View our webinar here: https://bit.ly/2lKNdWX
Many different impurities are present in or generated during biotherapy manufacturing. This webinar will address how process contaminates can arise from raw input materials, occur as residual processing agents, or form as reaction by-products. We will review strategies within product characterization to de-risk the manufacturing process, including the use of routine and high complexity assays; and the recommended testing to meet regulatory requirements for clinical submission. Learn methods to avoid costly pitfalls and implement procedures to expedite product quality decisions at critical junctures in your development plan. We will discuss two types of therapies:
Cell & Gene Therapies
Polyethylenimine (PEI) is a transfection agent used in nearly all cell and gene therapy products. We will review the regulations and the liquid chromatography with charged aerosol detection (LC-CAD) methodology to demonstrate PEI removal during the production process.
Monoclonal Antibodies (mAb) and Cell & Gene Therapies
During mAb manufacturing and inherent to Cell & Gene Therapies, a significant proportion of process impurities arise from the host cell used to express the drug. Host cell protein (HCP) impurities, present at PPM-levels, are a major immunogenicity risk because they can elicit an unpredictable immune response in patients. We will review why their complex and diverse nature makes them challenging to monitor, and theho best practices, specifically HCP identification by mass spectrometry, for detection.
Learning points:
1. Accurate detection and characterization of residual PEI in cell and gene therapy products
2. Effective detection and characterization of residual host cell proteins (HCP) in mAbs
3. Available technology and assays for quantifying process impurities
4. Current regulatory requirements for detecting, quantifying, and removing process impurities during biotherapy manufacturing
Sr no Contents
1 Introduction
2 Advantages and disadvantages
3 Types of nanoparticle
4 Classification of Nanoparticle
5 Polymers used in nanoparticles
6 Method of preparation
7 Evaluation of nanoparticles
8 Application of nanoparticles
9 References
Nanoparticles is derived from the Greek word Nano means extremely small.
Nanoparticles are sub Nano sized colloidal drug delivery systems .
Particle size ranges from 10-1000 nm in diameter .
They are made up of natural, synthetic or semi synthetic polymers carrying drugs or proteinaceous substances, i.e. antigen(s) .
Drugs are entrapped either in the polymer matrix as a particulates or solid solutions or may be bound to particle surface by physical adsorption or by chemical reaction.
Drug can be added during preparation of nanoparticles or to the previously prepared nanoparticles
Nanoparticles can act as controlled release system depending on their polymeric composition.
As a targeted drug carrier nanoparticles reduce drug toxicity
Less amount of dose required.
They enhance aqueous solubility of poorly soluble drug therefore increase its bioavailability, therapeutic efficacy and Reduces side effects.
Nanoparticles can be administer by various routes including oral, nasal, parenteral, intra-ocular etc.
A) AMPHIPHILIC MACROMOLECULE CROSS-LINKING
B) Polymerization method
C)Polymer precipitation method
Heat cross-linking
Chemical cross-linking
Emulsion chemical dehydration
By Crosslinking in W/O Emulsion
PH-induced aggregation
Counter ion induced aggregation
Emulsion polymerization a)Micellar nucleation and polymerization b)Homogenous nucleation and polymerization)
Dispersion polymerization
Interfacial polymerization
Emulsion solvent evaporation method
Double emulsion and evaporation method
Solvent displacement
Salting out
Nanoprecipitation
Niosomes is under the Novel drug delivery system. In which the drug are enclosed in the bilayer vesicle which is made up of the phospholipid. Niosomes are the similar to the liposomes both are made up of the bilayer of phospholipid. But in niosomes several advantages of over the liposomes.
Sr no Contents
1 Introduction
2 Advantages and disadvantages
3 Types of nanoparticle
4 Classification of Nanoparticle
5 Polymers used in nanoparticles
6 Method of preparation
7 Evaluation of nanoparticles
8 Application of nanoparticles
9 References
Nanoparticles is derived from the Greek word Nano means extremely small.
Nanoparticles are sub Nano sized colloidal drug delivery systems .
Particle size ranges from 10-1000 nm in diameter .
They are made up of natural, synthetic or semi synthetic polymers carrying drugs or proteinaceous substances, i.e. antigen(s) .
Drugs are entrapped either in the polymer matrix as a particulates or solid solutions or may be bound to particle surface by physical adsorption or by chemical reaction.
Drug can be added during preparation of nanoparticles or to the previously prepared nanoparticles
Nanoparticles can act as controlled release system depending on their polymeric composition.
As a targeted drug carrier nanoparticles reduce drug toxicity
Less amount of dose required.
They enhance aqueous solubility of poorly soluble drug therefore increase its bioavailability, therapeutic efficacy and Reduces side effects.
Nanoparticles can be administer by various routes including oral, nasal, parenteral, intra-ocular etc.
A) AMPHIPHILIC MACROMOLECULE CROSS-LINKING
B) Polymerization method
C)Polymer precipitation method
Heat cross-linking
Chemical cross-linking
Emulsion chemical dehydration
By Crosslinking in W/O Emulsion
PH-induced aggregation
Counter ion induced aggregation
Emulsion polymerization a)Micellar nucleation and polymerization b)Homogenous nucleation and polymerization)
Dispersion polymerization
Interfacial polymerization
Emulsion solvent evaporation method
Double emulsion and evaporation method
Solvent displacement
Salting out
Nanoprecipitation
Niosomes is under the Novel drug delivery system. In which the drug are enclosed in the bilayer vesicle which is made up of the phospholipid. Niosomes are the similar to the liposomes both are made up of the bilayer of phospholipid. But in niosomes several advantages of over the liposomes.
WHAT IS LIQUID LIQUID EXTRACTION?
STEPS OF LIQUID LIQUID EXTRACTION
SCHEMATIC DIAGRAM OF EXTRACTION PROCESS
WHERE WE CAN USE LIQUID LIQUID EXTRACTION
TERNARY SYSTEM
LIQUID LIQUID EQUILIBRIA
EXPERIMENTAL DETERMINATION OF LLE DATA
GRAPHICAL REPRESENTATION OF LLE DATA
EQUILATERAL TRIANGULAR DIAGRAM
EFFECTS OF TEMPERATURE ON ETD
RECTANGULAR TRIANGULAR DIAGRAM
CRITERIA FOR SOLVENT SELECTION
Micro-organisms need water in order to grow and reproduce. When moisture is removed from food, it does not kill the microbes but it does stop their growth. Dehydration reduces the water activity level, weight and the bulk of the food and helps to preserve the product.
The A-VAX Case Study involved the efforts of many individuals and would not have been made possible if it were not for the countless number of hours spent by the 5 participating companies (GlaxosmithKline, MedImmune, Merck, Pfizer, and sanofi pasteur).
Optimization of Tangential Flow Filtration Applications and Scale Up Consider...Merck Life Sciences
This presentation provides an introduction to tangential flow filtration applications for AAV and lentivirus and will review:
• Basics of tangential flow filtration (TFF)
• TFF AAV and lentivirus process overview
• Operating parameters optimization: flux-controlled microfiltration
• Scale up considerations
To learn more about this topic or collaborate with our technical experts, schedule a remote visit at our M Lab™ Collaboration Centers: www.merckmillipore.com/remotevisit
Production of Sterile Water for Injection. WFI (Water for Injection) Manufact...Ajjay Kumar Gupta
Sterilized Water is water that has been sterilized, to ensure an absence of any bacteria in the water. It is used for mixing infant formula for babies, for people with compromised immune systems, and to dilute or dissolve water soluble drugs for injections.
Sterile water is water that has no microorganisms living within it. As it cannot transfer pathogens, it is used mainly in the medical setting. Sterile water, though sometimes distilled, is not the same thing as distilled water. As some microorganisms can survive at high temperatures, simply boiling water may not be enough to sterilize it. Special, but not uncommon, equipment is required if one wishes to sterilize water.
See more
https://goo.gl/D7sLmv
https://goo.gl/9jNsi1
https://goo.gl/2RZ6X7
https://goo.gl/zansRg
Contact us:
Niir Project Consultancy Services
An ISO 9001:2015 Company
106-E, Kamla Nagar, Opp. Spark Mall,
New Delhi-110007, India.
Email: npcs.ei@gmail.com , info@entrepreneurindia.co
Tel: +91-11-23843955, 23845654, 23845886, 8800733955
Mobile: +91-9811043595
Website: www.entrepreneurindia.co , www.niir.org
Tags
Preparation Process for Water for Injection, Sterile Water for Injection, Production of Water for Injection, Sterilised Water for Injections, Production of Sterile Water for Injection, Manufacturing of Water for Injection, Preparation of Water for Injection, Preparation of Sterile Water for Injection, Pharmaceutical Water, Preparing Sterile Intravenous Products, Preparation of Pharmaceutical Water, Water for Injection in Pharmaceutical Industry, Sterile Pharmaceutical Products, Water for Pharmaceutical Use, How to Make Sterile Water?, Production Plant for Producing Sterile Water, Production of Sterile Water Injections for Pain Relief, Water for Injection for Pharmaceutical and Bio-Pharmaceutical Industries, Sterile Water for Injection Syringes: Highly Customizable, WFI (Water for Injection), Sterile Water Production, Water for Pharmaceutical Purposes, Aqua Ad Iniectabilia, Aqua Ad Injectionem, Production of Water for Injection for Pharmaceutical, Production of WFI, WFI (Water for Injection) production, Intravenous (IV) Solution Manufacturing, Dextrose Saline (I.V.Fluids) Manufacturing Plant, I.V. Fluids Manufacturing Industry, Production of Water for Injection (WFI), Producing Water for Injection (WFI), Pharmaceutical Water, Medical Water, Water for Injection & Purified Water for Pharmaceutical, Projects on Small Scale Industries, Small scale industries projects ideas, Sterile Water Based Small Scale Industries Projects, Project profile on small scale industries, How to Start Sterile Water Production Industry in India, Sterile Water Production Projects, New project profile on Sterile Water Production industries, Project Report on Sterile Water Production Industry, Detailed Project Report on Sterile Water Production, Project Report on Sterile Water Production
Breaking the Status Quo: Using Mass Spectrometry to detect Host Cell ProteinsMerck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3b3Tbcd
Measurement of host cell proteins is vital to ensuring a biotherapy's purity and a patient's safety. Biotherapies treat diseases with products produced by living organisms, as a result, host cell components must be characterized and controlled. We'll review new methods within product characterization for detection.
Trace amounts of host cell proteins can be present after the production and purification of any biopharmaceutical. Detection of these species requires highly specific techniques to accurately quantify even low levels of contamination. Host cell protein impurities, present at PPM-levels in biotherapies, are a major immunogenicity risk because they can elicit an unpredictable immune response in patients. Their complex and diverse nature makes them challenging to detect or monitor. With acceptance criteria for host residual DNA usually set at a very low level (often =1.0 pg of DNA per mg of drug substance), effective removal techniques and sensitive methods of detection are critical.
Antibody-based techniques, like the enzyme-linked immunosorbent assay (ELISA), have been used to assess the HCP load of biotherapeutics before and after process changes. However, these techniques do not necessarily detect qualitative changes in the HCP population. In this webinar, we will discuss how mass spectrometry (MS)-based approaches coupled with ELISA methods help detect qualitative and quantitative differences in HCP populations.
In this webinar, you will learn:
• Comprehensive HCP ID and semi-quantitation
• HC agnostic process
• Creation of process specific database
• Differential clearance of specific HCPs throughout purification steps
• Monitoring of problematic species e.g. immunogenic (PLBL2), lipases and proteases
• Explanation about why 90% of BLAs filed included this HCP MS data
Breaking the Status Quo: Using Mass Spectrometry to detect Host Cell ProteinsMilliporeSigma
Measurement of host cell proteins is vital to ensuring a biotherapy's purity and a patient's safety. Biotherapies treat diseases with products produced by living organisms, as a result, host cell components must be characterized and controlled. We'll review new methods within product characterization for detection.
Trace amounts of host cell proteins can be present after the production and purification of any biopharmaceutical. Detection of these species requires highly specific techniques to accurately quantify even low levels of contamination. Host cell protein impurities, present at PPM-levels in biotherapies, are a major immunogenicity risk because they can elicit an unpredictable immune response in patients. Their complex and diverse nature makes them challenging to detect or monitor. With acceptance criteria for host residual DNA usually set at a very low level (often =1.0 pg of DNA per mg of drug substance), effective removal techniques and sensitive methods of detection are critical.
Antibody-based techniques, like the enzyme-linked immunosorbent assay (ELISA), have been used to assess the HCP load of biotherapeutics before and after process changes. However, these techniques do not necessarily detect qualitative changes in the HCP population. In this webinar, we will discuss how mass spectrometry (MS)-based approaches coupled with ELISA methods help detect qualitative and quantitative differences in HCP populations.
In this webinar, you will learn:
• Comprehensive HCP ID and semi-quantitation
• HC agnostic process
• Creation of process specific database
• Differential clearance of specific HCPs throughout purification steps
• Monitoring of problematic species e.g. immunogenic (PLBL2), lipases and proteases
• Explanation about why 90% of BLAs filed included this HCP MS data
WHAT IS LIQUID LIQUID EXTRACTION?
STEPS OF LIQUID LIQUID EXTRACTION
SCHEMATIC DIAGRAM OF EXTRACTION PROCESS
WHERE WE CAN USE LIQUID LIQUID EXTRACTION
TERNARY SYSTEM
LIQUID LIQUID EQUILIBRIA
EXPERIMENTAL DETERMINATION OF LLE DATA
GRAPHICAL REPRESENTATION OF LLE DATA
EQUILATERAL TRIANGULAR DIAGRAM
EFFECTS OF TEMPERATURE ON ETD
RECTANGULAR TRIANGULAR DIAGRAM
CRITERIA FOR SOLVENT SELECTION
Micro-organisms need water in order to grow and reproduce. When moisture is removed from food, it does not kill the microbes but it does stop their growth. Dehydration reduces the water activity level, weight and the bulk of the food and helps to preserve the product.
The A-VAX Case Study involved the efforts of many individuals and would not have been made possible if it were not for the countless number of hours spent by the 5 participating companies (GlaxosmithKline, MedImmune, Merck, Pfizer, and sanofi pasteur).
Optimization of Tangential Flow Filtration Applications and Scale Up Consider...Merck Life Sciences
This presentation provides an introduction to tangential flow filtration applications for AAV and lentivirus and will review:
• Basics of tangential flow filtration (TFF)
• TFF AAV and lentivirus process overview
• Operating parameters optimization: flux-controlled microfiltration
• Scale up considerations
To learn more about this topic or collaborate with our technical experts, schedule a remote visit at our M Lab™ Collaboration Centers: www.merckmillipore.com/remotevisit
Production of Sterile Water for Injection. WFI (Water for Injection) Manufact...Ajjay Kumar Gupta
Sterilized Water is water that has been sterilized, to ensure an absence of any bacteria in the water. It is used for mixing infant formula for babies, for people with compromised immune systems, and to dilute or dissolve water soluble drugs for injections.
Sterile water is water that has no microorganisms living within it. As it cannot transfer pathogens, it is used mainly in the medical setting. Sterile water, though sometimes distilled, is not the same thing as distilled water. As some microorganisms can survive at high temperatures, simply boiling water may not be enough to sterilize it. Special, but not uncommon, equipment is required if one wishes to sterilize water.
See more
https://goo.gl/D7sLmv
https://goo.gl/9jNsi1
https://goo.gl/2RZ6X7
https://goo.gl/zansRg
Contact us:
Niir Project Consultancy Services
An ISO 9001:2015 Company
106-E, Kamla Nagar, Opp. Spark Mall,
New Delhi-110007, India.
Email: npcs.ei@gmail.com , info@entrepreneurindia.co
Tel: +91-11-23843955, 23845654, 23845886, 8800733955
Mobile: +91-9811043595
Website: www.entrepreneurindia.co , www.niir.org
Tags
Preparation Process for Water for Injection, Sterile Water for Injection, Production of Water for Injection, Sterilised Water for Injections, Production of Sterile Water for Injection, Manufacturing of Water for Injection, Preparation of Water for Injection, Preparation of Sterile Water for Injection, Pharmaceutical Water, Preparing Sterile Intravenous Products, Preparation of Pharmaceutical Water, Water for Injection in Pharmaceutical Industry, Sterile Pharmaceutical Products, Water for Pharmaceutical Use, How to Make Sterile Water?, Production Plant for Producing Sterile Water, Production of Sterile Water Injections for Pain Relief, Water for Injection for Pharmaceutical and Bio-Pharmaceutical Industries, Sterile Water for Injection Syringes: Highly Customizable, WFI (Water for Injection), Sterile Water Production, Water for Pharmaceutical Purposes, Aqua Ad Iniectabilia, Aqua Ad Injectionem, Production of Water for Injection for Pharmaceutical, Production of WFI, WFI (Water for Injection) production, Intravenous (IV) Solution Manufacturing, Dextrose Saline (I.V.Fluids) Manufacturing Plant, I.V. Fluids Manufacturing Industry, Production of Water for Injection (WFI), Producing Water for Injection (WFI), Pharmaceutical Water, Medical Water, Water for Injection & Purified Water for Pharmaceutical, Projects on Small Scale Industries, Small scale industries projects ideas, Sterile Water Based Small Scale Industries Projects, Project profile on small scale industries, How to Start Sterile Water Production Industry in India, Sterile Water Production Projects, New project profile on Sterile Water Production industries, Project Report on Sterile Water Production Industry, Detailed Project Report on Sterile Water Production, Project Report on Sterile Water Production
Breaking the Status Quo: Using Mass Spectrometry to detect Host Cell ProteinsMerck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3b3Tbcd
Measurement of host cell proteins is vital to ensuring a biotherapy's purity and a patient's safety. Biotherapies treat diseases with products produced by living organisms, as a result, host cell components must be characterized and controlled. We'll review new methods within product characterization for detection.
Trace amounts of host cell proteins can be present after the production and purification of any biopharmaceutical. Detection of these species requires highly specific techniques to accurately quantify even low levels of contamination. Host cell protein impurities, present at PPM-levels in biotherapies, are a major immunogenicity risk because they can elicit an unpredictable immune response in patients. Their complex and diverse nature makes them challenging to detect or monitor. With acceptance criteria for host residual DNA usually set at a very low level (often =1.0 pg of DNA per mg of drug substance), effective removal techniques and sensitive methods of detection are critical.
Antibody-based techniques, like the enzyme-linked immunosorbent assay (ELISA), have been used to assess the HCP load of biotherapeutics before and after process changes. However, these techniques do not necessarily detect qualitative changes in the HCP population. In this webinar, we will discuss how mass spectrometry (MS)-based approaches coupled with ELISA methods help detect qualitative and quantitative differences in HCP populations.
In this webinar, you will learn:
• Comprehensive HCP ID and semi-quantitation
• HC agnostic process
• Creation of process specific database
• Differential clearance of specific HCPs throughout purification steps
• Monitoring of problematic species e.g. immunogenic (PLBL2), lipases and proteases
• Explanation about why 90% of BLAs filed included this HCP MS data
Breaking the Status Quo: Using Mass Spectrometry to detect Host Cell ProteinsMilliporeSigma
Measurement of host cell proteins is vital to ensuring a biotherapy's purity and a patient's safety. Biotherapies treat diseases with products produced by living organisms, as a result, host cell components must be characterized and controlled. We'll review new methods within product characterization for detection.
Trace amounts of host cell proteins can be present after the production and purification of any biopharmaceutical. Detection of these species requires highly specific techniques to accurately quantify even low levels of contamination. Host cell protein impurities, present at PPM-levels in biotherapies, are a major immunogenicity risk because they can elicit an unpredictable immune response in patients. Their complex and diverse nature makes them challenging to detect or monitor. With acceptance criteria for host residual DNA usually set at a very low level (often =1.0 pg of DNA per mg of drug substance), effective removal techniques and sensitive methods of detection are critical.
Antibody-based techniques, like the enzyme-linked immunosorbent assay (ELISA), have been used to assess the HCP load of biotherapeutics before and after process changes. However, these techniques do not necessarily detect qualitative changes in the HCP population. In this webinar, we will discuss how mass spectrometry (MS)-based approaches coupled with ELISA methods help detect qualitative and quantitative differences in HCP populations.
In this webinar, you will learn:
• Comprehensive HCP ID and semi-quantitation
• HC agnostic process
• Creation of process specific database
• Differential clearance of specific HCPs throughout purification steps
• Monitoring of problematic species e.g. immunogenic (PLBL2), lipases and proteases
• Explanation about why 90% of BLAs filed included this HCP MS data
Introduction to Bioprocessing Sample SlidesPeteDeOlympio
Introduction to Bioprocessing
Monday, January 19, 8:30 AM-5:30 PM – Tuesday, January 20, 8:30 AM-12:30 PM
View sample slides
CHI’s Introduction to Bioprocessing training seminar offers a comprehensive survey of the steps needed to produce today’s complex biopharmaceuticals, from early development through commercial. The seminar begins with a brief introduction to biologic drugs and the aspects of protein science that drive the intricate progression of analytical and process steps that follows. We then step through the stages of bioprocessing, beginning with the development of cell lines and ending at the packaging of a finished drug product. The seminar also explores emerging process technologies, facility design considerations and the regulatory and quality standards that govern our industry throughout development. The important roles played by the analytical and formulation in developing and gaining approval for a biopharmaceutical are also examined. This 1.5-day class is directed to attendees working in any aspect of industry, including scientific, technical, business, marketing or support functions, who would benefit from a detailed overview of this field.
For full details visit chi-peptalk.com/peptalk_content.aspx?id=140088&libID=140059
Turning up the Compen-DIAL: Rapid Test Methods for Cell & Gene TherapiesMerck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3aeCPNB
Find out how we turn up the dial on quality control testing for cell and gene therapies through rapid methods for sterility, mycoplasma, and replication competent virus. We will review the current regulatory expectations as well as the benefits and limitations that come with each method.
Two of the biggest challenges with applying traditional quality control (QC) test methods to cell and gene therapies, is time to results, due to short shelf-life, and availability of sufficient sample, due to small production volumes.
So how can these challenges be overcome while still meeting regulatory expectations?
In this webinar we will discuss and review suitable methods for rapid testing of short-life cell and gene therapies that may also help conserve limited production material. We will look at benefits, limitations, and regulatory expectations for various QC needs including current and future rapid methods for sterility, mycoplasma and replication competent virus.
In this webinar, you will learn:
• Why the shelf life of a cell or gene therapy product may impact your QC testing strategy
• Current regulatory expectations surrounding rapid methods for sterility, mycoplasma and replication competent virus
• Potential impacts of pursuing a non-optimal QC testing strategy
Turning up the Compen-DIAL: Rapid Test Methods for Cell & Gene TherapiesMilliporeSigma
Watch the presentation of this webinar here: https://bit.ly/3aeCPNB
Find out how we turn up the dial on quality control testing for cell and gene therapies through rapid methods for sterility, mycoplasma, and replication competent virus. We will review the current regulatory expectations as well as the benefits and limitations that come with each method.
Two of the biggest challenges with applying traditional quality control (QC) test methods to cell and gene therapies, is time to results, due to short shelf-life, and availability of sufficient sample, due to small production volumes.
So how can these challenges be overcome while still meeting regulatory expectations?
In this webinar we will discuss and review suitable methods for rapid testing of short-life cell and gene therapies that may also help conserve limited production material. We will look at benefits, limitations, and regulatory expectations for various QC needs including current and future rapid methods for sterility, mycoplasma and replication competent virus.
In this webinar, you will learn:
• Why the shelf life of a cell or gene therapy product may impact your QC testing strategy
• Current regulatory expectations surrounding rapid methods for sterility, mycoplasma and replication competent virus
• Potential impacts of pursuing a non-optimal QC testing strategy
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
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
Overcome the challenges of Nucleic acid isolation from PCR inhibitor-rich mic...QIAGEN
This presentation will focus on nucleic acid extraction tools developed by QIAGEN that facilitate accurate non-biased community analysis and eliminate common amplification problems via the depletion of endogenous polymerase inhibitors using our patented Inhibitor Removal Technology.
Bioanalytical Method Development and Validation of Biosimilars: Lessons LearnedSai Babitha
Biosimilars are expected to be a significant growth driver for the pharmaceutical industry over the next decade, mainly because of the current market penetration of biologics and the need to provide payers cost savings over the originator therapeutics. Legislative support and regulatory guidance have facilitated their entry into pharmacy formularies of the future. Unlike small molecule generic drugs, biosimilars are heterogeneous proteins manufactured using cell-based systems of either microbial or mammalian origin. The use of living systems to manufacture drugs raises challenges in terms of product characterization and therapeutic equivalence to the innovator protein therapeutic. In this article, we share some lessons learned from developing
and validating pharmacokinetic and immunogenicity assays that support preclinicaland clinical comparative studies for the development of biosimilars.
Data driven strategies and considerations for scalable purification of Plasmi...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/2JeT1U9
Plasmid DNA (pDNA) presents unique manufacturing challenges. While research scale purification kits simplify small pDNA preparations, scalable manufacturing must leverage significant process understanding. This webinar presents scalable solutions for all downstream unit operations from harvest to bulk filtration.
Plasmid DNA (pDNA) has been an important scientific tool for decades, but as clinical and commercial applications increase, manufacturers of pDNA face pressure to optimize production activities to meet demand while maintaining critical quality attributes. Key challenges in pDNA manufacturing exist around purification unit operations due to its large size, high viscosity, shear sensitivity, and similarities between pDNA and impurities. Overcoming downstream challenges with scalable techniques requires in depth knowledge of unit operation parameters and holistic process understanding. Our work investigates parameters and key considerations for purification unit operations including harvest, lysis, clarification, tangential flow filtration, chromatography, and sterilizing grade filtration.
In this webinar, you will learn:
• Parameters for E. coli harvest using microfiltration tangential flow filtration
• Key considerations for scalable alkaline lysis
• Filter selection guidance for clarification of alkaline lysate
• Purification strategies using AEX chromatography resins and membranes
• Implementation considerations for ultrafiltration/diafiltration
• Watch-outs for sterile filtration
• Purification process flow for Plasmid DNA
The Viscosity Reduction Platform: Viscosity-reducing excipients for improveme...MilliporeSigma
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 PurificationMilliporeSigma
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...MilliporeSigma
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...MilliporeSigma
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...MilliporeSigma
Watch the presentation of this webinar: https://bit.ly/3Pjpjvr
Highlights of this webinar:
- Surface plasmon resonance as a powerful tool for biologic characterization including mAbs and ADCs.
- SPR allows rapid binding analysis in real time without using labels for SARS-CoV-2 receptor binding domain mutations.
- Kinetic data is indicative of possible neutralizing activity allowed assessment of neutralizing ability of therapeutic monoclonal antibodies.
- The application can provide preliminarily efficacy information and facilitated mAbs/ACDs candidate selection process
Detailed description:
Characterization of therapeutic monoclonal antibodies (mAbs) or Antibody drug conjugates (ADCs) is challenging due to their ability to bind to a variety of proteins via their Fc and Fab domains, giving rise to diverse biological functions associated with each domain. The Fc domain of mAbs interacts with Fc receptors with varying affinities, which can influence biological processes such as Complement-dependent cytotoxicity (CDC) and Antibody-dependent cellular cytotoxicity (ADCC), transcytosis, phagocytosis, and/or serum half-life.
An important characteristic of an antibody is its Fc effector function. Antibodies can be engineered to obtain desired binding of the Fc region to Fc receptors expressed on effector cells. Hence, it is crucial to evaluate the binding interaction of mAbs/ADC with Fc receptors in the early phase of drug development to understand the potential biological activity of the product in vivo.
Surface Plasmon Resonance (SPR) is a powerful technique to establish binding kinetics in real-time, label free, and high sensitivity with low sample consumption. Along with target antigen binding, it is crucial to evaluate the binding interaction of antibodies and ADCs with Fc receptors. Our SPR case studies investigated the impact on binding kinetics of ADCs with different linkers and the binding interactions of SARS-CoV-2 spike protein variants and evaluated the neutralizing ability of therapeutic mAbs. SPR characterisation can be facilitated in all stages of the product life cycle to ensure the quality and safety of mAbs and ADCs.
The Role of BioPhorum Extractables Data in the Effective Adoption of Single-U...MilliporeSigma
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
The Future of Pharma- and Biopharmaceutical AuditsMilliporeSigma
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
Identity testing by NGS as a means of risk mitigation for viral gene therapiesMilliporeSigma
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...MilliporeSigma
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...MilliporeSigma
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
How does the ICH Q5A revision impact viral safety strategies for biologics?MilliporeSigma
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...MilliporeSigma
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...MilliporeSigma
Watch the presentation of this webinar here: https://bit.ly/3Nbb5ug
Get insights and best practices from a multinational team establishing a platform for vaccine production. See how a long-term collaboration on a bench-scale process used to produce a Virus Like Particle (VLP) vaccine for SARS-CoV-2 was successfully converted to a robust GMP-compatible, scalable process.
The COVID-19 pandemic further emphasized the need for collaboration in the development of urgently needed vaccines and therapeutics. In this webinar, we take you behind the scenes of our collaboration with Technovax and Innovative Biotech in which a scalable VLP vaccine platform was optimized for use in a production facility in Nigeria in response to the need for local production of SARS-CoV-2 vaccines. The flexibility and robustness of the platform will enable its rapid deployment to support the West African pandemic readiness program. Initial development of the VLP process began in late 2019 and by March 2020, was already adapted for production of a SARS-CoV-2 vaccine.
In this webinar, you will learn:
• About building a priceless collaborative network with integrated solutions
• Virus-Like Particle Vaccines
• Process Development Overview and Challenges
• Pre-clinical Results and Next Steps
Presented by:
Jose M. Galarza, PhD,
President and Founder of TechnoVax
Naomi Baer,
Business development consultant, Emerging Biotech, BioProcess division
Youssef Gaabouri, Eng. ,
Associate Director, Head of Sales Middle East & Africa, BioProcess division
Risk-Based Qualification of X-Ray Sterilization for Single-Use SystemsMilliporeSigma
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 ...MilliporeSigma
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...MilliporeSigma
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...MilliporeSigma
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
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.
EU GMP Annex 1 Draft - Closed System Design Consideration with Single-Use Sys...MilliporeSigma
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!
Telehealth Psychology Building Trust with Clients.pptxThe Harvest Clinic
Telehealth psychology is a digital approach that offers psychological services and mental health care to clients remotely, using technologies like video conferencing, phone calls, text messaging, and mobile apps for communication.
Explore our infographic on 'Essential Metrics for Palliative Care Management' which highlights key performance indicators crucial for enhancing the quality and efficiency of palliative care services.
This visual guide breaks down important metrics across four categories: Patient-Centered Metrics, Care Efficiency Metrics, Quality of Life Metrics, and Staff Metrics. Each section is designed to help healthcare professionals monitor and improve care delivery for patients facing serious illnesses. Understand how to implement these metrics in your palliative care practices for better outcomes and higher satisfaction levels.
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
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.
The dimensions of healthcare quality refer to various attributes or aspects that define the standard of healthcare services. These dimensions are used to evaluate, measure, and improve the quality of care provided to patients. A comprehensive understanding of these dimensions ensures that healthcare systems can address various aspects of patient care effectively and holistically. Dimensions of Healthcare Quality and Performance of care include the following; Appropriateness, Availability, Competence, Continuity, Effectiveness, Efficiency, Efficacy, Prevention, Respect and Care, Safety as well as Timeliness.
How many patients does case series should have In comparison to case reports.pdfpubrica101
Pubrica’s team of researchers and writers create scientific and medical research articles, which may be important resources for authors and practitioners. Pubrica medical writers assist you in creating and revising the introduction by alerting the reader to gaps in the chosen study subject. Our professionals understand the order in which the hypothesis topic is followed by the broad subject, the issue, and the backdrop.
https://pubrica.com/academy/case-study-or-series/how-many-patients-does-case-series-should-have-in-comparison-to-case-reports/
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.
Process Impurities: Don’t Let PEI or HCP Derail Your BioTherapy
1. The life science business of Merck KGaA, Darmstadt, Germany
operates as MilliporeSigma in the U.S. and Canada.
Process Impurities:
Don’t Let PEI or HCP Derail
Your Biotherapy
Janice Lord & Omar Lamm
September 12, 2019
2. The life science business of Merck KGaA, Darmstadt, Germany
operates as MilliporeSigma in the U.S. and Canada.
Process Impurities:
Don’t Let PEI or HCP Derail
Your Biotherapy
Janice Lord & Omar Lamm
September 12, 2019
3. The life science business
of Merck KGaA, Darmstadt,
Germany operates as
MilliporeSigma in the U.S.
and Canada.
4. The manufacturing of a biotherapy involves multiple inputs,
ranging in complexity from a transfection reagent to the host
cell in which the therapy is manufactured. All of these process
components should be removed prior to the therapy being
available for human use.
During today’s webinar we will review strategies within product
characterization to de-risk the manufacturing process for cell
and gene therapies and monoclonal antibodies (mAbs).
We will focus on how we effectively detect and characterize:
• polyethylenimine (PEI), used in cell and gene therapy
products; and
• host cell proteins (HCPs), a factor in mAb therapies and
cell and gene therapies.
Introduction
6. Agenda
PEI Description and Use
Analytical Challenges
1
2
4
3
Testing guidelines / guidance
5
Our Method for PEI
detection & quantification:
UHPLC-CAD
GMP Processes / Method
Validation
7. 7
Cell and Gene Therapy: Safety & Characterization Testing
Plasmid or
Virus
Master Cell Bank (MCB)
Working Cell Bank
(WCB)
Process Development
(Growth/Production/Modification)
Plasmid Stock
Master/Working Virus Bank
(MVB/WVB)
Drug Substance
Drug Product
Cell
Identity
Safety
Stability
Lot Release
Testing
QA/QC
In-
Process
Testing
Identity
Purity
Safety
Identity
Purity
Safety
8. Gene transfection agent
Spontaneously adheres to and condenses DNA to
form spherical complexes that are readily
endocyclosed by cells. Once inside the cells, DNA
is released into the cytoplasm
Released DNA undergoes transcription and
translation giving rise to protein products or
Is used as a template for production of viral
vectors
Free PEI can cause cell death and induce cellular
stress responses
8
Description and Uses
PEI
Other uses
Polymeric coating for nanoparticles to deliver
anti-cancer agents
Increasing attachment of weakly anchoring cells
in cell culture
Cationic (positively charged) polymer with surfactant properties
9. 9
Testing Guidelines / Regulations for PEI
Regulatory requirements
ICH Q6B (1999): 2.3 Process controls / 2.3.1 Process-related considerations
• Evidence is required to show that PEI is removed (or controlled at an acceptable level) in
cell and gene therapy products.
When to test for PEI
• Development of manufacturing process
• Not needed once evidence demonstrating PEI removed/controlled
• As part of development, monitor PEI levels throughout the manufacturing process to
confirm removal of PEI.
• Justification for exclusion from LRT is provided if PEI removal is confirmed
10. Method development needs to overcome all these challenges
PEI does not contain
chromophores
PEI has multiple
positive charges
PEI binds
irreversibly to
silica based
columns
10
PEI is not an easy molecule to analyze
Analytical Challenges: Why you Should Outsource
Interference occurs
with
peptides/proteins
PEI is not a single
molecule and exists
in several forms
PEI has poor
aqueous
solubility and is
poorly soluble at
high pH
11. PEI
What form and Molecular Weight is used
Who is the supplier
Obtain a sample of the PEI used from the supplier
Solubility information
Sample Matrix
What other components are in the sample matrix
How much of each component is in the matrix
If the method is to be used for IPC, consider matrix components
at each stage
Obtain/make placebos
Outsourcing
Avoid need for capital expenditure
Choose partner with established latest technology and expertise
11
Analytical Challenges: Why you Should Outsource
Key information to know to get started measuring PEI
Repeating units
Linear
Branched
12. PEI Detection Types
12
PEI does not have chromophores i.e. does not absorb uv or visible light
Need alternative modes of detection
Evaporative light scattering detection (ELSD)
LC eluent is nebulized, mobile phase is evaporated from the droplets leaving particles. Particles
scatter light in an optical cell. The amount of light scattering is related to the mass of the particles
May lack sensitivity when looking for residual levels of PEI
Mass spectrometry
Separates molecules according to their mass to charge ratio
Major advantage is that as well as detection and quantification, MS can be used to confirm identity.
Disadvantages: cost and time
Complexation with UV absorbing moiety, then UV detection
Reaction has to be specific for PEI
Charged aerosol detection (CAD)
Similar to ELSD except the dry particles are charged using a high voltage then collected and
measured with an electrometer.
Provides near uniform response regardless of the analyte
13. Method: UHPLC-CAD
PEI Detection Workflow
13
PEI extracted from sample
matrix
Extract separated into
component parts via High Liquid
Chromatography (UHPLC)
The eluent from the UHPLC is
nebulized in the CAD and heated to
create dry particles.
AUC for PEI signal is used to
determine concentration
The particles are charged using
high voltage. The charged
particles are collected and
measured with an electrometer.
14. Separate or remove matrix components
Sample Preparation
14
Points to consider
Relative
Solubility of
components
Enzymatic
digestion
Solid phase
extraction
Precipitation
Centrifugation
15. 15
Summary
PEI Detection through UHPLC-CAD
Increasing Regulatory scrutiny
Sensitive, robust and validated methods are needed to determine residual levels of PEI in
CGT products
Outsourcing partner
Avoid the need for capital investment in new equipment and could be a quicker route to
reliable results
Other impurities that fit this method under
consideration
Triton, Tween, etc.
17. We will now focus on how we effectively detect and characterize host
cell proteins (HCPs), a factor in mAb therapies and cell and gene
therapies.
Host Cell Proteins: Identification by Mass Spectrometry
HCP impurities, present at PPM-levels, are a major
immunogenicity risk because they can elicit an unpredictable
immune response in patients.
We will review why their complex and diverse nature makes them
challenging to monitor and the best practices, specifically HCP
identification by mass spectrometry, for detection.
18. Agenda
HCP – Potential impacts on biotherapies
Why traditional HCP identification approaches are not satisfactory
1
2
3
Progressive techniques for HCP
identification: HCP by MS
19. Immunogenicity
• The ability of a particular substance, such as an
antigen or epitope, to provoke an immune
response in the body of a human and other
animal.
Lipases
• Enzymatic cleavage of fats or fatty acids
(polysorbate)
Proteases
• Enzymatic cleavage of proteins
19
Host Cell Proteins
How Can They Impact my Biotherapy?
20. Immunogenicity—case presented at BPI 2016 forum featured a
product expressed by a customized proprietary CHO cell line that elicited
anti-HCP antibodies in patients during clinical trials.
• Known offenders
• Various in silico options hitting the market
20
Host Cell Proteins
Immunogenicity
• USP General Chapter <1106> for a more in-depth discussion of factors influencing
immunogenicity. When patients receive more than one biotherapeutic protein with their
associated impurities, immunogenicity is an even greater concern.
21. One such CHO protein is phospholipase B-
like 2 (PLBL2), which has been observed
at different levels in mAbs produced using
platform processes.
Levels >10 ng/mL caused nonlinear
dilutions in a platform HCP ELISA assay.
Recently, degradation of polysorbate
surfactant used in protein formulations
was found to result from the presence of
trace phospholipase levels in mAbs
produced by CHO cells and enzymes from
a human cell line.
21
Host Cell Proteins
Lipase Activity
22. Understanding the Concern
ICH and USP
22
International Council for Harmonization (ICH) of Technical Requirements
• Drug Substance Critical Quality Attributes
For biotechnological/biological products, impurities may be process-related or product-related. Process-
related impurities include: cell substrate-derived impurities (e.g., Host Cell Proteins (HCP) and
Host Cell DNA.
• Residual Host Cell Protein Measurement in Biopharmaceuticals
Targets, alert limits, and reject limits—requires biological products to be “...free of extraneous
material except that which is unavoidable...”
Safety considerations in setting limits—high-dose products may contain a higher mass of residual
HCPs per dose but the potential effect is not necessarily predictable of a clinical outcome. In some
cases, very low levels of certain HCPs have been shown to have clinical effects.
United States Pharmacopeia (USP)
23. Agenda
HCP – Potential impacts on biotherapies
Why traditional HCP identification approaches are not
satisfactory
1
2
3
Progressive techniques for HCP
identification: HCP by MS
24. Current Standard of HCP Measurement - ELISA
24
Sensitivity but lack of specificity
• Polyclonal anti-HCP antibodies recognize a very wide range of possible HCPs
• The first proteomic study of CHO-K1 identified about 6,000 proteins1.
• Typically, a single HCP numerical value is reported for such assay results, representing the ratio of HCPs
(ng) to product (mg). That value can reflect a single protein or a collection of several such impurities.
• Furthermore, if a potentially significant copurifying impurity is nonimmunogenic (or weakly
immunogenic), then the assay could miss it.
• Likewise, if a copurifying impurity is highly immunogenic, the assay could overquantify its value. For
these reasons, orthogonal analytical methods often are used to ensure product purity2.
1. Baycin-Hizal D, et al. Proteomic Analysis of Chinese Hamster Ovary Cells. J. Proteome Res. 11, 2012: 5265–5276.
2. Zhu-Shimoni J, et al. Host Cell Protein Testing By ELISAs and the Use of Orthogonal Methods. Biotechnol. Bioeng. 111(12) 2014: 2367–2379.
25. Current Standard - ELISA
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Regardless of the immunization or purification strategy chosen, both regulators and industry consider
it critical to characterize the resulting anti-HCP reagent’s degree of immunospecificity.
Key characterization elements include:
• Assessing the reagent’s lack of cross-reactivity with the protein product itself
Assessing its ability to detect low-abundance and/or low–molecular-weight HCP species
• Assessing the detection of HCP subpopulations that are enriched in downstream steps
• Demonstrating the percentage of the total host cell proteome that the mAbs can detect.
26. 26
• Clone selection
• Downstream Optimization
- Differential binding and elution
• Scale-up
- It wasn’t there before?
• Tech Transfer
- Minor differences could affect copurification
• Reagent control and bridging
• Dilutional nonlinearity
26
Non-Specific ELISA – What are we Missing?
27. Agenda
HCP Sources and Concerns
Why traditional HCP identification approaches are
not satisfactory
1
2
3
Progressive techniques for HCP
identification: HCP by MS
28. 28
HCP by Mass Spec – Comprehensive ID
The Goal –
100% ID of all HCPs above
a certain threshold
(e.g. 10ppm)
Challenges:
• Complex mixtures (harvested cell-culture)
• Process related impurities (e.g. Protein A)
• Sample prep related impurities (e.g. PNGase F,
skin keratins, etc.)
• PTM variations as well as incomplete cleavages
• Database
• API signal intensity
29. Approach:
• Database – host cell proteome, etc.
• Sample prep
• LC/MS (DDA)
• Data analysis
• Assignments
• Focus on ID rather than absolute quantitation
(semi-quantitative)
• Minimize or eliminate unassigned masses
29
HCP by Mass Spec – Comprehensive ID
30. • 1D LC-MS assay for individual HCP identification, quantification, and monitoring
- Sample preparation – denaturation, reduction and alkylation, digestion
• First analysis step is the HCP discovery assay via data independent MSE acquisition
using 90 minute peptide separations
• Second analysis step samples are analyzed by higher-throughput HCP monitoring
assays using MSE acquisitions with 30 minute peptide separations
• Data acquired in RAW format and processed e.g. with Progenesis QI for proteomics
• In summary – The Discovery Assay populates the database and the Monitoring
Assay references this database for subsequent purification steps
HCP Detection Workflow
30
31. Utility of multiple fractionations for the identification of
low-abundance peptides from a complex mixture
31
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3338939/
32. Determining which HCPs qualify for removal
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HCPs identified across
six PTG1 preparations.
33. Roundtable Discussion – CASSS 2018
33
Quantitation/Detection:
• Some companies are removing the mAb to gain more sensitivity of
HCPs.
• A lot of people are using MRM for quantitation of HCPs and Orbitraps
and/or QTOFs for identification.
• For relative quantitation for HCPs, some people use abundance
obtained during HCP identification analysis and for absolute HCP
quantitation, they use a quantitation through a targeted MRM.
34. HCP by Mass Spec – Quantitation by MS
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Do we need absolute quantitation on all HCPs?
• No – let’s focus on the problematic ones
• Minimal development time
• SLI with MRM for wide dynamic range and low RSD – choose signature peptides
• Typical to see multiple per assay
• Waters Corporation published absolute quantitation for PLBL2 in mAb at ppb level
using Xevo TQ-S Tandem Quadruple MS
35. Identify HCP(s) of interestDependent on various reagents
Assay development (> 6 months)Assay development ($100k+)
What’s Next? HCP – Protein Specific Quantitation by ELISA
1
2
4
3
35
36. Roundtable Discussion – CASSS 2018
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What is the future?
Most agree that we need both (LC-MS/MS and ELISA) because they are very
powerful together. How do we prove the robustness of LC-MS/MS to the FDA if
all industry is using different instruments, samples preparation, and software?
It may be difficult to align HCP analysis by LC-MS/MS because there are so
many different modalities: Gene therapy, monoclonal antibodies, bi-specifics,
vaccines, and fusion proteins. Everybody agrees that there’s a prompt need for
FDA to provide guidance for HCP analysis.
37. 1. Risk mitigation
Scale up
Tech transfer
2. Trend of expectation
Submission trends
USP
Response letters
3. Process Characterization
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HCP by Mass Spec
Why Should we Adopt
38. Cell and Gene Therapy
• Accurate detection and characterization of residual PEI in cell and gene therapy
products
Monoclonal Antibodies
• Effective detection and characterization of residual host cell proteins (HCPs)
Combined Learnings
• Available technology and assays for quantifying process and product impurities
• Current regulatory requirements for detecting, quantifying, and removing
impurities during biotherapy manufacturing
Today’s Take-Aways for Product Characterization
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