Biotherapeutic manufacturing processes are at greater risk of contamination than classic small molecule processes and therefore require different control strategies. Understanding the source, options for control, and potential impact of bioburden throughout downstream biopharmaceutical processes is beneficial to process developers, production operators and pharmaceutical microbiologists. Process designs that reduce the risks of bioburden contamination will decrease process related failures and the resulting painful, time-consuming investigations.
Register for our webinar here: https://bit.ly/2SyJrgz
Bioburden control: Strategies to address bioburden control in downstream proc...Merck Life Sciences
Biotherapeutic manufacturing processes are at greater risk of contamination than classic small molecule processes and therefore require different control strategies. Understanding the source, options for control, and potential impact of bioburden throughout downstream biopharmaceutical processes is beneficial to process developers, production operators and pharmaceutical microbiologists. Process designs that reduce the risks of bioburden contamination will decrease process related failures and the resulting painful, time-consuming investigations.
In this webinar, you will learn:
• Biotherapeutic manufacturing processes are at greater risk of contamination than classic small molecule processes and therefore require different control strategies.
• Understanding the source, options for control, and potential impact of bioburden throughout downstream biopharmaceutical processes is beneficial to process developers, production operators and pharmaceutical microbiologists.
• Process designs that reduce the risks of bioburden contamination will decrease process related failures and the resulting painful, time-consuming investigations.
Register for our webinar here: https://bit.ly/3c4q9rr
For an unparalleled experience throughout the life cycle of your therapy, BioReliance® world-class biosafety solutions offer a full range of GMP cell banking services, cell line and virus bank characterization, viral clearance and lot release testing. Merck’s complete biosafety testing solutions, paired with our long-standing reputation for quality and expertise, will give you the mission-critical capabilities to bring safe, life-changing medicines to market.
Endotoxin Control and Clearance in BiomanufacturingMilliporeSigma
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.
Keeping the (Adventitious) Virus Out of the (Adeno-Associated) VirusMerck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/2VRylbi
How can you keep an adventitious virus from contaminating your gene therapy that is delivered by an adeno virus vector? As viral vector bioprocessing advances, regulatory requirements for viral safety will as well. Learn how to define your viral clearance strategy for AAV delivered gene therapies.
How do you define a strategy for viral clearance for a process that inherently aims at purifying a virus?
Gene delivery using AAV has received a boost from two major approvals and the nearly 300 programs in the clinic. Novel gene therapies using viral vectors enable companies to transform the lives of people living with certain rare and ultra-rare diseases where treatments are often not available currently. Amongst a multitude of challenges in viral vector bioprocessing, uncertainty in regulatory expectations is a major challenge to gene therapy developers. Regulatory requirements are evolving as the science and manufacturing matures with more stringent measures for viral safety assurance expected for future approvals.
Learn how to implement techniques for adventitious virus removal in your viral vector process; we will focus on strategies for viral clearance along your journey towards commercial readiness of AAV-based processes.
In this webinar, you will learn:
• AAV process flows and focus areas for viral safety
• Strategies for implementing viral clearance measures in bioprocessing
• Case studies and data driven approaches on log reduction values (LRV) in a viral vector process
• Best practices and evaluation roadmaps on conducting viral clearance studies
Presented by: Ratish Krishnan, Senior Strategy Consultant, Novel Modalities Bioprocessing
Process Development for Cell Therapy and Viral Gene TherapyMerck Life Sciences
Today’s viral vector manufacturing processes remain challenging. Process development is a critical enabler to bring safe, effective, sustainable products to market to address patient needs. When done properly, it can reduce the timeline of the project and the cost of producing the therapeutic product.
The webinar discusses our strategies for developing lentivirus and adeno associated virus (AAV) and the impact these early decisions can have on commercial readiness.
Watch the interactive webinar now: https://bit.ly/2VplwQq
Single-Use Tangential Flow Filtration for Closed ProcessingMerck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3b7vD60
Closed processing involves use of physical barriers to separate processing fluid from the external environment. This approach reduces capital expenditures and clean room classification while accelerating time to market. This webinar will present a TFF process run in a closed mode.
Closed processing with single-use technologies is a critical enabler for efficient and robust manufacturing for novel modalities as well as continuous biomanufacturing processing. It can also reduce the dependence on classified clean rooms for traditional modalities. This approach helps to mitigate the risk of contamination by adventitious agents while enhancing operator safety.
In this presentation, we discuss the implementation of closed processing for downstream applications and present the design and performance testing of a single use manufacturing-scale tangential flow filtration system to be able to operate in both functionally and fully closed mode.
In this webinar, you will learn:
• The context of closed processing
• Differences between closed and functionally closed processing
• The drivers for adoption
• Its practical implementation to a TFF step
Validation of Tangential Flow Filtration in Biotech ProcessesMerck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3hUKfd7
The objective of validation of a unit operation is to demonstrate with a high degree of confidence that the process performs consistently. The present seminar will focus on the validation of the unit operation of TFF and will provide an overview of the regulatory landscape, the validation master plan, approaches to membrane re-use, cleaning validation, and best practices.
In this webinar, you will learn:
• Validation of TFF
• Validation master plan
• Membrane reuse and cleaning
• TFF scale down models
Speaker: Dr. Subhasis Banerjee,
Principal Technical Application Expert, Bioprocessing APAC
Bioburden control: Strategies to address bioburden control in downstream proc...Merck Life Sciences
Biotherapeutic manufacturing processes are at greater risk of contamination than classic small molecule processes and therefore require different control strategies. Understanding the source, options for control, and potential impact of bioburden throughout downstream biopharmaceutical processes is beneficial to process developers, production operators and pharmaceutical microbiologists. Process designs that reduce the risks of bioburden contamination will decrease process related failures and the resulting painful, time-consuming investigations.
In this webinar, you will learn:
• Biotherapeutic manufacturing processes are at greater risk of contamination than classic small molecule processes and therefore require different control strategies.
• Understanding the source, options for control, and potential impact of bioburden throughout downstream biopharmaceutical processes is beneficial to process developers, production operators and pharmaceutical microbiologists.
• Process designs that reduce the risks of bioburden contamination will decrease process related failures and the resulting painful, time-consuming investigations.
Register for our webinar here: https://bit.ly/3c4q9rr
For an unparalleled experience throughout the life cycle of your therapy, BioReliance® world-class biosafety solutions offer a full range of GMP cell banking services, cell line and virus bank characterization, viral clearance and lot release testing. Merck’s complete biosafety testing solutions, paired with our long-standing reputation for quality and expertise, will give you the mission-critical capabilities to bring safe, life-changing medicines to market.
Endotoxin Control and Clearance in BiomanufacturingMilliporeSigma
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.
Keeping the (Adventitious) Virus Out of the (Adeno-Associated) VirusMerck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/2VRylbi
How can you keep an adventitious virus from contaminating your gene therapy that is delivered by an adeno virus vector? As viral vector bioprocessing advances, regulatory requirements for viral safety will as well. Learn how to define your viral clearance strategy for AAV delivered gene therapies.
How do you define a strategy for viral clearance for a process that inherently aims at purifying a virus?
Gene delivery using AAV has received a boost from two major approvals and the nearly 300 programs in the clinic. Novel gene therapies using viral vectors enable companies to transform the lives of people living with certain rare and ultra-rare diseases where treatments are often not available currently. Amongst a multitude of challenges in viral vector bioprocessing, uncertainty in regulatory expectations is a major challenge to gene therapy developers. Regulatory requirements are evolving as the science and manufacturing matures with more stringent measures for viral safety assurance expected for future approvals.
Learn how to implement techniques for adventitious virus removal in your viral vector process; we will focus on strategies for viral clearance along your journey towards commercial readiness of AAV-based processes.
In this webinar, you will learn:
• AAV process flows and focus areas for viral safety
• Strategies for implementing viral clearance measures in bioprocessing
• Case studies and data driven approaches on log reduction values (LRV) in a viral vector process
• Best practices and evaluation roadmaps on conducting viral clearance studies
Presented by: Ratish Krishnan, Senior Strategy Consultant, Novel Modalities Bioprocessing
Process Development for Cell Therapy and Viral Gene TherapyMerck Life Sciences
Today’s viral vector manufacturing processes remain challenging. Process development is a critical enabler to bring safe, effective, sustainable products to market to address patient needs. When done properly, it can reduce the timeline of the project and the cost of producing the therapeutic product.
The webinar discusses our strategies for developing lentivirus and adeno associated virus (AAV) and the impact these early decisions can have on commercial readiness.
Watch the interactive webinar now: https://bit.ly/2VplwQq
Single-Use Tangential Flow Filtration for Closed ProcessingMerck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3b7vD60
Closed processing involves use of physical barriers to separate processing fluid from the external environment. This approach reduces capital expenditures and clean room classification while accelerating time to market. This webinar will present a TFF process run in a closed mode.
Closed processing with single-use technologies is a critical enabler for efficient and robust manufacturing for novel modalities as well as continuous biomanufacturing processing. It can also reduce the dependence on classified clean rooms for traditional modalities. This approach helps to mitigate the risk of contamination by adventitious agents while enhancing operator safety.
In this presentation, we discuss the implementation of closed processing for downstream applications and present the design and performance testing of a single use manufacturing-scale tangential flow filtration system to be able to operate in both functionally and fully closed mode.
In this webinar, you will learn:
• The context of closed processing
• Differences between closed and functionally closed processing
• The drivers for adoption
• Its practical implementation to a TFF step
Validation of Tangential Flow Filtration in Biotech ProcessesMerck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3hUKfd7
The objective of validation of a unit operation is to demonstrate with a high degree of confidence that the process performs consistently. The present seminar will focus on the validation of the unit operation of TFF and will provide an overview of the regulatory landscape, the validation master plan, approaches to membrane re-use, cleaning validation, and best practices.
In this webinar, you will learn:
• Validation of TFF
• Validation master plan
• Membrane reuse and cleaning
• TFF scale down models
Speaker: Dr. Subhasis Banerjee,
Principal Technical Application Expert, Bioprocessing APAC
Implementing and Managing Pre-use Post-sterilization Integrity Testing (PUPSIT)MilliporeSigma
This presentation explores best practices and case studies in aseptic processing, including how to implement and manage PUPSIT. You will learn:
• Integrity Testing – the background on IT itself, why it is important, and how it works
• Filtration setups and single-use technology
• The PUPSIT debate and how PUPSIT can be achieved with current technology, final filling, formulation, filtration
To learn more about this topic or collaborate with our technical experts, schedule a remote visit at our M Lab™ Collaboration Centers: www.emdmillipore.com/remotevisit
EU GMP Annex 1 Draft: Implications on Sterilizing Grade Filter ValidationMerck Life Sciences
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.
Looking for insights into current global regulatory expectations for viral safety? Read the special report from BioProcess International, in collaboration with Martin Wisher, Senior Regulatory Consultant focusing on BioReliance biosafety® services.
Using Single-use Technology to Overcome the Challenges of ADC ProcessingMerck Life Sciences
Participate in the interactive webinar: http://bit.ly/SU-ADCWebinar
Challenges of ADC manufacturing can be tackled by adopting single-use technology. Solutions will be presented about how to overcome concerns and implement a processing platform, supported through a strong vendor-manufacturer relationship.
Explore our webinar library: www.merckmillipore.com/webinars
Watch the presentation of this webinar here: https://bit.ly/3tDy8Ei
Recent PDA/BioPhorum publications outline risks for PUPSIT in sterilizing filtration. This webinar will summarize the key points and best practices for implementing PUPSIT.
PDA and BioPhorum have partnered to form a task force whose goal was to provide the industry and regulators with scientific data and analysis on the potential risks and benefits of implementing PUPSIT to improve sterility assurance. This webinar will describe the data generated by the task force studies and discuss considerations and best practices when implementing PUPSIT.
In this webinar, you will learn:
• How changing industry perspectives help overcome regulatory concerns and may influence regulatory perspective
• How improved process understanding affects risk assessment
• How improved final fill assembly design simplifies PUPSIT
Parvovirus Filtration Best Practices - 25 Years of Hands-On ExperienceMerck Life Sciences
In this webinar, you will learn:
- how to measure filter performance and capacity,
- how to optimize filter virus removal capability,
- and avoid potential pit-falls
Detailed description:
This webinar will cover all aspects of parvovirus filtration best practices: process development/ optimization, pilot scale-up, and validation and explain the important connections between these activities. The rationale for the recommended best practices will be explained by discussing the underlying mechanisms that control filter performance.
Implementing and Managing Pre-use Post-sterilization Integrity Testing (PUPSIT)Merck Life Sciences
This presentation explores best practices and case studies in aseptic processing, including how to implement and manage PUPSIT. You will learn:
• Integrity Testing – the background on IT itself, why it is important, and how it works
• Filtration setups and single-use technology
• The PUPSIT debate and how PUPSIT can be achieved with current technology, final filling, formulation, filtration
To learn more about this topic or collaborate with our technical experts, schedule a remote visit at our M Lab™ Collaboration Centers: www.merckmillipore.com/remotevisit
Webinar: Post Approval Changes in Biologics Manufacturing - A Practical Asses...MilliporeSigma
Participate in the interactive webinar: http://bit.ly/PACWebinar
Post-approval changes for biologics manufacturing processes are complicated and challenging with the current global diverse regulatory environment. Here, we will present approaches to make these changes more efficient using a risk-based approach.
Explore our webinar library: www.emdmillipore.com/webinars
Aseptic Process Sampling to address Risk of Contamination & Containment in co...MilliporeSigma
Watch this webinar here: bit.ly/asepticwebinar2020
In this webinar, you will learn:
- The challenges tied to contamination control within a biopharmaceutical environment.
- What closed processing is, and how sampling solutions are an integral component towards that end.
- Advantages of sterile sampling from both a technical and economical viewpoint; with the review of a technical study confirming contamination risk reduction and total cost of ownership.
- Recommendations and requirements stated by these major regulatory authorities around the monitoring of the manufacturing process with the execution of sampling.
Detailed description:
Biopharmaceutical manufacturers are required to ensure drug product quality attributes for patient safety. Strong contamination control strategies should be considered early in process design, and have direct influence on the production environment and equipment selection.
Sampling at each step is a critical component in maintaining a contamination control strategy. Regulators are critical in the sampling process, as it predicts the state of the product or process, and needs to be Representative. A case study will be presented that demonstrates a closed, robust sampling solution capable of maintaining a sterile flow path when challenged with Brevundimonas diminuta. The sampling option you select can help support your goal in achieving a closed process, improving your risk mitigation strategy and product safety.
Key to Successful Formulation Development for Lipid Based RNA Delivery and Va...MilliporeSigma
In this webinar, we will discuss:
• The application of RNA therapeutics and the different drug delivery routes used in the clinic.
• Design principles for developing lipids-based RNA formulations.
• Critical parameters to consider for cost effective development and consistent performance of RNA therapeutics and vaccines.
RNA therapeutics are changing the way we address diseases. Applications range from gene therapy, oncology, to vaccines for infectious diseases such as COVID-19.
The performance of RNA therapeutics critically depends on its formulation. Key decisions have to be made early on in the drug development process; choosing the appropriate drug delivery method and novel excipients. Raw material source and judicious choice of chemistry, ultimately determine the quality of novel lipid excipients which, in turn, has a big impact on the performance, reproducibility, costs, and regulatory approval timelines. This webinar will propose solutions to maximize the probability of success while formulating RNA therapeutics and vaccines.
Participate in the interactive webinar now: https://bit.ly/2xXMZlm
Explore our webinar library: www.emdmillipore.com/webinars
Quality by Design Principles Applied to Sterilizing Filtration by Michael PayneMilliporeSigma
Key regulatory documents and regulatory thinking now includes quality by design (QbD). This webinar focuses on how to integrate practical QbD activities into the process and analytical aspects of sterile medicinal product sterilizing filtration and qualification.
In this webinar, you will learn to:
• Focus on practical QbD terms and approaches
• Highlight critical product quality aspects of sterile medicinal products
• Develop design and control spaces for sterilizing filtration
• Easily integrate QbD into the process and analytical operations in early phase development and into manufacturing phase production
Abstract:
Final sterilizing filtration is the last operation in downstream processing to assure the sterility of medicinal products. Poorly defined product attributes process parameters may attract regulatory scrutiny, affect final product sterility and patient safety. A better understanding of QbD concepts and principles allows for better process and analytical monitoring and control at both early and final phase production. The webinar will show how currently available process cGMP information can be practically incorporated into QbD product quality attributes and process parameters. This is especially vital for the third party conducted laboratory work such as bacterial retention and leachable studies.
Pharmaceutical Microbiology: Current and Future Challenges Tim Sandle, Ph.D.
The changing environment for pharmaceutical microbiology
Limitations of methods
Need for new (rapid) methods
Separating people form processes
Single-use technologies
Environmental monitoring programme
Best practices
Rapid methods
Contamination control strategy
Objectionable organisms
Burkholderia cepacia complex
Upcoming USP 665 - Level of Characterization of Single-Use Systems Today and ...MilliporeSigma
Register for the interactive, on-demand webinar now: https://bit.ly/USP665
Single-use plastic systems are being utilized more frequently especially for COVID-19 vaccine manufacturing. However, there are issues regarding standardization of quality information that limits implementation efficiencies. One of the challenges is the evaluation of leachables derived from a variety of different plastic components in a timely manner.
Since the USP <665> highlights a risk assessment approach with no typical pass/fail limit, approaches to decision-making based on the extractables data package will be reviewed. In addition, we will highlight legacy testing requirements which may not be necessary once USP <665> is implemented.
In this webinar, we will discuss:
- Regulatory expectations of extractables and leachables assessment today and tomorrow
- The right criteria that need to be assessed to select the type and quality of plastic materials for use in biopharmaceutical manufacturing
The two most commonly used within microbiology are
HACCP (which originated in the food industry) and FMEA
(developed for engineering). This article explores these two
approaches, first with a description of HACCP, followed by a
description and case study of FMEA in sterility testing.
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.
Biopharmaceutical manufacturing processes are complex, challenging and utilize living organisms to produce safe and efficacious biopharmaceuticals. These molecules themselves have high molecular weights and complex structures that will exhibit heterogeneity such that at any given vial contains not one active ingredient but a population of biologically active molecules which must have maximal benefit to the patient with minimal deleterious effects. The necessity for controlling variation in processes, and hence product, is self-evident when we consider how our actions affect the lives of the patients our products are developed for. This presentation focuses on understanding the various origins of process variation and examines strategies for reducing their impact or eliminating them all together.
http://parker.com/dh
Process development considerations for quality and safety of vaccinesDr. Priyabrata Pattnaik
"New Technologies Symposium" presentation at Annual General Meeting of Developing Country Vaccine Manufacturers Network (DCVMN), 5th-7th October 2015, Bangkok, Thailand.
Implementing and Managing Pre-use Post-sterilization Integrity Testing (PUPSIT)MilliporeSigma
This presentation explores best practices and case studies in aseptic processing, including how to implement and manage PUPSIT. You will learn:
• Integrity Testing – the background on IT itself, why it is important, and how it works
• Filtration setups and single-use technology
• The PUPSIT debate and how PUPSIT can be achieved with current technology, final filling, formulation, filtration
To learn more about this topic or collaborate with our technical experts, schedule a remote visit at our M Lab™ Collaboration Centers: www.emdmillipore.com/remotevisit
EU GMP Annex 1 Draft: Implications on Sterilizing Grade Filter ValidationMerck Life Sciences
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.
Looking for insights into current global regulatory expectations for viral safety? Read the special report from BioProcess International, in collaboration with Martin Wisher, Senior Regulatory Consultant focusing on BioReliance biosafety® services.
Using Single-use Technology to Overcome the Challenges of ADC ProcessingMerck Life Sciences
Participate in the interactive webinar: http://bit.ly/SU-ADCWebinar
Challenges of ADC manufacturing can be tackled by adopting single-use technology. Solutions will be presented about how to overcome concerns and implement a processing platform, supported through a strong vendor-manufacturer relationship.
Explore our webinar library: www.merckmillipore.com/webinars
Watch the presentation of this webinar here: https://bit.ly/3tDy8Ei
Recent PDA/BioPhorum publications outline risks for PUPSIT in sterilizing filtration. This webinar will summarize the key points and best practices for implementing PUPSIT.
PDA and BioPhorum have partnered to form a task force whose goal was to provide the industry and regulators with scientific data and analysis on the potential risks and benefits of implementing PUPSIT to improve sterility assurance. This webinar will describe the data generated by the task force studies and discuss considerations and best practices when implementing PUPSIT.
In this webinar, you will learn:
• How changing industry perspectives help overcome regulatory concerns and may influence regulatory perspective
• How improved process understanding affects risk assessment
• How improved final fill assembly design simplifies PUPSIT
Parvovirus Filtration Best Practices - 25 Years of Hands-On ExperienceMerck Life Sciences
In this webinar, you will learn:
- how to measure filter performance and capacity,
- how to optimize filter virus removal capability,
- and avoid potential pit-falls
Detailed description:
This webinar will cover all aspects of parvovirus filtration best practices: process development/ optimization, pilot scale-up, and validation and explain the important connections between these activities. The rationale for the recommended best practices will be explained by discussing the underlying mechanisms that control filter performance.
Implementing and Managing Pre-use Post-sterilization Integrity Testing (PUPSIT)Merck Life Sciences
This presentation explores best practices and case studies in aseptic processing, including how to implement and manage PUPSIT. You will learn:
• Integrity Testing – the background on IT itself, why it is important, and how it works
• Filtration setups and single-use technology
• The PUPSIT debate and how PUPSIT can be achieved with current technology, final filling, formulation, filtration
To learn more about this topic or collaborate with our technical experts, schedule a remote visit at our M Lab™ Collaboration Centers: www.merckmillipore.com/remotevisit
Webinar: Post Approval Changes in Biologics Manufacturing - A Practical Asses...MilliporeSigma
Participate in the interactive webinar: http://bit.ly/PACWebinar
Post-approval changes for biologics manufacturing processes are complicated and challenging with the current global diverse regulatory environment. Here, we will present approaches to make these changes more efficient using a risk-based approach.
Explore our webinar library: www.emdmillipore.com/webinars
Aseptic Process Sampling to address Risk of Contamination & Containment in co...MilliporeSigma
Watch this webinar here: bit.ly/asepticwebinar2020
In this webinar, you will learn:
- The challenges tied to contamination control within a biopharmaceutical environment.
- What closed processing is, and how sampling solutions are an integral component towards that end.
- Advantages of sterile sampling from both a technical and economical viewpoint; with the review of a technical study confirming contamination risk reduction and total cost of ownership.
- Recommendations and requirements stated by these major regulatory authorities around the monitoring of the manufacturing process with the execution of sampling.
Detailed description:
Biopharmaceutical manufacturers are required to ensure drug product quality attributes for patient safety. Strong contamination control strategies should be considered early in process design, and have direct influence on the production environment and equipment selection.
Sampling at each step is a critical component in maintaining a contamination control strategy. Regulators are critical in the sampling process, as it predicts the state of the product or process, and needs to be Representative. A case study will be presented that demonstrates a closed, robust sampling solution capable of maintaining a sterile flow path when challenged with Brevundimonas diminuta. The sampling option you select can help support your goal in achieving a closed process, improving your risk mitigation strategy and product safety.
Key to Successful Formulation Development for Lipid Based RNA Delivery and Va...MilliporeSigma
In this webinar, we will discuss:
• The application of RNA therapeutics and the different drug delivery routes used in the clinic.
• Design principles for developing lipids-based RNA formulations.
• Critical parameters to consider for cost effective development and consistent performance of RNA therapeutics and vaccines.
RNA therapeutics are changing the way we address diseases. Applications range from gene therapy, oncology, to vaccines for infectious diseases such as COVID-19.
The performance of RNA therapeutics critically depends on its formulation. Key decisions have to be made early on in the drug development process; choosing the appropriate drug delivery method and novel excipients. Raw material source and judicious choice of chemistry, ultimately determine the quality of novel lipid excipients which, in turn, has a big impact on the performance, reproducibility, costs, and regulatory approval timelines. This webinar will propose solutions to maximize the probability of success while formulating RNA therapeutics and vaccines.
Participate in the interactive webinar now: https://bit.ly/2xXMZlm
Explore our webinar library: www.emdmillipore.com/webinars
Quality by Design Principles Applied to Sterilizing Filtration by Michael PayneMilliporeSigma
Key regulatory documents and regulatory thinking now includes quality by design (QbD). This webinar focuses on how to integrate practical QbD activities into the process and analytical aspects of sterile medicinal product sterilizing filtration and qualification.
In this webinar, you will learn to:
• Focus on practical QbD terms and approaches
• Highlight critical product quality aspects of sterile medicinal products
• Develop design and control spaces for sterilizing filtration
• Easily integrate QbD into the process and analytical operations in early phase development and into manufacturing phase production
Abstract:
Final sterilizing filtration is the last operation in downstream processing to assure the sterility of medicinal products. Poorly defined product attributes process parameters may attract regulatory scrutiny, affect final product sterility and patient safety. A better understanding of QbD concepts and principles allows for better process and analytical monitoring and control at both early and final phase production. The webinar will show how currently available process cGMP information can be practically incorporated into QbD product quality attributes and process parameters. This is especially vital for the third party conducted laboratory work such as bacterial retention and leachable studies.
Pharmaceutical Microbiology: Current and Future Challenges Tim Sandle, Ph.D.
The changing environment for pharmaceutical microbiology
Limitations of methods
Need for new (rapid) methods
Separating people form processes
Single-use technologies
Environmental monitoring programme
Best practices
Rapid methods
Contamination control strategy
Objectionable organisms
Burkholderia cepacia complex
Upcoming USP 665 - Level of Characterization of Single-Use Systems Today and ...MilliporeSigma
Register for the interactive, on-demand webinar now: https://bit.ly/USP665
Single-use plastic systems are being utilized more frequently especially for COVID-19 vaccine manufacturing. However, there are issues regarding standardization of quality information that limits implementation efficiencies. One of the challenges is the evaluation of leachables derived from a variety of different plastic components in a timely manner.
Since the USP <665> highlights a risk assessment approach with no typical pass/fail limit, approaches to decision-making based on the extractables data package will be reviewed. In addition, we will highlight legacy testing requirements which may not be necessary once USP <665> is implemented.
In this webinar, we will discuss:
- Regulatory expectations of extractables and leachables assessment today and tomorrow
- The right criteria that need to be assessed to select the type and quality of plastic materials for use in biopharmaceutical manufacturing
The two most commonly used within microbiology are
HACCP (which originated in the food industry) and FMEA
(developed for engineering). This article explores these two
approaches, first with a description of HACCP, followed by a
description and case study of FMEA in sterility testing.
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.
Biopharmaceutical manufacturing processes are complex, challenging and utilize living organisms to produce safe and efficacious biopharmaceuticals. These molecules themselves have high molecular weights and complex structures that will exhibit heterogeneity such that at any given vial contains not one active ingredient but a population of biologically active molecules which must have maximal benefit to the patient with minimal deleterious effects. The necessity for controlling variation in processes, and hence product, is self-evident when we consider how our actions affect the lives of the patients our products are developed for. This presentation focuses on understanding the various origins of process variation and examines strategies for reducing their impact or eliminating them all together.
http://parker.com/dh
Process development considerations for quality and safety of vaccinesDr. Priyabrata Pattnaik
"New Technologies Symposium" presentation at Annual General Meeting of Developing Country Vaccine Manufacturers Network (DCVMN), 5th-7th October 2015, Bangkok, Thailand.
Aseptic Process Sampling to address Risk of Contamination & Containment in co...Merck Life Sciences
In this webinar, you will learn:
- The challenges tied to contamination control within a biopharmaceutical environment.
- What closed processing is, and how sampling solutions are an integral component towards that end.
- Advantages of sterile sampling from both a technical and economical viewpoint; with the review of a technical study confirming contamination risk reduction and total cost of ownership.
- Recommendations and requirements stated by these major regulatory authorities around the monitoring of the manufacturing process with the execution of sampling.
Detailed description:
Biopharmaceutical manufacturers are required to ensure drug product quality attributes for patient safety. Strong contamination control strategies should be considered early in process design, and have direct influence on the production environment and equipment selection.
Sampling at each step is a critical component in maintaining a contamination control strategy. Regulators are critical in the sampling process, as it predicts the state of the product or process, and needs to be Representative. A case study will be presented that demonstrates a closed, robust sampling solution capable of maintaining a sterile flow path when challenged with Brevundimonas diminuta. The sampling option you select can help support your goal in achieving a closed process, improving your risk mitigation strategy and product safety.
Streamlining Biopharmaceutical Cell Line Development - Reducing risk and decr...MilliporeSigma
CHO cells with their unique characteristics, represent the major expression system within the biopharmaceutical industry. However, one of the major challenges in cell line development is to identify those rare, high-producing clones in a huge population of non-expressing or low-expressing cell lines. This leads to laborious and time consuming cell line development processes. This webinar will educate the audience about challenges faced with traditional expression systems and how the CHO cell line with the glutamine synthethase knock-out via Zinc Finger Nucleases provides benefits for fast and efficient cell line development as well as stable and high titer expression. We will explore additional cell line engineering targets that can be modified to engineer a cell line that mitigates risks and removes bottlenecks throughout the biopharmaceutical process.
In this webinar, you will learn:
• What are the benefits of using an optimized/engineered expression system?
• What can be done throughout the cell line development process to mitigate risks and remove bottlenecks?
• Applications of cell line engineering for further upstream biopharmaceutical enhancements.
Streamlining Biopharmaceutical Cell Line Development - Reducing risk and decr...Merck Life Sciences
CHO cells with their unique characteristics, represent the major expression system within the biopharmaceutical industry. However, one of the major challenges in cell line development is to identify those rare, high-producing clones in a huge population of non-expressing or low-expressing cell lines. This leads to laborious and time consuming cell line development processes. This webinar will educate the audience about challenges faced with traditional expression systems and how the CHO cell line with the glutamine synthethase knock-out via Zinc Finger Nucleases provides benefits for fast and efficient cell line development as well as stable and high titer expression. We will explore additional cell line engineering targets that can be modified to engineer a cell line that mitigates risks and removes bottlenecks throughout the biopharmaceutical process.
In this webinar, you will learn:
• What are the benefits of using an optimized/engineered expression system?
• What can be done throughout the cell line development process to mitigate risks and remove bottlenecks?
• Applications of cell line engineering for further upstream biopharmaceutical enhancements.
Find your filter. What’s best for your process? MilliporeSigma
Selecting the right aseptic filter for your process can be complicated: today’s biomanufacturer has many filter choices each offering distinct benefits. Understanding the specific needs for individual operations, in terms of flux, capacity, bioburden reduction or sterilizing performance, gamma or thermal compatibility and single or multi-use will inform decisions that have implications for the life of the process. This webinar will provide general customer guidance and explain the benefits and disadvantages of different options to help guide customers to the most appropriate filter for their operation.
In this webinar, you will learn:
- How filter design impacts performance
- Important criteria for filter selection
- New choices and options to maximize productivity for biomanufacturers
Selecting the right aseptic filter for your process can be complicated: today’s biomanufacturer has many filter choices each offering distinct benefits. Understanding the specific needs for individual operations, in terms of flux, capacity, bioburden reduction or sterilizing performance, gamma or thermal compatibility and single or multi-use will inform decisions that have implications for the life of the process. This webinar will provide general customer guidance and explain the benefits and disadvantages of different options to help guide customers to the most appropriate filter for their operation.
In this webinar, you will learn:
- How filter design impacts performance
- Important criteria for filter selection
- New choices and options to maximize productivity for biomanufacturers
Webinar: Evaluating Viral Clearance for Continuous ProcessesMerck Life Sciences
Participate in the interactive webinar now: http://bit.ly/ViralClearanceWebinar
Is viral clearance a hurdle to implementing continuous processing? We’ll share virus spiking alternatives that may pave the way for effectively evaluating viral clearance by chromatography steps in a continuous process.
Explore our webinar library: www.merckmillipore.com/webinars
Webinar: Evaluating Viral Clearance for Continuous ProcessesMilliporeSigma
Participate in the interactive webinar now: http://bit.ly/ViralClearanceWebinar
Is viral clearance a hurdle to implementing continuous processing? We’ll share virus spiking alternatives that may pave the way for effectively evaluating viral clearance by chromatography steps in a continuous process.
Explore our webinar library: www.emdmillipore.com/webinars
Innovation in Filter Validation and Technology TransferMilliporeSigma
Regulatory and manufacturing requirements exist to perform product-specific microbial retention testing on sterilizing filters. The implementation of a Quality by Design approach to microbial retention testing supports a paradigm that would obviate the need for product-specific testing for early stage products that do not have the quantity of material required to easily and efficiently perform such testing. Process and product parameters were varied to determine their effect on microbial retention.
To learn more about this topic or collaborate with our technical experts, schedule an in-person or remote visit at our M Lab™ Collaboration Centers: www.emdmillipore.com/mlab
Process Development for Cell Therapy and Viral Gene TherapyMilliporeSigma
Today’s viral vector manufacturing processes remain challenging. Process development is a critical enabler to bring safe, effective, sustainable products to market to address patient needs. When done properly, it can reduce the timeline of the project and the cost of producing the therapeutic product.
The webinar discusses our strategies for developing lentivirus and adeno associated virus (AAV) and the impact these early decisions can have on commercial readiness.
Watch the interactive webinar now: https://bit.ly/2VplwQq
The Viscosity Reduction Platform: Viscosity-reducing excipients for improveme...MilliporeSigma
Protein viscosity is a major challenge in preparing highly concentrated protein formulations suitable for subcutaneous injection. Recently, the Viscosity Reduction Platform (VRP) was introduced and its technical key features and benefits for formulations were discussed. However, highly viscous solutions do not only pose a challenge when administering a drug to a patient, they can also impose technical limitations in the manufacturing process.
This white paper evaluates the effect of the excipients in the Viscosity Reduction Platform on ultrafiltration processes used to produce a highly concentrated formulation of a monoclonal antibody (mAb). Two filtration methods are demonstrated in this work.
Find more information about the Viscosity Reduction Platform on our website: https://www.sigmaaldrich.com/products/pharma-and-biopharma-manufacturing/formulation/viscosity-reduction-platform
Use of Excipients in Downstream Processing to Improve Protein PurificationMilliporeSigma
Excipients are used to improve the stability of protein-based therapeutics by protecting the protein against a range of stress conditions such as temperature changes, pH changes, or agitation. Similar stresses are applied to proteins during downstream purification. Shifts in pH during Protein A chromatography, subsequent incubations at low pH for virus inactivation, and changes in conductivity in ion exchange chromatography can lead to aggregation, fragmentation, or other chemical modifications of the therapeutic protein. Given the potential impact on the protein’s structural integrity, there is a need for approaches to reduce the risk presented by the conditions during downstream processing. For example, integration of a solution to prevent aggregation of proteins would be a more efficient strategy than implementing steps to remove multimeric forms.
This white paper highlights the results from a recent paper by Stange et. al., in which protein stabilizing excipients such as polyols, sugars, and polyethylene glycol (PEG4000) were used as buffer system additives. Effect of the excipients on elution patterns, stabilization of the monomer antibody, host-cell protein removal, virus inactivation rates and binding capacity of cation exchange chromatography were explored.
Exploring the protein stabilizing capability of surfactants against agitation...MilliporeSigma
Agitation of therapeutic protein solutions during manufacturing, shipping and handling is one of the major initiators for protein aggregation and particle formation during the life history of a protein drug. Adsorption of protein molecules to liquid-air interfaces leads to the formation of highly concentrated protein surface films. The rupture of these protein films due to various mechanical processes can then result in the appearance of protein aggregates and particles in the bulk solution phase.
One technique to stabilize proteins against stress induced by liquid-air interfaces is the use of non-ionic surfactants. About 91% of antibody formulations commercially available in 2021 contained a surfactant. Polysorbate 20 and 80, composed of a hydrophilic polyoxyethylene sorbitan and hydrophobic fatty acid esters, made up the largest part being employed in 87% of said formulations.
Despite their frequent use in parenteral drug products, concerns have been raised for decades about the application of polysorbates as surfactants in biopharmaceutical formulations. Autoxidation of polysorbate, caused by residual peroxides in polysorbates, can damage the proteins and can further drive the oxidative degradation of polysorbate. Chemical and enzymatic hydrolysis of polysorbate may lead to the formation of free fatty acid particles, which may become visible; and both mechanisms eventually lead to the reduction in polysorbate concentration. Therefore, the purpose of the current study was to compare various molecules for their capabilities to reduced agitation-induced protein aggregation and particle formation; and furthermore, investigate their underlying protein stabilizing mechanisms.
The Viscosity Reduction Platform: Viscosity Reducing Excipients for Protein F...MilliporeSigma
Protein viscosity is one of the major obstacles in preparing highly concentrated protein formulations suitable for subcutaneous injection.
This whitepaper examines how combining an amino acid with a second viscosity-reducing excipient circumvents adverse effects on protein stability and improves viscosity-reducing capacity.
To find more information about the Viscosity Reduction Platform, please visit our website: https://sigmaaldrich.com/products/pharma-and-biopharma-manufacturing/formulation/viscosity-reduction-platform
Characterization of monoclonal antibodies and Antibody drug conjugates by Sur...MilliporeSigma
Watch the presentation of this webinar: https://bit.ly/3Pjpjvr
Highlights of this webinar:
- Surface plasmon resonance as a powerful tool for biologic characterization including mAbs and ADCs.
- SPR allows rapid binding analysis in real time without using labels for SARS-CoV-2 receptor binding domain mutations.
- Kinetic data is indicative of possible neutralizing activity allowed assessment of neutralizing ability of therapeutic monoclonal antibodies.
- The application can provide preliminarily efficacy information and facilitated mAbs/ACDs candidate selection process
Detailed description:
Characterization of therapeutic monoclonal antibodies (mAbs) or Antibody drug conjugates (ADCs) is challenging due to their ability to bind to a variety of proteins via their Fc and Fab domains, giving rise to diverse biological functions associated with each domain. The Fc domain of mAbs interacts with Fc receptors with varying affinities, which can influence biological processes such as Complement-dependent cytotoxicity (CDC) and Antibody-dependent cellular cytotoxicity (ADCC), transcytosis, phagocytosis, and/or serum half-life.
An important characteristic of an antibody is its Fc effector function. Antibodies can be engineered to obtain desired binding of the Fc region to Fc receptors expressed on effector cells. Hence, it is crucial to evaluate the binding interaction of mAbs/ADC with Fc receptors in the early phase of drug development to understand the potential biological activity of the product in vivo.
Surface Plasmon Resonance (SPR) is a powerful technique to establish binding kinetics in real-time, label free, and high sensitivity with low sample consumption. Along with target antigen binding, it is crucial to evaluate the binding interaction of antibodies and ADCs with Fc receptors. Our SPR case studies investigated the impact on binding kinetics of ADCs with different linkers and the binding interactions of SARS-CoV-2 spike protein variants and evaluated the neutralizing ability of therapeutic mAbs. SPR characterisation can be facilitated in all stages of the product life cycle to ensure the quality and safety of mAbs and ADCs.
The Role of BioPhorum Extractables Data in the Effective Adoption of Single-U...MilliporeSigma
Regulatory expectation does require patient safety evaluations with supporting data for manufacturing components that directly come into contact with drug manufacturing process streams. Readily available extractables data can help manufacturers using singleuse technology to accelerate product qualifications, risk assessments and process optimization
This white paper guides you on how to save time and resources with supplier-provided single-use system extractables data and gives you an overview about the overall strategy for Extractables & Leachables. At the end you will find a case study.
Find more information about filters and single-use components on our website: https://www.sigmaaldrich.com/DE/en/services/product-services/emprove-program/emprove-filter-and-single-use-component-portfolio
The Future of Pharma- and Biopharmaceutical AuditsMilliporeSigma
Watch the recording of this presentation here: https://bit.ly/3zTOpe4
Detailed description:
SARS-CoV-2 showed us that technology supports us during our inspection activity even if on-site visits are not possible. Travel restrictions of various kinds will remain a risk in the future. The use of new technologies has shown that inspections and audits can be carried out despite these restrictions. We will focus on what possibilities the new technologies offer and take a look at the future of inspections and audits.
In this webinar, you will learn:
• Regulatory overview of remote audits
• The technologies needed to support the audit process
• What types of inspections are possible with the use of these technologies
• How audits may look in the future
Presented by:
Daniel Buescher, Product Manager - Digital Solutions
Moving your Gene Therapy from R&D to IND: How to navigate the Regulatory Land...MilliporeSigma
Watch the recording of this presentation here: https://bit.ly/3SqOsoP
Novel therapies, including cell and gene therapies, continue to be central to innovation in healthcare and represent the fastest growing area of therapeutic medicine. As a consequence, the number of gene therapies undergoing clinical trials has increased significantly in the last five years.
Manufacturing processes for these novel therapeutics are very complex with a high risk of contamination. Regulatory agencies world-wide have responded by issuing guidance to outline their expectations for development and manufacture of cell and gene therapies. Currently, regulatory guidance is not harmonized globally and can often lead to confusion within industry and increased risk of non-compliance.
In this webinar, we'll answer:
• Which regulatory guidelines do you need to comply for your INDs?
• When do you start implementing GMPs and validated assays?
• How do you get your QC testing strategy ‘right the first time’?
• How do you ensure testing is not your rate limiting step for the IND submission?
Presented by:
Manjula Aysola, Senior Regulatory Consultant
Dr. Alison Armstrong, Sr. Director, Technical and Scientific Solutions
Identity testing by NGS as a means of risk mitigation for viral gene therapiesMilliporeSigma
Watch the presentation of this webinar here: https://bit.ly/3RijkHC
Detailed description:
Imagine you’ve just completed a manufacturing run for your viral vector. Identity testing is performed to confirm the vector sequence. But when the results come back the data reveals unexpected sequence variants! With an appropriate risk mitigation testing strategy, this situation can be prevented.
The situation described above is not hypothetical, and happens more that you think, costing valuable time and resources.
Investigatory testing has shown that sequence variants present in starting materials (e.g. plasmids) are likely to make their way to the final product. Adequate identification of low-level variants with an appropriately sensitive method is critical in ensuring the quality of the final product. A risk-based testing strategy, in the context of identity, for viral vector manufacturing will be presented, focusing on key testing points. NGS assays for identity and variant detection will be highlighted due to their extremely sensitive nature compared to traditional approaches.
In this webinar, we'll explore:
• Regulatory requirements for identity testing
• NGS applications for identity testing as compared to traditional methods
• A case study on the impact of not establishing a proper risk-based testing strategy
Presented by: Bradley Hasson, Director of Lab Operations for NGS Services
Latest advancements of melt based 3D printing technologies for oral drug deli...MilliporeSigma
Watch the presentation of this webinar here: https://bit.ly/3A2WcH4
The application of polymer excipients in 3D printing manufacturing is usually limited due to the concerns of filament strength, high processing temperature and large scale manufacturing.
Latest technology developments are targeting a direct melt deposition to simplify the process and enable a constant and efficient process. Two different processing approaches will be presented:
The advanced melt drop deposition, where individual three dimensional geometries can be created by depostition of polymer droplets and the MED® 3D printing technology which allows by precise layer-by-layer deposition to produce objects with well-designed geometric structures.
In this webinar, you will learn:
• Latest advancements of melt based 3D printing approaches
• Application examples for the individual technologies
• Deep dive in the MED® 3D printing technology to design dedicated drug release profiles
Presented by:
Dr. Thomas Kipping, Head of Drug Carriers
Dr. Xianghao Zuo, Deputy Director of R&D, Triastek
CAR-T Manufacturing Innovations that Work - Automating Low Volume Processes a...MilliporeSigma
Watch the presentation of this webinar here: https://bit.ly/3NDNIKe
Automated, fit-for-purpose tools are essential in CAR-T processing to support sustainable manufacturing of clinical and market-approved cell therapy products. This webinar will discuss how the ekko™ Acoustic Cell Processing System uses acoustic technology as a touchless approach to manipulate cells, enabling a modular tool across the CAR-T manufacturing workflow. Typical performance of templated ekko™ System processes for DMSO washout of leukapheresis material, low volume and high cell concentrate for electroporation preparation, and harvest of expanded T cells will be reviewed.
This webinar will also give an early glimpse at the ekko™ Select System for unmatched T cell selection.
In this webinar, you will:
• Uncover how the ekko™ System supports the broad industrialization of cell therapy, with particular focus on how to achieve low volume, high concentrate cell product for critical transduction and transfection steps
• Discover how ekko™ System for wash and concentrate processes throughout the cell therapy workflow achieve high cell recovery, viability, and effective residual removal
• Preview to ekko™ Select, our cell therapy selection platform, to achieve unmatched ease-of-use with direct processing from leukopaks reducing the need for preparation steps
Presented by:
Benjamin Ross-Johnsrud, Acoustic Technology Expert
Robert Scott, Mechanical Engineer III
How does the ICH Q5A revision impact viral safety strategies for biologics?MilliporeSigma
Watch the presentation of this webinar here: https://bit.ly/3t7X9tg
How does the ICH Q5A revision impact viral safety strategies for biologics?
Biologics continue to grow at a fast pace. Manufactured using cell lines of human or animal origin, these are at risk of viral contamination making safety strategies critical. A comprehensive risk mitigation strategy using multiple orthogonal measures is a regulatory expectation. ICH Q5A, the globally-harmonized guideline outlines the expectations. ICH Q5A is currently being revised to address recent scientific advancements including novel therapeutic modalities, new manufacturing paradigms, updates in viral clearance applications, and alternate detection technologies. We’ll discuss the expected changes and potential impact on viral safety strategies with case studies and examples.
In this webinar, you will learn about:
• The Importance of virus testing in biologics products
• Regulatory landscape, expectations for the Q5A revision
• What's new and changing
• Examples of alternate testing schedules, impact on viral clearance
Presented by:
Manjula Aysola, Senior Regulatory Consultant
Alison Armstrong, PhD, Sr. Director, Technical and Scientific Solutions
Improve Operational Efficiency by Over 30% with Product, Process, & Systems A...MilliporeSigma
Watch the presentation of this webinar here: https://bit.ly/3adaxWh
When implementing new automation systems, organizations must consider things like deployment time, user adoption, and costs.
They must also consider the cost of doing nothing – that is, what competitive advantage is lost in standing still? What time and quality is lost in repetitive, manual tasks rather than an automated, digital workflow? What operational efficiencies are lost?
In this webinar we examine how a product, process, and system agnostic automation platform can be deployed faster than traditional system specific software while bringing greater operational efficiencies (in many cases over 30% improvement).
To remain competitive in the market, biopharma manufacturers must adopt automation and digital technologies, but most plants still have island of automation consisting of independently functioning, standalone unit operations. This results in operational inefficiency, regulatory concerns, and a poor understanding of the process and product life cycle.
Taking the first, right step must include considering risks, costs, timelines, and technology alternatives. Traditional automation approaches tied to specific systems, processes, and products are, by their nature, limited; while an agnostic platform will address current biomanufacturing business challenges and ensure future readiness. With the right platform, a phased automation implementation can yield operational efficiency gains of up to 30% and improved product quality and regulatory compliance.
In this webinar, let's explore:
• Challenges of automation and digital technology adoption
• What a product, process, and system agnostic platform entails
• Applications and benefits of a process orchestration platform
• Ensuring future readiness with process orchestration
Presented by:
Braj Nandan Thakur, Global Product Manager - Automation
Insights from a Global Collaboration Accelerating Vaccine Development with an...MilliporeSigma
Watch the presentation of this webinar here: https://bit.ly/3Nbb5ug
Get insights and best practices from a multinational team establishing a platform for vaccine production. See how a long-term collaboration on a bench-scale process used to produce a Virus Like Particle (VLP) vaccine for SARS-CoV-2 was successfully converted to a robust GMP-compatible, scalable process.
The COVID-19 pandemic further emphasized the need for collaboration in the development of urgently needed vaccines and therapeutics. In this webinar, we take you behind the scenes of our collaboration with Technovax and Innovative Biotech in which a scalable VLP vaccine platform was optimized for use in a production facility in Nigeria in response to the need for local production of SARS-CoV-2 vaccines. The flexibility and robustness of the platform will enable its rapid deployment to support the West African pandemic readiness program. Initial development of the VLP process began in late 2019 and by March 2020, was already adapted for production of a SARS-CoV-2 vaccine.
In this webinar, you will learn:
• About building a priceless collaborative network with integrated solutions
• Virus-Like Particle Vaccines
• Process Development Overview and Challenges
• Pre-clinical Results and Next Steps
Presented by:
Jose M. Galarza, PhD,
President and Founder of TechnoVax
Naomi Baer,
Business development consultant, Emerging Biotech, BioProcess division
Youssef Gaabouri, Eng. ,
Associate Director, Head of Sales Middle East & Africa, BioProcess division
Risk-Based Qualification of X-Ray Sterilization for Single-Use SystemsMilliporeSigma
Watch the presentation of this webinar here: https://bit.ly/3vQf0qv
In the single-use bioprocess industry, X-ray irradiation warrants consideration as an alternate sterilization technology. Using a risk-based qualification testing strategy is important when evaluating and implementing equivalent ionizing irradiation sterilization methods.
The urgent need for life-saving therapies as a result of the global pandemic has reinforced the criticality of flexibility in pharmaceutical manufacturing, including sterilization. The single-use bioprocess industry traditionally has employed gamma irradiation sterilization. X-ray irradiation is being considered as an additional sterilization technology for business and supply continuity. We will share a risk-based qualification testing strategy including Extractables and data generated to support comparability of gamma irradiation and X-ray irradiation as equivalent ionizing irradiation sterilization methods.
In this webinar, you will learn about:
• The comparison of gamma and X-ray irradiation sterilization
• A risk-based qualification test strategy
• Data evaluation of gamma versus X-ray sterilized single-use components
Presented by:
Monica Cardona,
Global Senior Program Manager
Paul Killian, Ph.D.,
R&D Director, Analytical Technologies
Rapid Replication Competent Adenovirus (rRCA) Detection: Accelerate your Lot ...MilliporeSigma
Watch the presentation of this webinar here: https://bit.ly/3MJ4u9V
Testing for presence of replication competent adenovirus (RCA) is a key component to ensure patient safety and a requirement for all biologicals manufactured using adenoviral vectors. For many adenoviral-based products, the RCA assay is a rate-limiting assay for lot release.
Join this webinar to learn about a rapid RCA detection assay currently in development, which combines a 7-day culture assay with a highly sensitive molecular endpoint specific for RCA. The method can detect presence of as little as 1 RCA in adenoviral vector material at an approximate concentration of 5x107 - 2x108 vector particles (VP)/mL, making it a suitable method to meet regulatory requirements while accelerating your lot release timelines.
In this webinar, you will learn about:
• Regulatory framework for adenoviral vector products
• Considerations for lot release testing of adenoviral-based therapies
• Advantages of a rapid method for RCA testing on production lot material
Presented by:
Axel Fun, Ph.D.,
Principal Scientist
Alberto Santana, MBA,
Product Manager, Biologics Biosafety Testing
The High Intensity Sweeteners Neotame and Sucralose: 2 Ways to ace the Patien...MilliporeSigma
Watch the presentation of this webinar here: https://bit.ly/3vQyN7K
Bitter medicines are an important issue, especially for pediatric applications. As several APIs have bitter tasting components, high intensity sweeteners for taste optimization are of great interest. Join our webinar to discover our new sweetener toolbox enabling safe and stable formulations.
Mask bitter aftertaste for a sweeter pill to swallow! Patients’ compliance and the therapeutic benefit are supported by a pleasant taste of pharmaceutical formulations. With the high intensity sweeteners Neotame and Sucralose, you have efficient tools at hand which are superior to other sweeteners in many aspects:
• excellent sugar-like taste profile
• outstanding sweetness factors
• use effectiveness
• enhanced stability
We will present our new toolbox of two high performance sweeteners and focus on aspects of stability, safety, the application in various dosage forms, and market perception.
In this webinar, you will learn:
• How to optimize the patients' taste experience of your pharmaceuticals
• How sweeteners can be differentiated by their sensory profiles and features
• How our new product offering Neotame can be effectively used in your targeted formulations
Presented by:
Almut von der Brelie,
Senior Manager Strategic Marketing, Excipients for Solid Applications
The Developability Classification System (DCS): Enabling an Optimized Approac...MilliporeSigma
This whitepaper by Dr. Daniel Joseph Price outlines how poorly soluble drug formulations can be designed using the developability classification system (DCS).
The DCS identifies the root cause of low solubility and enables lean, cost-effective and effective formulations to be developed.
#solubility #pharmaceuticalmanufacturing #oralsoliddosage #drugdevelopment
How to Accelerate and Enhance ADC TherapiesMilliporeSigma
In this webinar, you will learn about:
The advantages of using advanced intermediates to develop ADC therapies
How to increase ADC solubility and efficiency
Fast, small-scale ADC library generation
Seamless supply chain with reduced complexity and regulatory support
The ADCore product line offers versatile intermediates that simplify the synthesis of common ADC payloads (dolastatins, maytansinoids, and PBDs) by greatly reducing the number of synthetic steps. This translates to savings in development and manufacturing costs and shorter timelines to the clinic. To address the poor solubility of many ADC payloads, ChetoSensar™ was developed to significantly increase the hydrophilicity of the drug linker, which has been shown to also substantially increase the efficacy of ADCs and broaden the therapeutic window.
Lastly, the ADC Express™ service leverages conjugation chemistry and analytical expertise to help design and quickly synthesize sets of potential ADC therapies suitable for screening to simplify candidate selection and get ADC therapies to market faster.
India Clinical Trials Market: Industry Size and Growth Trends [2030] Analyzed...Kumar Satyam
According to TechSci Research report, "India Clinical Trials Market- By Region, Competition, Forecast & Opportunities, 2030F," the India Clinical Trials Market was valued at USD 2.05 billion in 2024 and is projected to grow at a compound annual growth rate (CAGR) of 8.64% through 2030. The market is driven by a variety of factors, making India an attractive destination for pharmaceutical companies and researchers. India's vast and diverse patient population, cost-effective operational environment, and a large pool of skilled medical professionals contribute significantly to the market's growth. Additionally, increasing government support in streamlining regulations and the growing prevalence of lifestyle diseases further propel the clinical trials market.
Growing Prevalence of Lifestyle Diseases
The rising incidence of lifestyle diseases such as diabetes, cardiovascular diseases, and cancer is a major trend driving the clinical trials market in India. These conditions necessitate the development and testing of new treatment methods, creating a robust demand for clinical trials. The increasing burden of these diseases highlights the need for innovative therapies and underscores the importance of India as a key player in global clinical research.
CHAPTER 1 SEMESTER V - ROLE OF PEADIATRIC NURSE.pdfSachin Sharma
Pediatric nurses play a vital role in the health and well-being of children. Their responsibilities are wide-ranging, and their objectives can be categorized into several key areas:
1. Direct Patient Care:
Objective: Provide comprehensive and compassionate care to infants, children, and adolescents in various healthcare settings (hospitals, clinics, etc.).
This includes tasks like:
Monitoring vital signs and physical condition.
Administering medications and treatments.
Performing procedures as directed by doctors.
Assisting with daily living activities (bathing, feeding).
Providing emotional support and pain management.
2. Health Promotion and Education:
Objective: Promote healthy behaviors and educate children, families, and communities about preventive healthcare.
This includes tasks like:
Administering vaccinations.
Providing education on nutrition, hygiene, and development.
Offering breastfeeding and childbirth support.
Counseling families on safety and injury prevention.
3. Collaboration and Advocacy:
Objective: Collaborate effectively with doctors, social workers, therapists, and other healthcare professionals to ensure coordinated care for children.
Objective: Advocate for the rights and best interests of their patients, especially when children cannot speak for themselves.
This includes tasks like:
Communicating effectively with healthcare teams.
Identifying and addressing potential risks to child welfare.
Educating families about their child's condition and treatment options.
4. Professional Development and Research:
Objective: Stay up-to-date on the latest advancements in pediatric healthcare through continuing education and research.
Objective: Contribute to improving the quality of care for children by participating in research initiatives.
This includes tasks like:
Attending workshops and conferences on pediatric nursing.
Participating in clinical trials related to child health.
Implementing evidence-based practices into their daily routines.
By fulfilling these objectives, pediatric nurses play a crucial role in ensuring the optimal health and well-being of children throughout all stages of their development.
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.
Struggling with intense fears that disrupt your life? At Renew Life Hypnosis, we offer specialized hypnosis to overcome fear. Phobias are exaggerated fears, often stemming from past traumas or learned behaviors. Hypnotherapy addresses these deep-seated fears by accessing the subconscious mind, helping you change your reactions to phobic triggers. Our expert therapists guide you into a state of deep relaxation, allowing you to transform your responses and reduce anxiety. Experience increased confidence and freedom from phobias with our personalized approach. Ready to live a fear-free life? Visit us at Renew Life Hypnosis..
QA Paediatric dentistry department, Hospital Melaka 2020Azreen Aj
QA study - To improve the 6th monthly recall rate post-comprehensive dental treatment under general anaesthesia in paediatric dentistry department, Hospital Melaka
How many patients does case series should have In comparison to case reports.pdfpubrica101
Pubrica’s team of researchers and writers create scientific and medical research articles, which may be important resources for authors and practitioners. Pubrica medical writers assist you in creating and revising the introduction by alerting the reader to gaps in the chosen study subject. Our professionals understand the order in which the hypothesis topic is followed by the broad subject, the issue, and the backdrop.
https://pubrica.com/academy/case-study-or-series/how-many-patients-does-case-series-should-have-in-comparison-to-case-reports/
Leading the Way in Nephrology: Dr. David Greene's Work with Stem Cells for Ki...Dr. David Greene Arizona
As we watch Dr. Greene's continued efforts and research in Arizona, it's clear that stem cell therapy holds a promising key to unlocking new doors in the treatment of kidney disease. With each study and trial, we step closer to a world where kidney disease is no longer a life sentence but a treatable condition, thanks to pioneers like Dr. David Greene.
Leading the Way in Nephrology: Dr. David Greene's Work with Stem Cells for Ki...
Bioburden control: Strategies to address bioburden control in downstream processing
1. Merck KGaA
Darmstadt, Germany
April 30, 2020
Somasundaram Gopalakrishnan
Senior Technical Consultant Asia Pacific
Technology Management, Process Solutions
Strategies to Address
Bioburden Control in
Downstream Processing
2. Strategies to Address Bioburden Control in Downstream Processing
The life science business of
Merck KGaA, Darmstadt, Germany
operates as MilliporeSigma
in the U.S. and Canada.
3. Objectives
1 Understand the impact of
bioburden excursions
2 Recognize sources of
bioburden
3 Develop strategies to
mitigate risk
Strategies to Address Bioburden Control in Downstream Processing
5. 30
Percent
1- 6Months
1-14Million Euro
Percent of process deviations
caused by contamination*
Length of time to complete
an investigation
Operations cost
*Sources Langer 2013, Wiebe 2014
Biologics in-process contamination
Strategies to Address Bioburden Control in Downstream Processing
6. 30
Percent
1- 6Months
1-14Million Euro
*Sources Langer 2013, Wiebe 2014
Biologics in-process contamination
Impact
Productivity losses
Material replacement costs
Batch loss
Interruption of product supply
Delay in clinical development
Strategies to Address Bioburden Control in Downstream Processing
9. Facility & Environment
Equipment
Processes
Materials
Utilities
Personnel
Each source
contributes
to the
process
bioburden
profile
Sources of bioburden
Origin?
Staphylococcus
Bacillus
Non-fermenting
Gram Negative rods
Aspergillus
Source: Public domain CDC/
Robert Simmons
Strategies
to Address
Bioburden
Control in
Downstream
Processing
10. Downstream
Where?
Risk profile and control strategies differ throughout the process
Secondary
Clarification
Chromatography
Protein A
Final FillingFinal Sterile
Filtration
Concentration
& Formulation
Bulk Storage
and Transport
Viral
Inactivation
Chromatography
CEX
Virus Filtration
Clearance
Ultrafiltration /
Diafiltration
Bioreactor
Primary
Clarification
MCB WCB Seed Train
Raw Materials
Filtration Bioburden
Reduction
Bioburden
Reduction
Chromatography
AEX
Bioburden
Reduction
Bioburden
Reduction
Final Fill
Risk Areas
Upstream
Downstream
Strategies to Address Bioburden Control in Downstream Processing
11. Case Study
Bioburden excursions in the Protein A Pool
Chrom
Protein A
Bulk
Storage and
Transport
Viral
Inactivation
Chrom
CEX
Virus
Filtration
Clearance
Ultrafiltration
Diafiltration
Bioburden
Reduction
Bioburden
Reduction
Chrom
AEX
Bioburden
Reduction
Bioburden
Reduction
Situation
• Spore-forming bioburden alert-level excursions in the
Protein A pool over several campaigns
Root Cause
• Failure to recognize a trend in the pattern of excursions
• Sanitization solution was not sporicidal
• Sub-optimal sanitization process
Corrective and Preventative Actions
• Scale down studies with a new sanitizer and
optimization of sanitization conditions
• Process scale verification
Strategies to Address Bioburden Control in Downstream Processing
12. Case Study
Bioburden action-level excursions in the UF/DF step
Chrom
Protein A
Bulk
Storage and
Transport
Viral
Inactivation
Chrom
CEX
Virus
Filtration
Clearance
Ultrafiltration
Diafiltration
Bioburden
Reduction
Bioburden
Reduction
Chrom
AEX
Bioburden
Reduction
Bioburden
Reduction
Situation
• Bioburden and endotoxin exceeded action levels in
multiple batches
• Intensive investigation of the process and support areas
Root Cause
• Bioburden formation in the TFF cassettes due to inadequate
cleaning and storage processes
Corrective and Preventative Actions
• Improve cleaning and storage processes
• Sterilization or sanitization of buffer tanks
• Assessment of the water for injection (WFI) system and
transfer lines
• Introduction of bioburden reducing filters
• Validation of hold times and storage conditions
• Revision of bioburden limits based on process capability
Buffer, Sanitizer, and
Storage Solutions
Operations
WFI
Operation
Suvarna K. et. al. “Case Studies of Microbial Contamination in Biologic Product”,
American Pharmaceutical Review 14(1) January/February 2011.
Strategies to Address Bioburden Control in Downstream Processing
13. Case Study
Sporadic bioburden action-level excursions
Chrom
Protein A
Bulk
Storage and
Transport
Viral
Inactivation
Chrom
CEX
Virus
Filtration
Clearance
Ultrafiltration
Diafiltration
Bioburden
Reduction
Bioburden
Reduction
Chrom
AEX
Bioburden
Reduction
Bioburden
Reduction
Situation
• Sporadic mixed bioburden excursions at multiple
points in the downstream process
Root Cause
• Aseptic connections of equipment and sampling devices
Corrective and Preventative Actions
• Short term:
• Retrained operators in aseptic techniques
• Long term:
• Reduced the number of aseptic connections
• Implemented sterile to sterile connectors and steam
to sterile connectors.
• Introduced a facility-wide sterile sampling system
Strategies to Address Bioburden Control in Downstream Processing
14. Case Study
Bulk solution contamination with Bacillus species
Chrom
Protein A
Bulk
Storage and
Transport
Viral
Inactivation
Chrom
CEX
Virus
Filtration
Clearance
Ultrafiltration
Diafiltration
Bioburden
Reduction
Bioburden
Reduction
Chrom
AEX
Bioburden
Reduction
Bioburden
Reduction
Situation
• Prefiltration bioburden load was 20 x the
specification
• Bacillus species suggested a steam-in-place issue
Root Cause
• Equipment design: improper pipe slope resulted in
cold spots that were insufficiently sterilized
Corrective and Preventative Actions
• Discard (scrap) the batch
• Redesign piping
• Requalify SIP (steam-in-place) cycle
• New processes will use single-use storage systems
Strategies to Address Bioburden Control in Downstream Processing
15. Many routes for microbial ingress
Downstream bioburden excursions are often the result of
Improper cleaning, storage, or sanitization
Suboptimal system design
Aseptic connections
Sampling
Lapses in aseptic technique
Intensive risk assessments could have prevented many of these
contaminations or excursions
Key Points
Sources of bioburden
Strategies
to Address
Bioburden
Control in
Downstream
Processing
18. The risk profile varies from upstream to final fill
Risk Hammock
Upstream Downstream Finish and Fill
Operations
Risk
High
Low
Aseptic AsepticBioburden Controlled
“The level of effort, formality and
documentation of the quality risk
management process should align
with the level of risk”
(ICH Q9A)
Strategies
to Address
Bioburden
Control in
Downstream
Processing
20. Microbiological Profile
Get to know the bioburden in your neighborhood
Who are
we?
How many
of us? Will we cause
you
trouble?
Where are
we
from?
Strategies to Address Bioburden Control in Downstream Processing
21. Focus Objective
Fault
Tree
Analysis
FMEA HACCP
Statistical
Methods
Ishekawa
(Fish
Bone)
Risk
Assessment
Risk Identification
Risk Analysis
Risk Evaluation X
Risk
Control
Risk Reduction X X
Risk Acceptance X X
Risk Review X
Risk Communication X X
Characterize Process Risk
Multiple tools are available
Adapted from Roenninger S., Hertlein M. “Which Risk assessment fits best?”
Logfile No 15 November 2011 1-4 Maas & Peither AG GMP Publishing
Very suitable
Limited suitability
X Not suitable
Strategies
to Address
Bioburden
Control in
Downstream
Processing
22. What parts of the process could
introduce bioburden?
(Hu)Man Mother Nature Material
MethodMachine
Hygiene
Training
Air Handling Water
Sanitizers
Disinfectants
Buffers
Chromatography
Gaskets
Water System
Storage Buffer
Load cells
Mixer
Mixing
Compounding
Hold Time
Room Cleaning
Transfer
Transfer
Testing
Sampling
Weighing
Measurement
Calibration
Microscopy
Humidity
Tubing / Piping
Filters
Resin
Tanks
Pump
Transfer Panel
Steam Generator
Aseptic Technique
Clean room
Filtration
Pump
Air compressor
Pressure
Flow Rate
Time
Temperature
Enumeration
Insects
Animals i.e. Rodents
Microorganisms
Mass
Columns
Experience
ChromatogramData Acquisition
Packing Installing
Bioburden profile
Strategies to Address Bioburden Control in Downstream Processing
23. CMC Biotech Working Group: A-Mab: A case Study in Bioprocess Development
Score
• Probability of occurrence
• Severity
• Ability to detect
• Criticality
Prioritize
How can I put the risks into
perspective?
Strategies to Address Bioburden Control in Downstream Processing
24. Key Points
Characterize the microbial profile of the process
Utilize a combination of assessment tools
A cross-functional team is crucial to the process
Your bioburden risk mitigation strategy should address
Patient safety
Drug supply
Business risk
Assess Risks
Strategies to Address Bioburden Control in Downstream Processing
26. Bioburden profile
What microorganisms are present?
How many?
Variation over time?
Toxin producing?
Spore formers?
Material Origin
Material consistency
Supplier transparency
Quality management system
Quality philosophy
Material Characteristics
Growth Promoting
Bacteriostatic
Bactericidal
Risk Mitigation
Material Considerations
Mitigate
Strategies to Address Bioburden Control in Downstream Processing
27. Risk
Cell disruption results in byproducts
Sanitizer Modes of Action
Bacterial spores
• Spore coat penetration
Vegetative bacteria
• Cell wall and cytoplasmic disruption
Fungi
• Cell wall and cytoplasmic disruption
Virus
• Capsid and nucleic acid damage
Risk Mitigation Sanitization and Storage
Modes of action of sanitizers
Reduce bioburden load
Material selection
Containment
• Single-use
• Closed sampling
• Pre-packed columns
Removal
• Filtration
Mitigate
Strategies to Address Bioburden Control in Downstream Processing
28. Prevent Contamination by Containment
Implement Single-use Systems and Closed Sampling
Eliminate
bioburden
contribution
Prevent
microbial
ingress
Minimize
process
validation
Mitigate
Strategies to Address Bioburden Control in Downstream Processing
29. Upstream Process
Bioreactor protection
Drug supply continuity
Business risk mitigation
Downstream Process
Bioburden Reduction
Assure drug substance purity
Final Fill
Regulatory requirements
Drug product sterility assurance
Assure patient safety
What is your objective?
Risk-based filter selection What filtration option is best
for my process?
Strategies to Address Bioburden Control in Downstream Processing
30. Goal: Minimize in-process bioburden
• No requirement to validate sterility
• Reduce bioburden proliferation
• With other controls, bioburden reduction
filters may provide sufficient process safety
• Prefiltration can increase filter capacity and
improve efficiency
Bioburden reduction filters (0.45 or 0.2 m)
• May be sufficient for intermediate processing steps
• May be used as prefilters upstream of sterilizing-
grade filters
• Manufacturers may validate bacterial reduction, but
not sterilizing performance
Sterilizing-grade rated filters (0.2 m)
Manufacturers must validate bacterial removal
Traditionally used for intermediate processing steps
Downstream Filtration
Minimize Bioburden What filtration option is best for
my downstream process?
Strategies to Address Bioburden Control in Downstream Processing
31. Mitigate Risks
Key Points
A downstream bioburden control risk mitigation strategy addresses
drug supply continuity, business risk, and patient safety
The act of sanitization, while effective, can release microbial
byproducts into the process
Single-use systems prevent microbial ingress and reduce bioburden
contribution
Closed sterile sampling prevents false-positive tests
Filtration choice is dependent upon risk assessment, capacity, and
cost per liter
Mitigate
Strategies to Address Bioburden Control in Downstream Processing
33. Downstream Monitoring
What do I test for? Where? Why?
Chromatography
Protein A
Bulk Storage
and Transport
Viral
Inactivation
Chromatography
CEX
Virus Filtration
Clearance
Ultrafiltration /
Diafiltration
Bioburden
Reduction
Bioburden
Reduction
Chromatography
AEX
Bioburden
Reduction
Bioburden
Reduction
Bioburden
Virus
Mycoplasma
Endotoxin
V
M
B
E
B
E
B
E
B
E
V
E
V
E
B
E
B
E
M
Monitor
Strategies to Address Bioburden Control in Downstream Processing
34. Monitor
How much is too much?
“Unlike non-sterile dosage forms, there are no recommended bioburden levels provided in
regulatory guidelines or compendia for the [downstream] protein purification processes of
biologic or other biopharmaceutical products, therefore, manufacturers are responsible for
setting bioburden control levels for biologic production processes.”
“The BPOG Bioburden Working Group conducted a member survey of bioburden action levels
and found that the majority of biologic processes action levels were set between 1-10
CFU/mL.”
Bain, D. “Microbial Monitoring For Biological Drug Substance Manufacturing: An Industry Perspective”
BioPhorum Operations Group. 2015.
Strategies to Address Bioburden Control in Downstream Processing
35. Downstream processing is considered a low-bioburden controlled
process
Bioburden monitoring is a supporting tool in a risk mitigation
strategy
Appropriately set action and alert levels coupled with data trending
permit timely responses
Key Points
Mitigation Strategy
Monitor
Strategies to Address Bioburden Control in Downstream Processing
37. Strategies to address bioburden control in downstream processing
Final Points
Bioburden excursions present real and under-appreciated risks
For every publically disclosed contamination event, there are countless others
Implications of bioburden excursions can be significant
Investigational and decontamination costs, production downtime, lost revenues due to drug
stock-out, regulatory fines, loss of consumer confidence
Multiple approaches are needed to provide the required control
Low bioburden processes require as much attention as sterile processes.
A robust risk mitigation strategy uses a three-pronged approach of
Risk assessment
Mitigation
Monitoring
Strategies to Address Bioburden Control in Downstream Processing
38. Langer, E. “Biopharm Shows Signs of Maturity”. Pharmaceutical Manufacturing, in: Biopharmaceutical manufacturing Excellence Within a
Rapidly Changing Landscape, pp 20-25, 2013. Link
Wiebe, M. “Update on the CAACB Virus Contamination Project”. presented at 2014 PDA/FDA Virus & TSE Safety Conference 2014.
von Wintzingerode, V. “Biologics Production: Impact of Bioburden Contaminations of Non-Sterile Process Intermediates on Patient Safety and
Product Quality”. American Pharmaceutical Review. 20(3). April 2017. Link
Suvarna K. et. al. “Case Studies of Microbial Contamination in Biologic Product”, American Pharmaceutical Review 14(1) January/February
2011. Link
K. Suvarna “Case Studies of Microbial Contamination in Biologic Product” presented at PDA 5th Annual Global Conference on Pharmaceutical
Microbiology, October 2010.
Roenninger S., Hertlein M. “Which Risk assessment fits best?” Logfile No 15 November 2011 1-4 Maas & Peither AG GMP Publishing.
Oliver J. “3D risk assessment model”, Journal of Validation Technology, Autumn 2008, page 70-76. Link
Bain, D. “Microbial Monitoring For Biological Drug Substance Manufacturing: An Industry Perspective” BioPhorum Operations Group. 2015.
Link
CMC Biotech Working Group: A-Mab: A case Study in Bioprocess Development. Link
PDA, “Technical Report No. 69 Bioburden and Biofilm Management in Pharmaceutical Manufacturing Operations. Parenteral Drug Association.
2015.
Strategies to address bioburden control in downstream processing
Recommended Reading
Strategies
to Address
Bioburden
Control in
Downstream
Processing
39. Acknowledgments
• Kerry Roche Lentine, Director, Technology Management, Global Growth Programs
Strategies to Address Bioburden Control in Downstream Processing