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Cell Culture Videos & On-Demand Webinars

Listen and watch our cell culture webinars to learn about the latest technologies, experimental tips and troubleshooting strategies for your processes.

Vaccine Cell Bank and Virus Seed Characterization

Oct | 2017
  • Presenter: Martin Wisher, Senior Director, Global Head of Regulatory Affairs, BioReliance® Services
  • Abstract
    This webinar will present regulatory requirements for cell bank and virus seed characterization from different organizations worldwide. Learn about new technologies for determination of cell substrates & virus seed stocks and detection of agent contamination.

    The characterization of cell substrates, virus seed stocks and virus harvests, used in human vaccine production, for identity and purity is required by regulators worldwide. This presentation will give you an overview of the regulatory requirements given in the latest guidance documents from the US FDA, WHO, European Pharmacopoeia and ICH. It will highlight differences between these documents and describe new technologies for determining the identity of cell substrates and virus seed stocks as well as detecting adventitious agent contamination.

    In this webinar, you will learn:
    • about the importance of characterising cell banks and virus seed stocks in order to meet worldwide regulatory requirements.
    • the difference between guidance documents from different organizations worldwide
    • new technologies for determining the identity of cell substrates and virus seed stocks
    • detecting adventitious agent contamination

Viral Risk Mitigation Strategies: Key Considerations in the Prevention and Detection of Viral Contamination

Sept | 2017
  • Presenter: Alison A. Armstrong, PhD, Senior Director, Global Head of Field Development Services
  • Abstract
    Regulatory guidelines have defined industry best practices around adventitious virus contamination and risk mitigation in terms of patient safety.

    Today, the industry is taking a closer look at minimizing the business risk associated with viral contamination and is taking a more directed view of risk mitigation. This approach includes virus prevention and detection, in addition to removal.

    From cell culture seed train to final fill vial, this presentation will describe:
    • Potential risks associated with different areas of biotech processes
    • What can be done to minimize adventitious virus risk in those areas.
    The overarching strategy of risk mitigation will include evaluation of raw materials, modified expression systems, environmental controls, upstream and downstream processing, as well as testing and regulatory considerations.

Scalable Suspension Culture for the Generation of Billions of Human Induced Pluripotent Stem Cells using Single-Use Bioreactors

April | 2017
  • Presenter: Chee Keong Kwok, MSc. Stem Cell and Regenerative Medicine Group, Institute of Anatomy and Cell Biology at the University of Würzburg, Germany
  • Abstract
    Register today to watch our webinar discussing how you can reduce the risk of aggregation in bioprocessing.

    Single-use bioreactors represent a promising approach to the challenges of producing human induced pluripotent stem cells in quantities required for cell therapy applications. Discover the process of obtaining 2 billion hiPSCs in only 14 days.

    The production of human induced pluripotent stem cells (hiPSCs) in quantities that are relevant for cell-based therapies and cell-loaded implants through standard adherent culture is hardly achievable and lacks process scalability. A promising approach to overcoming these hurdles is the culture of hiPSCs in suspension. We present optimization of stirred suspension culture using single-use bioreactors. Vessels have been investigated for their suitability in the expansion of two hiPSC lines inoculated as a single cell suspension, with a free scalability between volumes of 50 and 2 400 mL. The simple and robust 2-step process reported here first generates hiPSC aggregates of 324 ± 71 µm diameter in 7 days in 125 mL spinner flasks. These are subsequently dissociated into a single cell suspension for inoculation in 3 000 mL bioreactors, finally yielding hiPSC aggregates of 198 ± 58 µm after 7 additional days.

    In both spinner flasks and bioreactors, hiPSCs can be cultured as aggregates for more than 40 days in suspension, maintain an undifferentiated state as confirmed by the expression of pluripotency markers TRA-1-60, TRA-1-81, SSEA-4, OCT4, and SOX2. Moreover, we show targeted differentiation of expanded cells into neural progeny and cardiomyocytes. Taken together, we expanded 16 × 106 hiPSCs into 2 × 109 hiPSCs in 14 days. This quantity of hiPSCs readily meets the requirements of cell-based therapies and brings their clinical potential closer to fruition.

    In this webinar you will learn:
    • Scalable expansion of induced pluripotent stem cells.
    • The required yield for cell therapy applications.
    • Optimization of stirred suspension culture.
    • Simple and robust two-step process.
    • Targeted differentiation of expanded hiPSC cells into neural progeny cardiomyocytes.

Challenges and Options in High Viscosity Tangential Flow Filtration

April | 2017
  • Presenter: Dr. Paul Beckett, Technology Manager Life Sciences, EMEA
  • Abstract
    Overview of available TFF solutions for achieving high viscosity of monoclonal antibodies and plasma IgG, and strategies for reliable cycle-to-cycle cleaning.

    Current trends in the bioprocessing industry are driving mAb and plasma producers to formulate at higher protein concentrations. As a result, formulating using tangential flow filtration (TFF) may be limited in reaching these concentrations due to high pressures caused by highly viscous feed streams. Filtration devices used during processing have to be optimized in order to handle both high viscosity and pressures while maintaining high flux and excellent product recovery.

    In this webinar, we will review a recent study in which a family of filtration devices was evaluated to characterize the impact of membrane material and channel geometry on process performance and cleanability when working with high concentration feed streams. The results show the performance of each filtration device over multiple re-uses and presents a solution that can overcome process limitations due to high viscosity formulations.

    In this webinar you will learn:
    • Options to achieve higher concentration
    • Cleaning recommendations for TFF cassettes used in high viscosity feedstreams
    • Performance comparison between device design in TFF cassettes

Product Aggregation in Bioprocessing: Origins, Prevention, and Removal

March | 2017
  • Presenter: Dr. Paul Beckett, Technology Manager Life Sciences, EMEA
  • Abstract
    The tendency for most biological products to self-associate and aggregate, often irreversibly, is a considerable challenge in process management and design, as aggregated product leads to patient safety concerns, process challenges and lost yield. Therefore, it is important to reduce the aggregation of the biological product during processing and to remove aggregates efficiently and effectively.

    In this webinar you will learn:
    • How and why biological product aggregates form within a bioprocessing environment, based on process conditions and biochemistry, and how these are detected
    • Strategies for reducing the risk of aggregation at each stage of the process
    • Proven methods for removal of aggregates effectively

Genetic Engineering of CHO Cells for Viral Resistance to MVM

Dec. | 2016
  • Presenter: Joaquina Mascarenhas, Ph.D., Senior R&D Scientist/Team Lead CHOZN® Cell Line Development and Engineering
  • Abstract
    Contamination by the parvovirus Minute Virus of Mice (MVM) remains a continuing challenge and on average we see one major episode of MVM contamination every ~5 years. Although infrequent, infection of a fermenter can be catastrophic for a producer, resulting in the loss of product, temporary withdrawal from the market and extensive clean down costs, which can reach a total in the tens of millions of dollars. In addition to the loss of associated revenue, a contamination event can also have a potential impact on drug supply, patient safety and have regulatory implications. 

    In this work, we evaluated engineering a CHO parental cell line to create a new host cell line that would be resistant to MVM infection by eliminating the major receptors used by the virus to enter cells. The goal was to engineer a host cell line resistant to MVM infection, while maintaining desired productivity and product quality profiles. While the exact functional receptor for MVM binding to CHO cell surface is unknown, sialic acid on the cell surface has been implicated. The CMP-sialic acid transporter, solute carrier family 35A1 (Slc35A1) is responsible for transporting sialic acid into the Golgi. Knocking out function of this gene in a cell results in asialylated glycan structures, thus eliminating the ability of MVM to bind to and enter the cell. While the wildtype cells displayed immediate loss of viability and inhibition in cell growth upon MVM infection, the absence of sialic acid on the SLC35A1 knock-out cell line lead to complete resistance to MVM infection. This approach could be applied to different CHO host cell lines, as well as therapeutic protein producing clonal cell lines. Incorporation of viral resistance to the MVM virus in the CHO host and subsequent production cell lines adds yet another level of "defense" to the current risk mitigation strategies used, adding even greater assurance of production of safely delivered cell derived products. 

    In this webinar you will learn: 
    • How genetic engineering technologies can be used to create viral resistance in CHO cells 
    • How to include genetically engineered MVM resistance into a viral risk strategy 
    • How to validate viral resistance in CHO cells 

Review of a Supplier's Quality Control while Manufacturing Single-Use Systems

Nov. | 2016
  • Presenter: Michael Felo, Director Mobius Single-Use, Merck
  • Abstract
    Single-Use systems, enabling faster more cost effective bio-pharma manufacturing, must also meet high quality parameters and standards while conducting component qualification, manufacturing operations, inprocess testing, and final product release.

    For single use systems, quality control during the manufacturing process is critical. In a traditional stainless-steel system, the end user has significant control over the design, construction, qualification and validation, and maintenance of the system. When implementing a single-use system, the supplier of the single use product takes responsibility for many of these functions from the user. It is therefore important that the single use supplier has established and follows a strong quality control system. This presentation will highlight the quality systems, processes, facilities, and personnel required to assure the performance, robustness, and sterility of single use systems.

    In this webinar you will learn:

    • The process used to qualify components, suppliers and sub-suppliers
    • Managing documentation control, change control, process particulate control, risk mitigation practices
    • See examples of Extractables Testing, Validation of MFG processes, MFG Controls, Sterilization Qualification, Realease Testing and Certification, Integrity Assurance

Processing of Small Biological Molecules by TFF

Nov. | 2016
  • Presenter: Emily Peterson, Biomanufacturing Engineer, Merck
  • Abstract
    Strategies to overcome key limitations and challenges such as higher molecular osmotic pressure and lower membrane permeability when customizing small molecule (3-10 kDa) TFF processing.

    Due to their higher osmotic pressures and mass transfer coefficients, small molecules in the range of 3 – 10 kDa, like insulin, often require unique processing conditions as compared to those of larger molecules. TFF processing strategies developed for larger molecule applications may not be appropriate and can lead to an increase in process variability and sub-optimal performance.

    This webinar explores:

    • The key limitations and challenges typically observed with small biological molecule TFF processing
    • Explains the strategies required for optimal success with your TFF step

Advanced Perfusion Processes: Design Criteria and Strategies

July | 2016
  • Presenter: Dr. Jochen B. Sieck, Head of Laboratory Cell Culture Performance R&D, Life Science Division, Merck KGaA, Darmstadt, Germany
  • Abstract
    Rising cost pressures in the biopharma industry and the demand for biopharmaceutical companies to diversify their biologics portfolio require them to manufacture in smaller and more flexible plants. New high-density cell culture processes, such as concentrated perfusion, present suitable solutions to adapt to these new manufacturing conditions and to facilitate a shift toward single-use technologies.

    Perfusion processing relies on the constant addition of fresh medium and the removal of spent medium from an operating bioreactor. The next generation of perfusion processes might require an increased medium depth; this is partly because of low perfusion rates of 1-2 reactor volumes per day, which sometimes are even smaller than that.

    In this webinar we will discuss:

    • The selection and optimization of scale-down models
    • Suitability of single-use bioreactors
    • Approaches for medium development
    • Balancing nutrients
    • Performance optimization using multi-variate approaches

Delivering More Efficient Therapeutic Protein Expression Systems Through Cell Line Engineering Applications

June | 2016
  • Presenter: Trissa Borgschulte, Head of Cell Line Development and Engineering, Merck
  • Abstract
    Historically cell line performance has been enhanced through media, feed and process optimization, primarily through trying to meet the basic nutritional requirements of the cells so that they can sustain high growth and productivity throughout the production runs.

    However, the omics (genomics, transciptomics and metabolomics) era, sequencing of the CHO genome and enhancements in genome editing technologies over the past several years have enabled scientists to take a more direct route in cell line optimization through the modification of specific genes that have direct implications on cell culture performance, protein quality attributes and upstream and downstream manufacturing processes. These targets include but are not limited to genes that may be involved in cell cycle regulation, cellular metabolism, cellular transcription and translation, the secretory pathway and protein glycosylation or other post-translational modifications.

    In this webinar we will discuss specific genetic modifications that have been made to CHO cell lines and how these modifications can lead to more efficient expression systems.

Serum-free Media for Therapeutic Cell Manufacturing – Challenges and Innovations

May | 2016
  • Presenter: Aletta Schnitzler, Ph.D., Senior Scientist, Merck
  • Abstract
    The need for high quality materials that are animal origin-free and compatible with a limited number of downstream processing steps will increase as cell therapies achieve clinical success. Large scale manufacturing necessitates transition from planar culture to technologies such as stirred tank bioreactors where culture of suspension cells or adherent-dependent cells on microcarriers is enabled.

    This webinar will discuss challenges and solutions to the elimination of animal-derived components from cell culture processes, with focus on human mesenchymal stromal/stem cells (hMSCs). Fetal bovine serum in particular is associated with regulatory, supply, and consistency challenges, yet a wide range of performance has been observed between different serum-free media formulations for expansion of hMSCs in planar formats. Moreover, a positive performance in static culture is not necessarily predictive of that under agitated conditions with microcarriers, highlighting ongoing challenges to the generation of a fully chemically-defined and scalable cell culture medium. Through use of pharma-grade basal media manufactured with advanced milling technology and EMPROVE® raw materials, as well as transition to serum-free supplementation and process development activities, the robust expansion of hMSCs across platforms has been achieved.

Implementing Single Use Technologies – Plasma Case Study

April | 2016
  • Presenter: Sue Walker, Product Manager, Formulation and Final Fill Applications, Merck
  • Abstract
    In general, the plasma industry is facing pressure to provide a safe, efficacious and secure supply of plasma products on a worldwide basis while at the same time, there is limited capacity for processing. One solution for this problem that is gaining acceptance in the biopharmaceutical industry is the use of flexible facilities containing single use equipment. But operations focusing on plasma processing face some unique challenges that can impact the implementation of single use technologies including batch sizes, historical fractionation processes and large scale chromatography.

    A facility design exercise utilizing a combination of single-use technologies and classical stainless steel equipment can represent an attractive option for plasma applications to address these unique challenges.

    This webinar will discuss considerations for the implementation of single-use technologies for plasma applications and facilities focusing on operational flexibility, overall process timing and economics.

The Chronicles of a Biosimilar Production Facility

April | 2016
  • Presenter: Sébastien Ribault, Director of Provantage® BioDevelopment, Merck
  • Abstract
    As many biologics will or have come off patent, the opportunity for competition, and potentially lower biologics costs through biosimilars, is created. Barriers to entry, the main one being product manufacturing as relatively minor changes in the process may impact quality or safety, exist. Coupled with the need for manufacturing flexibility and agility for commercial success, you are faced with a challenging dichotomy.

    In this webinar, we will discuss the challenges you face in designing and constructing a single production facility that can produce different biosimilar monoclonal antibodies, from clinical studies through commercial production. We will look forward 10 to 15 years and consider different production scales utilizing SU equipment in conjunction with flexible facility design, and potential economic impacts.

Change Control Process: Securing Your Supply Chain for Filters

Jan. | 2016
  • Presenter: Kenneth Muzykewicz, Director of Membrane Process and Technology, Merck
  • Abstract
    Changes happen. Suppliers go out of business. Plants consolidate. Drug product lifecycles exceed the lifecycles of the raw materials on which they’re reliant. We are committed to controlling, managing and communicating changes in the most stringent and highest quality manner to ensure your security of supply. In this webinar, Kenneth Muzykewicz will provide you with an overview of our change control process for critical raw materials within our filters.

    Join us for this webinar as we will focus on our:

    • Validation strategy & philosophy
    • Step by step approach to validation
    • Success criteria

    And learn how we:

    • Demonstrate no adverse effect on product performance
    • Define equivalence
    • Minimize the impact of change on your process

cGMP Implementation of Single Use Upstream Technologies

Jan. | 2016
  • Presenter: Flavien Thuet, New Technology Engineer, Merck
  • Abstract
    Single-use technologies at the 2000 L scale have become the gold standard to deliver a fast, flexible and cost-effective solution for production of recombinant proteins in a cGMP environment. With the aim to deliver a faster, simpler and cheaper solution compared to conventional stainless steel equipment, the identification of a relevant single-use cell culture platform for a multi-product facility should rely on several considerations; primarily, a platform that benefits from a clear definition of the design space from bench to production scale to minimize process development efforts. But beyond the need for a scalable platform to achieve the desired cell density, product yield and quality across scales, other considerations should be evaluated at the right point in time during the build of a cGMP upstream suite. For instance, during the design phase the combination of single-use equipment, raw materials, and facility layout should reduce the manipulations that commonly lead to human errors.

    This presentation will explain how media preparation, cell culture in the bioreactor and clarification steps can be integrated within the same upstream suite using single-use technologies.

    Additionally, practical considerations following single-use implementation will be discussed, including facility and equipment design, installation, qualification, operator training and cell culture performance.

Influenza Vaccine Production Using Cell Culture with Microcarriers

Oct. | 2015
  • Presenter: Michael McGlothlen, Manager, Upstream Process Innovation
    Center, Merck
  • Abstract
    This webinar focuses on the development of an upstream MDCK cell based influenza A/WS/33 flu production process using Cytodex3 microcarriers in a 3L Mobius® Single-Use stir tank bioreactor. Initial development of the cell based process was performed in 250mL Corning baffled shake flasks to evaluate microcarrier concentration, inoculation and cell growth. The developed process was then optimized for cell growth and virus production by evaluating process control parameters such as; pH, dissolved oxygen and agitation in the 3L Mobius® system. The developed process is capable of achieving peak cell densities of 3e6 cells/mL on 4 g/L of Cytodex3 microcarriers with ~ 35,000HAU/mL of influenza virus.

    We will explore:
    • Microcarrier concentration, inoculation, and cell growth
    • Optimizing cell growth and virus production by evaluating process control parameters
    • Developing a process to achieve peak cell densities to produce a large volume of vaccine in a short timeframe

Developing a cGMP Cell Therapy Manufacturing Strategy

Aug. | 2015
  • Presenter: Martha Rook, Director, Stem Cell Bioprocessing, Merck
  • Abstract
    When making the translation from research to the clinic, demonstrating efficacy is only the first step to developing a successful cell therapy product. Long-term commercial viability requires early process scalability coupled with high quality ancillary materials that offer a safe and sustainable supply.

    We will present a model for translating a human bone marrow Mesenchymal Stem Cell flask based process to a scalable manufacturing process including media, reagents, stirred tank bioreactor expansion, and harvest. Maintaining key quality attributes at all scales is a focus along with assays to consider for demonstrating equivalence between processes.

    A well thought out strategy for cGMP processing requirements from phase I trials to commercialization is essential in successfully translating a potential therapy to a commercial product.

Mobius® Single-Use Bioreactors Scalability: Bench to Clinical Scale

July | 2015
  • Presenter: Janice Simler, Global Product Manager for Bioreactor and Clarification Systems, Merck
  • Abstract
    To successfully implement a large scale single-use bioreactor platform, equivalent performance, i.e. scalability, with smaller sized bioreactors across the platform must be demonstrated. With the recent development of a single-use clinical scale (2000 L) bioreactor, the Merck bioreactor portfolio now spans from the bench-scale (3 L), through the small-scale (50 L) and pilot-scale (200 L) up to the manufacturing process volume range. The performance design space of the entire Mobius® Single-use Bioreactor platform was characterized using several key engineering parameters including oxygen mass transfer coefficient (kLa), power per unit volume, Reynolds number (Re), mixing time and tip speed. Based on a detailed understanding of the dynamic performance capabilities of each bioreactor across the platform, appropriate process parameters can be selected to achieve scalable performance. This presentation will highlight how a detailed understanding of the performance design space of each sized bioreactor can enable the selection of process parameters at each scale that will enable scalable performance across the platform.

Biosimilar Upstream Process Development - The Challenges and Promises

April | 2015
  • Presenter: Rong Rong Zhu, Senior Scientist, Merck
  • Abstract
    The need of affordable medicines and the anticipation of many blockbuster patent expirations have created great opportunities for Biosimilars development with expected current global revenues of $1.9-2.6B in 2015 and growth rates of 20% annually. Unlike small molecule drugs, biotherapeutics are produced from living cells and product qualities are not only defined by their structures but also determined by manufacturing processes. One of the major challenges in Biosimilar manufacturing is to produce biomolecules as similar to the originator’s molecules without the knowledge of originators’ manufacturing conditions. Biosimilar companies are looking for the tools with focus on upstream process development which can produce Biosimilars with targeted product quality as originators’. This talk will give a few case studies on how upstream process changes (cell line, cell culture media and harvest time) affect product qualities. Can we find the links between process parameter changes and product quality? We will discuss methods to achieve consistency in biosimilar manufacturing by reducing raw material variability. Please join us for the presentation and discussions.

Perfusion-based Bioprod Applications Using Mobius® Bioreactors

Nov. | 2014
  • Presenter: Michael Cunningham, Process Development Scientist, Merck
  • Abstract
    Manufacturing of biotherapeutics is evolving to encompass widespread use of single-use technologies in order to control costs and optimize operational flexibility. Single-use bioreactors are commonly used for both process development and commercial production of monoclonal antibodies (mAbs) and recombinant proteins. While utilization of these systems have routinely employed batch and fed-batch modes of operation generate recombinant products from mammalian expression systems, the use of the bioreactor for perfusion in this operational space has yet to be sufficiently characterized and implemented.

Compacted Cell Culture Media - Improving Solubility and Stability

Nov. | 2014
  • Presenter: Nikolai Stankiewicz, Head of Technology Transfer Laboratory, Merck
  • Abstract
    Dry powder cell culture media formulations provide many advantages with respect to shipping and storage. However to leverage these benefits, they need to be highly soluble, homogeneous and convenient to handle. An improvement of dry powder media properties can be achieved by the combination of optimized milling procedures and suitable formulation technologies. Starting from a homogeneous dry powder medium, the roller compaction technology is able to fix this homogeneity in larger compactate particles (> 1000 µm) so that de-mixing can be prevented. Additionally, the presented roller compaction offers several other advantages, specifically product stability, based on the fact that only pressure and no water is needed in the production process. Applying media as compactates also reduces dust formation and improves the flowability, making the handling of these cell culture media much more convenient. But the key advancement of using compacted media is the acceleration of the dissolution speed. In this webinar, we will present data underlining the advantages of compacted media and the stability of raw materials using UPLC and LC-MS methods completed with results from fed-batch cultivation experiments based on compacted cell culture media.

Novel Single-Use Bioreactor Technologies for Cell-based Vaccines

June | 2014
  • Presenter: Sylvain Ribaud, Field Marketing Consultant, Upstream Process Solutions, Merck
  • Abstract
    The current trend to develop multi-product facilities requires flexibility of manufacturing equipment for culture of adherent or suspension cells with a corresponding reduction in process complexity. The ultimate goal is to reduce cost and contamination risks and to allow rapid scale-up from lab to production scale. For vaccines in particular, the identification of a single, scalable, single-use bioreactor platform is critical for rapid process development success. Because vaccine processes utilize a wide variety of cell types for production, a single-use bioreactor platform must incorporate a range of novel single-use technologies that provide optimal cell culture performance. This webinar discusses the single-use design considerations and key process parameters that enable rapid and reliable scale-up from lab to pilot for the production of viral vaccines. Scientific data obtained with 3L and 50L single-use stirred tank bioreactors for the cultivation of adherent MDCK mammalian cells on microcarriers, as well as for virus production in EB66® cells, are presented.

Improvement of Cell-freezing Technologies and Disposable Bioreactors: Toward a Fully Closed USP Process

May | 2014
  • Presenter: Aurore Lahille, New Technology Supervisor, Biodevelopment, Merck
  • Abstract
    Biotech processes still contain a number of open and at risk transfer steps including the cell culture step when transferring from a frozen vial to containers such as shake flasks. This critical expansion step may take several days or weeks and can delay development or production timelines due to contamination. In order to mitigate risk, a study on bag freezing conditions and the scalability of single-use bioreactors (SUB) was performed coupling traditional technologies and new technologies (disposable bags, cases and bioreactor), in order to define a fully-closed USP process. This study evaluated cells in bags in a fully-closed operation for freezing, thawing and inoculation in a 1250 L bioreactor. The first trial of seven different CHO cell lines was performed, demonstrating the feasibility of this approach. This method was combined with SUBs commonly used for process development and as seeding or production bioreactors. From 2010 to 2013, a study was conducted to evaluate the performance of SUBs at various scales from 3 L to 200 L. This evaluation was performed for seeding applications and clinical material production. Several clinical runs at 200 L and 1250 L were completed to ensure a meaningful comparison. In addition, glass and stainless steel bioreactors of different sizes ranging from 3.6 L to 1250 L were compared. This presentation discusses how to develop a fully-closed USP process by coupling cell freezing in bags and single-use bioreactors up to production scale.

Scalability and Robustness of the Mobius® Bioreactor Platform

March | 2014
  • Presenter: Lee Madrid, Ph.D., Consulting Engineer, Merck
  • Abstract
    Upstream processing is shifting to single-use bioreactors due to their advantages over traditional stainless steel reactors. The Mobius® single-use bioreactor platform consists of 3 L, 50 L and 200 L vessels that are scalable and robust in cell culture applications. This presentation will compare our scalable platform from 3 L to 50 L to 200 L. We will describe the engineering and cell culture performance, as well as the ability of these reactors to function as seed and production vessels. A comparison of mixing time, volumetric mass transfer capabilities, temperature mapping and power input will define the process design space where accurate monitoring and control can take place. In addition to physical characterization comparison, data presented will also include CHO cell production in a GMP and process development environment.

Essentials in Reliable Quality of Dry Powder Mammalian Cell Culture Media: Raw Materials and Production Process Development

March | 2014
  • Presenter: Dr. Jörg von Hagen, Head of Process Development and Launch Management, Merck
  • Abstract
    Please join Dr. Jörg von Hagen, as he addresses current bottlenecks in media & feeds.

The Importance of Media Selection and Scale-down Models for High-titer Expression in CHO Cells

March | 2014
  • Presenter: Sebastien Ribault, Director, Bioproduction & Development, Merck
  • Abstract
    The quest for a viable industrial biotechnology process generally starts with the generation of a cell line expressing the protein of interest. In many cases, the search for the best-producing clone is often like looking for a needle in a haystack. While clonal selection is emphasized, the metabolic aspect is often neglected and optimization of the media and associated feeds used for the upstream process is less of a focus.

    Most companies spend several months, if not years, developing their own generic medium and feed platforms, or have opted to use commercial ones. Medium and feed platform assessment is being performed earlier in the product development process and clone screening is conducted increasingly in fed-batch conditions. Media selection is a crucial step as is the ability to use the first data generated at very small scale (such as spin tubes) to define large-scale behavior. Therefore, it is important to have the right screening tools with lower working volumes available.

    With so many variants of the CHO cell line, generic media and associated supplements, it is difficult to select one media and associate it with a CHO-derived cell line. We have found that screening 3 to 6 clones against 5 to 10 media is an effective way to find the best clone/media/feed combination.

    This webinar will assess our screening scale-down model through a “generic” CHO media assessment. We will define the conditions of a standardized platform, allowing us to scale up from spin tubes to 3L and then to 200 L. A comparison of the various scales used in this template will be presented.

Microcarriers in Single-use Culturing of Adherent Cells

Nov. | 2013
  • Presenter: Lee Madrid, Ph.D., Senior Consulting Engineer, Merck
  • Abstract
    This webinar will discuss the cultivation of adherent mammalian cells on microcarriers utilizing our 3L and 50L Mobius® CellReady single-use stirred tank bioreactors. We will outline how Cytodex® and Solohill® collagen coated microcarriers were tested as part of a mixing study to assess feasibility of the mixing system under various power per unit volume conditions. We will then present our evaluation of the normalized mixing speeds required by the 3L and 50L bioreactors to achieve a suspension of the microcarriers. In addition, we will demonstrate how the bioreactors enabled efficient growth of Madin-Darby Canine Kidney Cells (MDCK), a cell line traditionally used in influenza vaccine production, as well as Human Mesenchymal Stem Cells (hMSCs).

Advanced Cell Culture Media for CHO Fed-Batch Applications: Design of CHO Cell Culture Media Targeting Cell Growth, Productivity and Final Product Quality Attributes

Oct. | 2013
  • Presenter: Glenn P. Godwin, R&D Manager, Cell Culture Development, Merck
  • Abstract
    Cell culture media and feed supplements supporting CHO cell lines and fed-batch manufacturing processes require significant optimization to demonstrate and validate acceptable performance. In order to accelerate product development timelines and expedite the simultaneous screening of multiple components or factors, while reducing the process scale & total resources required, we have successfully implemented high throughput (HTP) approaches for basal media and feed supplement development.

    Join in this discussion to find out how DOE and HTP approaches, combined with investigation of critical product quality attributes, raw material impacts and final scalability of media and feed formulations can be successfully implemented.

Stainless Steel vs Single-Use Technologies

June | 2013
  • Presenter: Sébastien Ribault, Ph.D., Director, Bioproduction & Development, Merck
  • Abstract
    This webinar explains the benefits of using disposable equipment in your manufacturing process. We compare stainless steel, glass and single-use technologies, highlighting how comparable they are regarding titers and molecule quality, as well as the differences regarding operational and financial aspects. This webinar highlights studies performed to evaluate the performances of single-use equipment from early process development through to the manufactured drug substance using a fed-batch process. Process performance was compared in single-use, glass and stainless steel bioreactors. Several clinical runs at various scales using different types of cells such as CHO and NS0 and molecules including numerous MAbs and Fc-Fusion proteins were performed. We discuss how the results offer insights into scalability and comparability of the different systems and technologies. Finally, we review the time, resources and cost of the various operation options available to process developers.

Using a 3-L Disposable Bioreactor to Increase Your Throughput Development Capacity

May | 2012
  • Presenter: David Balbuena, Process Development and QC Manager, Merck
  • Abstract
    During therapeutic protein process development, it is critical for the process to be efficient and economical, particularly when you have limited capacities. One method to address these concerns is to use a disposable bioreactor, which is designed to greatly reduce turnaround time, enabling operators to focus on other value-added activities. Disposable 3-L bioreactors can provide similar results as glass versions and can also be representative of large scale processing. This webinar will present data that shows how disposable bioreactors can support process development activities. A comparison of disposable 3-L bioreactors, 1250-L stainless steel bioreactors and reusable 3-L bioreactors will be shown.