This webinar, presented by two world-class experts in polymer based parenteral controlled-release drug delivery technologies, will provide insights into formulation technologies from small molecules up to biologics.
There is an increasing interest in long-acting injectables as drugs administered through injection help to increase patient compliance due to reduced frequency of administration while providing the same therapeutic efficiency. Depending from the nature of the drug, the optimum polymer technology is to be selected.
Prof. Dr. Mäder focus on how to select the appropriate PLA/PLGA polymer for small drug molecule applications. He will provide an overview of drug delivery systems, most important formulation techniques and appropriate characterization methods along with application examples.
Alternative polymer systems are required for peptide and protein controlled-release formulations. Dr. Rob Steendam introduces InnoCore´s SynBioSys® biodegradable polymer system demonstrating excellent safety, control over release kinetics and effective preservation of structural integrity and bioactivity of biologics. InnoCore Pharmaceuticals and SynBioSys® multi-block polymer introduction, challenges in development of controlled-release formulations of biological therapeutics including various examples and development and cGMP manufacturing at InnoCore are key elements of his presentation.
In this webinar, you will learn:
• drug delivery systems
• most important formulation techniques
• appropriate characterization methods along with application examples
Long acting injectable microparticle formulation - a new dimension for peptid...Merck Life Sciences
Explore the clinical benefits and applications of sustained release drug delivery with this presentation. Access the findings from a technical feasibility study as well as a case study on sustained release microparticle formulation for a sensitive peptide.
Addressing Downstream Challenges with Complex InjectablesMerck Life Sciences
The complex injectable market is gaining traction in the injectable therapies, however manufacturing of it is critical. In this webinar, lets brainstorm on the downstream criticalities of these molecules and how to handle the same.
QBD Quality by design for Immediate release dosage formKushal Saha
Traditional approach of formulating a new drug product is an exhaustive task and involves a number of resources like man, money, time and experimental efforts. While, using this Quality by Design (QBD) approach one can get the pharmaceutical product of desired (best) quality with minimizing above resources as well as knowing the influence of one factor over the desired associated process. Hence aim of this study is the understanding of QBD approach to design product and manufacturing process to get desired pharmaceutical product. QBD follows the concepts of ICH guidelines (Q8, Q9 & Q10) which are essential for processing a pharmaceutical process. In this presentation we are going to focus upon QBD for immediate release dosage forms.
Polymer based drug delivery systems for parenteral controlled release: from s...MilliporeSigma
This webinar, presented by two world-class experts in polymer based parenteral controlled-release drug delivery technologies, will provide insights into formulation technologies from small molecules up to biologics.
There is an increasing interest in long-acting injectables as drugs administered through injection help to increase patient compliance due to reduced frequency of administration while providing the same therapeutic efficiency. Depending from the nature of the drug, the optimum polymer technology is to be selected.
Prof. Dr. Mäder focus on how to select the appropriate PLA/PLGA polymer for small drug molecule applications. He will provide an overview of drug delivery systems, most important formulation techniques and appropriate characterization methods along with application examples.
Alternative polymer systems are required for peptide and protein controlled-release formulations. Dr. Rob Steendam introduces InnoCore´s SynBioSys® biodegradable polymer system demonstrating excellent safety, control over release kinetics and effective preservation of structural integrity and bioactivity of biologics. InnoCore Pharmaceuticals and SynBioSys® multi-block polymer introduction, challenges in development of controlled-release formulations of biological therapeutics including various examples and development and cGMP manufacturing at InnoCore are key elements of his presentation.
In this webinar, you will learn:
• drug delivery systems
• most important formulation techniques
• appropriate characterization methods along with application examples
Long acting injectable microparticle formulation - a new dimension for peptid...Merck Life Sciences
Explore the clinical benefits and applications of sustained release drug delivery with this presentation. Access the findings from a technical feasibility study as well as a case study on sustained release microparticle formulation for a sensitive peptide.
Addressing Downstream Challenges with Complex InjectablesMerck Life Sciences
The complex injectable market is gaining traction in the injectable therapies, however manufacturing of it is critical. In this webinar, lets brainstorm on the downstream criticalities of these molecules and how to handle the same.
QBD Quality by design for Immediate release dosage formKushal Saha
Traditional approach of formulating a new drug product is an exhaustive task and involves a number of resources like man, money, time and experimental efforts. While, using this Quality by Design (QBD) approach one can get the pharmaceutical product of desired (best) quality with minimizing above resources as well as knowing the influence of one factor over the desired associated process. Hence aim of this study is the understanding of QBD approach to design product and manufacturing process to get desired pharmaceutical product. QBD follows the concepts of ICH guidelines (Q8, Q9 & Q10) which are essential for processing a pharmaceutical process. In this presentation we are going to focus upon QBD for immediate release dosage forms.
Polymer based drug delivery systems for parenteral controlled release: from s...MilliporeSigma
This webinar, presented by two world-class experts in polymer based parenteral controlled-release drug delivery technologies, will provide insights into formulation technologies from small molecules up to biologics.
There is an increasing interest in long-acting injectables as drugs administered through injection help to increase patient compliance due to reduced frequency of administration while providing the same therapeutic efficiency. Depending from the nature of the drug, the optimum polymer technology is to be selected.
Prof. Dr. Mäder focus on how to select the appropriate PLA/PLGA polymer for small drug molecule applications. He will provide an overview of drug delivery systems, most important formulation techniques and appropriate characterization methods along with application examples.
Alternative polymer systems are required for peptide and protein controlled-release formulations. Dr. Rob Steendam introduces InnoCore´s SynBioSys® biodegradable polymer system demonstrating excellent safety, control over release kinetics and effective preservation of structural integrity and bioactivity of biologics. InnoCore Pharmaceuticals and SynBioSys® multi-block polymer introduction, challenges in development of controlled-release formulations of biological therapeutics including various examples and development and cGMP manufacturing at InnoCore are key elements of his presentation.
In this webinar, you will learn:
• drug delivery systems
• most important formulation techniques
• appropriate characterization methods along with application examples
This PPt Help Students For Improving Their Konwledge about Colon Drug Delivery. In this PPt I Covered All Essential Points About Colon Targeted Drug Delivery System.
Easy & to the point Topics are clearly given in this presentation..
Thanks & Best Regard
(Anurag Pandey) B.Pharm
Contact :- anurag.dmk05@gmail.com (Facebook & Gmail both)
Hot melt extrusion with PVA – solubility enhancement, supersaturation perform...MilliporeSigma
Hot melt extrusion has successfully emerged as an innovative manufacturing technology in pharmaceutical industry for the creation of amorphous solid dispersions (ASDs).
In this webinar you will learn about the potential of hot melt extrusion to overcome challenges in API solubility and bioavailability by using polyvinyl alcohol (PVA) as a matrix polymer. We will provide an overview about different types of solid dispersions and their evolution in the pharmaceutical field. A brief introduction in hot melt extrusion processing will be given as well as actual formulation trends. You will get insights in potential down-stream options to create your final dosage form and you will gain ideas on how to speed up your formulation development.
A detailed background of PVA will be provided including its physical properties as well as its regulatory status. PVA is more than a polymer. Due to its amphiphilic structure it has the potential to improve the supersaturation of low soluble APIs and to prevent precipitation after release. This highlights the versatility of PVA as an advanced polymer for HME applications and we will guide you through our latest research activities so that you can leverage our knowledge to improve your formulations.
This webinar includes:
- The current status and further potential of HME in pharmaceutical industry
- Advantages of PVA in the field of ASDs: Solubility improvement, impact on supersaturation potential, stability data generated on sample formulations & downstream options
- Deep dive into latest research activities: Permeation studies with Caco-2 cell membranes, pH shift studies to investigate supersaturation potential, ongoing research activities to get to know a more detailed understanding of matrix systems and their intermolecular interactions
In this webinar, you will learn:
- which potential hot melt extrusion has, to overcome challenges in API solubility and bioavailability by using polyvinyl alcohol (PVA)
- why PVA is more than just a polymer
- how to create your final dosage form and speed up your formulation development
This PPt Help Students For Improving Their Konwledge about Colon Drug Delivery. In this PPt I Covered All Essential Points About Colon Targeted Drug Delivery System.
Easy & to the point Topics are clearly given in this presentation..
Thanks & Best Regard
(Anurag Pandey) B.Pharm
Contact :- anurag.dmk05@gmail.com (Facebook & Gmail both)
Hot melt extrusion with PVA – solubility enhancement, supersaturation perform...MilliporeSigma
Hot melt extrusion has successfully emerged as an innovative manufacturing technology in pharmaceutical industry for the creation of amorphous solid dispersions (ASDs).
In this webinar you will learn about the potential of hot melt extrusion to overcome challenges in API solubility and bioavailability by using polyvinyl alcohol (PVA) as a matrix polymer. We will provide an overview about different types of solid dispersions and their evolution in the pharmaceutical field. A brief introduction in hot melt extrusion processing will be given as well as actual formulation trends. You will get insights in potential down-stream options to create your final dosage form and you will gain ideas on how to speed up your formulation development.
A detailed background of PVA will be provided including its physical properties as well as its regulatory status. PVA is more than a polymer. Due to its amphiphilic structure it has the potential to improve the supersaturation of low soluble APIs and to prevent precipitation after release. This highlights the versatility of PVA as an advanced polymer for HME applications and we will guide you through our latest research activities so that you can leverage our knowledge to improve your formulations.
This webinar includes:
- The current status and further potential of HME in pharmaceutical industry
- Advantages of PVA in the field of ASDs: Solubility improvement, impact on supersaturation potential, stability data generated on sample formulations & downstream options
- Deep dive into latest research activities: Permeation studies with Caco-2 cell membranes, pH shift studies to investigate supersaturation potential, ongoing research activities to get to know a more detailed understanding of matrix systems and their intermolecular interactions
In this webinar, you will learn:
- which potential hot melt extrusion has, to overcome challenges in API solubility and bioavailability by using polyvinyl alcohol (PVA)
- why PVA is more than just a polymer
- how to create your final dosage form and speed up your formulation development
Hot melt extrusion with PVA – solubility enhancement, supersaturation perform...Merck Life Sciences
Hot melt extrusion has successfully emerged as an innovative manufacturing technology in pharmaceutical industry for the creation of amorphous solid dispersions (ASDs).
In this webinar you will learn about the potential of hot melt extrusion to overcome challenges in API solubility and bioavailability by using polyvinyl alcohol (PVA) as a matrix polymer. We will provide an overview about different types of solid dispersions and their evolution in the pharmaceutical field. A brief introduction in hot melt extrusion processing will be given as well as actual formulation trends. You will get insights in potential down-stream options to create your final dosage form and you will gain ideas on how to speed up your formulation development.
A detailed background of PVA will be provided including its physical properties as well as its regulatory status. PVA is more than a polymer. Due to its amphiphilic structure it has the potential to improve the supersaturation of low soluble APIs and to prevent precipitation after release. This highlights the versatility of PVA as an advanced polymer for HME applications and we will guide you through our latest research activities so that you can leverage our knowledge to improve your formulations.
This webinar includes:
- The current status and further potential of HME in pharmaceutical industry
- Advantages of PVA in the field of ASDs: Solubility improvement, impact on supersaturation potential, stability data generated on sample formulations & downstream options
- Deep dive into latest research activities: Permeation studies with Caco-2 cell membranes, pH shift studies to investigate supersaturation potential, ongoing research activities to get to know a more detailed understanding of matrix systems and their intermolecular interactions
In this webinar, you will learn:
- which potential hot melt extrusion has, to overcome challenges in API solubility and bioavailability by using polyvinyl alcohol (PVA)
- why PVA is more than just a polymer
- how to create your final dosage form and speed up your formulation development
SOLID DISPERSION
Definition: The technology is the science of dispersing one or more active ingredients in an inert matrix in the solid stage.
Need of solid dispersion:
Increases Oral bioavailability of a drug
Increased dissolution rate.
Enhanced release of drugs from ointment.
Improved the solubility & stability.
The concept of solid dispersion was originally proposed by Sekiguchi & obi.
Increasing the dissolution, absorption & therapeutic efficacy of drugs in dosage forms.
Increasing solubility in water.
Improving the oral absorption and bioavailability of BCS Class II drugs.
Utility of new synthetic molecules for the management of plant parasitic nema...AmanSahu590141
Utility of new synthetic molecules for the management of plant parasitic nematodes
✓How noval chemical molecules are better than old nematicides
✓Their function & mode of action
Definition of polymer
Types of Biodegradable polymers
Examples Biodegradable polymers
Application of Biodegradable polymers
Methods of Studying Polymer Degradation
Advantages of Biodegradable polymers
Personalized medicine involves the prescription of specific therapeutics best suited for an individual based on their genetic or proteomic profile. This talk discusses current approaches in drug discovery/development, the role of genetics in drug metabolism, and lawful/ethical issues surrounding the deployment of new health technology.
Similar to Polymer based drug delivery systems for parenteral controlled release: from small molecules to biologics (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
Rapid replication competent adenovirus (rRCA) detection: Accelerate your lot ...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3MJ4u9V
Testing for presence of replication competent adenovirus (RCA) is a key component to ensure patient safety and a requirement for all biologicals manufactured using adenoviral vectors. For many adenoviral-based products, the RCA assay is a rate-limiting assay for lot release.
Join this webinar to learn about a rapid RCA detection assay currently in development, which combines a 7-day culture assay with a highly sensitive molecular endpoint specific for RCA. The method can detect presence of as little as 1 RCA in adenoviral vector material at an approximate concentration of 5x107 - 2x108 vector particles (VP)/mL, making it a suitable method to meet regulatory requirements while accelerating your lot release timelines.
In this webinar, you will learn about:
• Regulatory framework for adenoviral vector products
• Considerations for lot release testing of adenoviral-based therapies
• Advantages of a rapid method for RCA testing on production lot material
Presented by:
Axel Fun, Ph.D.,
Principal Scientist
Alberto Santana, MBA,
Product Manager, Biologics Biosafety Testing
The High Intensity Sweeteners Neotame and Sucralose: 2 Ways to ace the Patien...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3vQyN7K
Bitter medicines are an important issue, especially for pediatric applications. As several APIs have bitter tasting components, high intensity sweeteners for taste optimization are of great interest. Join our webinar to discover our new sweetener toolbox enabling safe and stable formulations.
Mask bitter aftertaste for a sweeter pill to swallow! Patients’ compliance and the therapeutic benefit are supported by a pleasant taste of pharmaceutical formulations. With the high intensity sweeteners Neotame and Sucralose, you have efficient tools at hand which are superior to other sweeteners in many aspects:
• excellent sugar-like taste profile
• outstanding sweetness factors
• use effectiveness
• enhanced stability
We will present our new toolbox of two high performance sweeteners and focus on aspects of stability, safety, the application in various dosage forms, and market perception.
In this webinar, you will learn:
• How to optimize the patients' taste experience of your pharmaceuticals
• How sweeteners can be differentiated by their sensory profiles and features
• How our new product offering Neotame can be effectively used in your targeted formulations
Presented by:
Almut von der Brelie,
Senior Manager Strategic Marketing
Excipients for Solid Applications
The Developability Classification System (DCS): Enabling an Optimized Approac...Merck Life Sciences
This whitepaper by Dr. Daniel Joseph Price outlines how poorly soluble drug formulations can be designed using the developability classification system (DCS).
The DCS identifies the root cause of low solubility and enables lean, cost-effective and effective formulations to be developed.
#solubility #pharmaceuticalmanufacturing #oralsoliddosage #drugdevelopment
In this webinar, you will learn about:
The advantages of using advanced intermediates to develop ADC therapies
How to increase ADC solubility and efficiency
Fast, small-scale ADC library generation
Seamless supply chain with reduced complexity and regulatory support
The ADCore product line offers versatile intermediates that simplify the synthesis of common ADC payloads (dolastatins, maytansinoids, and PBDs) by greatly reducing the number of synthetic steps. This translates to savings in development and manufacturing costs and shorter timelines to the clinic. To address the poor solubility of many ADC payloads, ChetoSensar™ was developed to significantly increase the hydrophilicity of the drug linker, which has been shown to also substantially increase the efficacy of ADCs and broaden the therapeutic window.
Lastly, the ADC Express™ service leverages conjugation chemistry and analytical expertise to help design and quickly synthesize sets of potential ADC therapies suitable for screening to simplify candidate selection and get ADC therapies to market faster.
R3 Stem Cells and Kidney Repair A New Horizon in Nephrology.pptxR3 Stem Cell
R3 Stem Cells and Kidney Repair: A New Horizon in Nephrology" explores groundbreaking advancements in the use of R3 stem cells for kidney disease treatment. This insightful piece delves into the potential of these cells to regenerate damaged kidney tissue, offering new hope for patients and reshaping the future of nephrology.
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.
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
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
CRISPR-Cas9, a revolutionary gene-editing tool, holds immense potential to reshape medicine, agriculture, and our understanding of life. But like any powerful tool, it comes with ethical considerations.
Unveiling CRISPR: This naturally occurring bacterial defense system (crRNA & Cas9 protein) fights viruses. Scientists repurposed it for precise gene editing (correction, deletion, insertion) by targeting specific DNA sequences.
The Promise: CRISPR offers exciting possibilities:
Gene Therapy: Correcting genetic diseases like cystic fibrosis.
Agriculture: Engineering crops resistant to pests and harsh environments.
Research: Studying gene function to unlock new knowledge.
The Peril: Ethical concerns demand attention:
Off-target Effects: Unintended DNA edits can have unforeseen consequences.
Eugenics: Misusing CRISPR for designer babies raises social and ethical questions.
Equity: High costs could limit access to this potentially life-saving technology.
The Path Forward: Responsible development is crucial:
International Collaboration: Clear guidelines are needed for research and human trials.
Public Education: Open discussions ensure informed decisions about CRISPR.
Prioritize Safety and Ethics: Safety and ethical principles must be paramount.
CRISPR offers a powerful tool for a better future, but responsible development and addressing ethical concerns are essential. By prioritizing safety, fostering open dialogue, and ensuring equitable access, we can harness CRISPR's power for the benefit of all. (2998 characters)
Navigating the Health Insurance Market_ Understanding Trends and Options.pdfEnterprise Wired
From navigating policy options to staying informed about industry trends, this comprehensive guide explores everything you need to know about the health insurance market.
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.
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.
One of the most developed cities of India, the city of Chennai is the capital of Tamilnadu and many people from different parts of India come here to earn their bread and butter. Being a metropolitan, the city is filled with towering building and beaches but the sad part as with almost every Indian city
Nursing Care of Client With Acute And Chronic Renal Failure.ppt
Polymer based drug delivery systems for parenteral controlled release: from small molecules to biologics
1. Merck KGaA
Darmstadt, Germany
Polymer based drug delivery systems for parenteral
controlled release: from small molecules to biologics
25th October 2018
Webinar
2. The life science business of
Merck KGaA, Darmstadt, Germany
operates as MilliporeSigma
in the U.S. and Canada.
2
3. 3
Prof. Dr. Karsten Mäder
Part I: General considerations
and DDS for small molecules
Dr. Rob Steendam
Part II: SynBiosys®
- Biodegradable
Polymer Platform for Long-Acting
Injectable Biologics
Polymer based drug delivery systems for parenteral controlled
release: from small molecules to biologics
6. 1. … low uptake and high variability of PK after oral administration
2. … rapid excretion and fast metabolism
3. … low concentrations in the desired location
4. … high toxicity
Many drugs show…
SyringeImagefrom
DatabaseCenterforLife
ScienceDBCLS).
PLA / PLGA polymers play a key role
Medical need for injectable DDS with sustained release
6
7. The concept of sustained release with PLA / PLGA
Drug
Polymer
Other excipients
Process
CR-DDS
Slow and constant release
days
Constant drug level
Toxic effects
No effect
7
8. 1. Tunable drug release from days to several months
Less injections, no infusion
2. High drug concentration at the desired location
Better cure
3. Decreased overall dose
Less side effects
Possible benefits of injectables with controlled release
8
9. Systemic effects
Breast cancer
Prostate cancer
Schizophrenia
Diabetis
Growth deficiency
…
Local effects
Inner eye
Brain
Joints
Ear
Bone marrow
…
Application examples
Location specific considerations Mainly intramuscular or
subcutaneous administration
9
11. Slower polymer degradation with
1. Molecular weight
2. Ratio lactic / glycolic acid
3. L-lactic acid vs. D,L-lactic acid
4. Polymers with esterified end groups
EXPANSORB®
DLG 50-6A (Acid) DLG 50-6E (Ester)
Polymer selection: PLA/PLGA
L-lactic acid
D-lactic acid
Glycolic acid
COOH
11
12. Drug molecules are different in many aspects
large
medium
poorly water soluble
Risperidone
Dexamethasone
Leuprolide
small
water soluble
5-FUNa-Pamidronate
12
Sensitive
13. Different polymer based DDS
Preformed Implants In-situ forming implants Microparticles
Micro- and Nanocapsules
E.Lehner&K.Mäder
C.Janich&K.Mäder
Micro- and nanofibersNanoparticles
13
J.Zech&K.Mäder
14. 1. Dissolving in
a. Organic solvents (polymers, drugs)
b. Aqueous solvents (drugs)
1. Extrusion
2. Mixing / Shearing
3. Spray Drying
4. …
Commonly used processes to make DDS
Processing
Drug Delivery
System
Excipients
(polymers, surfactants, …)
Drug
High shear forces
High temperatures
Hydrolysis
Toxic solvents (CH2Cl2)
14
DANGER
15. Preformed Implants
Monolithic
Made by extrusion
In situ forming implants
Formed in vivo
Different principles
(e.g. solvent or
temperature induced)
Microparticles
Multiparticulate
Made by dissolution – dispersion
techniques
Selection of DDS: Implants vs. microparticles
15
Tunable size and release
profile, smaller needles
for injection
Use of organic solvents,
Often burst release,
Danger of particle
aggregation (T>Tg)
Easy
formulation
process
Difficult control of
implant shape,
sometimes injection
of organic solvents
No organic solvents,
better storage stability,
less burst release
Extrusion stress:
(temperature, shear)
Larger needle for injection
16. PLGA Microparticles for hydrophobic drugs
Hydrophic drug
PLGA
CH2Cl2
PLGA + Drug
SOLUTION in CH2Cl2
I
II IIa
Spray drying
IIb
Emulsification / solvent
evaporation
o/w-emulsion
(liquid droplets)
CH2Cl2 removal
s/w-suspension
(solid particles)
Addition of
organic liquid:
1.solvent for
CH2Cl2
2.antisolvent
for PLGA
IIc
Coacervation
16
17. PLGA Microparticles for hydrophilic drugs
PLGA CH2Cl2
H2O
PLGA solution
in CH2Cl2
Drug solution
in H2O
W1/O-emulsion
PLGA in o-phase
Drug in w1-phase
CH2Cl2 removal
Suspension
(solid particles)
17
I
II IIa
Spray drying
w1/o/w2-
emulsion
(liquid droplets)
IIb
Emulsification / solvent
evaporation
Addition of
organic liquid:
1.solvent for
CH2Cl2
2.antisolvent
for PLGA
IIc
Coacervation
Hydrophic
drug
19. Most Important Release Mechanisms
Fredenberg et al.: Int J Pharm. 2011, 415(1-2):34-52
Diffusion
through pores
Diffusion through
the polymer
Osmotic pumping Erosion
19
20. Diffusion
According to Einstein & Smoluchowski:
x2
average = 2 D t
Microparticles / Nanoparticles:
Ratio Diffusion Distance: 1 000 : 1
Ratio Diffusion Time: 1 000 000 : 1
20
21. Polymer Drug D [cm2
/s] Source
PLGA
(Tg > 37°C)
(brittle)
5-FU
8.5*10-12 N. Faisant et al. Int. J.
Pharm. 314 (2006)
189–197
5-FU
5*10-11
to 1*10-13
Siepmann et al. J. Contr.
Rel. 96, 123-134 (2004)
Ibuprofen,
Lidocain
10-11
to 1*10-13
Klose et al. / Int. J.
Pharm. 354 (2008)
95–103
PCL
(Tg < 37°C; rubbary)
Testosterone
estradiol-17β
8.31*10-8
0.728*10-8
Zhang et al, J. Contr.
Rel. 29, (1994),
157-161
Diffusion coefficients in biodegradable polymers
21
22. Average Diffusion lengths: Nano- vs. microparticles
22
D = 2*10-9
cm2
/s D = 2*10-12
cm2
/s
1 s 632 nm 20 nm
10 s 2 µm 63.2 nm
100 s 6.32 µm 200 nm
1000 s (16.7 min) 20 µm
632 nm
10000 s (2.78 h) 63.2 µm 2 µm
100000 s (27.8 h) 200 µm 6.32 µm
1000000 s (11.6 d) 632 µm 20 µm
22
23. Drug Release Might be Quite Complex
Fredenberg et al.:Int J Pharm. 2011, 415(1-2):34-52
23
CAN WE GET CONTROL?
Drug
Carrier
Biological
Environment
24. 1. Autocatalytic degradation with possible very low pH-values (pH2)
2. Larger microparticles degrade faster than smaller
3. Stirring might lead to slower release and degradation
PLGA challenges and surprises
Li, S.M., Garreau, H. & Vert, M. J Mater Sci: Mater Med
(1990) 1: 131.
24
26. Importance of size (II)
Hydrophilic drug
PLGA microparticles
Smaller
PLGA particles
Larger drug
particles
26
27. DDS Size and shape
PLGA mass and molar mass
Monomer content
Glass transition temperature Tg
Content of water and organic solvents
Drug content and physical state, degradation products
Analytical control of…DrugPLGA
27
28. Control from production to patient
Production Shipping Storage Administration
Avoid:
High temperatures
Humidity
Light
Mechanical damage
28
29. Drug Release might be quite complex:
Fredenberg et al.:Int J Pharm. 2011, 415(1-2):34-5229
32. Take home message: PLGA and small molecules
Drug release results
Drug release results from interplay between drug, polymer and environment.
Release optimisation
Release optimisation requires appropriate analytical measurements
of important parameters.
Drug release from PLA / PLGA
Drug release from PLA / PLGA might be complex, but not unpredictable!
1
2
3
32
34. Marketed PLGA-based parenteral sustained release products
PLA / PLGA are the
standard polymer
platform of choice
for long-acting
injectables
GelsImplantsmicroparticles
…. but only for
small molecules
and peptides
There are no marketed PLGA/PLA polymer-based sustained release drug
delivery products of biologicals.34
Image(s) by courtesy of InnoCore Pharmaceuticals
35. Increasing market share protein therapeutics
There is a need for sustained release drug delivery systems
for development of Long-Acting Injectable Biologics
# https://sciex.com/community/blogs/blogs/the-future-of-biologics-
drug-development-is-today
The number of protein-based therapeutics is rapidly increasing
US$ 140 billion (2016) to grow to US$ 218 billion by 2023 (CAGR 6.5%)
(alliedmarketresearch.com)
35
Image(s) by courtesy of InnoCore Pharmaceuticals
36. Large Peptides and Proteins
Proteins are intrinsically fragile molecules
Complex 3-dimensional molecules
Hydrophilic, charged and relatively large size
Short half-life (t½)
Oral incompatibility
Poor stability
Threats for proteins
High temperatures
Organic solvents
Hydrophobic surfaces
High shear
Enzymes
pH changes
Protein degradation
Unfolding
Aggregation
Fragmentation
Chemical modification
Loss of biological activity
Reduced therapeutic efficacy
Undesired immune response
Reduced shelf life
Challenges in Formulation of Biologicals
36
Image(s) by courtesy of InnoCore Pharmaceuticals
37. PLGAs are not suitable for sustained release of biologicals
Adsorption
Proteins adsorb to hydrophobic surface of PLGA
Irregular biphasic release kinetics
Degradation controlled release due to rigid polymer
matrix which does not allow protein diffusion
In situ pH drop
Formation of acidic microenvironment due to
accumulation of acidic degradation products ( pH 2)↓
Acylation
Nucleophilic primary amines can interact with
the carboxylic acid end-groups of PLGA or PLGA
degradation products
Sustained release of large peptides and proteins
Peptide acylation in PLGA-
based Sandostatin LAR
Irregular release of Bovine
Serum Albumin from PLGA
Classical PLGA/PLA formulations not suitable for sustained release of
biologicals due to their rigidity and acidic microenvironment formation
Ghassemi et al, Pharm Res (2012) 29:110–120
37
39. SynBiosys®
Hydrophilic Polymer Platform Designed for Delivery of Biologicals
OH
OH
HO
HO
Well-known, clinically-proven safe monomers and chemistry to create
customized multi-block copolymers for delivery of any biological
Monomers
Lactide ε-caprolactone
Prepolymers
(chain-extender)
1,4-butanediisocyanate
Multi-block copolymer
with unique molecular
architecture
Polyethylene glycol 1,4-butanediol
(initiators)
39
40. Hydrophilic Amorphous Domains
Absorbs water and swells to form
a hydrogel-like structure
− Diffusion-controlled release
Hydrophobic Crystalline Domains
Physical X-links: provide structural integrity
− Control the degree of swelling
Polymer Matrix Erosion and Degradation
Degrades through hydrolysis
No accumulation of acidic degradation products
No acidic microenvironment / in situ pH drop
Multi-block co-polymers with
phase-separated morphology
Hydrophilic amorphous domains
Hydrophobic crystalline domains
SynBiosys®
Designed for Delivery of Large Peptides and Proteins
Unlike traditional sustained release polymers, SynBiosys® provides a
suitable micro-environment to maintain protein integrity and activity40
Image(s) by courtesy of InnoCore Pharmaceuticals
41. Tools to control drug release
Polymer
− swelling degree
− degradation rate
Microencapsulation process
Variables for Fine-Tuning
PEG molecular weight
PEG content
Co-monomer type
Co-monomer weight fraction
Block ratio
Molecular weight
SynBiosys®
Control of protein release kinetics by modifying polymer composition
Block ratio
Effect of block ratio of LP10L20-LL40 polymer on BSA release
41
Polymer Grade Block ratio PEG content
Swelling
degree
10LP10L20-LL40 10/90 5 wt.% 1.02
20LP10L20-LL40 20/80 10 wt.% 1.07
30LP10L20-LL40 30/70 15 wt.% 1.15
50LP10L20-LL40 50/50 25 wt.% 1.30
Image(s) by courtesy of InnoCore Pharmaceuticals
42. SynBiosys®
Biocompatible polymer platform and safe degradation products
Extensive ISO-10993 biocompatibility / toxicity data package (summary is available)
In vivo biocompatibility & degradation (implants, microspheres, coatings)
Various routes of administration: subcutaneous, intramuscular, intra-articular, intravitreal, intracardiac
Multiple species: rats, rabbits, mini-pigs, pigs, horses, primates
Proven clinical safety – Combo®
sirolimus eluting dual therapy stent:
approved and marketed since 2013 by OrbusNeich
COMBO® is a registered trademark of OrbusNeich42
Monomer Degr. product Excreted as Route
Lactic acid Pyruvic acid CO2 + H2O Urine, breathe
Glycolic acid Pyruvic acid CO2 + H2O Urine, breathe
ε-Caprolactone ω-hydroxy heaxanoic acid ω-hydroxy heaxanoic acid Urine
PEG PEG PEG Urine
1,4-Butanediisocyanate 1,4-Butanediamine (putrescine) 1,4-Butanediamine Urine, breathe
1,4-Butanediol 1,4-Butanediol 1,4-Butanediol Urine
43. SynBiosys®
Versatile portfolio of proprietary Drug Delivery Systems
Microparticles Solid Implants DE Coatings Injectable Gels
SynBiosys biodegradable polymers are suitable for various long-acting
(injectable) sustained release drug delivery systems
43
Image(s) by courtesy of InnoCore Pharmaceuticals
44. SynBiosys®
Microparticles
Proprietary process to manufacture uniformly-sized microparticles
Membrane emulsification
44
Narrow Particle Size Distribution
PARTICLE DIAMETER µM
Image(s) by courtesy of InnoCore Pharmaceuticals
45. SynBiosys®
Microparticles
Unsurpassed injectability due to uniformly-sized microparticles
Drug type Maximum drug dose (mg)a
mg/mL SC (2 mL) IM (4 mL)
Small molecules ≤ 150 ≤ 300 ≤ 600
Peptide ≤ 75 ≤ 150 ≤ 300
Protein/antibody ≤ 60 ≤ 120 ≤ 240
Smaller needles (less painful injection)
Reduced immunogenicity due to absence of
undersized (< 10 µm) particles
High API doses due to highly concentrated
microsphere suspensions (more API)
45 Image(s) by courtesy of InnoCore Pharmaceuticals
47. SynBiosys®
Sustained Release Microparticles of Peptides
Time (Days)
CumulativeReleaseCumulativeRelease
Peptide A
Peptide B
47
Peptide A Peptide B
MW 2.5 kDa 4.5 kDa
Indication Undisclosed Undisclosed
RoA Local injection SubQ injection
Microencapsulation process W/O/W +
lyo (aseptic)
W/O/W +
lyo (aseptic)
Size (d50) ∼ 30 - 70 µm ∼ 30 µm
Drug loading 10-15% 10%
Injection volume 50 µL 0.7 mL
MSP suspension concentration > 20% > 20%
Needle gauge 27 G 27 G
Release duration 5-6 months 2-4 weeks
(Formulati-on)
Image(s) by courtesy of InnoCore Pharmaceuticals
48. Insulin-like growth factor-1 (IGF-1)
MW 7,655 Da
5 wt.% IGF (500 µg/10mg MSP)
SynBiosys®
Sustained Release Microparticles of Proteins
Hepatocyte growth factor (HGF)
MW 69,000 Da
2 wt.% HGF (200 µg HGF/10mg MSP)
Release controlled by block ratio of SynBiosys®
multi-block copolymer
CumulativeRelease
Time (Days)
CumulativeRelease
Time (Days)
48
49. Bioactivity of IGF-1 is preserved
IGF-1 signal transduction pathway
Activity of released IGF-1 assayed in vitro
A431 was used as reporter cell line
Signal transduction pathway activation was
analyzed 10 min after IGF-1 addition
Structural integrity of IGF-1 is preserved
SDS-PAGE
IGF-1 released after different time points was
structurally fully intact
no formation of fragments or aggregated IGF-1
SynBiosys®
Microparticles
Protein Integrity and Bioactivity
1 2 3 4 5 6 7 8 9 10
IGF-1
CBB-stain
37
25
20
15
10
5
KDa Marker 1 2 3 4 5 6 7 8 9 10
IGF-1
CBB-stain
37
25
20
15
10
5
KDa Marker
37
25
20
15
10
5
KDa Marker
-- pAKT
-- pIGF-1 R
0 0.78 1.563.126.25 12.5 ng/ml
-- β-actin
Protein maintains structure and activity after microencapsulation
and subsequent release from SynBiosys®
microparticles49
Image(s) by courtesy of InnoCore Pharmaceuticals
50. SynBiosys®
Microparticles
Examples of SynBiosys®
-based Long Acting Injectable Biologics
50
Therapy / indication Drug molecule Formulation type
Route of
Administration
Ocular disease Protein Microparticle Intravitreal
Sexual dysfunction Protein Microparticle SubQ
Ischemic heart disease IGF-1 / HGF Microparticle Intra-arterial
Diabetes GLP-1 analogue Microparticle SubQ
Cancer Antibody Microparticle SubQ / IM
Prostate cancer Goserelin Solid implant SubQ
Cancer Peptide Microparticle SubQ / IM
Osteoarthritis Protein Microparticle Intra-articular
52. Sustained release solutions from Small Molecules to Large Proteins
Small MoleculesSmall Molecules PeptidesPeptides ProteinsProteins
< 1 kDa< 1 kDa 1 – 10 kDa1 – 10 kDa > 10 kDa> 10 kDa
A versatile portfolio of polymers and DDS to formulate
any API into a fit for purpose Drug Product
52
EXPANSORB® is a registered trademark
of Groupe PCAS, Longjumeau, France
SynBiosys® is a registered trademark of Innocore
Pharmaceuticals, Groningen, Netherlands
53. Collaboration and Development Services
Preclinical development and cGMP manufacturing
53
API
&
TPP
R&D
Feasibility study
GLP
Optimization &
Scale-up
Clinical
Trials
Commercial
Manufacturing
& Sales
Merck KGaA / InnoCore CooperationPARTNER
Polymer Supply
Drug
Delivery
System
Optimization
Process scale-up
Analytical
validation
Production of
GLP tox material
GMP
Production CTM
Tech Transfer
cGMP production
clinical supplies
QC testing
Batch release
Stability studies
Analytical
development
Polymer
Formulation
development
ATM prodution
POC in vivo
PK/PD studies
GLP tox
studies
Phase I/II
clinical studies
Manufacturing
Partner/CMO
Mark. & Sales
PARTNER
PARTNER
55. Unique biodegradable polymer platform for long-acting injectable biologics
Sustained release of biologicals for up to 6 months
Preservation of integrity and bioactivity
Excellent injectability (small needles) and high API doses due to uniformly sized microparticles
Safe and clinically validated platform
Development services from PoC up to cGMP manufacturing of clinical supplies
Proven track record in effectively working with partners to formulate their biological
therapeutics into unique and commercially viable drug delivery products
Partnering and business opportunities
Chronic and site-specific diseases
Small molecules – peptides - recombinant proteins, etc
New therapies, new RoA, repurposing of existing API, supergenerics
Effective patent protection > 2038
SynBiosys®
Key features SynBiosys®
Microparticle Technology Proposition
55
57. Take Home Message
Parenteral Controlled Release of Small Molecules and Biologics
57
controlled drug release results from the interplay between drug, polymer and environment.
release optimization requires appropriate analytical measurements of important parameters.
the Synbiosys technology is a unique multiblock copolymer platform for sustained release of biologics.
PLA/ PLGA polymers and Synbiosys technology together deliver the tools to formulate any API into a fit for purpose
drug product.
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With this webinar we demonstarted that:
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PEG, caprolactone, lactide, glycolide, 1,4-butanediisocyanate, 1,4-butanediol
Based on API characteristics (Molecular size, solubility, etc.) and Target product profile (TPP), especially release duration, prepolymers (‘blocks’) are selected (from stock) and chain-extended / linked together in the desired block ratio as to obtain a multi-block copolymer with the required physico-chemical characteristics (hydrophilicity, swelling degree, degradation rate) as to allow the development of sustained release formulations with the intended release kinetics (duration of release, release rate, release profile).