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.
How to Accelerate and Enhance ADC TherapiesMilliporeSigma
In this webinar, you will learn about:
The advantages of using advanced intermediates to develop ADC therapies
How to increase ADC solubility and efficiency
Fast, small-scale ADC library generation
Seamless supply chain with reduced complexity and regulatory support
The ADCore product line offers versatile intermediates that simplify the synthesis of common ADC payloads (dolastatins, maytansinoids, and PBDs) by greatly reducing the number of synthetic steps. This translates to savings in development and manufacturing costs and shorter timelines to the clinic. To address the poor solubility of many ADC payloads, ChetoSensar™ was developed to significantly increase the hydrophilicity of the drug linker, which has been shown to also substantially increase the efficacy of ADCs and broaden the therapeutic window.
Lastly, the ADC Express™ service leverages conjugation chemistry and analytical expertise to help design and quickly synthesize sets of potential ADC therapies suitable for screening to simplify candidate selection and get ADC therapies to market faster.
In this webinar, you will learn:
How Single-Use helps to simplify ADC manufacturing
Safety and Integrity of the complete process
Flexibility and adaptability to changing needs
How to speed up the synthesis of high-potent payloads and improve the bioavailability of the ADC
Detailed description:
The development of an ADC is a long journey that can be speeded-up with the adoption of proper manufacturing tools and new linker-payload solutions. Single-Use equipment applied to the GMP manufacturing of ADC means operator safety, decreased risk of contamination, scalability, reproducibility, flexibility, small footprint, lower cost, and saved time through efficiency (easy setup and cleanup, no need for cleaning validation). The adoption of payload intermediates such as DolCoreTM and MayCoreTM can speed your development project up, while innovative linkers like ChetoSensarTM increase its chances of success. This webinar explains how these technologies improve the ADC production process end-to-end, ultimately enhancing patient safety.
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
Commercializing antibody-drug conjugates: a CMO’s journeyMerck Life Sciences
Watch the webinar here: https://bit.ly/2YLDzTE
This webinar will take you through the story of a CMO preparing for the manufacture of a Commercial Antibody Drug Conjugate (ADC).
Join us to learn about how we grew as a CMO to develop a Commercial ADC program. We will walk through the full timeline from development, process risk assessment and control strategy development and validation, finishing off with preparation for a Commercial ADC Pre-Approval Inspection Audit.
In this webinar you will learn how to:
• Properly structure your development work
• Perform a thorough process risk assessment
• Prepare for pre-approval inspection
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.
Considerations for Manufacturing Commercial Antibody Drug Conjugates (ADCs) -...MilliporeSigma
ADC manufacturing presents a unique set of challenges as compared to the well established practices employed for more traditional biologic products.
The development and commercialization of key intermediates, complex small-molecule APIs and biologic drug substances shouldn’t be such a headache. The uniqueness, versatility, and complexity involved in each project only means you need to make sure you’re well informed when it comes to the dos and don'ts of manufacturing commercial Antibody Drug Conjugates (ADCs). Tune in to hear a CMO perspective for an in-depth understanding on the subject of manufacturing commercial ADCs. Our team will discuss all of the considerations that must be addressed to successfully manufacture ADCs.
In this webinar you will learn:
- Facility Design and Cleaning Validation
- Advantages of Single Use Systems
- Process Control and Regulatory Strategies
Streamlining Biopharmaceutical Cell Line Development - Reducing risk and decr...Merck Life Sciences
CHO cells with their unique characteristics, represent the major expression system within the biopharmaceutical industry. However, one of the major challenges in cell line development is to identify those rare, high-producing clones in a huge population of non-expressing or low-expressing cell lines. This leads to laborious and time consuming cell line development processes. This webinar will educate the audience about challenges faced with traditional expression systems and how the CHO cell line with the glutamine synthethase knock-out via Zinc Finger Nucleases provides benefits for fast and efficient cell line development as well as stable and high titer expression. We will explore additional cell line engineering targets that can be modified to engineer a cell line that mitigates risks and removes bottlenecks throughout the biopharmaceutical process.
In this webinar, you will learn:
• What are the benefits of using an optimized/engineered expression system?
• What can be done throughout the cell line development process to mitigate risks and remove bottlenecks?
• Applications of cell line engineering for further upstream biopharmaceutical enhancements.
How to Accelerate and Enhance ADC TherapiesMilliporeSigma
In this webinar, you will learn about:
The advantages of using advanced intermediates to develop ADC therapies
How to increase ADC solubility and efficiency
Fast, small-scale ADC library generation
Seamless supply chain with reduced complexity and regulatory support
The ADCore product line offers versatile intermediates that simplify the synthesis of common ADC payloads (dolastatins, maytansinoids, and PBDs) by greatly reducing the number of synthetic steps. This translates to savings in development and manufacturing costs and shorter timelines to the clinic. To address the poor solubility of many ADC payloads, ChetoSensar™ was developed to significantly increase the hydrophilicity of the drug linker, which has been shown to also substantially increase the efficacy of ADCs and broaden the therapeutic window.
Lastly, the ADC Express™ service leverages conjugation chemistry and analytical expertise to help design and quickly synthesize sets of potential ADC therapies suitable for screening to simplify candidate selection and get ADC therapies to market faster.
In this webinar, you will learn:
How Single-Use helps to simplify ADC manufacturing
Safety and Integrity of the complete process
Flexibility and adaptability to changing needs
How to speed up the synthesis of high-potent payloads and improve the bioavailability of the ADC
Detailed description:
The development of an ADC is a long journey that can be speeded-up with the adoption of proper manufacturing tools and new linker-payload solutions. Single-Use equipment applied to the GMP manufacturing of ADC means operator safety, decreased risk of contamination, scalability, reproducibility, flexibility, small footprint, lower cost, and saved time through efficiency (easy setup and cleanup, no need for cleaning validation). The adoption of payload intermediates such as DolCoreTM and MayCoreTM can speed your development project up, while innovative linkers like ChetoSensarTM increase its chances of success. This webinar explains how these technologies improve the ADC production process end-to-end, ultimately enhancing patient safety.
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
Commercializing antibody-drug conjugates: a CMO’s journeyMerck Life Sciences
Watch the webinar here: https://bit.ly/2YLDzTE
This webinar will take you through the story of a CMO preparing for the manufacture of a Commercial Antibody Drug Conjugate (ADC).
Join us to learn about how we grew as a CMO to develop a Commercial ADC program. We will walk through the full timeline from development, process risk assessment and control strategy development and validation, finishing off with preparation for a Commercial ADC Pre-Approval Inspection Audit.
In this webinar you will learn how to:
• Properly structure your development work
• Perform a thorough process risk assessment
• Prepare for pre-approval inspection
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.
Considerations for Manufacturing Commercial Antibody Drug Conjugates (ADCs) -...MilliporeSigma
ADC manufacturing presents a unique set of challenges as compared to the well established practices employed for more traditional biologic products.
The development and commercialization of key intermediates, complex small-molecule APIs and biologic drug substances shouldn’t be such a headache. The uniqueness, versatility, and complexity involved in each project only means you need to make sure you’re well informed when it comes to the dos and don'ts of manufacturing commercial Antibody Drug Conjugates (ADCs). Tune in to hear a CMO perspective for an in-depth understanding on the subject of manufacturing commercial ADCs. Our team will discuss all of the considerations that must be addressed to successfully manufacture ADCs.
In this webinar you will learn:
- Facility Design and Cleaning Validation
- Advantages of Single Use Systems
- Process Control and Regulatory Strategies
Streamlining Biopharmaceutical Cell Line Development - Reducing risk and decr...Merck Life Sciences
CHO cells with their unique characteristics, represent the major expression system within the biopharmaceutical industry. However, one of the major challenges in cell line development is to identify those rare, high-producing clones in a huge population of non-expressing or low-expressing cell lines. This leads to laborious and time consuming cell line development processes. This webinar will educate the audience about challenges faced with traditional expression systems and how the CHO cell line with the glutamine synthethase knock-out via Zinc Finger Nucleases provides benefits for fast and efficient cell line development as well as stable and high titer expression. We will explore additional cell line engineering targets that can be modified to engineer a cell line that mitigates risks and removes bottlenecks throughout the biopharmaceutical process.
In this webinar, you will learn:
• What are the benefits of using an optimized/engineered expression system?
• What can be done throughout the cell line development process to mitigate risks and remove bottlenecks?
• Applications of cell line engineering for further upstream biopharmaceutical enhancements.
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
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
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
Moving your Gene Therapy from R&D to IND: How to navigate the Regulatory Land...MilliporeSigma
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
An Integrated Approach to Ensure Viral Vector and Gene Therapy Commercial Rea...Merck Life Sciences
Come learn more about our integrated approach to ensure viral vector and gene therapy commercial readiness. We will discuss topics relating to process development for viral vector manufacturing, biosafety testing and commercial readiness.
Significant progress has been made for the use of viral vectors for gene therapy. Promising clinical trial results as well as recent FDA approval for CAR-T cell therapy to treat certain children and young adults with B-cell lymphoblastic leukemia have signaled advancements in the field. This marks a historic action, providing opportunities for new viral vector technologies to transform medicine and the way patients are treated and even cured. The need for process development for viral vector manufacturing to improve yield to meet patient demand, biosafety testing for product characterization, potency and safety and commercial readiness to accelerate therapy to-market are critically important. Here, we emphasis an integrated approach that allows our customers solutions to ensure viral vector and gene therapy commercial readiness to meet the growing market need.
In this webinar, you will learn:
● Process development advances for production scale-up of viral vectors for gene therapy
● Methods specific for viral gene therapy product characterization, purity, potency, safety and release testing
● Commercial readiness through our US and UK Centers of Excellence for viral product manufacturing
In the new world of connected healthcare, medical device manufacturers are challenged with cybersecurity issues to comply with the new FDA regulations. We examine the 5 domain areas of cybersecurity which apply to IoT HealthCare Vendors/ Providers.
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
Biosimilars are biological generics drugs.They undergo a rigorous evaluation to get approved.How to prove biosimilariy from analytical comparability is explained using a recently approved US FDA bio-similar monoclonal antibody.
How Molecular Structure Influences Potency of a Therapeutic BiologicMerck Life Sciences
This review will give the listener an understanding of how the molecular structure, and the different ways they can be measured, influences binding and affects potency of a therapeutic biologic.
Product characterization is key to successful biological drug development. Comprehensive characterization of new therapeutic monoclonal antibodies requires a deep understanding of their structural and functional critical quality attributes (CQAs) which may impact product potency, stability and safety. Various analytical approaches can be used to characterize the effects of changes during the process of generating a biological drug.
This webinar will review some of the approaches to N-glycan profiling of monoclonal antibodies using Mass Spectrometry (MS), including Hydrogen Deuterium Exchange (HDX-MS) analytics. Using the Humira monoclonal antibody, the effect of glycosylation on the Fc-region mediated effector function was assessed with binding and CDC and ADCC activity assays. This review will give the listener an understanding of how the molecular structure, and the different ways they can be measured, influences binding and affects potency of a therapeutic biologic.
In this webinar you will learn:
- HDX-MS - when and why to use
- Glycosylation effects assessment by activity assays
Production and purification of Viral vectors for gene and cell therapy appli...Dr. Priyabrata Pattnaik
Presentation at "2016 Osong BioExcellence - Renaissance in Immunotherapy" at South Korea, an event jointly hosted by Kbio Health and Merck on 6th October 2016.
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)
Account-Based Marketing (ABM) is a growth strategy that relies on marketing and sales working closely together to influence multiple stakeholders for a select set of high-value companies. Our virtual Knoxville HUG event on June 30th focused on the five steps for building and executing an ABM strategy and HubSpot's new tools that support ABM.
“Challenges of biosimilar product development and experience gained”
Shows the development process for biosimilars, focusing specifically on the company’s experience
Unveiling the Potential of your AAV Gene Therapy: Orthogonal methods to under...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3pCCjPF
Ensure your Adeno-Associated Virus (AAV) is safe throughout its entire drug development journey. Learn methods that will help you speed to clinic, potentially treating diseases sooner and with greater effectiveness.
The potential of gene therapies to cure previously untreatable diseases has spurred the development of novel drugs, including those based on Adeno-Associated Virus (AAV). As with all biopharmaceuticals, it is important to identify and monitor the critical quality attributes (CQAs) of these products to ensure their safety and efficacy.
In this webinar, we will present a range of orthogonal methods to understand and define the CQAs of AAV products. These include assays for the confirmation of capsid protein identity and quantity, as well as the characterization of important product-related impurities, such as aggregates. Together these methods represent a comprehensive analytical testing package to support the characterization and lot release of AAV products.
In this webinar, you will learn:
• How to identify and monitor the critical quality attributes (CQAs) of your AAV therapy
• What assays to utilize to confirm capsid protein identity and quantity
• Why you need look to product characterization to identify and remove important product-related impurities
Why a Build-Your-Own Healthcare Data Platform Will Fall Short and What to Do ...Health Catalyst
Health system may have some compelling reasons for choosing to build a data platform versus partner with a healthcare analytics vendor on a commercial solution. However, while organizations may think they’re saving money, gaining control and security, and more by opting for a homegrown approach, they’ll more than likely encounter challenges, hidden costs, and limitations. In comparison to a commercial-grade, healthcare-specific platform from a vendor, build-your-own solutions fall short when it comes to domain-specific content, technical expertise, total cost of ownership, and more. Organizations that partner on a vended platform vastly improve their chances of optimizing and scaling their analytic investment over time and achieving measurable improvement.
Biosimilar Development Regulatory, Analytical, and Clinical Considerations SGS
The development pathway of a biosimilar is unlike that of a novel biotherapeutic. While there is an increased requirement for analytics throughout a biosimilars development project, and a Phase II clinical trial is generally omitted, careful consideration must be given to the planning of the other phases of development. Many regulatory authorities reference a “step-by-step” approach to establishing biosimilarity. This presentation will provide a look at the multi-stage development for a biosimilar, including a review of the regulatory landscape, structural characterization techniques for biosimilarity assessment, and early phase clinical research challenges
Payload Core Product Line Accelerates ADC Clinical TimelinesMerck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3ddy1sT
Innovators currently must endure years of development and manufacturing to arrive at the most commonly used cGMP payloads. Explore our core product line for dolastatin and maytansinoid payloads which can get developers to the clinic faster while reducing risk.
Dolastatins are antimitotic peptides which exhibit highly potent cytotoxic effects in cancer cells. Due to their pronounced antitumor effects, dolastatins have demonstrated clinical success as payloads for ADCs. However, innovators still face numerous challenges when developing and manufacturing ADC therapies, leading to increased costs and delayed timelines. Our core product line aims to address these challenges.
DOLCore™ product is a versatile and advanced intermediate that can simplify the synthesis of dolastatin payloads by reducing the number of synthesis steps from 15-20 to four or fewer. The value of DOLCore™ translates to significant savings in development and manufacturing costs driven by risk reduction in payload synthesis and avoidance of supply chain disruption.
In this webinar, you will learn about:
• Advantages of dolastatin over other payloads in ADC therapies
• Proprietary DOLCore™ and MayCore™ products
• Flexibility to make new or established dolastatins
• Rapid synthesis technology accelerating the path to drug commercialization
• Seamless supply chain with reduced complexity and regulatory support
Presented by: David Goeddel, Ph.D., Director of API R&D
Payload Core Product Line Accelerates ADC Clinical TimelinesMilliporeSigma
Watch the presentation of this webinar here: https://bit.ly/3ddy1sT
Innovators currently must endure years of development and manufacturing to arrive at the most commonly used cGMP payloads. Explore our core product line for dolastatin and maytansinoid payloads which can get developers to the clinic faster while reducing risk.
Dolastatins are antimitotic peptides which exhibit highly potent cytotoxic effects in cancer cells. Due to their pronounced antitumor effects, dolastatins have demonstrated clinical success as payloads for ADCs. However, innovators still face numerous challenges when developing and manufacturing ADC therapies, leading to increased costs and delayed timelines. Our core product line aims to address these challenges.
DOLCore™ product is a versatile and advanced intermediate that can simplify the synthesis of dolastatin payloads by reducing the number of synthesis steps from 15-20 to four or fewer. The value of DOLCore™ translates to significant savings in development and manufacturing costs driven by risk reduction in payload synthesis and avoidance of supply chain disruption.
In this webinar, you will learn about:
• Advantages of dolastatin over other payloads in ADC therapies
• Proprietary DOLCore™ and MayCore™ products
• Flexibility to make new or established dolastatins
• Rapid synthesis technology accelerating the path to drug commercialization
• Seamless supply chain with reduced complexity and regulatory support
Presented by: David Goeddel, Ph.D., Director of API R&D
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
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
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
Moving your Gene Therapy from R&D to IND: How to navigate the Regulatory Land...MilliporeSigma
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
An Integrated Approach to Ensure Viral Vector and Gene Therapy Commercial Rea...Merck Life Sciences
Come learn more about our integrated approach to ensure viral vector and gene therapy commercial readiness. We will discuss topics relating to process development for viral vector manufacturing, biosafety testing and commercial readiness.
Significant progress has been made for the use of viral vectors for gene therapy. Promising clinical trial results as well as recent FDA approval for CAR-T cell therapy to treat certain children and young adults with B-cell lymphoblastic leukemia have signaled advancements in the field. This marks a historic action, providing opportunities for new viral vector technologies to transform medicine and the way patients are treated and even cured. The need for process development for viral vector manufacturing to improve yield to meet patient demand, biosafety testing for product characterization, potency and safety and commercial readiness to accelerate therapy to-market are critically important. Here, we emphasis an integrated approach that allows our customers solutions to ensure viral vector and gene therapy commercial readiness to meet the growing market need.
In this webinar, you will learn:
● Process development advances for production scale-up of viral vectors for gene therapy
● Methods specific for viral gene therapy product characterization, purity, potency, safety and release testing
● Commercial readiness through our US and UK Centers of Excellence for viral product manufacturing
In the new world of connected healthcare, medical device manufacturers are challenged with cybersecurity issues to comply with the new FDA regulations. We examine the 5 domain areas of cybersecurity which apply to IoT HealthCare Vendors/ Providers.
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
Biosimilars are biological generics drugs.They undergo a rigorous evaluation to get approved.How to prove biosimilariy from analytical comparability is explained using a recently approved US FDA bio-similar monoclonal antibody.
How Molecular Structure Influences Potency of a Therapeutic BiologicMerck Life Sciences
This review will give the listener an understanding of how the molecular structure, and the different ways they can be measured, influences binding and affects potency of a therapeutic biologic.
Product characterization is key to successful biological drug development. Comprehensive characterization of new therapeutic monoclonal antibodies requires a deep understanding of their structural and functional critical quality attributes (CQAs) which may impact product potency, stability and safety. Various analytical approaches can be used to characterize the effects of changes during the process of generating a biological drug.
This webinar will review some of the approaches to N-glycan profiling of monoclonal antibodies using Mass Spectrometry (MS), including Hydrogen Deuterium Exchange (HDX-MS) analytics. Using the Humira monoclonal antibody, the effect of glycosylation on the Fc-region mediated effector function was assessed with binding and CDC and ADCC activity assays. This review will give the listener an understanding of how the molecular structure, and the different ways they can be measured, influences binding and affects potency of a therapeutic biologic.
In this webinar you will learn:
- HDX-MS - when and why to use
- Glycosylation effects assessment by activity assays
Production and purification of Viral vectors for gene and cell therapy appli...Dr. Priyabrata Pattnaik
Presentation at "2016 Osong BioExcellence - Renaissance in Immunotherapy" at South Korea, an event jointly hosted by Kbio Health and Merck on 6th October 2016.
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)
Account-Based Marketing (ABM) is a growth strategy that relies on marketing and sales working closely together to influence multiple stakeholders for a select set of high-value companies. Our virtual Knoxville HUG event on June 30th focused on the five steps for building and executing an ABM strategy and HubSpot's new tools that support ABM.
“Challenges of biosimilar product development and experience gained”
Shows the development process for biosimilars, focusing specifically on the company’s experience
Unveiling the Potential of your AAV Gene Therapy: Orthogonal methods to under...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3pCCjPF
Ensure your Adeno-Associated Virus (AAV) is safe throughout its entire drug development journey. Learn methods that will help you speed to clinic, potentially treating diseases sooner and with greater effectiveness.
The potential of gene therapies to cure previously untreatable diseases has spurred the development of novel drugs, including those based on Adeno-Associated Virus (AAV). As with all biopharmaceuticals, it is important to identify and monitor the critical quality attributes (CQAs) of these products to ensure their safety and efficacy.
In this webinar, we will present a range of orthogonal methods to understand and define the CQAs of AAV products. These include assays for the confirmation of capsid protein identity and quantity, as well as the characterization of important product-related impurities, such as aggregates. Together these methods represent a comprehensive analytical testing package to support the characterization and lot release of AAV products.
In this webinar, you will learn:
• How to identify and monitor the critical quality attributes (CQAs) of your AAV therapy
• What assays to utilize to confirm capsid protein identity and quantity
• Why you need look to product characterization to identify and remove important product-related impurities
Why a Build-Your-Own Healthcare Data Platform Will Fall Short and What to Do ...Health Catalyst
Health system may have some compelling reasons for choosing to build a data platform versus partner with a healthcare analytics vendor on a commercial solution. However, while organizations may think they’re saving money, gaining control and security, and more by opting for a homegrown approach, they’ll more than likely encounter challenges, hidden costs, and limitations. In comparison to a commercial-grade, healthcare-specific platform from a vendor, build-your-own solutions fall short when it comes to domain-specific content, technical expertise, total cost of ownership, and more. Organizations that partner on a vended platform vastly improve their chances of optimizing and scaling their analytic investment over time and achieving measurable improvement.
Biosimilar Development Regulatory, Analytical, and Clinical Considerations SGS
The development pathway of a biosimilar is unlike that of a novel biotherapeutic. While there is an increased requirement for analytics throughout a biosimilars development project, and a Phase II clinical trial is generally omitted, careful consideration must be given to the planning of the other phases of development. Many regulatory authorities reference a “step-by-step” approach to establishing biosimilarity. This presentation will provide a look at the multi-stage development for a biosimilar, including a review of the regulatory landscape, structural characterization techniques for biosimilarity assessment, and early phase clinical research challenges
Payload Core Product Line Accelerates ADC Clinical TimelinesMerck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3ddy1sT
Innovators currently must endure years of development and manufacturing to arrive at the most commonly used cGMP payloads. Explore our core product line for dolastatin and maytansinoid payloads which can get developers to the clinic faster while reducing risk.
Dolastatins are antimitotic peptides which exhibit highly potent cytotoxic effects in cancer cells. Due to their pronounced antitumor effects, dolastatins have demonstrated clinical success as payloads for ADCs. However, innovators still face numerous challenges when developing and manufacturing ADC therapies, leading to increased costs and delayed timelines. Our core product line aims to address these challenges.
DOLCore™ product is a versatile and advanced intermediate that can simplify the synthesis of dolastatin payloads by reducing the number of synthesis steps from 15-20 to four or fewer. The value of DOLCore™ translates to significant savings in development and manufacturing costs driven by risk reduction in payload synthesis and avoidance of supply chain disruption.
In this webinar, you will learn about:
• Advantages of dolastatin over other payloads in ADC therapies
• Proprietary DOLCore™ and MayCore™ products
• Flexibility to make new or established dolastatins
• Rapid synthesis technology accelerating the path to drug commercialization
• Seamless supply chain with reduced complexity and regulatory support
Presented by: David Goeddel, Ph.D., Director of API R&D
Payload Core Product Line Accelerates ADC Clinical TimelinesMilliporeSigma
Watch the presentation of this webinar here: https://bit.ly/3ddy1sT
Innovators currently must endure years of development and manufacturing to arrive at the most commonly used cGMP payloads. Explore our core product line for dolastatin and maytansinoid payloads which can get developers to the clinic faster while reducing risk.
Dolastatins are antimitotic peptides which exhibit highly potent cytotoxic effects in cancer cells. Due to their pronounced antitumor effects, dolastatins have demonstrated clinical success as payloads for ADCs. However, innovators still face numerous challenges when developing and manufacturing ADC therapies, leading to increased costs and delayed timelines. Our core product line aims to address these challenges.
DOLCore™ product is a versatile and advanced intermediate that can simplify the synthesis of dolastatin payloads by reducing the number of synthesis steps from 15-20 to four or fewer. The value of DOLCore™ translates to significant savings in development and manufacturing costs driven by risk reduction in payload synthesis and avoidance of supply chain disruption.
In this webinar, you will learn about:
• Advantages of dolastatin over other payloads in ADC therapies
• Proprietary DOLCore™ and MayCore™ products
• Flexibility to make new or established dolastatins
• Rapid synthesis technology accelerating the path to drug commercialization
• Seamless supply chain with reduced complexity and regulatory support
Presented by: David Goeddel, Ph.D., Director of API R&D
The Butterfly Effect: How to see the impact of small changes to your ADCMilliporeSigma
Watch this webinar here: https://bit.ly/31PRr2z
Small changes to the design of antibody-drug conjugate can have a dramatic effect on its structure and biological activity. Effective product characterization is essential to understanding the impact of these changes. Here we discuss methods to provide insight at critical junctures in ADC development.
There are many different design considerations facing developers of antibody-drug conjugates: these variables must be tuned to achieve the right balance of efficacy and safety. For example, the choice of linker can influence an ADC's potency, toxicity and pharmacokinetics.
In this webinar we explore the influence of various PEG linkers on the structure of a model ADC by identifying specific sites of conjugation by peptide mapping, investigating changes in higher order structure by HDX mass spectrometry, and examining the impact on binding by SPR spectroscopy.
We demonstrate that employing a range of orthogonal methods is critical to understanding the structure-function relationships of an ADC.
In this webinar, you will learn about:
• How the choice of linker can influence an ADC's activity
• Information-rich methods to probe ADC structure and function
• Effective strategies for thorough characterization of ADC products
The Butterfly Effect: How to see the impact of small changes to your ADCMerck Life Sciences
Watch this webinar here: https://bit.ly/31PRr2z
Small changes to the design of antibody-drug conjugate can have a dramatic effect on its structure and biological activity. Effective product characterization is essential to understanding the impact of these changes. Here we discuss methods to provide insight at critical junctures in ADC development.
There are many different design considerations facing developers of antibody-drug conjugates: these variables must be tuned to achieve the right balance of efficacy and safety. For example, the choice of linker can influence an ADC's potency, toxicity and pharmacokinetics.
In this webinar we explore the influence of various PEG linkers on the structure of a model ADC by identifying specific sites of conjugation by peptide mapping, investigating changes in higher order structure by HDX mass spectrometry, and examining the impact on binding by SPR spectroscopy.
We demonstrate that employing a range of orthogonal methods is critical to understanding the structure-function relationships of an ADC.
In this webinar, you will learn about:
• How the choice of linker can influence an ADC's activity
• Information-rich methods to probe ADC structure and function
• Effective strategies for thorough characterization of ADC products
Prof Clive Badman OBE
Presentation at EIPG - Royal Pharmaceutical Society Scientific Symposium "Advances in Technology Impacting the Pharmaceutical Industry" at the University of Strathclyde, Glasgow 2015.
Antibody drug conjugates for cancer therapy - prospects and challenges htpDoriaFang
Antibody-drug conjugates (ADCs) are a rapidly evolving class of anticancer therapeutics consisting of antibodies attached to potent cytotoxic drugs via chemical linkers. What're the prospects and challenges of Antibody-Drug Conjugates for cancer therapy?
Employing Innovative Platform Manufacturing and Biosafety Testing for your Ge...Merck Life Sciences
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
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
CoreRx is a contract pharmaceutical development and manufacturing organization that helps get you into the clinic faster, providing a complete spectrum of cGMP solutions for pharmaceutical dosage form development. Our wide range of support services, extensive instrumentation and rigorous quality systems provide timely results communicated in a clear, efficient and consistent manner.
CoreRx, is a contract pharmaceutical development and manufacturing organization that helps get you into the clinic faster, providing a complete spectrum of cGMP solutions for pharmaceutical dosage form development. Our wide range of support services, extensive instrumentation and rigorous quality systems provide timely results communicated in a clear, efficient and consistent manner.
Tackling the challenges of single-use manufacturing for ADCsMilliporeSigma
Watch the full webinar here: https://bit.ly/2Ix3uud
In this webinar, you will learn:
• How SU assemblies are used in the ADC development space
• Recommendations for consistent transfer of SU processes to manufacturing
• Understand if SU technology is right for your product
• Evaluate the pros and cons of SU for ADCs
Antibody Drug Conjugates (ADCs) are a class of biomolecules that has seen rapid growth with multiple new commercial products in 2020. Adoption of SU systems has been slow due to concerns for safe handling of organic solvents and the toxic small molecule payload. Recent advances in Single-use technology have overcome these concerns and now provide understanding of the suitability, scalability, and fluid compatibility of both the single-use components as well as the supporting hardware and controls. In this webinar, we show how the single-use technology can deliver consistent and scalable ADC chemistry and functionality with desired final product specifications and high yield.
Tackling the challenges of single-use manufacturing for ADCsMerck Life Sciences
You can watch the webinar here: https://bit.ly/2Ix3uud
In this webinar, you will learn:
• How SU assemblies are used in the ADC development space
• Recommendations for consistent transfer of SU processes to manufacturing
• Understand if SU technology is right for your product
• Evaluate the pros and cons of SU for ADCs
Antibody Drug Conjugates (ADCs) are a class of biomolecules that has seen rapid growth with multiple new commercial products in 2020. Adoption of SU systems has been slow due to concerns for safe handling of organic solvents and the toxic small molecule payload. Recent advances in Single-use technology have overcome these concerns and now provide understanding of the suitability, scalability, and fluid compatibility of both the single-use components as well as the supporting hardware and controls. In this webinar, we show how the single-use technology can deliver consistent and scalable ADC chemistry and functionality with desired final product specifications and high yield.
ADC Production - A Journey made safer and fasterMilliporeSigma
In this webinar, you will learn:
How Single-Use helps to simplify ADC manufacturing
Safety and Integrity of the complete process
Flexibility and adaptability to changing needs
How to speed up the synthesis of high-potent payloads and improve the bioavailability of the ADC
Detailed description:
The development of an ADC is a long journey that can be speeded-up with the adoption of proper manufacturing tools and new linker-payload solutions. Single-Use equipment applied to the GMP manufacturing of ADC means operator safety, decreased risk of contamination, scalability, reproducibility, flexibility, small footprint, lower cost, and saved time through efficiency (easy setup and cleanup, no need for cleaning validation). The adoption of payload intermediates such as DolCoreTM and MayCoreTM can speed your development project up, while innovative linkers like ChetoSensarTM increase its chances of success. This webinar explains how these technologies improve the ADC production process end-to-end, ultimately enhancing patient safety.
Accelerate innovation and manufacturing in cell and gene therapy.pptxGenScript ProBio
The rapid expansion of the gene and cell therapy pipeline created constraints to accessing contract capacities around the globe. Innovation in gene and cell therapy expanded many drug development pipelines, and startups that are lacking internal production capacities heavily rely on contract manufacturing organizations (CDMO).
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
Moving your Gene Therapy from R&D to IND: How to navigate the Regulatory Land...Merck Life Sciences
Watch the recording of this presentation here: https://bit.ly/3SqOsoP
Novel therapies, including cell and gene therapies, continue to be central to innovation in healthcare and represent the fastest growing area of therapeutic medicine. As a consequence, the number of gene therapies undergoing clinical trials has increased significantly in the last five years.
Manufacturing processes for these novel therapeutics are very complex with a high risk of contamination. Regulatory agencies world-wide have responded by issuing guidance to outline their expectations for development and manufacture of cell and gene therapies. Currently, regulatory guidance is not harmonized globally and can often lead to confusion within industry and increased risk of non-compliance.
In this webinar, we'll answer:
• Which regulatory guidelines do you need to comply for your INDs?
• When do you start implementing GMPs and validated assays?
• How do you get your QC testing strategy ‘right the first time’?
• How do you ensure testing is not your rate limiting step for the IND submission?
Presented by:
Manjula Aysola, Senior Regulatory Consultant
Dr. Alison Armstrong, Sr. Director, Technical and Scientific Solutions
Identity testing by NGS as a means of risk mitigation for viral gene therapiesMerck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3RijkHC
Detailed description:
Imagine you’ve just completed a manufacturing run for your viral vector. Identity testing is performed to confirm the vector sequence. But when the results come back the data reveals unexpected sequence variants! With an appropriate risk mitigation testing strategy, this situation can be prevented.
The situation described above is not hypothetical, and happens more that you think, costing valuable time and resources.
Investigatory testing has shown that sequence variants present in starting materials (e.g. plasmids) are likely to make their way to the final product. Adequate identification of low-level variants with an appropriately sensitive method is critical in ensuring the quality of the final product. A risk-based testing strategy, in the context of identity, for viral vector manufacturing will be presented, focusing on key testing points. NGS assays for identity and variant detection will be highlighted due to their extremely sensitive nature compared to traditional approaches.
In this webinar, we'll explore:
• Regulatory requirements for identity testing
• NGS applications for identity testing as compared to traditional methods
• A case study on the impact of not establishing a proper risk-based testing strategy
Presented by: Bradley Hasson, Director of Lab Operations for NGS Services
Latest advancements of melt based 3D printing technologies for oral drug deli...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3A2WcH4
The application of polymer excipients in 3D printing manufacturing is usually limited due to the concerns of filament strength, high processing temperature and large scale manufacturing.
Latest technology developments are targeting a direct melt deposition to simplify the process and enable a constant and efficient process. Two different processing approaches will be presented:
The advanced melt drop deposition, where individual three dimensional geometries can be created by depostition of polymer droplets and the MED® 3D printing technology which allows by precise layer-by-layer deposition to produce objects with well-designed geometric structures.
In this webinar, you will learn:
• Latest advancements of melt based 3D printing approaches
• Application examples for the individual technologies
• Deep dive in the MED® 3D printing technology to design dedicated drug release profiles
Presented by:
Dr. Thomas Kipping, Head of Drug Carriers
Dr. Xianghao Zuo, Deputy Director of R&D, Triastek
CAR-T Manufacturing Innovations that Work - Automating Low Volume Processes a...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3NDNIKe
Automated, fit-for-purpose tools are essential in CAR-T processing to support sustainable manufacturing of clinical and market-approved cell therapy products. This webinar will discuss how the ekko™ Acoustic Cell Processing System uses acoustic technology as a touchless approach to manipulate cells, enabling a modular tool across the CAR-T manufacturing workflow. Typical performance of templated ekko™ System processes for DMSO washout of leukapheresis material, low volume and high cell concentrate for electroporation preparation, and harvest of expanded T cells will be reviewed.
This webinar will also give an early glimpse at the ekko™ Select System for unmatched T cell selection.
In this webinar, you will:
• Uncover how the ekko™ System supports the broad industrialization of cell therapy, with particular focus on how to achieve low volume, high concentrate cell product for critical transduction and transfection steps
• Discover how ekko™ System for wash and concentrate processes throughout the cell therapy workflow achieve high cell recovery, viability, and effective residual removal
• Preview to ekko™ Select, our cell therapy selection platform, to achieve unmatched ease-of-use with direct processing from leukopaks reducing the need for preparation steps
Presented by:
Benjamin Ross-Johnsrud, Acoustic Technology Expert
Robert Scott, Mechanical Engineer III
Viral safety of biologics: What's changing with the ICH Q5A revision?Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3t7X9tg
How does the ICH Q5A revision impact viral safety strategies for biologics?
Biologics continue to grow at a fast pace. Manufactured using cell lines of human or animal origin, these are at risk of viral contamination making safety strategies critical. A comprehensive risk mitigation strategy using multiple orthogonal measures is a regulatory expectation. ICH Q5A, the globally-harmonized guideline outlines the expectations. ICH Q5A is currently being revised to address recent scientific advancements including novel therapeutic modalities, new manufacturing paradigms, updates in viral clearance applications, and alternate detection technologies. We’ll discuss the expected changes and potential impact on viral safety strategies with case studies and examples.
In this webinar, you will learn about:
• The Importance of virus testing in biologics products
• Regulatory landscape, expectations for the Q5A revision
• What's new and changing
• Examples of alternate testing schedules, impact on viral clearance
Presented by:
Manjula Aysola, Senior Regulatory Consultant
Alison Armstrong, PhD, Sr. Director, Technical and Scientific Solutions
Insights from a Global Collaboration Accelerating Vaccine Development with an...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3Nbb5ug
Get insights and best practices from a multinational team establishing a platform for vaccine production. See how a long-term collaboration on a bench-scale process used to produce a Virus Like Particle (VLP) vaccine for SARS-CoV-2 was successfully converted to a robust GMP-compatible, scalable process.
The COVID-19 pandemic further emphasized the need for collaboration in the development of urgently needed vaccines and therapeutics. In this webinar, we take you behind the scenes of our collaboration with Technovax and Innovative Biotech in which a scalable VLP vaccine platform was optimized for use in a production facility in Nigeria in response to the need for local production of SARS-CoV-2 vaccines. The flexibility and robustness of the platform will enable its rapid deployment to support the West African pandemic readiness program. Initial development of the VLP process began in late 2019 and by March 2020, was already adapted for production of a SARS-CoV-2 vaccine.
In this webinar, you will learn:
• About building a priceless collaborative network with integrated solutions
• Virus-Like Particle Vaccines
• Process Development Overview and Challenges
• Pre-clinical Results and Next Steps
Presented by:
Jose M. Galarza, PhD,
President and Founder of TechnoVax
Naomi Baer,
Business development consultant, Emerging Biotech, BioProcess division
Youssef Gaabouri, Eng. ,
Associate Director, Head of Sales Middle East & Africa, BioProcess division
Risk-Based Qualification of X-Ray Sterilization for Single-Use SystemsMerck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3vQf0qv
In the single-use bioprocess industry, X-ray irradiation warrants consideration as an alternate sterilization technology. Using a risk-based qualification testing strategy is important when evaluating and implementing equivalent ionizing irradiation sterilization methods.
The urgent need for life-saving therapies as a result of the global pandemic has reinforced the criticality of flexibility in pharmaceutical manufacturing, including sterilization. The single-use bioprocess industry traditionally has employed gamma irradiation sterilization. X-ray irradiation is being considered as an additional sterilization technology for business and supply continuity. We will share a risk-based qualification testing strategy including Extractables and data generated to support comparability of gamma irradiation and X-ray irradiation as equivalent ionizing irradiation sterilization methods.
In this webinar, you will learn about:
• The comparison of gamma and X-ray irradiation sterilization
• A risk-based qualification test strategy
• Data evaluation of gamma versus X-ray sterilized single-use components
Presented by:
Monica Cardona,
Global Senior Program Manager
Paul Killian, Ph.D.,
R&D Director, Analytical Technologies
Rapid replication competent adenovirus (rRCA) detection: Accelerate your lot ...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3MJ4u9V
Testing for presence of replication competent adenovirus (RCA) is a key component to ensure patient safety and a requirement for all biologicals manufactured using adenoviral vectors. For many adenoviral-based products, the RCA assay is a rate-limiting assay for lot release.
Join this webinar to learn about a rapid RCA detection assay currently in development, which combines a 7-day culture assay with a highly sensitive molecular endpoint specific for RCA. The method can detect presence of as little as 1 RCA in adenoviral vector material at an approximate concentration of 5x107 - 2x108 vector particles (VP)/mL, making it a suitable method to meet regulatory requirements while accelerating your lot release timelines.
In this webinar, you will learn about:
• Regulatory framework for adenoviral vector products
• Considerations for lot release testing of adenoviral-based therapies
• Advantages of a rapid method for RCA testing on production lot material
Presented by:
Axel Fun, Ph.D.,
Principal Scientist
Alberto Santana, MBA,
Product Manager, Biologics Biosafety Testing
The High Intensity Sweeteners Neotame and Sucralose: 2 Ways to ace the Patien...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3vQyN7K
Bitter medicines are an important issue, especially for pediatric applications. As several APIs have bitter tasting components, high intensity sweeteners for taste optimization are of great interest. Join our webinar to discover our new sweetener toolbox enabling safe and stable formulations.
Mask bitter aftertaste for a sweeter pill to swallow! Patients’ compliance and the therapeutic benefit are supported by a pleasant taste of pharmaceutical formulations. With the high intensity sweeteners Neotame and Sucralose, you have efficient tools at hand which are superior to other sweeteners in many aspects:
• excellent sugar-like taste profile
• outstanding sweetness factors
• use effectiveness
• enhanced stability
We will present our new toolbox of two high performance sweeteners and focus on aspects of stability, safety, the application in various dosage forms, and market perception.
In this webinar, you will learn:
• How to optimize the patients' taste experience of your pharmaceuticals
• How sweeteners can be differentiated by their sensory profiles and features
• How our new product offering Neotame can be effectively used in your targeted formulations
Presented by:
Almut von der Brelie,
Senior Manager Strategic Marketing
Excipients for Solid Applications
The Developability Classification System (DCS): Enabling an Optimized Approac...Merck Life Sciences
This whitepaper by Dr. Daniel Joseph Price outlines how poorly soluble drug formulations can be designed using the developability classification system (DCS).
The DCS identifies the root cause of low solubility and enables lean, cost-effective and effective formulations to be developed.
#solubility #pharmaceuticalmanufacturing #oralsoliddosage #drugdevelopment
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!
Introducing our novel Sf9 rhabdovirus-negative (Sf-RVN®) Platform.pdfMerck Life Sciences
The Baculovirus Expression Vector System (BEVS) is a powerful eucaryotic vector system and Spodoptera frugiperda (Sf) cell lines are widely used as hosts for BEVS. However, the majority of Sf9 and Sf21 cell lines contain a Sf-rhabdovirus which is considered a process contaminant and must be eliminated during the process. To improve the safety profile of the BEVS production method, we offer a Sf9 rhabdovirus-negative (Sf-RVN®) cell line with companion chemically defined medium. Combined, they form the Sf-RVN® Platform which provides a performant rhabdovirus-free BEVS alternative to produce recombinant protein, VLP and AAV and enhances risk mitigation.
The Importance of Community Nursing Care.pdfAD Healthcare
NDIS and Community 24/7 Nursing Care is a specific type of support that may be provided under the NDIS for individuals with complex medical needs who require ongoing nursing care in a community setting, such as their home or a supported accommodation facility.
CHAPTER 1 SEMESTER V PREVENTIVE-PEDIATRICS.pdfSachin Sharma
This content provides an overview of preventive pediatrics. It defines preventive pediatrics as preventing disease and promoting children's physical, mental, and social well-being to achieve positive health. It discusses antenatal, postnatal, and social preventive pediatrics. It also covers various child health programs like immunization, breastfeeding, ICDS, and the roles of organizations like WHO, UNICEF, and nurses in preventive pediatrics.
Defecation
Normal defecation begins with movement in the left colon, moving stool toward the anus. When stool reaches the rectum, the distention causes relaxation of the internal sphincter and an awareness of the need to defecate. At the time of defecation, the external sphincter relaxes, and abdominal muscles contract, increasing intrarectal pressure and forcing the stool out
The Valsalva maneuver exerts pressure to expel faeces through a voluntary contraction of the abdominal muscles while maintaining forced expiration against a closed airway. Patients with cardiovascular disease, glaucoma, increased intracranial pressure, or a new surgical wound are at greater risk for cardiac dysrhythmias and elevated blood pressure with the Valsalva maneuver and need to avoid straining to pass the stool.
Normal defecation is painless, resulting in passage of soft, formed stool
CONSTIPATION
Constipation is a symptom, not a disease. Improper diet, reduced fluid intake, lack of exercise, and certain medications can cause constipation. For example, patients receiving opiates for pain after surgery often require a stool softener or laxative to prevent constipation. The signs of constipation include infrequent bowel movements (less than every 3 days), difficulty passing stools, excessive straining, inability to defecate at will, and hard feaces
IMPACTION
Fecal impaction results from unrelieved constipation. It is a collection of hardened feces wedged in the rectum that a person cannot expel. In cases of severe impaction the mass extends up into the sigmoid colon.
DIARRHEA
Diarrhea is an increase in the number of stools and the passage of liquid, unformed feces. It is associated with disorders affecting digestion, absorption, and secretion in the GI tract. Intestinal contents pass through the small and large intestine too quickly to allow for the usual absorption of fluid and nutrients. Irritation within the colon results in increased mucus secretion. As a result, feces become watery, and the patient is unable to control the urge to defecate. Normally an anal bag is safe and effective in long-term treatment of patients with fecal incontinence at home, in hospice, or in the hospital. Fecal incontinence is expensive and a potentially dangerous condition in terms of contamination and risk of skin ulceration
HEMORRHOIDS
Hemorrhoids are dilated, engorged veins in the lining of the rectum. They are either external or internal.
FLATULENCE
As gas accumulates in the lumen of the intestines, the bowel wall stretches and distends (flatulence). It is a common cause of abdominal fullness, pain, and cramping. Normally intestinal gas escapes through the mouth (belching) or the anus (passing of flatus)
FECAL INCONTINENCE
Fecal incontinence is the inability to control passage of feces and gas from the anus. Incontinence harms a patient’s body image
PREPARATION AND GIVING OF LAXATIVESACCORDING TO POTTER AND PERRY,
An enema is the instillation of a solution into the rectum and sig
Antibiotic Stewardship by Anushri Srivastava.pptxAnushriSrivastav
Stewardship is the act of taking good care of something.
Antimicrobial stewardship is a coordinated program that promotes the appropriate use of antimicrobials (including antibiotics), improves patient outcomes, reduces microbial resistance, and decreases the spread of infections caused by multidrug-resistant organisms.
WHO launched the Global Antimicrobial Resistance and Use Surveillance System (GLASS) in 2015 to fill knowledge gaps and inform strategies at all levels.
ACCORDING TO apic.org,
Antimicrobial stewardship is a coordinated program that promotes the appropriate use of antimicrobials (including antibiotics), improves patient outcomes, reduces microbial resistance, and decreases the spread of infections caused by multidrug-resistant organisms.
ACCORDING TO pewtrusts.org,
Antibiotic stewardship refers to efforts in doctors’ offices, hospitals, long term care facilities, and other health care settings to ensure that antibiotics are used only when necessary and appropriate
According to WHO,
Antimicrobial stewardship is a systematic approach to educate and support health care professionals to follow evidence-based guidelines for prescribing and administering antimicrobials
In 1996, John McGowan and Dale Gerding first applied the term antimicrobial stewardship, where they suggested a causal association between antimicrobial agent use and resistance. They also focused on the urgency of large-scale controlled trials of antimicrobial-use regulation employing sophisticated epidemiologic methods, molecular typing, and precise resistance mechanism analysis.
Antimicrobial Stewardship(AMS) refers to the optimal selection, dosing, and duration of antimicrobial treatment resulting in the best clinical outcome with minimal side effects to the patients and minimal impact on subsequent resistance.
According to the 2019 report, in the US, more than 2.8 million antibiotic-resistant infections occur each year, and more than 35000 people die. In addition to this, it also mentioned that 223,900 cases of Clostridoides difficile occurred in 2017, of which 12800 people died. The report did not include viruses or parasites
VISION
Being proactive
Supporting optimal animal and human health
Exploring ways to reduce overall use of antimicrobials
Using the drugs that prevent and treat disease by killing microscopic organisms in a responsible way
GOAL
to prevent the generation and spread of antimicrobial resistance (AMR). Doing so will preserve the effectiveness of these drugs in animals and humans for years to come.
being to preserve human and animal health and the effectiveness of antimicrobial medications.
to implement a multidisciplinary approach in assembling a stewardship team to include an infectious disease physician, a clinical pharmacist with infectious diseases training, infection preventionist, and a close collaboration with the staff in the clinical microbiology laboratory
to prevent antimicrobial overuse, misuse and abuse.
to minimize the developme
One of the most developed cities of India, the city of Chennai is the capital of Tamilnadu and many people from different parts of India come here to earn their bread and butter. Being a metropolitan, the city is filled with towering building and beaches but the sad part as with almost every Indian city
CHAPTER 1 SEMESTER V - ROLE OF PEADIATRIC NURSE.pdfSachin Sharma
Pediatric nurses play a vital role in the health and well-being of children. Their responsibilities are wide-ranging, and their objectives can be categorized into several key areas:
1. Direct Patient Care:
Objective: Provide comprehensive and compassionate care to infants, children, and adolescents in various healthcare settings (hospitals, clinics, etc.).
This includes tasks like:
Monitoring vital signs and physical condition.
Administering medications and treatments.
Performing procedures as directed by doctors.
Assisting with daily living activities (bathing, feeding).
Providing emotional support and pain management.
2. Health Promotion and Education:
Objective: Promote healthy behaviors and educate children, families, and communities about preventive healthcare.
This includes tasks like:
Administering vaccinations.
Providing education on nutrition, hygiene, and development.
Offering breastfeeding and childbirth support.
Counseling families on safety and injury prevention.
3. Collaboration and Advocacy:
Objective: Collaborate effectively with doctors, social workers, therapists, and other healthcare professionals to ensure coordinated care for children.
Objective: Advocate for the rights and best interests of their patients, especially when children cannot speak for themselves.
This includes tasks like:
Communicating effectively with healthcare teams.
Identifying and addressing potential risks to child welfare.
Educating families about their child's condition and treatment options.
4. Professional Development and Research:
Objective: Stay up-to-date on the latest advancements in pediatric healthcare through continuing education and research.
Objective: Contribute to improving the quality of care for children by participating in research initiatives.
This includes tasks like:
Attending workshops and conferences on pediatric nursing.
Participating in clinical trials related to child health.
Implementing evidence-based practices into their daily routines.
By fulfilling these objectives, pediatric nurses play a crucial role in ensuring the optimal health and well-being of children throughout all stages of their development.
Health Education on prevention of hypertensionRadhika kulvi
Hypertension is a chronic condition of concern due to its role in the causation of coronary heart diseases. Hypertension is a worldwide epidemic and important risk factor for coronary artery disease, stroke and renal diseases. Blood pressure is the force exerted by the blood against the walls of the blood vessels and is sufficient to maintain tissue perfusion during activity and rest. Hypertension is sustained elevation of BP. In adults, HTN exists when systolic blood pressure is equal to or greater than 140mmHg or diastolic BP is equal to or greater than 90mmHg. The
Nursing Care of Client With Acute And Chronic Renal Failure.ppt
How to Accelerate and Enhance ADC Therapies
1. The life science business of Merck KGaA,
Darmstadt, Germany operates as
MilliporeSigma in the U.S. and Canada.
How to Accelerate and
Enhance ADC Therapies
Ross Bemowski, Ph.D., Associate Director API R&D
Jeff Carroll, Team Lead ADC Express
2. The life science business
of Merck KGaA, Darmstadt,
Germany operates as
MilliporeSigma in the U.S.
and Canada
3. Agenda
1
2
3 ADC Express™ Services
Jeff Carroll, Team Lead
Chetosensar™ Technology
Ross Bemowski, Ph.D.
ADCore Payload Intermediates
Ross Bemowski, Ph.D.
4. 4
Antibody-Drug Conjugate Composition
Specific for a tumor-associated
antigen that has restricted
expression on normal cells.
Designed to kill target
cells when internalized
and released.
Attaches the cytotoxic agent to the
antibody and are designed to be stable in
circulation and release the cytotoxic agent
inside targeted cells.
Payloads
typically are
cytotoxic small
molecules
Antibody
Payload
Linker
Dolastatins – 40%
Maytansinoids – 25%
PBD’s – 10%
Webinar: How to Accelerate and Enhance ADC Therapies
5. Products to accelerate and enhance ADC drug discovery
and development
Webinar: How to Accelerate and Enhance ADC Therapies
5
ADCore Product Line
ChetoSensar™ Technology
Discovery/
Pre-Clinical
cGMP Clinical
Development for
Phases 1 and 2
Phase 3 and
Commercial
ADC Express™ Services
Lead
Candidate
ADC
3
ADC
2
ADC
1
DOLCore™ Intermediate MAYCore™ Intermediate PBDCore™ Intermediate
7. Payloads Used in ADC Development
75% of Payloads Arise from 3 Commonly Used Classes
Tubulin inhibitors
Derived from a sea hare
5 Commercial ADCs
Dolastatins
Maytansines
Tubulin inhibitors
Derived from an African shrub
1 Commercial ADC
PBD Dimers
DNA damaging agents
Derived from streptomyces
1 Commercial ADC
Webinar: How to Accelerate and Enhance ADC Therapies
7
8. 8
Where Do Developers Get these Payloads?
Purchase commonly used payloads
Synthesize novel payloads
Clinical / Commercial
Research
License
CDMO
Internally develop/manufacture
Webinar: How to Accelerate and Enhance ADC Therapies
9. Traditional
Approach
Drug companies must currently:
Find a qualified CMO – potent compounds
Invest > 5 MEUR per program
Invest 2 to 4 years for drug development
Invest in ongoing royalty and licensing fees
Avoid FTO issues
Deal with ongoing supply chain, quality, and
regulatory issues
Does a more efficient approach exist?
16 Chemical Steps
9
Historic Pathway to Developing Drug Conjugate Payloads
Webinar: How to Accelerate and Enhance ADC Therapies
10. Solid quality and regulatory platform – DMF/Dossier
Supply chain complexity reduced – Flexibility
Advantages of the payload core platform include
speed to market and FTO - Years
1
2
3
10
Imagine starting a marathon at mile 21…
Webinar: How to Accelerate and Enhance ADC Therapies
11. ADCore Product Line
PBDCore™ Intermediate
Webinar: How to Accelerate and Enhance ADC Therapies
11
PBDCore™ Intermediate can
be used to make diverse and
highly potent PBDs
Newly launched!
Simplify your Payload Synthesis
DOLCore™ Intermediate
DOLCore™ shortens
synthesis of dolastatin
payloads to 4 or fewer steps
Launched 2021
MAYCore™ Intermediate
MAYCore™ can be
modified to meet your
specific maytansine linker-
payload needs
Versatility
Can be
modified to
meet your
specific
linker-
payload
needs
Speed
Reduce the
number of
synthesis
steps
Reduced-
risk
Supply chain
risk reduction
– Ready
stock
available
High Quality
Chemical
processes
optimized to
ensure
quality
Reg.
Support
Phase
appropriate
regulatory
documents
available
Royalty-free
Royalty-free
license
Exclusivity
Earlier
market
exclusivity of
the
commercial
drug
Saving more
patients lives
12. DOLCore™ Increases Speed to Clinic and Reduces Risk
Traditional
Approach
Via DOLCore™
Intermediate
16 chemical Steps
3 chemical Steps
12
Webinar: How to Accelerate and Enhance ADC Therapies
13. Diversity in your payload synthesis
PBDCore™ Intermediate: Versatility Your Payload Needs
• PBDCore™ intermediate is a
versatile product that enables
late-stage modifications:
- Protecting groups can be
selectively cleaved under
mild conditions
- Ketone (purple) serves
as a functional handle
for cross-coupling
methodologies
Versatility
PBDCore™ Intermediate
Access diverse PBD Payloads
Webinar: How to Accelerate and Enhance ADC Therapies
13
14. Webinar: How to Accelerate and Enhance ADC Therapies
14
Any linker can be
conjugated to MAYCore™
intermediate
Low D-ala-MAYCore™
content
High diastereopurity
maintained in process
Key Features
MAYCore™ Intermediate
MAYCore™ Intermediate: High quality product suitable for all
published maytansine linkers
Problematic impurity controlled
15. 15 Webinar: How to Accelerate and Enhance ADC Therapies
• Only significant conjugatable impurity is D-ala-epimer
• Controlled to <2.5 A% in process
• Typically, <0.4 A% total other impurities
MAYCore™ Intermediate process impurities are well controlled
16. Webinar: How to Accelerate and Enhance ADC Therapies
16
ADCore – Accelerating Your Path to the Clinic
Synthesis Simplified
ADCore products allow for quick procurement of a cGMP supply of your desired drug linker
High Quality cGMP Intermediates
Highly pure intermediates made through well defined processes
Full regulatory support
Ready Now!
ADCore materials are available now for purchase royalty free
Contact us for information about free samples
18. A solution is needed for the hydrophobicity problem
Requires lowering of
DAR
Subsequent loss of
efficacy and smaller
therapeutic window
Side effects
Major modifications needed:
Drug-to-antibody ratio (DAR)
Change formulation
Payload selection
Conjugation site
Increased use of co-solvent Project termination
Additional investments needed
(time, $/€, people)
Increased development risk
Potential IP / FTO restraints
Further development
ADC poorly soluble
Implications
Solubility is a technical obstacle for today’s ADC
“I am aware of two Small Biotechs that even
went bankrupt because they could not
solve the solubility issue”
- Tier 1 US-based Univ. professor -
~22% of ADC clinical terminations were
caused by poor ADC solubility = loss of 2 to 3
programs advancing to commercial,
~15B€ loss over 10 years
Webinar: How to Accelerate and Enhance ADC Therapies
18
19. Our Chito-oligosaccharide enhances solubility
Consider it Solved!
19
ChetoSensar™ technology
is a
drug enabler
ChetoSensar™
Technology
Chito-oligosaccharide
Payload (=drug)
Antibody
Linker
Webinar: How to Accelerate and Enhance ADC Therapies
19
20. Incorporating ChetoSensar™ technology (CO) into an ADC
reduces hydrophobicity
0 5 10 15 20 25
m
AU
0
20
40
60
80
100
120
D
AD
1 A, Sig=280,4 R
e
f=o
ff (IS18IS018 2018-01-23 08-05-23_H
IC
18IS0180000003.D
)
10.631
D
AD
1 A, Sig=280,4 R
e
f=o
ff (IS18IS018 2018-01-23 08-05-23_H
IC
18IS0180000010.D
)
11.984
13.928
D
AD
1 A, Sig=280,4 R
e
f=o
ff (IS18IS018 2018-01-23 08-05-23_H
IC
18IS0180000018.D
)
0 5 10 15 20 25
mAU
0
20
40
60
80
100
120
DAD1 A, Sig=280,4 Ref=off (IS18IS018 2018-01-23 08-05-23_HIC18IS0180000003.D)
10.631
DAD1 A, Sig=280,4 Ref=off (IS18IS018 2018-01-23 08-05-23_HIC18IS0180000008.D)
12.168
14.141
DAD1 A, Sig=280,4 Ref=off (IS18IS018 2018-01-23 08-05-23_HIC18IS0180000015.D)
Hydrophilic
hydrophili
c
Hydrophobic
t/min
ADC
Absorption
Antibody alone
ADC + CO
Antibody alone
CO
Webinar: How to Accelerate and Enhance ADC Therapies
20
Hydrophobicity is a key
criteria that influences the
solubility,
permeability and
potency
of a drug
HIC Chromatogram
21. Many constructs have been prepared
Great flexibility with linkers, payloads and antibodies
Linkers
Disulfide
Cat B
Maleimide
ß-Gluc
Payloads
Dolastatins
Maytansines
Duocarmycin
CBI Dimers
PBD Dimers
SN38
Antibodies
Various IgG formats
Engineered
Bispecific
Conjugation
Technologies
Chemical coupling
Enzymatic coupling
Site specific
Stochastic
Webinar: How to Accelerate and Enhance ADC Therapies
21
22. Chemotherapeutics
Maximum tolerated dose (MTD)
Minimum effective dose (MED)
Maximum tolerated dose
Minimum effective dose
Traditional ADC ADC with ChetoSensar™
Improved potency
no additional side
effects
Possible fine-tuning
-several Payloads
possible
-different Linker
Maximum tolerated dose
Minimum effective dose
Therapeutic
window
MTD/MED
Drug
dose
ChetoSensar™ technology broadens the therapeutic
window
Increased solubility and
superior performance for
Interchain Maleimide
Cat B- MMAE ADC with
ChetoSensar™ was seen
in in-vivo studies
Webinar: How to Accelerate and Enhance ADC Therapies
22
23. ChetoSensar™ ADC achieves tumor regression close to baseline
Efficacy
0
400
800
1200
1600
2000
31 41 51 61 71 81 91
Tumor
Volume
in
mm³
days
Vehicle, PBS
Only vc-MMAE; DAR 4, 6mg/kg
vc-MMAE w/ ChetoSensarTM; DAR 4, 6mg/kg
With 1/3 of dose, ChetoSensar™ conjugated ADC gives same result as standard ADC
At same dose, ChetoSensar™-ADC led to rapid and complete tumor regression
Median results report from a group of 8 mice
Key Takeaways
Webinar: How to Accelerate and Enhance ADC Therapies
23
SK-OV-3 Xenograph
24. ChetoSensar™ achieves tumor regression with proprietary
payload
0
200
400
600
800
1000
1200
1400
1600
1800
2000
0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80
Tumor
Volume
(mm³)
Study Days
MKN45 Xenograph
No side effects or body weight loss observed with Duocarmycin
8 of 10 animal tumor free, no regrowth observed
ChetoSensar™ successfully used in internal R&D projects
Key Takeaways
Vehicle, PBS
10 mg/kg ADC, without ChetoSensarTM
10 mg/kg ADC, with ChetoSensarTM
Webinar: How to Accelerate and Enhance ADC Therapies
24
25. • Significantly increases hydrophilicity of challenging payloads
• Can be used with a wide selection of linkers, payloads, and
conjugation technologies
• Demonstrated increases in efficacy across multiple ADCs
Webinar: How to Accelerate and Enhance ADC Therapies
25
ChetoSensar™ Technology: Consider it Dis-solved!
27. Approvals have nearly doubled the last 3 years
Webinar: How to Accelerate and Enhance ADC Therapies
27
The ADC industry 2022
ADC Approval year linker payload
Mylotarg 2017;2000 AcBut (lysosome cleavable) Calicheamicin
Adcentris 2011 VC Protease cleavable MMAE
Kadcyla 2013 Non-cleavable DM1
Besponsa 2017 Hydrazone cleavable Calicheamicin
Polivy 2019 VC-PAB cleavable MMAE
Padcev 2019 VC-PAB cleavable MMAE
Enhertu 2019 Cathepsine
cleavable
Exatecan
(camptothecin)
Trodelvy 2020 pH sensitive
cleavable, PEG8
camptothecin
Blenrep 2020 Non-cleavable MMAF
Zynlonta 2021 Cathepsine
cleavable PEG8
Tesirine (PBD)
Tivdak 2021 VC-PAB cleavable MMAE
Noticeable increase in different payloads and linkers
28. Webinar: How to Accelerate and Enhance ADC Therapies
28
How can the ADC industry keep accelerating?
The Hurdles
Optimization of a new ADC requires
− developing a mAb that effectively binds to target and manufactures well
− choosing the appropriate payload that retains efficacy once delivered
− developing linkers that
− impart overall in vivo stability
− help prevent fast clearance to improve pharmacokinetics
− release the payload appropriately at target to retain therapeutic function
Each arm has its own challenges when it
comes to optimization
29. Webinar: How to Accelerate and Enhance ADC Therapies
29
Can we learn from the success of other industries?
Small Molecule Medicinal Chemistry R&D
thrived in the 90’s when library formats were adopted
libraries produced dozens of compounds at a time
enabled Structure Activity Relations (SAR) to efficiently identify lead candidates
But ADCs are much more complex than small molecules
single point, custom modifications around linkers, payloads, and loading require large
time and money commitments
changing one component of the ADC could influence/alter the behavior of the others
making predictions challenging
30. Webinar: How to Accelerate and Enhance ADC Therapies
30
How Can ADC ExpressTM Help You With Candidate Selection?
30
mAb1
Lead Candidate
ADC3
/4
ADC2
ADC1
GLP & GMP
(Development,
Clinical &
Commercial)
Customer Our Company
Multiple ADCs
Our services for mAb, drug linker, and ADC conjugation development are fully
integrated to help accelerate your path to GMP and commercial manufacturing
PBDs
Camptothecins
Auristatins
Maytansines
Payloads
Linkers and
Solubility Enhancers
noncleavable
PEGs
cleavable
ChetoSensarTM
Evaluating more combinations should result in better ADCs
31. Understand the payload to predict which enablers are needed
Webinar: How to Accelerate and Enhance ADC Therapies
31
ADC ExpressTM can help with linker selection
Our HPLC hydrophobicity screens can help plan for your library needs.
We can compare your custom linkers to help predict their behavior as well.
Reference
Code
Compound Class RT
RRT vs.
Standard
A irinotecan 10.161 1.21
B auristatin 10.377 1.24
C maytansinoid 13.248 1.58
D DNA chelator (PBD) 13.928 1.66
E maytansinoid (DM1) 14.107 1.68
32. TmAb+Duocarmycin ADC study with and without solubilizers
Webinar: How to Accelerate and Enhance ADC Therapies
32
Hydrophobic characterization of DAR species
0
2
4
6
8
10
12
0 2 4 8
HIC
RT
(min)
Duocarmycin DAR Species
Linker Effect on Duocarmycin
DAR Species
No Enabler Branched PEG 8 Chetosensar
Data from Internal ADC Express Trials; J.Ramsay
Species evaluation can help predict what DAR target to go after.
In this case, the Chetosensar™ DAR 8 shows comparable
hydrophobicity to the native mAb.
33. Webinar: How to Accelerate and Enhance ADC Therapies
33
TmAb ADCs with varying payloads and linkers
Hydrophobic characterization of ADCs
0
2
4
6
8
10
12
Duoc. Cheto-MMAE Cheto-Duoc. Cheto-CBI Dimer PEG8-Duoc
HIC
RT
(min)
DAR Species of Various ADC Combinations
HIC Screen of DAR Species
DAR 4 DAR 8
Data from Internal ADC Express Trials; J. Ramsay
HIC profiling can directly evaluate payloads, enablers and DAR
34. Ligand ka (1041/Ms) kd (10-4, 1/s) KD (nM) Relative % KD
T mAb ADC PEG4 1.22 1.42e 11.6 52.3
T mAb ADC PEG8 0.88 1.05e 11.9 51.0
T mAb ADC PEG12 2.53 1.66e 6.56 92.5
T mAb ADC PEG24 3.06 3.47e 11.3 53.7
T mAb ADC SMCC 2.56 1.69e 6.60 92.0
RS (T mAb) 1.19 0.721 6.07 NA
Overall antigen binding activities decreased relative to the unconjugated TmAb
PEG 12 and SMCC linker activity had neglectable impact on binding affinity
Data indicated linker size influenced the binding activities for different linkers with similar
DAR using the same payload
Kinetic data including association (ka), dissociation (kd), and equilibrium dissociation
constant (KD) allows primarily efficacy data with low sample requirement
Surface plasmon resonance (SPR) comparability analysis
Understand binding as early as possible
34 Webinar: How to Accelerate and Enhance ADC Therapies
35. Work with an experienced CDMO at the start of your program
Webinar: How to Accelerate and Enhance ADC Therapies
35
Where to start building an ADC library
ADC Express™ Services can be your partner who
− understands and is experienced with various conjugation
chemistries
− can help design your target ADCs of interest
− knows how to get the right pieces in place
− can quickly generate the appropriate constructs
− has the analytical methods in place to provide reliable
characterization for each ADC
Why guess at which ADC will be the best?
Leverage our expertise to make every ADC of interest and test them
Head-to-head!
36. Products to Accelerate and Enhance
ADC Drug Discovery and Development
Webinar: How to Accelerate and Enhance ADC Therapies
36
ADCore Payload Intermediates
ChetoSensar™ Technology
Discovery/
Pre-Clinical
cGMP Clinical
Development for
Phases 1 and 2
Phase 3 and
Commercial
ADC Express™ Services
Lead
Candidate
ADC
3
ADC
2
ADC
1
DOLCore™ Intermediate MAYCore™ Intermediate PBDCore™ Intermediate
37. Our Vertically Integrated ADC Supply Chain
St Louis, MO:
ADC Express™ Services
ADC Clinical and Commercial
development and production
Clinical MFG suite
expansion complete in
2022
Madison/Verona,
WI:
Manufacturing site for ADCore
products/ChetoSensar™
technology
Linker/Payload development
through commercial production
65 M € GMP MFG expansion
complete 2022
Martillac, France:
Cell line development to BDS
mAb clinical development and
manufacturing
Commercial MFG ready in
2022
Sheboygan, WI:
Custom non-GMP starting
materials
Schaffhausen,
Switzerland
PEG linkers for downstream
conjugation
Bangalore, India:
Custom non-GMP starting
materials
37 Webinar: How to Accelerate and Enhance ADC Therapies