provide guidelines to test for their presence at multiple stages in production. This webinar reviews the strategies for monitoring replication competent lentiviruses. We describe current methods and address: Sample types, testing volumes, and expected results.
In this webinar, you will learn about:
• The latest FDA regulatory guidelines on replication competent lentivirus (RCL) testing
• Methods used to monitor RCL
• Considerations on sample type and volume requirements
This document discusses biosafety testing for cell and gene therapies performed by BioReliance, a testing services division of Merck KGaA. It outlines the comprehensive testing performed at various stages of development, including testing of cell banks, viral vectors, and final drug products. Testing evaluates important product attributes like identity, purity, potency and residuals to ensure safety and quality. A wide range of assays are used to characterize products and identify potential contaminants.
Setting up for successful lot release testing by Edmund AngMilliporeSigma
Is your lot release testing strategy ready for global commercialization?
In this webinar, you will learn:
• CMC testing requirements with CHO production platform for global commercialization
• Lot release testing of product intermediates and final product
• Product-specific qualification study
• Alternative rapid testing methods to advance lot release testing
CHO cells continue to serve as a key cell substrate for the manufacturing of recombinant proteins that span beyond therapeutic monoclonal antibodies and including subunit vaccines.
In this presentation, we will cover the CMC testing requirements with CHO production platform for global commercialization, Lot release testing of product intermediates and final product, product-specific qualification study and highlight the application of new testing methods and the benefits they bring to advance Lot Release Testing.
This document discusses strategies for orphan biopharmaceutical process development using contract development and manufacturing organizations (CDMOs). It notes that orphan biopharmaceuticals often require smaller scale and more flexible manufacturing. The document outlines considerations for clinical and commercial process development, including using single-use technologies, quality by design principles, and ensuring fidelity between clinical and commercial manufacturing processes. It emphasizes characterizing processes early and getting the process design right the first time for orphan drugs.
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
The document discusses design controls, which are a set of quality practices and procedures incorporated into the design and development process to control the design process and ensure medical device specifications meet user needs and intended use. It provides an overview of the seven key elements of design controls according to FDA regulations: design and development planning, design input, design output, design review, design verification, design validation, and design changes. It emphasizes that design controls are important for medical device safety and quality.
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
Promises and Challenges of Manufacturing and Testing Viral Producer Cell LinesMerck Life Sciences
To date, manufacturing of lentivirus (LV) vectors for gene therapy commonly relies on transient transfection of adherent HEK293 cells. This method is costly, time-consuming, difficult to scale-up and poorly reproducible, rendering large-scale applicability to fulfill increasing demand of LV in clinical pipelines cumbersome. The use of suspension-adapted transient producer cell lines for LV production has overcome some of these challenges. Furthermore, successful creation of stable producer cell lines would allow creation of master and working cell banks easily amenable to commercial production. The ideal producer cell lines should demonstrate stability in growth and gene expression, and be easily adaptable to chemically defined culture conditions and optimized for high-titer virus production. The availability of more robust producer cell lines thus represents an important scalable first step towards manufacturing processes that are conducive to large-scale production. Ultimately, these producer cell lines must be screened to satisfy various biosafety and regulatory implications.
In this webinar, you will learn:
• Process development for transient and stable producer cell lines
• Screening of cellular gene targets via CRISPR to improve LV production from producer cell lines
• cGMP and Regulatory readiness: Cell line characterization and release testing through BioReliance® global service offering
Evolving Trends in mAb Production ProcessesKBI Biopharma
Monoclonal antibodies (mAbs) have established themselves as the leading biopharmaceutical therapeutic modality. The establishment of robust manufacturing platforms are key for antibody drug discovery efforts to seamlessly translate into clinical and commercial successes. Several drivers are
influencing the design of mAb manufacturing processes. The advent of biosimilars is driving a desire to achieve lower cost of goods and globalize biologics manufacturing. High titers are now
routinely achieved for mAbs in mammalian cell culture. These drivers have resulted in significant evolution in process platform approaches. Additionally, several new trends in bioprocessing havearisen in keeping with these needs. These include the consideration of alternative expression systems, continuous biomanufacturing and non-chromatographic separation formats. This paper discusses these drivers in the context of the kinds of changes they are driving in mAb production processes.
Managing Process Scale-up and Tech Transfer MilliporeSigma
Are you involved with planning tech transfer of your drug product? Join this webinar to learn more about the regulations and considerations you need to consider and learnings from a case study.
According to ICH Q10, “The goal of technology transfer activities is to transfer product and process knowledge between development and manufacturing, and within or between manufacturing sites to achieve product realization. This knowledge forms the basis for the manufacturing process, control strategy, process validation approach, and ongoing continual improvement.”
As a result, there is an expectation for transfers to be performed in an organized, methodical manner with appropriate documentation. It is also expected that they happen between one Process Development group to another or to a Pilot Lab, from Process Development lab to clinical or commercial manufacturing, or from Process Development to external clinical manufacturing. Lastly, they may also happen between two company facilities at commercial scale, or between a company and an external contract manufacturing at commercial scale.
This presentation will cover points to consider for successful tech transfers with a focus on cGMP training requirements, and include lesson learned from real cases.
Presented by Guillaume Plane on September 22, 2016
Process Development for Cell Therapy and Viral Gene TherapyMilliporeSigma
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
Releasing Your AAV Therapy with Confidence: Regulatory Considerations and Key...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3icKkbZ
Ensuring the safety and quality of your AAV vector is of the utmost importance. Join this webinar for a high-level overview of the regulatory requirements for AAV testing throughout the manufacturing process, as well as a more detailed look at rcAAV and infectious titer assays.
Adeno-associated virus (AAV) vectors possess a number of advantages for use in human therapy including: high titer preparations, low immunogenicity, capacity to infect a wide range of cell types, and replication deficiency. Even with these advantages, there are biosafety concerns to consider when using AAV vectors.
This webinar will discuss key regulatory considerations across the manufacturing process, from the helper/packaging plasmids through to lot release testing. We will highlight critical assays that are required and delve into specifics on replication competent AAV testing and infectious titer determination by TCID50.
In this webinar, you will learn:
• Critical biosafety considerations for AAV vectors based on the latest regulatory guidance
• How replication competent AAV testing fits into your bulk and final release testing package
• The benefits of routine and platform assays over custom assay development
Presented by:
Steven McDade, Senior Technical Specialist, Field Technology Management
Alfonso Lavorgna, Ph.D., Operations Manager, Virology Services
The purpose of this document is to present a potential design to the client for manufacture of a DNA vaccine facility in the United Kingdom. Facility will have capacity to produce 1 kg/annum of two plasmid products.
Pivotal factors considered in design and layout of DNA vaccine facility were compliance to good manufacturing practices (cGMP), effective production, regulatory guidelines, contamination minimisation and effective cleanliness.
Handling of raw materials and final product both on and off site has been studied to outline features and add-ups that can be implemented to minimise environmental impact: such measures include process safety and instrumentation. Impact of airborne particles, temperature, pressure and relative humidity on purity, efficacy and safety have been reduced through design of class 100 cleanrooms equipped with controlled-air environment accessible via airlock, HVAC and high efficiency particulate air filters (HEPA).
Additionally, principles of process control and instrumentation have been applied throughout design stage of project with aim of creating a process that is ultimately safe, and one that complies with safety regulations, efficient and economically stable. Compliance to current good manufacturing practices (cGMP) and regulations are achieved through incorporation of key cGMP components such as validation master plan (VMP), quality control (QC), cleaning-in-place (CIP), sterilisation-in-place (SIP), trained personnel and waste treatment process.
Economic evaluation of project indicates viability, net profit of £557,000,000 is a very lucrative figure for a 10-year investment. Project payback time of 5 months and entire project timeline of 1 year and 10 months demonstrates that this project is highly feasible and has potential to attract numerous investors.
Compressed Timelines for Breakthrough Therapies: Impact on Process Characteri...KBI Biopharma
This document discusses strategies for accelerating process characterization and validation timelines for biologics with breakthrough therapy designations. It recommends establishing a scalable single-use cell culture manufacturing platform. Process development should utilize high-throughput and single-use technologies. Process characterization can be accelerated by conducting experiments in parallel, leveraging prior clinical data, and using design of experiments approaches. Scale-down models should closely mimic commercial processes and be established using equivalent parameters like power input. This will allow process characterization data packages to support regulatory submissions within 9 months.
Modern BioManufacturing: Single-Use Technologies in Configurable, Prefabricat...MilliporeSigma
A co-webinar describing a solution to biopharma's challenge of rapidly and rationally expanding capacity by employing single-use technologies, a templated process train, and pre-fabricated mobile/modular cleanrooms.
Biopharmaceutical companies on the verge of investing into manufacturing or facilities expansion face many questions and challenges. Speed, agility, and flexibility are becoming more critical to executing their changing production and distribution strategies. Platform facility designs which integrate the latest procss technologies wthin innovative pre-fabricated cleanrooms are critical for addressing the trending desire to implement 'clonable' modular facilities that can be delivered in a timely fashion across multiple locations. Companies like Merck KGaA, Darmstadt, Germany and G-CON Manufacturing are working together to combine their technologies and develop simple yet robust platform solutions for industry.
As bioprocessing technologies intensify performance, volumetric requirements become less. As such, 2000L single-use bioreactors - or multiple bioreactors of similar or less volumes - now suffice for the production of novel or biosimilar recombinant proteins. Such a shift in the industry enables the development of more mobile, modular facility designs. We will describe the rationale for this collaboration and its result: a turn-key solution that integrates a templated process train with a rapidly-deployable facility platform. By combining the unique advantages found with the G-CON POD construction and the bioprocess technology expertise from within Merck KGaA, Darmstadt, Germany, the goal of creating a cost-effective, pre-fabricated alternative to historical 'stick built' facilities is being achieved. Additionally, the flexibility inherent to our approach provides for a greater configurability that confers more user-specified choice into the selection of options. Simple in concept, this solution is also robust, cost-effective, and conducive to tight timelines for implementation.
In this webinar you will learn:
- Basic options for facilities/capacity expansion
- The value of templated process trains employing single-use equipment
- How modular, prefabricated PODs® outfitted with such single-use bioprocessing equipment represent an attractive, cost-effective strategy for capacity expansion
POD® is a registered trademark of G-CON Manufacturing, Inc.
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
Edward Narke discussed the CMC pathway for biologics through clinical development and market approval. The goals are to better understand FDA requirements, visualize a cost-effective approach to manage manufacturing processes, and appreciate challenges in controlling safety, potency, and impurities. Biologics have complex structures that must be characterized and controlled. Assay methods, product specifications, stability data, and comparability between clinical and commercial materials are common reasons INDs are placed on clinical hold. Managing impurities, developing relevant potency assays, and collecting data continuously are important strategies to address these challenges over the course of development.
The document discusses developing vaccines for biodefense threats more rapidly using genome-derived epitope-driven vaccine (GD-EDV) design. Key components include immunoinformatics tools for epitope mapping, vaccine design algorithms, and rapid manufacturing once a pathogen genome is available. This approach aims to develop vaccines within 24 hours of obtaining a genome sequence to address urgent biothreats with unknown pathogens.
This presentation is about the relevance of vaccine as a public health tool against vaccine preventable diseases and the need to accelerate the development of vaccines against malaria and other diseases of global health importance in developing countries such as Nigeria.
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
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
Getting Biopharmaceutical Production Processes Right the First TimeKBI Biopharma
Strategies for rapid acceleration of cell line, upstream and downstream process development. A presentation by Ying Huang, Ph.D., Associate Director of Cell Line Development at KBI Biopharma. Presented at World Orphan Drug Congress. Washington DC. (2014)
Biosafety in Gene Therapy: Applying the latest regulatory guidance for RCL te...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/33WUiqE
Ensuring the safety and quality of your lentiviral vector is of the utmost importance. Attend this webinar to learn about testing strategies to monitor replication competent lentivirus. You will also hear about recent changes in regulatory guidance with regards to sample types and volumes tested.
The use of lentivirus vectors to produce groundbreaking gene therapies is on the rise. Ensuring the biosafety and quality of these vectors is achieved through a multi-tiered testing approach.
For lentivirus-based therapies, generation of replication competent particles is a potential risk. While improvements in design and manufacturing have decreased the probability of producing replication competent viruses, regulatory agencies provide guidelines to test for their presence at multiple stages in production. This webinar reviews the strategies for monitoring replication competent lentiviruses. We describe current methods and address: Sample types, testing volumes, and expected results.
In this webinar, you will learn about:
• The latest FDA regulatory guidelines on replication competent lentivirus (RCL) testing
• Methods used to monitor RCL
• Considerations on sample type and volume requirements
This document discusses biosafety testing for cell and gene therapies performed by BioReliance, a testing services division of Merck KGaA. It outlines the comprehensive testing performed at various stages of development, including testing of cell banks, viral vectors, and final drug products. Testing evaluates important product attributes like identity, purity, potency and residuals to ensure safety and quality. A wide range of assays are used to characterize products and identify potential contaminants.
Setting up for successful lot release testing by Edmund AngMilliporeSigma
Is your lot release testing strategy ready for global commercialization?
In this webinar, you will learn:
• CMC testing requirements with CHO production platform for global commercialization
• Lot release testing of product intermediates and final product
• Product-specific qualification study
• Alternative rapid testing methods to advance lot release testing
CHO cells continue to serve as a key cell substrate for the manufacturing of recombinant proteins that span beyond therapeutic monoclonal antibodies and including subunit vaccines.
In this presentation, we will cover the CMC testing requirements with CHO production platform for global commercialization, Lot release testing of product intermediates and final product, product-specific qualification study and highlight the application of new testing methods and the benefits they bring to advance Lot Release Testing.
This document discusses strategies for orphan biopharmaceutical process development using contract development and manufacturing organizations (CDMOs). It notes that orphan biopharmaceuticals often require smaller scale and more flexible manufacturing. The document outlines considerations for clinical and commercial process development, including using single-use technologies, quality by design principles, and ensuring fidelity between clinical and commercial manufacturing processes. It emphasizes characterizing processes early and getting the process design right the first time for orphan drugs.
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
The document discusses design controls, which are a set of quality practices and procedures incorporated into the design and development process to control the design process and ensure medical device specifications meet user needs and intended use. It provides an overview of the seven key elements of design controls according to FDA regulations: design and development planning, design input, design output, design review, design verification, design validation, and design changes. It emphasizes that design controls are important for medical device safety and quality.
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
Promises and Challenges of Manufacturing and Testing Viral Producer Cell LinesMerck Life Sciences
To date, manufacturing of lentivirus (LV) vectors for gene therapy commonly relies on transient transfection of adherent HEK293 cells. This method is costly, time-consuming, difficult to scale-up and poorly reproducible, rendering large-scale applicability to fulfill increasing demand of LV in clinical pipelines cumbersome. The use of suspension-adapted transient producer cell lines for LV production has overcome some of these challenges. Furthermore, successful creation of stable producer cell lines would allow creation of master and working cell banks easily amenable to commercial production. The ideal producer cell lines should demonstrate stability in growth and gene expression, and be easily adaptable to chemically defined culture conditions and optimized for high-titer virus production. The availability of more robust producer cell lines thus represents an important scalable first step towards manufacturing processes that are conducive to large-scale production. Ultimately, these producer cell lines must be screened to satisfy various biosafety and regulatory implications.
In this webinar, you will learn:
• Process development for transient and stable producer cell lines
• Screening of cellular gene targets via CRISPR to improve LV production from producer cell lines
• cGMP and Regulatory readiness: Cell line characterization and release testing through BioReliance® global service offering
Evolving Trends in mAb Production ProcessesKBI Biopharma
Monoclonal antibodies (mAbs) have established themselves as the leading biopharmaceutical therapeutic modality. The establishment of robust manufacturing platforms are key for antibody drug discovery efforts to seamlessly translate into clinical and commercial successes. Several drivers are
influencing the design of mAb manufacturing processes. The advent of biosimilars is driving a desire to achieve lower cost of goods and globalize biologics manufacturing. High titers are now
routinely achieved for mAbs in mammalian cell culture. These drivers have resulted in significant evolution in process platform approaches. Additionally, several new trends in bioprocessing havearisen in keeping with these needs. These include the consideration of alternative expression systems, continuous biomanufacturing and non-chromatographic separation formats. This paper discusses these drivers in the context of the kinds of changes they are driving in mAb production processes.
Managing Process Scale-up and Tech Transfer MilliporeSigma
Are you involved with planning tech transfer of your drug product? Join this webinar to learn more about the regulations and considerations you need to consider and learnings from a case study.
According to ICH Q10, “The goal of technology transfer activities is to transfer product and process knowledge between development and manufacturing, and within or between manufacturing sites to achieve product realization. This knowledge forms the basis for the manufacturing process, control strategy, process validation approach, and ongoing continual improvement.”
As a result, there is an expectation for transfers to be performed in an organized, methodical manner with appropriate documentation. It is also expected that they happen between one Process Development group to another or to a Pilot Lab, from Process Development lab to clinical or commercial manufacturing, or from Process Development to external clinical manufacturing. Lastly, they may also happen between two company facilities at commercial scale, or between a company and an external contract manufacturing at commercial scale.
This presentation will cover points to consider for successful tech transfers with a focus on cGMP training requirements, and include lesson learned from real cases.
Presented by Guillaume Plane on September 22, 2016
Process Development for Cell Therapy and Viral Gene TherapyMilliporeSigma
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
Releasing Your AAV Therapy with Confidence: Regulatory Considerations and Key...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3icKkbZ
Ensuring the safety and quality of your AAV vector is of the utmost importance. Join this webinar for a high-level overview of the regulatory requirements for AAV testing throughout the manufacturing process, as well as a more detailed look at rcAAV and infectious titer assays.
Adeno-associated virus (AAV) vectors possess a number of advantages for use in human therapy including: high titer preparations, low immunogenicity, capacity to infect a wide range of cell types, and replication deficiency. Even with these advantages, there are biosafety concerns to consider when using AAV vectors.
This webinar will discuss key regulatory considerations across the manufacturing process, from the helper/packaging plasmids through to lot release testing. We will highlight critical assays that are required and delve into specifics on replication competent AAV testing and infectious titer determination by TCID50.
In this webinar, you will learn:
• Critical biosafety considerations for AAV vectors based on the latest regulatory guidance
• How replication competent AAV testing fits into your bulk and final release testing package
• The benefits of routine and platform assays over custom assay development
Presented by:
Steven McDade, Senior Technical Specialist, Field Technology Management
Alfonso Lavorgna, Ph.D., Operations Manager, Virology Services
The purpose of this document is to present a potential design to the client for manufacture of a DNA vaccine facility in the United Kingdom. Facility will have capacity to produce 1 kg/annum of two plasmid products.
Pivotal factors considered in design and layout of DNA vaccine facility were compliance to good manufacturing practices (cGMP), effective production, regulatory guidelines, contamination minimisation and effective cleanliness.
Handling of raw materials and final product both on and off site has been studied to outline features and add-ups that can be implemented to minimise environmental impact: such measures include process safety and instrumentation. Impact of airborne particles, temperature, pressure and relative humidity on purity, efficacy and safety have been reduced through design of class 100 cleanrooms equipped with controlled-air environment accessible via airlock, HVAC and high efficiency particulate air filters (HEPA).
Additionally, principles of process control and instrumentation have been applied throughout design stage of project with aim of creating a process that is ultimately safe, and one that complies with safety regulations, efficient and economically stable. Compliance to current good manufacturing practices (cGMP) and regulations are achieved through incorporation of key cGMP components such as validation master plan (VMP), quality control (QC), cleaning-in-place (CIP), sterilisation-in-place (SIP), trained personnel and waste treatment process.
Economic evaluation of project indicates viability, net profit of £557,000,000 is a very lucrative figure for a 10-year investment. Project payback time of 5 months and entire project timeline of 1 year and 10 months demonstrates that this project is highly feasible and has potential to attract numerous investors.
Compressed Timelines for Breakthrough Therapies: Impact on Process Characteri...KBI Biopharma
This document discusses strategies for accelerating process characterization and validation timelines for biologics with breakthrough therapy designations. It recommends establishing a scalable single-use cell culture manufacturing platform. Process development should utilize high-throughput and single-use technologies. Process characterization can be accelerated by conducting experiments in parallel, leveraging prior clinical data, and using design of experiments approaches. Scale-down models should closely mimic commercial processes and be established using equivalent parameters like power input. This will allow process characterization data packages to support regulatory submissions within 9 months.
Modern BioManufacturing: Single-Use Technologies in Configurable, Prefabricat...MilliporeSigma
A co-webinar describing a solution to biopharma's challenge of rapidly and rationally expanding capacity by employing single-use technologies, a templated process train, and pre-fabricated mobile/modular cleanrooms.
Biopharmaceutical companies on the verge of investing into manufacturing or facilities expansion face many questions and challenges. Speed, agility, and flexibility are becoming more critical to executing their changing production and distribution strategies. Platform facility designs which integrate the latest procss technologies wthin innovative pre-fabricated cleanrooms are critical for addressing the trending desire to implement 'clonable' modular facilities that can be delivered in a timely fashion across multiple locations. Companies like Merck KGaA, Darmstadt, Germany and G-CON Manufacturing are working together to combine their technologies and develop simple yet robust platform solutions for industry.
As bioprocessing technologies intensify performance, volumetric requirements become less. As such, 2000L single-use bioreactors - or multiple bioreactors of similar or less volumes - now suffice for the production of novel or biosimilar recombinant proteins. Such a shift in the industry enables the development of more mobile, modular facility designs. We will describe the rationale for this collaboration and its result: a turn-key solution that integrates a templated process train with a rapidly-deployable facility platform. By combining the unique advantages found with the G-CON POD construction and the bioprocess technology expertise from within Merck KGaA, Darmstadt, Germany, the goal of creating a cost-effective, pre-fabricated alternative to historical 'stick built' facilities is being achieved. Additionally, the flexibility inherent to our approach provides for a greater configurability that confers more user-specified choice into the selection of options. Simple in concept, this solution is also robust, cost-effective, and conducive to tight timelines for implementation.
In this webinar you will learn:
- Basic options for facilities/capacity expansion
- The value of templated process trains employing single-use equipment
- How modular, prefabricated PODs® outfitted with such single-use bioprocessing equipment represent an attractive, cost-effective strategy for capacity expansion
POD® is a registered trademark of G-CON Manufacturing, Inc.
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
Edward Narke discussed the CMC pathway for biologics through clinical development and market approval. The goals are to better understand FDA requirements, visualize a cost-effective approach to manage manufacturing processes, and appreciate challenges in controlling safety, potency, and impurities. Biologics have complex structures that must be characterized and controlled. Assay methods, product specifications, stability data, and comparability between clinical and commercial materials are common reasons INDs are placed on clinical hold. Managing impurities, developing relevant potency assays, and collecting data continuously are important strategies to address these challenges over the course of development.
The document discusses developing vaccines for biodefense threats more rapidly using genome-derived epitope-driven vaccine (GD-EDV) design. Key components include immunoinformatics tools for epitope mapping, vaccine design algorithms, and rapid manufacturing once a pathogen genome is available. This approach aims to develop vaccines within 24 hours of obtaining a genome sequence to address urgent biothreats with unknown pathogens.
This presentation is about the relevance of vaccine as a public health tool against vaccine preventable diseases and the need to accelerate the development of vaccines against malaria and other diseases of global health importance in developing countries such as Nigeria.
ADVANCES IN USING THE T-MAX PRECISION™ VACCINE PLATFORM AGAINST MAJOR VIRAL ...iQHub
The document summarizes MBF Therapeutics' T-Max Precision DNA vaccine technology and its potential applications. Key points:
- T-Max uses proprietary DNA plasmids encoding antigen sequences to directly stimulate T-cells and induce strong mucosal immunity, addressing limitations of current vaccines.
- Studies show T-Max vaccines for African swine fever and SARS-CoV-2 induce robust CD8+ T-cell responses in pigs and humans.
- The technology could help address significant unmet needs in animal and human vaccines for diseases like influenza, tuberculosis, and others.
This document summarizes a presentation given by Dr. Rajesh Jain on thermostable vaccines. It discusses Panacea Biotec's vaccine portfolio and manufacturing capabilities. It then covers the need for vaccines across all age groups, concepts of vaccines and challenges with cold chains. Finally, it explores various approaches to developing thermostable vaccines, including technologies like ThermoVax and challenges in bringing such vaccines to market.
Insights from a Global Collaboration Accelerating Vaccine Development with an...MilliporeSigma
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
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
This document discusses cell culture based vaccine production. It begins by introducing different types of vaccines and traditional egg-based vaccine production methods and their limitations. It then describes the importance and advantages of cell culture based production, including types of cells used. The key steps of the cell culture based production process are outlined, including strain selection, bulk production, purification, virus inactivation, formulation, quality control testing, and lot release. Examples are given of specific vaccines produced through cell culture methods like influenza, rabies, and dengue vaccines. The conclusion discusses the potential for cell culture to replace egg-based methods and future research perspectives.
This document discusses cell culture based vaccine production. It begins by introducing different types of vaccines and traditional egg-based vaccine production methods and their limitations. It then describes the importance and advantages of cell culture based methods, including types of cells used. The key steps of the cell culture based production process are outlined, including strain selection, bulk production, purification, virus inactivation, formulation, quality control testing, and lot release. Specific cell culture based vaccines for influenza, rabies, dengue, and Ebola are discussed. The conclusion emphasizes the potential for cell culture to replace egg-based methods by producing vaccines faster and in larger quantities to meet global demand.
Plants have potential as bioreactors for producing vaccines. The document discusses developing a plant-derived vaccine for HPV type 16 using tobacco chloroplasts. HPV type 16 causes most cervical cancers. Current HPV vaccines are expensive and require refrigeration. The methodology develops a modified HPV L1 gene expressing capsomeres, which are fused to an adjuvant and expressed in tobacco chloroplasts. This plant-derived vaccine is more cost effective and stable than current options. It could help reduce the burden of cervical cancer in developing countries.
This document discusses the production and manufacturing of vaccines. It describes two main types of vaccine production: traditional egg-based methods and newer cell-based methods using mammalian cells. The egg-based methods have been used for 60 years to produce seasonal flu vaccines but they have disadvantages like mutations during adaptation and long production times. Cell-based methods using dog kidney cells or other mammalian cells have advantages like faster production and reduced mutations but they have higher costs. The document also mentions clinical development of vaccines during a pandemic is urgent to protect the public with limited time constraints.
Plasmid Manufacturing Service from GenScript ProBioGenScript ProBio
GenScript ProBio offers the best Plasmid Manufacturing Service and employs a GMP-compliant plasmid production process that allows customers to replicate DNA used in experiments with minimal additional effort. By employing this process, Genscript can provide plasmids produced at the highest quality standards. For more information, visit our website. https://www.genscriptprobio.com/gct-proplasmid.html
This document provides an overview of HIV vaccines, including definitions, estimates of herd immunity thresholds for different diseases, types of vaccines, strategies for preventive and therapeutic HIV vaccines, and summaries of clinical trials. It discusses DNA vaccines, viral vector vaccines, dendritic cell vaccines, therapeutic vaccine candidates, and the Canadian HIV Vaccines Initiative.
This document summarizes a seminar presentation on the production of DNA vaccines. It begins by discussing the importance of vaccines in addressing infectious diseases and problems with traditional vaccines. It then covers topics like the advantages of DNA vaccines over recombinant protein vaccines, designing plasmid DNA constructs for vaccines, antigen expression systems, successful DNA vaccines to date, delivery methods like needle-free injection and microspheres, and the use of adjuvants to enhance vaccine activity.
Oncolytic Virus Therapy Development - Creative BiolabsCreative-Biolabs
Oncolytic virotherapy is cancer treatment using a native or reprogrammed virus that has the potential to targeting and killing cancerous cell. Taking advantage of the OncoVirapy™ platform, Creative Biolabs provides customized, standardized, and reliable and high-quality oncolytic virus therapy development services for clients globally.
Development and strategies of cell-culture technology for influenza vaccine [...Vishal Doshi
This document discusses strategies for improving cell culture technology for influenza vaccine production. It outlines the development of cell lines like MDCK and PER.C6 that are used for large-scale vaccine production. Reasons for low viral yields in cell culture include low cell density, cell death, and strains not growing well. Strategies to improve yields include manipulating the cell line, virus strain, infection conditions, and culture conditions to optimize cell survival and virus replication. The goal is to establish robust and scalable cell culture processes for purer and faster influenza vaccine production compared to egg-based methods.
This document summarizes safety considerations for DNA vaccines. It discusses safety issues related to the genetic elements of DNA vaccines, including the potential for antibiotic resistance gene transfer and germline integration. It also discusses safety concerns regarding the microbial production host, such as endotoxin production and genetic instability. The document proposes strategies to improve safety, including using replication origins with narrow host range, non-antibiotic selection markers, artificial promoter and signal sequences with low human homology, and gram-positive microbial hosts like Lactococcus lactis that do not produce endotoxins.
This document summarizes key aspects of vaccine development and production. It discusses the types of vaccines including live-attenuated, inactivated, subunit, recombinant peptide, DNA, and viral vector vaccines. Production involves growing microorganisms or cells, purification, formulation with adjuvants or stabilizers, characterization, storage, and licensing. New technologies aim to develop vaccines for diseases lacking vaccines, and improve safety, efficacy, and heat stability of existing vaccines.
Mechanism of different types of vaccines in developmentEmilioMolina23
This document discusses five main types of vaccine technologies: live-attenuated vaccines, inactivated vaccines, subunit vaccines, viral vector vaccines, and messenger RNA (mRNA) vaccines. For each technology, it provides examples of existing vaccines and candidates in development for COVID-19. Live-attenuated vaccines contain weakened live pathogens, while inactivated vaccines use killed whole pathogens. Subunit vaccines contain fragments of pathogens, and viral vector vaccines use harmless viruses to deliver genetic code for antigens. mRNA vaccines teach the body to produce protein antigens to trigger immunity. The Pfizer and Moderna COVID-19 vaccines are mRNA-based.
Presentation on conventional vaccine (Quality Control and Production aspects)Sunny Rathee
The document discusses the production and quality control of vaccines. It begins by introducing vaccines and their purpose of stimulating immunity. It then covers the history of vaccines, classifications of vaccines, and properties of an ideal vaccine. The document discusses the differences between conventional and novel vaccines. It provides details on the preparation and standardization of several common vaccines, including polio, smallpox, typhoid, BCG, and cholera vaccines. The production process of vaccines is summarized as selecting strains, growing microorganisms, isolating and purifying the product, inactivating microorganisms, and formulating and testing the final vaccine.
Similar to Platform Technologies to Accelerate Novel Vaccine Development and Manufacturing (20)
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
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
Risk-Based Qualification of X-Ray Sterilization for Single-Use SystemsMerck Life Sciences
The document discusses testing done to qualify the use of x-ray sterilization for a Lynx S2S connector. Physical, chemical, and biological tests were performed on connectors that underwent either x-ray or gamma sterilization. Test results showed comparable extractable levels, thermal properties, and chromatographic profiles between the two sterilization methods. This provides evidence that x-ray sterilization is a suitable alternative to gamma sterilization for this connector.
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
The webinar discusses services from MilliporeSigma to accelerate antibody-drug conjugate (ADC) development through their ADC Express and ADCore product lines. ADC Express provides integrated antibody, linker, payload, and conjugation services to generate multiple ADC candidates for evaluation. The ADCore product line offers intermediates that simplify payload synthesis and accelerate development timelines. ChetoSensar technology incorporates a chito-oligosaccharide to enhance ADC solubility and efficacy.
Regulatory Considerations for Excipients used in Lipid NanoparticlesMerck Life Sciences
Lipid excipients and delivery systems such as lipid nanoparticles (LNPs) are essential for a wide variety of therapeutics including mRNA vaccines and therapeutics and gene therapy.
The purity and safety of novel, synthetic lipid excipients must be demonstrated due to their central role in the function of the drug product, distinct physicochemical properties, and the potential for interaction with other ingredients or the physicochemical environment. These excipients must comply with challenging and complex regulatory requirements, similar to those expected of the active pharmaceutical ingredient itself.
This whitepaper provides an overview of the regulatory classification of lipid nanoparticles, liposomes and novel excipients. Specific requirements outlined in guidance documents are shared along with strategies to stay ahead of emerging regulatory challenges.
To find more information about synthetic lipids for pharmaceutical applications and gene therapy, please visit our website:
https://www.sigmaaldrich.com/DE/en/products/pharma-and-biopharma-manufacturing/formulation/synthetic-lipids
https://www.sigmaaldrich.com/US/en/products/pharma-and-biopharma-manufacturing/formulation/synthetic-lipids
EU GMP Annex 1 Draft - Closed System Design Consideration with Single-Use Sys...Merck Life Sciences
Biopharmaceutical manufacturing capacities have expanded dramatically which has resulted in an increased demand for single-use systems (SUS) as they have their own advantages. Although SUS are well established in the biopharmaceutical industry there is limited guidance on regulatory expectations. Please attend the webinar to learn more!
End-tidal carbon dioxide (ETCO2) is the level of carbon dioxide that is released at the end of an exhaled breath. ETCO2 levels reflect the adequacy with which carbon dioxide (CO2) is carried in the blood back to the lungs and exhaled.
Non-invasive methods for ETCO2 measurement include capnometry and capnography. Capnometry provides a numerical value for ETCO2. In contrast, capnography delivers a more comprehensive measurement that is displayed in both graphical (waveform) and numerical form.
Sidestream devices can monitor both intubated and non-intubated patients, while mainstream devices are most often limited to intubated patients.
This particular slides consist of- what is Pneumothorax,what are it's causes and it's effect on body, risk factors, symptoms,complications, diagnosis and role of physiotherapy in it.
This slide is very helpful for physiotherapy students and also for other medical and healthcare students.
Here is a summary of Pneumothorax:
Pneumothorax, also known as a collapsed lung, is a condition that occurs when air leaks into the space between the lung and chest wall. This air buildup puts pressure on the lung, preventing it from expanding fully when you breathe. A pneumothorax can cause a complete or partial collapse of the lung.
R3 Stem Cell Therapy: A New Hope for Women with Ovarian FailureR3 Stem Cell
Discover the groundbreaking advancements in stem cell therapy by R3 Stem Cell, offering new hope for women with ovarian failure. This innovative treatment aims to restore ovarian function, improve fertility, and enhance overall well-being, revolutionizing reproductive health for women worldwide.
This particular slides consist of- what is hypotension,what are it's causes and it's effect on body, risk factors, symptoms,complications, diagnosis and role of physiotherapy in it.
This slide is very helpful for physiotherapy students and also for other medical and healthcare students.
Here is the summary of hypotension:
Hypotension, or low blood pressure, is when the pressure of blood circulating in the body is lower than normal or expected. It's only a problem if it negatively impacts the body and causes symptoms. Normal blood pressure is usually between 90/60 mmHg and 120/80 mmHg, but pressures below 90/60 are generally considered hypotensive.
NURSING MANAGEMENT OF PATIENT WITH EMPHYSEMA .PPTblessyjannu21
Prepared by Prof. BLESSY THOMAS, VICE PRINCIPAL, FNCON, SPN.
Emphysema is a disease condition of respiratory system.
Emphysema is an abnormal permanent enlargement of the air spaces distal to terminal bronchioles, accompanied by destruction of their walls and without obvious fibrosis.
Emphysema of lung is defined as hyper inflation of the lung ais spaces due to obstruction of non respiratory bronchioles as due to loss of elasticity of alveoli.
It is a type of chronic obstructive
pulmonary disease.
It is a progressive disease of lungs.
TEST BANK FOR Health Assessment in Nursing 7th Edition by Weber Chapters 1 - ...rightmanforbloodline
TEST BANK FOR Health Assessment in Nursing 7th Edition by Weber Chapters 1 - 34.
TEST BANK FOR Health Assessment in Nursing 7th Edition by Weber Chapters 1 - 34.
TEST BANK FOR Health Assessment in Nursing 7th Edition by Weber Chapters 1 - 34.
Joker Wigs has been a one-stop-shop for hair products for over 26 years. We provide high-quality hair wigs, hair extensions, hair toppers, hair patch, and more for both men and women.
English Drug and Alcohol Commissioners June 2024.pptxMatSouthwell1
Presentation made by Mat Southwell to the Harm Reduction Working Group of the English Drug and Alcohol Commissioners. Discuss stimulants, OAMT, NSP coverage and community-led approach to DCRs. Focussing on active drug user perspectives and interests
As Mumbai's premier kidney transplant and donation center, L H Hiranandani Hospital Powai is not just a medical facility; it's a beacon of hope where cutting-edge science meets compassionate care, transforming lives and redefining the standards of kidney health in India.
CHAPTER 1 SEMESTER V COMMUNICATION TECHNIQUES FOR CHILDREN.pdfSachin Sharma
Here are some key objectives of communication with children:
Build Trust and Security:
Establish a safe and supportive environment where children feel comfortable expressing themselves.
Encourage Expression:
Enable children to articulate their thoughts, feelings, and experiences.
Promote Emotional Understanding:
Help children identify and understand their own emotions and the emotions of others.
Enhance Listening Skills:
Develop children’s ability to listen attentively and respond appropriately.
Foster Positive Relationships:
Strengthen the bond between children and caregivers, peers, and other adults.
Support Learning and Development:
Aid cognitive and language development through engaging and meaningful conversations.
Teach Social Skills:
Encourage polite, respectful, and empathetic interactions with others.
Resolve Conflicts:
Provide tools and guidance for children to handle disagreements constructively.
Encourage Independence:
Support children in making decisions and solving problems on their own.
Provide Reassurance and Comfort:
Offer comfort and understanding during times of distress or uncertainty.
Reinforce Positive Behavior:
Acknowledge and encourage positive actions and behaviors.
Guide and Educate:
Offer clear instructions and explanations to help children understand expectations and learn new concepts.
By focusing on these objectives, communication with children can be both effective and nurturing, supporting their overall growth and well-being.
The Importance of Black Women Understanding the Chemicals in Their Personal C...bkling
Certain chemicals, such as phthalates and parabens, can disrupt the body's hormones and have significant effects on health. According to data, hormone-related health issues such as uterine fibroids, infertility, early puberty and more aggressive forms of breast and endometrial cancers disproportionately affect Black women. Our guest speaker, Jasmine A. McDonald, PhD, an Assistant Professor in the Department of Epidemiology at Columbia University in New York City, discusses the scientific reasons why Black women should pay attention to specific chemicals in their personal care products, like hair care, and ways to minimize their exposure.
The Importance of Black Women Understanding the Chemicals in Their Personal C...
Platform Technologies to Accelerate Novel Vaccine Development and Manufacturing
1. The life science business of Merck KGaA,
Darmstadt, Germany operates as
MilliporeSigma in the U.S. and Canada.
Platform Technologies to
Accelerate Novel Vaccine
Development and
Manufacturing
David Loong PhD
Senior Consultant, Novel Modalities, Asia Pacific,
BioProcessing Strategy
Josephine Cheng
Senior Consultant, Core Modalities, Asia Pacific,
BioProcessing Strategy
2. The life science business
of Merck KGaA, Darmstadt,
Germany operates as
MilliporeSigma in the U.S.
and Canada
5. Eradication
of diseases such as
smallpox
3 million
deaths prevented
every year
Reduction
from 125 to 2 Polio endemic countries in 30 years
5
A preparation that is
administered to stimulate the
body's immune response against
a specific infectious agent or
disease
Introduction
Vaccines
5
6. Our mission
Enabling the industry to
produce
better faster safer
vaccines
to improve access,
globally
Vaccines are a major contribution to overall Global Health
6
7. Scalability
Need to be able to produce huge amount of doses in
a short time
Global vaccine manufacturing capacity may not be
sufficient for COVID19
Time
The typical vaccine paradigm doesn’t allow
adequate response to tackle outbreaks
Cost
Vaccine development & licensure requires
>$500 million
No guaranteed long-term market
Major Challenges in Vaccine manufacturing with Outbreak & Pandemic
A Paradigm Shift with Pandemics
7
8. A Paradigm Shift in Vaccine Manufacturing
Time is compressed, phases overlap
Phase 1
Target ID, development partner
selection & Pre-clinical trials
Phase 2a Phase 3 Licensure
Small-scale clinical trial material
Manufacturing scale-up,
commercial scale, process
validation
Large-scale
manufacturing
Clinical development
Target ID,
development
partner selection &
Pre-clinical trials
Safety/
Dose
selection
Safety/efficacy
Manufacturing development, scale up,
clinical lots, commercial scale,
validation of process
Large-scale manufacturing
Go or no-go
decision to invest in
candidate
First trial in
humans
Efficacy trial in
humans
Evaluation trial
in humans
Go or no-go
decision to
invest in
candidate
First in humans
(safety)
Regulatory pathway for
emergency authorization
Efficacy trial
Traditional
paradigm
+10years
Outbreak
paradigm
1-3 years
Adapted from NEJM, Lurie et al, March 30th, 2020
8
9. How they have influenced vaccine manufacturing
Pandemics and outbreaks
2021
9
10. • Global capacity is constrained to respond
to COVID19 need
• The “unknown” preparedness remain the
biggest challenge
• Next time, how can we minimize risks
and be better prepared?”
A Paradigm Shift
Lessons learned and Approaches
▪ Acceleration of development is
needed.
▪ Prepare for scalability once
vaccine is developed.
▪ Platform Technology to reduce
changes & increase production
capabilities.
10
11. Inactivated
virus
Vaccines compose of
dead virus
DNA
vaccines
Vaccines compose of
snippets of pathogen
genes
Vaccine by modalities
Traditional vaccine
Recombinant
protein
Vaccines with protein or a
protein fragment of the
pathogen, assembled to
closely resemble viruses
Conjugated
vaccine
Vaccines compose of
sugars that mimic bacteria
pathogen on a carrier
protein that increase
immune response
Viral vector
vaccine
Vaccines that use a virus
to deliver snippets of
pathogen genes into
human cells
Virus-like
particles
Vaccines with protein or
a protein fragment of
the pathogen, with a
structure closely
resemble the pathogen
Modern to cutting edge vaccine
Live attenuated
virus
Vaccines compose
of weakened virus
Toxoid
Vaccines compose
of inactivated toxin
Vaccines compose
of inactivated
bacteria
Whole bacteria
RNA
vaccines
Vaccines compose of
snippets of pathogen
genes
1921 1924 1945 1955 1986 - 2006 1986 - 1991 1987 - 1991 2019 2020 2021
« One bug – one drug » « One platform – multiple vaccines»
Improvements towards effective, safe, and affordable vaccine
A vaccine platform is any underlying technology,
a mechanism, delivery method, or cell line that
can be used to develop multiple vaccines.
Replication
incompetent
Replication
competent
Various expression
systems
Synthetic
mRNA
Self-amplifying
(saRNA)
11
15. A VLP has the shape of virus but no genetic materials, good immune
response & no risk of pathogenicity
Virus Like Particles – a versatile platform
• Virus-like particles (VLPs) are biological nanoparticles composed
of viral structural proteins, frequently major proteins in the capsid
or envelop.
• Contain repetitive high-density displays of viral surface proteins
that elicit strong immune responses.
• Self-assemble into structures morphologically resembling viruses.
• No genetic material – no replications, non-infectious.
• 20 to 200 nm in size and is similar to the size of the
corresponding viruses, allows them to be taken up by dendritic
cells (DCs) and antigen-presenting cells (APCs).
• Can be produced in a variety of cell culture systems, against
different strains of a virus other than those for which the vaccine
was formulated.
• They sometimes require adjuvants to increase their
immunogenicity
• Proven technology: Hepatitis B, Human Papillomavirus vaccines
15
16. VLPs are either non-enveloped or enveloped
VLPs can be divided into two groups:
Non-enveloped (“naked”) and Enveloped.
Each groups could be classified based on the
number of viral surface proteins.
Non-
enveloped
HBV, HPV
Enveloped
CMV
Source:Appl Microbiol Biotechnol (2015) 99:10415–10432
Transfus Med Hemother. 2010 Dec; 37(6): 365–375
VLP designs examples
(a) 1 layer - 1 proteins Hepatitis B
(b) 1 layer- 2 proteins SARS Coronavirus
VLPs
(c) 2 layers-2 proteins Papillomavirus L1
and L2
(d) 2 layers- multiple proteins FMDV-VLPs
(e) 3 layers- multiple proteins Bluetongue virus,
rotavirus
(f) 1 layer-1 protein Influenza virus
(g) 1 layer – 2 proteins Hantaviruses
(h) 2 layers- 2 proteins Hepatitis C
(j) 2 layers – multiple proteins SARS coronavirus
VLP
eVLP
16
17. Production & Purification of VLP-Based Vaccine
Insect Cell / Baculovirus VLP Production Platform
UF/DF
Baculovirus
Inactivation
Purification
Chromatography
Media and Inoculum
Preparation
Cell growth in
Bioreactor and
Virus Inoculation
Bioburden
Reduction
Primary
Clarification
Sterile
Filtration
Polishing
Chromatography
UF/DF
Removal
17
18. Bacteria Yeast Mammalian
Cell
Plants Insect Cell
VLP Type Non-
enveloped
Non-enveloped
Enveloped
Non-enveloped
Enveloped
Non-enveloped
Enveloped
Non-enveloped
Enveloped
Secretory
Expression
- + ++ + ++
Speed +++ +++ ++ ++ ++
Cost + + +++ ++ ++
Scalability +++ +++ ++ ++ ++
VLP Complexity + ++ ++ ++ +++
Yield +++ ++ + ++ ++
Reported Yields 4.38 g/L
Polyomavirus VP1
400 mg/L
Hepatitis B Surface
Antigen
500 mg/L
Adeno-associated
Virus
3 g/kg
Papillomavirus L1
662 mg/L
Rotavirus VP2, VP6
and VP7
Different VLP Production Systems
Source: Shiyu Dai et.al. Journal of Immunological Sciences (2018).
- No successful cases reported; + Low; ++ Medium; +++ High
Linda et al., Biotechnology and Bioengineering, Vol. 111, No. 3, March, 2014
18
19. VLP Technology
Challenges
1 pH, solubility, shear,
proteolytic
2 Adsorption
Shear
filtration
chromatography resolution
3
Endotoxin removal in bacterial
expression systems
Difficulties in baculovirus (BV)
removal (VLPs with similar sizes
and/or surface charge at a given
pH)
Stability
yields
Contaminant
Removal
19
Overall, depending on the expression platform of VLPs, the
production processes should be designed to accommodate the best
compromise between throughput, yield and quality needs meeting
the desired purity and potency, and the cost.
20. 1. Disease Target: Hepatitis C
170 million people infected, over 350,000
deaths/year
Causes cirrhosis and liver cancer
Current therapies only partially effective, costly
and poorly tolerated
No vaccine currently exists
2. VLP produced in Sf9 insect cells co-infected with
MLV-GAG and HCV-E1E2 using baculovirus
Purification process optimization for VLP-based Vaccine
Case sharing collaboration with iBET
iBET: Instituto de Biologia Experimental e
Tecnológica, Oeiras, Portugal
Sf9
ANTIGENS
E1 and E2 envelope
glycoproteins from
Hepatitis C virus
STRUCTURE
Capsid and envelope
from retrovirus
(murine leukemia
virus)
20
21. 21
Production & Purification of VLP-Based Vaccine
Process Challenges
Scalable production in bioreactor
Efficient purification
High recovery of VLP
Baculovirus clearance
VLP
Baculovirus
1
2
3
4
22. Production & Purification of VLP-Based Vaccine
Cell culture Optimization
Cell growth obtained using
Mobius® 3L Bioreactor
Western blot analysis of VLPs
using three markers
• Comparable cell and VLP properties between disposable and glass bioreactors.
• Increased agitation rate, increased cell density of inoculation, replacing the micro-
sparger with an open-pipe sparger improved the performance of the single-use
bioreactor.
• Reproducible performance of the disposable bioreactor.
22
23. Unlike centrifugation (CFG),
depth filtration resulted in ~70% DNA clearance
0% 20% 40% 60% 80% 100%
10 μm → 5 μm → 0.6 μm
10 μm → 0.6 μm
5 μm → 0.6 μm
5 μm → 0.3 μm
CFG → 0.6 μm
CFG → 0.3 μm
CFG
VLP recovery
HepC VLP clarification
Production & Purification of VLP-Based Vaccine
Clarification Optimization
Clarification
• Filter-only clarification train can be
used without compromising recovery
yield of VLPs.
• Filter cascade composed of a Polygard®
CN 5 μm filter followed by a 0.3 μm
depth filter showed the highest
recovery of HCV-VLP, improving on
centrifugation/2° depth filtration
• Moderate DNA removal with depth
filtration was seen
23
24. 24
Virus-Like Paricle Vaccine Training
90%
35%
85%
80%
28%
91%
58%
90%
96%
38%
0%
25%
50%
75%
100%
HCV-VLP
recovery %
BV removal % Total Protein
removal %
DNA removal
%
HCP
removal%
Pellicon® (PES 100 kD) Pellicon® (CRC 300 kD)
Both membranes were fully retentive of the VLP
Better removal of
baculovirus, DNA,
and host-cell
protein!
Optimization of TFF for Concentration and Purification
Purification Results
UF/DF
Pellicon® cassette with 300
kD regenerated cellulose
membrane offered the best
combination of recovery
and purification
4-5X concentration
achieved
24
25. ▪ Successfully purified VLPs using Fractogel®
TMAE commercial resins
▪ Yield of >60% with ~2 LRV baculovirus can
be achieved with a flow-through/wash
purification strategy
▪ Options to increase recovery or purification
depending on product value by varying process
conditions
Separation of VLP from Baculovirus
Anion Exchange Chromatography for VLP Purification
Higher flow rate
OR
Higher load conductivity
Recovery LRV
Flow rate (mL/min)
NaCl
(mM)
Higher recovery
AND
Lower BV LRV
Inputs: [NaCl] (100/200/300 mM) and flow rate (100/200/400 cm/hr)
Responses: % VLP recovery and Baculovirus LRV
Purification
Recovery
25
26. All components were
integrated in a templatable and
scalable process that made it
possible to achieve the desired
yield and recovery
Summary iBET collaboration
• A Mobius® 3L single-use bioreactor was
successfully used to produce a VLP-based
vaccine in an insect cell culture system
• Downstream processing was optimized using
Polygard® CN 5.0→0.3 μm depth filters, followed
by UF/DF using a Pellicon® cassette with
Ultracel® 300 kDa Membrane
• VLPs were purified using Fractogel® EMD TMAE
resins and Eshmuno® resin prototypes
26
28. Viral Vectors shuffle genetic messages into cells for making target
antigens without getting human sick
A Trojan-horse Vaccine
1. A live vector vaccine is a a vaccine that uses a
weakened or harmless microorganism to transport
pieces of antigen in order to stimulate an immune
response.
2. Common viral vectors are adenovirus, canarypox,
lentivirus, and alphaviruses.
3. They transfect their own DNA into the host cell,
which is later expressed to produced new viral
particles.
4. Viral vectors are genetically modified to have non-
replicating viral vectors (e.g. adenovirus) and
replicating viral vectors (e.g. weakened Measles).
5. Benefits including strong immue response, possible
to encode several antigens (multi-diseases),
relatively inexpensive and stable to transport.
Widely used for vaccines and cancer drug.
6. Risk of reversion of virulence, potential cancerous
cell cancerous phenotype.
28
29. Adenovirus based vaccine pipelines
Adenovirus (AV) is most commonly used in vaccine development
Vaccine Target Type Company Approval year Comments
Ad5-
EBOV
Ebola Ad5
CanSino &
Beijing Institute
of Biotechnology,
China
2017
Lyophilized
1 dose
Zabdeno
®
Ad26.ZE
BOV
Ebola
AdVac®
(Ad26)
Johnson &
Johnson (Janssen
Vaccines)
2020
Liquid frozen
2 doses, boost:
Mvabea®
(MVA-
BN-Filo) with a
different vector
Vaccine Type Phase Company
AZD1222 Adenovirus EUA
AstraZeneca & University of
Oxford
Ad5-nCoV Adenovirus EUA CanSino & China’s military
research unit
Ad26COVS1 Adenovirus EUA Johnson & Johnson
Current approved adenovirus based vaccines
Current COVID-19 adenovirus*
*As of date July 2021
• Human adenoviruses and many
animal adenoviruses (monkeys,
cattle, sheep, swine, dogs),
belong to the genus
Mastadenovirus
• Adenovirus in its natural form
is a pathogen for common cold.
The AV used for vaccine
developments are specially
genetically modified NOT to
cause any diseases and
generally regarded as safe.
• Non-Enveloped viruses with a
ds-DNA, 70-90 nm in size,
small enough to go through
sterile filtration.
29
30. Schematic Adenovirus manufacturing process
Viral Vector Manufacturing
Raw materials Media prep Amplification &
inoculation
Cell culture Clarification
(I & II)
Bioburden
removal
Nucleic acid
digestion
Concentration
Bioburden
removal
AEX Chrom
Concentration
& Diafiltration
Formulation
Sterile
filtration
Final Filling
Lysis
SEC or
AEX chrom
Upstream Downstream
Formulation & Fill Finish Downstream
30
32. Simian Adenovirus
platform for vaccines
32
Objectives:
• GMP process
• Easy to operate
• Single use
• >50% efficiency
• Phase 1 scale: >5x1013 VP (1000 doses)
• Readily scalable to 5x1014
• Vaccine candidate: Rabies vaccine
« ChAdOx2-RabGP »
33. Transition to a new manufacturing process
Reduced handling, compressed process
Benzonase®
Nuclease
Clarification
Millistak+®
filters
Concentration/
Diafiltration
Pellicon® 2
cassettes
Membrane
chromatography
Natrix®
membrane
Diafiltration/
Formulation
Pellicon® 2
cassettes
Final filtration
Durapore® filters
Mobius®
Bioreactor
Centrifugation Ultra-centrifugation
Shake flasks
33
34. Conclusion
Accelerating vaccine development & manufacturing is possible
GMP ready for
various
adenoviruses
Full single
use process
Project met
initial goals
>2000 doses/4L
culture
18 months
project
Collaboration
between
supplier/
manufacturer
is key
5 days process
time:
« outbreak »
ready
34
35. What is the advantage of a platform?
The Need to Platform
1. Supports bioprocessing standardization
2. Reduce process development time
3. Reduce significant manufacturing changes
4. Ease regulatory approval
At the Jenner Institute, in 2 months, process development was
done based on the previously developed platform
Optimization of critical unit operations were done hand in hand
with Merck engineers
35
37. The rise of nucleic acid technologies
Nucleic acids require a delivery system to be effective
Naked Encapsulated
DNA RNA
Target gene
DNA
Plasmid DNA is the
common approach
mRNA
Lipid nanoparticles
formation using lipids
and/or polymers to
protect from nucleases &
endosomes
Intravenous or lymphatic
injection route
siRNA Antisense
RNA
Local administration
at target site
Rapid degradation
Intratumoral,
intranodal or subq
Other types of RNA
37
38. mRNA technology
Two types of mRNA constructs are being actively used
Non-Replicating mRNA (NRM) Self Amplifying mRNA (SAM)
Number of
nucleotides
2000 – 3000 nt ~ 10 000 nt
Type Single-stranded Single-stranded
Size 660 – 990 kDa 3300 kDa
Potency Low levels of proteins
High levels of proteins
Enhanced protein expression
Immunity
No theoretical risk of anti-vector immunity
with non-viral delivery systems
No anti-vector effect has been observed
yet
Potential interactions between encoded
non-structural proteins and host factors
require additional investigation.
Concentration
needed/dose
~50-200ug/dose ~1ug/dose
5’ UTR GOI 3’ UTR
5’ cap A A A A A A A A 5’ UTR GOI 3’ UTR
5’ cap A A A A A A A A
Replicase
38
39. mRNA technology
Advantages
1 RNA therapeutics are safer
than DNA therapeutics
(RNA does not integrate
into the Genom)
RNA is not infectious
RNA is produced using a
cell-free enzymatic
transcription reaction or
chemical synthesis
2 Production of RNA-
based vaccines is
faster compared to
production of
traditional vaccines
Good scalability
3
Producing RNA
vaccines is less
expensive than
producing the full
antigen protein
4
For any outbreak
RNA vaccines are
more flexibel, any
desired RNA for any
desired protein of
interest can be
prepared in short time
for each individual
patient (personalized
medicine)
Safety
Time
COst
Flexibility
39
39
40. mRNA technology
Challenges
1 Single stranded
Highly negatively charged
Rapid degradation of RNA
caused by endonucleases
Cold-chain
2 Exogenous mRNA is
immunostimulatory, as it is
recognized by a variety of
innate immune receptors
In applications such as
protein-replacement
therapies, activation of the
innate immune system by
toll-like receptors by IVT
mRNA is not desired
3 The in vivo Delivery of
RNA is very inefficient
RNA vaccines have a
lower immunogenicity
compared to traditional
vaccines, so higher doses
are needed
RNA instability
Immune modulation
Efficiency
40
40
41. Generate pDNA coding for the RNA polymerase promoter and the targeted mRNA construct
mRNA manufacturing starts with a plasmid template
Plasmid process
Fermentation Clarification Purification
with Chrom
(2-3 steps)
Final
Filtration
Concentration
and Diafiltration
(UF/DF)
Thaw cells
E.coli+pDNA
Cell Harvest Cell Lysis Concentration
and Diafiltration
(UF/DF)
Plasmid facility mRNA facility
pDNA
Non replicating mRNA
Self amplifying mRNA
pDNA
41
42. High-performing and single-use chromatography devices simplify the
process
Plasmid process
• Superior productivity and flexibility for multi-
product/multi-purpose manufacturing of plasmids
• Ideally suited for the capture of small and mid-sized
Plasmids (<20kbp)
• Yield: ≥80 % of ccc-form, >95 % RNA removal
• Short cycle time: 35 min
• Caustic stability enables efficient cleaning (1M NaOH)
• Re-use in rapid-cycling operation mode allows for cost
reduction
Natrix® Q Chromatography membrane
Plasmid
Size
Plasmid
Titer
µg/ml
Initial pDNA
Purity
A260 based
Operating
Capacity
mg/mL MV
Yield
%
pDNA Eluate
Purity
A260 based
5.7 kb 45 4.0 % 10 ≥ 80
≥ 80 %
pDNA
13 kb 33 2.4 % 4 ≥ 77
≥ 90 %
pDNA
20 kb 25 0.7 % 1 ≥ 65
≥ 62 %
pDNA
Case study
Feed characteristics
• Original E. coli lysates from alkaline lysis, clarified by
centrifugation/depth filtration, supplemented with optimal NaCl
to eliminate RNA interference, pH 5.0, finally 0.22 µm filtered
• Plasmids ranging from small to large size
• Varying initial pDNA purity ranging from 0.7% - 4%
Results
42
43. mRNA manufacturing
Scale-up considerations
Lab scale
• Solvent extraction
• Precipitation steps
• Hazardous solvents
• Scalability issues
• Lack of process development expertise
• Replace extraction & precipitation with chrom, TFF
• GMP compliance
• Risk assessment for Rnase-free biopharma materials,
process equipment, raw material & solutions
• Complex development of efficient & safe encapsulation
systems
• Challenges in sterile filtration of large mRNA complexes
• Cold-chain distribution to point of care
Manufacturing Scale
Make Purify Formulate
pDNA
Linearization
Chrom, UF/DF In vitro
Transcription
Chrom, UF/DF Enzymatic
capping
Chromatography UF/DF Encapsulation
& Formulation
Final Sterile
Filtration
43
44. mRNA manufacturing
Process objectives: quality
Make Purify Formulate
pDNA
Linearization
Chrom, UF/DF In vitro
Transcription
Chrom, UF/DF Enzymatic
capping
Chromatography UF/DF Encapsulation
& Formulation
Final Sterile
Filtration
mRNA
product
• mRNA Size/MW
• mRNA integrity, potency
• Encapsulation efficiency
• Capping efficiency
• Impurities: dsRNA, DNA template, nucleoside
triphosphates, RNA polymerase
• Appearance, pH, osmolality, subvisible
particles, elemental impurities and residual
solvents
Quality Control
Quality Attributes
mRNA structure
Purity
Low impurities promotes mRNA expression
• 5’ Cap: Affect innate sensing and protein
• UTRs: Maximize gene expression
• GOI or Coding Sequence Region Gene of Interest
• 3’ Poly-A-tail: Enhances translation & protects mRNA
Efficient delivery system (nanoparticle)
44
45. mRNA formulation
Encapsulation is crucial for mRNA stability and delivery efficiency
Drug Delivery Technologies
Lipids Lipid Nanoparticle
(LNP)
Polymers
Liposomes
Lipoplexes
Polyplexes
mRNA in
aqueous
solution
Sterile Filtration &
Fill and Finish
mRNA LNP
formation
LNP Formulation
UF/DF &
Final formulation
Encapsulation
Lipids in
organic
solvent
mRNA
LNP rug
product
LNP is most commonly
used for mRNA delivery
Each LNP consists of four different
lipids allowing the mRNA to be carried
in it and protected from degradation
45
47. COVID pipeline analysis
(July.15,2021)
1
1
2
2
19
18
9
16
21
24
71
1
2
2
2
5
16
10
16
18
36
0 20 40 60 80 100 120
VVnr + Antigen Presenting Cell
Cellular based vaccine
Bacterial vector (Replicating)
VVr + Antigen Presenting Cell
Live attenuated bacterial vector
Live attenuated virus
Viral vector (Replicating)
Virus like particle
Inactivated virus
DNA based vaccine
Viral vector (Non-replicating)
RNA based vaccine
Protein subunit
Total Pipelines in COVID-19 Vaccine
Pre-Clinical Clinical Trials
PS > VV > mRNA > pDNA > IV > VLP
47
48. Summary
Platform technology can reduce the
development time and cost, whilst
minimizing process changes between
vaccines.
Platform technologies can provide high
level of flexibility and can be quickly
adjusted for variants especially in
pandemic and outbreaks.
Choosing which platform to use depends
on available assets and resources, overall
cost, targeted diseases, etc.
All products going forward needs to
approve safety and efficacy by the
regulatory authorities.
1
2
3
48
4
49. Fedosiuk et al.
Silva et al.
Peixoto et al.
Dr Anissa Boumlic
Elina Gousseinov
Claire Scanlan
Thomas Parker
Nargisse El Hajjami
Manuel Brantner
Matthieu Perret
Sandra Hon
Acknowlegement:
Thank you for listening!
49