This document discusses protein aggregation in biopharmaceutical development and analytical methods used to characterize aggregates. It provides an overview of how protein aggregation occurs and factors influencing aggregate formation. Methods to monitor and control aggregates during development are described, highlighting the importance of integrating formulation, manufacturing processes, and analytics. A case study is presented on using subvisible particulate analysis during process development of an IgG monoclonal antibody, where flow microscopy and dynamic light scattering detected higher particle levels when the viral filtration load was handled turbulently, linking handling conditions to membrane fouling and the need for gentler methods. The summary emphasizes the role of protein aggregation challenges in biologics development and technical solutions explored.
Significant advances in analytical technology over the past few years have improved the quantification and characterization capabilities for subvisible ( 1 - 100 μm) and submicron particles (≤1 μm). As the technology continues to improve so do the expectations of regulatory agencies for sponsors to characterize particles in these size ranges. However, multiple orthogonal methods are required to span the entire range and accurately characterize the particle profile. Each instrument has its own limitations based on detection method and properties of therapeutic protein products that must be well understood to generate high-quality data. Written by Amber Fradkin, Ph.D. Associate Director, R&D, KBI Biopharma
EU GMP Annex 1 Draft: Implications on Sterilizing Grade Filter ValidationMilliporeSigma
Watch the presentation of this webinar here: https://bit.ly/3kk0Qs1
In this webinar, you will learn:
- About the GMP Annex 1 draft regulatory overview
- How to incorporate the integrity testing & PUPSIT in the filtration systems validation
- How to design a bacterial retention test in terms of organism selection and single vs multiple use validation
Detailed description:
In this webinar we will discuss the implications of the EU GMP Annex 1 draft on the filtration of medicinal products and how this impacts the validation studies.
Bacterial Retention Testing is a critical part of the manufacturing validation process and is required by all regulatory bodies worldwide. Using case studies, our experts will explain how the Annex 1 draft is incorporated into the filtration systems validation exercise, specifically for integrity testing & PUPSIT (Pre-Use Post Sterilization Integrity Testing), the selection and justification of the appropriate test organism, and validation implications of single versus multiple use.
This document discusses the statutory requirements and considerations for approving generic transdermal drug products using a similarity (Q3) approach. It notes that generic transdermal patches must demonstrate similarity to the reference product in chemistry, manufacturing, formulation characteristics, and in-vitro drug release and permeation profiles using validated testing methods. A key consideration is that the generic product must not have a greater potential for skin reactions and its adhesion properties must not be inferior to the reference product. The document concludes that a similarity approach is possible if the generic product matches the reference product in dosage form, strength, ingredients, physical and chemical properties, and shows similar drug release through in-vitro testing.
The document discusses bioanalytical sample preparation. It begins with an introduction to sample preparation as an essential step in the bioanalytical process. Sample preparation techniques discussed include protein precipitation, liquid-liquid extraction, and solid phase extraction. Protein precipitation involves denaturing proteins to isolate analytes. Liquid-liquid extraction uses differential solubility to separate analytes between immiscible liquid phases. Solid phase extraction selectively retains analytes on a solid sorbent under specific conditions. The document provides details on each technique's principles, steps involved, advantages, and disadvantages.
Almac provides chemistry and manufacturing solutions for APIs from discovery through commercialization. They offer multi-purpose GMP manufacturing facilities, process R&D, preclinical through commercial API supply, analytical development and validation, potent API production, biotransformation, micronization, and process validation using quality by design approaches. Almac has expertise in chemical development, biocatalysis, physical sciences, formulation development, and analytical services to support clients' API needs.
Quality for Biologics ' New ReportCritical quality attributes, process and change control, product variation, characterisation, and regulatory concernsSales of biologics grew by 20% in 2007, far faster than sales of small molecule drugs, which grew by not much more than 5%. The number of biologics being launched is also growing very rapidly, accounting for more than 25% of launches in 2007. But biologics are not like small molecules ' they are more complex to develop, test and produce. Any change in production may have a direct effect on both safety and efficacy. Making sure that development, testing and production is done correctly can be expensive, but getting it wrong can be even more expensive and may be disastrous for patients and for the companies involved.This unique 300 page report can help you to understand the processes involved ' knowledge that can save time and money and even make the difference between success and failure. The report covers all aspects of the subject including' Critical quality attributes ' Manufacturing process parameters' Process analytical technology' Physicochemical analysis,' Bioassays, ' Formulation and specifications' Product- and process-related impurities' Aggregation ' Non-clinical testing' Clinical development, ' Post-marketing period' Regulatory authority expectations' Risk management ' Comparability concernsQuality for Biologics is edited by Dr Nicole Lyscom and is written by senior industry experts from leading companies and organisations including:UCBUCB-CelltechEli LillyAmgenRocheParexel ConsultingGenentech
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.
In our final webinar of the MDC Connects Series 2021 | A Guide to Complex Medicines.
This slide deck takes a closer look at the advantages of good formulation.
Claire Patterson, Seda Pharmaceutical Development Services
Significant advances in analytical technology over the past few years have improved the quantification and characterization capabilities for subvisible ( 1 - 100 μm) and submicron particles (≤1 μm). As the technology continues to improve so do the expectations of regulatory agencies for sponsors to characterize particles in these size ranges. However, multiple orthogonal methods are required to span the entire range and accurately characterize the particle profile. Each instrument has its own limitations based on detection method and properties of therapeutic protein products that must be well understood to generate high-quality data. Written by Amber Fradkin, Ph.D. Associate Director, R&D, KBI Biopharma
EU GMP Annex 1 Draft: Implications on Sterilizing Grade Filter ValidationMilliporeSigma
Watch the presentation of this webinar here: https://bit.ly/3kk0Qs1
In this webinar, you will learn:
- About the GMP Annex 1 draft regulatory overview
- How to incorporate the integrity testing & PUPSIT in the filtration systems validation
- How to design a bacterial retention test in terms of organism selection and single vs multiple use validation
Detailed description:
In this webinar we will discuss the implications of the EU GMP Annex 1 draft on the filtration of medicinal products and how this impacts the validation studies.
Bacterial Retention Testing is a critical part of the manufacturing validation process and is required by all regulatory bodies worldwide. Using case studies, our experts will explain how the Annex 1 draft is incorporated into the filtration systems validation exercise, specifically for integrity testing & PUPSIT (Pre-Use Post Sterilization Integrity Testing), the selection and justification of the appropriate test organism, and validation implications of single versus multiple use.
This document discusses the statutory requirements and considerations for approving generic transdermal drug products using a similarity (Q3) approach. It notes that generic transdermal patches must demonstrate similarity to the reference product in chemistry, manufacturing, formulation characteristics, and in-vitro drug release and permeation profiles using validated testing methods. A key consideration is that the generic product must not have a greater potential for skin reactions and its adhesion properties must not be inferior to the reference product. The document concludes that a similarity approach is possible if the generic product matches the reference product in dosage form, strength, ingredients, physical and chemical properties, and shows similar drug release through in-vitro testing.
The document discusses bioanalytical sample preparation. It begins with an introduction to sample preparation as an essential step in the bioanalytical process. Sample preparation techniques discussed include protein precipitation, liquid-liquid extraction, and solid phase extraction. Protein precipitation involves denaturing proteins to isolate analytes. Liquid-liquid extraction uses differential solubility to separate analytes between immiscible liquid phases. Solid phase extraction selectively retains analytes on a solid sorbent under specific conditions. The document provides details on each technique's principles, steps involved, advantages, and disadvantages.
Almac provides chemistry and manufacturing solutions for APIs from discovery through commercialization. They offer multi-purpose GMP manufacturing facilities, process R&D, preclinical through commercial API supply, analytical development and validation, potent API production, biotransformation, micronization, and process validation using quality by design approaches. Almac has expertise in chemical development, biocatalysis, physical sciences, formulation development, and analytical services to support clients' API needs.
Quality for Biologics ' New ReportCritical quality attributes, process and change control, product variation, characterisation, and regulatory concernsSales of biologics grew by 20% in 2007, far faster than sales of small molecule drugs, which grew by not much more than 5%. The number of biologics being launched is also growing very rapidly, accounting for more than 25% of launches in 2007. But biologics are not like small molecules ' they are more complex to develop, test and produce. Any change in production may have a direct effect on both safety and efficacy. Making sure that development, testing and production is done correctly can be expensive, but getting it wrong can be even more expensive and may be disastrous for patients and for the companies involved.This unique 300 page report can help you to understand the processes involved ' knowledge that can save time and money and even make the difference between success and failure. The report covers all aspects of the subject including' Critical quality attributes ' Manufacturing process parameters' Process analytical technology' Physicochemical analysis,' Bioassays, ' Formulation and specifications' Product- and process-related impurities' Aggregation ' Non-clinical testing' Clinical development, ' Post-marketing period' Regulatory authority expectations' Risk management ' Comparability concernsQuality for Biologics is edited by Dr Nicole Lyscom and is written by senior industry experts from leading companies and organisations including:UCBUCB-CelltechEli LillyAmgenRocheParexel ConsultingGenentech
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.
In our final webinar of the MDC Connects Series 2021 | A Guide to Complex Medicines.
This slide deck takes a closer look at the advantages of good formulation.
Claire Patterson, Seda Pharmaceutical Development Services
Excipients selection for high risk formulations Smita RajputMerck Life Sciences
Are you choosing the right excipients for your high risk application? Find out how to select the right excipients and enable your process optimization to improve the total cost of ownership.
In this webinar, you will learn:
• Selection of right excipients for high risk formulation is very critical step
• Low Endotoxin and low bioburden limits are important aspect while selecting raw materials
• Strong regulatory support is crucial for high risk formulation
Excipients selection for high risk formulations like parenteral and ophthalmic applications is very challenging. Excipients should be inert with high purity for such dosage forms because trace amounts of impurities present in excipients can interact with active pharmaceutical ingredient (API) which results in instability of the formulation. This presentation discusses how to select the right excipients for high-risk applications and gives guidance for process optimization by choosing the best combination of filters and excipients to improve the total cost of ownership.
Polymer based drug delivery systems for parenteral controlled release: from s...Merck Life Sciences
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
The document summarizes the development process for a biologic product from cell line generation to characterization. It involves:
1) Developing a stable CHO cell line expressing the target protein through cloning and selection.
2) Establishing master and working cell banks for upstream production.
3) Developing purification and viral clearance downstream processes.
4) Formulating the drug substance and filling it into vials as the drug product.
5) Characterizing the protein structure, activity, immunological properties, purity and stability according to ICH guidelines.
ISO 10993 Biological Evaluation of Medical Devices UpdateNAMSA
The ISO 10993 Biological Evaluation of Medical Devices Update covers the revisions/updates that were discussed at the TC194 meeting in Mishima, Japan in April of 2014.
Ich guidelines for stability testing of biotechnological biological products (1)Dr Raj kumar Kudari
This document provides guidelines for stability testing of biotechnological and biological products. It discusses selecting representative batches of drug substance and drug product for testing, establishing a stability-indicating profile including potency, purity, and other characteristics, and testing under various storage conditions like temperature, humidity, and accelerated/stress conditions. The guidelines aim to ensure biologics maintain biological activity and avoid degradation during their intended storage period.
A seminar on applications of various analytical techniquePatel Parth
This document provides information on preformulation studies for new drug development. It discusses:
1. The purpose of preformulation studies is to understand the characteristics of drug components and optimize dosage form manufacturing.
2. Preformulation studies establish the identity, properties, and compatibility of new drug substances to support formulation development and regulatory filings.
3. A variety of analytical techniques are used in preformulation studies including spectroscopy, chromatography, and thermal analysis to characterize drug substances and excipients.
Sterile filtration of complex injectables by Partha BanerjeeMerck Life Sciences
Sterile filtration and filter validation remain a critical segment during the development of these segments of products. Let's find the same by understanding a checklist and visualize certain case studies.
As the sterile injectable market continues to see rapid growth (~10% to 15% per annum) – outpacing the growth of oral products – it is natural to see the diversity of parenteral product formulations increasing in parallel. The definition of complexity in parenteral formulation development is broad. It varies based on the stage of development and the specific nature of the challenge. A notionally simple, stable reproducible laboratory formulation may carry a level of complexity in aseptic control if routine means of sterilization are unavailable.
Sterile filtration process intensification can bring significant benefits to manufacturers in terms of manufacturing flexibility, reduction of risks, better turn around time, thus achieving significantly higher productivity. We will identify these scenarios with case studies to reduce complications in manufacturing and process development.
Sterile filtration of complex injectables by Partha BanerjeeMerck Life Sciences
The document discusses considerations for sterile filtration of complex injectables such as liposomes, emulsions, and viscous formulations. It notes that sterile filtration is widely used for liposome sterilization but poses challenges due to the small size of liposomes and bacteria. Key parameters for liposomes include particle size distribution, zeta potential, and stability. The talk addresses regulatory guidelines for liposome characterization and manufacturing. It also outlines best practices for sterile filtration of oils, emulsions and viscous drugs to optimize the filtration process.
Edward Narke discussed the CMC pathway for biologics through clinical development and market approval. The goals are to better understand FDA requirements, visualize a cost-effective approach to manage manufacturing processes, and appreciate challenges in controlling safety, potency, and impurities. Biologics have complex structures that must be characterized and controlled. Assay methods, product specifications, stability data, and comparability between clinical and commercial materials are common reasons INDs are placed on clinical hold. Managing impurities, developing relevant potency assays, and collecting data continuously are important strategies to address these challenges over the course of development.
In this webinar, you will learn:
Sources of endotoxin contamination
Contamination control strategy
Endotoxin removal strategies
Detailed description:
Endotoxin, a lipopolysaccharide (LPS), is a type of pyrogen and is a component of the exterior cell wall of Gram-negative bacteria. To ensure safety on patient’s endotoxin content in the drug should always be controlled. In a biological processing it may emanate from facility, utility, raw materials, process, and personnel. In this webinar we discuss the regulatory norms, strategies for prevention & removal of endotoxin to ensure that the final drug product is safe.
Drug delivery system for biotech product considering stability aspects and mo...zobaida mostarin nishi
Drug delivery is becoming a whole interdisciplinary and
an independent field of research and is gaining the attention of
pharmaceutical makers, medical doctors, and industry. A
targeted and safe drug delivery could improve the performance
of some classical medicines already on the market and,
moreover, will have implications for the development and
the success of new therapeutic strategies, such as peptide and
protein delivery, glycoprotein administration, gene therapy and
RNA interference.
This document summarizes a view from the biosimilar industry on implementing the WHO guidelines for evaluating biosimilar products. It makes three key points:
1) The WHO guidelines provide important global harmonization and clear guidance for regulators and industry on developing biosimilars. They confirm the principles of biosimilarity used in other regional guidelines.
2) Developing biosimilars requires a standalone manufacturing process and demonstrating comparability through extensive quality, preclinical, and clinical testing, including a comparative Phase III study. This development strategy is different than for generic drugs.
3) Experience from manufacturing changes for originator products can be applied to biosimilar development and approval according to the WHO guidelines. This
In vitro studies are critical to drug and wellness product development due to their ability to provide a basis for clinical in vivo studies for predicting best delivery model to take Go/No-Go decision. Our solution on in vitro analyses can provide proof of concept on delivery dosage form in the early stages or reverse pharmacology development of the active process, when the selectivity and possible interactions of the candidate drug towards the desired therapeutic target are established.
Cell Culture Media Filtration – Filter Selection and SizingMilliporeSigma
The purpose of this application note is to provide estimated filtration areas for different sterilizing-grade filters with a panel of media used for Chinese Hamster Ovary (CHO) cell culture processes.
The MIT Consortium on Adventitious Agent Contamination in Biomanufacturing aims to identify best practices for preventing contamination of biomanufacturing processes. The Consortium will provide a collaborative environment for member companies to share experiences and develop solutions. Initial projects include collecting and analyzing industry virus contamination data in a confidential manner to determine risk factors and mitigation strategies. The goal is to advance practices for ensuring product safety and quality.
The document discusses the objectives and guidelines of the International Council for Harmonization (ICH) for stability testing of pharmaceutical products. It provides an overview of the key ICH guidelines for stability testing (Q1A-Q1F) and describes the principles of stability testing including establishing re-test periods and shelf lives. It also discusses the different types of stability testing, protocols, study designs like bracketing and matrixing, and key parameters for evaluation.
Practice school session: PreformulationNamdeo Shinde
This document discusses preformulation studies, which characterize a drug molecule's physical and chemical properties to develop a safe, effective, and stable dosage form. Preformulation helps assess a molecule's suitability for development and reduces risks. It provides data to screen lead compounds and guide appropriate dosage design. The objective is to select the right drug substance, excipients, and packaging to minimize issues in later development stages. Key preformulation study parameters include solubility, permeability, compatibility, and properties like pH and polymorphism. Preformulation assists both drug discovery and development.
The document introduces Matthew and states that his favorite food is [BLANK]. It mentions that his hobbies include [BLANK] and his favorite holiday is [BLANK]. It also states that the best games he's played are [BLANK] and the coolest thing he's ever done is ride an [BLANK]. The rest of the document appears to be citations.
Ever given a thought on how machine intelligent the softwares are getting nowadays? Lets imagine a situation when you surf a video on youtube and you are not given any recommendations for similar videos, Or a situation when none of the irritating mails we get automatically go to our spam folder? Life would not be as easy as it currently is.
Machine learning is getting in trend and so we thought about Integrating Apache Mahout with AEM to simply make our AEM applications smarter and interesting!
Mahout helps us in 3 different ways:
1. Recommendations
2. Classification
3. Clustering
We will focus on a typical use case of developing E-commerce applications in AEM and providing product recommendations on the basis of user search history.
Excipients selection for high risk formulations Smita RajputMerck Life Sciences
Are you choosing the right excipients for your high risk application? Find out how to select the right excipients and enable your process optimization to improve the total cost of ownership.
In this webinar, you will learn:
• Selection of right excipients for high risk formulation is very critical step
• Low Endotoxin and low bioburden limits are important aspect while selecting raw materials
• Strong regulatory support is crucial for high risk formulation
Excipients selection for high risk formulations like parenteral and ophthalmic applications is very challenging. Excipients should be inert with high purity for such dosage forms because trace amounts of impurities present in excipients can interact with active pharmaceutical ingredient (API) which results in instability of the formulation. This presentation discusses how to select the right excipients for high-risk applications and gives guidance for process optimization by choosing the best combination of filters and excipients to improve the total cost of ownership.
Polymer based drug delivery systems for parenteral controlled release: from s...Merck Life Sciences
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
The document summarizes the development process for a biologic product from cell line generation to characterization. It involves:
1) Developing a stable CHO cell line expressing the target protein through cloning and selection.
2) Establishing master and working cell banks for upstream production.
3) Developing purification and viral clearance downstream processes.
4) Formulating the drug substance and filling it into vials as the drug product.
5) Characterizing the protein structure, activity, immunological properties, purity and stability according to ICH guidelines.
ISO 10993 Biological Evaluation of Medical Devices UpdateNAMSA
The ISO 10993 Biological Evaluation of Medical Devices Update covers the revisions/updates that were discussed at the TC194 meeting in Mishima, Japan in April of 2014.
Ich guidelines for stability testing of biotechnological biological products (1)Dr Raj kumar Kudari
This document provides guidelines for stability testing of biotechnological and biological products. It discusses selecting representative batches of drug substance and drug product for testing, establishing a stability-indicating profile including potency, purity, and other characteristics, and testing under various storage conditions like temperature, humidity, and accelerated/stress conditions. The guidelines aim to ensure biologics maintain biological activity and avoid degradation during their intended storage period.
A seminar on applications of various analytical techniquePatel Parth
This document provides information on preformulation studies for new drug development. It discusses:
1. The purpose of preformulation studies is to understand the characteristics of drug components and optimize dosage form manufacturing.
2. Preformulation studies establish the identity, properties, and compatibility of new drug substances to support formulation development and regulatory filings.
3. A variety of analytical techniques are used in preformulation studies including spectroscopy, chromatography, and thermal analysis to characterize drug substances and excipients.
Sterile filtration of complex injectables by Partha BanerjeeMerck Life Sciences
Sterile filtration and filter validation remain a critical segment during the development of these segments of products. Let's find the same by understanding a checklist and visualize certain case studies.
As the sterile injectable market continues to see rapid growth (~10% to 15% per annum) – outpacing the growth of oral products – it is natural to see the diversity of parenteral product formulations increasing in parallel. The definition of complexity in parenteral formulation development is broad. It varies based on the stage of development and the specific nature of the challenge. A notionally simple, stable reproducible laboratory formulation may carry a level of complexity in aseptic control if routine means of sterilization are unavailable.
Sterile filtration process intensification can bring significant benefits to manufacturers in terms of manufacturing flexibility, reduction of risks, better turn around time, thus achieving significantly higher productivity. We will identify these scenarios with case studies to reduce complications in manufacturing and process development.
Sterile filtration of complex injectables by Partha BanerjeeMerck Life Sciences
The document discusses considerations for sterile filtration of complex injectables such as liposomes, emulsions, and viscous formulations. It notes that sterile filtration is widely used for liposome sterilization but poses challenges due to the small size of liposomes and bacteria. Key parameters for liposomes include particle size distribution, zeta potential, and stability. The talk addresses regulatory guidelines for liposome characterization and manufacturing. It also outlines best practices for sterile filtration of oils, emulsions and viscous drugs to optimize the filtration process.
Edward Narke discussed the CMC pathway for biologics through clinical development and market approval. The goals are to better understand FDA requirements, visualize a cost-effective approach to manage manufacturing processes, and appreciate challenges in controlling safety, potency, and impurities. Biologics have complex structures that must be characterized and controlled. Assay methods, product specifications, stability data, and comparability between clinical and commercial materials are common reasons INDs are placed on clinical hold. Managing impurities, developing relevant potency assays, and collecting data continuously are important strategies to address these challenges over the course of development.
In this webinar, you will learn:
Sources of endotoxin contamination
Contamination control strategy
Endotoxin removal strategies
Detailed description:
Endotoxin, a lipopolysaccharide (LPS), is a type of pyrogen and is a component of the exterior cell wall of Gram-negative bacteria. To ensure safety on patient’s endotoxin content in the drug should always be controlled. In a biological processing it may emanate from facility, utility, raw materials, process, and personnel. In this webinar we discuss the regulatory norms, strategies for prevention & removal of endotoxin to ensure that the final drug product is safe.
Drug delivery system for biotech product considering stability aspects and mo...zobaida mostarin nishi
Drug delivery is becoming a whole interdisciplinary and
an independent field of research and is gaining the attention of
pharmaceutical makers, medical doctors, and industry. A
targeted and safe drug delivery could improve the performance
of some classical medicines already on the market and,
moreover, will have implications for the development and
the success of new therapeutic strategies, such as peptide and
protein delivery, glycoprotein administration, gene therapy and
RNA interference.
This document summarizes a view from the biosimilar industry on implementing the WHO guidelines for evaluating biosimilar products. It makes three key points:
1) The WHO guidelines provide important global harmonization and clear guidance for regulators and industry on developing biosimilars. They confirm the principles of biosimilarity used in other regional guidelines.
2) Developing biosimilars requires a standalone manufacturing process and demonstrating comparability through extensive quality, preclinical, and clinical testing, including a comparative Phase III study. This development strategy is different than for generic drugs.
3) Experience from manufacturing changes for originator products can be applied to biosimilar development and approval according to the WHO guidelines. This
In vitro studies are critical to drug and wellness product development due to their ability to provide a basis for clinical in vivo studies for predicting best delivery model to take Go/No-Go decision. Our solution on in vitro analyses can provide proof of concept on delivery dosage form in the early stages or reverse pharmacology development of the active process, when the selectivity and possible interactions of the candidate drug towards the desired therapeutic target are established.
Cell Culture Media Filtration – Filter Selection and SizingMilliporeSigma
The purpose of this application note is to provide estimated filtration areas for different sterilizing-grade filters with a panel of media used for Chinese Hamster Ovary (CHO) cell culture processes.
The MIT Consortium on Adventitious Agent Contamination in Biomanufacturing aims to identify best practices for preventing contamination of biomanufacturing processes. The Consortium will provide a collaborative environment for member companies to share experiences and develop solutions. Initial projects include collecting and analyzing industry virus contamination data in a confidential manner to determine risk factors and mitigation strategies. The goal is to advance practices for ensuring product safety and quality.
The document discusses the objectives and guidelines of the International Council for Harmonization (ICH) for stability testing of pharmaceutical products. It provides an overview of the key ICH guidelines for stability testing (Q1A-Q1F) and describes the principles of stability testing including establishing re-test periods and shelf lives. It also discusses the different types of stability testing, protocols, study designs like bracketing and matrixing, and key parameters for evaluation.
Practice school session: PreformulationNamdeo Shinde
This document discusses preformulation studies, which characterize a drug molecule's physical and chemical properties to develop a safe, effective, and stable dosage form. Preformulation helps assess a molecule's suitability for development and reduces risks. It provides data to screen lead compounds and guide appropriate dosage design. The objective is to select the right drug substance, excipients, and packaging to minimize issues in later development stages. Key preformulation study parameters include solubility, permeability, compatibility, and properties like pH and polymorphism. Preformulation assists both drug discovery and development.
The document introduces Matthew and states that his favorite food is [BLANK]. It mentions that his hobbies include [BLANK] and his favorite holiday is [BLANK]. It also states that the best games he's played are [BLANK] and the coolest thing he's ever done is ride an [BLANK]. The rest of the document appears to be citations.
Ever given a thought on how machine intelligent the softwares are getting nowadays? Lets imagine a situation when you surf a video on youtube and you are not given any recommendations for similar videos, Or a situation when none of the irritating mails we get automatically go to our spam folder? Life would not be as easy as it currently is.
Machine learning is getting in trend and so we thought about Integrating Apache Mahout with AEM to simply make our AEM applications smarter and interesting!
Mahout helps us in 3 different ways:
1. Recommendations
2. Classification
3. Clustering
We will focus on a typical use case of developing E-commerce applications in AEM and providing product recommendations on the basis of user search history.
This document summarizes a report published by the Bio-Process Systems Alliance (BPSA) regarding recommendations for testing, evaluation, and control of particulates from single-use process equipment. The BPSA is a trade association that facilitates implementation of single-use technologies through various initiatives. The report was created by a working group consisting of subject matter experts from single-use technology suppliers and end users. It provides guidance on characterizing and minimizing particulate levels throughout the lifecycle of single-use technologies, including manufacturing, storage, handling and end use. It also discusses investigation and mitigation of particulate deviations. The BPSA recommends further work to develop standardized measurement methods, application-specific requirements, a catalog of particle types,
1) The co-op student worked at Bristol-Myers Squibb to optimize protein purification chromatography conditions and improve impurity clearance.
2) High-throughput screening was used to evaluate different buffer and resin combinations. Process conditions were optimized to separate variants and improve purity.
3) The student met project goals including developing chromatography methods, characterizing protein populations, and providing insights into improving processes. The work focused on optimizing the initial protein A capture step to reduce downstream purification needs.
US Pharma presentation on clone screen strategy for monoclonality using Solen...IanTaylor50
Presentation by a Cell Metric CLD customer in US about their use of the system in clone screening for cell line development.
This presentation is made available courtesy of Momenta Pharmaceuticals and IBC Conferences
The document discusses stage 3 process validation which involves measuring critical quality attributes to ensure a reproducible manufacturing process. It provides an overview of current good manufacturing practice regulations regarding in-process controls and process validation. The document outlines the three stages of process validation according to FDA and EU guidelines: process design, process qualification, and continued process verification. It emphasizes establishing a control strategy to monitor and control variability throughout the product lifecycle.
Investing in Process Development for Increased MSC Production in Stirred Tank...MilliporeSigma
Interested in developing a robust cell therapy manufacturing platform? In this webinar we will share information in the form of case studies that highlight strategies to optimize your cell therapy production process.
Industry trends in regenerative medicine highlight a critical need for closed cell culture systems that support scalable manufacturing of adherent cell therapies. Typical static in vitro culture methods, however, are often too cumbersome and inefficient to support commercial scale production of mesenchymal stem/stromal cells (MSCs). Single-use stirred tank bioreactor systems are a platform that can address this limitation and have been proven effective for microcarrier-based production of adherent cell therapies. Implementation of optimized process control strategies for parameters such as dissolved oxygen (DO) and agitation rate are key to making an efficient transition from planar culture to stirred tank bioreactors. Herein, a stepwise approach to process development for MSC expansion in a small-scale single-use bioreactor is presented. Case studies focus on strategies to optimize DO control and agitation rates for bone marrow derived MSCs in microcarrier culture, highlighting improvements in process efficiency. In the first case study, the impact different gassing methods have on DO control and whether hypoxic growth conditions affect MSC function are examined. The second case study demonstrates the application of Zwietering’s equation for suspension of solids to overcome scaling challenges often associated with microcarrier culture in stirred tanks. Strategies to further improve the seeding process for bioreactor culture will also be reviewed. Identifying optimal seeding and process control strategies for microcarrier-based bioreactor expansion of adherent cells is paramount for the development of robust cell therapy manufacturing platforms.
In this webinar, you will learn about:
· Process development approaches for production scale-up of mesenchymal stem cells (MSCs)
· Implementing single-use, closed systems for manufacturing cell therapies
· Case studies focusing on strategies to optimize DO control and agitation rates for microcarrier-based cultures
Investing in Process Development for Increased MSC Production in Stirred Tank...Merck Life Sciences
This document discusses process development for manufacturing mesenchymal stem cells (MSCs) using microcarrier-based suspension culture in bioreactors. It outlines challenges in scaling up MSC production, including maintaining optimal hydrodynamic conditions and controlling dissolved oxygen. A case study demonstrates that MSCs expanded at 50L scale on microcarriers in a bioreactor retain their multipotent characteristics. The document also proposes strategies for optimizing a closed seed train to decrease manufacturing risks and costs compared to traditional planar seeding methods.
Pharmaceutical Product & Process Design & QualityAjaz Hussain
A reflection on progress made, and challenges to be addressed, in realizing the desired state articulated by the the FDA Initiative on Pharmaceutical Quality for the 21st Century.
The CMC Journey in the Regulation of Biologicsenarke
Journey in the Development of Biologics Through End of Phase 3
Our Goals
To better understand the FDA’s CMC requirements and expectations for biologic manufacturing and product testing
To better visualize a cost-effective, risk-managed approach to manage these manufacturing processes and products through clinical development into market approval
To better appreciate the challenges involved with controlling safety, potency, and impurity profiles for these products
The document discusses ways to accelerate vaccine development and manufacturing. It proposes adopting a template and platform approach to streamline process development. A template provides a standardized starting point for each vaccine's development process. A platform accumulates expertise across multiple vaccines using common unit operations, parameters, and facilities. This approach can speed development times, lower costs, simplify supply chains, and facilitate technology transfer and manufacturing.
In our final webinar of the MDC Connects Series 2021 | A Guide to Complex Medicines.
This slide deck takes a closer look at overcoming the challenges of scaling up a complex medicine.
Graham Worrall and Emily Port, CPI
Use of Microfluidic Capillary Gel Electrophoresis for Release and Stability T...Mike Smith
The document summarizes the development and use of a microfluidic capillary gel electrophoresis (CGE) platform method for the release and stability testing of monoclonal antibodies. The method was developed to improve on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis. The platform method involved designing experimental conditions through design of experiments, validating the method using multiple examples, and then efficiently implementing the method for new products through a sample verification procedure. The method has been transferred to multiple Good Manufacturing Practice laboratories, though a primary challenge has been a high invalid rate. A case study demonstrated how applying a "go and see" approach through identifying gaps helped reduce the invalid rate over time.
Mycenax is a CDMO located in Taiwan that provides services for biologics development from cell line development through fill/finish. They have expertise in mammalian and microbial manufacturing up to 2000L scale using disposable technology. Mycenax has 7 biosimilars in development and is evaluating opportunities for novel biologics. They aim to be a full service CDMO partner for biologics development and manufacturing.
#InvitroStudies are critical to the #drug and #wellness product #development due to their ability to provide a basis for #clinical in vivo studies for predicting best delivery model to take Go/No-Go decision. #Our solution on in vitro analyses can provide proof of concept on delivery dosage form in the early stages or reverse pharmacology #development of the active process, when the selectively and possible interactions of the active process, when the selectivity and possible interactions of the candidate drug towards the desired therapeutic target are established. Our team can provide solution map on case to case basis for your specific requirement . For more details please visit on https://www.stabicon.com/In-Vitro.php
The document discusses issues with the Drug Regulatory Authority of Pakistan's (DRAP) recommendations for batch sizes in product development and stability studies, which contradict international regulatory science norms. Specifically, DRAP recommends a batch size of only 2,500 tablets for lab-scale trials and stability testing every 1-2 weeks, rather than the accepted standards of at least 25% of pilot-scale batch size and testing every 3-6 months. The author argues this approach is not supported by any scientific reference and could compromise drug quality, safety and efficacy. The document advocates for DRAP to align its practices with international guidelines from organizations like the International Council for Harmonization to strengthen regulatory systems in Pakistan and better serve patients and industry.
The document discusses key differences between biotherapeutics (large molecule medicines produced from living cells) and small molecule medicines. Biotherapeutics are much larger and more complex structures than small molecules. Their development, manufacturing, and regulatory evaluation require specialized considerations and standards due to their sensitivity, potential for immunogenicity, and structural complexity. The document outlines the complex manufacturing processes required for biotherapeutics, regulatory frameworks for evaluating manufacturing changes and ensuring comparability over the product lifecycle, and calls for dedicated legislation and guidance to appropriately regulate biotherapeutic development, approval, and post-marketing activities.
The document discusses developing curriculum to support careers in biomanufacturing and the bioeconomy. It proposes hands-on workshops for teachers and students to learn biomanufacturing concepts and techniques. These include transforming bacteria, purifying proteins through various types of chromatography, and analyzing purified proteins through electrophoresis. The goal is to promote STEM education and careers in the growing biomanufacturing industry.
This document discusses in-process quality control of suspensions and emulsions. It defines in-process quality control as controlling manufacturing procedures from raw materials to final product packaging. Key tests for suspensions include appearance, particle size, zeta potential, viscosity, sedimentation rate and redispersibility. Maintaining proper pH, drug content uniformity and monitoring manufacturing areas are also important. Tests for emulsions include appearance, droplet size, viscosity, creaming index and phase separation. Proper documentation of quality control procedures and parameters is necessary to ensure batch uniformity and quality.
In process quality control of suspensions and emulsionsceutics1315
This document discusses in-process quality control of suspensions and emulsions. It defines in-process quality control as controlling manufacturing procedures from raw materials to final product packaging. Key tests for suspensions include appearance, particle size, zeta potential, viscosity, sedimentation rate and redispersibility. Maintaining proper pH, drug content uniformity and monitoring manufacturing areas are also important. Tests for emulsions include appearance, droplet size, viscosity, creaming index and phase separation. Proper documentation of quality control procedures and parameters is necessary to ensure batch uniformity and quality.
The Role of BPOG Extractables Data in the Effective Adoption of Single-Use Sy...Merck Life Sciences
The successful adoption of single-use technologies in a biopharmaceutical process largely relies on confidently selecting the right components for use in the fluid path of a product, within a specific process. An important step in choosing such components requires generating an extractables profile, which can be done by carefully selecting the solvent streams and extraction conditions to model the product and process steps complemented with the right analytical strategy.
In this webinar, you will learn:
● An approach to adopt the BioPhorum Operations Group (BPOG) extractables protocol as a baseline testing strategy.
● How to apply extractables data to a specific process followed by a systematic, risk-based safety assessment approach used for comparing known safety concern thresholds.
● The important stages in the risk assessment process as demonstrated by case studies from typical drug manufacturing processes where single-use components were used.
Presentation by Juliëtte van den Dolder from Noviocell; From technology to business. During SMB meeting on December 15, 2016 at SMB Life Sciences / Novio Tech Campus in Nijmegen, NL.
Similar to Bioworld Taiwan Danny Chou Feb292016 (20)
1. Aggregation Properties of
Therapeutic Proteins Revealed by
New Analytical Methods
Danny K. Chou, PharmD, PhD
President, Compassion BioSolution, LLC
Biologics world Taiwan 2016
25th, February 2016
2. Presentation Outline
• How protein aggregation occurs and the dominant
forces that control the formation of aggregates and
particulates.
• How does protein aggregation affect development
and commercial viability of biopharmaceuticals
• How do you monitor and control formation of
aggregates and particles? What is the state-of the-
art analytical approach?
• Why proper integration of formulation, container-
closure, and analytical technology is essential to the
success of a biologics development program.
3. Success Drivers in Biologic Drug Development
• Thanks to the favorable clinical profile of biologics
and increasing market demand the growth in
development of biopharmaceuticals is already
surpassing that of conventional drugs.
• Along with this trend the challenges of
biopharmaceutical development has become a
significant barrier to entry and sustainable
commercial success
• Commercial success requires both innovative
technical development and management of unique
challenges associated with the nature of biologics
• One of the these key technical challenges is protein
aggregation
4. Why Are Proteins so Difficult to Develop?
Putting Things Into Perspective With Respect
to Size of Biologic Molecules
*NEJM 2011
5. What is Protein Aggregation and Why is
it Important?
• Protein aggregates: “High molecular weight
proteins composed of multimers of natively
conformed or denatured monomers”
(Rosenberg, 2006)
• Aggregates can reduce biological activity, or
worse, induce immune response, but the
mechanism is still not very well understood
• Immunogenicity is a major product SAFETY
concern
6. Protein Aggregation – Mechanisms
• Protein therapeutics are highly complex in terms of size, structure
and function.
• Structural flexibility presents a higher risk for physical instability as
well as a major regulatory concern on product quality and safety.
Krishnamurthy et al. BioProcess International, 2008
7. Phenomenon of Protein Aggregation –
What Do We Know at the Present?
• Both conformational and colloidal stability play a role
Chi et al., Pharm. Res. 20:1325, 2003
8. Contributing Factors to Formation of
Soluble Protein Aggregates and Particles
Bioprocessing from
start to end
Physical/chemical Stresses:
pH, ionic strength, temperature,
chemical modification, light,
agitation, mechanical shock, freeze-
thaw, etc.
Air/Solid-Liquid Interfaces:
Protein contact with tubings, pumps,
pipes, vessels, filters, columns, etc.
Foreign Particles:
Stainless steel, glass, plastic, rubber,
tungsten, silicone oil, etc.
Fermentation/cell
culture
Purification
Filling
Packaging
Shipping
Storage
Administration
9. Not all Aggregates or Particles are the same….
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Visible Protein Particles
Visible Extraneous Particles
10. Why is protein aggregation relevant to
biopharmaceutical development and
manufacturing?
• Protein aggregation has long been suspected as a
having a role in safety and efficacy of biologics
13. Orthogonal Techniques that Cover
Various Particle Size Ranges
0.001 um 0.01 um 0.1 um 1 um 10 um 100 um 600 um
SEC, AUC
DLS Flow microscopy
HIAC / Light Obscuration
Visual
1 nm 10 nm 100 nm 1000 nm
Subvisible aggregates
Silicone droplets
Nano-emulsions &
suspensions
Visible aggregates
Emulsions & suspensions
Glass, rubber, plastic, etc.,
particles
RMM
Nanosight
14. Extended characterization per USP<1787>
Technique Size Range
Light obscuration 2-300 um
Electrical senzing zone (Coulter) 0.4-1600 um
Laser diffraction 0.1-3500 mm
Light microscopy 0.3 um to 1 um
Flow imaging analysis 1 um-100 um for
size distribution;
5-100 um for
morphology
Electron microscopy (EM): Scanning EM,
scanning transmission EM, and transmission
EM
A to mm
Fourier Transform Infrared (FTIR)
microspectroscopy
10 um to 1 mm
Dispersive-Raman microspectroscopy 0.5 um to 1 mm
Electron microscopy (EM) with energy-
dispersive X-ray spectrometry (EDS)
A to mm for
imaging
Size and
distribution
Size and
morphology
Characterization
15. Criteria for Ideal Methodology
• Detects SVPs ranging from 0.1 – 100 µmSize Range
• Ideal if it allows for validation and setting
acceptable limits.
Particle Count
• Protein Aggregate vs Silicone Oil Droplet
vs External Inclusions (Metal, rubber etc.)
Particle Type
• Recording of particle image; Provision for
visual identification and analysis.Image of Particle
• Stable Aggregates vs Dilution-dependent
Transient aggregates.
No prior sample
manipulation
16. While This Field Continues to Evolve
There is an Opportunity in Front of Us
• SVP testing can be applied during process
development to optimize processing
conditions and reduce impurities
• Proper integration of orthogonal technique is
a powerful way to improve formulation
robustness and assess drug product- delivery
device compatibility
17.
18. Case 1: Use of Subvisible Particulate (SVP)
Analysis During Process Development
Background:
• IgG monoclonal antibody (mAb A)
• Manufactured at 2k L scale for Phase I and Phase II
clinical testing
• 3 Column Purification Platform
• Affinity, Cation, Anion
• Virus filtration in final position prior to UF/DF
19. Validation Study of VF Performance (mAb A)
0
100
200
300
400
500
600
0 200 400 600
VProFlux(LMH)
Volumetric Throughput (L/m2)
1% XMuLV Run 1
1% XMuLV Run 2
Decoupled No Virus
1% MVM Run 1
1% MVM Run 2
Coupled No Virus
• Achieved only 53% of target throughput
• Only non-spiked coupled train (with pre-filter) exceeded target
• Decoupled trains displayed both cake formation and pore plugging type fouling
• Visible particle formation post transfer of feed into reservoirs
• Conclusion: FAIL. Requires revalidation
Concentration mg/mL 7.9
*Target Throughput L/m2
(g/m2)
> 318
(2510)
**Achieved Throughput L/m2
( g/m2
)
168
(1330)
* Target based on production scale
** Achieved based on worst VF performance
20. Key Goals for Viral Filtration Validation Study of
mAb A
• Overcoming filter fouling
– Minimize factors linked to particulate formation
• Optimize strategies for handling VF load when
conducting VF validation
• Measuring sub visible particles (SVP)
– Establish SVP analytical techniques and apply to VF loads
– Correlating SVP formation and distribution as function of VF
handling practices
23. Quantitative Particle Detection of mAb A
During Viral Filtration
• Particle concentration increased as a result of turbulent, “non gentle” conditions
• Handling conditions were linked to membrane fouling; therefore new methods
need to be developed to minimize particle formation in an effort to increase
process efficiency while reducing cost
222761
61594
7169 4512 2671
9122
1005
69267
7213 2776 1823 946 3582 372
-3.E+04
2.E+04
7.E+04
1.E+05
2.E+05
2.E+05
1-2um 2-4um 4-6um 6-8um 8-10um > 10um > 25um
ParticlespermL(P/ML)
Particle Size ( μm)
Non Gentle
Gentle Handling
1-2 μm 2-4 μm 4-6 μm 5-8 μm 8-10 μm >10 μm >25 μm
24. Orthogonal Particle Detection Method: DLS
Dynamic Light Scattering
• DLS (dynamic light scattering, also known
as quasi-elastic light scattering), uses light
scattering of a laser beam and very fast
decay measurement to determine the
hydrodynamic radius and polydispersity of
the species present.
• It can measure radii down to 0.5 nm and
determine radii for two populations with
radii at least 5-fold different, with best
results if 10-fold different
Kuebler S. “Characterizing stable protein formulations.” Genetic Engineering & Biotechnology News 27.20 (2007). Accessed September 4,
2013 from http://genengnews.com.
EXPERIMENT
“Gently” handled VF feed was loaded directly onto microplate for DLS testing
“Non Gentle” handled VF load experienced turbulence (3x pour and swirl) to
mimic validation handling practices prior to testing
Over the duration of one hour, DLS data was collected
25. “Gently” handled samples
5-6 nm
“Non-Gently”
handled samples
5-6 nm
Aggregates of mAb
• DLS can be used as an orthogonal approach for SVP detection
• Detected differences in handling conditions (5-6 nm mAbs vs. large particles)
• Non-monomer particles were detected as a result of “non gentle” conditions
• 20nm VPro pore size, may be increasingly susceptible to membrane fouling
due to handling conditions
Qualitative Particle Detection of VF Load
26. Impact of Process Change on Process
Efficiency and Cost for mAb A
• By modifying formulation of in-process material and handling techniques,
particle formation was mitigated, enabling flux to maintain > 100 LMH and target
throughputs were exceeded
• With 1% spikes of both feeds, was able to show adequate log clearance
0
50
100
150
200
250
300
350
400
450
0 100 200 300 400 500 600
VProFlux(LMH)
Volumetric Throughput (L/m2)
1% MVM N=1
1% MVM N=2
1% XMuLV N=1
1% XMuLV N=2
Concentration mg/mL 7.0
*Target Throughput L/m2
(g/m2)
> 318
(2510)
**Achieved Throughput L/m2
( g/m2
)
517
(3620)
* Target based on production scale
** Achieved based on worst VF performance
27. Case 2: Use of SVP Analysis During
Combination Product Development
• Drug product-container compatibility is a critical
factor in the successful development of biologic
combination products
• SVP testing was conducted to evaluate stability of
a high concentration mAb formulation (mAb B), in
different brands/types of pre-filled syringes (PFS)
28. Glass PFS Plastic PFS
Brand Brand X MySafill®
Packaging
Material
Glass
(borosilicate)
Plastic
(Cyclo Olefin Polymer )
Pros Scratch resistant,
Transparent
Low protein adsorption*,
Tungsten not required,
Retractable needle,
Cons Breakage,
Tungsten,
Alkali oxide,
Negatively charged Surface
Higher leachable profile,
More easily scratched
*In selected cases
Glass PFS and MySafill® (a new polymer PFS with
integrated safety feature) were directly compared
with respect to their impact on stability of mAb B
29. What is Different about MySafill®?
Same injection technique as the conventional pre-filled syringe; retraction of
needle is activated by pressing the plunger rod after completion of injection
Courtesy of Medical Chain International
30. Shaking Experiment – Visual Observation
Active
Control
Glass PFS
A
Glass PFS
B
Glass PFS
C MySafill
Active
Shaken
Glass PFS
A
Glass PFS
B
Glass PFS
C
MySafill
31. Shaking Experiment – SEC-HPLC
96.0
96.4
96.8
97.2
97.6
98.0
98.4
98.8
%MAINPEAK
Control Shaken
Glass A Glass CGlass B MySafill
32. Shaking Experiment - Flow Microscopy
-10000
0
10000
20000
30000
40000
50000
60000
70000
PARTICLECONC.(PARTICLES/ML)
Flow Microscopy (Average of 2 Consecutive Runs)
Control Shaken
Glass PFS A Glass PFS B Glass PFS C MySafill PFS Placebo
33. Morphology of Particles is Important
for Identification
Glass PFS Agitated in bad formulation Glass PFS Agitated in good formulation
MySafill Agitated in bad formulation MySafill Agitated in good formulation
34. Effect of Stress Method on Aggregate
Morphology
Images of mechanical stress-induced
particles in IgG solution
Images of thermal stress-induced
particles in IgG solution
35. Container Material & Formulation Impact on
Subvisible Particle Formation upon Agitation
(Flow Microscopy)
0
2000
4000
6000
8000
10000
12000
14000
16000
BD Glass Syringe (no
agitation)
BD Glass Syringe
agitated (No PS 20)
Glass Syringe agitated
(with PS 20)
MySafill (no agitation) MySafill agitated (no
PS 20)
MySfaill agitated (with
PS 20)
2-4um
4-6um
6-8um
8-10um
10-25um
greater than 25um
ParticleConcentration
(particles/mL)
Glass, No Agitation Glass-PS, Agitation Glass+PS, Agitation Plastic, No Agitation Plastic-PS, Agitation Plastic+PS, Agitation
Proper integration of formulation, delivery device, and analytical technology
is essential
36. The ‘Triad’ of Biologics Drug
Product Development
Formulation
To Achieve
Stability and
Process
Efficiency
New Analytics
Enable
True Product
Characterization
Innovative
Delivery
Technology
IV to SC
Improved patient care and chance of commercial success
Current Situation
The Future of Biologics Marketplace The ‘pinnacle’ is not as hard to reach
as it may seem
37. The Best Selling Brand of a Biologic in Asia
Lack of proper integration in biologic drug product development will manifests itself
38. Conclusions
• New technologies are enabling better understanding of
protein aggregation pathway as well as early detection,
which is the first step towards effective control of this key
quality attribute
• Protein aggregate/subvisible particle analysis should
begin ‘upstream’ of drug product development (stable
drug product begins with stable drug substance)
• One can speed up drug product development and
ensure long term sustainability by optimizing biologics
formulation and integrating it with delivery device and
analytical technology.
• The increased regulatory and market expectation for
high quality biopharmaceuticals creates opportunities for
those who fully embrace drug product formulation,
analytical, and drug delivery expertise. These are the
backbone of every successful commercial product!
39. Thank you!
Compassion BioSolution, LLC
Danny K. Chou, PharmD, PhD
E-mail: pharmd98@gmail.com
Phone (USA): 303-483-3690
Compassionbiosolution.com