This presentation discusses pre-use post-sterilization integrity testing (PUPSIT) of sterile filters. It provides background on regulatory guidance for integrity testing critical filters before and after use. Masking studies were conducted where flawed filters were exposed to blocking solutions, and in some cases the flaws were able to mask and pass post-use integrity testing. The risk of masking was found to be highly dependent on process conditions like blocking rate and solution concentration. The presentation discusses considerations for final filtration assembly design to enable PUPSIT like using redundant filters and multi-purpose ports. It addresses challenges with maintaining sterility and pressure during PUPSIT.
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 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.
Potential Impact of Draft Annex 1 on Sterilizing FiltrationMilliporeSigma
The document discusses potential impacts of proposed changes to regulations outlined in Draft Annex 1 regarding sterilizing filtration and single-use systems. Key points include:
- Draft Annex 1 provides more specific recommendations around sterile filtration processes, including validating the filtration system, testing filter integrity before and after use, and carrying out final sterile filtration as close as possible to filling.
- It emphasizes minimizing aseptic connections and qualifying components based on critical quality attributes.
- Recent regulatory guidelines from EMA and PICS have aligned on topics like process validation, continuous verification, and sterilization requirements, showing increased harmonization across agencies.
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.
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.
Quality by Design Principles Applied to Sterilizing Filtration by Michael PayneMilliporeSigma
Key regulatory documents and regulatory thinking now includes quality by design (QbD). This webinar focuses on how to integrate practical QbD activities into the process and analytical aspects of sterile medicinal product sterilizing filtration and qualification.
In this webinar, you will learn to:
• Focus on practical QbD terms and approaches
• Highlight critical product quality aspects of sterile medicinal products
• Develop design and control spaces for sterilizing filtration
• Easily integrate QbD into the process and analytical operations in early phase development and into manufacturing phase production
Abstract:
Final sterilizing filtration is the last operation in downstream processing to assure the sterility of medicinal products. Poorly defined product attributes process parameters may attract regulatory scrutiny, affect final product sterility and patient safety. A better understanding of QbD concepts and principles allows for better process and analytical monitoring and control at both early and final phase production. The webinar will show how currently available process cGMP information can be practically incorporated into QbD product quality attributes and process parameters. This is especially vital for the third party conducted laboratory work such as bacterial retention and leachable studies.
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!
Integrity testing is a critical operation, especially for sterilizing grade filters used in biopharmaceutical processing. When performed correctly, an integrity test is a fast, definitive, non-destructive way to assure filter retention performance. Fortunately, there are few ways a non-integral filter will pass the integrity test, eliminating the possibility a non-retentive filter is used undetected. Unfortunately, there are a lot of ways an integral filter can fail the integrity test, resulting in retests, lost time, productivity and potentially lost product.
In this webinar you will:
- Gain confidence in your integrity testing results
- Provide justification for retests
- Understand specific challenges and eliminate them to assure the integrity test can be performed correctly the first time
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 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.
Potential Impact of Draft Annex 1 on Sterilizing FiltrationMilliporeSigma
The document discusses potential impacts of proposed changes to regulations outlined in Draft Annex 1 regarding sterilizing filtration and single-use systems. Key points include:
- Draft Annex 1 provides more specific recommendations around sterile filtration processes, including validating the filtration system, testing filter integrity before and after use, and carrying out final sterile filtration as close as possible to filling.
- It emphasizes minimizing aseptic connections and qualifying components based on critical quality attributes.
- Recent regulatory guidelines from EMA and PICS have aligned on topics like process validation, continuous verification, and sterilization requirements, showing increased harmonization across agencies.
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.
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.
Quality by Design Principles Applied to Sterilizing Filtration by Michael PayneMilliporeSigma
Key regulatory documents and regulatory thinking now includes quality by design (QbD). This webinar focuses on how to integrate practical QbD activities into the process and analytical aspects of sterile medicinal product sterilizing filtration and qualification.
In this webinar, you will learn to:
• Focus on practical QbD terms and approaches
• Highlight critical product quality aspects of sterile medicinal products
• Develop design and control spaces for sterilizing filtration
• Easily integrate QbD into the process and analytical operations in early phase development and into manufacturing phase production
Abstract:
Final sterilizing filtration is the last operation in downstream processing to assure the sterility of medicinal products. Poorly defined product attributes process parameters may attract regulatory scrutiny, affect final product sterility and patient safety. A better understanding of QbD concepts and principles allows for better process and analytical monitoring and control at both early and final phase production. The webinar will show how currently available process cGMP information can be practically incorporated into QbD product quality attributes and process parameters. This is especially vital for the third party conducted laboratory work such as bacterial retention and leachable studies.
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!
Integrity testing is a critical operation, especially for sterilizing grade filters used in biopharmaceutical processing. When performed correctly, an integrity test is a fast, definitive, non-destructive way to assure filter retention performance. Fortunately, there are few ways a non-integral filter will pass the integrity test, eliminating the possibility a non-retentive filter is used undetected. Unfortunately, there are a lot of ways an integral filter can fail the integrity test, resulting in retests, lost time, productivity and potentially lost product.
In this webinar you will:
- Gain confidence in your integrity testing results
- Provide justification for retests
- Understand specific challenges and eliminate them to assure the integrity test can be performed correctly the first time
Filter Validation and Regulatory aspectsbala murugan
The document discusses various aspects of filter validation including:
1) Common materials used in filters include regenerated cellulose, nylon, polyamides, and polyether sulfones.
2) Porosity refers to the total empty space in a filter and affects its performance.
3) Validation tests include bacterial challenge tests, bubble point tests, and diffusion tests to evaluate a filter's effectiveness.
4) Bubble point tests determine a filter's pore size while diffusion tests measure gas flow rates through a filter.
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!
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.
Implementing and Managing Pre-use Post-sterilization Integrity Testing (PUPSIT)MilliporeSigma
This document summarizes a presentation given at a conference on aseptic processing. It discusses challenges implementing pre-use integrity testing (PUPSIT) of sterile filters for final product filtration and provides case studies of both successful and unsuccessful filtration setups. The presentation addresses common issues like filter sizing, complex product formulations that impact integrity testing, and assembly details. It promotes the ability to achieve PUPSIT with current single-use technology and filtration setup options.
The document summarizes the key changes in the new draft of EU GMP Annex 1 regarding sterile product manufacturing. Some of the major changes include a stronger emphasis on quality risk management and the requirement for a formal contamination control strategy. There is also a focus on advances in sterile manufacturing technology as well as clarifying ambiguities in the current Annex. The new draft contains additional guidance on cleanroom classification limits and testing, environmental monitoring, and controlling exposure times during aseptic processing to minimize contamination risks.
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
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
Visual inspection of parenteral products is conducted to detect defective units and ensure compliance with regulatory requirements that injectable products be free of visible particles. All filled containers undergo 100% visual inspection against black and white backgrounds under controlled lighting. Inspections are usually manual but can also be automated. Post-inspection sampling is required and failures can result in batch rejection. Any particles detected must be characterized to identify the source and ensure appropriate corrective actions. Recalls are sometimes necessary when particles are found, posing a risk to patient safety. Thorough training and documentation are needed to support consistent visual inspection.
This document provides an overview of air handling systems (AHUs) and HVAC qualification for pharmaceutical facilities. It contains sections on introduction, types of clean rooms, principles of clean rooms, HVAC components, regulatory requirements, contamination control, air flow patterns, and HVAC qualification steps including user requirement specification, design qualification, and installation qualification. The objective is to understand the need for pharmaceutical air handling systems and their technical and qualification requirements.
Good Manufacturing PracticeFor LVP,SVP, ophthalmic veterinary medicine, bulk chemicals & invitro diagnostic
For Good business Practice
A control process gives reproducibility & product consistency with in known limits
Provides license to do business.
Qualification of membrane filtration apparatusPRAVADA
This document discusses the validation of membrane filtration processes. It defines qualification as ensuring equipment is properly installed and works as expected. There are four types of qualification: design, installation, operational, and performance. Membrane filtration separates solids from liquids using a porous membrane. Validation of membrane filters includes testing reproducibility, sterilization, integrity, operating conditions, inertness, antimicrobial activity, endotoxins, and toxicity to ensure the filter performs as intended. Regular performance qualification is important to check the filter maintains consistent performance over time.
Bioburden control: Strategies to address bioburden control in downstream proc...Merck Life Sciences
Biotherapeutic manufacturing processes are at greater risk of contamination than classic small molecule processes and therefore require different control strategies. Understanding the source, options for control, and potential impact of bioburden throughout downstream biopharmaceutical processes is beneficial to process developers, production operators and pharmaceutical microbiologists. Process designs that reduce the risks of bioburden contamination will decrease process related failures and the resulting painful, time-consuming investigations.
In this webinar, you will learn:
• Biotherapeutic manufacturing processes are at greater risk of contamination than classic small molecule processes and therefore require different control strategies.
• Understanding the source, options for control, and potential impact of bioburden throughout downstream biopharmaceutical processes is beneficial to process developers, production operators and pharmaceutical microbiologists.
• Process designs that reduce the risks of bioburden contamination will decrease process related failures and the resulting painful, time-consuming investigations.
Register for our webinar here: https://bit.ly/3c4q9rr
A review article on visual inspection program for sterile injectable product ...Palash Das
This document provides an overview of the manual visual inspection process for sterile injectable products. It discusses the risks of particulate contamination throughout the manufacturing process and identifies potential sources such as environment, materials, equipment, utilities and methods. The document outlines the typical manufacturing process flow and emphasizes the importance of controlling the aseptic process through measures like qualified equipment and facilities, validated processes, and trained personnel. It examines the key aspects of developing an inspection program including inspector qualification, process establishment, and regulatory expectations around ensuring products are free of visible defects.
This document discusses key considerations for the aseptic manufacturing of sterile pharmaceutical products. It covers classification of clean areas, environmental monitoring, preparation and filtration of solutions, personnel requirements, equipment sterilization, and validation of aseptic processes. The main objectives are to prevent microbial contamination and maintain sterility throughout manufacturing.
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.
This document summarizes guidelines for media fill validation and USFDA process validation approaches. It discusses media fill validation, including why it is required, how to conduct media fill tests, parameters that affect sterility, and requalification requirements. It provides details on media fill procedures for liquid, powder, and lyophilized products. Frequency of media fills depends on production batch size, with more runs required for initial qualification and after certain changes. The document also introduces the USFDA's process validation lifecycle approach, which focuses on validating processes throughout the product lifecycle rather than just at startup.
Aseptic / sterile- “ A state of control attained by using an aseptic work area and performing activities in a manner that precludes microbiological contamination of the exposed sterile product”
EU GMP Annex 1 – Implications on Filtration and Single Use Technology by Soma...MilliporeSigma
The draft EU GMP Annex 1 provides additional guidance on sterile filtration and single-use systems. It emphasizes minimizing contamination risks through engineering controls like preassembled equipment. It recommends considering a second sterile filter immediately before filling due to filtration risks. It also provides more specific recommendations around filter selection, validation, and system design to ensure sterility and product quality.
Aseptic Process Sampling to address Risk of Contamination & Containment in co...Merck Life Sciences
In this webinar, you will learn:
- The challenges tied to contamination control within a biopharmaceutical environment.
- What closed processing is, and how sampling solutions are an integral component towards that end.
- Advantages of sterile sampling from both a technical and economical viewpoint; with the review of a technical study confirming contamination risk reduction and total cost of ownership.
- Recommendations and requirements stated by these major regulatory authorities around the monitoring of the manufacturing process with the execution of sampling.
Detailed description:
Biopharmaceutical manufacturers are required to ensure drug product quality attributes for patient safety. Strong contamination control strategies should be considered early in process design, and have direct influence on the production environment and equipment selection.
Sampling at each step is a critical component in maintaining a contamination control strategy. Regulators are critical in the sampling process, as it predicts the state of the product or process, and needs to be Representative. A case study will be presented that demonstrates a closed, robust sampling solution capable of maintaining a sterile flow path when challenged with Brevundimonas diminuta. The sampling option you select can help support your goal in achieving a closed process, improving your risk mitigation strategy and product safety.
Webinar: Closed Sampling, a Critical Component for Every Risk Mitigation Stra...Merck Life Sciences
Participate in the interactive webinar now: http://bit.ly/ClosedSamplingWebinar
Sampling should never put your process or sample at risk of contamination resulting in loss of time, money or regulatory scrutiny. This webinar discusses simple and effective sampling options to implement a secure sampling operation across your entire process driving towards closed manufacturing.
Explore our webinar library: www.merckmillipore.com/webinars
Filter Validation and Regulatory aspectsbala murugan
The document discusses various aspects of filter validation including:
1) Common materials used in filters include regenerated cellulose, nylon, polyamides, and polyether sulfones.
2) Porosity refers to the total empty space in a filter and affects its performance.
3) Validation tests include bacterial challenge tests, bubble point tests, and diffusion tests to evaluate a filter's effectiveness.
4) Bubble point tests determine a filter's pore size while diffusion tests measure gas flow rates through a filter.
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!
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.
Implementing and Managing Pre-use Post-sterilization Integrity Testing (PUPSIT)MilliporeSigma
This document summarizes a presentation given at a conference on aseptic processing. It discusses challenges implementing pre-use integrity testing (PUPSIT) of sterile filters for final product filtration and provides case studies of both successful and unsuccessful filtration setups. The presentation addresses common issues like filter sizing, complex product formulations that impact integrity testing, and assembly details. It promotes the ability to achieve PUPSIT with current single-use technology and filtration setup options.
The document summarizes the key changes in the new draft of EU GMP Annex 1 regarding sterile product manufacturing. Some of the major changes include a stronger emphasis on quality risk management and the requirement for a formal contamination control strategy. There is also a focus on advances in sterile manufacturing technology as well as clarifying ambiguities in the current Annex. The new draft contains additional guidance on cleanroom classification limits and testing, environmental monitoring, and controlling exposure times during aseptic processing to minimize contamination risks.
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
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
Visual inspection of parenteral products is conducted to detect defective units and ensure compliance with regulatory requirements that injectable products be free of visible particles. All filled containers undergo 100% visual inspection against black and white backgrounds under controlled lighting. Inspections are usually manual but can also be automated. Post-inspection sampling is required and failures can result in batch rejection. Any particles detected must be characterized to identify the source and ensure appropriate corrective actions. Recalls are sometimes necessary when particles are found, posing a risk to patient safety. Thorough training and documentation are needed to support consistent visual inspection.
This document provides an overview of air handling systems (AHUs) and HVAC qualification for pharmaceutical facilities. It contains sections on introduction, types of clean rooms, principles of clean rooms, HVAC components, regulatory requirements, contamination control, air flow patterns, and HVAC qualification steps including user requirement specification, design qualification, and installation qualification. The objective is to understand the need for pharmaceutical air handling systems and their technical and qualification requirements.
Good Manufacturing PracticeFor LVP,SVP, ophthalmic veterinary medicine, bulk chemicals & invitro diagnostic
For Good business Practice
A control process gives reproducibility & product consistency with in known limits
Provides license to do business.
Qualification of membrane filtration apparatusPRAVADA
This document discusses the validation of membrane filtration processes. It defines qualification as ensuring equipment is properly installed and works as expected. There are four types of qualification: design, installation, operational, and performance. Membrane filtration separates solids from liquids using a porous membrane. Validation of membrane filters includes testing reproducibility, sterilization, integrity, operating conditions, inertness, antimicrobial activity, endotoxins, and toxicity to ensure the filter performs as intended. Regular performance qualification is important to check the filter maintains consistent performance over time.
Bioburden control: Strategies to address bioburden control in downstream proc...Merck Life Sciences
Biotherapeutic manufacturing processes are at greater risk of contamination than classic small molecule processes and therefore require different control strategies. Understanding the source, options for control, and potential impact of bioburden throughout downstream biopharmaceutical processes is beneficial to process developers, production operators and pharmaceutical microbiologists. Process designs that reduce the risks of bioburden contamination will decrease process related failures and the resulting painful, time-consuming investigations.
In this webinar, you will learn:
• Biotherapeutic manufacturing processes are at greater risk of contamination than classic small molecule processes and therefore require different control strategies.
• Understanding the source, options for control, and potential impact of bioburden throughout downstream biopharmaceutical processes is beneficial to process developers, production operators and pharmaceutical microbiologists.
• Process designs that reduce the risks of bioburden contamination will decrease process related failures and the resulting painful, time-consuming investigations.
Register for our webinar here: https://bit.ly/3c4q9rr
A review article on visual inspection program for sterile injectable product ...Palash Das
This document provides an overview of the manual visual inspection process for sterile injectable products. It discusses the risks of particulate contamination throughout the manufacturing process and identifies potential sources such as environment, materials, equipment, utilities and methods. The document outlines the typical manufacturing process flow and emphasizes the importance of controlling the aseptic process through measures like qualified equipment and facilities, validated processes, and trained personnel. It examines the key aspects of developing an inspection program including inspector qualification, process establishment, and regulatory expectations around ensuring products are free of visible defects.
This document discusses key considerations for the aseptic manufacturing of sterile pharmaceutical products. It covers classification of clean areas, environmental monitoring, preparation and filtration of solutions, personnel requirements, equipment sterilization, and validation of aseptic processes. The main objectives are to prevent microbial contamination and maintain sterility throughout manufacturing.
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.
This document summarizes guidelines for media fill validation and USFDA process validation approaches. It discusses media fill validation, including why it is required, how to conduct media fill tests, parameters that affect sterility, and requalification requirements. It provides details on media fill procedures for liquid, powder, and lyophilized products. Frequency of media fills depends on production batch size, with more runs required for initial qualification and after certain changes. The document also introduces the USFDA's process validation lifecycle approach, which focuses on validating processes throughout the product lifecycle rather than just at startup.
Aseptic / sterile- “ A state of control attained by using an aseptic work area and performing activities in a manner that precludes microbiological contamination of the exposed sterile product”
EU GMP Annex 1 – Implications on Filtration and Single Use Technology by Soma...MilliporeSigma
The draft EU GMP Annex 1 provides additional guidance on sterile filtration and single-use systems. It emphasizes minimizing contamination risks through engineering controls like preassembled equipment. It recommends considering a second sterile filter immediately before filling due to filtration risks. It also provides more specific recommendations around filter selection, validation, and system design to ensure sterility and product quality.
Aseptic Process Sampling to address Risk of Contamination & Containment in co...Merck Life Sciences
In this webinar, you will learn:
- The challenges tied to contamination control within a biopharmaceutical environment.
- What closed processing is, and how sampling solutions are an integral component towards that end.
- Advantages of sterile sampling from both a technical and economical viewpoint; with the review of a technical study confirming contamination risk reduction and total cost of ownership.
- Recommendations and requirements stated by these major regulatory authorities around the monitoring of the manufacturing process with the execution of sampling.
Detailed description:
Biopharmaceutical manufacturers are required to ensure drug product quality attributes for patient safety. Strong contamination control strategies should be considered early in process design, and have direct influence on the production environment and equipment selection.
Sampling at each step is a critical component in maintaining a contamination control strategy. Regulators are critical in the sampling process, as it predicts the state of the product or process, and needs to be Representative. A case study will be presented that demonstrates a closed, robust sampling solution capable of maintaining a sterile flow path when challenged with Brevundimonas diminuta. The sampling option you select can help support your goal in achieving a closed process, improving your risk mitigation strategy and product safety.
Webinar: Closed Sampling, a Critical Component for Every Risk Mitigation Stra...Merck Life Sciences
Participate in the interactive webinar now: http://bit.ly/ClosedSamplingWebinar
Sampling should never put your process or sample at risk of contamination resulting in loss of time, money or regulatory scrutiny. This webinar discusses simple and effective sampling options to implement a secure sampling operation across your entire process driving towards closed manufacturing.
Explore our webinar library: www.merckmillipore.com/webinars
Webinar: Closed Sampling, a Critical Component for Every Risk Mitigation Stra...MilliporeSigma
Participate in the interactive webinar now: http://bit.ly/ClosedSamplingWebinar
Sampling should never put your process or sample at risk of contamination resulting in loss of time, money or regulatory scrutiny. This webinar discusses simple and effective sampling options to implement a secure sampling operation across your entire process driving towards closed manufacturing.
Explore our webinar library: www.emdmillipore.com/webinars
This document summarizes a report published by the Bio-Process Systems Alliance (BPSA) regarding recommendations for testing, evaluation, and control of particulates from single-use process equipment. The BPSA is a trade association that facilitates implementation of single-use technologies through various initiatives. The report was created by a working group consisting of subject matter experts from single-use technology suppliers and end users. It provides guidance on characterizing and minimizing particulate levels throughout the lifecycle of single-use technologies, including manufacturing, storage, handling and end use. It also discusses investigation and mitigation of particulate deviations. The BPSA recommends further work to develop standardized measurement methods, application-specific requirements, a catalog of particle types,
This document provides guidance for ensuring sterility in the manufacture of sterile medicinal products through a contamination control strategy (CCS). The CCS should establish robust assurance of contamination prevention from microbial, endotoxin/pyrogen and particulate sources. It involves identifying risks to product quality using quality risk management and putting in place controls like facility design, equipment qualification, environmental monitoring, personnel training and change control to minimize these risks. The CCS must describe all elements of the manufacturing process and be reviewed periodically for effectiveness in assuring sterility of the final product.
This document discusses validation of membrane filtration processes. It begins by introducing membrane filtration and its uses in sterilization. The objectives of validation are to consistently produce the desired results when following standard operating procedures. Validation is necessary to ensure safety, quality, and consistency. The document outlines the various elements that must be validated including filter reproducibility, sterilization, integrity testing, operating conditions, shedding, and microbial challenge testing. It provides details on how to validate each of these elements. The validation report summarizes the findings and conclusions.
Sterile filtration of complex injectables by Partha BanerjeeMerck Life Sciences
Sterile filtration and filter validation remain a critical segment during the development of these segments of products. Let's find the same by understanding a checklist and visualize certain case studies.
As the sterile injectable market continues to see rapid growth (~10% to 15% per annum) – outpacing the growth of oral products – it is natural to see the diversity of parenteral product formulations increasing in parallel. The definition of complexity in parenteral formulation development is broad. It varies based on the stage of development and the specific nature of the challenge. A notionally simple, stable reproducible laboratory formulation may carry a level of complexity in aseptic control if routine means of sterilization are unavailable.
Sterile filtration process intensification can bring significant benefits to manufacturers in terms of manufacturing flexibility, reduction of risks, better turn around time, thus achieving significantly higher productivity. We will identify these scenarios with case studies to reduce complications in manufacturing and process development.
Sterile filtration of complex injectables by Partha BanerjeeMerck Life Sciences
The document discusses considerations for sterile filtration of complex injectables such as liposomes, emulsions, and viscous formulations. It notes that sterile filtration is widely used for liposome sterilization but poses challenges due to the small size of liposomes and bacteria. Key parameters for liposomes include particle size distribution, zeta potential, and stability. The talk addresses regulatory guidelines for liposome characterization and manufacturing. It also outlines best practices for sterile filtration of oils, emulsions and viscous drugs to optimize the filtration process.
Cleaning validation is important to ensure safety and prevent contamination during pharmaceutical production. It involves collecting data to prove cleaning procedures consistently remove residues to acceptable limits. Key aspects of validation include defining cleaning procedures, acceptance criteria, sampling methods, and analytical techniques. Validation should continue if procedures or products change. Overall, cleaning validation demonstrates equipment is suitably cleaned between batches to maintain quality as required by cGMP regulations.
Challenges using Multiple Single-use Systems: Functionality versus Extractabl...MilliporeSigma
As single-use technologies continue to expand in pharmaceutical manufacturing processes, the risk assessment for extractables and leachables becomes increasingly complex. Join this webinar to obtain guidance on how to perform risk evaluation on a process with multiple single-use components.
A Single-Use System (SUS) is typically designed for a specific process step. In many cases, single-use components are chosen based on their functionality. The challenge arises when there are multiple processing steps-- as the different applications and product matrices are evaluated, the complexity of the risk assessment increases. Complexity includes component evaluation, process conditions, and model solvents streams which ultimately relates to the patient safety risk.
This webinar will evaluate the different single-use components with respect to compatibility and extractables and leachables. A case study will be used to demonstrate the complexity and potential concerns when performing a risk evaluation on the manufacturing process.
In this webinar, you will learn:
- Risk assessment of extractables
- Single-use component evaluation
- Complexity when evaluating multiple assemblies
Challenges using Multiple Single-use Systems: Functionality versus Extractabl...Merck Life Sciences
As single-use technologies continue to expand in pharmaceutical manufacturing processes, the risk assessment for extractables and leachables becomes increasingly complex. Join this webinar to obtain guidance on how to perform risk evaluation on a process with multiple single-use components.
A Single-Use System (SUS) is typically designed for a specific process step. In many cases, single-use components are chosen based on their functionality. The challenge arises when there are multiple processing steps-- as the different applications and product matrices are evaluated, the complexity of the risk assessment increases. Complexity includes component evaluation, process conditions, and model solvents streams which ultimately relates to the patient safety risk.
This webinar will evaluate the different single-use components with respect to compatibility and extractables and leachables. A case study will be used to demonstrate the complexity and potential concerns when performing a risk evaluation on the manufacturing process.
In this webinar, you will learn:
- Risk assessment of extractables
- Single-use component evaluation
- Complexity when evaluating multiple assemblies
Sterile filtration of complex injectables by Partha BanerjeeMilliporeSigma
Sterile filtration and filter validation remain a critical segment during the development of these segments of products. Let's find the same by understanding a checklist and visualize certain case studies.
As the sterile injectable market continues to see rapid growth (~10% to 15% per annum) – outpacing the growth of oral products – it is natural to see the diversity of parenteral product formulations increasing in parallel. The definition of complexity in parenteral formulation development is broad. It varies based on the stage of development and the specific nature of the challenge. A notionally simple, stable reproducible laboratory formulation may carry a level of complexity in aseptic control if routine means of sterilization are unavailable.
Sterile filtration process intensification can bring significant benefits to manufacturers in terms of manufacturing flexibility, reduction of risks, better turn around time, thus achieving significantly higher productivity. We will identify these scenarios with case studies to reduce complications in manufacturing and process development.
Leak tests in parenteral preparations s majzoob-20-july2015Sayeh Majzoob
The document discusses container-closure integrity testing (CCIT) for parenteral preparations. It aims to provide an overview of CCIT, including why leaks are important to avoid, different leak testing methods, criteria for choosing a suitable method, calibration and validation requirements, and regulatory aspects. The document covers visual inspection, bubble tests, dye tests, microbial ingress tests, vacuum decay methods, pressure decay methods, and high voltage leak detection. It discusses deterministic versus probabilistic methods and FDA regulatory requirements for CCIT and particulate matter.
This document discusses aseptic processing practices and media fill testing (MFT). It outlines the module topics which include describing risks of aseptic processing, sterile processing GMP expectations, support systems, and validating worst case media fills. It explains the two main approaches for making sterile products - terminal sterilization and aseptic processing, noting media fills are required for validation of aseptic processing. The importance of media fills for sterility assurance is emphasized over sterility testing alone. Risks associated with aseptic processing are higher than terminal sterilization if poor operator technique introduces contamination.
Webinar: How a Helium Manufacturing Release Test Increases Integrity Assuranc...Merck Life Sciences
The document discusses MilliporeSigma's helium integrity test technology for validating the integrity of single-use systems. It provides an overview of regulatory guidance on integrity testing, outlines MilliporeSigma's three pillar strategy for integrity assurance, and describes how the helium integrity test works and its ability to detect defects down to 2 microns in size. Mobius single-use assemblies are tested using this method and receive a certificate of quality to verify 100% integrity testing.
Webinar: How a Helium Manufacturing Release Test Increases Integrity Assuranc...MilliporeSigma
Register now to participate in the interactive, on-demand webinar: https://event.on24.com/wcc/r/3633644/850DBDCF39356D977DE6158F85BFAAC1?partnerref=SlideShare
In this webinar, you will learn:
- Different approaches for integrity testing single-use systems
- The benefits of the helium integrity test for increased integrity assurance in critical single-use systems
Detailed description:
Helium integrity testing is an industry-proven test that detects defects in single-use systems. This sensitive test reduces the risk of leaks or microbial ingress into manufacturing processes so manufacturers can be confident their entire systems, including tubing and connection points, are integral. This is especially critical during freezing, thawing, transportation and storage. This webinar will describe development and validation of the helium integrity test and demonstrate how it can benefit critical single-use process steps.
1. The document discusses cosmetic microbiology, including legislation from the European Union and FDA that cosmetics must be safe for consumers.
2. Preservation efficacy testing methods like USP 51, ISO 11930, and European Pharmacopoeia test the effectiveness of preservatives in cosmetics by inoculating products with microorganisms like bacteria and fungi.
3. The cosmetics industry predominantly uses standard plate counts to test preservation, but challenges include using higher inoculums or microbes isolated from manufacturing environments to better evaluate preservative systems.
SMi Presents the 5th Annual Conference on
Pharmaceutical Microbiology 20 - 21 JAN 2016
Pioneering new techniques for the prevention
detection and management of microorganisms
Single use technology: a regulatory perspectiveTGA Australia
An overview of the regulation of single use technology including Good Manufacturing Practice requirements and the types of deficiencies and issues observed at inspections
Similar to Does PUPSIT Reduce Risk for Sterile Filtration? (20)
The Viscosity Reduction Platform: Viscosity-reducing excipients for improveme...Merck Life Sciences
Protein viscosity is a major challenge in preparing highly concentrated protein formulations suitable for subcutaneous injection. Recently, the Viscosity Reduction Platform (VRP) was introduced and its technical key features and benefits for formulations were discussed. However, highly viscous solutions do not only pose a challenge when administering a drug to a patient, they can also impose technical limitations in the manufacturing process.
This white paper evaluates the effect of the excipients in the Viscosity Reduction Platform on ultrafiltration processes used to produce a highly concentrated formulation of a monoclonal antibody (mAb). Two filtration methods are demonstrated in this work.
Find more information about the Viscosity Reduction Platform on our website: https://www.sigmaaldrich.com/products/pharma-and-biopharma-manufacturing/formulation/viscosity-reduction-platform
Use of Excipients in Downstream Processing to Improve Protein PurificationMerck Life Sciences
Excipients are used to improve the stability of protein-based therapeutics by protecting the protein against a range of stress conditions such as temperature changes, pH changes, or agitation. Similar stresses are applied to proteins during downstream purification. Shifts in pH during Protein A chromatography, subsequent incubations at low pH for virus inactivation, and changes in conductivity in ion exchange chromatography can lead to aggregation, fragmentation, or other chemical modifications of the therapeutic protein. Given the potential impact on the protein’s structural integrity, there is a need for approaches to reduce the risk presented by the conditions during downstream processing. For example, integration of a solution to prevent aggregation of proteins would be a more efficient strategy than implementing steps to remove multimeric forms.
This white paper highlights the results from a recent paper by Stange et. al., in which protein stabilizing excipients such as polyols, sugars, and polyethylene glycol (PEG4000) were used as buffer system additives. Effect of the excipients on elution patterns, stabilization of the monomer antibody, host-cell protein removal, virus inactivation rates and binding capacity of cation exchange chromatography were explored.
Exploring the protein stabilizing capability of surfactants against agitation...Merck Life Sciences
Agitation of therapeutic protein solutions during manufacturing, shipping and handling is one of the major initiators for protein aggregation and particle formation during the life history of a protein drug. Adsorption of protein molecules to liquid-air interfaces leads to the formation of highly concentrated protein surface films. The rupture of these protein films due to various mechanical processes can then result in the appearance of protein aggregates and particles in the bulk solution phase.
One technique to stabilize proteins against stress induced by liquid-air interfaces is the use of non-ionic surfactants. About 91% of antibody formulations commercially available in 2021 contained a surfactant. Polysorbate 20 and 80, composed of a hydrophilic polyoxyethylene sorbitan and hydrophobic fatty acid esters, made up the largest part being employed in 87% of said formulations.
Despite their frequent use in parenteral drug products, concerns have been raised for decades about the application of polysorbates as surfactants in biopharmaceutical formulations. Autoxidation of polysorbate, caused by residual peroxides in polysorbates, can damage the proteins and can further drive the oxidative degradation of polysorbate. Chemical and enzymatic hydrolysis of polysorbate may lead to the formation of free fatty acid particles, which may become visible; and both mechanisms eventually lead to the reduction in polysorbate concentration. Therefore, the purpose of the current study was to compare various molecules for their capabilities to reduced agitation-induced protein aggregation and particle formation; and furthermore, investigate their underlying protein stabilizing mechanisms.
The Viscosity Reduction Platform: Viscosity Reducing Excipients for Protein F...Merck Life Sciences
Protein viscosity is one of the major obstacles in preparing highly concentrated protein formulations suitable for subcutaneous injection.
This whitepaper examines how combining an amino acid with a second viscosity-reducing excipient circumvents adverse effects on protein stability and improves viscosity-reducing capacity.
To find more information about the Viscosity Reduction Platform, please visit our website: https://sigmaaldrich.com/products/pharma-and-biopharma-manufacturing/formulation/viscosity-reduction-platform
Characterization of monoclonal antibodies and Antibody drug conjugates by Sur...Merck Life Sciences
Watch the presentation of this webinar: https://bit.ly/3Pjpjvr
Highlights of this webinar:
- Surface plasmon resonance as a powerful tool for biologic characterization including mAbs and ADCs.
- SPR allows rapid binding analysis in real time without using labels for SARS-CoV-2 receptor binding domain mutations.
- Kinetic data is indicative of possible neutralizing activity allowed assessment of neutralizing ability of therapeutic monoclonal antibodies.
- The application can provide preliminarily efficacy information and facilitated mAbs/ACDs candidate selection process
Detailed description:
Characterization of therapeutic monoclonal antibodies (mAbs) or Antibody drug conjugates (ADCs) is challenging due to their ability to bind to a variety of proteins via their Fc and Fab domains, giving rise to diverse biological functions associated with each domain. The Fc domain of mAbs interacts with Fc receptors with varying affinities, which can influence biological processes such as Complement-dependent cytotoxicity (CDC) and Antibody-dependent cellular cytotoxicity (ADCC), transcytosis, phagocytosis, and/or serum half-life.
An important characteristic of an antibody is its Fc effector function. Antibodies can be engineered to obtain desired binding of the Fc region to Fc receptors expressed on effector cells. Hence, it is crucial to evaluate the binding interaction of mAbs/ADC with Fc receptors in the early phase of drug development to understand the potential biological activity of the product in vivo.
Surface Plasmon Resonance (SPR) is a powerful technique to establish binding kinetics in real-time, label free, and high sensitivity with low sample consumption. Along with target antigen binding, it is crucial to evaluate the binding interaction of antibodies and ADCs with Fc receptors. Our SPR case studies investigated the impact on binding kinetics of ADCs with different linkers and the binding interactions of SARS-CoV-2 spike protein variants and evaluated the neutralizing ability of therapeutic mAbs. SPR characterisation can be facilitated in all stages of the product life cycle to ensure the quality and safety of mAbs and ADCs.
The Role of BioPhorum Extractables Data in the Effective Adoption of Single-U...Merck Life Sciences
Regulatory expectation does require patient safety evaluations with supporting data for manufacturing components that directly come into contact with drug manufacturing process streams. Readily available extractables data can help manufacturers using singleuse technology to accelerate product qualifications, risk assessments and process optimization
This white paper guides you on how to save time and resources with supplier-provided single-use system extractables data and gives you an overview about the overall strategy for Extractables & Leachables. At the end you will find a case study.
Find more information about filters and single-use components on our website: https://www.sigmaaldrich.com/DE/en/services/product-services/emprove-program/emprove-filter-and-single-use-component-portfolio
Watch the recording of this presentation here: https://bit.ly/3zTOpe4
Detailed description:
SARS-CoV-2 showed us that technology supports us during our inspection activity even if on-site visits are not possible. Travel restrictions of various kinds will remain a risk in the future. The use of new technologies has shown that inspections and audits can be carried out despite these restrictions. We will focus on what possibilities the new technologies offer and take a look at the future of inspections and audits.
In this webinar, you will learn:
• Regulatory overview of remote audits
• The technologies needed to support the audit process
• What types of inspections are possible with the use of these technologies
• How audits may look in the future
Presented by:
Daniel Buescher, Product Manager - Digital Solutions
Moving your Gene Therapy from R&D to IND: How to navigate the Regulatory Land...Merck Life Sciences
Watch the recording of this presentation here: https://bit.ly/3SqOsoP
Novel therapies, including cell and gene therapies, continue to be central to innovation in healthcare and represent the fastest growing area of therapeutic medicine. As a consequence, the number of gene therapies undergoing clinical trials has increased significantly in the last five years.
Manufacturing processes for these novel therapeutics are very complex with a high risk of contamination. Regulatory agencies world-wide have responded by issuing guidance to outline their expectations for development and manufacture of cell and gene therapies. Currently, regulatory guidance is not harmonized globally and can often lead to confusion within industry and increased risk of non-compliance.
In this webinar, we'll answer:
• Which regulatory guidelines do you need to comply for your INDs?
• When do you start implementing GMPs and validated assays?
• How do you get your QC testing strategy ‘right the first time’?
• How do you ensure testing is not your rate limiting step for the IND submission?
Presented by:
Manjula Aysola, Senior Regulatory Consultant
Dr. Alison Armstrong, Sr. Director, Technical and Scientific Solutions
Identity testing by NGS as a means of risk mitigation for viral gene therapiesMerck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3RijkHC
Detailed description:
Imagine you’ve just completed a manufacturing run for your viral vector. Identity testing is performed to confirm the vector sequence. But when the results come back the data reveals unexpected sequence variants! With an appropriate risk mitigation testing strategy, this situation can be prevented.
The situation described above is not hypothetical, and happens more that you think, costing valuable time and resources.
Investigatory testing has shown that sequence variants present in starting materials (e.g. plasmids) are likely to make their way to the final product. Adequate identification of low-level variants with an appropriately sensitive method is critical in ensuring the quality of the final product. A risk-based testing strategy, in the context of identity, for viral vector manufacturing will be presented, focusing on key testing points. NGS assays for identity and variant detection will be highlighted due to their extremely sensitive nature compared to traditional approaches.
In this webinar, we'll explore:
• Regulatory requirements for identity testing
• NGS applications for identity testing as compared to traditional methods
• A case study on the impact of not establishing a proper risk-based testing strategy
Presented by: Bradley Hasson, Director of Lab Operations for NGS Services
Latest advancements of melt based 3D printing technologies for oral drug deli...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3A2WcH4
The application of polymer excipients in 3D printing manufacturing is usually limited due to the concerns of filament strength, high processing temperature and large scale manufacturing.
Latest technology developments are targeting a direct melt deposition to simplify the process and enable a constant and efficient process. Two different processing approaches will be presented:
The advanced melt drop deposition, where individual three dimensional geometries can be created by depostition of polymer droplets and the MED® 3D printing technology which allows by precise layer-by-layer deposition to produce objects with well-designed geometric structures.
In this webinar, you will learn:
• Latest advancements of melt based 3D printing approaches
• Application examples for the individual technologies
• Deep dive in the MED® 3D printing technology to design dedicated drug release profiles
Presented by:
Dr. Thomas Kipping, Head of Drug Carriers
Dr. Xianghao Zuo, Deputy Director of R&D, Triastek
CAR-T Manufacturing Innovations that Work - Automating Low Volume Processes a...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3NDNIKe
Automated, fit-for-purpose tools are essential in CAR-T processing to support sustainable manufacturing of clinical and market-approved cell therapy products. This webinar will discuss how the ekko™ Acoustic Cell Processing System uses acoustic technology as a touchless approach to manipulate cells, enabling a modular tool across the CAR-T manufacturing workflow. Typical performance of templated ekko™ System processes for DMSO washout of leukapheresis material, low volume and high cell concentrate for electroporation preparation, and harvest of expanded T cells will be reviewed.
This webinar will also give an early glimpse at the ekko™ Select System for unmatched T cell selection.
In this webinar, you will:
• Uncover how the ekko™ System supports the broad industrialization of cell therapy, with particular focus on how to achieve low volume, high concentrate cell product for critical transduction and transfection steps
• Discover how ekko™ System for wash and concentrate processes throughout the cell therapy workflow achieve high cell recovery, viability, and effective residual removal
• Preview to ekko™ Select, our cell therapy selection platform, to achieve unmatched ease-of-use with direct processing from leukopaks reducing the need for preparation steps
Presented by:
Benjamin Ross-Johnsrud, Acoustic Technology Expert
Robert Scott, Mechanical Engineer III
Viral safety of biologics: What's changing with the ICH Q5A revision?Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3t7X9tg
How does the ICH Q5A revision impact viral safety strategies for biologics?
Biologics continue to grow at a fast pace. Manufactured using cell lines of human or animal origin, these are at risk of viral contamination making safety strategies critical. A comprehensive risk mitigation strategy using multiple orthogonal measures is a regulatory expectation. ICH Q5A, the globally-harmonized guideline outlines the expectations. ICH Q5A is currently being revised to address recent scientific advancements including novel therapeutic modalities, new manufacturing paradigms, updates in viral clearance applications, and alternate detection technologies. We’ll discuss the expected changes and potential impact on viral safety strategies with case studies and examples.
In this webinar, you will learn about:
• The Importance of virus testing in biologics products
• Regulatory landscape, expectations for the Q5A revision
• What's new and changing
• Examples of alternate testing schedules, impact on viral clearance
Presented by:
Manjula Aysola, Senior Regulatory Consultant
Alison Armstrong, PhD, Sr. Director, Technical and Scientific Solutions
Improve Operational Efficiency by Over 30% with Product, Process, & Systems A...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3adaxWh
When implementing new automation systems, organizations must consider things like deployment time, user adoption, and costs.
They must also consider the cost of doing nothing – that is, what competitive advantage is lost in standing still? What time and quality is lost in repetitive, manual tasks rather than an automated, digital workflow? What operational efficiencies are lost?
In this webinar we examine how a product, process, and system agnostic automation platform can be deployed faster than traditional system specific software while bringing greater operational efficiencies (in many cases over 30% improvement).
To remain competitive in the market, biopharma manufacturers must adopt automation and digital technologies, but most plants still have island of automation consisting of independently functioning, standalone unit operations. This results in operational inefficiency, regulatory concerns, and a poor understanding of the process and product life cycle.
Taking the first, right step must include considering risks, costs, timelines, and technology alternatives. Traditional automation approaches tied to specific systems, processes, and products are, by their nature, limited; while an agnostic platform will address current biomanufacturing business challenges and ensure future readiness. With the right platform, a phased automation implementation can yield operational efficiency gains of up to 30% and improved product quality and regulatory compliance.
In this webinar, let's explore:
• Challenges of automation and digital technology adoption
• What a product, process, and system agnostic platform entails
• Applications and benefits of a process orchestration platform
• Ensuring future readiness with process orchestration
Presented by:
Braj Nandan Thakur, Global Product Manager - Automation
Insights from a Global Collaboration Accelerating Vaccine Development with an...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3Nbb5ug
Get insights and best practices from a multinational team establishing a platform for vaccine production. See how a long-term collaboration on a bench-scale process used to produce a Virus Like Particle (VLP) vaccine for SARS-CoV-2 was successfully converted to a robust GMP-compatible, scalable process.
The COVID-19 pandemic further emphasized the need for collaboration in the development of urgently needed vaccines and therapeutics. In this webinar, we take you behind the scenes of our collaboration with Technovax and Innovative Biotech in which a scalable VLP vaccine platform was optimized for use in a production facility in Nigeria in response to the need for local production of SARS-CoV-2 vaccines. The flexibility and robustness of the platform will enable its rapid deployment to support the West African pandemic readiness program. Initial development of the VLP process began in late 2019 and by March 2020, was already adapted for production of a SARS-CoV-2 vaccine.
In this webinar, you will learn:
• About building a priceless collaborative network with integrated solutions
• Virus-Like Particle Vaccines
• Process Development Overview and Challenges
• Pre-clinical Results and Next Steps
Presented by:
Jose M. Galarza, PhD,
President and Founder of TechnoVax
Naomi Baer,
Business development consultant, Emerging Biotech, BioProcess division
Youssef Gaabouri, Eng. ,
Associate Director, Head of Sales Middle East & Africa, BioProcess division
Risk-Based Qualification of X-Ray Sterilization for Single-Use SystemsMerck Life Sciences
The document discusses testing done to qualify the use of x-ray sterilization for a Lynx S2S connector. Physical, chemical, and biological tests were performed on connectors that underwent either x-ray or gamma sterilization. Test results showed comparable extractable levels, thermal properties, and chromatographic profiles between the two sterilization methods. This provides evidence that x-ray sterilization is a suitable alternative to gamma sterilization for this connector.
Rapid replication competent adenovirus (rRCA) detection: Accelerate your lot ...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3MJ4u9V
Testing for presence of replication competent adenovirus (RCA) is a key component to ensure patient safety and a requirement for all biologicals manufactured using adenoviral vectors. For many adenoviral-based products, the RCA assay is a rate-limiting assay for lot release.
Join this webinar to learn about a rapid RCA detection assay currently in development, which combines a 7-day culture assay with a highly sensitive molecular endpoint specific for RCA. The method can detect presence of as little as 1 RCA in adenoviral vector material at an approximate concentration of 5x107 - 2x108 vector particles (VP)/mL, making it a suitable method to meet regulatory requirements while accelerating your lot release timelines.
In this webinar, you will learn about:
• Regulatory framework for adenoviral vector products
• Considerations for lot release testing of adenoviral-based therapies
• Advantages of a rapid method for RCA testing on production lot material
Presented by:
Axel Fun, Ph.D.,
Principal Scientist
Alberto Santana, MBA,
Product Manager, Biologics Biosafety Testing
The High Intensity Sweeteners Neotame and Sucralose: 2 Ways to ace the Patien...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3vQyN7K
Bitter medicines are an important issue, especially for pediatric applications. As several APIs have bitter tasting components, high intensity sweeteners for taste optimization are of great interest. Join our webinar to discover our new sweetener toolbox enabling safe and stable formulations.
Mask bitter aftertaste for a sweeter pill to swallow! Patients’ compliance and the therapeutic benefit are supported by a pleasant taste of pharmaceutical formulations. With the high intensity sweeteners Neotame and Sucralose, you have efficient tools at hand which are superior to other sweeteners in many aspects:
• excellent sugar-like taste profile
• outstanding sweetness factors
• use effectiveness
• enhanced stability
We will present our new toolbox of two high performance sweeteners and focus on aspects of stability, safety, the application in various dosage forms, and market perception.
In this webinar, you will learn:
• How to optimize the patients' taste experience of your pharmaceuticals
• How sweeteners can be differentiated by their sensory profiles and features
• How our new product offering Neotame can be effectively used in your targeted formulations
Presented by:
Almut von der Brelie,
Senior Manager Strategic Marketing
Excipients for Solid Applications
The Developability Classification System (DCS): Enabling an Optimized Approac...Merck Life Sciences
This whitepaper by Dr. Daniel Joseph Price outlines how poorly soluble drug formulations can be designed using the developability classification system (DCS).
The DCS identifies the root cause of low solubility and enables lean, cost-effective and effective formulations to be developed.
#solubility #pharmaceuticalmanufacturing #oralsoliddosage #drugdevelopment
The webinar discusses services from MilliporeSigma to accelerate antibody-drug conjugate (ADC) development through their ADC Express and ADCore product lines. ADC Express provides integrated antibody, linker, payload, and conjugation services to generate multiple ADC candidates for evaluation. The ADCore product line offers intermediates that simplify payload synthesis and accelerate development timelines. ChetoSensar technology incorporates a chito-oligosaccharide to enhance ADC solubility and efficacy.
Can Allopathy and Homeopathy Be Used Together in India.pdfDharma Homoeopathy
This article explores the potential for combining allopathy and homeopathy in India, examining the benefits, challenges, and the emerging field of integrative medicine.
Comprehensive Rainy Season Advisory: Safety and Preparedness Tips.pdfDr Rachana Gujar
The "Comprehensive Rainy Season Advisory: Safety and Preparedness Tips" offers essential guidance for navigating rainy weather conditions. It covers strategies for staying safe during storms, flood prevention measures, and advice on preparing for inclement weather. This advisory aims to ensure individuals are equipped with the knowledge and resources to handle the challenges of the rainy season effectively, emphasizing safety, preparedness, and resilience.
This particular slides consist of- what is hypotension,what are it's causes and it's effect on body, risk factors, symptoms,complications, diagnosis and role of physiotherapy in it.
This slide is very helpful for physiotherapy students and also for other medical and healthcare students.
Here is the summary of hypotension:
Hypotension, or low blood pressure, is when the pressure of blood circulating in the body is lower than normal or expected. It's only a problem if it negatively impacts the body and causes symptoms. Normal blood pressure is usually between 90/60 mmHg and 120/80 mmHg, but pressures below 90/60 are generally considered hypotensive.
TEST BANK For Accounting Information Systems, 3rd Edition by Vernon Richardso...rightmanforbloodline
TEST BANK For Accounting Information Systems, 3rd Edition by Vernon Richardson, Verified Chapters 1 - 18, Complete Newest Version
TEST BANK For Accounting Information Systems, 3rd Edition by Vernon Richardson, Verified Chapters 1 - 18, Complete Newest Version
TEST BANK For Accounting Information Systems, 3rd Edition by Vernon Richardson, Verified Chapters 1 - 18, Complete Newest Version
Let's Talk About It: Breast Cancer (What is Mindset and Does it Really Matter?)bkling
Your mindset is the way you make sense of the world around you. This lens influences the way you think, the way you feel, and how you might behave in certain situations. Let's talk about mindset myths that can get us into trouble and ways to cultivate a mindset to support your cancer survivorship in authentic ways. Let’s Talk About It!
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Does PUPSIT Reduce Risk for Sterile Filtration?
1. The life science business of Merck KGaA,
Darmstadt, Germany operates as
MilliporeSigma in the U.S. and Canada.
Does PUPSIT reduce
risk for sterile
filtration?
Janmeet Anant, Senior Regulatory Consultant
Andrew Koch, Sterile Filtration Technology Manager
18 March 2021
2. The life science business
of Merck KGaA, Darmstadt,
Germany operates as
MilliporeSigma in the U.S.
and Canada
3. Agenda
1
2
3
Regulatory Background of Pre-Use Post
Sterilization Integrity Test (PUPSIT)
Masking study - PUPSIT
Final Filtration Assemblies –
Design/Implementation
4 Q & A
5. Why Integrity Test Critical Filters?
Filtration is required as a terminal sterilization step for biologics
Product Safety
• Sterile filtration is the most critical
step to assure microbial safety
• Pre-use: confirm manufacturer’s
specifications, confirm no damage
during sterilization
• Post-use: confirm filter provides
expected bacterial retention
Business practice
Guidance and regulations
Corporate practices
Does PUPSIT reduce risk for sterile filtration? | 18 March 2021
5
6. There is no common filtration set-up
Points to Consider to Design a Sterile Filtration Process
How
many?
Device
design
Filter
Design
Integrity
test
Flushing
In/out
isolator?
Product
recovery
Choosing the right
number of filters:
single, dual, redundant
Pre-use and post-use
filter integrity test
Filters in or out of the
isolator?
Stacked vs. pleated
Flush bag vs. barrier
filters
Downstream blow down
Does PUPSIT reduce risk for sterile filtration? | 18 March 2021
6
7. Supplier
End-User
Integrity Testing of sterilizing grade filter
A critical element of overall sterility assurance strategy
Validated sterilizing membrane
Validated sterilizing filter
Bacterial retention validation
testing (WCC)
Process Validation and Control
Batch integrity test
Does PUPSIT reduce risk for sterile filtration? | 18 March 2021
7
8. Historical Regulatory Guidance: Pre-Use Integrity Test
“Integrity testing of the filter can be performed prior to
process and should be routinely performed post-use.”
Guidance for Industry. Sterile Drug Products Produced by Aseptic
Processing - Current Good Manufacturing Practice. U.S. Department of
Health and Human Services Food and Drug Administration. September
2004. Pharmaceutical CGMPs
FDA Aseptic Processing
guidelines, 2004
“ The integrity of the sterilised filter should be verified
before use and should be confirmed immediately after
use by an appropriate method such as a bubble point,
diffusive flow or pressure hold test.”
EudraLex. The Rules Governing Medicinal Products in the European
Union. Volume 4. EU Guidelines to Good Manufacturing Practice
Medicinal Products for Human and Veterinary Use. Annex 1. Manufacture
of Sterile Medicinal Products. EUROPEAN COMMISSION. Brussels, 25
November 2008
EMA Annex 1, 2008
Does PUPSIT reduce risk for sterile filtration? | 18 March 2021
8
9. Critical Liquid Filters
When to Integrity Test?
Does PUPSIT reduce risk for sterile filtration? | 18 March 2021
9
10. Filter Integrity Testing
Protects the Patient from microbial contamination
This possibility is called “blinding” or “flaw masking”
Filter
Life
Cycle
Manufacture Sterilization Filtration
Integral Non-Integral Appears
Integral
• Is post-use filter integrity testing sufficient to detect filter failure?
• Is there a possibility that a filter pass the post-use test and have allowed bacterial penetration
during filtration?
Does PUPSIT reduce risk for sterile filtration? | 18 March 2021
10
11. Historical Positions on PUPSIT
Industry position
• Low value, flaw masking is uncommon
• PUPSIT adds risk, may compromise aseptic pathway
• Adds complexity, stresses filter
European regulatory position
• Essential: filtration is risky, flaw masking is a risk
• Industry just does not want to do it, risk assessments are
biased
FDA position
• Nothing official
• Decisions should be risk based
11
12. Regulatory -
EU GMP Annex 1 draft, 2020:
Integrity test before use and
post-use
“…[PUPSIT] may not always
be possible after sterilization due
to process constraints (e.g. the
filtration of very small volumes of
solution). In these cases, an
alternative approach may be taken
as long as a thorough risk
assessment has been performed
and compliance is achieved by the
implementation of appropriate
controls to navigate any risk of
non-sterility.
Industry -
PDA Technical Report 26:
“Integrity testing alone is
insufficient to assure the sterility
of the filtrate. At least two other
elements must be in place:
The production controls and
quality assurance systems
used by the filter
manufacturer ...
And the validation studies
used to show that a particular
combination of product,
processing conditions and
sterilizing grade filter will meet
the requirements of the
bacterial challenge test.”
Establish minimum
Bubble Point
Membrane manufacturing
and testing
Device manufacturing
and testing
Validation studies
End-user integrity test
Integrity test of "sterilizing filter” alone is insufficient
Evolving Perspective – Sterility Assurance
Does PUPSIT reduce risk for sterile filtration? | 18 March 2021
12
14. PUPSIT Consortium Initiated
• Biophorum and PDA Memo of
Understanding (Dec 2017)
• Goal: Gather data and evaluate potential
risks on the merit of PUPSIT to provide
guidance to industry
• Joint effort of filter suppliers and
drug manufacturers
14
15. Flaw must be large enough to pass
microbiological contamination
Flaw must be small enough to be
closed by clogging
Material must be present that can
plug the defect to such an extent
that it is not detectible by post-use
integrity testing
Conditions Necessary for Masking
Does PUPSIT reduce risk for sterile filtration? | 18 March 2021
15
16. PUPSIT
Risk
Masking
Risk
• Increased complexity of the
filtration set-up
• Manipulation of the sterilized
filtrate side
• Microbial ingress of the
filtrate side
• Product dilution with wetting
fluid
• With product wetting,
unknown effects on the
product by the test gas and
time
• …
• Flawed filter will not be
detected by the post-use test
• Microbial penetration
potential not being detected
• Sterilization process
detriments are not detected
• …
The Risk Balance
We Need Data for Resolution
16
17. • Blocking/masking trials performed with
various filters to see whether masking is
possible
• Filter suppliers tested marginally flawed filter
elements
• Test protocol established and reviewed by
European regulators
• Results from bacterial challenge tests were
reviewed to determine if there was any
change in pre-use and post-use integrity test
values
• Results from multiple trials with abroad range
of solutions were reviewed
Masking Trials and Data Mining
Masking Trials
Data mining
The Approach
Does PUPSIT reduce risk for sterile filtration? | 18 March 2021
17
18. Problems and Solutions
Collaboration Team PDA/BPOG
What Has Been Done?
1. Masking studies: can masking occur?
2. Data mining of available bacterial challenge test data
3. Identifying known and potential failure modes of
sterilizing grade filters
Deliverables
1. Developing a risk assessment template to
determine if PUPSIT is warranted
2. Identify best practices for performing PUPSIT
3. Presenting findings to Regulatory
Does PUPSIT reduce risk for sterile filtration? | 18 March 2021
18
19. Determination of Test Parameters
Test Fluid
Ovaltine™: proteinaceous malt, cocoa extract → mimics biologics solution well
Blocking rate
Foulant concentration
24 g/L
worst
case
0.8g/L
mimic
typical
biologic
Masking Trials - Test Fluid
Typical area of
capacity use
Worst case
blockage,
commonly not
used in
terminal sterile
filtration
Does PUPSIT reduce risk for sterile filtration? | 18 March 2021
19
20. • Filter manufacturers collected marginal flawed 10” filter cartridges
Determination of Test Parameters
Masking Trials – Phase 1 Test Protocol
Filters wet and IT
(BP or diffusion)
All integrity tests were performed with
automated integrity test systems
Exposed to blocking
solution (24 g/L Ovaltine™)
at 10 psig to
>90% blocking
Filters
flushed with water (50
L/m2) and IT
(BP or diffusion)
24 g/L
Ovaltine™
>90%
blocking
>90%
24g/L
Worst Case
Scenario
Foulant
Concentration
Blocking
Rate
20
21. Masking trials of flawed 10” filters, tested under worst-case conditions (> 90% blocked)
24 filters tested → 2 passed (masking occurred) and 22 failed the post-use integrity test
Take-home messages
• Confirmed that ‘worst-case’ blocking rate and foulant concentrations
can mask minor flaws in 10% of cases
• Unlikely a high blocking rate would be seen at a terminal filtration
step
>90%
blocking
Masking Trials
Phase 1- Results
24 g/L
Ovaltine™
>90%
blocking
Next steps
• Phase 2 trials at different blocking rates and foulant concentrations
24 g/L
Ovaltine™
>90%
blocking
92%
8%
Masking Phase 1
Failed Pass
Does PUPSIT reduce risk for sterile filtration? | 18 March 2021
21
22. Masking Trials, 47 mm discs, laser drilled flaw
44 integrity tests were performed at 0.8 g/L
→ 2 passed the post use integrity test (masked) (81% and 97%
blockage) and 42 failed the post use integrity test
8 integrity tests were performed at 24 g/L
→ very difficult to filter through a 47 mm disk; all failed post use integrity
test
Take-home messages
• We verified, using Ovaltine, that only at very high blocking rates filter flaws
may be masked: no passing post-use integrity tests (masking) on blockage
rates less than 75% irrespective of fouling solution concentration
• Filter masking does not always happen as 16 out of 18 47 mm disc filters at a
blockage rate >80% failed the post-use test (no masking)
• Filter flaw masking is highly dependent on the product and process
conditions.
Masking Trials
Phase 2- Test Protocol
96%
4%
Masking Phase 2
Failed Pass
Does PUPSIT reduce risk for sterile filtration? | 18 March 2021
22
23. ✓Masking of sterilizing grade filter flaws may occur under extreme circumstances of fouling and blocking.
➢All filters with blocking below 75% failed the post use integrity test (no masking occurred).
➢The few filters that passed the post use integrity test (i.e. masked) were blocked more than 80%
✓Masking of defects in filters pore blocking is highly dependent on the process, product and filter capacity
conditions
Masking Trials
Summary of trials with flawed filters
PUPSIT
Risk
Masking
Risk
Does PUPSIT reduce risk for sterile filtration? | 18 March 2021
23
24. ✓Filterability trials and understanding product and process conditions could be used to determine whether
masking is a possibility or not
➢Prefilters can be used to reduce fouling of sterilizing filters will minimize the risk of filter masking
✓Decisions should balance the risks of PUPSIT implementation vs possibility of filter masking
✓More information on the Masking Studies, Data Mining Studies, Risk Assessments, and PUSPIT
Implementation Considerations are available in publications from the Task Force
Task Force Conclusions
PUPSIT
Risk
Masking
Risk
Does PUPSIT reduce risk for sterile filtration? | 18 March 2021
24
26. PUPSIT Best Practices-Things I Have Learned Along the Way…
SURF Design Considerations
Does PUPSIT reduce risk for sterile filtration? | 18 March 2021
26
27. Process Design Considerations
Designed for PUPSIT
Not Designed for PUPSIT
•Number of filters in system
•Single stage
•Dual stage
•Redundant
•Flushing
•Flush bag (catch can) or barrier
filter
•Product Recovery
•Blow down through filter
•Downstream blow down
Does PUPSIT reduce risk for sterile filtration? | 18 March 2021
27
28. Redesigned Port Minimizes Contamination Risk
Aseptic actuation
PUPSIT & product
recovery
Aseptic sampling
Aseptic Multi-
Purpose Port
(AMPP)
Does PUPSIT reduce risk for sterile filtration? | 18 March 2021
28
29. Number of Filters in the System
Designs for final filtration systems
Single Filter Dual Filter Redundant
✓ Compliance with regulatory guidance
for <10 CFU/100 ml
✓ Minimizes plugging risk for secondary filter
BENEFITS
No back-up in the event of primary
filter failure
Higher hold-up volume
Higher cost
Higher system complexity
CONSIDERATIONS
✓Minimum hold-up volume
✓Minimum flushing requirements
✓Ease of handling and operation
✓Lower filter cost
BENEFITS
No back-up in the event of primary filter failure
Minimal feed bioburden control
High probability of filter plugging
CONSIDERATIONS
✓Compliance with regulatory guidance for
<10 CFU/100 ml
✓Low plugging risk for primary filter
✓Potential batch recovery if one filter fails
integrity test
BENEFITS
Higher hold-up volume
Higher cost
Higher system complexity
CONSIDERATIONS
Bulk
Product
Sterile
Filter
Bulk
Product
Sterile
Filter
Sterile
Filter
Intermediate
Product Hold
Bulk
Product
Sterile
Filter
Sterile
Filter
Bulk Product
Bioburden
Reduction
Filter
Sterile
Filter
Does PUPSIT reduce risk for sterile filtration? | 18 March 2021
29
30. Regulatory Guidance – Redundant Filters
FDA Aseptic Processing Guidelines, 2004
“Use of redundant sterilizing filters should be considered in
many cases”
•Guidance for Industry. Sterile Drug Products Produced by Aseptic Processing -
Current Good Manufacturing Practice. U.S. Department of Health and Human
Services Food and Drug Administration. September 2004. Pharmaceutical
CGMPs
EMA Annex 1, 2008
“Due to the potential additional risks of the filtration method
as compared with other sterilization processes, a second
filtration via a further sterilised micro-organism retaining
filter, immediately prior to filling, may be advisable. The
final sterile filtration should be carried out as close as
possible to the filling point.”
•EudraLex. The Rules Governing Medicinal Products in the European
Union. Volume 4. EU Guidelines to Good Manufacturing Practice Medicinal
Products for Human and Veterinary Use. Annex 1. Manufacture of Sterile
Medicinal Products. EUROPEAN COMMISSION. Brussels, 25 November 2008
Does PUPSIT reduce risk for sterile filtration? | 18 March 2021
30
31. Sterilizing
Filter
Vent Filter
Sterilizing
Filter
Redundant sterile filtration may be done in:
− Conventional hardware such as stainless
steel
− Single-use pre-sterilized systems
− Hybrid (mix of stainless steel and
single-use) systems
Three key criteria
1. The space between the two sterilizing filters must be kept sterile
during the entire operation
2. Each sterilizing filter must be capable of being integrity tested
independently in compliance with the relevant regulations or
guidelines
3. Both sterile filters must be traceable to a relevant filter validation
Criteria for a Redundant Filtration System
Does PUPSIT reduce risk for sterile filtration? | 18 March 2021
31
32. Remove –
Wetting Liquid
Test Gas
While
Maintaining
downstream
Sterility
Atmospheric pressure
(test)
Practical Challenges when Performing PUPSIT
Class C
Filling Line
Sterilizing
Product
Filter
Water Gas
Does PUPSIT reduce risk for sterile filtration? | 18 March 2021
32
33. Current Practice 2
Pre-use test: to flush derivation tank
B
C
Filling Line
Sterilizing
Product
Filter
A
Catch can or
flush volume
tank
Option 1: Catch Can
✓ Extractables are removed
from filtration line
❖ Wetting volume to re-wet
and re-test is limited by flush
tank capacity
❖ Flush tank handling and
preparation is cumbersome
❖ Carboy or flush tank vent
filter to be tested
Points to consider
Does PUPSIT reduce risk for sterile filtration? | 18 March 2021
33
34. B
C
Filling Line
Sterilizing
Product
Filter
A
Phobic/Philic
Hybrid filter
Option 2: Barrier Filter
✓ Unlimited flush volumes
✓ Line blowdown
✓ Passive draining
✓ Lowest filtrate line complexity
✓ One filters to test off-line with
IPA/water wetting solution
❖ Breathing capacity profile linked
to Phobic material and chemistry
Points to consider
Barrier filters contain hydrophilic and hydrophobic sterilizing
membranes
Does PUPSIT reduce risk for sterile filtration? | 18 March 2021
34
35. What is a Barrier Filter?
One disk
pair
3 x Hydrophilic
membranes
1 x Hydrophobic
membrane
Gas
Liquid
Condensate
Barrier filters can pass both
liquid and gas.
Does PUPSIT reduce risk for sterile filtration? | 18 March 2021
35
37. Recovery: Post Process Product Recovery
• During processing the entire system is flooded
with product
• Gas will not pass through the wet membrane
below the bubble point pressure
• To displace downstream liquid with gas requires
either exceeding the bubble point OR applying low
pressure through the vent between the product
filters
• Displaces downstream liquid
Or Low pressure
gas
High pressure
gas
Does PUPSIT reduce risk for sterile filtration? | 18 March 2021
37
38. Blow-down through final
filter
(Exceed filter bubble
point > 50 psi)
Blow-down after final
filter
(Air introduced
downstream)
Post Process Product Recovery
+ No added downstream
fittings
+ No downstream
manipulations
− Requires proper validation
− Risks product foaming
− Downstream component
pressure limits
+ Low pressure
+ Low shear/foaming
+ No added filter validation
concern
− Requires sterile gas filter
• That will require testing
− Requires downstream
fittings and manipulations
Does PUPSIT reduce risk for sterile filtration? | 18 March 2021
38
39. ▪ Filter mix-up – which filter did I test ?
▪ Clamp Sequence
For every step, you need to make sure you know where the
liquid is going and where the air is going
▪ Make sure vent filter does not get wet. Keep it elevated
▪ Make sure vents on filters are closed at the start
▪ Make sure vents are at the high point
Learn From My Mistakes
Does PUPSIT reduce risk for sterile filtration? | 18 March 2021
39
40. Example of Valve Sequencing
Clamp # Clamp Location
Description
Flushing Filter
F 1
Flushing
Filter F 2
Integrity
Test F1
Integrity
Test F2
F1
Blowdow
n
F2
Blowdown
Processing
1 Process Inlet OPEN OPEN CLOSED CLOSED CLOSED CLOSED OPEN
2 F1 Airline CLOSED CLOSED OPEN CLOSED OPEN CLOSED CLOSED
3 Downstream of
F1
CLOSED OPEN CLOSED CLOSED CLOSED CLOSED OPEN
4 F1 Millipak
®
Barrier filter
CLOSED CLOSED OPEN CLOSED OPEN CLOSED CLOSED
5 F2 Airline CLOSED CLOSED CLOSED OPEN CLOSED OPEN CLOSED
6 F2 Millipak
®
Barrier filter
CLOSED CLOSED CLOSED OPEN CLOSED OPEN CLOSED
7 Process Outlet CLOSED CLOSED CLOSED CLOSED CLOSED CLOSED OPEN
Monitoring fluid and air
is complicated. Developing a detailed
SOP will reduce risk.
Utilizing a transparent or translucent
filter will help reduce operator error
Does PUPSIT reduce risk for sterile filtration? | 18 March 2021
40
41. A high number of PUPSIT failures are due to insufficient
wetting:
• Indicated by a marginal failure
• Bubble point that up is up to 30% lower than the
specification
• Diffusional flow rate that is up to 50% higher than the
specification
Check Manufacturer’s recommendations:
• Flush volumes
• Wetting pressure / flow rate
• Pressure hold for static soaking
Filter Wetting Best Practices
Does PUPSIT reduce risk for sterile filtration? | 18 March 2021
41
42. Handling Single-use Assemblies:
Implementation
• Consider the fixture of the assemblies in relation to the
filling line
• A support frame is recommended
• Frames need to be custom-made
• Assembly is unique to the needs of each end-user
• Designs will vary from plant to plant and even from
process to process
• Difficult to have a ‘one size fits all’ approach to
assemblies
• Frames are usually stainless steel
• Easily designed and fabricated
• Creates a familiar feel for the operator
Does PUPSIT reduce risk for sterile filtration? | 18 March 2021
42
43. 1. Flaw masking is possible with severely blocked filters
• PUPSIT mitigates the impact of masking
• For the majority of filtration operations, flaw masking is unlikely to occur
2. Users should assess the risk of flaw masking based on their fluid stream and process
conditions
3. If there is a reasonable risk of flaw masking, the default should be to perform PUPSIT
4. If there is negligible risk of flaw masking, it is recommended users consider a risk-based
approach to the implementation of PUPSIT
5. Improving the design of the final filtration assembly can simplify PUPSIT and product recovery
Conclusions
Does PUPSIT reduce risk for sterile filtration? | 18 March 2021
43
44. Document Acceptance/Publication
Data mining to Determine the Influence of
Fluid Properties on the Integrity Test Values
Published in the PDA
https://journal.pda.org/content/early/2020/05/28/pdajpst.2019.011387
Test Process and Results of Potential
Masking of Sterilizing Grade Filters
Published in the PDA
https://journal.pda.org/content/early/2020/05/28/pdajpst.2019.011189
PDA Points to Consider for Risks Associated
with Sterilizing Grade Filters and Sterilizing
Filtration
Published in the PDA
https://www.pda.org/bookstore/product-detail/5748-points-to-consider-
pupsit1
PDA Points to Consider for Implementation of
Pre-Use Post Sterilization Integrity Testing
(PUPSIT)
Published in the PDA
https://www.pda.org/bookstore/product-detail/5790-points-to-consider-
pupsit2
Capstone Article Published in the PDA Letter June 2020
https://www.pda.org/pda-letter-portal/home/full-article/the-use-of-
scientific-data-to-assess-and-control-risks-associated-with-sterilizing-
filtration
Publications
https://www.biophorum.com/resource/sterile-filtration-qrm-
pupsit/
Does PUPSIT reduce risk for sterile filtration? | 18 March 2021
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