This document provides guidance on optimizing ultrafiltration and diafiltration processes using tangential flow filtration with Pellicon cassettes. It describes performing a series of basic optimization experiments to determine key processing parameters like transmembrane pressure, feed flow rate, and product concentration. The goal is to develop a robust process that delivers high product quality and yield at an optimized scale. The document provides detailed step-by-step instructions for setting up and running experiments to optimize the process.
Optimization of Tangential Flow Filtration Applications and Scale Up Consider...Merck Life Sciences
This presentation provides an introduction to tangential flow filtration applications for AAV and lentivirus and will review:
• Basics of tangential flow filtration (TFF)
• TFF AAV and lentivirus process overview
• Operating parameters optimization: flux-controlled microfiltration
• Scale up considerations
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
This presentation provides an introduction to tangential flow filtration and reviews the following:
- TFF process basics and terminology
- TFF membrane technology
- TFF hardware, devices and systems
- Growing applications and the future
To learn more about this topic or collaborate with our technical experts, schedule an in-person or remote visit at our M Lab™ Collaboration Centers: www.merckmillipore.com/mlab
This document summarizes Pellicon 2 filters and holders for tangential flow filtration. It describes their applications in biopharmaceutical processes, superior performance from void-free membranes, reliable linear scalability from lab to production scale, and choice of feed channel screens and membranes for optimal performance. Key benefits include high flux, product recovery, process reliability and validation support. A selection guide provides information on recommended membranes for different molecular weight cut-offs and applications.
Tangential flow filtration (TFF) is a type of filtration where the fluid flows parallel to the filter surface rather than perpendicular. This allows particles to be swept along the membrane surface rather than building up. TFF has advantages over normal flow filtration like being faster, more efficient, and able to concentrate and exchange buffers in one system. Key steps in TFF include flushing, sanitizing, integrity testing, buffer conditioning, processing like concentration and diafiltration, product recovery, cleaning, and storage. Process parameters like transmembrane pressure, flux, and fouling must be optimized for each application.
Introduction to Tangential Flow Filtration (TFF)MilliporeSigma
This presentation provides an introduction to tangential flow filtration and reviews the following:
- TFF process basics and terminology
- TFF membrane technology
- TFF hardware, devices and systems
- Growing applications and the future
To learn more about this topic or collaborate with our technical experts, schedule an in-person or remote visit at our M Lab™ Collaboration Centers: www.emdmillipore.com/mlab
An Efficient and cGMP-friendly Solution to Diafiltration for Intensified or C...Merck Life Sciences
This document presents a new continuous diafiltration (CDF) system as an efficient solution for intensified or continuous bioprocessing. The CDF system uses tank cycling to keep the membrane in use for diafiltration for most of the time. A 24-hour demonstration of the CDF system showed stable and consistent performance over 24 cycles with less than 6% variation in key parameters like cycle time, flux, conductivity, yield and product concentration. The CDF solution provides 6-8 fold higher membrane utilization compared to batch diafiltration with comparable buffer usage but significantly reduced footprint and linear scalability. It is a robust solution for continuous processing that does not require process re-development.
Optimization of Tangential Flow Filtration Applications and Scale Up Consider...MilliporeSigma
This presentation provides an introduction to tangential flow filtration applications for AAV and lentivirus and will review:
• Basics of tangential flow filtration (TFF)
• TFF AAV and lentivirus process overview
• Operating parameters optimization: flux-controlled microfiltration
• Scale up considerations
To learn more about this topic or collaborate with our technical experts, schedule a remote visit at our M Lab™ Collaboration Centers: www.emdmillipore.com/remotevisit
Single-Pass Tangential Flow Filtration (SPTFF) Theory and PracticeMerck Life Sciences
This document discusses single-pass tangential flow filtration (SPTFF) and provides examples of its use. SPTFF concentrates product in a single pass through a filter assembly without recirculating retentate, allowing for continuous operation. It can reduce process volumes and intensify downstream unit operations like chromatography. The document reviews SPTFF applications, development, and implementation, including a case study where SPTFF concentrated a clarified cell culture harvest 2.5x, reducing a protein A chromatography capture step cycle time from 4.25 to 2 hours while maintaining product quality and yield.
Optimization of Tangential Flow Filtration Applications and Scale Up Consider...Merck Life Sciences
This presentation provides an introduction to tangential flow filtration applications for AAV and lentivirus and will review:
• Basics of tangential flow filtration (TFF)
• TFF AAV and lentivirus process overview
• Operating parameters optimization: flux-controlled microfiltration
• Scale up considerations
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
This presentation provides an introduction to tangential flow filtration and reviews the following:
- TFF process basics and terminology
- TFF membrane technology
- TFF hardware, devices and systems
- Growing applications and the future
To learn more about this topic or collaborate with our technical experts, schedule an in-person or remote visit at our M Lab™ Collaboration Centers: www.merckmillipore.com/mlab
This document summarizes Pellicon 2 filters and holders for tangential flow filtration. It describes their applications in biopharmaceutical processes, superior performance from void-free membranes, reliable linear scalability from lab to production scale, and choice of feed channel screens and membranes for optimal performance. Key benefits include high flux, product recovery, process reliability and validation support. A selection guide provides information on recommended membranes for different molecular weight cut-offs and applications.
Tangential flow filtration (TFF) is a type of filtration where the fluid flows parallel to the filter surface rather than perpendicular. This allows particles to be swept along the membrane surface rather than building up. TFF has advantages over normal flow filtration like being faster, more efficient, and able to concentrate and exchange buffers in one system. Key steps in TFF include flushing, sanitizing, integrity testing, buffer conditioning, processing like concentration and diafiltration, product recovery, cleaning, and storage. Process parameters like transmembrane pressure, flux, and fouling must be optimized for each application.
Introduction to Tangential Flow Filtration (TFF)MilliporeSigma
This presentation provides an introduction to tangential flow filtration and reviews the following:
- TFF process basics and terminology
- TFF membrane technology
- TFF hardware, devices and systems
- Growing applications and the future
To learn more about this topic or collaborate with our technical experts, schedule an in-person or remote visit at our M Lab™ Collaboration Centers: www.emdmillipore.com/mlab
An Efficient and cGMP-friendly Solution to Diafiltration for Intensified or C...Merck Life Sciences
This document presents a new continuous diafiltration (CDF) system as an efficient solution for intensified or continuous bioprocessing. The CDF system uses tank cycling to keep the membrane in use for diafiltration for most of the time. A 24-hour demonstration of the CDF system showed stable and consistent performance over 24 cycles with less than 6% variation in key parameters like cycle time, flux, conductivity, yield and product concentration. The CDF solution provides 6-8 fold higher membrane utilization compared to batch diafiltration with comparable buffer usage but significantly reduced footprint and linear scalability. It is a robust solution for continuous processing that does not require process re-development.
Optimization of Tangential Flow Filtration Applications and Scale Up Consider...MilliporeSigma
This presentation provides an introduction to tangential flow filtration applications for AAV and lentivirus and will review:
• Basics of tangential flow filtration (TFF)
• TFF AAV and lentivirus process overview
• Operating parameters optimization: flux-controlled microfiltration
• Scale up considerations
To learn more about this topic or collaborate with our technical experts, schedule a remote visit at our M Lab™ Collaboration Centers: www.emdmillipore.com/remotevisit
Single-Pass Tangential Flow Filtration (SPTFF) Theory and PracticeMerck Life Sciences
This document discusses single-pass tangential flow filtration (SPTFF) and provides examples of its use. SPTFF concentrates product in a single pass through a filter assembly without recirculating retentate, allowing for continuous operation. It can reduce process volumes and intensify downstream unit operations like chromatography. The document reviews SPTFF applications, development, and implementation, including a case study where SPTFF concentrated a clarified cell culture harvest 2.5x, reducing a protein A chromatography capture step cycle time from 4.25 to 2 hours while maintaining product quality and yield.
Single-Pass Tangential Flow Filtration (SPTFF) Theory and PracticeMilliporeSigma
This document discusses single-pass tangential flow filtration (SPTFF) and provides examples of its use. SPTFF concentrates product in a single pass through a filter assembly without recirculating retentate, allowing for continuous operation. It can reduce process volumes and intensify downstream unit operations like chromatography. The document reviews SPTFF principles, applications, implementation including process development, and case studies using SPTFF to concentrate harvests prior to protein A capture and improve column productivity.
Cross Flow or Tangential Flow Membrane Filtration (TFF) to Enable High Solids...njcnews777
Cross Flow or Tangential Flow Filtration (TFF) Membrane Plants are used in Desalination, Brackish Groundwater Treatment, High Chloride Surface Water Treatment, Waste Water Treatment Plant Effluent Reuse, Biopharmaceutical, Food & Protein Applications for removal of undesired constituents and harvesting of desireable products. Cross flow membrane filtration technology has been used widely in industry globally. Filtration membranes can be polymeric or ceramic, depending upon the application. The principles of cross-flow filtration are used in reverse osmosis, nanofiltration, ultrafiltration and microfiltration. When purifying water, it can be very cost effective in comparison to the traditional evaporation methods. Techniques to improve performance of cross flow filtration include:
Backwashing: In backwashing, the transmembrane pressure is periodically inverted by the use of a secondary pump, so that permeate flows back into the feed, lifting the fouling layer.
Clean-in-place: Clean-in-place systems are typically used to remove fouling from membranes after extensive use. The CIP process may use detergents, reactive agents such as sodium hypochlorite and acids and alkalis such as citric acid and sodium hydroxide.
Concentration: The volume of the fluid is reduced by allowing permeate flow to occur. Solvent, solutes, and particles smaller than the membrane pore size pass through the membrane, while particles larger than the pore size are retained, and thereby concentrated. In bioprocessing applications, concentration may be followed by diafiltration.
Diafiltration: In order to effectively remove permeate components from the slurry, fresh solvent may be added to the feed to replace the permeate volume, at the same rate as the permeate flow rate, such that the volume in the system remains constant. This is analogous to the washing of filter cake to remove soluble components. Dilution and re-concentration is sometimes also referred to as "diafiltration."
Selecting the right aseptic filter for your process can be complicated: today’s biomanufacturer has many filter choices each offering distinct benefits. Understanding the specific needs for individual operations, in terms of flux, capacity, bioburden reduction or sterilizing performance, gamma or thermal compatibility and single or multi-use will inform decisions that have implications for the life of the process. This webinar will provide general customer guidance and explain the benefits and disadvantages of different options to help guide customers to the most appropriate filter for their operation.
In this webinar, you will learn:
- How filter design impacts performance
- Important criteria for filter selection
- New choices and options to maximize productivity for biomanufacturers
Selection, sizing, and operation of bioprocess filtration trains for optimal ...Merck Life Sciences
To increase filter lifetime and improve the economics of filtering bioprocess streams, a prefilter is often installed upstream of a final sterilizing-grade filter. However, determining the economic optimum prefilter and final filter configuration can be challenging. Numerous prefilter options are available, the prefilter to final filter area ratio must be determined, and operating conditions must be selected that will both satisfy the filtration requirements and provide for an economical process that minimizes the filtration system footprint.
One approach towards achieving an optimal filtration system design is to test the bioprocess fluid with several filter configuration combinations and at a range of operating conditions. However, this can be a daunting task and even impractical given the high cost and limited availability of valuable bioprocess fluids. A better approach is to run a limited filtration trial and use a mathematical model that can accurately predict the behavior of the prefilter and final filter under different conditions.
In this webinar we describe a filtration model and test methodology to rapidly and efficiently design an optimal dual-stage filtration process. The model and methodology were applied to Milligard® PES filters, a new class of autoclavable and gamma sterilizable PES membrane prefilters that are designed to protect microfiltration and nanofiltration final filters in bioprocess streams. We show how a model fit to the data from one set of filtration conditions can be used to predict filtration performance at other prefilter to final filter area ratios and operating conditions, and to determine the economic optimum filtration configuration.
In this webinar, you will learn:
- How filters for microfiltration of biological fluids work.
- The effect of operating conditions on filtration performance.
- How to design an optimal series filtration (prefilter and final filter) process.
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
Scale-up of high area filters for microfiltration of biological fluids - Poin...MilliporeSigma
Scale-up of high area filters for biological fluid microfiltration requires accounting for multiple factors to ensure reliable scaling. Key factors include variability in membrane and device properties, process conditions, and non-membrane pressure losses. High area filters have increased productivity but scaling is more complex. Proper device design and narrowing the performance range of small-scale devices improves scaling accuracy. Accounting for pleat density, height, and support permeability is important. High area filters scale linearly for plugging streams but non-linearly for streams where surface caking occurs. A scaling tool with identical pleat structure confirms expected performance.
Normal Flow Filtration: Design and Scale UpMilliporeSigma
This presentation explores bioprocessing filtration best practices, including design and scale up methods. You will learn:
• What is filtration?
• Filter capacity and fouling models
• Filter sizing approaches
• Scale up considerations
To learn more about this topic or collaborate with our technical experts, schedule a remote visit at our M Lab™ Collaboration Centers: www.emdmillipore.com/remotevisit
This presentation provides an introduction to the M Lab™ Collaboration Centers, an overview of chromatography theory, and highlights the benefits of next-generation chromatography.
To learn more about this topic or collaborate with our technical experts, schedule an in-person or remote visit at our M Lab™ Collaboration Centers: www.merckmillipore.com/mlab
Find your filter. What’s best for your process? MilliporeSigma
Selecting the right aseptic filter for your process can be complicated: today’s biomanufacturer has many filter choices each offering distinct benefits. Understanding the specific needs for individual operations, in terms of flux, capacity, bioburden reduction or sterilizing performance, gamma or thermal compatibility and single or multi-use will inform decisions that have implications for the life of the process. This webinar will provide general customer guidance and explain the benefits and disadvantages of different options to help guide customers to the most appropriate filter for their operation.
In this webinar, you will learn:
- How filter design impacts performance
- Important criteria for filter selection
- New choices and options to maximize productivity for biomanufacturers
This document provides information to help users choose the right filtration products for their applications, including:
- An overview of Millipore's filtration product lines such as pleated filters, depth filters, and tangential flow filters.
- A quick reference guide comparing Millipore's filter formats and products.
- Application guides with recommendations for filtration solutions for processes like buffer preparation, cell culture, protein purification, and final drug product filling.
- Details on Millipore's range of disposable and pre-sterilized product options.
The document is intended to be a starting point for filtration selection and provides resources for further assistance from Millipore representatives. Proper testing is still required to
Validation of Tangential Flow Filtration in Biotech ProcessesMerck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3hUKfd7
The objective of validation of a unit operation is to demonstrate with a high degree of confidence that the process performs consistently. The present seminar will focus on the validation of the unit operation of TFF and will provide an overview of the regulatory landscape, the validation master plan, approaches to membrane re-use, cleaning validation, and best practices.
In this webinar, you will learn:
• Validation of TFF
• Validation master plan
• Membrane reuse and cleaning
• TFF scale down models
Speaker: Dr. Subhasis Banerjee,
Principal Technical Application Expert, Bioprocessing APAC
Parvovirus Filtration Best Practices - 25 Years of Hands-On ExperienceMilliporeSigma
In this webinar, you will learn:
- how to measure filter performance and capacity,
- how to optimize filter virus removal capability,
- and avoid potential pit-falls
Detailed description:
This webinar will cover all aspects of parvovirus filtration best practices: process development/ optimization, pilot scale-up, and validation and explain the important connections between these activities. The rationale for the recommended best practices will be explained by discussing the underlying mechanisms that control filter performance.
Technology Trends in Bioprocessing PurificationMilliporeSigma
This presentation reviews current trends in bioprocessing purification and includes key considerations for continuous processing and connected polishing for monoclonal antibodies. Topics include:
• Market trends and the evolution of next-generation processes
• Intensified capture processing
• Continuous virus inactivation
• Connected flow-through polishing
To learn more about this topic or collaborate with our technical experts, schedule an in-person or remote visit at our M Lab™ Collaboration Centers: www.emdmillipore.com/mlab
Selection, sizing, and operation of bioprocess filtration trains for optimal ...MilliporeSigma
This document discusses the selection, sizing, and operation of bioprocess filtration trains for optimal performance. It covers background on membrane types used in biopharma processing including ultrafiltration, virus retentive, and microfiltration membranes. It then discusses filtration mechanisms, series filtration, and modeling approaches to predict filter performance and sizing including classical fouling models and combined blocking and adsorption models. Experimental data is presented to validate the predictive capability of the combined blocking and adsorption fouling model for sizing filters in a series configuration.
Pellicon® 3 cassettes with Biomax® membranes are tangential flow filtration devices designed for high flux and low protein binding. They are suitable for filtration of solutions containing proteins and are compatible with harsh cleaning chemicals. The cassettes are available in different sizes for scale-up and scale-down from research to manufacturing. They provide high product recovery and consistency due to automated manufacturing.
A brief summary of Water System in pharmaceuticals including its production and distribution with regulatory and qualification requirements. This presentation gives a basic layout to non-engineering people a basic understanding of Water System in Pharmaceutical.
Dissolution procedure development and validation, USP 1092Md. Saddam Nawaz
This document discusses the development and validation of dissolution procedures according to USP<1092>. It provides general comments on the purpose of dissolution testing and discusses key aspects of developing a discriminating and reproducible method, including choice of medium, apparatus, study design, sampling, and validation. The document outlines factors to consider for various dosage forms and provides examples of typical dissolution conditions and acceptance criteria.
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.
This document discusses various types of filtration methods used to separate solids from liquids. It describes two main types of filter media: surface filters that trap particles on the filter surface and depth filters that retain particles within a granular bed. Factors to consider when selecting a filter media include its ability to retain solids, resistance to flow and chemicals, and cost. Continuous filters like rotary drum vacuum filters and tangential flow filtration are widely used in industry due to their ability to operate continuously.
This document provides information on various membrane types for syringe filters, including nylon, CA, PTFE, PVDF, PES, MCE. It discusses the properties of each membrane, including hydrophilicity, protein binding, chemical compatibility, temperature resistance and suitable applications. Product codes and specifications are provided for syringe filters with these different membrane types in 13mm, 25mm and 30mm diameters and 0.22 and 0.45 micrometer pore sizes.
Ann enjoys various activities including volleyball, reading young adult novels, spending time with her boyfriend and friends on social media. She is interested in conspiracy theories and social justice issues. She believes media has a huge influence on how communities react to social justice issues by allowing faster and wider spread of information, both accurate and inaccurate. She questions whether lack of information from the government on issues like ISIS is due to politics, and whether early media involvement exacerbated unrest in Ferguson before all facts were known.
Single-Pass Tangential Flow Filtration (SPTFF) Theory and PracticeMilliporeSigma
This document discusses single-pass tangential flow filtration (SPTFF) and provides examples of its use. SPTFF concentrates product in a single pass through a filter assembly without recirculating retentate, allowing for continuous operation. It can reduce process volumes and intensify downstream unit operations like chromatography. The document reviews SPTFF principles, applications, implementation including process development, and case studies using SPTFF to concentrate harvests prior to protein A capture and improve column productivity.
Cross Flow or Tangential Flow Membrane Filtration (TFF) to Enable High Solids...njcnews777
Cross Flow or Tangential Flow Filtration (TFF) Membrane Plants are used in Desalination, Brackish Groundwater Treatment, High Chloride Surface Water Treatment, Waste Water Treatment Plant Effluent Reuse, Biopharmaceutical, Food & Protein Applications for removal of undesired constituents and harvesting of desireable products. Cross flow membrane filtration technology has been used widely in industry globally. Filtration membranes can be polymeric or ceramic, depending upon the application. The principles of cross-flow filtration are used in reverse osmosis, nanofiltration, ultrafiltration and microfiltration. When purifying water, it can be very cost effective in comparison to the traditional evaporation methods. Techniques to improve performance of cross flow filtration include:
Backwashing: In backwashing, the transmembrane pressure is periodically inverted by the use of a secondary pump, so that permeate flows back into the feed, lifting the fouling layer.
Clean-in-place: Clean-in-place systems are typically used to remove fouling from membranes after extensive use. The CIP process may use detergents, reactive agents such as sodium hypochlorite and acids and alkalis such as citric acid and sodium hydroxide.
Concentration: The volume of the fluid is reduced by allowing permeate flow to occur. Solvent, solutes, and particles smaller than the membrane pore size pass through the membrane, while particles larger than the pore size are retained, and thereby concentrated. In bioprocessing applications, concentration may be followed by diafiltration.
Diafiltration: In order to effectively remove permeate components from the slurry, fresh solvent may be added to the feed to replace the permeate volume, at the same rate as the permeate flow rate, such that the volume in the system remains constant. This is analogous to the washing of filter cake to remove soluble components. Dilution and re-concentration is sometimes also referred to as "diafiltration."
Selecting the right aseptic filter for your process can be complicated: today’s biomanufacturer has many filter choices each offering distinct benefits. Understanding the specific needs for individual operations, in terms of flux, capacity, bioburden reduction or sterilizing performance, gamma or thermal compatibility and single or multi-use will inform decisions that have implications for the life of the process. This webinar will provide general customer guidance and explain the benefits and disadvantages of different options to help guide customers to the most appropriate filter for their operation.
In this webinar, you will learn:
- How filter design impacts performance
- Important criteria for filter selection
- New choices and options to maximize productivity for biomanufacturers
Selection, sizing, and operation of bioprocess filtration trains for optimal ...Merck Life Sciences
To increase filter lifetime and improve the economics of filtering bioprocess streams, a prefilter is often installed upstream of a final sterilizing-grade filter. However, determining the economic optimum prefilter and final filter configuration can be challenging. Numerous prefilter options are available, the prefilter to final filter area ratio must be determined, and operating conditions must be selected that will both satisfy the filtration requirements and provide for an economical process that minimizes the filtration system footprint.
One approach towards achieving an optimal filtration system design is to test the bioprocess fluid with several filter configuration combinations and at a range of operating conditions. However, this can be a daunting task and even impractical given the high cost and limited availability of valuable bioprocess fluids. A better approach is to run a limited filtration trial and use a mathematical model that can accurately predict the behavior of the prefilter and final filter under different conditions.
In this webinar we describe a filtration model and test methodology to rapidly and efficiently design an optimal dual-stage filtration process. The model and methodology were applied to Milligard® PES filters, a new class of autoclavable and gamma sterilizable PES membrane prefilters that are designed to protect microfiltration and nanofiltration final filters in bioprocess streams. We show how a model fit to the data from one set of filtration conditions can be used to predict filtration performance at other prefilter to final filter area ratios and operating conditions, and to determine the economic optimum filtration configuration.
In this webinar, you will learn:
- How filters for microfiltration of biological fluids work.
- The effect of operating conditions on filtration performance.
- How to design an optimal series filtration (prefilter and final filter) process.
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
Scale-up of high area filters for microfiltration of biological fluids - Poin...MilliporeSigma
Scale-up of high area filters for biological fluid microfiltration requires accounting for multiple factors to ensure reliable scaling. Key factors include variability in membrane and device properties, process conditions, and non-membrane pressure losses. High area filters have increased productivity but scaling is more complex. Proper device design and narrowing the performance range of small-scale devices improves scaling accuracy. Accounting for pleat density, height, and support permeability is important. High area filters scale linearly for plugging streams but non-linearly for streams where surface caking occurs. A scaling tool with identical pleat structure confirms expected performance.
Normal Flow Filtration: Design and Scale UpMilliporeSigma
This presentation explores bioprocessing filtration best practices, including design and scale up methods. You will learn:
• What is filtration?
• Filter capacity and fouling models
• Filter sizing approaches
• Scale up considerations
To learn more about this topic or collaborate with our technical experts, schedule a remote visit at our M Lab™ Collaboration Centers: www.emdmillipore.com/remotevisit
This presentation provides an introduction to the M Lab™ Collaboration Centers, an overview of chromatography theory, and highlights the benefits of next-generation chromatography.
To learn more about this topic or collaborate with our technical experts, schedule an in-person or remote visit at our M Lab™ Collaboration Centers: www.merckmillipore.com/mlab
Find your filter. What’s best for your process? MilliporeSigma
Selecting the right aseptic filter for your process can be complicated: today’s biomanufacturer has many filter choices each offering distinct benefits. Understanding the specific needs for individual operations, in terms of flux, capacity, bioburden reduction or sterilizing performance, gamma or thermal compatibility and single or multi-use will inform decisions that have implications for the life of the process. This webinar will provide general customer guidance and explain the benefits and disadvantages of different options to help guide customers to the most appropriate filter for their operation.
In this webinar, you will learn:
- How filter design impacts performance
- Important criteria for filter selection
- New choices and options to maximize productivity for biomanufacturers
This document provides information to help users choose the right filtration products for their applications, including:
- An overview of Millipore's filtration product lines such as pleated filters, depth filters, and tangential flow filters.
- A quick reference guide comparing Millipore's filter formats and products.
- Application guides with recommendations for filtration solutions for processes like buffer preparation, cell culture, protein purification, and final drug product filling.
- Details on Millipore's range of disposable and pre-sterilized product options.
The document is intended to be a starting point for filtration selection and provides resources for further assistance from Millipore representatives. Proper testing is still required to
Validation of Tangential Flow Filtration in Biotech ProcessesMerck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3hUKfd7
The objective of validation of a unit operation is to demonstrate with a high degree of confidence that the process performs consistently. The present seminar will focus on the validation of the unit operation of TFF and will provide an overview of the regulatory landscape, the validation master plan, approaches to membrane re-use, cleaning validation, and best practices.
In this webinar, you will learn:
• Validation of TFF
• Validation master plan
• Membrane reuse and cleaning
• TFF scale down models
Speaker: Dr. Subhasis Banerjee,
Principal Technical Application Expert, Bioprocessing APAC
Parvovirus Filtration Best Practices - 25 Years of Hands-On ExperienceMilliporeSigma
In this webinar, you will learn:
- how to measure filter performance and capacity,
- how to optimize filter virus removal capability,
- and avoid potential pit-falls
Detailed description:
This webinar will cover all aspects of parvovirus filtration best practices: process development/ optimization, pilot scale-up, and validation and explain the important connections between these activities. The rationale for the recommended best practices will be explained by discussing the underlying mechanisms that control filter performance.
Technology Trends in Bioprocessing PurificationMilliporeSigma
This presentation reviews current trends in bioprocessing purification and includes key considerations for continuous processing and connected polishing for monoclonal antibodies. Topics include:
• Market trends and the evolution of next-generation processes
• Intensified capture processing
• Continuous virus inactivation
• Connected flow-through polishing
To learn more about this topic or collaborate with our technical experts, schedule an in-person or remote visit at our M Lab™ Collaboration Centers: www.emdmillipore.com/mlab
Selection, sizing, and operation of bioprocess filtration trains for optimal ...MilliporeSigma
This document discusses the selection, sizing, and operation of bioprocess filtration trains for optimal performance. It covers background on membrane types used in biopharma processing including ultrafiltration, virus retentive, and microfiltration membranes. It then discusses filtration mechanisms, series filtration, and modeling approaches to predict filter performance and sizing including classical fouling models and combined blocking and adsorption models. Experimental data is presented to validate the predictive capability of the combined blocking and adsorption fouling model for sizing filters in a series configuration.
Pellicon® 3 cassettes with Biomax® membranes are tangential flow filtration devices designed for high flux and low protein binding. They are suitable for filtration of solutions containing proteins and are compatible with harsh cleaning chemicals. The cassettes are available in different sizes for scale-up and scale-down from research to manufacturing. They provide high product recovery and consistency due to automated manufacturing.
A brief summary of Water System in pharmaceuticals including its production and distribution with regulatory and qualification requirements. This presentation gives a basic layout to non-engineering people a basic understanding of Water System in Pharmaceutical.
Dissolution procedure development and validation, USP 1092Md. Saddam Nawaz
This document discusses the development and validation of dissolution procedures according to USP<1092>. It provides general comments on the purpose of dissolution testing and discusses key aspects of developing a discriminating and reproducible method, including choice of medium, apparatus, study design, sampling, and validation. The document outlines factors to consider for various dosage forms and provides examples of typical dissolution conditions and acceptance criteria.
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.
This document discusses various types of filtration methods used to separate solids from liquids. It describes two main types of filter media: surface filters that trap particles on the filter surface and depth filters that retain particles within a granular bed. Factors to consider when selecting a filter media include its ability to retain solids, resistance to flow and chemicals, and cost. Continuous filters like rotary drum vacuum filters and tangential flow filtration are widely used in industry due to their ability to operate continuously.
This document provides information on various membrane types for syringe filters, including nylon, CA, PTFE, PVDF, PES, MCE. It discusses the properties of each membrane, including hydrophilicity, protein binding, chemical compatibility, temperature resistance and suitable applications. Product codes and specifications are provided for syringe filters with these different membrane types in 13mm, 25mm and 30mm diameters and 0.22 and 0.45 micrometer pore sizes.
Ann enjoys various activities including volleyball, reading young adult novels, spending time with her boyfriend and friends on social media. She is interested in conspiracy theories and social justice issues. She believes media has a huge influence on how communities react to social justice issues by allowing faster and wider spread of information, both accurate and inaccurate. She questions whether lack of information from the government on issues like ISIS is due to politics, and whether early media involvement exacerbated unrest in Ferguson before all facts were known.
radmin3.5 is th greatest software Read me_A_N_S_O_O_
Radmin is remote control software that allows users to access and control remote computers running Radmin Server from computers running Radmin Viewer. Radmin Server must be installed on the remote computer and Radmin Viewer on the local computer used to access the remote machine. The document provides information on system requirements, installation instructions for both Radmin Server and Viewer, how to establish a connection between them, and contact details for support.
This document provides information on Millipore's ultrafiltration membrane products for macromolecule processing. It describes four product lines - Biomax PB, Ultracel PLC, Ultracel PL, and Viresolve membranes. For each product line, it lists the key features and applications. It also includes specifications sheets that provide further details on each individual membrane type, such as molecular weight cutoff range, material composition, flux rates and dimensions. The document is intended to help users select the appropriate ultrafiltration membrane for their specific application.
This document is a vision board divided into 4 sections: business, personal, physical, and spiritual. It appears to be an organizational tool for setting goals and visualizing success in different areas of one's life.
La alfabetización como estrategia de aprendizajeDiego Puchana
El documento habla sobre el analfabetismo digital. Define el analfabetismo digital como la falta de conocimiento y mal uso de dispositivos tecnológicos. Explica que las personas mayores son más afectadas porque les resulta difícil aprender y adaptarse a las herramientas tecnológicas. Propone posibles soluciones como invertir en infraestructura, implementar programas educativos y reducir costos de servicios para mejorar el acceso a la tecnología. Finalmente, señala que el uso adecuado de la tecnología permite estar preparado
This document is a vision board divided into 4 sections: business, personal, physical, and spiritual. It appears to be an organizational tool for setting goals and visualizing success in different areas of one's life.
syringe filters are most common type of filtration devices in small scale applications.we use syringe filters mostly for preparing samples of HPLC, GC, Atomic Absorption and ...
depends on what solutions we use, different types of membranes apply in syringe filters.
please see this file to find out more about syringe filters.
فیلترهای سرسرنگی را میتوان محبوب ترین انواع فیلتر در کاربردهای آزمایشگاهی برشمرد. این فیلترها بیش از همه برای آماده سازی نمونه های کروماتوگرافی و جذب اتمی کاربرد دارند.
انواع مختلفی از ممبران (غشاء) با توجه به موادی که قرار است فیلتر شوند در فیلتر سر سرنگی به کار برده میشود. برای آشنایی بیشتر با انواع فیلترهای سرنگی این راهنما را مطالعه فرمایید.
Enhancing Sensitivities and Peak Capacities for UHPLC-MS Fast Gradient Analys...Sandy Simmons
When compared to 1.7 μm fully porous materials, the ultra-high
efficiency and low backpressures provided by Kinetex core-shell
2.6 μm columns, provides users opportunities to go beyond what
is traditionally accepted for UHPLC runs
Intensified mAb polishing: linking single-pass tangential flow filtration wit...Frédéric Sengler
Process intensification is an approach to improve operational
throughput by running a manufacturing process or unit operation
differently. In mAb purification, intensified processing can remove
bottlenecks created by high bioreactor titers, increase manufacturing
flexibility for multi-product facilities, and reduce cost of goods while
increasing the focus on product quality.
This work focuses on intensifying the anion exchange (AEX) mAb
polishing step. AEX polishing is commonly used to provide clearance
of host cell protein (HCP) and virus impurities.
The mAb polishing
step can be intensified by pre-concentrating the AEX feed
material using Single-Pass Tangential Flow Filtration (SPTFF).
4 modeling and control of distillation column in a petroleum processnazir1988
This document describes the modeling and simulation of a condensate distillation column in a petroleum process. It presents a calculation procedure to model the column based on an energy balance structure using reflux rate and boilup rate as inputs to control distillate purity and bottom product impurity. A nonlinear dynamic model of the column is developed and simulated in MATLAB. The simulation shows the column can maintain product quality under normal operations but quality decreases with disturbances like changes in feed rate. A reduced-order linear model is then developed for use in model-reference adaptive control to improve disturbance rejection.
An Efficient and cGMP-friendly Solution to Diafiltration for Intensified or C...MilliporeSigma
View the recording here: https://bit.ly/2M6cTYD
Abstract:
Diafiltration is a critical unit operation in the downstream purification train for nearly all monoclonal antibodies and other therapeutic biomolecules, with a particular application being the final formulation step. It provides a cost-effective, efficient, and robust method for achieving > 3 logs of buffer exchange. As the biomanufacturing industry strives for more efficient and cost-conscious processes and facilities by adapting templates to be more flexible, handle larger batch sizes, require lower plant footprint, and run in an integrated or continuous mode, diafiltration has been one of the last unit operations to change. Updated technologies for chromatography, clarification, and concentration have been developed in recent years, offering significant improvements over their existing batch processing equivalents. However, it has been challenging to develop a similar intensified and continuous technology for diafiltration that exceeds established expectations around unit operation productivity while maintaining a process that is easily implementable and suitable for GMP manufacturing.
Our approach to intensified, continuous diafiltration bases the process design on membrane utilization, as opposed to flux and process time typically used for batch designs. The result is a flexible solution that offers 6-8-fold decrease in membrane area, up to 3-fold reduction in pump passes and a substantial footprint reduction. Buffer usage, extent of buffer exchange, and product yield are equivalent to a traditional constant-volume diafiltration process. The process development approach, system components, and process control rely on well-established methods and technologies, reducing risk during scaleup and manufacturing implementation.
In this webinar, you will learn:
- A new process design for continuous diafiltration and its operational robustness over a 24-hour run
- Benefits of implementing this version of intensified or continuous diafiltration in your process train
This document discusses minimum flow systems for pumps. It describes three types of pump recycle systems used to protect pumps from operating at low flows: continuous recycle systems using an orifice, control loop systems using a control valve, and automatic recirculation systems. It provides guidance on applying each type, including considerations for sizing recycle flows, locating flow meters and control valves, dealing with pressure drops, and routing recycle lines. The document asks how pump capacity should be stated if a pump has a continuous 30 gpm recycle flow added to its 100 gpm normal flow.
A Novel Approach to Diafiltration for Intensified or Continuous ProcessingMilliporeSigma
Diafiltration (DF) is at the heart of the final downstream process step for a majority of mAb-based and other therapeutic molecules. However, as process templates have adapted to be more flexible, handle larger batch sizes, require lower plant footprint, and run in an integrated or continuous mode, DF has been one of the last unit operations to change. This poster describes a solution for continuous diafiltration that includes the following characteristics:
• Requires only a small modification to standard operating strategies
• Delivers a continuous process
• Yields significant reductions in membrane area and system size
To learn more about this topic or collaborate with our technical experts, schedule an in-person or remote visit at our M Lab™ Collaboration Centers: www.emdmillipore.com/mlab
The document provides instructions for a 1-hour competition using an ultrafiltration-reverse osmosis (UF-RO) filtration system to collect drinking water. Contestants must (1) collect a minimum of 3 litres of water from the RO filter with total dissolved solids (TDS) of 15 ppm or below and (2) collect as much additional water as possible from the UF permeate tank with TDS of 50 ppm or below. Points will be awarded based on the total volume of water collected in both tanks. The document outlines operating procedures and restrictions for the UF and RO processes, including allowable pressure ranges and a prohibition on operating functions simultaneously.
This document discusses single-pass tangential flow filtration (SPTFF) as an alternative to batch ultrafiltration. SPTFF uses multiple membrane filter modules or sections in series to concentrate and diafilter solutions in a single pass, achieving higher conversion than batch systems. It compares SPTFF to batch ultrafiltration, outlines how SPTFF works, and presents testing results demonstrating its performance for intermediate concentration and final formulation of IVIG.
Single-Pass TFF (SPTFF) Evaluation in a mAb Process to Debottleneck Tank Size...Frédéric Sengler
Single-pass TFF is a new way to use an existing technology.
The product feed is constantly concentrated during a single
pass through serialized TFF device up to the targeted final
concentration. A recirculation loop is not required, simplifying
hardware settings and reducing hold up volume and footprint.
This allows higher product recovery while reducing the risk
of product damage associated with traditional recirculation.
Single-pass TFF is also a convenient way to reduce volumes,
helping to eliminate tank bottlenecks.
In this poster we will highlight a mAb case study, where SPTFF
is applied to overcome these challenges.
1. This document discusses the scale up considerations for producing capsules in a pilot plant setting. It covers the various unit operations involved in capsule production like mixing, granulation, drying, lubrication, filling and finishing.
2. Key factors that must be considered during scale up for each unit operation are discussed, such as blender load, mixing time, drying temperature and airflow, amount of lubricant added, filling machine parameters, and polishing methods. Process controls and quality checks are also important to ensure quality and reproducibility.
3. Proper facility layout and environmental controls are required to maintain cGMP standards as the capsule production process is scaled up.
UPLC provides faster, more sensitive and efficient separations compared to HPLC by using sub-2 μm particles. It operates at higher pressures of up to 100 MPa. Smaller particle sizes and columns allow for shorter run times, lower detection limits, less solvent usage and improved resolution. Key aspects of UPLC instrumentation include high-pressure binary pumps, low-volume injection systems, 1.7 μm particle columns, and detectors adapted for smaller flow cells like tunable UV detectors. UPLC finds applications in pharmaceutical analysis, natural products analysis, and metabolomics studies.
Care and use manual waters x bridge columnsJohn Omondi
This document provides guidance on using Waters XBridge chromatography columns. Key points:
- XBridge columns offer excellent peak shape, efficiency, and stability across a range of pH and mobile phases. Each column undergoes quality testing to ensure reproducible performance.
- Proper column installation, equilibration, and efficiency testing are described to optimize column life and separation quality. Sample preparation tips help avoid contamination.
- Operating guidelines cover using guard columns, pH limits, solvents, pressures, and temperatures for different XBridge chemistries. Troubleshooting tips and column storage procedures ensure long term column usability.
1. The test plan aims to prove that two types of lungs (Superfobic and G3) can control gas concentration below 5 PPM for at least 23k liters over their expected 5 year lifetime when used in printing machines.
2. Tests will be conducted on 8 lung units over 2.5 months, measuring DO level, flow rate, vacuum pressure, and ink properties weekly to evaluate if the lungs can maintain low gas concentration over time and different usage conditions.
3. The lungs will be operated 16 hours per day to simulate continuous usage, and data will be analyzed monthly to check for failures like blocked pores or membrane breakdown.
One slider for qualification and validation of depyrogenation and sterilizati...Palash Das
This document provides a qualification and validation matrix for a sterilization tunnel. It outlines various tests to verify performance, including air velocity, filter leakage, differential pressure, airflow visualization, conveyor speed, non-viable particle count, heat distribution, and endotoxin challenge studies. For each test, it describes the purpose, acceptance criteria, test frequency, and methodology. The goal is to ensure the sterilization tunnel achieves proper depyrogenation and sterilization through regular performance testing.
Equilibrium data and related information gathered from a liquid-liquid extraction laboratory “shake test” can provide information for process feasibility and column-type selection in the scaleup of liquid-liquid extraction processes
Most chemical engineers have had the experience of dealing with problematic separations, and most have a general understanding of distillation processes. When it comes to liquid-liquid extraction (LLE) processes (Figure 1), however, the details of how these processes work are often less clear. Most academic chemical engineering degree programs do not heavily emphasize liquid-liquid extraction, and most chemical engineering graduates did not receive more than a few days of instruction on generating equilibrium data for LLE in their degree programs.
PAMS: A Study of Performance in Low and High Humidity EnvironmentsPerkinElmer, Inc.
This document discusses the effects of humidity on the analysis of low-level ozone precursor compounds (0.3-1 ppbv) using a gas chromatography system. An experimental setup was designed to dynamically dilute a PAMS gas standard under both high (77% RH) and dry humidity conditions. The results showed that the chromatograms and peak intensities were virtually identical between the high and low humidity samples, indicating that high humidity has little negative impact on the analysis of these compounds at low ppbv levels. This finding allows the use of dry gas standards without needing to prepare humidified standards.
Lanthanum Carbonate Centrifuge Trial Report 2Richard Lewis
The purpose of the Lanthanum carbonate centrifuge trial was to determine if Lanthanum carbonate could be successfully centrifuged to meet specifications and achieve feed rates for Phase I goals. There were two trials performed using different cloth sizes. Trial 1 used a 20 micron cloth and Trial 2 used a 30 micron cloth. Both trials produced lanthanum carbonate solids within specifications but the loading phase took up most of the cycle time due to filtrate build up on the cake. The 30 micron cloth improved feed rates but still had long loading times. Overall the trials demonstrated lanthanum carbonate can be centrifuged to meet Phase I rate goals.
HPLC is a separation technique that uses tightly packed columns containing small particles of a stationary phase. HPLC can separate mixtures and is useful for analyzing pharmaceuticals, food, biological samples, and more. It works by pumping a pressurized mobile phase through the column, separating compounds as they are retained at different rates on the stationary phase. Key components of an HPLC system include the pump, injector, column, and detector. HPLC provides sensitive, rapid, and high-resolution separations for a variety of applications.
The document discusses batch and continuous manufacturing processes. It defines batch processes as those that operate on discrete quantities of materials in a non-continuous manner, with periods of inactivity between batches. Continuous processes receive and process raw materials into finished units in an uninterrupted flow. Batch processes are useful for small volumes of specialty chemicals and allow scheduling maintenance between batches, while continuous processes are better for large volumes and bulk chemicals with fewer startups/shutdowns. The document also discusses controlling temperature and pressure in batch processes, as well as controlling fluid flow and storage vessel levels in continuous processes. Valve positioners are described as a way to reduce hysteresis in control valves and improve response time.
Similar to A hands on guide to ultrafiltration1 (20)
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
Rasamanikya is a excellent preparation in the field of Rasashastra, it is used in various Kushtha Roga, Shwasa, Vicharchika, Bhagandara, Vatarakta, and Phiranga Roga. In this article Preparation& Comparative analytical profile for both Formulationon i.e Rasamanikya prepared by Kushmanda swarasa & Churnodhaka Shodita Haratala. The study aims to provide insights into the comparative efficacy and analytical aspects of these formulations for enhanced therapeutic outcomes.
Here is the updated list of Top Best Ayurvedic medicine for Gas and Indigestion and those are Gas-O-Go Syp for Dyspepsia | Lavizyme Syrup for Acidity | Yumzyme Hepatoprotective Capsules etc
Osteoporosis - Definition , Evaluation and Management .pdfJim Jacob Roy
Osteoporosis is an increasing cause of morbidity among the elderly.
In this document , a brief outline of osteoporosis is given , including the risk factors of osteoporosis fractures , the indications for testing bone mineral density and the management of osteoporosis
share - Lions, tigers, AI and health misinformation, oh my!.pptxTina Purnat
• Pitfalls and pivots needed to use AI effectively in public health
• Evidence-based strategies to address health misinformation effectively
• Building trust with communities online and offline
• Equipping health professionals to address questions, concerns and health misinformation
• Assessing risk and mitigating harm from adverse health narratives in communities, health workforce and health system
Promoting Wellbeing - Applied Social Psychology - Psychology SuperNotesPsychoTech Services
A proprietary approach developed by bringing together the best of learning theories from Psychology, design principles from the world of visualization, and pedagogical methods from over a decade of training experience, that enables you to: Learn better, faster!
Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Kat...rightmanforbloodline
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Katzung, Verified Chapters 1 - 66, Complete Newest Version.
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Katzung, Verified Chapters 1 - 66, Complete Newest Version.
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Katzung, Verified Chapters 1 - 66, Complete Newest Version.
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Katzung, Verified Chapters 1 - 66, Complete Newest Version.
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Kat...
A hands on guide to ultrafiltration1
1. Application Note
To Place an Order or Receive
Technical Assistance
+98-21-22024327-8 Ext 612
Arash Abed
Mobile: 09128911277
Email: abed@mabnateyf.com
A Hands-On Guide to Ultrafiltration/Diafiltration
Optimization using Pellicon® Cassettes
In ultrafiltration (UF) tangential flow filtration (TFF) systems,
operating parameter selection will have far reaching impact
as the process is scaled to full-scale manufacturing levels.
While there are many factors that contribute to final system
design, several key parameters should be optimized early in
the process development phase. The goal is to develop a
robust process with the following success criteria: superior
product quality, consistent and high product yield, repro-ducible
process flux and time, and a cleaning regime that
allows extended membrane reuse.
The following basic experiments should be considered
during development of processing methodology:
Optimization
– Impact of transmembrane pressure (TMP) and
feed flow on process flux and retention
– Impact of product concentration and buffer conditions
on process flux and retention
– Impact of diavolumes on buffer exchange and
contaminant removal
Paper design and full process simulation with chosen
processing parameters
Typically, the first three experiments are performed
sequentially to bracket process performance and obtain
data for analysis. This information is then combined with
actual manufacturing considerations (batch volume, process
time, etc.) to design a process simulation. The purpose of a
process simulation is to duplicate the entire manufacturing
process in a scale-down format, to confirm sizing, and to
assess preliminary product quality and yield. The intent is
to develop an optimized process, on the bench, that will
efficiently scale-up to meet full-scale manufacturing
expectations.
Figure 1. Basic Optimization Experiments
Sequence Purpose
1. TMP Excursion
at Initial
Concentration
(Cb initial)
Determine TMP for UF/DF
Determine Feed Flow (QF) for UF/DF
Demonstrate Flux Stability
Confirm Retention of Product
↓
2. Concentration /
Volume Reduction
(Cb initial → Cb final)
Determine Flux as Function
of Concentration
Determine Placement
of Diafiltration Step
Determine Flux as Function
of Buffer Conditions
↓
3. TMP Excursion
at Final
Concentration
(Cb final)
Determine TMP for UF/DF
Determine Feed Flow (QF) for UF/DF
Confirm Retention of Product
↓
4. Diafiltration /
Buffer Exchange
Determine Diavolume Requirement
Confirm Retention of Product
during DF
↓
5. Product Recovery Crude Assessment of Step Yield
Product Quality Evaluation
Use this step-by-step guide
to develop a robust UF/
DF process with Pellicon®
cassettes (cutoffs of
100 kD and lower) that will
deliver superior product
quality, reproducible
results, and high yields.
2. 2
The following are step-by-step protocols for basic
optimization experiments.
Set-up and Installation Procedure
Refer to the Maintenance Procedures for Pellicon and
Pellicon 2 Cassette Filters (P17512) or the Pellicon 3 Filters
Installation and User Guide (AN1065EN00) when performing
actual set-up and installation of Pellicon cassettes.
1. Assemble the TFF system as shown in Figure 2.
2. Install the Pellicon cassette(s) (Pellicon 2 Mini with 0.1 m2
membrane area, Pellicon 3 with 0.11 m2 membrane area)
in the appropriate Pellicon holder.
3. Flush the system with water, clean with the appropriate
cleaning agent (per appropriate maintenance guide), and
flush again.
Equilibration Procedure
1. Add 3 L/m2 of the appropriate buffer to the feed tank.
Example: 0.1 m2 membrane area x 3 L/m2 = 0.3 L buffer
2. Direct the retentate and permeate to a waste container.
3. Start the feed pump and achieve the following conditions
by partially closing the retentate valve and adjusting the
pump speed:
– Feed flow of 5 L/min/m2
– Retentate pressure of 2 – 15 psi (0.14 – 1.03 bar)
to achieve approximately 30% conversion
4. When half the buffer has been flushed, put the system
in total recycle mode1 and recirculate for 10 minutes;
verify that the pH and conductivity in the system have
been equilibrated to the level of the starting buffer.
5. Direct the retentate and permeate to a waste container.
6. When the feed tank level reaches the minimum level,
open the retentate valve fully and stop the feed pump
to prevent the introduction of air into the system.
Part 1. TMP Excursion
at Ini tia l Con cen tration
1. Add sufficient volume of product to the feed reservoir
such that final volume or concentration target can be
reached or slightly exceeded (approximately 1 – 1.5 L
of final product at final concentration per m2).
Example: if Cinitial = 10 g/L and Cretentate = 80 g/L,
then the concentration factor is 8X. If the minimum
achievable final volume for 0.1 m2 is 0.1 L, calculate the
required initial volume:
Vinitial = Vminimum x VCF = 0.1 L x 8X = 0.8 L
2. Open the retentate valve fully and configure system in
total recycle mode.
3. Start the feed pump and achieve the following
conditions by partially closing the retentate valve
and adjusting the pump speed:
– Recommended feed flow (QF) rate for
the membrane device, typically 5 L/min/m2
for Pellicon 2 and 3 cassettes
– Minimal TMP, typically 2 – 5 psi (0.14 – 0.34 bar)
for more open membranes and 10 psi (0.69 bar)
for tighter membranes.
Tight membranes
(1 kD, 5 kD, etc.)
Can use large TMP increases since
optimum is typically > 30 psi
Open membranes
(50 kD, 100 kD, etc.)
Can use small TMP increases since
optimum is typically < 10 psi
4. Recirculate the product for 10 – 15 minutes and
ensure that stable process flux is achieved 2 .
5. Record temperatures, pressures, and flows; sample
feed and permeate for product retention 3 .
6. Increase TMP by 5 – 10 psid (0.34 – 0.69 bar) by
manipulating the retentate valve while keeping the feed
flow constant. For more open membranes increase
by 2 – 5 psid (0.14 – 0.34 bar). Repeat steps 4 and 5.
7. Repeat step 6 until flux begins to level off 4 ;
typically 4 – 6 TMP values are evaluated in total.
8. Open the retentate valve fully and allow system to
continue in a total recycle.
9. Increase or decrease the feed flow by 2 – 3 L/min/m2
and repeat steps 4 through 8. If desired, a third feed
flow rate can be investigated.
10. Plot the data as shown in Figure 3.
Figure 2. Schematic of a TFF System
?^^]
MZgd
K^m^gmZm^
OZeo^
IK
?bemkZmbhg
JK
J?
?^^] Fh]ne^
Infi
JI
I?
II
=bZ_bemkZmbhg
;n__^k K^m^gmZm^
I^kf^Zm^
?^^]
3. 3
MFIqnklbhgZmMph?^^]?ehpl
?^^]?enq6.E(fbg(f+
?^^]¼I6+)ilb]
Optimum Point
MFI6+.ilb]
C_61/EFA
Optimum Point
MFI6,)ilb]
C_6*.)EFA
?^^]?enq6.E(fbg(f+
?^^]¼I6+)ilb]
Table 1. Membrane Area vs. Pump Feed Rate (Figure 3)
Q1 = 5 L/min/m2 Q2 = 3 L/min/m2 Q1/Q2
A [m2] Volume / Time / 150 LMH Volume / Time / 86 LMH 0.57
QF [L/min] (5 L/min/m2) x Volume / Time / 150 LMH (3 L/min/m2) x Volume / Time / 86 LMH 0.95
Calculations
The appropriate combination of feed flow rate and TMP
will maximize flux while minimizing the impact of pumping
and shear on the product. The appropriate combination of
these two parameters will also minimize processing time
and/or membrane area. To calculate the optimum feed flow,
compare the required membrane area with the required
pump rate at each of the two feed flow conditions, as
shown in Table 1.
Membrane Area [m2] =
Process Volume [L] / (Flux [LMH] x Process Time [h])
In Figure 3:
AreaQ1 = 0.57 x AreaQ2
Pump feed rate [L/min] =
Feed flux [L/min/m2] x Area [m2]
In Figure 3:
Pump feed rateQ1 = 0.95 x Pump feed rateQ2
In this example it is advantageous to run at the higher
feed flow, Q1, since it only requires 57% of the membrane
area used at the lower feed flow rate at almost the
identical pump feed rate.
Note:
• Anticipated final volume of over-concentrated product
must exceed minimum working volume of membrane
system at selected feed flow rate (QF); avoid
introduction of air and maintain uniform mixing
at end of volume reduction.
• Move from least to greatest fouling conditions:
– Do not test into pressure-independent regime
(past the knee of the flux vs. TMP curve) 4
– Avoid exceeding 30 – 40% conversion ratios
• Check hysteresis if possible by returning the system
to the initial conditions and taking a final flux
measurement; compare initial flux performance
to final flux performance at initial conditions.
• Ensure that choice of TMP and feed flow have
corresponding retention values that are acceptable
( 0.998) at both initial and final product
concentration and in each buffer 5 .
• There is often very little performance difference
versus feed flow rate at low product concentration.
However, at the higher concentrations that will be
investigated in Parts 2 and 3, the benefits of different
feed flow rates should become more pronounced.
Figure 3. TMP Excursion at Two Feed Flows
+))
*/)
*+)
1)
-)
)
MFI!ilb]
?enq!EFA
) *) +) ,) -) .)
?^^]?enq6,E(fbg(f+
?^^]¼I6*)ilb]
?^^]?enq6,E(fbg(f+
?^^]¼I6*)ilb]
4. 4
Part 2. Con cen tration
1. Use the product from Part 1 in the starting buffer.
Based on desired final product concentration factor,
add additional feed volume as needed to ensure
sufficient volume at end of concentration 6.
2. Sample feed to confirm product concentration.
3. Put the system in total recycle.
4. Start the feed pump and achieve the optimum TMP and
feed flow as determined in Part 1 by partially closing
the retentate valve and adjusting the pump speed.
5. Direct the permeate to a separate container to
concentrate product and reduce volume.
6. Record temperatures, pressures, and flows throughout
the concentration; sample feed and permeate for
product retention 7.
7. Concentrate slightly beyond desired final product
concentration.
8. Repeat the TMP excursion outlined in Part 1 to
determine optimum TMP at the final concentration in
the starting buffer.
9. Diafilter with one diavolume to get product into final
buffer and dilute with final buffer back to initial
concentration.
10. Repeat the TMP excursion to determine the optimum
TMP at the initial concentration in the final buffer.
11. Repeat Part 2 steps 2 – 7 once in final buffer using the
optimum TMP as determined above.
12. Plot the data as shown in Figure 4, remembering
to apply a temperature correction in the flux
calculations8.
Calculations
The tradeoff between flux and diafiltration buffer volume
create an optimum bulk concentration at which to perform
diafiltration; this can be calculated using the DF optimiza-tion
Plotting the DF optimization parameter as a function of
product concentration yields the optimum concentrations
for diafiltration in both the starting and final buffers, as
shown in Figure 5.
))
))
))
))
))
))
))
))
)
Figure 4. Flux vs. Concentration
?enq!EFA
?enqol'hg^gmkZmbhg
LmZkmbg`
;n__^k
=bZ_bemkZmbhg
;n__^k
)'* * *) *)) *)))
Ikh]nmhg^gmkZmbhgT`(EV
parameter at each data point:
DF Optimization Parameter =
*)))
1))
/))
-))
+))
)
=?HimbfbsZmbhgIZkZf^m^k
Concentration [g/L] x Flux [LMH]
LmZkmbg`;n__^k
him6+2')`(E
=?HimbfbsZmbhg
?bgZe;n__^k
him6..')`(E
LmZkmbg`
;n__^k
Optimum
Cb for DF
) +) -) /) 1) *)) *+)
Ikh]nmhg^gmkZmbhgT`(EV
LmZkmbg`;n__^k
=bZ_bemkZmbhg;n__^k
?bgZe;n__^k
him6..')`(E
LmZkmbg`;n__^k
him6+2')`(E
=bZ_bemkZmbhg
;n__^k
Figure 5. DF Optimization
There is an alternative approach that may be used to
calculate the optimum concentration at which to perform
diafiltration (Copt). It assumes that the product is completely
retained and that the passage of the permeating species is
constant.
If the flux versus concentration data is plotted as
shown in Figure 4, then the gel concentration, Cg, is the
concentration at which the permeate flux reaches zero
(example: ~ 80 g/L in the starting buffer, ~110 g/L in the
final buffer). The optimum concentration at which to
perform diafiltration is then calculated as9:
Copt [g/L] = Cg [g/L] / e
In Figure 4:
Starting buffer Copt = 80 / 2.71828 = 29.4 g/L
Final buffer Copt = 110 / 2.71828 = 40.5 g/L
The Cg/e method can only be used when the flux vs.
concentration data allows for accurate extrapolation
to zero flux.
5. 5
Note:
• Ensure enough feed material and appropriate system
working volume in order to achieve the final
concentration.
• Based on the results of the additional TMP excursions
performed in Part 2, the TMPs used for concentration
in both the starting and final buffers should be
changed and the concentration should be repeated
to obtain more accurate data.
– If the optimum TMP for the dilute solution occurs
in the pressure-independent region (past the knee
of the curve) for the concentrated solution, then
the TMP should be decreased to the lowest
optimum value.
– If the optimum TMP for the dilute solution occurs
within the pressure-dependent region (before the
knee of the curve) for the concentrated solution,
then the TMP may be increased to the highest
optimum value to further optimize the flux and
reduce the processing time.
• Optimum concentration for diafiltration will be
different for each buffer; choose an average or
the most conservative.
– Restrictions on buffer usage or minimum
recirculation volume often dictate the
concentration at which diafiltration occurs.
– If the required final concentration is significantly
less than the optimum concentration for
diafiltration, over concentration followed by dilution
is a possible option, although rarely chosen. It
should only be considered in cases where
diafiltration buffer is limited and the product is
stable at the higher concentrations.
Part 3. TMP Excursion at Fina l
Con cen tration
1. Use the product from Part 2 at the final concentration in
the final buffer.
2. Repeat steps 2 – 10 of Part 1.
Calculations
Reference Part 1.
Note
Reference Part 1 and Part 2 notes.
6. 6
Part 4. Diafi ltration
1. Use the product from Part 3 at the optimum
concentration for diafiltration; dilute as needed using
the final buffer.
2. Configure the system for constant volume diafiltration.
3. Start the feed pump and achieve the optimum TMP and
feed flow as determined in Part 1 and Part 3.
4. Diafilter the product with the chosen number of
diavolumes:
– Choose the number of diavolumes based on the
product purity specifications (if known, see calculation
below) and add a safety factor of 2 diavolumes, or
– Use 3 – 5 diavolumes as an initial estimate
for upstream UF/DF steps, or
– Use 7 – 12 diavolumes as an initial estimate for
final formulation UF/DF steps
5. Record temperatures, pressures, and flows at every
diavolume; sample feed and permeate for both product
retention, and retention and concentration of the
contaminant of interest.
6. Plot the data as shown in Figure 6.
Calculations
The percentage of the original contaminant in the retentate
at each diavolume can be calculated from the retention
values using the following:
Remaining Contaminant [%] =
100 x e (Retention – 1) x N
where N is the number of diavolumes.
However, since contaminant concentration is being
directly measured in each feed sample throughout diafiltration,
plot these concentrations as a percentage of the
original and use the above equation to plot several lines of
theoretical retention, as shown in Figure 6. This plot will
help demonstrate the contaminant removal at various
retentions.
Select the whole number of diavolumes based on the
acceptable contaminant levels for the product; always add
2 – 3 diavolumes as a 10-fold safety factor for critical
diafiltration steps, such as final formulation. For upstream
steps, add 1 – 2 diavolumes. If the goal of diafiltration is not
to wash out a contaminant but rather to reach a target pH
or conductivity, then the measurement of that quality can
be plotted against the number of diavolumes instead.
Note:
• If it appears necessary to diafilter past ~14
diavolumes, any dead-legs or poor mixing areas in the
system will increase the apparent retention of the
contaminant and make further removal difficult.
• Ensure that choice of TMP and feed flow have
corresponding product retention values that are
acceptable ( 0.998) throughout diafiltration.
Figure 6. Contaminant Removal vs. Diavolumes
*))
*)
*
)'*
)')*
)'))*
hgmZfbgZgmK^mZbg^]
Th_hkb`bgZeV
hgmZfbfZgmK^fhoZeol'=bZohenf^l
) . *) *.
=bZohenf^l
K6)'-
K6)'+
K6)
7. 7
Part 5. Prod uct Re covery
There are various methods for product recovery at
large-scale.10 However, at small-scale, sufficient product
recovery can be achieved by manually tilting the system and
breaking the piping at low-points to drain the product.
Samples of the final retentate should then be analyzed for
product concentration and quality.
1. After the product has been drained from the system,
add one system volume of diafiltration buffer to the
feed tank.
2. Recirculate at the selected feed flow rate with
the retentate valve fully open for 10 minutes.
3. Recover the buffer in a separate container using the
same methods that were used to recover the product.
Samples of this buffer rinse should be analyzed for
product concentration.
4. After the product is recovered, the system should be
cleaned with the appropriate solutions.11
Calculations
Ideally, the total product mass recovered in the retentate,
permeate, and buffer flush as well as unrecoverable holdup
volume should equal the total mass of product in the feed.
If the total product mass recovered is less than the initial
product mass, it is typically due to adsorption and/or
solubility losses during processing.12 However, it is impor-tant
to perform a mass balance and calculate total yield to
ensure optimum process parameters.
Note:
• All calculations are estimates; during these
optimization steps, the product has undergone more
processing than normal. Product degradation and yield
may be slightly affected. For a true indication of
processing on product quality, perform the entire
optimized process using fresh feed and new
membranes.
• Product can be very viscous when recovered and may
affect assays; perform serial dilutions for more
accurate assay results.
• Actual yield and mass balance percentages should be
close to 100% and/or theoretical yield. If significant
losses occur, process parameters (including membrane
type) may have to be changed and then re-optimized.
• In a robust process, adsorption and solubility losses
should be very low.
Actual Yield [%] =
100 x (Vretentate [L] x Cretentate [g/L]) / (Vinitial [L] x Cinitial [g/L])
Mass Balance [%] =
100 x {(Vretentate [L] x Cretentate [g/L]) + (Vpermeate [L] x Cpermeate [g/L]) + (Vrinse [L] x Crinse [g/L])} / (Vinitial [L] x Cinitial [g/L])
The theoretical yield can also be calculated based on the
membrane retention and compared to the actual yield.
Theoretical Yield [%] = 100 x e (Retention – 1)(N + lnX)
where N = number of diavolumes and X = concentration
factor.
8. 8
Pape r Desi gn and
Process Sim ulation
The optimization parameters obtained from the previous
experiments can be combined to design a full process
simulation: concentration, diafiltration, (concentration,) and
recovery. If time permits, a process simulation should be
run immediately following the optimization work, and should
employ the following:
• New set of cassettes; same membrane type,
same cassette path length
• Fresh feedstock
• Fresh buffer(s)
• Optimized process parameters
• See detailed process simulation calculations below.
After performing the process simulation, the system
should be cleaned with the appropriate solution according
to Millipore recommendations.11 If possible, the process
should be rerun using the cleaned membranes to determine
the effectiveness of the cleaning cycle and the consistency
of membrane performance from run-to-run. If the cleaning
cycle does not prove effective, the cleaning parameters or
cleaning solutions will need to be changed and the cleaning
cycle will have to be tested again.
Calculations
The membrane area can be optimized to allow the entire
process (both concentration and diafiltration) to be
completed in the specified timeframe (3 – 4 hours is
recommended). The average flux for each concentration
and diafiltration step can be estimated from the optimiza-tion
data and combined with the desired volumes to be
processed. The approximate required membrane area can
then be calculated for both manufacturing scale and
scale-down runs.
Assume an example process scenario (this would have
been determined by optimization data, DF parameter, etc.):
• 2.9X Concentration:
10 g/L to 29 g/L; flux decreases from 150 LMH to 80 LMH
• 7X Diafiltration:
29 g/L; flux increases from 80 LMH to 85 LMH
• 3.4X Concentration:
29 g/L to 100 g/L; flux decreases from 85 LMH to 20 LMH
• Desired process time is 4 hours
Manufacturing scale volumes as determined by the
customer:
• Feed volume = 5000 L
• Retentate volume at end of 2.9X concentration =
5000 L/2.9 = 1724 L
• Permeate volume removed during 2.9X concentration =
5000 L – 1724 L = 3276 L
• 7X Diafiltration buffer volume = 7 x 1724 L = 12,068 L
• Retentate volume at end of 3.4X Concentration =
1724 L/3.4 = 507 L
• Permeate volume removed during 3.4X concentration =
1724 L – 507 L = 1217 L
9. 9
Average process flux for concentration step:13
Javg = Jfinal + 0.33 (Jinitial – Jfinal) = Jinitial x 0.33 + Jfinal x 0.67
For 2.9X concentration:
Javg = 150 LMH x 0.33 + 80 LMH x 0.67 = 103 LMH
For 3.4X concentration:
Javg = 85 LMH x 0.33 + 20 LMH x 0.67 = 41 LMH
Average process flux for diafiltration step:
For diafiltration the average flux can be estimated as the
initial and final process flux during the diafiltration step.
Required area:
Area = [(Permeate volume/Average flux) Concentration + (Permeate volume/Average flux) Diafiltration + … ] / Time
In this example:
Area = [(3,276 L/103 LMH) + (12,068 L/83 LMH) + (1,217 L/41 LMH)] / 4 hours = 51.6 m2
Add 20% safety factor:
Area = 62 m2
To perform a scale-down process simulation, the same
volume to area ratio is used and scaled based on either the
feed volume that can be used for the simulation or the area
of the desired filtration device. For example, if the process
is to be performed on one Pellicon 2 Mini cassette (with an
area of 0.1 m2), then the required feed volume will be:
Scale-down feed volume =
0.1 m2 x (5000 L/62 m2) = 8 L
Instead, if there is a specific volume of feedstock to
process (example: 25 L), then the required membrane
area will be:
Scale-down membrane area =
25 L x (62 m2/5000 L) = 0.3 m2
The process parameters, including Pellicon device type,
should be consistent between scales, allowing the process
to be completed in a similar timeframe with similar fluxes,
pressures and loadings. The concentration factors, number
of diavolumes and feed quality should be kept consistent at
all scales to ensure robust scalability. However, to demon-strate
process robustness and repeatability, the process
should be tested at pilot scale before proceeding to
manufacturing.
10. 10
Defini tions
Transmembrane Pressure (TMP)
The average applied pressure from the feed to the
permeate side of the membrane.
TMP [bar] = [(PF + PR)/2] - PP
Pressure Drop (ΔP)
The difference in pressure along the feed channel of the
membrane from inlet to outlet.
ΔP [bar] = PF – PR
Conversion Ratio (CR)
The fraction of the feed side flow that passes through the
membrane to the permeate.
CR [–] = QP / QF
Apparent Sieving (Sapp)
The fraction of a particular protein that passes through the
membrane to the permeate stream based on the measurable
protein concentrations in the feed and permeate streams.
A sieving coefficient can be calculated for each protein
in a feedstock.
Sapp [–] = (Concentration in permeate, CP) /
(Concentration in feed, Cb)
Intrinsic Sieving (Si)
The fraction of a particular protein that passes through
the membrane to the permeate stream. However, it is based
on the protein concentration at the membrane surface.
Although it cannot be directly measured, it provides a
better understanding of the membrane’s inherent separa-tion
characteristics.
[–] = (Concentration in permeate, CP) /
Si
(Concentration at membrane wall, Cw)
Retention (R)
The fraction of a particular protein that is retained by the
membrane. It can also be calculated as either apparent or
intrinsic retention. Retention is often also called rejection.
Rapp [–] = 1 – Sapp or Ri = 1 – Si
Permeate Flux ( Jf )
The permeate flow rate normalized for the area of
membrane (m2) through which it is passing.
Mass Flux (Jm )
The mass flow of protein through the membrane normalized
for the area of membrane (m2) through which it is passing.
Jm [g m–2 h–1] = QP x CP / area
Volume Concentration Factor (VCF or X)
The amount that the feed stream has been reduced in
volume from the initial volume. For instance, if 20 L of
feedstock are processed by ultrafiltration until 18 L have
passed through to the permeate and 2 L are left in the
retentate, a ten-fold concentration has been performed so
the Volume Concentration Factor is 10. In a Fed-Batch
concentration process, where the bulk feedstock is held in
an external tank and added to the TFF operation continu-ously
as permeate is removed, VCF should be calculated
based only on the volume that has been added to the
TFF operation.
VCF or X [–] = Total starting feed volume added to
the operation / current retentate volume
Concentration Factor (CF)
The amount that the product has been concentrated in the
feed stream. This depends on both the volume concentra-tion
factor and the retention. As with the VCF, for a
Fed-Batch concentration process, calculate CF based only
on the volume of feedstock added to the TFF application.
CF [–] = Final product concentration /
initial product concentration = VCF(R
app)
Diavolume (DV or N)
A measure of the extent of washing that has been per-formed
during a diafiltration step. It is based on the volume
of diafiltration buffer introduced into the unit operation
compared to the retentate volume. If a constant-volume
diafiltration is being performed, where the retentate volume
is held constant and diafiltration buffer enters at the same
rate that permeate leaves, a diavolume is calculated as:
DV or N [–] = Total buffer volume introduced
to the operation during
diafiltration/retentate volume
11. 11
Refe ren ces /Foo tno tes
1. Total recycle means retentate and permeate lines
return to feed vessel
2. If process flux is unstable, it may be necessary to allow
additional time or investigate other membrane options
3. Retention samples are not required at every data point;
sampling at lowest and highest TMP is typical
4. The point at which the flux levels off is defined as the
point around which the slope of the flux vs. TMP curve
decreases to ≤ 50% of the previous slope. This point is
also referred to as the “knee” of the curve.
5. These other conditions are described in more detail
in Parts 2 and 3.
6. Example: 10X concentration with a final volume of
300 mL requires (300 mL x 10) = 3 L of feed
7. Retention samples are not required at every data point;
initial and final concentration are typical. Typical data
recording interval is approximately every 10 – 15
minutes.
8. See Guide: Maintenance Procedures for Pellicon and
Pellicon 2 Cassette Filters (P17512) or Pellicon 3 Filters
Installation and User Guide (AN1065EN00)
9. Ng P, Lundblad J, and Mitra G, Optimization of Solute
Separation by Diafiltration, Separation Science, 11(5):
499-502, 1976.
10. See Technical Brief: Protein Concentration and
Diafiltration by Tangential Flow Filtration (TB032)
11. See Guide: Maintenance Procedures for Pellicon and
Pellicon 2 Cassette Filters (P17512) or Pellicon 3 Filters
Installation and User Guide (AN1065EN00)
12. See Technical Note: Increase Product Yield in Your UF/DF
Processes (AN1026EN00)
13. Average flux can also be calculated for each step
by dividing the total process volume by the
total process time