Single-use fermentors offer potential advantages over stainless steel fermentors for microbial fermentation processes. This document compares the production capacity and process economics of single-use versus stainless steel strategies. It finds that annual production capacity can increase up to 100% with single-use equipment due to faster batch changeovers. This increased throughput allows more batches to be produced in a shorter time period, outweighing the higher per-batch costs of single-use equipment. Single-use fermentors provide increased flexibility and reduced cross-contamination risk compared to stainless steel.
Scalability of a Single-use Bioreactor Platform for Biopharmaceutical Manufac...KBI Biopharma
Increasing adoption of single-use technologies for bioprocessing along with higher titers from cell culture bioreactor processes has allowed clinical and even commercial manufacturing to be successfully performed in 2000 L-scale single-use bioreactors. Several biopharmaceutical manufacturers have successfully adopted single-use bioreactors for production. However, information about process scalability from glass bioreactors to 2000 L single-use bioreactors for different types of CHO cell lines is not widely available. Here we provide an overview of the key
differences between single-use and conventional stainless steel bioreactors, and highlight factors that are employed while scaling-up from small-scale glass bioreactors to 2000 L-scale single-use bioreactors. Several case studies focusing on process performance across scales into single-use bioreactors are provided. This analysis confirms that the 2000 L-scale single-use bioreactorsystem can be robustly employed for biopharmaceutical manufacturing.
Modern BioManufacturing: Single-Use Technologies in Configurable, Prefabricat...Merck Life Sciences
A co-webinar describing a solution to biopharma's challenge of rapidly and rationally expanding capacity by employing single-use technologies, a templated process train, and pre-fabricated mobile/modular cleanrooms.
Biopharmaceutical companies on the verge of investing into manufacturing or facilities expansion face many questions and challenges. Speed, agility, and flexibility are becoming more critical to executing their changing production and distribution strategies. Platform facility designs which integrate the latest process technologies within innovative pre-fabricated cleanrooms are critical for addressing the trending desire to implement 'clonable' modular facilities that can be delivered in a timely fashion across multiple locations. Companies like Merck KGaA, Darmstadt, Germany and G-CON Manufacturing are working together to combine their technologies and develop simple yet robust platform solutions for industry.
As bioprocessing technologies intensify performance, volumetric requirements become less. As such, 2000L single-use bioreactors - or multiple bioreactors of similar or less volumes - now suffice for the production of novel or biosimilar recombinant proteins. Such a shift in the industry enables the development of more mobile, modular facility designs. We will describe the rationale for this collaboration and its result: a turn-key solution that integrates a templated process train with a rapidly-deployable facility platform. By combining the unique advantages found with the G-CON POD construction and the bioprocess technology expertise from within Merck KGaA, Darmstadt, Germany, the goal of creating a cost-effective, pre-fabricated alternative to historical 'stick built' facilities is being achieved. Additionally, the flexibility inherent to our approach provides for a greater configurability that confers more user-specified choice into the selection of options. Simple in concept, this solution is also robust, cost-effective, and conducive to tight timelines for implementation.
In this webinar you will learn:
- Basic options for facilities/capacity expansion
- The value of templated process trains employing single-use equipment
- How modular, prefabricated PODs® outfitted with such single-use bioprocessing equipment represent an attractive, cost-effective strategy for capacity expansion
POD® is a registered trademark of G-CON Manufacturing, Inc.
Scaling Strategies with Stirred Single-Use Bioreactors from Bench to Clinical...Merck Life Sciences
This presentation introduces the general principles of scaling strategies with stirred single-use bioreactors, discusses key engineering parameters, and concludes with a case study of how these strategies are applied to Mobius® bioreactors from 2 liters to 2000 liters.
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
Single use technology: a regulatory perspectiveTGA Australia
An overview of the regulation of single use technology including Good Manufacturing Practice requirements and the types of deficiencies and issues observed at inspections
Scaling Strategies with Stirred Single-Use Bioreactors from Bench to Clinical...MilliporeSigma
This presentation introduces the general principles of scaling strategies with stirred single-use bioreactors, discusses key engineering parameters, and concludes with a case study of how these strategies are applied to Mobius® bioreactors from 2 liters to 2000 liters.
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
Scalability of a Single-use Bioreactor Platform for Biopharmaceutical Manufac...KBI Biopharma
Increasing adoption of single-use technologies for bioprocessing along with higher titers from cell culture bioreactor processes has allowed clinical and even commercial manufacturing to be successfully performed in 2000 L-scale single-use bioreactors. Several biopharmaceutical manufacturers have successfully adopted single-use bioreactors for production. However, information about process scalability from glass bioreactors to 2000 L single-use bioreactors for different types of CHO cell lines is not widely available. Here we provide an overview of the key
differences between single-use and conventional stainless steel bioreactors, and highlight factors that are employed while scaling-up from small-scale glass bioreactors to 2000 L-scale single-use bioreactors. Several case studies focusing on process performance across scales into single-use bioreactors are provided. This analysis confirms that the 2000 L-scale single-use bioreactorsystem can be robustly employed for biopharmaceutical manufacturing.
Modern BioManufacturing: Single-Use Technologies in Configurable, Prefabricat...Merck Life Sciences
A co-webinar describing a solution to biopharma's challenge of rapidly and rationally expanding capacity by employing single-use technologies, a templated process train, and pre-fabricated mobile/modular cleanrooms.
Biopharmaceutical companies on the verge of investing into manufacturing or facilities expansion face many questions and challenges. Speed, agility, and flexibility are becoming more critical to executing their changing production and distribution strategies. Platform facility designs which integrate the latest process technologies within innovative pre-fabricated cleanrooms are critical for addressing the trending desire to implement 'clonable' modular facilities that can be delivered in a timely fashion across multiple locations. Companies like Merck KGaA, Darmstadt, Germany and G-CON Manufacturing are working together to combine their technologies and develop simple yet robust platform solutions for industry.
As bioprocessing technologies intensify performance, volumetric requirements become less. As such, 2000L single-use bioreactors - or multiple bioreactors of similar or less volumes - now suffice for the production of novel or biosimilar recombinant proteins. Such a shift in the industry enables the development of more mobile, modular facility designs. We will describe the rationale for this collaboration and its result: a turn-key solution that integrates a templated process train with a rapidly-deployable facility platform. By combining the unique advantages found with the G-CON POD construction and the bioprocess technology expertise from within Merck KGaA, Darmstadt, Germany, the goal of creating a cost-effective, pre-fabricated alternative to historical 'stick built' facilities is being achieved. Additionally, the flexibility inherent to our approach provides for a greater configurability that confers more user-specified choice into the selection of options. Simple in concept, this solution is also robust, cost-effective, and conducive to tight timelines for implementation.
In this webinar you will learn:
- Basic options for facilities/capacity expansion
- The value of templated process trains employing single-use equipment
- How modular, prefabricated PODs® outfitted with such single-use bioprocessing equipment represent an attractive, cost-effective strategy for capacity expansion
POD® is a registered trademark of G-CON Manufacturing, Inc.
Scaling Strategies with Stirred Single-Use Bioreactors from Bench to Clinical...Merck Life Sciences
This presentation introduces the general principles of scaling strategies with stirred single-use bioreactors, discusses key engineering parameters, and concludes with a case study of how these strategies are applied to Mobius® bioreactors from 2 liters to 2000 liters.
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
Single use technology: a regulatory perspectiveTGA Australia
An overview of the regulation of single use technology including Good Manufacturing Practice requirements and the types of deficiencies and issues observed at inspections
Scaling Strategies with Stirred Single-Use Bioreactors from Bench to Clinical...MilliporeSigma
This presentation introduces the general principles of scaling strategies with stirred single-use bioreactors, discusses key engineering parameters, and concludes with a case study of how these strategies are applied to Mobius® bioreactors from 2 liters to 2000 liters.
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
Key to Successful Formulation Development for Lipid Based RNA Delivery and Va...MilliporeSigma
In this webinar, we will discuss:
• The application of RNA therapeutics and the different drug delivery routes used in the clinic.
• Design principles for developing lipids-based RNA formulations.
• Critical parameters to consider for cost effective development and consistent performance of RNA therapeutics and vaccines.
RNA therapeutics are changing the way we address diseases. Applications range from gene therapy, oncology, to vaccines for infectious diseases such as COVID-19.
The performance of RNA therapeutics critically depends on its formulation. Key decisions have to be made early on in the drug development process; choosing the appropriate drug delivery method and novel excipients. Raw material source and judicious choice of chemistry, ultimately determine the quality of novel lipid excipients which, in turn, has a big impact on the performance, reproducibility, costs, and regulatory approval timelines. This webinar will propose solutions to maximize the probability of success while formulating RNA therapeutics and vaccines.
Participate in the interactive webinar now: https://bit.ly/2xXMZlm
Explore our webinar library: www.emdmillipore.com/webinars
Bioburden control: Strategies to address bioburden control in downstream proc...Merck Life Sciences
Biotherapeutic manufacturing processes are at greater risk of contamination than classic small molecule processes and therefore require different control strategies. Understanding the source, options for control, and potential impact of bioburden throughout downstream biopharmaceutical processes is beneficial to process developers, production operators and pharmaceutical microbiologists. Process designs that reduce the risks of bioburden contamination will decrease process related failures and the resulting painful, time-consuming investigations.
In this webinar, you will learn:
• Biotherapeutic manufacturing processes are at greater risk of contamination than classic small molecule processes and therefore require different control strategies.
• Understanding the source, options for control, and potential impact of bioburden throughout downstream biopharmaceutical processes is beneficial to process developers, production operators and pharmaceutical microbiologists.
• Process designs that reduce the risks of bioburden contamination will decrease process related failures and the resulting painful, time-consuming investigations.
Register for our webinar here: https://bit.ly/3c4q9rr
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.merckmillipore.com/mlab
EU GMP Annex 1 Draft - Closed System Design Consideration with Single-Use Sys...MilliporeSigma
Biopharmaceutical manufacturing capacities have expanded dramatically which has resulted in an increased demand for single-use systems (SUS) as they have their own advantages. Although SUS are well established in the biopharmaceutical industry there is limited guidance on regulatory expectations. Please attend the webinar to learn more!
EU GMP Annex 1 – Implications on Filtration and Single Use Technology by Soma...MilliporeSigma
What are the major drivers for the new Annex 1? Join us to know more about implications for Filters & Single Use.
In this webinar, you will learn:
• Closed Processing and Single Use Technology implementation
• Points to consider using Single Use Technology
• Sterile Filtration
The Annex 1 “Manufacture of sterile medicinal products” of the EU GMP Guide is currently being revised. A first draft of the revised version was published in 2017 and released for public comment. The second draft as of February 2020 was open for targeted consultation via stakeholder from selected industry organisations. The current Annex 1 draft emphasises Contamination Control Strategy (CCS) multiple times and as a key consideration.
In this webinar, you will learn:
Sources of endotoxin contamination
Contamination control strategy
Endotoxin removal strategies
Detailed description:
Endotoxin, a lipopolysaccharide (LPS), is a type of pyrogen and is a component of the exterior cell wall of Gram-negative bacteria. To ensure safety on patient’s endotoxin content in the drug should always be controlled. In a biological processing it may emanate from facility, utility, raw materials, process, and personnel. In this webinar we discuss the regulatory norms, strategies for prevention & removal of endotoxin to ensure that the final drug product is safe.
Aseptic Process Sampling to address Risk of Contamination & Containment in co...MilliporeSigma
Watch this webinar here: bit.ly/asepticwebinar2020
In this webinar, you will learn:
- The challenges tied to contamination control within a biopharmaceutical environment.
- What closed processing is, and how sampling solutions are an integral component towards that end.
- Advantages of sterile sampling from both a technical and economical viewpoint; with the review of a technical study confirming contamination risk reduction and total cost of ownership.
- Recommendations and requirements stated by these major regulatory authorities around the monitoring of the manufacturing process with the execution of sampling.
Detailed description:
Biopharmaceutical manufacturers are required to ensure drug product quality attributes for patient safety. Strong contamination control strategies should be considered early in process design, and have direct influence on the production environment and equipment selection.
Sampling at each step is a critical component in maintaining a contamination control strategy. Regulators are critical in the sampling process, as it predicts the state of the product or process, and needs to be Representative. A case study will be presented that demonstrates a closed, robust sampling solution capable of maintaining a sterile flow path when challenged with Brevundimonas diminuta. The sampling option you select can help support your goal in achieving a closed process, improving your risk mitigation strategy and product safety.
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
EU GMP Annex 1 – Implications on Filtration and Single Use Technology by Soma...Merck Life Sciences
What are the major drivers for the new Annex 1? Join us to know more about implications for Filters & Single Use.
In this webinar, you will learn:
• Closed Processing and Single Use Technology implementation
• Points to consider using Single Use Technology
• Sterile Filtration
The Annex 1 “Manufacture of sterile medicinal products” of the EU GMP Guide is currently being revised. A first draft of the revised version was published in 2017 and released for public comment. The second draft as of February 2020 was open for targeted consultation via stakeholder from selected industry organisations. The current Annex 1 draft emphasises Contamination Control Strategy (CCS) multiple times and as a key consideration.
Process equipment characterization – how standardized extractables data suppo...Merck Life Sciences
View the recording here: https://bit.ly/35KIwBb
Biopharmaceutical Industry recently increased adoption of Single-Use systems and components in manufacturing process operations. Drug manufacturers are responsible for the characterization of SU components and systems used for the production to ensure patient safety. SUS Suppliers are encouraged by BPOG and BPSA to provide comprehensive extractables data package to support drug manufacturer’s E&L assessments.
This webinar will give an overview of the E&L evaluation workflow and practical study approaches from both supplier and end-user perspective, in accordance with the latest industry’s standards and upcoming USP <665> requirements. Case studies will be presented on how the data from suppliers are used to mitigate risk associated to SU materials, highlighting the key role of collaboration between the supplier and the drug manufacturer.
Extractables profiles for chromatography resins - adapted approach of upcomin...Merck Life Sciences
Watch the webinar here: https://bit.ly/36JaZpx
In biopharmaceutical industry there is a trend towards comprehensive risk assessments of drug manufacturing processes. Extractables studies for chromatography resins based on the adapted requirements of the upcoming USP <665> support risk evaluation for your specific chromatography steps.
In this webinar, you will learn about:
- Study design for extractables profiles of chromatography resins
- The new category Emprove® Chromatography
- Communication of extractables data as part of Emprove® Dossiers
Description:
Detailed information on any component or material in contact with the drug substance/ product is required to conduct a compreshensive risk assessment of a biopharmaceutical manufacturing process. No explicit guidelines providing required testing procedures for chromatography steps are in place yet. In the upcoming USP <665> chapter chromatography steps are in focus as well as any other plastic or polymeric component and can as such assessed as to the described criteria. To support our chromatography resin users an adapted extractables study approach was developed. The webinar will demonstrate our study design and the communication of the extractables profiles within our Emprove® Program.
USP <665> draft standard : A rational risk-based approach to characterization...Merck Life Sciences
This webinar will cover risk-based characterization of filters and single-use systems used in biopharmaceutical manufacturing according to USP <665>.
Novel innovative biomanufacturing systems such as single-use assemblies often comprise of polymeric materials. There is a lack of standards for characterization of these polymeric systems. USP <665> draft standard is the first standard in development addressing this topic. This chapter recommends risk assessment with respect to patient safety, risk level assignment and risk level appropriate characterization of components.
In this webinar we will discuss:
● Risk assessment to assign a risk level
● Risk level based testing
● Our approach for compliance
● Emprove™ Dossiers for Filters and Single-use systems
Biopharmaceutical Process Development: Good Manufacturing Practices or Breaki...Chris Willmott
These are the slides from a presentation "Biopharmaceutical Process Development: Good Manufacturing Practices or Breaking Bad?" given by Andrew Warr as part of the 2015 Careers After Biological Sciences programme at the University of Leicester UK
CAR-T Manufacturing Innovations that Work - Automating Low Volume Processes a...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3NDNIKe
Automated, fit-for-purpose tools are essential in CAR-T processing to support sustainable manufacturing of clinical and market-approved cell therapy products. This webinar will discuss how the ekko™ Acoustic Cell Processing System uses acoustic technology as a touchless approach to manipulate cells, enabling a modular tool across the CAR-T manufacturing workflow. Typical performance of templated ekko™ System processes for DMSO washout of leukapheresis material, low volume and high cell concentrate for electroporation preparation, and harvest of expanded T cells will be reviewed.
This webinar will also give an early glimpse at the ekko™ Select System for unmatched T cell selection.
In this webinar, you will:
• Uncover how the ekko™ System supports the broad industrialization of cell therapy, with particular focus on how to achieve low volume, high concentrate cell product for critical transduction and transfection steps
• Discover how ekko™ System for wash and concentrate processes throughout the cell therapy workflow achieve high cell recovery, viability, and effective residual removal
• Preview to ekko™ Select, our cell therapy selection platform, to achieve unmatched ease-of-use with direct processing from leukopaks reducing the need for preparation steps
Presented by:
Benjamin Ross-Johnsrud, Acoustic Technology Expert
Robert Scott, Mechanical Engineer III
EU GMP Annex 1 Draft: Implications on Sterilizing Grade Filter ValidationMilliporeSigma
Watch the presentation of this webinar here: https://bit.ly/3kk0Qs1
In this webinar, you will learn:
- About the GMP Annex 1 draft regulatory overview
- How to incorporate the integrity testing & PUPSIT in the filtration systems validation
- How to design a bacterial retention test in terms of organism selection and single vs multiple use validation
Detailed description:
In this webinar we will discuss the implications of the EU GMP Annex 1 draft on the filtration of medicinal products and how this impacts the validation studies.
Bacterial Retention Testing is a critical part of the manufacturing validation process and is required by all regulatory bodies worldwide. Using case studies, our experts will explain how the Annex 1 draft is incorporated into the filtration systems validation exercise, specifically for integrity testing & PUPSIT (Pre-Use Post Sterilization Integrity Testing), the selection and justification of the appropriate test organism, and validation implications of single versus multiple use.
Implementing and Managing Pre-use Post-sterilization Integrity Testing (PUPSIT)Merck Life Sciences
This presentation explores best practices and case studies in aseptic processing, including how to implement and manage PUPSIT. You will learn:
• Integrity Testing – the background on IT itself, why it is important, and how it works
• Filtration setups and single-use technology
• The PUPSIT debate and how PUPSIT can be achieved with current technology, final filling, formulation, filtration
To learn more about this topic or collaborate with our technical experts, schedule a remote visit at our M Lab™ Collaboration Centers: www.merckmillipore.com/remotevisit
Complete single-use ADC technology from development through scale-upMerck Life Sciences
With an expected high annual growth rate of the global Antibody-drug Conjugate (ADC) market, it is essential that CMO’s have robust manufacturing platforms to ensure successful transfer to GMP production.
Single-Use Technologies provide many advantages, including improved safety, lower costs and greater flexibility. This webinar will outline the advantages of a Single Use Platform and give a case study on how it can be used to manufacture ADC projects.
In this webinar, you will learn:
● How single-use technologies can provide benefits for ADC manufacturing
● Why a solid manufacturing platform is crucial for a successful transfer to GMP production
● How a case study demonstrates the advantages of single-use equipment in a scale up to GMP production
Upcoming USP 665 - Level of Characterization of Single-Use Systems Today and ...MilliporeSigma
Register for the interactive, on-demand webinar now: https://bit.ly/USP665
Single-use plastic systems are being utilized more frequently especially for COVID-19 vaccine manufacturing. However, there are issues regarding standardization of quality information that limits implementation efficiencies. One of the challenges is the evaluation of leachables derived from a variety of different plastic components in a timely manner.
Since the USP <665> highlights a risk assessment approach with no typical pass/fail limit, approaches to decision-making based on the extractables data package will be reviewed. In addition, we will highlight legacy testing requirements which may not be necessary once USP <665> is implemented.
In this webinar, we will discuss:
- Regulatory expectations of extractables and leachables assessment today and tomorrow
- The right criteria that need to be assessed to select the type and quality of plastic materials for use in biopharmaceutical manufacturing
FABRICATION OF A SIMPLE BUBBLE COLUMN CO2 CAPTURE UNIT UTILIZING MICROALGAE ijbbjournal
This paper focuses on the fabrication of a vertical column CO2 bioreactor and the experimentation of
microalgae. On the manufacturing aspect of the project, the base design was modelled on Solidworks and
assigned a material. The model was then loaded onto a finite element analysis (FEA) software to determine
various engineering stresses and strains to confirm the specimen’s strength. Once the simulation had
completed, the model was ready for 3-D printing. The species of microalgae to be used in this study was
Chlorella Vulgaris. The medium solution was prepared by mixing many types of salts suitable for this type
of algae. Experimental trials of algae growth were conducted mainly to see whether the algae would indeed
grow more rapidly using the developed medium. After failure in early trials, some experiments were
conducted to determine which concentration of stock solution would be the most ideal for the algae to grow
in. These early experiments proved the major impacts of the concentration of the medium on the rate of
growth of the algae. The knowledge gained in these experiments will be instrumental during the next stages
of this project.
FABRICATION OF A SIMPLE BUBBLE COLUMN CO2 CAPTURE UNIT UTILIZING MICROALGAEijbbjournal
This paper focuses on the fabrication of a vertical column CO2 bioreactor and the experimentation of
microalgae. On the manufacturing aspect of the project, the base design was modelled on Solidworks and
assigned a material. The model was then loaded onto a finite element analysis (FEA) software to determine
various engineering stresses and strains to confirm the specimen’s strength. Once the simulation had
completed, the model was ready for 3-D printing. The species of microalgae to be used in this study was
Chlorella Vulgaris. The medium solution was prepared by mixing many types of salts suitable for this type
of algae. Experimental trials of algae growth were conducted mainly to see whether the algae would indeed
grow more rapidly using the developed medium. After failure in early trials, some experiments were
conducted to determine which concentration of stock solution would be the most ideal for the algae to grow
in. These early experiments proved the major impacts of the concentration of the medium on the rate of
growth of the algae. The knowledge gained in these experiments will be instrumental during the next stages
of this project.
Key to Successful Formulation Development for Lipid Based RNA Delivery and Va...MilliporeSigma
In this webinar, we will discuss:
• The application of RNA therapeutics and the different drug delivery routes used in the clinic.
• Design principles for developing lipids-based RNA formulations.
• Critical parameters to consider for cost effective development and consistent performance of RNA therapeutics and vaccines.
RNA therapeutics are changing the way we address diseases. Applications range from gene therapy, oncology, to vaccines for infectious diseases such as COVID-19.
The performance of RNA therapeutics critically depends on its formulation. Key decisions have to be made early on in the drug development process; choosing the appropriate drug delivery method and novel excipients. Raw material source and judicious choice of chemistry, ultimately determine the quality of novel lipid excipients which, in turn, has a big impact on the performance, reproducibility, costs, and regulatory approval timelines. This webinar will propose solutions to maximize the probability of success while formulating RNA therapeutics and vaccines.
Participate in the interactive webinar now: https://bit.ly/2xXMZlm
Explore our webinar library: www.emdmillipore.com/webinars
Bioburden control: Strategies to address bioburden control in downstream proc...Merck Life Sciences
Biotherapeutic manufacturing processes are at greater risk of contamination than classic small molecule processes and therefore require different control strategies. Understanding the source, options for control, and potential impact of bioburden throughout downstream biopharmaceutical processes is beneficial to process developers, production operators and pharmaceutical microbiologists. Process designs that reduce the risks of bioburden contamination will decrease process related failures and the resulting painful, time-consuming investigations.
In this webinar, you will learn:
• Biotherapeutic manufacturing processes are at greater risk of contamination than classic small molecule processes and therefore require different control strategies.
• Understanding the source, options for control, and potential impact of bioburden throughout downstream biopharmaceutical processes is beneficial to process developers, production operators and pharmaceutical microbiologists.
• Process designs that reduce the risks of bioburden contamination will decrease process related failures and the resulting painful, time-consuming investigations.
Register for our webinar here: https://bit.ly/3c4q9rr
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.merckmillipore.com/mlab
EU GMP Annex 1 Draft - Closed System Design Consideration with Single-Use Sys...MilliporeSigma
Biopharmaceutical manufacturing capacities have expanded dramatically which has resulted in an increased demand for single-use systems (SUS) as they have their own advantages. Although SUS are well established in the biopharmaceutical industry there is limited guidance on regulatory expectations. Please attend the webinar to learn more!
EU GMP Annex 1 – Implications on Filtration and Single Use Technology by Soma...MilliporeSigma
What are the major drivers for the new Annex 1? Join us to know more about implications for Filters & Single Use.
In this webinar, you will learn:
• Closed Processing and Single Use Technology implementation
• Points to consider using Single Use Technology
• Sterile Filtration
The Annex 1 “Manufacture of sterile medicinal products” of the EU GMP Guide is currently being revised. A first draft of the revised version was published in 2017 and released for public comment. The second draft as of February 2020 was open for targeted consultation via stakeholder from selected industry organisations. The current Annex 1 draft emphasises Contamination Control Strategy (CCS) multiple times and as a key consideration.
In this webinar, you will learn:
Sources of endotoxin contamination
Contamination control strategy
Endotoxin removal strategies
Detailed description:
Endotoxin, a lipopolysaccharide (LPS), is a type of pyrogen and is a component of the exterior cell wall of Gram-negative bacteria. To ensure safety on patient’s endotoxin content in the drug should always be controlled. In a biological processing it may emanate from facility, utility, raw materials, process, and personnel. In this webinar we discuss the regulatory norms, strategies for prevention & removal of endotoxin to ensure that the final drug product is safe.
Aseptic Process Sampling to address Risk of Contamination & Containment in co...MilliporeSigma
Watch this webinar here: bit.ly/asepticwebinar2020
In this webinar, you will learn:
- The challenges tied to contamination control within a biopharmaceutical environment.
- What closed processing is, and how sampling solutions are an integral component towards that end.
- Advantages of sterile sampling from both a technical and economical viewpoint; with the review of a technical study confirming contamination risk reduction and total cost of ownership.
- Recommendations and requirements stated by these major regulatory authorities around the monitoring of the manufacturing process with the execution of sampling.
Detailed description:
Biopharmaceutical manufacturers are required to ensure drug product quality attributes for patient safety. Strong contamination control strategies should be considered early in process design, and have direct influence on the production environment and equipment selection.
Sampling at each step is a critical component in maintaining a contamination control strategy. Regulators are critical in the sampling process, as it predicts the state of the product or process, and needs to be Representative. A case study will be presented that demonstrates a closed, robust sampling solution capable of maintaining a sterile flow path when challenged with Brevundimonas diminuta. The sampling option you select can help support your goal in achieving a closed process, improving your risk mitigation strategy and product safety.
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
EU GMP Annex 1 – Implications on Filtration and Single Use Technology by Soma...Merck Life Sciences
What are the major drivers for the new Annex 1? Join us to know more about implications for Filters & Single Use.
In this webinar, you will learn:
• Closed Processing and Single Use Technology implementation
• Points to consider using Single Use Technology
• Sterile Filtration
The Annex 1 “Manufacture of sterile medicinal products” of the EU GMP Guide is currently being revised. A first draft of the revised version was published in 2017 and released for public comment. The second draft as of February 2020 was open for targeted consultation via stakeholder from selected industry organisations. The current Annex 1 draft emphasises Contamination Control Strategy (CCS) multiple times and as a key consideration.
Process equipment characterization – how standardized extractables data suppo...Merck Life Sciences
View the recording here: https://bit.ly/35KIwBb
Biopharmaceutical Industry recently increased adoption of Single-Use systems and components in manufacturing process operations. Drug manufacturers are responsible for the characterization of SU components and systems used for the production to ensure patient safety. SUS Suppliers are encouraged by BPOG and BPSA to provide comprehensive extractables data package to support drug manufacturer’s E&L assessments.
This webinar will give an overview of the E&L evaluation workflow and practical study approaches from both supplier and end-user perspective, in accordance with the latest industry’s standards and upcoming USP <665> requirements. Case studies will be presented on how the data from suppliers are used to mitigate risk associated to SU materials, highlighting the key role of collaboration between the supplier and the drug manufacturer.
Extractables profiles for chromatography resins - adapted approach of upcomin...Merck Life Sciences
Watch the webinar here: https://bit.ly/36JaZpx
In biopharmaceutical industry there is a trend towards comprehensive risk assessments of drug manufacturing processes. Extractables studies for chromatography resins based on the adapted requirements of the upcoming USP <665> support risk evaluation for your specific chromatography steps.
In this webinar, you will learn about:
- Study design for extractables profiles of chromatography resins
- The new category Emprove® Chromatography
- Communication of extractables data as part of Emprove® Dossiers
Description:
Detailed information on any component or material in contact with the drug substance/ product is required to conduct a compreshensive risk assessment of a biopharmaceutical manufacturing process. No explicit guidelines providing required testing procedures for chromatography steps are in place yet. In the upcoming USP <665> chapter chromatography steps are in focus as well as any other plastic or polymeric component and can as such assessed as to the described criteria. To support our chromatography resin users an adapted extractables study approach was developed. The webinar will demonstrate our study design and the communication of the extractables profiles within our Emprove® Program.
USP <665> draft standard : A rational risk-based approach to characterization...Merck Life Sciences
This webinar will cover risk-based characterization of filters and single-use systems used in biopharmaceutical manufacturing according to USP <665>.
Novel innovative biomanufacturing systems such as single-use assemblies often comprise of polymeric materials. There is a lack of standards for characterization of these polymeric systems. USP <665> draft standard is the first standard in development addressing this topic. This chapter recommends risk assessment with respect to patient safety, risk level assignment and risk level appropriate characterization of components.
In this webinar we will discuss:
● Risk assessment to assign a risk level
● Risk level based testing
● Our approach for compliance
● Emprove™ Dossiers for Filters and Single-use systems
Biopharmaceutical Process Development: Good Manufacturing Practices or Breaki...Chris Willmott
These are the slides from a presentation "Biopharmaceutical Process Development: Good Manufacturing Practices or Breaking Bad?" given by Andrew Warr as part of the 2015 Careers After Biological Sciences programme at the University of Leicester UK
CAR-T Manufacturing Innovations that Work - Automating Low Volume Processes a...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3NDNIKe
Automated, fit-for-purpose tools are essential in CAR-T processing to support sustainable manufacturing of clinical and market-approved cell therapy products. This webinar will discuss how the ekko™ Acoustic Cell Processing System uses acoustic technology as a touchless approach to manipulate cells, enabling a modular tool across the CAR-T manufacturing workflow. Typical performance of templated ekko™ System processes for DMSO washout of leukapheresis material, low volume and high cell concentrate for electroporation preparation, and harvest of expanded T cells will be reviewed.
This webinar will also give an early glimpse at the ekko™ Select System for unmatched T cell selection.
In this webinar, you will:
• Uncover how the ekko™ System supports the broad industrialization of cell therapy, with particular focus on how to achieve low volume, high concentrate cell product for critical transduction and transfection steps
• Discover how ekko™ System for wash and concentrate processes throughout the cell therapy workflow achieve high cell recovery, viability, and effective residual removal
• Preview to ekko™ Select, our cell therapy selection platform, to achieve unmatched ease-of-use with direct processing from leukopaks reducing the need for preparation steps
Presented by:
Benjamin Ross-Johnsrud, Acoustic Technology Expert
Robert Scott, Mechanical Engineer III
EU GMP Annex 1 Draft: Implications on Sterilizing Grade Filter ValidationMilliporeSigma
Watch the presentation of this webinar here: https://bit.ly/3kk0Qs1
In this webinar, you will learn:
- About the GMP Annex 1 draft regulatory overview
- How to incorporate the integrity testing & PUPSIT in the filtration systems validation
- How to design a bacterial retention test in terms of organism selection and single vs multiple use validation
Detailed description:
In this webinar we will discuss the implications of the EU GMP Annex 1 draft on the filtration of medicinal products and how this impacts the validation studies.
Bacterial Retention Testing is a critical part of the manufacturing validation process and is required by all regulatory bodies worldwide. Using case studies, our experts will explain how the Annex 1 draft is incorporated into the filtration systems validation exercise, specifically for integrity testing & PUPSIT (Pre-Use Post Sterilization Integrity Testing), the selection and justification of the appropriate test organism, and validation implications of single versus multiple use.
Implementing and Managing Pre-use Post-sterilization Integrity Testing (PUPSIT)Merck Life Sciences
This presentation explores best practices and case studies in aseptic processing, including how to implement and manage PUPSIT. You will learn:
• Integrity Testing – the background on IT itself, why it is important, and how it works
• Filtration setups and single-use technology
• The PUPSIT debate and how PUPSIT can be achieved with current technology, final filling, formulation, filtration
To learn more about this topic or collaborate with our technical experts, schedule a remote visit at our M Lab™ Collaboration Centers: www.merckmillipore.com/remotevisit
Complete single-use ADC technology from development through scale-upMerck Life Sciences
With an expected high annual growth rate of the global Antibody-drug Conjugate (ADC) market, it is essential that CMO’s have robust manufacturing platforms to ensure successful transfer to GMP production.
Single-Use Technologies provide many advantages, including improved safety, lower costs and greater flexibility. This webinar will outline the advantages of a Single Use Platform and give a case study on how it can be used to manufacture ADC projects.
In this webinar, you will learn:
● How single-use technologies can provide benefits for ADC manufacturing
● Why a solid manufacturing platform is crucial for a successful transfer to GMP production
● How a case study demonstrates the advantages of single-use equipment in a scale up to GMP production
Upcoming USP 665 - Level of Characterization of Single-Use Systems Today and ...MilliporeSigma
Register for the interactive, on-demand webinar now: https://bit.ly/USP665
Single-use plastic systems are being utilized more frequently especially for COVID-19 vaccine manufacturing. However, there are issues regarding standardization of quality information that limits implementation efficiencies. One of the challenges is the evaluation of leachables derived from a variety of different plastic components in a timely manner.
Since the USP <665> highlights a risk assessment approach with no typical pass/fail limit, approaches to decision-making based on the extractables data package will be reviewed. In addition, we will highlight legacy testing requirements which may not be necessary once USP <665> is implemented.
In this webinar, we will discuss:
- Regulatory expectations of extractables and leachables assessment today and tomorrow
- The right criteria that need to be assessed to select the type and quality of plastic materials for use in biopharmaceutical manufacturing
FABRICATION OF A SIMPLE BUBBLE COLUMN CO2 CAPTURE UNIT UTILIZING MICROALGAE ijbbjournal
This paper focuses on the fabrication of a vertical column CO2 bioreactor and the experimentation of
microalgae. On the manufacturing aspect of the project, the base design was modelled on Solidworks and
assigned a material. The model was then loaded onto a finite element analysis (FEA) software to determine
various engineering stresses and strains to confirm the specimen’s strength. Once the simulation had
completed, the model was ready for 3-D printing. The species of microalgae to be used in this study was
Chlorella Vulgaris. The medium solution was prepared by mixing many types of salts suitable for this type
of algae. Experimental trials of algae growth were conducted mainly to see whether the algae would indeed
grow more rapidly using the developed medium. After failure in early trials, some experiments were
conducted to determine which concentration of stock solution would be the most ideal for the algae to grow
in. These early experiments proved the major impacts of the concentration of the medium on the rate of
growth of the algae. The knowledge gained in these experiments will be instrumental during the next stages
of this project.
FABRICATION OF A SIMPLE BUBBLE COLUMN CO2 CAPTURE UNIT UTILIZING MICROALGAEijbbjournal
This paper focuses on the fabrication of a vertical column CO2 bioreactor and the experimentation of
microalgae. On the manufacturing aspect of the project, the base design was modelled on Solidworks and
assigned a material. The model was then loaded onto a finite element analysis (FEA) software to determine
various engineering stresses and strains to confirm the specimen’s strength. Once the simulation had
completed, the model was ready for 3-D printing. The species of microalgae to be used in this study was
Chlorella Vulgaris. The medium solution was prepared by mixing many types of salts suitable for this type
of algae. Experimental trials of algae growth were conducted mainly to see whether the algae would indeed
grow more rapidly using the developed medium. After failure in early trials, some experiments were
conducted to determine which concentration of stock solution would be the most ideal for the algae to grow
in. These early experiments proved the major impacts of the concentration of the medium on the rate of
growth of the algae. The knowledge gained in these experiments will be instrumental during the next stages
of this project.
Cleaner Production opportunities and its benefits in Biotech Industryijsrd.com
Biotechnology is said to be used as tool for cleaner production. There has been much discussion regarding potential environmental benefits and hazards associated with biotechnology. Biotechnology is increasingly being viewed as a major weapon against environmental damage. Cleaner production is considered as a part of this strategy and yet there is still widespread ignorance about this emerging technology but there are many areas in biotech industry where application of cleaner production can be beneficial economically as well as environmentally. There are many sectors of biotechnology; each sector has different process and products. By analyzing process of each class of biotechnology, Cleaner production opportunities can be generated specifically. Major processes in this industry where cleaner production can be applied are heat transfer, mass transfer, mechanical operations, separation techniques, etc. cleaner production at smaller level may also leads to benefits in overall economy and waste minimization in process. Cleaner production aims at waste reduction, onsite recovery, product modification and energy conservation. Although there are several barriers to cleaner production but it can be overcome considering the benefits obtained from cleaner production.
Single-Use-Bioreactors-A-Comprehensive-Examination.
Single-use bioreactors (SUBs) have revolutionized biopharmaceutical production, offering advantages over traditional bioreactors.
Green VTT has commitment to develop technologies for the bio-economy to benefit society through prosperity through less environmental burden. Industrial biomaterials spearhead program is targeting new value added applications on non-food related biomass in the fields of marked industrial importance, such as packaging, composites and appliances. The development is based on long research activity in the fields of biomass fractionation and converting as well deep expertise on the material sciences, converting technologies and application.
This Research Highlights focuses on novel biopolymers from forest industry side-streams that have been developed for bio-packing applications, like oxygen and grease barrier materials for fibre webs. Development of translucent and mouldable fibre based packaging and modification and regeneration of cellulose enabled new openings. The main achievement is, however, the nanocellulose development that has progressed to the international top level, enabling VTT partners to move to the industrial scale test runs and pilot decisions. Research and development in the area of industrial biomaterials has a positive impact on chemical, forest and packing industry.
Assessment of Biowalls: An Overview of Plant and Microbial-Based Indoor Air Purification System
`
For more information, Please see websites below:
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Organic Edible Schoolyards & Gardening with Children =
http://scribd.com/doc/239851214 ~
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Double Food Production from your School Garden with Organic Tech =
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Free School Gardening Art Posters =
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Increase Food Production with Companion Planting in your School Garden =
http://scribd.com/doc/239851159 ~
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Healthy Foods Dramatically Improves Student Academic Success =
http://scribd.com/doc/239851348 ~
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City Chickens for your Organic School Garden =
http://scribd.com/doc/239850440 ~
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Simple Square Foot Gardening for Schools - Teacher Guide =
http://scribd.com/doc/239851110 ~
Kirsi-Marja Oksman-Caldentey presented VTT's wide and novel expertise in Industrial Biotechnology in the Polish-Finnish Innovation Forum in Helsinki June 8, 2016.
1. December 2015 13(11)si BioProcess International A
GE Healthcare
Comparing single-use and stainless steel
strategies for microbial fermentation
Ken Clapp, Eva Lindskog, Kjell Eriksson, and Sandeep Kristiansson
Process economy and
production capacity
2. B BioProcess International 13(11)si December 2015
Figure 1: Production schedules for a single-product facility using either (a) stainless steel or (b) single-use equipment; in the
former, one complete culture (including equipment preparation) takes four working days to complete. With single-use
equipment, the culture can be harvested after only three days, saving a full working day.
0Preparations
Weighingofmediacomponentsandadditive
Handlingofdisposablesandchemicalsatwarehouse
MixmediaasaconcentratefortheSSfermentor
Mixandautoclave/filteradditives
Assembleandautoclavefermentortubings
Production
Preparationsinfermentorroom
Pressureholdtestoffermentor
Calibratefermentorsensors,connecttubing
Connectandaddmedia,WFI,additivestofermentor
SIPoffermentor(includingmediaandsensors)
Inoculation
Additionofnonautoclavableadditives
FermentationFirstbatchSecondbatch
Heattreatmentforproductreleaseandharvest
CIP
Wastedisposal
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BatchDuration
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Assembleandautoclavefermentortubings
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Production
Sensorandtubinginstallationandconnection
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Inoculation
Heattreatmentforproductreleaseandharvest
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Wastedisposal
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(A)
(B)
3. December 2015 13(11)si BioProcess International 1
S
ingle-use technology spans a vast array of
applications and associated products.
Single-use components have been
incorporated into subsystems and overall
systems alike. Disposable filters, fittings,
connectors, and tubing (among other things) have
been a mainstay of bioprocess operations for
decades. Proper application, selection, and
implementation of disposables have been essential
to improving biopharmaceutical end-product
quality, reducing cost, and simplifying operations.
In recent years, single-use technology has been
migrating into many unit operations. Of interest for
this discussion are fermentors for microbial culture.
Like some components mentioned above, single-use
bioreactors have been implemented for over a decade.
Practical implementation, commercial availability,
and lack of scalability were early limitations to
adoption and use of such systems. That was until the
WAVE Bioreactor system burst onto the market,
sowing the seed for growth of single-use bioreactors
and fermentors across the market.
With the commercial availability of such
systems, end users had a new option for process
development and production that would not rely
on operational complexities and utility
requirements of conventional sterilize-in-place
(SIP) or autoclavable systems. The resulting
freedom allowed for revisiting old ways of working
and the opportunity to consider new ways to think
about bioprocessing, including a focus on cost
structures prevalent in the industry.
At first, the idea of a “plastic bag” bioreactor
was met with some skepticism. However, benefits
came with appropriate application and proper
implementation of the technology. Success with
the rocking platform made way for single-use
stirred-tank bioreactors to emerge. They could rely
on decades of design and performance experience
established by their stainless steel counterparts.
Despite all that experience, here too the
technology was adopted cautiously. But single-use
bioreactors have found their place and become a
foundation of bioproduction based on animal
(particularly mammalian) cell culture.
Success with single-use systems in large-scale cell
culture — along with advances in material science,
improvements in design understanding, and a
resurgence of microbe-based biologics production —
are converging to create exceptional opportunities.
Whereas for animal cell culture, little was known
initially about single-use bioreactor scalability and
long-term viability, the same is not true for single-
use fermentors and microbial
culture. Cell culture in single-use
bioreactors has created a body of
knowledge related to process
equipment, single-use bag assemblies,
and their integrated operability. That
body of knowledge can serve as a
springboard for microbial applications and
should lower their threshold for adoption.
It is important to note, however, that just as for
cell culture processes, single-use technology may
not apply to each and every microbial process. It is
the responsibility of practitioners to properly assess
their own applications, select appropriate
technology, and manage its implementation.
Adopting a technology just for the sake of doing
so can prevent consideration of important variables
and may not lead to successful outcomes. The
motivation to incorporate a single-use fermentor
into a development or production environment
must be based on an understanding of the value it
brings to a given company and product.
Implementing single-use technology also means
accepting change, challenging conventional
thinking, and reconsidering established ways of
working. With all this in mind, GE Healthcare
presents the following process-economic model as
a contribution to discussions about implementing
single-use fermentors.
Process-Economic Comparison
GE Healthcare has compared production capacity
and process economy between stainless steel and
single-use equipment in microbial processes.
Economic simulations are based on an Escherichia
coli domain antibody (DAb) process, with
production scenarios considered for both single-
and multiproduct facilities.
This study shows that annual production
capacity can be increased up to 100% over
stainless steel with a single-use strategy, primarily
because of faster batch change-over procedures.
With that increased production capacity, a defined
number of batches can be produced in a shorter
time using disposables (e.g., in a manufacturing
campaign or during process development).
Increased batch throughput presents a greater
profit opportunity, a benefit that can outweigh the
higher production cost per batch associated with
the single-use alternative. With the decreased
financial risk, the business case for single-use
equipment becomes more agile than for stainless
steel equipment that incurs higher fixed costs.
special
report
4. 2 BioProcess International 13(11)si December 2015
Background: Microbial fermentation is used for
manufacturing a broad range of products in the
biopharmaceutical industry, including small
nonglycosylated proteins such as human growth
hormone, peptides such as insulin, organic
molecules such as antibiotics, and vaccines against
pneumonia and cholera. Recently, biosimilars,
biobetters, and antibody fragments have been
added to the list of products produced by
fermentation processes.
The primary advantages of microbial
fermentation include straightforward cloning
procedures, simple culture conditions, and rapid
culture growth. By comparison with eukaryotic
cells, microorganisms are less complex and limited
in, for example, their ability to perform
posttranslational modifications. Extensive research
has been conducted to enhance microbial
expression systems, including glycoengineering to
enable correct protein glycosylation capability. The
dominant organisms in today’s biomanufacturing
are E. coli and Pseudomonas fluorescens bacteria,
Saccharomyces cerevisiae and Pichia pastoris yeasts,
and Aspergillus filamentous fungi.
Historically, bioreactors and fermentors have
been constructed of stainless steel or glass. At the
end of the 1990s, however, plastics entered the
scene, providing for the possibility of using
disposables and single-use equipment in culture
processes. Adoption of early single-use rocking
WAVE Bioreactor systems showed that users could
save both time and money through this novel
disposable approach. Soon, Xcellerex bioreactors
(with their bottom magnetic drive) pioneered the
single-use stirred tank field, enabling use of
disposables from small-scale process development to
2,000-L manufacturing scale. Although both
rocking and stirred-tank systems were designed for
mammalian cell culture, they also have found use in
some microbial processes with lower optical density
(OD) requirements.
Microbial biomanufacturers are also interested in
the benefits of single-use bioreactors: increased
process flexibility, reduced cross-contamination
risk, and higher batch throughput. However, the
associated engineering requirements are more
challenging for fermentors used in microbial
processes than for bioreactors used in animal cell
culture. Sufficient mass transfer of oxygen and
removal of excess metabolic heat are some specific
requirements of a microbial process. The Xcellerex
XDR-50 MO system was the first single-use
stirred-tank fermentor purpose-designed for
microbial cultivation. A 50-L fermentor system was
introduced in 2007 and is currently used in both
process development and good manufacturing
practice (GMP)–compliant production of
recombinant proteins and vaccines. The XDR-50
MO fermentor exhibits performance comparable
with stainless steel systems, accommodating an OD
as high as 375 in a P. fluorescens culture producing a
monoclonal antibody (1). Success with the 50-L
fermentor led to the announcement of a larger
500-L XDR-500 MO fermentor in 2015.
What remains to be understood are the
process-economic implications of using disposables
for microbial biomanufacturing: to identify
scenarios in which single-use solutions can be
more favorable than traditional stainless steel
equipment. Here, such questions are discussed
Table 1: Capital investment costs
Stainless Steel System Single-Use System
Biostat D-DCU 50-L single O2
enrichment bioreactor with
control unit
Xcellerex XDR-50 MO
fermentor system
Bioreactor vessel load cells Exhaust condenser for
XDR-50 MO
System clean-in-place (CIP) and
steam-in-place (SIP) operations
Temperature control
unit (TCU) for XDR-50
MO
Extended documentation Xcellerex XDM Quad
single-use mixing
system
Substrate pump
Pressure hold test
Table 2: Unit operations for qualification and cleaning
validation (NA = not applicable)
Unit Operation
Stainless
Steel
Single-
Use
IQ/OQ of fermentor and control
unit (establishing of protocols)
Included Included
IQ/OQ of fermentor and control
unit: factory acceptance test
(FAT) and site acceptance test
(SAT)
Included Included
IQ/OQ of fermentor and control
unit (reporting)
Included Included
OQ temperature mapping of SIP
procedure
Included NA
PQ of fermentor (using
bioindicators for stainless steel
system) and control unit
Included Included
Cleaning validation Included NA
Sterile medium hold test Included NA
IQ/OQ of mixing unit
(establishing of protocols)
NA Included
IQ/OQ of mixing unit (FAT and
SAT)
NA Included
IQ/OQ of mixing unit (reporting) NA Included
Analytics for cleaning validation
and sterile medium hold test
Included NA
5. December 2015 13(11)si BioProcess International 3
based on a model setup for an E. coli DAb
production process run at 50-L scale (2). Data and
assumptions were validated; that is, prices and
costs were verified to generate a nonbiased and
realistic outcome that should facilitate decisions
related to microbial production scenarios.
Process-Economic Model: A model E. coli DAb
process was used to assess process economy in four
hypothetical production scenarios involving both
single-use and stainless steel equipment in single-
product and multiproduct facilities: single-product
facilities with stainless steel and single-use
equipment, and multiproduct facilities with
stainless steel and single-use equipment.
The scope of this process-economic simulation
is limited to the upstream fermentation process
and DAb production phase.
Other unit operations (e.g.,
downstream processing) have
been omitted for simplicity. The
single-use fermentor unit selected
for this investigation was the
Xcellerex XDR-50 MO system, and a
Biostat D-DCU 50-L stainless steel
fermentor (Sartorius Stedim Biotech) was used as
a reference. Specific objectives for this
investigation include the following:
• Investigation of equipment-choice effects on
production capacity
• Estimation of batch-production costs for
processes in which either stainless steel or single-
use equipment was used
special
report
Figure 2: Production schedules for a multiproduct facility using either (a) stainless steel or (b) single-use equipment; the time
dedicated to maintenance (red) is equal in both scenarios, whereas the time dedicated to cleaning and associated analyses (yellow)
is shortened with single-use equipment. The time needed for carry-over calculations, reporting, and quality assurance (QA) approval
(blue), included in the stainless steel scenario is omitted from the single-use scenario. If five batches are harvested (green) in each
campaign, then 67 batches can be harvested annually with stainless steel and 135 annual batches with single-use equipment.
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(A)
(B)
6. 4 BioProcess International 13(11)si December 2015
• Understanding of how equipment strategy
affects total annual cost at different batch
throughputs
• Assessment of profit opportunity for different
equipment strategies.
General Assumptions: Several general
assumptions were made. Availability for
fermentation was set at 300 days/year; the remaining
time would be dedicated to annual maintenance.
Capital investments (including 10% interest) and
qualification costs are spread over the number of
batches that can be produced during the equipment’s
depreciation period (10 years). Labor costs are set at
US$100/hour. Fermentation is assumed to run
overnight, with two operators present to monitor the
process (same for all scenarios). Labor is divided into
two shifts: 6:00 am to 2:00 pm and 2:00–10:00 pm.
And no batch failure rate was considered.
The aim of this study was to make an objective
comparison between single-use and stainless steel
fermentors to provide a representative assessment
of the two alternatives and aid in understanding
their respective strengths and weaknesses. Hence,
all assumptions and costs were verified with data
or information from existing processes whenever
possible. The following specific assumptions were
made:
• For single-product facilities (scenarios 1 and
2, single-use and multise, respectively), only one
product would be produced and the 300-day
production capacity used to 100%.
• For multiproduct facilities (scenarios 3 and 4,
single-use and multiuse, respectively), the facility
would produce different products and use its 300-day
production capacity to 100%. Products were assumed
to be produced in five-batch campaigns each.
Cost Categories: The model includes five cost
categories: capital investments (Table 1);
installation and operation qualifications (IQ/OQ ),
performance qualification (PQ ), and cleaning
validation (Table 2); annual requalification and
maintenance (Table 3); process-related costs (Table
4); and disposables, chemicals, water for injection
(WFI), steam, and similar necessities (Table 5).
The process-related costs listed in Table 4 includes
system preparations before fermentation and the
fermentation process itself. Costs of qualifications,
cleaning validation, annual requalification, and
maintenance (as well as production-related costs)
were estimated by evaluating the labor in hours
required for each respective unit operation.
Some elements were omitted from the model
because certain needs and procedures are identical
for all scenarios or have minimal differential cost
effects. Those with identical needs include a seed-
culture generation procedure using shaker flasks;
the type and amount of culture medium
components and supplements; minor hardware
such as scales and tube welders; minor disposables
(e.g., C-Flex tubing, pump tubing, syringe filters,
vials, and so on); the number of autoclave cycles
for tubing sterilization (cost for steam and
electricity); nitrogen for calibration of dissolved
oxygen (DO) sensors; and general facility
requirements. Elements with minimal impact on
overall cost include energy consumption per batch
and air and oxygen demands (which are slightly
higher for single-use equipment because of its
lower maximum stirring speed). The model
excludes a cost of goods sold (CoGS) calculation
for given amounts of final product because of the
small production volumes assumed.
Results
Production Capacity: Production schedules were
developed for stainless steel and single-use
fermentation scenarios in a single-product facility.
Stainless steel fermentation batches can be
harvested every third day, allowing for a
maximum of 100 batches per year at 100%
capacity use with the assumption of 300 available
days. Under the same conditions, single-use
Figure 3: Production capacity for the four scenarios included
in this study
0
Single-Product
Facility
NumberofBatchesAnnually
Multiproduct
Facility
Stainless steel
Single-use
20
40
60
80
100
120
140
160
Table 3: Unit operations for annual requalification and
maintenance (NA = not applicable)
Unit Operation Stainless Steel Single-Use
OQ temperature
mapping of SIP
procedure (annual
retesting)
Included NA
Cleaning validation
(annual recovery study)
Included NA
Annual maintenance of
fermentor system
Included Included
7. December 2015 13(11)si BioProcess International 5
fermentation batches could be harvested every
second day, allowing for a maximum of 150
batches per year.
For the production scenario in Figure 1, a batch
produced in single-use fermentation equipment will
take 33% less time to complete than one made in
stainless steel. Figure 2 outlines production
schedules for both scenarios in a multiproduct
facility. The stainless steel equipment supports
production of 67 batches/year, about 13 full
production campaigns annually. The corresponding
numbers for single-use equipment is 135 batches/
year in 27 full campaigns. For this multiproduct
facility, production capacity can be doubled with
single-use equipment over stainless steel.
Figure 3 summarizes production capacities for
all four scenarios. Throughput is higher in the
single-product facility than in the multiproduct
facility. And in both, single-use equipment enables
a higher throughput than does stainless steel.
However, the difference between single-use and
stainless steel equipment is most prominent in the
multiproduct-facility scenario.
Cost Analyses and Profit Opportunities
Cost/Batch: The total cost per batch was calculated
for all four scenarios, and detailed analysis was
based on assessing costs for six main categories:
capital investments, qualification, annual
maintenance and requalification, production
preparations, production (fermentation), and
consumables (disposables, facility media, and
chemicals). The costs for a batch production in
stainless steel scenarios served as a reference when
normalized and set to 1.00 for all categories.
Figure 4 summarizes the results.
Total cost and individual cost profiles are very
similar for both facility scenarios. Relative to
stainless steel processes, the total cost per batch is
higher for single-use processes: 29% higher in a
single-product facility and 25% higher in a
multiproduct facility. The higher batch cost with
single-use equipment comes from an increased
consumables cost. For stainless steel, however,
capital investments, qualification costs, and annual
maintenance costs are all higher. That can be
expected because a facility based on stainless steel
reusable equipment requires more fixed
infrastructure. Production-related costs are
comparable for all scenarios.
Costs for Varying Facility Use Rates: Batch cost
analysis was based on the assumption that each
facility’s production capacity is fully used. In
reality, however, many facilities
run at lower use rates, which
changes the dynamics of this
cost-calculation model. In certain
cases (e.g., during a manufacturing
start-up scenario), use rate might be
very low. If only four batches are
required for toxicology studies during the
first year and an additional 15 batches for phase 1
studies during the second year, for example, a
company would still need to invest in the
equipment early on. So equipment qualification
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Table 4: Unit operations for production activities (NA = not
applicable)
Unit Operation
Stainless
Steel
Single-
Use
Handling of disposables and
chemicals
Included Included
Weighing of medium
components and additives
Included Included
Mixing of medium and additives Included Included
Autoclave/filter additives Included Included
Assemble fermentor tubing Included Included
Autoclave fermentor tubing Included Included
Connect tubing to fermentor Included Included
Connect medium and additives
to fermentor tubing
Included Included
Preparations in fermentation
room
Included Included
Calibration of fermentor sensors Included Included
Sterilization of sensors NA Included
Installation of single-use
fermentor bag and sensors
NA Included
CIP of fermentor Included NA
Pressure hold test of fermentor Included NA
Transfer medium concentrate
(including autoclavable
additives) and WFI to stainless
steel system
Included NA
SIP of fermentor including
sensors
Included NA
Filtration of additives (non-
autoclavable) into stainless steel
system
Included NA
Transfer medium to single-use
fermentor bag via filtration
NA Included
Transfer additives to single-use
fermentor bag
NA Included
Inoculation of bacterial cell
culture
Included Included
Fermentation Included Included
Heat treatment before harvest Included Included
CIP of fermentor Included NA
SIP of fermentor Included NA
Waste disposal Included Included
8. 6 BioProcess International 13(11)si December 2015
and costs for annual maintenance and
requalification also would need to be considered.
To investigate this further, analysts used four,
15, 30, 50, 100, and 150 annual batches as input
data for the model and calculated the annual costs
for stainless steel and single-use scenarios,
respectively (Figure 5a). At low use rates, data
show that a single-use strategy is more beneficial
from an annual cost perspective. For 4 and 15
batches annually, that strategy is associated with
~27% and ~10% lower costs, respectively, than
with a stainless steel strategy.
The main reason for the lower cost with single-
use equipment is less time spent on equipment
qualification. For stainless steel equipment, over
three times as much time is spent on qualification
activities. When that time is translated to cost, the
resulting annual cost for maintenance of stainless
steel equipment is 21 times higher than that for
single-use equipment. Maintenance cost remains
constant regardless of equipment use rate. As use
rate increases, however, the difference between
stainless steel and single-use strategies levels out.
At 30 batches annually, their annual costs are
more or less equal.
As the number of batches increases, the
stainless steel strategy is a feasible alternative up to
100 batches annually, when the production
capacity becomes limiting for that scenario. For
capacity needs over 100 annual batches, the single-
use strategy would be the preferred alternative. For
an extreme case in which a facility is not used at
all during a whole year, our model shows that the
annual costs for capital investment (assuming a
10-year depreciation cycle and interest rate of
10%) and for qualification, annual maintenance,
and requalification are 122% higher for a facility
based on stainless steel equipment. So single-use
equipment offers flexibility and benefits at both
low and high capacity needs.
Profit: This study is based on fermentors at a
50-L scale, but few (if any) manufacturing
processes run at this scale. More appropriate 50-L
applications include process development, pilot-
scale production of clinical material, and seed
preparations for larger-sized fermentors. However,
GE Healthcare’s analysts were interested in profit
dynamics of single-use and stainless steel
strategies, so they performed a profit calculation.
Revenue of one million US dollars was assumed
for each batch, and the production cost was
subtracted from that to obtain a gross profit figure.
This calculation was performed for both the
stainless steel and single-use scenarios in a single-
product facility, and the result was plotted against
total capacity use for both scenarios (Figure 5b).
Clearly, the profit opportunity is higher for the
single-use alternative. Increased batch throughput is
the main reason for that outcome, in which benefits
essentially outnumber the slightly higher production
cost per batch for the single-use scenario.
Discussion
GE Healthcare analysists set up a model to
understand the cost and capacity implications of
single-use equipment in microbial fermentation
processes compared with reference scenarios based
on stainless steel equipment. The main conclusion
from this study is that a substantial amount of
time can be saved with single-use equipment. For
a single-product facility based on single-use
equipment, batches can be harvested every second
day; with stainless steel equipment, harvest takes
place every third day. Thus, disposables enable a
relatively higher facility throughput. For a single-
product facility, 50% more batches (150 batches)
can be produced annually using single-use
equipment than with stainless steel equipment
(100 batches).
For a multiproduct facility, the capacity
difference is even more pronounced, with a
doubled annual throughput with single-use
Table 5: Disposables, facilities, and chemicals included in this
study (NA = not applicable)
Unit Operation
Stainless
Steel
Single-
Use
XDA single-use fermentor bag NA Included
Plus Quad MBA single-use mixing
bag for medium preparation
NA Included
Probe sheath NA Included
Tap water for CIP (NaOH/acid
solutions)
Included NA
WFI for CIP (final rinse) Included NA
NaOH solution for CIP Included NA
Acid solution for CIP Included NA
Black steam for heating of CIP
solutions
Included NA
Steam for SIP Included NA
Plant steam for system heating
during fermentation
Included NA
Air vent filter inlet (Sartofluor
Junior, Sartorius Stedim Biotech
GmbH)
Included NA
Air vent filter outlet (Sartofluor
mini, Sartorius Stedim Biotech
GmbH)
Included NA
GE ULTA HC, 6-inch filter for
medium transfer to system
NA Included
9. December 2015 13(11)si BioProcess International 7
equipment (135 batches) relative to stainless steel
(67 batches). The higher productivity of a single-
use facility is related to omitting the need for
equipment cleaning and cleaning validation
procedures after a campaign.
In a facility based on stainless steel, the final
equipment clean-in-place (CIP) procedure at the
end of each campaign is followed by cleaning
validation. Equipment swab samples commonly
are analyzed for total organic carbon (TOC), and
final rinse water typically is analyzed for both
TOC and endotoxins. Analytical results are
usually available five days after sampling. The
time for carry-over calculations, reporting, and
quality assurance (QA) approval of the resulting
report is estimated to take an additional two days.
So this seven-day cleaning validation procedure is
significantly reduced or eliminated by a single-use
fermentor, in which all materials that come into
contact with process fluids are disposed of after
use. During the downtime of that stainless steel
fermentor, a single-use
fermentor can be up and
running to produce additional
batches.
In a multiproduct facility, not
only the equipment, but also the
production suite needs to be cleaned
before starting a new campaign for a different
product. Facility cleaning procedures include
emptying production suites followed by cleaning
of walls, ceilings, and floors. Cleaning verification
is conducted through environmental monitoring
performed by quality control (QC) personnel.
However, the environmental risk from a
production suite can be assessed from previous
analytical results. The final QC results and QA
approval of the environmental monitoring report
therefore are not required typically before starting
a new campaign. Instead, the critical activity is
equipment cleaning and associated validation,
which become the limiting factors for facilities
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Figure 4: Relative cost per batch in (a) single-product and (b) multiproduct facilities using either stainless steel (SS) or single-use
(SU) equipment; the cost for batch production using SS equipment is used as reference and set to 1.00 for all categories.
1.00
1.00
1.00
1.00 1.00
1.0
1.00
0.52
0.23
0.03
0.87 0.93
9.9
1.29
Capital
investm
ent
Qualifications,etc.
Annual
m
aintenance
and
requalification
Production
preparations
Production:
ferm
entation
Consumables
(disposables,
facility media,
chemicals, etc.)
Total
Total
Stainless steel
Single-use
1.00
1.00
1.00
1.00 1.00
1.0
1.00
0.39
0.17
0.02
0.84 0.93
9.9
1.25
(A)
(B)
Capital
investm
ent
Qualifications,etc.
Annual
m
aintenance
and
requalification
Production
preparations
Production:
ferm
entation
Consumables
(disposables,
facility media,
chemicals, etc.)
10. 8 BioProcess International 13(11)si December 2015
using stainless steel equipment due to the risk of
product carry-over. With single-use equipment,
however, that specific risk is nonexistent. A risk-
based strategy may be used for valuable time
savings, and a new campaign can be started the
day after sampling for environmental monitoring.
The improved productivity achievable with
single-use equipment also can have implications
beyond increasing the total capacity of a production
facility. During product development, for example,
shorter process times can contribute to significant
time savings and a decrease in overall development
time. That in turn can make positive financial
impact and speed access to market. With single-
use equipment, more batches can be produced in a
set product development period, allowing more
experiments to be conducted. That can generate
additional regulatory support data to aid in
development of a strong chemistry, manufacturing,
and control (CMC) documentation package. It also
can help to eliminate poor therapeutic candidates
earlier in development, ultimately saving money
that would otherwise be wasted on them.
When studying batch costs, GE Healthcare
analysts found that the total cost per batch at a
100% equipment use rate is 25–29% higher for a
single-use scenario than for a stainless steel
scenario. Consumables are the category that drives
most costs for single-use scenarios. That includes
disposable fermentor bags, mixing apparatus,
tubing, and sterile filtration consumables. However,
the fixed-cost burden — including capital
investment, annual maintenance, and qualification
costs — is higher for stainless steel equipment.
Those fixed costs remain whether or not a facility is
in use, whereas variable consumable costs incur only
when a facility is actually in use for production of
profit-generating biologics.
The implications of having a larger portion of
fixed costs rather than a variable operational costs
become apparent with production scenarios
running at a low facility use rate (e.g., in a start-up
company). At low facility use rates (<30 batches/
year), the annual costs are lower for facilities based
on single-use equipment. As the number of
batches increases, stainless steel equipment
becomes the less expensive alternative until the
point at which production capacity becomes a
limiting factor. In this process-economic model,
that point comes at 100 batches/year. If a higher
production capacity is required, single-use
equipment again becomes the preferred option.
The vast majority of microbial-based GMP
manufacturing processes are performed at scales
much larger than 50 L. However, an initial
assessment of profit dynamics shows that profit
opportunity is higher for a single-use strategy than
for stainless steel because of larger batch
throughputs. To examine process economics at
larger production scales, the model used herein
would be adjusted to each specific scenario.
However, the general principles applied in this
study should be valid for microbial fermentation
processes at all scales.
Choosing Single Use
Several conclusions can be drawn from these
results. A single-use equipment strategy is
Figure 5: Annual total production cost by (a) number of
batches produced and (b) annual accumulated profit against
total capacity use are analyzed for single-use and stainless
steel equipment. (a) Total production cost by number of
batches produced annually in single-use and stainless steel
scenarios; after 100 batches, the maximum annual production
capacity is reached using stainless steel equipment. With
single-use equipment, 150 batches can be produced annually.
(b) Total accumulated profit is plotted against total annual
capacity use; for the stainless steel scenario, 100% capacity
represents 100 batches; for the single-use scenario, 100%
capacity represents 150 batches.
0 100 200
TotalAnnualProductionCost
Batches
Stainless steel
Single-use
400 100806020
AccumulatedProfit
Capacity Use (%)
Stainless steel
Single-use
(A)
(B)
11. December 2015 13(11)si BioProcess International 9
advantageous in microbial fermentation under the
following conditions:
• When a certain number of batches must be
produced in the shortest possible time (single-use
equipment offers an agile solution, for example, in
early product development, production of clinical-
trial or toxicity study materials, or in vaccine surge
capacity scenarios)
• When high production capacities are needed
(here, a single-use strategy enabled a 50% higher
batch capacity over stainless steel in a single-
product scenario and a 100% higher capacity in a
multiproduct scenario)
• At full facility use (profit opportunity was
higher for the single-use alternative, with 150
annual batches, than for the stainless steel
alternative, with 100 batches annually)
• If facility-use rates are low (lower up-front
capital investment and low costs for annual
maintenance and qualification lessens fixed costs
associated with single-use equipment compared
with stainless steel).
For Further Consideration: This modeling
exercise was instructive, and the scenario results
are informative. Both are thought-provoking.
Perhaps this discussion has prompted more
questions than it provided answers. Although the
model was created to be practical and unbiased, it
is still dominated by GE Healthcare’s preexisting
knowledge of current processes and workflows.
For practical reasons, it was also restricted to the
fermentation process only. Expanding the
application and implementation of single-use
technology to specific unit operation systems (e.g.,
bioreactors, purification, and so on) would provide
either a requirement or an opportunity to rethink
existing ways of working, depending on your
perspective.
Consider having a blank slate on which to
establish an ideal fermentation process based on
single-use technology. Is that ideal process founded
on a scaled-out set of disposable fermentors, or does
it rely on one assuming the role of an N – 1 or N – 2
fermentor for seeding larger stainless steel
equipment? In either case, what is the most
beneficial working volume? Would the host
organism stay the same? Could an organism be
engineered to maximize the potential of a single-
use–based fermentation strategy? What would the
facility be like? Could it be fully optimized for
single-use technology implementation both up- and
downstream, from the ground up? Do microbial
fermentation processes demand a hybrid equipment
facility? How does the building
footprint of a scaled-out process
compare with that of a scaled-up
process? Would a corresponding
reduction in utility requirements
convert to even greater cost savings and
higher net profits? How much faster could
a drug be brought to market?
Regardless of the form that the ideal
fermentation process and facility might take,
single-use bioreactors have forever altered the
buyer–seller relationship. Shared information about
materials and process constituents, especially as
they relate to adverse interactions, has become
essential to end-product quality. Security of supply
is critical to both process development and
production. Supply agreements are important to
codifying physical supply and achieving appropriate
buyer cost targets. Single-use–based fermentation
stands to benefit from all this experience.
Disclaimer
Results and conclusions presented herein are valid for this
specific study only. Other study conditions and assumptions
could significantly affect the outcome. The overall finding of
this study is that despite the higher batch cost, single-use
fermentation equipment can generate more batches
annually. So if all batches lead to sold product, the single-use
alternative would contribute to a higher gross profit.
References
1 Application Note 29-0564-39 AB. Microbial
Fermentation in Single-Use Xcellerex XDR-50 MO Fermentor
System. GE Healthcare Bio-Sciences AB: Uppsala, Sweden,
September 2013; www.gelifesciences.com/gehcls_images/
GELS/Related%20Content/Files/1392320581787/
litdoc29056439_20140213234550.pdf.
2 Application Note 29-1341-11 AA. Comparable E. coli
Growth and Domain Antibody (DAb) Expression in Single-Use and
Stainless Steel Fermentor Formats. GE Healthcare Bio-Sciences
AB: Uppsala, Sweden, May 2015; www.gelifesciences.com/
gehcls_images/GELS/Related%20Content/
Files/1432051180778/litdoc29134111_20150519175927.pdf. •
Corresponding author Ken Clapp is senior global product
manager, Eva Lindskog is upstream marketing leader,
Kjell Eriksson is a senior scientist, and Sandeep
Kristiansson is a senior research engineer, all in life
sciences at GE Healthcare Bio-Sciences Corporation, 100
Results Way, Marlborough, MA 01752; 1-484-695-5844;
ken.clapp@ge.com; www.gelifesciences.com.
WAVE Bioreactor and Xcellerex are trademarks of GE
Healthcare. Biostat is a trademark of Sartorius Stedim
Biotech. C-Flex is a registered trademark of Saint-Gobain
Performance Plastics.
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report