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Engineering Conferences International

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Full-Text Articles in Biomedical Engineering and Bioengineering

A Novel Technique To Characterize The Surface Hydrophobicity Of Proteins Using Inverse Liquid Chromatography, Dilip Sethi, Sarah Hedberg, Daryl Williams Jul 2019

A Novel Technique To Characterize The Surface Hydrophobicity Of Proteins Using Inverse Liquid Chromatography, Dilip Sethi, Sarah Hedberg, Daryl Williams

Biological and Pharmaceutical Complex Fluids III: Protein Self-Assembly, Rheology and Interfacial Properties

This work presents a novel technique to characterize the surface hydrophobicity and other surface properties of proteins. The surface properties of industrial and therapeutic proteins are key to understanding their behavior in-situ, in the laboratory and in processes. Protein surface hydrophobicity is a marker for three dimensional structure, stability and function. Inverse Liquid Chromatography of Proteins (ILCP) with small molecule hydrophobic probes can be used to obtain direct measurements of the surface hydrophobicity of column resin-bound proteins using changes in probe retention behavior. The dimensionless hydrophobicity factor (Hf) for Lysozyme and BSA was obtained with changing pH and temperature ...


Biophysical Characterization Approaches To Aid The Selection Of Protein Formulations By Predicting Their Physical Stability During Long-Term Storage, Hristo Svilenov, Gerhard Winter Jul 2019

Biophysical Characterization Approaches To Aid The Selection Of Protein Formulations By Predicting Their Physical Stability During Long-Term Storage, Hristo Svilenov, Gerhard Winter

Biological and Pharmaceutical Complex Fluids III: Protein Self-Assembly, Rheology and Interfacial Properties

The formulation of therapeutic proteins is a critical process which aims at finding the most suitable conditions that impede protein degradation during long-term storage. One degradation path of high interest is the non-native aggregation1. The latter can be greatly suppressed by the selection of suitable solution conditions2. Over the years, various biophysical techniques have been explored as tools to quickly select the most promising formulations for long-term storage.

In this talk, we share the experience in our lab how some of these techniques can be integrated into protein formulation studies. We discuss the application of differential scanning calorimetry ...


Aggregation Challenges In The Formulation Development Of Multi-Dose Peptide Products, Jingtao Zhang, Katelyn Smith, Wei Xu, Yongchao Su, Suzanne D’Addio, Yogita Krishnamachari, Jameson Bothe, Daniel Yin, Xinpei Mao Jul 2019

Aggregation Challenges In The Formulation Development Of Multi-Dose Peptide Products, Jingtao Zhang, Katelyn Smith, Wei Xu, Yongchao Su, Suzanne D’Addio, Yogita Krishnamachari, Jameson Bothe, Daniel Yin, Xinpei Mao

Biological and Pharmaceutical Complex Fluids III: Protein Self-Assembly, Rheology and Interfacial Properties

The formulation development of parenteral peptide therapeutics frequently encounters aggregation challenges. In-depth biophysical understanding of the molecule and formulation are required to achieve formulation robustness. Further, unique considerations need to be given for peptide products that require multi-dose as the use of preservatives can promote aggregation while preservative effectiveness can also be impacted by its interaction with the peptide. This presentation will focus on the reversible and irreversible fibril aggregates in peptide formulations. Biophysical characterization of aggregation and formulation will be discussed in detail. Formation of reversible aggregates and the impact of excipients especially preservatives will be discussed. For the ...


Conference Program, Samiul Amin, Paolo Arosio, Miguel Rodrigues Jul 2019

Conference Program, Samiul Amin, Paolo Arosio, Miguel Rodrigues

Biological and Pharmaceutical Complex Fluids III: Protein Self-Assembly, Rheology and Interfacial Properties

No abstract provided.


Conference Program, Erin Buckley, Christophe Moser, Brian Pogue, David Sampson Jun 2019

Conference Program, Erin Buckley, Christophe Moser, Brian Pogue, David Sampson

Advances in Optics for Biotechnology, Medicine and Surgery XVI

No abstract provided.


Novel Supply Chain And Process Modeling For Cell Therapy Manufacturing And Distribution, Chip White, Ben Wang, Kan Wang, Reid Bishop, Aaron Levine, Brian Liu, Bhavya Divvela, Aubrey Incorvaia, Kris Saha, Tava Das Jan 2019

Novel Supply Chain And Process Modeling For Cell Therapy Manufacturing And Distribution, Chip White, Ben Wang, Kan Wang, Reid Bishop, Aaron Levine, Brian Liu, Bhavya Divvela, Aubrey Incorvaia, Kris Saha, Tava Das

Advancing Manufacture of Cell and Gene Therapies VI

We present a two-level hierarchical supply chain model of (autologous) CAR-T cell therapy that serves as the basis for the development of strategies to: 1) deliver cell therapy products that are safe and have a high level of efficacy, 2) minimize fulfillment time and variability, and 3) reduce total manufacturing and logistics costs while reducing the risk of patient morbidity and mortality. The model consists of two integral components: (1) an agent-based program for a “single manufacturing facility” that simulates the manufacturing and quality control process of cell therapy; and (2) a supply chain network program that evaluates different supply ...


Key Engineering Challenges In The Biomanufacturing Of Lentiviral Viral Vectors, Peter Jones Jan 2019

Key Engineering Challenges In The Biomanufacturing Of Lentiviral Viral Vectors, Peter Jones

Advancing Manufacture of Cell and Gene Therapies VI

No Abstract.


Tangential Flow Filtration And Scalability In Viral Vector Purification, Eni Sterjanaj, Heather Mall, Rachel Legmann, Jacky Dang Jan 2019

Tangential Flow Filtration And Scalability In Viral Vector Purification, Eni Sterjanaj, Heather Mall, Rachel Legmann, Jacky Dang

Advancing Manufacture of Cell and Gene Therapies VI

Pall Biotech has linearly scalable tangential flow filtration technology that can cover processing volume ranges from less than a liter to over 2000 liters. Manual assemblies can be used with Pall TFF filters in scales under 20L and programmable skids are available for larger scales. In this document TFF linear scalability of up to 200 liters is covered starting from a 7L initial volume and maintaining similar pressures, processing times and yields at all scales. Using this scalable technology Pall biotech can help biologics companies go to clinical trials and to commercial scale manufacturing successfully.

Please click Additional Files below ...


Conference Program, Dolores Baksh, Rod Rietze, Ivan Wall Jan 2019

Conference Program, Dolores Baksh, Rod Rietze, Ivan Wall

Advancing Manufacture of Cell and Gene Therapies VI

No abstract provided.


Workshop Agenda, Fernanda Masri Jan 2019

Workshop Agenda, Fernanda Masri

Advancing Manufacture of Cell and Gene Therapies VI

No abstract provided.


Development Of A Closed Car-T Manufacturing Process, Loo-Yong Steven Kee, Calley Hirsch, Devina Ramsaroop, Elizabeth Csaszar, Danylo Sirskyj, Aaron Dulgar-Tulloch Jan 2019

Development Of A Closed Car-T Manufacturing Process, Loo-Yong Steven Kee, Calley Hirsch, Devina Ramsaroop, Elizabeth Csaszar, Danylo Sirskyj, Aaron Dulgar-Tulloch

Advancing Manufacture of Cell and Gene Therapies VI

The field of immunotherapy has emerged as a promising new type of treatment for cancer with the approval of the first two CAR-T therapies. The clinical success of T-cell based immunotherapies necessitates a robust manufacturing process for these products to be consistently produced at commercial scale. Our CAR-T workflow combines unit operation specific solutions for thaw of an apheresis unit, wash, CD3 selection, T-cell activation, lentiviral transduction, incubator- and reactor-based expansion culture, harvest, formulation, cryopreservation and thaw of CAR-T product. We have evaluated the impact of both serum-containing and xeno-free culture media, commercially available T-cell selection and activation reagents, closed ...


Single Use Disposable Biosettler Removes The Dead Cells And Cell Debris Selectively To Increase The Viability Percentage Of Mammalian Cells (E.G., Car-T) During Expansion, Dhinakar Kompala Jan 2019

Single Use Disposable Biosettler Removes The Dead Cells And Cell Debris Selectively To Increase The Viability Percentage Of Mammalian Cells (E.G., Car-T) During Expansion, Dhinakar Kompala

Advancing Manufacture of Cell and Gene Therapies VI

Current challenge in a FDA approved cell therapy product for adult B-cell leukemia is reported to be the percentage of viable cells after manufacturing is sometimes out of specified range. As the head of a large contract development and manufacturing organization observed, this fall in viability percentage during CAR-T cell manufacturing is a challenge to the whole industry.

We present a simple and powerful off-the-shelf solution to this big challenge in all mammalian cell culture expansion bioreactor system. Our single use disposable BioSettler has been demonstrated to be uniquely capable of removing dead cells and cell debris selectively from the ...


Scale-Up Study For Ex-Vivo Expansion Of Allogeneic Natural Killer Cells In Stirred-Tank Bioreactor, Juyoung Kim, Hyung Jin Nam, Sang Hyun Lee, Jong Beom Ku, Seung Ryel Han, Hye Jin Shin, Yu Kyeong Hwang, Sang Hoon Paik Jan 2019

Scale-Up Study For Ex-Vivo Expansion Of Allogeneic Natural Killer Cells In Stirred-Tank Bioreactor, Juyoung Kim, Hyung Jin Nam, Sang Hyun Lee, Jong Beom Ku, Seung Ryel Han, Hye Jin Shin, Yu Kyeong Hwang, Sang Hoon Paik

Advancing Manufacture of Cell and Gene Therapies VI

Natural killer (NK) cells are a type of lymphocyte in the blood that are responsible for innate and adaptive immune response, and they mature in the liver and bone marrow. Being a key role in host defense system with direct and indirect killing of virus-infected cells or cancer cells, NK cell has been considered an attractive candidate for cancer therapy. Peripheral blood shows the low frequency of NK cells, so ex vivo expansion method is important to obtain sufficient NK cells for therapeutic use. Currently, we successfully developed bioreactor process for NK cell expansion on lab-scale. Stirred-tank bioreactor could be ...


Conference Program, Kathy Chan May 2016

Conference Program, Kathy Chan

Cell Culture Engineering XV

No abstract provided.


Impact Of Poloxamer 188 Variability On Biologics Manufacturing: Mitigations And Causal Investigation, Salim Charaniya May 2016

Impact Of Poloxamer 188 Variability On Biologics Manufacturing: Mitigations And Causal Investigation, Salim Charaniya

Cell Culture Engineering XV

Poloxamer 188 (P188), a water-soluble, synthetic copolymer with hydrophilic as well as lipophilic properties, is widely used as a cell protectant for bubble-induced shear during cultivation of suspension-adapted mammalian cells for large-scale production of protein-based therapeutics. Poor cell growth and lower product yield has been recently observed at commercial scales in more than one Chinese hamster ovary-based manufacturing process within Roche network when specific lots of P188 were used. An investigation is being conducted to unearth the root cause of “poor-performing” P188 lots and to identify means to mitigate the product supply risks. P188 raw material is currently sourced from ...


Evaluating Sugar-Based Detergents As A Potential Alternative To Poloxamer Bubble Protectant, Jessica Wuu, Jayanthi Lakkyreddy, Steven Meier May 2016

Evaluating Sugar-Based Detergents As A Potential Alternative To Poloxamer Bubble Protectant, Jessica Wuu, Jayanthi Lakkyreddy, Steven Meier

Cell Culture Engineering XV

Poloxamer 188 (commonly referred to as Pluronic® F-68) is a commonly-used medium component which protects against bubble-induced shear in mammalian cell cultures. Recently, concerns have arisen due to limited sourcing and variable performance of this critical component. In 2008, Hu, et al.1 proposed the use of sugar-based detergents – specifically, maltopyranosides and glucopyranosides – as potential bubble protectants based on their rheological properties and relatively low toxicity to cells. This work explores the feasibility of these detergents using commercially relevant CHO cell lines and media. Detergent candidates were evaluated based on their tolerance by cells, stability in cell culture medium, and ...


A Host Cell Protein That May Impact Polysorbate Degradataion, Kelvin Lee May 2016

A Host Cell Protein That May Impact Polysorbate Degradataion, Kelvin Lee

Cell Culture Engineering XV

There is growing interest and concern related to host cell proteins. Current issues with host cell proteins include questions related to the various available analytical approaches and the sensitivity of those approaches as well as issues with purification strategies and the impact of host cell proteins downstream. The availability of a sequenced genome enables new opportunities to address problematic host cell proteins via cell line engineering. We studied difficult to remove host cell proteins in CHO cells with the goal of identifying host cell proteins that may be product associated with a number of monoclonal antibodies, that may copurify with ...


Troubleshooting The Recover Of Mater Cell Bank For A Commerical Product, Mei Shao, Kishan Rao May 2016

Troubleshooting The Recover Of Mater Cell Bank For A Commerical Product, Mei Shao, Kishan Rao

Cell Culture Engineering XV

Poor recoverability was observed for the Master Cell Bank (MCB) during the preparation of Working Cell Bank for a commercial product. The presentation will describe the investigation process, root causes identified and corrective actions implemented. A new Working Cell Bank was successfully manufactured after implementing the corrective actions. Our strategy to test the WCB prior to commercial manufacturing will also be discussed. In addition, preventative actions were also implemented as a result of the event.


Adapting An In-Licensed/Acquired Cell Culture Process To Platform Conditions, Raghunath Shivappa May 2016

Adapting An In-Licensed/Acquired Cell Culture Process To Platform Conditions, Raghunath Shivappa

Cell Culture Engineering XV

The use of platform materials and processes for new products help streamline process development, enhance predictability and efficiency during manufacturing, and simplify the raw materials supply chain. Although common, adaptation of cell expression systems can require a significant amount of process development work to achieve desired product yield, quality, and comparability. Here, we present a progressive development approach for evaluating platform media and feeds for an acquired cell culture process.

A CHO-DG 44 cell line expressing a novel antibody product was procured through acquisition. The original non-platform media and fed-batch process yielded titers of approximately 3 g/L. A study ...


Challenges In The Development And Adaptation Of Platform Process To Existing Pipeline, Edmund Scarfo May 2016

Challenges In The Development And Adaptation Of Platform Process To Existing Pipeline, Edmund Scarfo

Cell Culture Engineering XV

The development and use of platform processes have been adopted as an industry-wide strategy for enabling faster timelines for early clinical stages. However due to increasing product demands and the competitive landscape of antibody therapeutics in the industry, the development and use of a highly productive and economic upstream platform process has also become an adopted strategy. In keeping with industry standards, Takeda’s platform has evolved from upstream processes capable of achieving protein titers from 0.7-1.2 g/L to highly productive processes achieving titers in the range of 4.0-7.0 g/L. Unlike these earlier, low ...


A Holistic Approach To Facility Protection From Adventitious Agents – A Case Study, Matthew Osborne, Ronan Kelly, Ann Maria Mccrohan, Marie Murphy May 2016

A Holistic Approach To Facility Protection From Adventitious Agents – A Case Study, Matthew Osborne, Ronan Kelly, Ann Maria Mccrohan, Marie Murphy

Cell Culture Engineering XV

The Eli Lilly biologics manufacturing facility in Kinsale, Ireland has been operational since 2010 with a 100% cell culture contamination control success rate. The presentation will review the holistic approach to facility protection from adventitious agents that underpins this success including:

  • The risk assessment approach to points of entry and management via detectability and control measures
  • The approach to personnel training that considers human factors, increased vigilance and event simulations following strategies that are used in chemical synthesis process safety

The presentation will then focus on control of adventitious virus. The talk will briefly comment on the early warning measures ...


Nanofiltration As An Effective Means To Prevent Virus Contamination Of Cell Culture Processes, Christina Carbrello May 2016

Nanofiltration As An Effective Means To Prevent Virus Contamination Of Cell Culture Processes, Christina Carbrello

Cell Culture Engineering XV

While cell culture media is typically sterile filtered to remove bacteria and mycoplasma, many bioreactors remain unprotected from viral contamination. As awareness of the risk for viral contamination of cell culture processes grows, manufacturers are seeking virus barrier technologies to remove or inactivate viruses. Filtration is an ideal technology in terms of familiarity, ease of use and scalability. However, hurdles to its implementation remain, most notably, the high cost and large footprints required to implement filters designed for the downstream process and the concern that the small pore size of virus filters could impact cell culture performance. A filter specifically ...


The Oxygen Binding Protein, Hemoxcell(R), Increases Cho Cell Growth And Extends Viability By Enhancing Oxygen Delivery, Katrin Braasch May 2016

The Oxygen Binding Protein, Hemoxcell(R), Increases Cho Cell Growth And Extends Viability By Enhancing Oxygen Delivery, Katrin Braasch

Cell Culture Engineering XV

The continuous monitoring of cell growth and viability is an integral part of biopharmaceutical production. Measurements of changes in the polarizability of individual cells can identify early emerging sub-populations of apoptotic cells in a dielectrophoretic (DEP) cytometer designed at the University of Manitoba. In this instrument the trajectory of individual cells was tracked as they passed through a bank of electrodes (sensitivity: 0.1 µm; rate: 5 cells per second) designed to differentially perturb the cells according to their polarizability. This perturbation was recorded as a force index (FI), which was related to the electrical displacement of the cells. Using ...


The Differential Polarizability Of Cho Cells Can Be Used To Monitor Changes In Metabolism, Katrin Braasch May 2016

The Differential Polarizability Of Cho Cells Can Be Used To Monitor Changes In Metabolism, Katrin Braasch

Cell Culture Engineering XV

The continuous monitoring of cell growth and viability is an integral part of biopharmaceutical production. Measurements of changes in the polarizability of individual cells can identify early emerging sub-populations of apoptotic cells in a dielectrophoretic (DEP) cytometer designed at the University of Manitoba. In this instrument the trajectory of individual cells was tracked as they passed through a bank of electrodes (sensitivity: 0.1 µm; rate: 5 cells per second) designed to differentially perturb the cells according to their polarizability. This perturbation was recorded as a force index (FI), which was related to the electrical displacement of the cells. Using ...


Development And Application Of Glycosyltransferases For In Vitro Glycoengineering, Alfred Engel May 2016

Development And Application Of Glycosyltransferases For In Vitro Glycoengineering, Alfred Engel

Cell Culture Engineering XV

Glycosylation is an important posttranslational modification of proteins influencing protein folding, stability and regulation of the biological activity, e.g. IgG featuring terminal sialic acids were shown to suppress inflammatory response (ADCC) and increase serum half-life. Fully galactosylated structures seem to improve binding to the complement system (CDC).

Despite all efforts in cell-line engineering and process optimization to increase glycosylation homogeneity, today therapeutic proteins still show a heterogeneous glycosylation pattern, with large variations between bioprocesses and even from batch to batch. The use of glycosyltransferases for enzymatic synthesis of well-defined glycan structures will become an essential tool – at least in ...


Development Of Antibody Detection Methods For Active Product At The Cell Culture Stage, Gregory Walsh, Matthew Schraut, Jon Barricelli, Lada Laenen May 2016

Development Of Antibody Detection Methods For Active Product At The Cell Culture Stage, Gregory Walsh, Matthew Schraut, Jon Barricelli, Lada Laenen

Cell Culture Engineering XV

Development of new analytical methods to characterize the manufacturing process became necessary when the site wanted to implement process improvements to increase output from the bioreactor. The bioreactor process is monitored and controlled for dissolved oxygen content, glucose concentration, temperature, etc. and samples of the harvest are analyzed daily using an endpoint assay and a total protein method. Neither of the two methods can detect the total amount of product at the harvest stage; the endpoint assay will only detect active product and the total protein method will not discriminate between the cellular proteins and the active product. We have ...


Improvement Of Cho Specific Productivity Using Amino Acid Derivatives, Aline Zimmer, Caroline Hecklau, Sascha Pering, Alisa Schnellbaecher, Thomas Eichhorn May 2016

Improvement Of Cho Specific Productivity Using Amino Acid Derivatives, Aline Zimmer, Caroline Hecklau, Sascha Pering, Alisa Schnellbaecher, Thomas Eichhorn

Cell Culture Engineering XV

Industrial fed-batch cultivation of mammalian cells is used for the production of therapeutic proteins such as monoclonal antibodies. Besides medium ensuring initial growth, feeding is necessary to improve growth, viability and antibody production. Amino acids are key elements for the cellular metabolism but also for the quality of the recombinant protein produced. Several studies have already demonstrated the link between amino acid availability and sequence variants [1-3] or specific modifications like trisulfide bonds [4]. To avoid such modifications, the chemical modification of amino acids is an interesting alternative to modulate their overall solubility [5], stability or chemical reactivity.

In this ...


Deepening Knowledge On Cho Cells Metabolism Using Multiple Tracer Substrates, Ana Teixeira, Manuel Carrondo May 2016

Deepening Knowledge On Cho Cells Metabolism Using Multiple Tracer Substrates, Ana Teixeira, Manuel Carrondo

Cell Culture Engineering XV

Optimization of culture conditions through trial-and-error has led to much of the past progress on animal cell culture. Today, a renewed account of the underlying biologies through a “systems” view is providing a deeper knowledge of cellular physiology and laying the basis to reengineer desirable states of further increased culture performance. In this work, we took a comprehensive view of cellular metabolism by extensively profiling extracellular and intracellular metabolomes after 13C‑label supplementation in parallel labelling cultures of [1,2-13C]Glucose, [U-13C,15N]Asn, [U-13C,15N]Ser and [1-13C ...


Nmr-Based Design Of Chemically-Defined Protein-Free Feed Medium For The Cho Expression System, Marina Goldfeld May 2016

Nmr-Based Design Of Chemically-Defined Protein-Free Feed Medium For The Cho Expression System, Marina Goldfeld

Cell Culture Engineering XV

Recombinant expression of antibodies and other biotherapeutics relies heavily on the use of CHO cell lines. The product expression levels in these cell lines are dependent on the feed medium, one of the most important components of the cell culture process. We have developed a systematic approach to designing a chemically-defined feed medium through collaboration between Merck’s Process Development and Assay Development groups. Historically, feed media have been derived from non-chemically defined sources, such as bovine serum and yeast hydrolysate. While these media support robust cell growth and productivity, their chemically-complex nature has hindered efforts to increase the cells ...


How To Select The Most Suitable Media For Your Cells, Marcella Dalm May 2016

How To Select The Most Suitable Media For Your Cells, Marcella Dalm

Cell Culture Engineering XV

Many different media are available to culture CHO cells. Most are either growth supporting or productivity supporting. Ideally, the basal medium is a growth supporting medium, while the feed medium is supporting both growth and productivity. In this study two clones producing the same mAb are compared on their response to a range of basal media. Clone I is fast-growing and low-producing, while Clone II is slower-growing, but high-producing. A panel of eleven different basal media from different vendors was evaluated for growth, titer and metabolism.

An overview is given on the response of the cells to the different media ...