Regulatory agencies require characterization of AAV particle composition, including measurement of empty and full capsids. Analytical ultracentrifugation (AUC) provides a method to determine the percentage of empty, partial, and full capsids in a sample and fits into a multi-method approach to characterize identity, purity, biological activity, and safety of gene therapy products. Monitoring product impurities such as empty particles decreases safety risks.
Biosafety in Gene Therapy: Applying the latest regulatory guidance for RCL te...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/33WUiqE
Ensuring the safety and quality of your lentiviral vector is of the utmost importance. Attend this webinar to learn about testing strategies to monitor replication competent lentivirus. You will also hear about recent changes in regulatory guidance with regards to sample types and volumes tested.
The use of lentivirus vectors to produce groundbreaking gene therapies is on the rise. Ensuring the biosafety and quality of these vectors is achieved through a multi-tiered testing approach.
For lentivirus-based therapies, generation of replication competent particles is a potential risk. While improvements in design and manufacturing have decreased the probability of producing replication competent viruses, regulatory agencies provide guidelines to test for their presence at multiple stages in production. This webinar reviews the strategies for monitoring replication competent lentiviruses. We describe current methods and address: Sample types, testing volumes, and expected results.
In this webinar, you will learn about:
• The latest FDA regulatory guidelines on replication competent lentivirus (RCL) testing
• Methods used to monitor RCL
• Considerations on sample type and volume requirements
CAR-T (Cell Therapy) Nomenclature Review & Brand Equity Study. April 15, 2015Bill Smith
CAR-T (Cell Therapy) Nomenclature Review & Brand Equity Study. April 15, 2015.
Brand Acumen. The Global Leader in Pharmaceutical Name Development and Submission Strategy.
Real-Time quantitative PCR (qPCR) is a mainstream method that is used in research and diagnostic applications for quantification of gene expression. IDT has developed a robust and affordable qPCR master mix for use with probe-based qPCR in single and multiplex assays. In this presentation, we explore a variety of applications of PrimeTime® Gene Expression Master Mix. We cover the use of PrimeTime master mix with probe based assays from IDT. We also look at the use of PrimeTime master mix in multiplex applications without the loss of sensitivity that is commonly observed. Finally, we demonstrate the unmatched stability of PrimeTime master mix under ambient temperatures, saving your research money and minimizing on shipping delays.
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
It is very fast and new technique for detection and degradation of viral DNA and it is so helpful for us to understand how to degraded viral DNA... what type of function naturally present in bacteria........ so its very excellent technique
Liquid biopsy: Overcome Challenges of Circulating DNA with Automated and Stan...QIAGEN
Circulating cell-free DNA (ccfDNA) originating from malignant tumors, a developing fetus and also from inflammatory tissues, is present in the cell-free nucleic acids in plasma, serum and other body fluids and is considered a “liquid biopsy”. Access to ccfDNA for analysis allows for specific detection of certain disease states based on a simple blood sample. Circulating cell-free DNA shows distinctive properties – it is present mostly as shorter fragments of less than 500 bp and the concentration of ccfDNA in a plasma or serum sample is low (approximately 1–100 ng/ml) compared to cellular materials and varies considerably between different individuals.
Because of their fragmented nature and low concentration, ccfDNA presents a particular challenge for efficient extraction / purification and quantification, such as by qPCR. We present data on solutions for the following critical problems concerning the purification of ccfDNA for research and molecular diagnostic applications:
• Pre-analytical workflow (blood processing) for analyzing ccfDNA
• Optimization of ccfDNA extraction from plasma samples: low target concentrations require efficient ccfDNA enrichment from larger sample volumes
• Novel automated extraction of ccfDNA using the QIAsymphony SP instrument for liquid biopsy diagnostic applications.
Crispr-Cas9 system works on the concept of bacterial defence mechanism. The idea of which was replicated in eukaryotic cell in in- vitro condition by the researchers.
Biosafety in Gene Therapy: Applying the latest regulatory guidance for RCL te...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/33WUiqE
Ensuring the safety and quality of your lentiviral vector is of the utmost importance. Attend this webinar to learn about testing strategies to monitor replication competent lentivirus. You will also hear about recent changes in regulatory guidance with regards to sample types and volumes tested.
The use of lentivirus vectors to produce groundbreaking gene therapies is on the rise. Ensuring the biosafety and quality of these vectors is achieved through a multi-tiered testing approach.
For lentivirus-based therapies, generation of replication competent particles is a potential risk. While improvements in design and manufacturing have decreased the probability of producing replication competent viruses, regulatory agencies provide guidelines to test for their presence at multiple stages in production. This webinar reviews the strategies for monitoring replication competent lentiviruses. We describe current methods and address: Sample types, testing volumes, and expected results.
In this webinar, you will learn about:
• The latest FDA regulatory guidelines on replication competent lentivirus (RCL) testing
• Methods used to monitor RCL
• Considerations on sample type and volume requirements
CAR-T (Cell Therapy) Nomenclature Review & Brand Equity Study. April 15, 2015Bill Smith
CAR-T (Cell Therapy) Nomenclature Review & Brand Equity Study. April 15, 2015.
Brand Acumen. The Global Leader in Pharmaceutical Name Development and Submission Strategy.
Real-Time quantitative PCR (qPCR) is a mainstream method that is used in research and diagnostic applications for quantification of gene expression. IDT has developed a robust and affordable qPCR master mix for use with probe-based qPCR in single and multiplex assays. In this presentation, we explore a variety of applications of PrimeTime® Gene Expression Master Mix. We cover the use of PrimeTime master mix with probe based assays from IDT. We also look at the use of PrimeTime master mix in multiplex applications without the loss of sensitivity that is commonly observed. Finally, we demonstrate the unmatched stability of PrimeTime master mix under ambient temperatures, saving your research money and minimizing on shipping delays.
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
It is very fast and new technique for detection and degradation of viral DNA and it is so helpful for us to understand how to degraded viral DNA... what type of function naturally present in bacteria........ so its very excellent technique
Liquid biopsy: Overcome Challenges of Circulating DNA with Automated and Stan...QIAGEN
Circulating cell-free DNA (ccfDNA) originating from malignant tumors, a developing fetus and also from inflammatory tissues, is present in the cell-free nucleic acids in plasma, serum and other body fluids and is considered a “liquid biopsy”. Access to ccfDNA for analysis allows for specific detection of certain disease states based on a simple blood sample. Circulating cell-free DNA shows distinctive properties – it is present mostly as shorter fragments of less than 500 bp and the concentration of ccfDNA in a plasma or serum sample is low (approximately 1–100 ng/ml) compared to cellular materials and varies considerably between different individuals.
Because of their fragmented nature and low concentration, ccfDNA presents a particular challenge for efficient extraction / purification and quantification, such as by qPCR. We present data on solutions for the following critical problems concerning the purification of ccfDNA for research and molecular diagnostic applications:
• Pre-analytical workflow (blood processing) for analyzing ccfDNA
• Optimization of ccfDNA extraction from plasma samples: low target concentrations require efficient ccfDNA enrichment from larger sample volumes
• Novel automated extraction of ccfDNA using the QIAsymphony SP instrument for liquid biopsy diagnostic applications.
Crispr-Cas9 system works on the concept of bacterial defence mechanism. The idea of which was replicated in eukaryotic cell in in- vitro condition by the researchers.
NGS in Clinical Research: Meet the NGS Experts Series Part 1QIAGEN
Next generation sequencing has revolutionized clinical testing but has also created novel challenges. This presentation will give an overview of state of the art clinical NGS and discuss validation, clinical implementation as well as the migration from gene panels to exome sequencing for inherited disorders with clinical and genetic heterogeneity. In addition, important shortcomings such as difficulties with regions of high sequence homology will be discussed.
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
Get the right bispecific antibody as per your requirements. Creative Biolabs will perform the most suitable approach to fulfill your demands. Our team successfully produced all three types of bispecific antibodies using well-established methods.
RNA integrity and quality - Standardize RNA quality controlQIAGEN
RNA integrity and quality are critical to obtain meaningful and reliable downstream data. This slidedeck details the important considerations and critical factors in RNA preparation. It also highlights the need for quality control analysis and common methods for RNA integrity and quality assessment.
Webinar by BIS Research on Precision Oncology BiomarkersBIS Research Inc.
Precision oncology biomarkers are essential tools for tailoring cancer treatment to individual patients, as they provide insights into tumor biology and guide the selection of targeted therapies.
BIS conducted a deep intelligence webinar on the state-of-the-art technologies and emerging strategies used through the precision oncology biomarkers.
2011 course on Molecular Diagnostic Automation - Part 2 - AmplificationPatrick Merel
2011 course on Molecular Diagnostic Automation - Part 2 - Amplification.
This is from early 2011. Prices and Specifications of instruments may have changed.
Part 2 of 3
How CRISPR–Cas9 Screening will revolutionise your drug development programsHorizonDiscovery
CRISPR–Cas9 mediated genome editing provides a novel and highly efficient way to probe gene function. Using this technology, thousands of genes can be knocked out and their function assessed in a single experiment. This makes CRISPR–Cas9 screening a powerful tool for drug target ID and validation, understanding drug mechanisms of action and patient stratification.
In this webinar, we use our experience with CRISPR–Cas9 to discuss the power and applicability of CRISPR-Cas9 screening technologies. We focus on how to use this technology to address important biological questions, and consider what’s possible, what’s plausible and what constitutes a ‘hit’. We also highlight Horizon’s latest developments to the CRISPR-Cas9 screening platform.
Unlocking the Potential of mRNA Vaccines and TherapeuticsMerck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3lNmkf7
The therapeutic potential of mRNA has been studied for decades and this exciting modality could potentially disrupt the biological market, in particular vaccine and novel therapies. This webinar will highlight the potential of mRNA therapies and focus on the manufacturing process's associated challenges, solutions and perspectives from synthesis to delivery.
mRNA has emerged as a promising modality for a wide range of therapeutics and vaccines and could become the break-through technology of this century. mRNA-based platform technologies could enable a more rapid response to infectious diseases, outbreaks or pandemics and allow efficient gene replacements or cancer treatments. mRNA represents a safer alternative to DNA-based therapies and the technology has recently advanced to overcome stability and efficacy challenges. Because of that, the industrialization of this technology is just in its infancy stages and bottlenecks exist around scalability, purity, and delivery which are key to establish and deliver the promise of such platform. This webinar will shed light on the potential of mRNA therapies and focus on the manufacturing process's associated challenges, solutions and perspectives from synthesis to delivery.
In this webinar, you will learn:
• The potential behind using mRNA as a therapeutic and vaccine
• The mRNA production process
• The challenges around mRNA production
• The solutions and perspectives for a robust manufacturing process
• mRNA delivery systems and their manufacturing
NGS in Clinical Research: Meet the NGS Experts Series Part 1QIAGEN
Next generation sequencing has revolutionized clinical testing but has also created novel challenges. This presentation will give an overview of state of the art clinical NGS and discuss validation, clinical implementation as well as the migration from gene panels to exome sequencing for inherited disorders with clinical and genetic heterogeneity. In addition, important shortcomings such as difficulties with regions of high sequence homology will be discussed.
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
Get the right bispecific antibody as per your requirements. Creative Biolabs will perform the most suitable approach to fulfill your demands. Our team successfully produced all three types of bispecific antibodies using well-established methods.
RNA integrity and quality - Standardize RNA quality controlQIAGEN
RNA integrity and quality are critical to obtain meaningful and reliable downstream data. This slidedeck details the important considerations and critical factors in RNA preparation. It also highlights the need for quality control analysis and common methods for RNA integrity and quality assessment.
Webinar by BIS Research on Precision Oncology BiomarkersBIS Research Inc.
Precision oncology biomarkers are essential tools for tailoring cancer treatment to individual patients, as they provide insights into tumor biology and guide the selection of targeted therapies.
BIS conducted a deep intelligence webinar on the state-of-the-art technologies and emerging strategies used through the precision oncology biomarkers.
2011 course on Molecular Diagnostic Automation - Part 2 - AmplificationPatrick Merel
2011 course on Molecular Diagnostic Automation - Part 2 - Amplification.
This is from early 2011. Prices and Specifications of instruments may have changed.
Part 2 of 3
How CRISPR–Cas9 Screening will revolutionise your drug development programsHorizonDiscovery
CRISPR–Cas9 mediated genome editing provides a novel and highly efficient way to probe gene function. Using this technology, thousands of genes can be knocked out and their function assessed in a single experiment. This makes CRISPR–Cas9 screening a powerful tool for drug target ID and validation, understanding drug mechanisms of action and patient stratification.
In this webinar, we use our experience with CRISPR–Cas9 to discuss the power and applicability of CRISPR-Cas9 screening technologies. We focus on how to use this technology to address important biological questions, and consider what’s possible, what’s plausible and what constitutes a ‘hit’. We also highlight Horizon’s latest developments to the CRISPR-Cas9 screening platform.
Unlocking the Potential of mRNA Vaccines and TherapeuticsMerck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3lNmkf7
The therapeutic potential of mRNA has been studied for decades and this exciting modality could potentially disrupt the biological market, in particular vaccine and novel therapies. This webinar will highlight the potential of mRNA therapies and focus on the manufacturing process's associated challenges, solutions and perspectives from synthesis to delivery.
mRNA has emerged as a promising modality for a wide range of therapeutics and vaccines and could become the break-through technology of this century. mRNA-based platform technologies could enable a more rapid response to infectious diseases, outbreaks or pandemics and allow efficient gene replacements or cancer treatments. mRNA represents a safer alternative to DNA-based therapies and the technology has recently advanced to overcome stability and efficacy challenges. Because of that, the industrialization of this technology is just in its infancy stages and bottlenecks exist around scalability, purity, and delivery which are key to establish and deliver the promise of such platform. This webinar will shed light on the potential of mRNA therapies and focus on the manufacturing process's associated challenges, solutions and perspectives from synthesis to delivery.
In this webinar, you will learn:
• The potential behind using mRNA as a therapeutic and vaccine
• The mRNA production process
• The challenges around mRNA production
• The solutions and perspectives for a robust manufacturing process
• mRNA delivery systems and their manufacturing
Finding Optimal Compound Dosage for Anti-Aging DrugsWenlan Hu
Anti-aging compound becomes a very integral part of the compound market. However, the lack of experience in this field makes it very hard for testing CROs to fully understand the mechanism of actions as well as efficacy of the compound, particularly the optimal dosage for anti-aging use. In the following slide we are trying to share with you the best way to do testing on the substances that are designed for anti-aging use.
The compound characterization market is growing increasingly profitable and competitive at the same time. In order to develop a new compound product, the testing step is indispensable. Unlike drug discovery, compound testing is not as restrictive, but understanding the main workflow is still necessary to excel in the market. In order to help you improve both the efficiency and safety of compound testing, we developed the protocol to assist you in your findings.
Different compounds behave in distinguished manner when tested. A important aspect of compound development is to understand the mode of action of compounds. In order to achieve this goal, IVB use RNAseq and whole transcriptome analysis to assist the findings. Based on the findings, a well-round understanding of a compound can be generated, which assists the research findings in a efficient and timely way.
Современное лечение ВИЧ: модификация АРТ у пациентов с вирусологической супре...hivlifeinfo
Современное лечение ВИЧ: модификация АРТ у пациентов с вирусологической супрессией (2021) / Contemporary Management of HIV: Modifying ART in Virologically Suppressed Patients 2021
Keeping the (Adventitious) Virus Out of the (Adeno-Associated) VirusMilliporeSigma
Watch the presentation of this webinar here: https://bit.ly/2VRylbi
How can you keep an adventitious virus from contaminating your gene therapy that is delivered by an adeno virus vector? As viral vector bioprocessing advances, regulatory requirements for viral safety will as well. Learn how to define your viral clearance strategy for AAV delivered gene therapies.
How do you define a strategy for viral clearance for a process that inherently aims at purifying a virus?
Gene delivery using AAV has received a boost from two major approvals and the nearly 300 programs in the clinic. Novel gene therapies using viral vectors enable companies to transform the lives of people living with certain rare and ultra-rare diseases where treatments are often not available currently. Amongst a multitude of challenges in viral vector bioprocessing, uncertainty in regulatory expectations is a major challenge to gene therapy developers. Regulatory requirements are evolving as the science and manufacturing matures with more stringent measures for viral safety assurance expected for future approvals.
Learn how to implement techniques for adventitious virus removal in your viral vector process; we will focus on strategies for viral clearance along your journey towards commercial readiness of AAV-based processes.
In this webinar, you will learn:
• AAV process flows and focus areas for viral safety
• Strategies for implementing viral clearance measures in bioprocessing
• Case studies and data driven approaches on log reduction values (LRV) in a viral vector process
• Best practices and evaluation roadmaps on conducting viral clearance studies
Presented by: Ratish Krishnan, Senior Strategy Consultant, Novel Modalities Bioprocessing
Keeping the (Adventitious) Virus Out of the (Adeno-Associated) VirusMerck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/2VRylbi
How can you keep an adventitious virus from contaminating your gene therapy that is delivered by an adeno virus vector? As viral vector bioprocessing advances, regulatory requirements for viral safety will as well. Learn how to define your viral clearance strategy for AAV delivered gene therapies.
How do you define a strategy for viral clearance for a process that inherently aims at purifying a virus?
Gene delivery using AAV has received a boost from two major approvals and the nearly 300 programs in the clinic. Novel gene therapies using viral vectors enable companies to transform the lives of people living with certain rare and ultra-rare diseases where treatments are often not available currently. Amongst a multitude of challenges in viral vector bioprocessing, uncertainty in regulatory expectations is a major challenge to gene therapy developers. Regulatory requirements are evolving as the science and manufacturing matures with more stringent measures for viral safety assurance expected for future approvals.
Learn how to implement techniques for adventitious virus removal in your viral vector process; we will focus on strategies for viral clearance along your journey towards commercial readiness of AAV-based processes.
In this webinar, you will learn:
• AAV process flows and focus areas for viral safety
• Strategies for implementing viral clearance measures in bioprocessing
• Case studies and data driven approaches on log reduction values (LRV) in a viral vector process
• Best practices and evaluation roadmaps on conducting viral clearance studies
Presented by: Ratish Krishnan, Senior Strategy Consultant, Novel Modalities Bioprocessing
CRO Company for Mode of Action & Efficacy Test for Drugs | InvivoBiosystemsWenlan Hu
Compound testing takes shares of a huge part of the drug development and health-related compound market. In order to find a CRO that is both friendly for budget saving and efficient at the same time is not easy. IVB uses a three staged compound assessment which includes RNAseq, whole transcriptome analysis, and other techniques to help our clients better understand the mode of action and efficacy of a particular compound.
This slide focuses on the causes and risk factors associated with cancer. It delves into the complexities of cancer development, highlighting factors such as genetic mutations, environmental influences, and lifestyle choices. Through informative visuals and concise text, the slide aims to raise awareness about the various elements that contribute to the onset of cancer. By understanding these key factors, individuals can make informed decisions to minimize their risk and prioritize preventive measures. This information sets the stage for subsequent slides that explore diagnosis, treatment options, and advancements in cancer research.
Presentation from the 3rd Joint Meeting of the Antimicrobial Resistance and Healthcare-Associated Infections (ARHAI) Networks, organised by the European Centre of Disease Prevention and Control - Stockholm, 11-13 February 2015
Good Model Organism for Anti Aging TestingWenlan Hu
Drug testing is taking more attention than ever before in a fast growing market for longevity compounds. In order to succeed in a competitive market and develop a pipeline method for quick drug development, we need to understand and choose the most suitable model organism for aging studies. The following content is intended to provide information on how to choose the best model for anti-aging drug testing.
The emerging CRISPR/Cas9 gene editing technology greatly accelerates the R&D process in life sciences. Here, we briefly introduce CRISPR/Cas9 and its delivery strategies.
Similar to See the Whole Picture: Using SV-AUC for Empty/Full AAV Capsid Analysis (20)
The Viscosity Reduction Platform: Viscosity-reducing excipients for improveme...Merck Life Sciences
Protein viscosity is a major challenge in preparing highly concentrated protein formulations suitable for subcutaneous injection. Recently, the Viscosity Reduction Platform (VRP) was introduced and its technical key features and benefits for formulations were discussed. However, highly viscous solutions do not only pose a challenge when administering a drug to a patient, they can also impose technical limitations in the manufacturing process.
This white paper evaluates the effect of the excipients in the Viscosity Reduction Platform on ultrafiltration processes used to produce a highly concentrated formulation of a monoclonal antibody (mAb). Two filtration methods are demonstrated in this work.
Find more information about the Viscosity Reduction Platform on our website: https://www.sigmaaldrich.com/products/pharma-and-biopharma-manufacturing/formulation/viscosity-reduction-platform
Use of Excipients in Downstream Processing to Improve Protein PurificationMerck Life Sciences
Excipients are used to improve the stability of protein-based therapeutics by protecting the protein against a range of stress conditions such as temperature changes, pH changes, or agitation. Similar stresses are applied to proteins during downstream purification. Shifts in pH during Protein A chromatography, subsequent incubations at low pH for virus inactivation, and changes in conductivity in ion exchange chromatography can lead to aggregation, fragmentation, or other chemical modifications of the therapeutic protein. Given the potential impact on the protein’s structural integrity, there is a need for approaches to reduce the risk presented by the conditions during downstream processing. For example, integration of a solution to prevent aggregation of proteins would be a more efficient strategy than implementing steps to remove multimeric forms.
This white paper highlights the results from a recent paper by Stange et. al., in which protein stabilizing excipients such as polyols, sugars, and polyethylene glycol (PEG4000) were used as buffer system additives. Effect of the excipients on elution patterns, stabilization of the monomer antibody, host-cell protein removal, virus inactivation rates and binding capacity of cation exchange chromatography were explored.
Exploring the protein stabilizing capability of surfactants against agitation...Merck Life Sciences
Agitation of therapeutic protein solutions during manufacturing, shipping and handling is one of the major initiators for protein aggregation and particle formation during the life history of a protein drug. Adsorption of protein molecules to liquid-air interfaces leads to the formation of highly concentrated protein surface films. The rupture of these protein films due to various mechanical processes can then result in the appearance of protein aggregates and particles in the bulk solution phase.
One technique to stabilize proteins against stress induced by liquid-air interfaces is the use of non-ionic surfactants. About 91% of antibody formulations commercially available in 2021 contained a surfactant. Polysorbate 20 and 80, composed of a hydrophilic polyoxyethylene sorbitan and hydrophobic fatty acid esters, made up the largest part being employed in 87% of said formulations.
Despite their frequent use in parenteral drug products, concerns have been raised for decades about the application of polysorbates as surfactants in biopharmaceutical formulations. Autoxidation of polysorbate, caused by residual peroxides in polysorbates, can damage the proteins and can further drive the oxidative degradation of polysorbate. Chemical and enzymatic hydrolysis of polysorbate may lead to the formation of free fatty acid particles, which may become visible; and both mechanisms eventually lead to the reduction in polysorbate concentration. Therefore, the purpose of the current study was to compare various molecules for their capabilities to reduced agitation-induced protein aggregation and particle formation; and furthermore, investigate their underlying protein stabilizing mechanisms.
The Viscosity Reduction Platform: Viscosity Reducing Excipients for Protein F...Merck Life Sciences
Protein viscosity is one of the major obstacles in preparing highly concentrated protein formulations suitable for subcutaneous injection.
This whitepaper examines how combining an amino acid with a second viscosity-reducing excipient circumvents adverse effects on protein stability and improves viscosity-reducing capacity.
To find more information about the Viscosity Reduction Platform, please visit our website: https://sigmaaldrich.com/products/pharma-and-biopharma-manufacturing/formulation/viscosity-reduction-platform
Characterization of monoclonal antibodies and Antibody drug conjugates by Sur...Merck Life Sciences
Watch the presentation of this webinar: https://bit.ly/3Pjpjvr
Highlights of this webinar:
- Surface plasmon resonance as a powerful tool for biologic characterization including mAbs and ADCs.
- SPR allows rapid binding analysis in real time without using labels for SARS-CoV-2 receptor binding domain mutations.
- Kinetic data is indicative of possible neutralizing activity allowed assessment of neutralizing ability of therapeutic monoclonal antibodies.
- The application can provide preliminarily efficacy information and facilitated mAbs/ACDs candidate selection process
Detailed description:
Characterization of therapeutic monoclonal antibodies (mAbs) or Antibody drug conjugates (ADCs) is challenging due to their ability to bind to a variety of proteins via their Fc and Fab domains, giving rise to diverse biological functions associated with each domain. The Fc domain of mAbs interacts with Fc receptors with varying affinities, which can influence biological processes such as Complement-dependent cytotoxicity (CDC) and Antibody-dependent cellular cytotoxicity (ADCC), transcytosis, phagocytosis, and/or serum half-life.
An important characteristic of an antibody is its Fc effector function. Antibodies can be engineered to obtain desired binding of the Fc region to Fc receptors expressed on effector cells. Hence, it is crucial to evaluate the binding interaction of mAbs/ADC with Fc receptors in the early phase of drug development to understand the potential biological activity of the product in vivo.
Surface Plasmon Resonance (SPR) is a powerful technique to establish binding kinetics in real-time, label free, and high sensitivity with low sample consumption. Along with target antigen binding, it is crucial to evaluate the binding interaction of antibodies and ADCs with Fc receptors. Our SPR case studies investigated the impact on binding kinetics of ADCs with different linkers and the binding interactions of SARS-CoV-2 spike protein variants and evaluated the neutralizing ability of therapeutic mAbs. SPR characterisation can be facilitated in all stages of the product life cycle to ensure the quality and safety of mAbs and ADCs.
The Role of BioPhorum Extractables Data in the Effective Adoption of Single-U...Merck Life Sciences
Regulatory expectation does require patient safety evaluations with supporting data for manufacturing components that directly come into contact with drug manufacturing process streams. Readily available extractables data can help manufacturers using singleuse technology to accelerate product qualifications, risk assessments and process optimization
This white paper guides you on how to save time and resources with supplier-provided single-use system extractables data and gives you an overview about the overall strategy for Extractables & Leachables. At the end you will find a case study.
Find more information about filters and single-use components on our website: https://www.sigmaaldrich.com/DE/en/services/product-services/emprove-program/emprove-filter-and-single-use-component-portfolio
Watch the recording of this presentation here: https://bit.ly/3zTOpe4
Detailed description:
SARS-CoV-2 showed us that technology supports us during our inspection activity even if on-site visits are not possible. Travel restrictions of various kinds will remain a risk in the future. The use of new technologies has shown that inspections and audits can be carried out despite these restrictions. We will focus on what possibilities the new technologies offer and take a look at the future of inspections and audits.
In this webinar, you will learn:
• Regulatory overview of remote audits
• The technologies needed to support the audit process
• What types of inspections are possible with the use of these technologies
• How audits may look in the future
Presented by:
Daniel Buescher, Product Manager - Digital Solutions
Moving your Gene Therapy from R&D to IND: How to navigate the Regulatory Land...Merck Life Sciences
Watch the recording of this presentation here: https://bit.ly/3SqOsoP
Novel therapies, including cell and gene therapies, continue to be central to innovation in healthcare and represent the fastest growing area of therapeutic medicine. As a consequence, the number of gene therapies undergoing clinical trials has increased significantly in the last five years.
Manufacturing processes for these novel therapeutics are very complex with a high risk of contamination. Regulatory agencies world-wide have responded by issuing guidance to outline their expectations for development and manufacture of cell and gene therapies. Currently, regulatory guidance is not harmonized globally and can often lead to confusion within industry and increased risk of non-compliance.
In this webinar, we'll answer:
• Which regulatory guidelines do you need to comply for your INDs?
• When do you start implementing GMPs and validated assays?
• How do you get your QC testing strategy ‘right the first time’?
• How do you ensure testing is not your rate limiting step for the IND submission?
Presented by:
Manjula Aysola, Senior Regulatory Consultant
Dr. Alison Armstrong, Sr. Director, Technical and Scientific Solutions
Identity testing by NGS as a means of risk mitigation for viral gene therapiesMerck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3RijkHC
Detailed description:
Imagine you’ve just completed a manufacturing run for your viral vector. Identity testing is performed to confirm the vector sequence. But when the results come back the data reveals unexpected sequence variants! With an appropriate risk mitigation testing strategy, this situation can be prevented.
The situation described above is not hypothetical, and happens more that you think, costing valuable time and resources.
Investigatory testing has shown that sequence variants present in starting materials (e.g. plasmids) are likely to make their way to the final product. Adequate identification of low-level variants with an appropriately sensitive method is critical in ensuring the quality of the final product. A risk-based testing strategy, in the context of identity, for viral vector manufacturing will be presented, focusing on key testing points. NGS assays for identity and variant detection will be highlighted due to their extremely sensitive nature compared to traditional approaches.
In this webinar, we'll explore:
• Regulatory requirements for identity testing
• NGS applications for identity testing as compared to traditional methods
• A case study on the impact of not establishing a proper risk-based testing strategy
Presented by: Bradley Hasson, Director of Lab Operations for NGS Services
Latest advancements of melt based 3D printing technologies for oral drug deli...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3A2WcH4
The application of polymer excipients in 3D printing manufacturing is usually limited due to the concerns of filament strength, high processing temperature and large scale manufacturing.
Latest technology developments are targeting a direct melt deposition to simplify the process and enable a constant and efficient process. Two different processing approaches will be presented:
The advanced melt drop deposition, where individual three dimensional geometries can be created by depostition of polymer droplets and the MED® 3D printing technology which allows by precise layer-by-layer deposition to produce objects with well-designed geometric structures.
In this webinar, you will learn:
• Latest advancements of melt based 3D printing approaches
• Application examples for the individual technologies
• Deep dive in the MED® 3D printing technology to design dedicated drug release profiles
Presented by:
Dr. Thomas Kipping, Head of Drug Carriers
Dr. Xianghao Zuo, Deputy Director of R&D, Triastek
CAR-T Manufacturing Innovations that Work - Automating Low Volume Processes a...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3NDNIKe
Automated, fit-for-purpose tools are essential in CAR-T processing to support sustainable manufacturing of clinical and market-approved cell therapy products. This webinar will discuss how the ekko™ Acoustic Cell Processing System uses acoustic technology as a touchless approach to manipulate cells, enabling a modular tool across the CAR-T manufacturing workflow. Typical performance of templated ekko™ System processes for DMSO washout of leukapheresis material, low volume and high cell concentrate for electroporation preparation, and harvest of expanded T cells will be reviewed.
This webinar will also give an early glimpse at the ekko™ Select System for unmatched T cell selection.
In this webinar, you will:
• Uncover how the ekko™ System supports the broad industrialization of cell therapy, with particular focus on how to achieve low volume, high concentrate cell product for critical transduction and transfection steps
• Discover how ekko™ System for wash and concentrate processes throughout the cell therapy workflow achieve high cell recovery, viability, and effective residual removal
• Preview to ekko™ Select, our cell therapy selection platform, to achieve unmatched ease-of-use with direct processing from leukopaks reducing the need for preparation steps
Presented by:
Benjamin Ross-Johnsrud, Acoustic Technology Expert
Robert Scott, Mechanical Engineer III
Viral safety of biologics: What's changing with the ICH Q5A revision?Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3t7X9tg
How does the ICH Q5A revision impact viral safety strategies for biologics?
Biologics continue to grow at a fast pace. Manufactured using cell lines of human or animal origin, these are at risk of viral contamination making safety strategies critical. A comprehensive risk mitigation strategy using multiple orthogonal measures is a regulatory expectation. ICH Q5A, the globally-harmonized guideline outlines the expectations. ICH Q5A is currently being revised to address recent scientific advancements including novel therapeutic modalities, new manufacturing paradigms, updates in viral clearance applications, and alternate detection technologies. We’ll discuss the expected changes and potential impact on viral safety strategies with case studies and examples.
In this webinar, you will learn about:
• The Importance of virus testing in biologics products
• Regulatory landscape, expectations for the Q5A revision
• What's new and changing
• Examples of alternate testing schedules, impact on viral clearance
Presented by:
Manjula Aysola, Senior Regulatory Consultant
Alison Armstrong, PhD, Sr. Director, Technical and Scientific Solutions
Improve Operational Efficiency by Over 30% with Product, Process, & Systems A...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3adaxWh
When implementing new automation systems, organizations must consider things like deployment time, user adoption, and costs.
They must also consider the cost of doing nothing – that is, what competitive advantage is lost in standing still? What time and quality is lost in repetitive, manual tasks rather than an automated, digital workflow? What operational efficiencies are lost?
In this webinar we examine how a product, process, and system agnostic automation platform can be deployed faster than traditional system specific software while bringing greater operational efficiencies (in many cases over 30% improvement).
To remain competitive in the market, biopharma manufacturers must adopt automation and digital technologies, but most plants still have island of automation consisting of independently functioning, standalone unit operations. This results in operational inefficiency, regulatory concerns, and a poor understanding of the process and product life cycle.
Taking the first, right step must include considering risks, costs, timelines, and technology alternatives. Traditional automation approaches tied to specific systems, processes, and products are, by their nature, limited; while an agnostic platform will address current biomanufacturing business challenges and ensure future readiness. With the right platform, a phased automation implementation can yield operational efficiency gains of up to 30% and improved product quality and regulatory compliance.
In this webinar, let's explore:
• Challenges of automation and digital technology adoption
• What a product, process, and system agnostic platform entails
• Applications and benefits of a process orchestration platform
• Ensuring future readiness with process orchestration
Presented by:
Braj Nandan Thakur, Global Product Manager - Automation
Insights from a Global Collaboration Accelerating Vaccine Development with an...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3Nbb5ug
Get insights and best practices from a multinational team establishing a platform for vaccine production. See how a long-term collaboration on a bench-scale process used to produce a Virus Like Particle (VLP) vaccine for SARS-CoV-2 was successfully converted to a robust GMP-compatible, scalable process.
The COVID-19 pandemic further emphasized the need for collaboration in the development of urgently needed vaccines and therapeutics. In this webinar, we take you behind the scenes of our collaboration with Technovax and Innovative Biotech in which a scalable VLP vaccine platform was optimized for use in a production facility in Nigeria in response to the need for local production of SARS-CoV-2 vaccines. The flexibility and robustness of the platform will enable its rapid deployment to support the West African pandemic readiness program. Initial development of the VLP process began in late 2019 and by March 2020, was already adapted for production of a SARS-CoV-2 vaccine.
In this webinar, you will learn:
• About building a priceless collaborative network with integrated solutions
• Virus-Like Particle Vaccines
• Process Development Overview and Challenges
• Pre-clinical Results and Next Steps
Presented by:
Jose M. Galarza, PhD,
President and Founder of TechnoVax
Naomi Baer,
Business development consultant, Emerging Biotech, BioProcess division
Youssef Gaabouri, Eng. ,
Associate Director, Head of Sales Middle East & Africa, BioProcess division
Risk-Based Qualification of X-Ray Sterilization for Single-Use SystemsMerck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3vQf0qv
In the single-use bioprocess industry, X-ray irradiation warrants consideration as an alternate sterilization technology. Using a risk-based qualification testing strategy is important when evaluating and implementing equivalent ionizing irradiation sterilization methods.
The urgent need for life-saving therapies as a result of the global pandemic has reinforced the criticality of flexibility in pharmaceutical manufacturing, including sterilization. The single-use bioprocess industry traditionally has employed gamma irradiation sterilization. X-ray irradiation is being considered as an additional sterilization technology for business and supply continuity. We will share a risk-based qualification testing strategy including Extractables and data generated to support comparability of gamma irradiation and X-ray irradiation as equivalent ionizing irradiation sterilization methods.
In this webinar, you will learn about:
• The comparison of gamma and X-ray irradiation sterilization
• A risk-based qualification test strategy
• Data evaluation of gamma versus X-ray sterilized single-use components
Presented by:
Monica Cardona,
Global Senior Program Manager
Paul Killian, Ph.D.,
R&D Director, Analytical Technologies
The High Intensity Sweeteners Neotame and Sucralose: 2 Ways to ace the Patien...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3vQyN7K
Bitter medicines are an important issue, especially for pediatric applications. As several APIs have bitter tasting components, high intensity sweeteners for taste optimization are of great interest. Join our webinar to discover our new sweetener toolbox enabling safe and stable formulations.
Mask bitter aftertaste for a sweeter pill to swallow! Patients’ compliance and the therapeutic benefit are supported by a pleasant taste of pharmaceutical formulations. With the high intensity sweeteners Neotame and Sucralose, you have efficient tools at hand which are superior to other sweeteners in many aspects:
• excellent sugar-like taste profile
• outstanding sweetness factors
• use effectiveness
• enhanced stability
We will present our new toolbox of two high performance sweeteners and focus on aspects of stability, safety, the application in various dosage forms, and market perception.
In this webinar, you will learn:
• How to optimize the patients' taste experience of your pharmaceuticals
• How sweeteners can be differentiated by their sensory profiles and features
• How our new product offering Neotame can be effectively used in your targeted formulations
Presented by:
Almut von der Brelie,
Senior Manager Strategic Marketing
Excipients for Solid Applications
The Developability Classification System (DCS): Enabling an Optimized Approac...Merck Life Sciences
This whitepaper by Dr. Daniel Joseph Price outlines how poorly soluble drug formulations can be designed using the developability classification system (DCS).
The DCS identifies the root cause of low solubility and enables lean, cost-effective and effective formulations to be developed.
#solubility #pharmaceuticalmanufacturing #oralsoliddosage #drugdevelopment
In this webinar, you will learn about:
The advantages of using advanced intermediates to develop ADC therapies
How to increase ADC solubility and efficiency
Fast, small-scale ADC library generation
Seamless supply chain with reduced complexity and regulatory support
The ADCore product line offers versatile intermediates that simplify the synthesis of common ADC payloads (dolastatins, maytansinoids, and PBDs) by greatly reducing the number of synthetic steps. This translates to savings in development and manufacturing costs and shorter timelines to the clinic. To address the poor solubility of many ADC payloads, ChetoSensar™ was developed to significantly increase the hydrophilicity of the drug linker, which has been shown to also substantially increase the efficacy of ADCs and broaden the therapeutic window.
Lastly, the ADC Express™ service leverages conjugation chemistry and analytical expertise to help design and quickly synthesize sets of potential ADC therapies suitable for screening to simplify candidate selection and get ADC therapies to market faster.
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
Global launch of the Healthy Ageing and Prevention Index 2nd wave – alongside...ILC- UK
The Healthy Ageing and Prevention Index is an online tool created by ILC that ranks countries on six metrics including, life span, health span, work span, income, environmental performance, and happiness. The Index helps us understand how well countries have adapted to longevity and inform decision makers on what must be done to maximise the economic benefits that comes with living well for longer.
Alongside the 77th World Health Assembly in Geneva on 28 May 2024, we launched the second version of our Index, allowing us to track progress and give new insights into what needs to be done to keep populations healthier for longer.
The speakers included:
Professor Orazio Schillaci, Minister of Health, Italy
Dr Hans Groth, Chairman of the Board, World Demographic & Ageing Forum
Professor Ilona Kickbusch, Founder and Chair, Global Health Centre, Geneva Graduate Institute and co-chair, World Health Summit Council
Dr Natasha Azzopardi Muscat, Director, Country Health Policies and Systems Division, World Health Organisation EURO
Dr Marta Lomazzi, Executive Manager, World Federation of Public Health Associations
Dr Shyam Bishen, Head, Centre for Health and Healthcare and Member of the Executive Committee, World Economic Forum
Dr Karin Tegmark Wisell, Director General, Public Health Agency of Sweden
QA Paediatric dentistry department, Hospital Melaka 2020Azreen Aj
QA study - To improve the 6th monthly recall rate post-comprehensive dental treatment under general anaesthesia in paediatric dentistry department, Hospital Melaka
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
Medical Technology Tackles New Health Care Demand - Research Report - March 2...pchutichetpong
M Capital Group (“MCG”) predicts that with, against, despite, and even without the global pandemic, the medical technology (MedTech) industry shows signs of continuous healthy growth, driven by smaller, faster, and cheaper devices, growing demand for home-based applications, technological innovation, strategic acquisitions, investments, and SPAC listings. MCG predicts that this should reflects itself in annual growth of over 6%, well beyond 2028.
According to Chris Mouchabhani, Managing Partner at M Capital Group, “Despite all economic scenarios that one may consider, beyond overall economic shocks, medical technology should remain one of the most promising and robust sectors over the short to medium term and well beyond 2028.”
There is a movement towards home-based care for the elderly, next generation scanning and MRI devices, wearable technology, artificial intelligence incorporation, and online connectivity. Experts also see a focus on predictive, preventive, personalized, participatory, and precision medicine, with rising levels of integration of home care and technological innovation.
The average cost of treatment has been rising across the board, creating additional financial burdens to governments, healthcare providers and insurance companies. According to MCG, cost-per-inpatient-stay in the United States alone rose on average annually by over 13% between 2014 to 2021, leading MedTech to focus research efforts on optimized medical equipment at lower price points, whilst emphasizing portability and ease of use. Namely, 46% of the 1,008 medical technology companies in the 2021 MedTech Innovator (“MTI”) database are focusing on prevention, wellness, detection, or diagnosis, signaling a clear push for preventive care to also tackle costs.
In addition, there has also been a lasting impact on consumer and medical demand for home care, supported by the pandemic. Lockdowns, closure of care facilities, and healthcare systems subjected to capacity pressure, accelerated demand away from traditional inpatient care. Now, outpatient care solutions are driving industry production, with nearly 70% of recent diagnostics start-up companies producing products in areas such as ambulatory clinics, at-home care, and self-administered diagnostics.
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
Leading the Way in Nephrology: Dr. David Greene's Work with Stem Cells for Ki...Dr. David Greene Arizona
As we watch Dr. Greene's continued efforts and research in Arizona, it's clear that stem cell therapy holds a promising key to unlocking new doors in the treatment of kidney disease. With each study and trial, we step closer to a world where kidney disease is no longer a life sentence but a treatable condition, thanks to pioneers like Dr. David Greene.
Navigating Challenges: Mental Health, Legislation, and the Prison System in B...Guillermo Rivera
This conference will delve into the intricate intersections between mental health, legal frameworks, and the prison system in Bolivia. It aims to provide a comprehensive overview of the current challenges faced by mental health professionals working within the legislative and correctional landscapes. Topics of discussion will include the prevalence and impact of mental health issues among the incarcerated population, the effectiveness of existing mental health policies and legislation, and potential reforms to enhance the mental health support system within prisons.
Dehradun ❤CALL Girls 8901183002 ❤ℂall Girls IN Dehradun ESCORT SERVICE❤
See the Whole Picture: Using SV-AUC for Empty/Full AAV Capsid Analysis
1. The life science business of Merck KGaA, Darmstadt, Germany
operates as MilliporeSigma in the U.S. and Canada.
See the whole
picture: Using SV-
AUC for empty/full
AAV capsid analysis
Kamran Anwar, PhD
Daryl-Anne Watson
2. The life science business
of Merck KGaA, Darmstadt,
Germany operates as
MilliporeSigma in the U.S.
and Canada
3. Agenda
An Introduction to AAV
Regulatory expectations
Key technical requirements and data interpretation
1
2
3
4
How Empty/Full fits into the larger picture of
AAV characterization
5. See the whole picture: Using SV-AUC for empty/full AAV capsid analysis5
Ongoing Clinical Trials for Cell and Gene
Therapeutic Areas in 2019
0
50
100
150
200
250
300
350
400
450
500
Gene-Modified & Cell-
Based IO
Gene Therapy Cell Therapy Tissue Engineering
Phase I Phase II Phase III
Source, Alliance for Regenerative Medicine 2019 Report
NumberofClinicalTrials
1,066
Total trials in 2019
6. See the whole picture: Using SV-AUC for empty/full AAV capsid analysis6
While Adeno-associated virus (AAV) has limited packaging
capacity, it’s versatility makes it a compelling choice
Parvovirus family
- First discovered as an Adenovirus contaminant in 1965
- Known as a dependovirus which means it requires helper genes
from another source to replicate
Relatively stable
- Non-enveloped capsid provides protection towards low pH and
temperature changes
- Insensitive to freeze-thaw cycles and dehydration
Tissue tropism
- The serotype used can impact the therapeutic effectiveness of the
product
- Promoters can also be used to expand or limit the tissue selectivity
- Chimeras (a hybrid of 2 or more different serotypes) can enhance
tissue selectivity
• Delivery mechanism
- Delivering the GOI episomally decreases the likelihood of
insertional mutagenesis
Features Adeno-Associated Virus
Typical Use In vivo
Genome ssDNA
Virus Coat Non-enveloped
Diameter 18-26nm
Packaging Size 4.7kb
Infection Range Mostly dividing cells
Charge Positive
Integration Mostly non-integrating
Main advantage Non-pathogenic
Main disadvantage Small packaging capacity
3’ITR
Promoter
Gene of
interest
VP1, VP2, VP35’ Inverted
terminal repeat
(ITR)
7. 7
Current manufacturing platforms being employed to generate rAAV
Transfection Stable cell line Co-Infection
See the whole picture: Using SV-AUC for empty/full AAV capsid analysis
Source, Penaud-Budloo et al. 2018
e.g. HEK293 Cells e.g. HEK293, HeLa, A549 Cells e.g. HEK293 or BHK Cells e.g. Sf9 Cells
e.g. HSV e.g. Baculovirus
e.g. wtAdPlasmids
8. Generation & separation of defective particles are two of the
greatest challenges facing AAV developers today
EMPTY
FULL
• Adeno-associated virus (AAV) production gives rise to a
mixed population of viral particles
• The impact of these defective particles is largely
unknown, however, they are thought to:
Diminish product efficacy
Compete for receptor binding sites
Provoke an immune response
• However, a recent study suggested that the empty
particles could act as a decoy to overcome pre-existing
immunity towards AAV
• As the risk or benefit remains unclear, it is imperative to
monitor product composition and quality
See the whole picture: Using SV-AUC for empty/full AAV capsid analysis8
Empty Partial Full Other
10. Increase in Regulations for Cell and Gene Therapy Observed in the
Past Two Years
FDA: Content and review of CMC
information for
Human gene therapy INDs
Human somatic cell therapy INDs
EMA: Guideline on human cell-based,
gene therapy medicinal products
EMA: GMP for ATMPs
EU Draft : Annex 1 revision for
sterile medicinal products
PIC/S Annex 2A Draft guidance for
the manufacture of ATMPs
NIFDC. China: Quality Control of
CAR-T Cell Therapy Products and
Consideration for Non-clinical
Research
FDA: Potency tests for cellular and
gene therapy products
FDA Draft guidance on CMC and Retroviral
testing guidance
EMA Guideline on quality, non-clinical and
clinical aspects of medicinal products
containing genetically modified cells
FDA: Finalized guidance
Testing of retroviral vector-based
human gene therapy products for
replication competent retrovirus during
product manufacture and patient
follow-up.
Chemistry, manufacturing and control
(CMC) for human gene therapy INDs
ChP: General Chapter of Gene Therapy
Products for Human Use (draft)
2008 2011 2017 2018 2019 2020
10 See the whole picture: Using SV-AUC for empty/full AAV capsid analysis
11. • US FDA Guidance for Industry: Chemistry, manufacturing and control (CMC) for human gene
therapy Investigational New Drug Applications (INDs). (2020)
• US FDA Guidance for Industry: Testing of retroviral vector-based human gene therapy products for
replication competent retrovirus during product manufacture and patient follow-up. (2020)
• Draft guideline on quality, non-clinical and clinical requirements for investigational advanced
therapy medicinal products in clinical trials, EMA/CAT January 2019
• EMA Guideline on the quality, non-clinical and clinical aspects of gene therapy medicinal products.
EMA/CAT/80183/2014 March 2018
• European Commission Guideline on Good Manufacturing Practice specific to Advanced Therapy
Medicinal Products (2017)
• ICH Q5D: Derivation and Characterization of Cell Substrates used for Production of
Biotechnological /Biological Products (1997)
• ICH Q5A: Viral safety evaluation of biotechnology products derived from cell lines of human or
animal origin. (1997)
• WHO Recommendations for the evaluation of animal cell cultures as substrates for the manufacture
of biological medicinal products and for the characterization of cell banks. TRS 978, Annex 3 (2011)
Regulatory Guidance of note for Cell & Gene Therapy Products
11
FDA
EMA
ICH
WHO
See the whole picture: Using SV-AUC for empty/full AAV capsid analysis
12. FDA CMC Information for Human Gene
Therapy IND Applications, January 2020
(p30)
“For viral vectors, typical product-related impurities may
include defective interfering particles, non-infectious particles,
empty capsid particles, or replicating recombinant virus
contaminants. These impurities should be measured and
may be reported as a ratio, for example, full:empty particles or
virus particles:infectious units.”
Guideline on the quality, non-clinical and
clinical aspects of gene therapy medicinal
products (p17)
“For viral vectors, infectious titre should be quantified; the
number of particles (infectious/non-infectious, empty/genome
containing) should also be determined. Particle to infectivity
ratio should be included to define the content of the drug
substance.”
See the whole picture: Using SV-AUC for empty/full AAV capsid analysis12
Regulatory agencies consider empty particles as product
impurities
FDA
EMA
14. 14
Recombinant AAV Heterogeneity: Empty:Full by Transmission
Electron Microscopy (TEM)
See the whole picture: Using SV-AUC for empty/full AAV capsid analysis
AAV2 mixture of
empty and full capsids
Full
Empty
15. See the whole picture: Using SV-AUC for empty/full AAV capsid analysis15
A multi-faceted or “package” approach is recommended to
determine product composition
Analytical Ultracentrifugation
Electron Microscopy
ELISA + PCR
Anion-exchange chromatography
1
2
3
4
Theoretical calculation of empty capsids based on quantitation of
viral capsid proteins to determine virus particles/ml with viral
genome content assessment by PCR. Variability seen
Allows visualization of the particles but analysis is subjective.
Capsids with partial genomes can be challenging to identify
Determine percentage of empty/full capsids due to ability to
separate particles by mass, shape and size. Serotype-
independent
Separates viral particles based on capsid surface charge.
Needs to be optimized depending on capsid used.
Empty Partial Full
16. See the whole picture: Using SV-AUC for empty/full AAV capsid analysis16
Comparison of different analytical methods in determining
rAAV purity
17. OptimaTM AUC System
17
Analytical Ultracentrifugation (AUC)
Sedimentation velocity (SV) measures how fast macromolecules move in response to centrifugal force
Shape
Size
Mass
Moving molecules are scanned simultaneously by 2 independent optical systems:
UV Absorbance (selective)
Rayleigh Interference (RI)detection (non-selective)
SEDFIT analysis software
Cell
Rotor AN-50Ti
See the whole picture: Using SV-AUC for empty/full AAV capsid analysis
18. Measuring changes in sedimentation boundary movement gives us information about the mass and
shape of macromolecules.
Analytical Ultracentrifugation (AUC)
18
6.2 6.3 6.4 6.5 6.6 6.7 6.8 6.9 7
-0.1 -0.1
0 0
0.1 0.1
0.2 0.2
0.3 0.3
absorbance[OD]
Radial Distance (d)
Meniscus Boundaries (t,d)
Initial
Conc
See the whole picture: Using SV-AUC for empty/full AAV capsid analysis
19. 19
Requirements for Sedimentation Velocity AUC
Formulation buffer “recipe”
Sample volume of 400 µL
Sample concentration of 1E12 vp/ml minimum
Formulation buffer 1-2 mL
1
2
3
4
Avoid sugars and high concentrations of certain
buffering agents in the formulation buffer5
See the whole picture: Using SV-AUC for empty/full AAV capsid analysis
20. 20
Sedimentation Velocity Data Analysis
SEDFIT: Typical AAV profile containing different composition of capsids
empty partial full aggregates
See the whole picture: Using SV-AUC for empty/full AAV capsid analysis
21. See the whole picture: Using SV-AUC for empty/full AAV capsid analysis21
Sedimentation Velocity Data Analysis
Direct relationship with peak area and viral concentration
AAV8-LacZ (Rayleigh Interference) AAV8 empty (Rayleigh Interference)
22. 22
Sedimentation Velocity Data Analysis
Integration by SEDFIT helps calculate the different capsid
content by quantifying the area under the peaks
Initial integration of area containing all peaks of interest for total area
See the whole picture: Using SV-AUC for empty/full AAV capsid analysis
empty partial full aggregates
23. 23
Sedimentation Velocity Data Analysis
Followed by integration of individual peaks of interest
See the whole picture: Using SV-AUC for empty/full AAV capsid analysis
empty
24. 24
Sedimentation Velocity Data Analysis
Integration of individual peaks of interest
See the whole picture: Using SV-AUC for empty/full AAV capsid analysis
full
25. 25
Sedimentation Velocity Data Analysis
Area of peak
of interest
Total
area
Percent of AAV capsid in
mixture
Once the area of all peaks
of interest is determined by
integration, a simple
calculation then determines
the peak percentage
See the whole picture: Using SV-AUC for empty/full AAV capsid analysis
28. Characterization helps to answer crucial questions surrounding product
and process quality
Structural information
• Identity
• Product related impurities:
empty/full capsids
Aggregates
Degraded vector
AUC, SEC, electrophoresis, DLS
Biological activity
• Does it transduce cells efficiently?
• Transgene expression levels?
• Is the protein expressed functionally
active?
Structure
Binding/
infection of
target cells
Biological
Activity
How does my
vector
function?
What are the
physical/
structural
attributes of
my vector?
28 See the whole picture: Using SV-AUC for empty/full AAV capsid analysis
29. “Uniquely identify” a
product & distinguish it
from others. Good practice
to use different test
methods, e.g. peptide
mapping, LC-MS, ELISA,
PCR
Elucidation of structure and
other characteristics –
sequence analysis and
confirmation of the primary,
secondary, or higher order
structure; post-translational
modifications, e.g. CD, LC-
MS, RP-HPLC
Key characteristics of the
DS that can influence the
performance of the DP:
concentration, viability,
aggregation infectivity
should be listed in the CTD,
e.g. ELISA, SEC-HPLC
- Capsid protein purity, e.g.
proteins, DNA, cell debris,
reagents
- Defective or empty capsid
particles should be measured &
reported
- Aggregated, oxidated, degraded
vector, e.g. DLS, SEC-HPLC
1 3
2 4
Capsid Characterization, as defined by the Regulatory Agencies
Capsid Identity
Capsid titer
Capsid Characterization
Capsid Purity
Sources, https://www.fda.gov/vaccines-blood-biologics/biologics-guidances/cellular-gene-therapy-guidances
Rumachik N G et al (2020) bioRxiv, doi.org/10.1101/640169 ; C Muck, BASG (Austrian Agency for Health & Food Safety)
29
30. 30
Genome characterization takes a similar approach
1 3
2 4
Genome Identity
Genome titer
Genome Characterization
Genome Purity
“Uniquely identify” a
product & distinguish it
from others. Good practice
to use different test
methods, e.g. sequencing,
PCR
Ratio of positive to negative
DNA strands & vector
genome size, e.g. Agarose
alkaline electrophoresis,
Size variants distribution
Key characteristics of the
DS that can influence the
performance of the DP:
concentration, viability,
aggregation infectivity
should be listed in the CTD,
e.g. PCR
- Unwanted packaged sequences,
e.g. NGS, PCR
- Ratio of positive to negative
DNA strands
- Empty/Full genome content,
e.g. AUC
Sources, https://www.fda.gov/vaccines-blood-biologics/biologics-guidances/cellular-gene-therapy-guidances
Rumachik N G et al (2020) bioRxiv, doi.org/10.1101/640169 ; C Muck, BASG (Austrian Agency for Health & Food Safety)
31. HeLaRC32
Genomic copies
Measurement of the
number of virus
genomes in a
preparation
PCR based assay
Number of particles
ELISA based assays to
measure virus capsid
proteins
Concentration of
viral particles that
can transduce cells
Infectivity assays
Require appropriate
cell substrate for
propagation
Virus measurement
using PCR, ELISA, flow
cytometry, plaque/foci
formation.
Total Intact Viral
Particles
Infectious Titer Transgene Expression Functional Activity
Flow cytometry
Can also be used to
deduce transduction
efficiency
ELISA
Other (e.g.HPLC)
Biological effect
related to MOA in
physiologically
relevant system
A multi-faceted approach is recommended to assess Biological
Activity
See the whole picture: Using SV-AUC for empty/full AAV capsid analysis31
32. See the whole picture: Using SV-AUC for empty/full AAV capsid analysis32
Monitoring and controlling process & product impurities
decreases safety risk
Impurity
Host cell protein
Host cell DNA
Cell culture related components
Process reagents
Residual plasmid DNA
Empty or defective particles
33. 33
Summary
Regulatory agencies specify that AAV particle
composition should be measured, monitored and
reported
We recommend a package approach to determine the
viral preparation
The AUC assay provides a quantitative, serotype-
independent analysis and can be validated to GMP
with a product-specific validation approach
AAV characterization expectations are evolving as the
impact of less understood attributes of AAV are being
analyzed