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.
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.
EU GMP Annex 1 – Implications on Filtration and Single Use Technology by Soma...Merck Life Sciences
What are the major drivers for the new Annex 1? Join us to know more about implications for Filters & Single Use.
In this webinar, you will learn:
• Closed Processing and Single Use Technology implementation
• Points to consider using Single Use Technology
• Sterile Filtration
The Annex 1 “Manufacture of sterile medicinal products” of the EU GMP Guide is currently being revised. A first draft of the revised version was published in 2017 and released for public comment. The second draft as of February 2020 was open for targeted consultation via stakeholder from selected industry organisations. The current Annex 1 draft emphasises Contamination Control Strategy (CCS) multiple times and as a key consideration.
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
EU GMP Annex 1 Draft - Closed System Design Consideration with Single-Use Sys...MilliporeSigma
Biopharmaceutical manufacturing capacities have expanded dramatically which has resulted in an increased demand for single-use systems (SUS) as they have their own advantages. Although SUS are well established in the biopharmaceutical industry there is limited guidance on regulatory expectations. Please attend the webinar to learn more!
Quality by Design Principles Applied to Sterilizing Filtration by Michael PayneMerck Life Sciences
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.
EU GMP Annex 1 – Implications on Filtration and Single Use Technology by Soma...MilliporeSigma
What are the major drivers for the new Annex 1? Join us to know more about implications for Filters & Single Use.
In this webinar, you will learn:
• Closed Processing and Single Use Technology implementation
• Points to consider using Single Use Technology
• Sterile Filtration
The Annex 1 “Manufacture of sterile medicinal products” of the EU GMP Guide is currently being revised. A first draft of the revised version was published in 2017 and released for public comment. The second draft as of February 2020 was open for targeted consultation via stakeholder from selected industry organisations. The current Annex 1 draft emphasises Contamination Control Strategy (CCS) multiple times and as a key consideration.
What is likely to go into the revised Annex 1, including:
Terminal sterilisation vs aseptic processing
WFI produced by reverse osmosis
Guidance for media simulation trials
This remains speculative
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
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.
EU GMP Annex 1 – Implications on Filtration and Single Use Technology by Soma...Merck Life Sciences
What are the major drivers for the new Annex 1? Join us to know more about implications for Filters & Single Use.
In this webinar, you will learn:
• Closed Processing and Single Use Technology implementation
• Points to consider using Single Use Technology
• Sterile Filtration
The Annex 1 “Manufacture of sterile medicinal products” of the EU GMP Guide is currently being revised. A first draft of the revised version was published in 2017 and released for public comment. The second draft as of February 2020 was open for targeted consultation via stakeholder from selected industry organisations. The current Annex 1 draft emphasises Contamination Control Strategy (CCS) multiple times and as a key consideration.
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
EU GMP Annex 1 Draft - Closed System Design Consideration with Single-Use Sys...MilliporeSigma
Biopharmaceutical manufacturing capacities have expanded dramatically which has resulted in an increased demand for single-use systems (SUS) as they have their own advantages. Although SUS are well established in the biopharmaceutical industry there is limited guidance on regulatory expectations. Please attend the webinar to learn more!
Quality by Design Principles Applied to Sterilizing Filtration by Michael PayneMerck Life Sciences
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.
EU GMP Annex 1 – Implications on Filtration and Single Use Technology by Soma...MilliporeSigma
What are the major drivers for the new Annex 1? Join us to know more about implications for Filters & Single Use.
In this webinar, you will learn:
• Closed Processing and Single Use Technology implementation
• Points to consider using Single Use Technology
• Sterile Filtration
The Annex 1 “Manufacture of sterile medicinal products” of the EU GMP Guide is currently being revised. A first draft of the revised version was published in 2017 and released for public comment. The second draft as of February 2020 was open for targeted consultation via stakeholder from selected industry organisations. The current Annex 1 draft emphasises Contamination Control Strategy (CCS) multiple times and as a key consideration.
What is likely to go into the revised Annex 1, including:
Terminal sterilisation vs aseptic processing
WFI produced by reverse osmosis
Guidance for media simulation trials
This remains speculative
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
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.
Potential Impact of Draft Annex 1 on Sterilizing FiltrationMilliporeSigma
Access the interactive recording here: https://bit.ly/2mvFxs7
Abstract:
The support for EMA GMPs related to sterile medicinal products is Annex 1. EMA, PICS and WHO have collaborated on the largest and most comprehensive revision of Annex 1 since it was first written in 1997.
There are a number of proposed changes to the sections in Annex 1 dealing with filtration, integrity testing and single-use.
This presentation will compare the current version with the proposed changes and highlight areas of specific interest to companies who either manufacture in or export to EMA countries, PICS member countries, and WHO compliant countries.
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
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
Corrective Actions and Preventive Actions.Corrective Action Preventive Action (CAPA) is a process which investigates and solves problems, identifies causes, takes corrective action and prevents recurrence of the root causes. The ultimate purpose of CAPA is to assure the problem can never be experienced again. Corrective vs. Preventive Action. Quality professionals frequently express confusion as to the difference between corrective and preventive action. A corrective action deals with a nonconformity that has occurred, and a preventive action addresses the potential for a nonconformity to occur.
This presentation correlates the requirements of Annex 11 guidelines to other official regulations and guidance documents.
The correlation is organized in a tabular format.
In the row lists the contents of Annex 11 together with the paragraph numbers.
Rest of the rows correlate the section numbers of
Annex 11 Versions 1993
US FDA 21 CFR Part 211
US FDA Part 820 and
US FDA 21 CFR Part 11
EU GMP Annex 1 Draft - Closed System Design Consideration with Single-Use Sys...Merck Life Sciences
Biopharmaceutical manufacturing capacities have expanded dramatically which has resulted in an increased demand for single-use systems (SUS) as they have their own advantages. Although SUS are well established in the biopharmaceutical industry there is limited guidance on regulatory expectations. Please attend the webinar to learn more!
A vendor audit is a vehicle used by pharmaceutical companies, and other large companies as well, to inspect and evaluate a vendor’s quality management system, as well as its practices, products, and documentation.
The need to conduct vendor audits stems from a higher need for quality control in an industry that needs to be more regulated than any other industry in the world.
Reason why organizations use audits is to reduce cost and improve quality control
The objective of vendor audit is to develop an audit function comprising of qualified resources to effectively perform compliance audits to ensure that the contracts are being executed in accordance with the intent and address the net benefit to include cost recoveries, process improvement savings, fraud improvement and identification of hidden risks.
In order to reduce the cost pharmaceutical companies have increasingly become dependent on their supplier/ out sourcing partners for customer success. Though it has drastically reduced the production cost for companies, there is a heightened supplier risk and lack of visibility into supplier processes.
To gain an insight into supplier process and eliminate the risks, FDA encourages companies to conduct GMP supplier audit at the manufacturing premises of the supplier.
According to GMP code, it is sole responsibility of pharmaceutical industry to ensure that the suppliers manufacturing process, analytical tests and examinations are carried out reliably by the supplier and are in compliances with the applicable standards and regulations.
After the audit supplier must provide an appropriate corrective action plan with measures that that will be implemented by the supplier within a defined time frame to the manufacturer.
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.
Upcoming USP 665 - Level of Characterization of Single-Use Systems Today and ...Merck Life Sciences
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 pharmaceutical Quality by Design (QbD) is a systematic approach to development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management.
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.
Potential Impact of Draft Annex 1 on Sterilizing FiltrationMilliporeSigma
Access the interactive recording here: https://bit.ly/2mvFxs7
Abstract:
The support for EMA GMPs related to sterile medicinal products is Annex 1. EMA, PICS and WHO have collaborated on the largest and most comprehensive revision of Annex 1 since it was first written in 1997.
There are a number of proposed changes to the sections in Annex 1 dealing with filtration, integrity testing and single-use.
This presentation will compare the current version with the proposed changes and highlight areas of specific interest to companies who either manufacture in or export to EMA countries, PICS member countries, and WHO compliant countries.
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
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
Corrective Actions and Preventive Actions.Corrective Action Preventive Action (CAPA) is a process which investigates and solves problems, identifies causes, takes corrective action and prevents recurrence of the root causes. The ultimate purpose of CAPA is to assure the problem can never be experienced again. Corrective vs. Preventive Action. Quality professionals frequently express confusion as to the difference between corrective and preventive action. A corrective action deals with a nonconformity that has occurred, and a preventive action addresses the potential for a nonconformity to occur.
This presentation correlates the requirements of Annex 11 guidelines to other official regulations and guidance documents.
The correlation is organized in a tabular format.
In the row lists the contents of Annex 11 together with the paragraph numbers.
Rest of the rows correlate the section numbers of
Annex 11 Versions 1993
US FDA 21 CFR Part 211
US FDA Part 820 and
US FDA 21 CFR Part 11
EU GMP Annex 1 Draft - Closed System Design Consideration with Single-Use Sys...Merck Life Sciences
Biopharmaceutical manufacturing capacities have expanded dramatically which has resulted in an increased demand for single-use systems (SUS) as they have their own advantages. Although SUS are well established in the biopharmaceutical industry there is limited guidance on regulatory expectations. Please attend the webinar to learn more!
A vendor audit is a vehicle used by pharmaceutical companies, and other large companies as well, to inspect and evaluate a vendor’s quality management system, as well as its practices, products, and documentation.
The need to conduct vendor audits stems from a higher need for quality control in an industry that needs to be more regulated than any other industry in the world.
Reason why organizations use audits is to reduce cost and improve quality control
The objective of vendor audit is to develop an audit function comprising of qualified resources to effectively perform compliance audits to ensure that the contracts are being executed in accordance with the intent and address the net benefit to include cost recoveries, process improvement savings, fraud improvement and identification of hidden risks.
In order to reduce the cost pharmaceutical companies have increasingly become dependent on their supplier/ out sourcing partners for customer success. Though it has drastically reduced the production cost for companies, there is a heightened supplier risk and lack of visibility into supplier processes.
To gain an insight into supplier process and eliminate the risks, FDA encourages companies to conduct GMP supplier audit at the manufacturing premises of the supplier.
According to GMP code, it is sole responsibility of pharmaceutical industry to ensure that the suppliers manufacturing process, analytical tests and examinations are carried out reliably by the supplier and are in compliances with the applicable standards and regulations.
After the audit supplier must provide an appropriate corrective action plan with measures that that will be implemented by the supplier within a defined time frame to the manufacturer.
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.
Upcoming USP 665 - Level of Characterization of Single-Use Systems Today and ...Merck Life Sciences
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 pharmaceutical Quality by Design (QbD) is a systematic approach to development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management.
009 what are the systems validation protocol methods at atl 05 28-2015atlmarketing
If your product must meet the requirements of FDA cGMP, 21 CFR 210, 211, 820, ISO-9000, ISO-13485, or MDD/93/42/EEC (for the CE Mark), there are three very critical elements you must have to be in regulatory compliance. First, you must have a sound and strong Quality Management System (QMS). This is an expression of WHAT you do (your quality policies and structure). Second, you must have reliable Standard Operating Procedures (SOP’s). These are expressions of HOW YOU DO THINGS.
Missing in the above two items is an expression of HOW WELL YOU DO WHAT YOU DO? This is where you must establish your “Systems Validation Protocol” (SVP). Your SVP is an expression of how well your system is working (for example, this can be expressed in overall product conformance percentage or in defects per million for your various products). The SVP is a living and continuous document based on your quality records. The ATL White Paper “What Are The Systems Validation Protocol Methods At ATL?” is our attempt to share with you a sound approach to Systems Validation and the various protocols that you can use.
Quality by Design (Qbd) in Product Life Cycle Management (PLCM)Dr. Girish S Sonar
This presentation will cover introduction of QbD, benefits & misconception about QbD. Nowadays, the application of QbD in the PLCM is a widely used in the pharma industry to understand product thoroughly, reduce development and post approval cost and reduce failures. The topic is emphasis on QbD element, QbD stages, Optimization studies, Quality risk management, Risk management tools, Post submission phase and their relation.
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
Concept of quality
Total Quality Management
Quality by Design
Six sigma concept
Out of specification
Change control
Introduction to ISO 9000 series of quality systems standards,
ISO 14000,
NABL
GLP
Quality-by-Design In Pharmaceutical DevelopmentPrabhjot kaur
Quality-by-Design In Pharmaceutical Development: Introduction, ICH Q8 guideline, Regulatory and industry views on QbD, Scientifically based QbD - examples of application. M. Pharmacy 2nd Semester (Computer aided drug delivery system)
Quality by Design is a systematic approach to development that begins with predefined objectives and emphasizes understanding of the product and process, efficient process control, and quality risk management to improve the overall manufacturing quality. Implementing the Quality by Design (QbD) principles in manufacturing has resulted in reduced operating costs, highly efficient manufacturing processes and better positioning companies to meet increasing regulatory expectations.
QbD explains how to prioritize process parameters for screening designs, design robust processes using statistical design of experiments (DoE), bridge the bench and the commercial design spaces using mixing and scale-up calculations, quantify process risk, select suitable process analytical technology tools (PAT) and more.
To know more about Quality by Design training worldwide,
please contact us at -
Email: support@invensislearning.com
Phone - US +1-910-726-3695,
Website: https://www.invensislearning.com
The regulatory focus of facilities that manufacture therapeutic products for humans is centered on a product-process-facility attribute driven methodology where risk identification and mitigation are critical quality attributes. Under this methodology, the manufacturing process and the product requirements, not the building, become not only the main drivers for CD efforts, but must also provide a clear approach and understanding of how the building elements must be defined and operated in order to ensure patient safety in the manufacture of the product. This requires an enterprise approach to facility design focusing on:
Process-driven understanding around operational analysis
Regulatory philosophy
Business drivers
Management needs
Integrated hand-off to detailed design activities
QbD is new concept in pharmaceutical industries which is beneficial for producing and maintaining quality in product. With help of QbD a quality is built in product during manufacturing.
Analytical Quality by Design Concise Review on Approach to Enhanced Analytica...ijtsrd
In the last few decades, the pharmaceutical industry has been rapidly progressing by focussing on various aspects of formulation and analytical development such as product Quality, Safety, and Efficacy. It is reflected through the increase in number of product development by the increased use of scientific tools such as QbD Quality by Design and PAT Process Analytical Technology . ICH guidelines Q8 to Q11 have specified QbD implementation in API synthetic process and also in formulation as well as analytical development. QbD has earned considerable reputation by formulation developers. It has enhanced the inculcation of scientific outlook and assessment of risks at an early stage. In this review, we have focussed on the implementation AQbD for API synthetic process and analytical methods development. AQbD key tools are identification of ATP Analytical Target Profile , CQA Critical Quality Attributes with risk assessment, and, MODR method operable design region . AQbD intends to provide product with highest quality through the minimisation of risks and also by providing good input for PAT approach. Thus, AQbD can act as an effective method towards innovative approach of Analytical Method Development along with meeting the necessary desired specifications. Bhosale Abhilash | Darekar Shubhangi | Dr. V. U Barge | Dr. Ashok Bhosale "Analytical Quality by Design: Concise Review on Approach to Enhanced Analytical Method Development" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-4 | Issue-3 , April 2020, URL: https://www.ijtsrd.com/papers/ijtsrd30574.pdf Paper Url :https://www.ijtsrd.com/pharmacy/other/30574/analytical-quality-by-design-concise-review-on-approach-to-enhanced-analytical-method-development/bhosale-abhilash
This document has been prepared to provide a summary on the changes between ISO 13485:2003 and ISO 13485:2016. The documents contains the following:
a. Benefits of the new version of the standard.
b. Few key definitions
c. Mapping between the versions as per ISO.org.
d. Summary of key changes between the versions of the standard
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.
Global launch of the Healthy Ageing and Prevention Index 2nd wave – alongside...ILC- UK
The Healthy Ageing and Prevention Index is an online tool created by ILC that ranks countries on six metrics including, life span, health span, work span, income, environmental performance, and happiness. The Index helps us understand how well countries have adapted to longevity and inform decision makers on what must be done to maximise the economic benefits that comes with living well for longer.
Alongside the 77th World Health Assembly in Geneva on 28 May 2024, we launched the second version of our Index, allowing us to track progress and give new insights into what needs to be done to keep populations healthier for longer.
The speakers included:
Professor Orazio Schillaci, Minister of Health, Italy
Dr Hans Groth, Chairman of the Board, World Demographic & Ageing Forum
Professor Ilona Kickbusch, Founder and Chair, Global Health Centre, Geneva Graduate Institute and co-chair, World Health Summit Council
Dr Natasha Azzopardi Muscat, Director, Country Health Policies and Systems Division, World Health Organisation EURO
Dr Marta Lomazzi, Executive Manager, World Federation of Public Health Associations
Dr Shyam Bishen, Head, Centre for Health and Healthcare and Member of the Executive Committee, World Economic Forum
Dr Karin Tegmark Wisell, Director General, Public Health Agency of Sweden
The dimensions of healthcare quality refer to various attributes or aspects that define the standard of healthcare services. These dimensions are used to evaluate, measure, and improve the quality of care provided to patients. A comprehensive understanding of these dimensions ensures that healthcare systems can address various aspects of patient care effectively and holistically. Dimensions of Healthcare Quality and Performance of care include the following; Appropriateness, Availability, Competence, Continuity, Effectiveness, Efficiency, Efficacy, Prevention, Respect and Care, Safety as well as Timeliness.
LGBTQ+ Adults: Unique Opportunities and Inclusive Approaches to CareVITASAuthor
This webinar helps clinicians understand the unique healthcare needs of the LGBTQ+ community, primarily in relation to end-of-life care. Topics include social and cultural background and challenges, healthcare disparities, advanced care planning, and strategies for reaching the community and improving quality of care.
COVID-19 PCR tests remain a critical component of safe and responsible travel in 2024. They ensure compliance with international travel regulations, help detect and control the spread of new variants, protect vulnerable populations, and provide peace of mind. As we continue to navigate the complexities of global travel during the pandemic, PCR testing stands as a key measure to keep everyone safe and healthy. Whether you are planning a business trip, a family vacation, or an international adventure, incorporating PCR testing into your travel plans is a prudent and necessary step. Visit us at https://www.globaltravelclinics.com/
Trauma Outpatient Center is a comprehensive facility dedicated to addressing mental health challenges and providing medication-assisted treatment. We offer a diverse range of services aimed at assisting individuals in overcoming addiction, mental health disorders, and related obstacles. Our team consists of seasoned professionals who are both experienced and compassionate, committed to delivering the highest standard of care to our clients. By utilizing evidence-based treatment methods, we strive to help our clients achieve their goals and lead healthier, more fulfilling lives.
Our mission is to provide a safe and supportive environment where our clients can receive the highest quality of care. We are dedicated to assisting our clients in reaching their objectives and improving their overall well-being. We prioritize our clients' needs and individualize treatment plans to ensure they receive tailored care. Our approach is rooted in evidence-based practices proven effective in treating addiction and mental health disorders.
ICH Guidelines for Pharmacovigilance.pdfNEHA GUPTA
The "ICH Guidelines for Pharmacovigilance" PDF provides a comprehensive overview of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines related to pharmacovigilance. These guidelines aim to ensure that drugs are safe and effective for patients by monitoring and assessing adverse effects, ensuring proper reporting systems, and improving risk management practices. The document is essential for professionals in the pharmaceutical industry, regulatory authorities, and healthcare providers, offering detailed procedures and standards for pharmacovigilance activities to enhance drug safety and protect public health.
Navigating Challenges: Mental Health, Legislation, and the Prison System in B...Guillermo Rivera
This conference will delve into the intricate intersections between mental health, legal frameworks, and the prison system in Bolivia. It aims to provide a comprehensive overview of the current challenges faced by mental health professionals working within the legislative and correctional landscapes. Topics of discussion will include the prevalence and impact of mental health issues among the incarcerated population, the effectiveness of existing mental health policies and legislation, and potential reforms to enhance the mental health support system within prisons.
Medical Technology Tackles New Health Care Demand - Research Report - March 2...pchutichetpong
M Capital Group (“MCG”) predicts that with, against, despite, and even without the global pandemic, the medical technology (MedTech) industry shows signs of continuous healthy growth, driven by smaller, faster, and cheaper devices, growing demand for home-based applications, technological innovation, strategic acquisitions, investments, and SPAC listings. MCG predicts that this should reflects itself in annual growth of over 6%, well beyond 2028.
According to Chris Mouchabhani, Managing Partner at M Capital Group, “Despite all economic scenarios that one may consider, beyond overall economic shocks, medical technology should remain one of the most promising and robust sectors over the short to medium term and well beyond 2028.”
There is a movement towards home-based care for the elderly, next generation scanning and MRI devices, wearable technology, artificial intelligence incorporation, and online connectivity. Experts also see a focus on predictive, preventive, personalized, participatory, and precision medicine, with rising levels of integration of home care and technological innovation.
The average cost of treatment has been rising across the board, creating additional financial burdens to governments, healthcare providers and insurance companies. According to MCG, cost-per-inpatient-stay in the United States alone rose on average annually by over 13% between 2014 to 2021, leading MedTech to focus research efforts on optimized medical equipment at lower price points, whilst emphasizing portability and ease of use. Namely, 46% of the 1,008 medical technology companies in the 2021 MedTech Innovator (“MTI”) database are focusing on prevention, wellness, detection, or diagnosis, signaling a clear push for preventive care to also tackle costs.
In addition, there has also been a lasting impact on consumer and medical demand for home care, supported by the pandemic. Lockdowns, closure of care facilities, and healthcare systems subjected to capacity pressure, accelerated demand away from traditional inpatient care. Now, outpatient care solutions are driving industry production, with nearly 70% of recent diagnostics start-up companies producing products in areas such as ambulatory clinics, at-home care, and self-administered diagnostics.
This document is designed as an introductory to medical students,nursing students,midwives or other healthcare trainees to improve their understanding about how health system in Sri Lanka cares children health.
Deep Leg Vein Thrombosis (DVT): Meaning, Causes, Symptoms, Treatment, and Mor...The Lifesciences Magazine
Deep Leg Vein Thrombosis occurs when a blood clot forms in one or more of the deep veins in the legs. These clots can impede blood flow, leading to severe complications.
Deep Leg Vein Thrombosis (DVT): Meaning, Causes, Symptoms, Treatment, and Mor...
Quality by Design Principles Applied to Sterilizing Filtration by Michael Payne
1. The life science business of Merck KGaA,
Darmstadt, Germany operates as
MilliporeSigma in the U.S. and Canada.
Quality by Design
Principles Applied
to Sterilizing
Filtration
Michael Payne
Principal Biosafety Technical Consultant
November 2020
2. The life science business
of Merck KGaA, Darmstadt,
Germany operates as
MilliporeSigma in the U.S.
and Canada
3. Disclaimer:
Views expressed in this
talk constitute my
professional opinion.
Quality by Design Principles Applied to Sterilizing Filtration | November 2020
4. Quality by Design Principles Applied to Sterilizing Filtration | November 2020
Steve Jobs Image via Wikimedia Commons
“Design is a funny word.
Some people think design
means how it looks. But of
course, if you dig deeper,
it’s really how it works.”
4
5. Agenda
1 Concepts, Terminology & Target Focus
2 Regulatory Guidance
3
Example of Critical Aspects & Requirements
for Sterilizing Filtration
4 Product Lifecycle Comments
6. Quality by Design in the biopharmaceutical industry. RA = risk assessment; PC = process characterisation
Presentation Objectives & Scope
✓ Provide generic information
✓ Review Quality by Design (QbD)
✓ Focus on sterilizing filtration for aseptic filling
✓ Discuss current regulatory documents on sterilizing filtration
✓ Show how to gather information for a sterilizing filtration design space
❖Will not focus on Quality Risk Management
❖Will not focus on vendor / supplier product QbD
6
8. ✓ Must demonstrate that patient is not at risk from
drug product
✓ Must demonstrate drug product quality, safety,
identity, purity, & efficacy
Requirements for Final Filling Operations
Downstream of Purification and Final Filling considered greatest patient risk
8
Quality by Design Principles Applied to Sterilizing Filtration | November 2020
9. Sterile Medicinal Products by Aseptic Processing
Drug
Product
Sterilization
Process
Closure Sterilization
Process
Sterile
Closure
Excipient Sterilization
Process
Sterile
Excipient
Aseptic
Processing
Sterile
Drug
Product
Container Sterilization
Process
Sterile
Container
Sterile
Final
Product
Multiple sterilization process conditions each optimized for individual component type
Aseptic processing is then the focus of optimizing and troubleshooting9
10. Production Formulation / Filling Suite & its Filters
Stopper
Washer
Dryer
Autoclave
WFI
CIP
Freeze dryer
Formulation
Bioburden & Sterile
Filtration
Sterile
Filtration
Aseptic Filler
Prefilter Bioburden
Filter
WFI
API
Excipient
Sterile Hold Tank
Vial
Washing
Sterilizing
Filter
Depyrogenation
Clean Room
Utility Gas
Filters
Gassing
Filter
Blanket /
Transfer
Gas Filter
IT gas inlet
filter IT gas
inlet filter
Vent filter
Vent filter Vent filter
Vent filter
Drying
filter
Washing
filters
Vent filter
Protection
filter
Protection
filter
Circled filters have a critical duty – require full
qualification under defined range of conditions
Quality by Design Principles Applied to Sterilizing Filtration | November 202010
12. Quality cannot be tested into the product - should be built-in by good quality
systems & good manufacturing practices
Starting Points
We should have a systematic approach to
• Product specifications and design
• Process design & control
• Process performance & continuous improvement
• Knowledge retention and use
• We should have (or have access to)
• Drug product/substance and drug manufacturing process knowledge
• Scientific understanding of in the establishment of design, specifications and
manufacturing
• Company mission that patient safety & quality are paramount
• Understanding of quality risk management (QRM) & QbD
12
13. What do we know about Quality by Design (QbD)?
x QbD isn’t “new” (first draft 2004)
x QbD does not have to be focused on Design of Experiment (DoE)
✓ Quality system manages a product’s lifecycle
✓ Intended to increase process & product understanding, decrease patient risk
✓ Multidisciplinary & Multidepartmental exercise
✓ Applicable to whole manufacturing process OR a unit operation (one process
inside another process)
✓ Defines “opportunities for continuous improvement and real-time release”
✓ Expected by regulatory agencies
✓ Defines “'design space' and ‘what is and is not a change’”
13
14. Target
Target Range
Proven Acceptable Range
Observation ObservationDiscrepancy Discrepancy
Alert Limit
Action Limit
QbD Concept – Multidimensional Design Space (ICH Q8)
Knowledge space (information of the product / process / activity outside our company)
Design space (information on the product, process, activity inside our company)
• Demonstrated range of all process parameters (CPPs or KPPs) where process meets the
product’s Critical Quality Attributes (CQAs)
• Moving out of the design space is a change and may require post-approval change
Control space (how we control the product, process, activity inside our company)
14 Quality by Design Principles Applied to Sterilizing Filtration | November 2020
15. Example of Iterative QbD Workflow & Systemic Approach
From Quality by Design I Biopharmaceuticals
Anurag S Rathore & Helen Winkle, Nature Biotechnology 27, 26 - 34 (2009)
15 Quality by Design Principles Applied to Sterilizing Filtration | November 2020
16. QbD Concepts - Quality Target Product Profile (QTPP)
”prospective summary of the quality characteristics of a drug product that ideally will be
achieved to ensure the desired quality, taking into account safety and efficacy.” (ICHQ8)
What is the drug and what must it do to be safe, effective, (convenient)?
Intended use, dosage form, strengths, closure system (stability), route of administration, delivery
systems, mechanism of action
Concept brief (clinical, drug metabolism, pharmacokinetics, safety & marketing) to set product
specifications
Should have a target value or an acceptable range
Quality attribute is critical when it has an impact on the patient
Strength/Efficacy – Effect of wrong dose?
Purity/Safety – Effect of potentially harmful impurities?
Quality – degradants
16 Quality by Design Principles Applied to Sterilizing Filtration | November 2020
17. Example of Quality Target Product Profile (QTPP) - Mab
17
Source: CMC Biotech Working Group, (October 2009), A-Mab: A Case Study in Bioprocess Development, V2.1
Provides a
metric when
reviewing the
filtration
processes in all
clinical phases
Quality by Design Principles Applied to Sterilizing Filtration | November 2020
18. Raw material and component attributes & process
parameters linked to output product CQAs
From a Process Viewpoint
Courtesy of Engineers Journal July 2014
Source: How QbD and the FDA Process Validation Guidance Affect Product Development and Operations, Part 1, Peter H. Calcott, (November 2011), Bioprocess International
(http://www.bioprocessintl.com/analytical/downstream-validation/how-qbd-and-the-fda-process-validation-guidance-affect-product-development-and-operations-part-1-323457/
& Process parameters
18 Quality by Design Principles Applied to Sterilizing Filtration | November 2020
21. ICH Q10 and Change Management: Enabling Quality Improvement
Dr. Bernadette Doyle, GlaxoSmithKline
US FDA Use ICH Documents as Guidances
Focus on Product Lifecycle – Development to Removal from Market
Linkage of Q8 -> Q12
Joseph C. Famulare, “Workshop on Implementation of ICH Q8/Q9/Q10 and
Other Quality Guidelines” Beijing, China, 3-5 December 2008
Add ICH Q11 (Development and Manufacture of Drug Substances), ICH Q12 Lifecycle Management
21 Quality by Design Principles Applied to Sterilizing Filtration | November 2020
22. Traditional style sterile filtration system with bioburden
reduction filter and EMA/PICS/WHO compliant
22
Aseptic Filler
Sterile Hold
Tank
Vent FilterVent Filter
Sterilizing
Filter
Bioburden
Reduction
Filter
Sterilizing
Filter
Compounding
Formulation
“Due to the potential additional risks of
a sterile filtration process, as compared
with other sterilization processes, a
second filtration through a sterile
sterilizing grade filter, immediately
prior to filling, should be considered as
part of an overall CCS.”
(CCS = Contamination Control Strategy)
Annex 1 July 2020 Draft
Quality by Design Principles Applied to Sterilizing Filtration | November 2020
23. EMA Guideline on manufacture of the finished dosage form
– Effective January 2018 EMA/CHMP/QWP/245074/2015
Table of contents
1. Introduction (background)
2. Scope
3. Legal basis
4. Manufacture
− 4.1. Manufacturer(s)
− 4.2. Batch Formula
− 4.3. Description of Manufacturing
Process and Process Controls
− 4.4. Controls of Critical Steps and
Intermediates
− 4.5. Process Validation and/or Evaluation
Definitions
Control Strategy:
Critical Process Parameter (CPP):
Critical Quality Attribute (CQA):
Design Space
Hold Time:
− Real Time Release Testing:
References
Annex
23
24. Guideline on process validation for finished products -
information and data to be provided in regulatory submissions
– Effective November 2016 - EMA/CHMP/CVMP/QWP/BWP/70278/2012-Rev1,Corr.1
Table of contents
1. Introduction (background)
2. Scope
3. Legal basis
4. General considerations
5. Process validation
5.1. Traditional process validation
5.2. Continuous process verification
5.3. Hybrid approach
5.4. Design space verification
6. Scale-up
7. Post approval change control
8. Standard vs. non-standard methods of manufacture
Definitions
References
Annex I: Process validation scheme
Annex II: Standard/non-standard processes
24
Target
Target Range
Proven Acceptable Range
Observation ObservationDiscrepancy Discrepancy
Alert Limit
Action Limit
25. EMA Guideline on the sterilisation of the medicinal product,
active substance, excipient and primary container
- Effective 1 October 2019 - EMA/CHMP/CVMP/QWP/850374/2015
Table of contents
1. Introduction (background)
2. Scope
3. Legal basis
4. General requirements
− 4.1. Requirements for the manufacture of sterile medicinal
products and sterile components
− 4.1.1. Steam sterilisation
− 4.1.2. Dry heat sterilisation
− 4.1.3. Ionization radiation sterilisation
− 4.1.4. Gas sterilisation
− 4.1.5. Sterile filtration
− 4.1.6. Aseptic processing
− 4.2. Good manufacturing practice for sterile active substances,
sterile excipients and sterile containers
− 4.2.1. Active substances
− 4.2.2. Excipients
− 4.2.3. Containers
4.3. Selection of sterilisation method
5. Decision trees
6. Definitions
7. References
25
Key Document
Especially when used
with PICS/WHO
Annex 1 (Manufacture
of Sterile Medicinal
Product (currently
under 3rd review)
26. EMA Guideline on the sterilisation of the medicinal product, active
substance, excipient and primary container
4.1.5. Sterile filtration
This table mirrors many aspects of the
US FDA Compliance Guide for
Inspection of Sterile Drug Product
Facilities and ISO 13408-2
A CLOSE alignment across major
regulatory agencies and organisations.
Regulator highlights both critical (i.e
sterilizing) and moderately critical
(i.e. bioburden reduction) filter
AND shows some of what should be
qualified and what fluid should be
used
26 Quality by Design Principles Applied to Sterilizing Filtration | November 2020
27. DRAFT Annex 1 Manufacture of Sterile Medicinal
Products (Document Revised July 2020 – 3rd revision in 3 years)
Filtration of medicinal products which cannot be sterilized in their final container
“8.81 The selection of components for the filtration system and their interconnection and
arrangement within the filtration system, including pre-filters, should be based on the
critical quality attributes of the products, documented and justified.”
“8.87 iii. Filtration process conditions including:
• Fluid pre-filtration holding time and effect on bioburden.
• Filter conditioning, with fluid if necessary.
• Maximum filtration time/total time filter is in contact with fluid.
• Maximum operating pressure.
• Flow rate.
• Maximum filtration volume.
• Temperature.
• The time taken to filter a known volume of bulk solution and
the pressure difference to be used across the filter”
27
Alignment with
QbD Approach
Note the process
parameters
referenced
Quality by Design Principles Applied to Sterilizing Filtration | November 2020
28. Some Key Design Space Points in EMEA Documents
Design Space Defined
➢ The multidimensional combination and interaction of input variables (e.g., material
attributes) and process parameters that have been demonstrated to provide assurance of
quality.
➢ Working within the design space is not considered as a change.
➢ A design space will normally be developed at laboratory or pilot scale.
➢ During scale-up the commercial process is generally conducted and validated in a specific
area of the design space, defined as the target interval or Normal Operating Range (NOR).
➢ Movement out of the design space is considered to be a change and would normally initiate
a regulatory post approval change process.
➢ Design space is proposed by the applicant, supported by data and is subject to regulatory
assessment and approval
28
31. Objectives of Sterilizing Filter Discussion
• Identification of characteristics that could affect filter performance and
hence patient safety
• Review characteristics that should be determined in drug product
development
• Be a reminder of some characteristics that can be compromised during
drug product lifecycle
• Not to expand the design space but to define the design space
(early stage clinicals have a much smaller design space)
31 Quality by Design Principles Applied to Sterilizing Filtration | November 2020
32. 8 Elements of Sterilizing Filter Qualification
Should represent “worst case” process conditions, process fluid, & filter characteristics
all of which come from the qualified design space
Integrity
Testing
Compatibility
Sterilization
Extractables
& Leachables
Duty
Binding
Retention QS, VMP &
Documentation
Prove the filter meets all
performance & duty
requirements within
product & process
conditions.
Prove the sterilization
method is effective and does
not compromise the filter.
Prove the filter does not
unacceptably remove
stream components.
Prove the stream does not
adversely impact the filter
duty or process stream
Identify, quantify, and assess impact
of compounds that are added to
process product stream.
Prove the filter removes
bacteria from the stream
compliant with ASTM and
relevant regulations
Prove the filter’s
bacterial retention
capabilities with a non-
destructive test.
32 Quality by Design Principles Applied to Sterilizing Filtration | November 2020
33. Assumption is that drug product production is under GMP with robust QS
Quality System
ICH Quality Working Group Training. How ICH Q8, Q9, Q10 guidelines are working together throughout the product lifecycle. Nov 2010.
Product
Discontinuation
Commercial
Manufacturing
Technology
Transfer
Pharmaceutical
Development
Pharmaceutical Quality System
Investigational products
GMP
Management Responsibilities
Knowledge Management
Quality Risk Management
Process Performance & Product Quality Monitoring System
Corrective Action / Preventive Action (CA/PA) System
Change Management System
Management Review
Enablers
PQS
elements
Quality by Design Principles Applied to Sterilizing Filtration | November 2020
34. Some Considerations in Sterilizing Filtration for
Early Phase Clinical Trials
• Collect data as per xGMP
• Design space and control space are similar or same
• QbD objective is to collect data and expand
design space without affecting QTPP
• Critical equipment should be qualified
• Process conditions are sometimes based on convenience e.g. available equipment
but this may not represent conditions used in later process runs or clinical phases
• Sterilization processes are as per compendial requirements
• Filtration process parameters should be collected
• Time, pressure, flowrate, temperature, etc. (as per Annex 1)
• Keep the end in mind – phase 3 & manufacturing
• Gain knowledge of larger scale filling operating conditions during phase 2
Quality by Design Principles Applied to Sterilizing Filtration | November 2020
Image https://blogs.biomedcentral.com/on-medicine/2018/05/18/clinical-trials-and-trial-registration/
34
35. Division of the Elements of Sterilizing Filter Qualification
Part 1
Phase 1-2a – Development or Prior to Small Scale Tech Transfer
Integrity
Testing
Compatibility
Sterilization
Extractables
& Leachables
Duty
Binding
Retention QS, VMP &
Documentation
35 Quality by Design Principles Applied to Sterilizing Filtration | November 2020
36. Duplicate or Triplicate trials using small equipment provides;
Filter integrity testing (FIT) information
− Pre-use water bubble point
− Post-use product bubble point
− Water volume to flush to get pre-use value
Filter loading / capacity (L/m2) determines area
− Graph Volume/time vs Time
− Filtrate flowrate
Adsorption studies (active/excipient/preservative etc.)
− Take samples throughout filtration
− Graph concentration vs loading
− Determine volume for saturation
− Mimic filling process – e.g. hold / header tanks / bags
Compatibility
− Visual inspection / Weight change
Using small (~33-50mm) disk filter flow decay equipment.
Small Scale Membrane Trials in Process Development
36
Confirmed Outputs
✓ Filter MOC
✓ Filter Area
✓ Likely FIT result
✓ Flush volume
✓ Flowrate/Area (flux)
✓ Time for volume
Quality by Design Principles Applied to Sterilizing Filtration | November 2020
37. Collected during early phase using calculated area, flushing conditions
Filter Duty & Compatibility Data Confirmation
Scale-up Parameters to Hold Constant
➢ Loading (i.e. V/A), Flux (Q/A)
Process Parameters
➢ Feed fluid pretreatment
➢ Temperature, differential pressure, flowrate, volume
➢ Surface area
➢ Exposure time
Attributes
➢ Sacrifice volume before first container in batch
➢ Process yield
➢ Visual filter inspection before and after filtration
37
Confirmed Outputs
✓ Product preparation
✓ Filter preparation
✓ Filter area
✓ Flush / Discard volume
✓ Likely FIT result
Quality by Design Principles Applied to Sterilizing Filtration | November 2020
38. Applies to devices / elements used once OR complete single-use assemblies
What Single-use System is Specified
38
Ensure design is right – iterative process
Confirm effect of SUS on product
Experience with SUS process and
handling
Key Scaling Parameters - Keep the same
✓ MOC
✓ Sterilization method
✓ Product contact time
✓ Temperature – holding, storage, processing
✓ Volume / Contact Area
Complete Systems – example has 31 different components –
need vendor discussion on extractables data, compatibility, etc.
Quality by Design Principles Applied to Sterilizing Filtration | November 2020
Single-use devices
39. -Use physical measurements and biological indicators where appropriate
Filter / System Sterilization
Parameters
- Use validated system sterilization (autoclave / SIP / gamma)
- Use sterilizing filter documentation (e.g. CoQ, Validation Guide)
- Establish filter / system preparation (dry or wet)
- Conduct environmental monitoring
Attributes
Passed filter integrity test result
Visual filter inspection post SIP /Autoclave
SIP or Autoclave chart
Required F0
Quarterly gamma dose audit report
from vendor
39
C
C
B
C
R
B
R
R
C
RT
L
FLT
FC
TC
FB
R
Quality by Design Principles Applied to Sterilizing Filtration | November 2020
User History
Time
Temperature / Pressure
Normal
Operating
Space
Moist heat sterilization
Gamma sterilization
40. Division of the Elements of Sterilizing Filter Qualification
Part 2
– Phase 2b / Phase 3 or Part of Production Tech Transfer Discussion / Confirmation
Integrity
Testing
Compatibility
Sterilization
Extractables
& Leachables
Duty
Binding
Retention QS, VMP &
Documentation
40 Quality by Design Principles Applied to Sterilizing Filtration | November 2020
All circled items
need to be done
using confirmed
process conditions
and process fluids
41. Trending pre- and post-use results and deviations
Process Filter Integrity Confirmation
Parameters
- wetting fluid (water, buffer, product, excipient, etc.)
- wetting conditions (temperature, flowrate, volume, time, inlet/differential pressure)
- test gas (type, temperature)
- Post-use flushing volume
Attributes
Values before and/or after filtration
Test result incl. trending
Number of attempts to pass
41 Quality by Design Principles Applied to Sterilizing Filtration | November 2020
42. -Use physical measurements and biological indicators where appropriate
-Checking batch records and SOPs
Process Filter Sterilization
Parameters
- sterilization conditions (autoclave / SIP / gamma)
- Filter preparation (dry or wet)
- Sterilization conditions; temperature, time, inlet/differential pressure
- Whole cycle data is vital
Attributes
Passed pre & post-use integrity test result
Visual filter inspection after SIP
SIP or Autoclave chart
Required F0
Quarterly gamma dose audit report from vendor
User History
Time
Temperature / Pressure
Normal
Operating
Space
42
43. Definitions from PDA Technical Report #26
Extractables & Leachables (E&L)
Fluid
Contact
Surface
“Any chemical component that is removed from a material by the application
of an artificial or exaggerated force (e.g., solvent, temperature or time).”
Determined under “worst-case” conditions following a Model Stream
approach (e.g. BPOG)
Extractables
“A chemical component that migrates from a contact surface into a drug
product or process fluid during storage or normal use conditions.”
Determined with product under normal processing/storage
conditions.
• Solvent stream approach to identify the plastic compounds.
• Product testing (Interference between product and analytical
method has to be evaluated).
Leachables
Extractables will have a higher mass than leachables and are used in first part of
risk assessment for potential patient impact e.g. during early clinical stages
43 Quality by Design Principles Applied to Sterilizing Filtration | November 2020
44. e.g. Tubing, connectors, fittings, containers, bags, filters, etc.
Examples of Polymeric Extractables & Leachables
Oligomers
PVDF, PP, PE
Etc.
Additives and Degradants
Antioxidants, UV stabilizers,
Slip agents, etc.
Residual
Manufacturing
Solvents
Material of Construction
Contact Fluid Process
Conditions
Quantity
and
Type
44
Key Leachables Parameters
Contact fluid (media, buffer, process
intermediates, DS/ bulk, DP, etc.)
Contact material
Sterilization / Pre-treatment
Temperature
Contact time
Dilution ratio (V/A)
All process fluid interactions
DON’T forget the prefilter . . . . . And
formulation container if single-use
Quality by Design Principles Applied to Sterilizing Filtration | November 2020
45. - User and vendor partnership
Typical E & L Test Study Information & Interpretation
45 Quality by Design Principles Applied to Sterilizing Filtration | November 2020
BPOG GUIDE FOR EVALUATING
LEACHABLES RISK FROM POLYMERIC
SINGLE-USE SYSTEMS USED IN
BIOPHARMACEUTICAL
MANUFACTURING
Example of
information required
for E or L testing
https://bioprocessintl.com/upstream-processing/upstream-single-use-
technologies/recommendations-for-extractables-and-leachables-testing-182173/
46. Process Considerations of Filter Preparation & Filter
Location on Leachables – Key Process Understanding
Filtration system flushed before use
• Testing conditions (fluid, flowrate, volume, preparation, etc.)
• Acceptable levels of process residue (measurement, sampling, etc.)
• Risk to product (stability, toxicity, patient safety)
Filtration system not flushed before use
• Dilution calculation (use downstream volume)
• Risk to product (stability, toxicity, patient safety)
If Filter used for tank-to-tank transfer
• Dilution calculation (use total downstream volume)
If Filter used at true point-of-use
(no header tank or bag)
• All leachables are in final container – need product sacrifice
46 Quality by Design Principles Applied to Sterilizing Filtration | November 2020
47. 4 Interrelated factors can influence filter retention –> product sterility -> patient safety
Filter Retention Validation is a Combination of Parameters
Process
Size
Shape
pH
Osmolarity
Ionic strength
Surfactants
Differential Pressure
Flow rate
Microporous structure (pore morphology)
Temperature
Pore size distribution & membrane thickness
Membrane
Surface chemistry
Contact Time
Number
Organism
Product
Viscosity
Aggregation
Type
Concentration
47
1. Need to collect these
for all products
2. Prioritize high risk
products
3. Collaborate with
contract laboratory to;
• Determine grouping
• Establish design
space parameters
Often called
Bacterial Challenge Test
Bacterial Retention Test
Filter Integrity test value
48. Bacterial Retention Test Risk Factors
Conducted by qualified laboratories – user and vendor partnership
From PDA TR26
What to look for
in 3rd party
(mostly vendor)
laboratory test
report
This information
is used to confirm
the filter
retention
design space
Filter area
information
sterilization method
Required before
retention test can be
done
48 Quality by Design Principles Applied to Sterilizing Filtration | November 2020
49. Examples of Filter Process Parameters Checked
During Changes or when Grouping
Need to qualify all sterilising filters – example has 2 operations – sterile hold tank
fill, then product filling
Example - Looking for worst case process conditions from previous runs
✓ 1st Sterilising filter – high flowrate, shortest time, highest pressure, higher area
✓ 2nd Sterilising filter – low flowrate, longest time, lowest pressure, lower area
✓ Assumes sterilising filters MOC are the same
Should be explained in bacterial retention test protocol and report
Formulation Aseptic FillerSterile Hold
Tank
Vent
Filter
Vent
Filter
Sterilizing
Filter
Bioburden
Reduction
Filter
Sterilizing
Filter
49
50. Summarizing the Sterilizing Filter Design Space
Process Parameters
Times, pressure, temperature, flowrate (flux), volume (loading), sterilization method
and conditions, pretreatment, integrity test results, product yield
Product Attributes
Product pH / ionic strength / osmolarity, product concentrations
(active, excipient, preservative etc.), acceptable impurity levels,
Microbiological Attributes
Species / Identity, concentration
This data should already be available from quality, production,
validation, regulatory affairs documentation
50 Quality by Design Principles Applied to Sterilizing Filtration | November 2020
53. Quality by Design Principles Applied to Sterilizing Filtration | November 2020
Product Life Cycle Considerations
Phase 1
Environmental monitoring , filter sterilization method, batch size, filter area,
operating pressure, product stability, pre-flush?
Phase 2
• Process condition data collection, CAPA responses, change control activities
Phase 3
Sterilization, Integrity testing, capacity
Product Grouping for Retention Testing if Product becomes a Family
Use of parameter and attribute spreadsheets
Focus on products where DS concentration is the only formulation difference
Review all process parameters
Ensure process parameters are the same or inside the design space
53
54. Suggestions for checking before transferring filling operations
Product Life Cycle Considerations
Contract Filling or Site Transfer
Validation status of aseptic filling suite and services
Bacterial retention test done (if not then by whom)
Filling area environmental monitoring data review
Volume/Area, Flowrate/Area, time confirmed to be within established conditions
Sterilization conditions
Formulation preparation tank / container check (type, MOC), hold times
Process controls within established conditions
Change Control & Annual Product Review
Excursions / deviations checked
Change or Implement Single-use Systems
In-depth discussion required with change control team & vendor
54 Quality by Design Principles Applied to Sterilizing Filtration | November 2020
55. Examples of Filter Process Parameters to Check when
Changing or Transferring a Process
Quality by Design Principles Applied to Sterilizing Filtration | November 2020
Has the process been validated?
If so;
• Review older validations against
the current process conditions.
• Have there been filtration process
changes?
• Has the product formulation
changed since the validation?
These changes should be part of
change control checks for sterilising
filtration operations
57. ✓ Regulatory agencies look for product quality built into the process not tested into
the process
✓ Quality by Design (QbD) is a scientific approach to build-in & ensure quality in
drug products by emphasising process understanding, relationship between CPPs,
CQAs, QTPPs using a methodical approach including risk assessment
✓ Process control strategies help ensure that process parameters are maintained
within the desired range to ensure product quality and reliable process operation.
✓ QbD relatively “simple” in processes like sterilising filtration
✓ Developing a design space can be done using information already available from
previous batches (e.g. clinicals), previous testing especially bacterial retention
testing questionnaires
✓ Vendor support is valuable at many times during initial studies,
tech transfer, scale-up and process confirmation
Conclusion
57 Quality by Design Principles Applied to Sterilizing Filtration | November 2020
58. “Everything should be made
as simple as possible.
But not simpler.”
Thank YOu
Albert Einstein
Image via Creative Commons
60. Some Reference Materials
ICH Q8(R2). Pharmaceutical Development. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/q8r2-
pharmaceutical-development
ICH Q9 Quality Risk Management https://www.fda.gov/media/71543/download
ICH Q10 Pharmaceutical Quality System https://www.fda.gov/regulatory-information/search-fda-guidance-documents/q10-pharmaceutical-
quality-system
ICH Q11 Development and Manufacture of Drug Substances https://www.fda.gov/regulatory-information/search-fda-guidance-
documents/q11-development-and-manufacture-drug-substances
ICH Q12 Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management Core Guideline Guidance for Industry
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/q12-technical-and-regulatory-considerations-pharmaceutical-
product-lifecycle-management-core
Guideline on manufacture of the finished dosage form – Effective January 2018 - EMA/CHMP/QWP/245074/2015
Guideline on the sterilisation of the medicinal product, active substance, excipient and primary container - Effective 1 October 2019 -
EMA/CHMP/CVMP/QWP/850374/2015
Guideline on process validation for finished products - information and data to be provided in regulatory submissions – Effective November
2016 - EMA/CHMP/CVMP/QWP/BWP/70278/2012-Rev1,Corr.1
DRAFT Annex 1 Manufacture of Sterile Medicinal Products
https://ec.europa.eu/health/sites/health/files/files/gmp/2017_12_pc_annex1_consultation_document.pdf
PDA Technical Report No. 26, Revised 2008, Sterilizing Filtration of Liquids
PDA Technical Report No. 66 Application of Single-Use Systems in Pharmaceutical Manufacturing
BPOG www.biophorum.com/download/extractables-testing-of-polymeric-single-use-components-used-in-biopharmaceutical-manufacturing/
BPSA Recommendations for Extractables and Leachables Testing
CMC Biotech Working Group, (October 2009), A-Mab: A Case Study in Bioprocess Development, V2.1
Quality by Design I Biopharmaceuticals, Anurag S Rathore & Helen Winkle, Nature Biotechnology 27, 26 - 34 (2009)
When do you need to consider revalidating the performance of your sterilizing-grade filter? Merck Millipore AN32450000
60 Quality by Design Principles Applied to Sterilizing Filtration | November 2020