Purification Videos & On-Demand Webinars

Nov | 2017

• Presenters: Eric Youssef, Associate Director Plasma Initiative; and Santosh B. Rahane, Ph.D, Senior Research Scientist
• Abstract

  A webinar to discuss strategies to address Immunoglobulin (Ig) purification challenges by using Ion Exchange and Affinity chromatography media.
  
  The plasma industry is facing pressure to provide a safe, efficacious and secure supply of plasma products around the globe. There is a particular focus on the top leading product of this industry, Immunoglobulin. From a manufacturing perspective, many efforts have been set on increasing yield and safety using chromatography steps.
  
  In this webinar, you will learn more about how our Fractogel® EMD Ion-Exchange and Eshmuno® P anti-A/B affinity chromatography resins can support your purification goals by:

  • Enhancing yield and purity
  • Providing long and robust lifecycles

  Fractogel® EMD TMEA is an anion exchange chromatography resin, using our proprietary tentacle technology to effectively increase target protein binding capacity. Eshmuno® P anti-A and Eshmuno® P anti-B are two distinct affinity-based chromatography resins specifically designed to effectively remove anti-A and anti-B isoagglutinins, respectively.

Sept | 2017

• Presenter: Dr. Paul Beckett, Technology Manager Life Sciences, EMEA
• Abstract

  Improving vaccine purification yield and efficiency with custom TFF membranes.
  
  Vaccines save millions of lives every year and improve the quality of life for countless others. Unlike monoclonal antibodies, a greater diversity of molecular size exists for vaccine products, which makes a downstream process hard to template. In the case of conjugated polysaccharide vaccines, this is further complicated by the fact that a large number of strains and serotypes need to be conjugated into a multivalent vaccine to provide thorough immunity, and each serotype can behave differently during processing. One of the most critical purification steps in a conjugated polysaccharide vaccine process is the removal of unconjugated polysaccharide from the feed stream, which is typically performed via tangential flow filtration (TFF). A continuing challenge for the TFF step is that membranes are available in a limited set of nominal molecular weight cutoffs. This limited availability of specific pore size membranes often leads to yield sacrifices in order to maintain the required purity, which potentially impacts the reliability of vaccine supply. An advancement in the mPES membrane manufacturing process can enable better uniformity and improved control of the membrane pore size. This provides the capability of producing a custom TFF membrane best suited for a given process stream and therefore, enhance yield, purity, efficiency, and economics in new or existing vaccine processes.
  
  In this webinar, we will discuss:

  • Current process development challenges for conjugate polysaccharide vaccines (CPV)
  • How a custom membrane technology can be developed and implemented
  • How an industrial process yield and efficiency were improved with use of custom membranes in a case study

Sept | 2017

• Presenters: Michael Schulte, Head of R&D Chromatography
• Abstract

  This webinar will teach you how to complete a combined and optimized method for the complete downstream processing of recombinant human insulin and select the most suitable phase combinations.
  
  By 2035, 10% of the adult population, a total number of 600 million people worldwide, are projected to suffer from Diabetes. As a result, the demand for recombinant human insulin will increase significantly. The number of projects currently under way for the production of insulin biosimilars reflects this direction. This webinar focuses on the increasing need for recombinant human insulin purification in the downstream process. The capture and intermediate steps of the process use ion-exchange resins, while the polishing step uses high-performance reverse phase silica. The ion-exchange resins in the first steps should have high flowrates combined with high binding capacities as well as very low non-specific binding of process impurities such as pigments from the fermentation broth. For the final polishing step on RP-silica, it is critical to select a suitable combination of stationary and mobile phases since this combination heavily influences selectivity and process throughput. Finally, we will touch upon the use of tangential flow filtration to process the aqueous-organic value fraction during the reversed phase polishing step.
  
  In this webinar, you will learn:

  • How to complete a combined and optimized method for the complete downstream processing of recombinant human insulin
  • How to critically decipher and select the most suitable phase combinations for the process.

June | 2017

• Presenters: Eric Lacoste, Head of ADC Process Development Team at Sanofi
• Abstract

  This webinar highlights Tangential Flow Filtration (TFF) case studies during Antibody Drug Conjugate (ADC) process development within Sanofi and provides preliminary results on a novel single-use TFF capsule.
  
  ADC therapies have been a booming field within the last decade, and remain a key possibility for Paul Ehrlich’s vision of a “magic bullet” concept for personalized medicine. However, ADC process development and manufacturing remain very challenging due to the intrinsic complexity of these drug entities.
  
  The generic ADC process is composed of at least three steps: chemical reactions in aqueous buffer (including some organic solvent); purification and formulation steps. This webinar will highlight TFF case studies during ADC purification process development within Sanofi, and will provide preliminary results using a novel single-use TFF capsule. This new device is designed to replace standard TFF cassettes, providing the same level of performance while offering improved process containment.
  
  In this webinar, you will learn:

  • TFF process development
  • Implementation of a TFF capsule instead of cassette

June | 2017

• Presenter: Jonathan Steen, Principal Development Engineer
• Abstract

  Antibody drug conjugates (ADC) are a promising cancer therapeutic that combine antibody specificity with cytotoxic efficacy. 
  
  While tangential flow filtration (TFF) is used in several steps in an ADC manufacturing process, special considerations are required for the TFF step after conjugation of the antibody and cytotoxic agent due to increased toxicity and occasional presence of organic solvents. Currently, solvent-resistant TFF cassettes are a preferred option for ADC processing. They are usually not reused due to the small batch size and concerns regarding operator exposure. Next generation, fully encapsulated TFF devices are coming on the market that are designed to increase process flexibility and further improve operator safety. 
  
  This webinar will discuss best practices for TFF UF/DF step in ADC manufacturing and present a new encapsulated TFF device format for increased operator safety and plug-and-play simplicity. 
  
  You will learn: 

  • The best practices of the TFF process for ADC’s and available device options, including the existing TFF cassettes 
  • Upcoming TFF capsules designed for operator safety and plug-and-play simplicity 

May | 2017

• Presenter: Thomas Elich, Applications Engineer
• Abstract

  There is growing interest within the biopharmaceutical industry to improve individual unit operation performance by intensification and overall process train efficiency through linked and continuous processing.
  
  Single pass tangential flow filtration (SPTFF) technology can facilitate these process intensification efforts by modifying process intermediate volumes and concentrations without the need for recirculation. This webinar describes an approach linking SPTFF with Eshmuno Q anion exchange resin for intensified mAb polishing. Results are presented which show that by pre-concentrating the Eshmuno Q feed, improvements in resin loading, productivity, and process economics are realized as compared to using Eshmuno Q alone.
  
  In this webinar you will learn:

  • A new approach which combines SPTFF with Eshmuno Q chromatography resin for intensified polishing.
  • How intensified polishing improves Eshmuno Q resin utilization and streamlines processing.
  • Strategies to implement intensified polishing as either a batch step or combined with others in a continuous process.

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

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

Nov. | 2016

• Presenter: Emily Peterson, Biomanufacturing Engineer, MilliporeSigma
• 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

Oct. | 2016

• Presenter: Julie Murrell, Head of Cell Therapy Bioprocessing, MilliporeSigma
• Abstract

  This webinar reviews the findings of a recent survey conducted by the Economist Intelligence Unit and presents ways to navigate tomorrow's complex biopharma landscape in order to make novel therapies a reality.
  
  A recent survey conducted by the Economist Intelligence Unit highlights the new products that the biopharma industry identifies as most disruptive to their growth strategies in the next five years. The findings raise a challenge to biopharma to go beyond barriers to bringing new products to market by presenting ways to overcome these hurdles and make novel therapies a reality.

  In this webinar you will learn:

  • The impact of novel therapies on biopharma growth strategy
  • Manufacturing challenges associated with novel therapies
  • How to overcome barriers to bringing novel therapies to market

Oct. | 2016

• Presenter: Claire Scanlan, Process Development Scientist (PDS) & Manager for Central PDS Region in North America, MilliporeSigma
• Abstract

  One of the most critical steps in a vaccine manufacturing process is clarification, particularly harvest or lysate clarification.

  The methods employed can vary greatly due to:

  • The production system used
  • Product being harvested
  • The nature of the properties of the process fluid

  Centrifugation and/or microfiltration has historically dominated the vaccine process landscape, but the advent of newer normal flow filter options and the increased desire for disposable/single-use processes have expanded vaccine clarification choices.

  This webinar will detail the various clarification methods that can be successfully used for three vaccine types: viral, bacterial and polysaccharide vaccines. We will also focus on the wide-ranging uses of a novel depth filter for the efficient clarification of multiple vaccine types.

Oct. | 2016

• Presenter: Christopher Gillespie, R&D Manager and Head of Downstream, Next Generation Bioprocessing
• Abstract

  Platform processes for mAb manufacturing has become the norm for the majority of the bioprocess industry. MAb producers are today faced with increasing pressure from both internal and external sources (e.g. biosimilars, patent expirations, facility fit constraints, etc.), making investigations of process intensification approaches a necessity. This webinar will focus on our full range of mAb production solutions we have developed and are continuing to develop to address the needs of mAb producers today and in the future.

  In this webinar you will learn:

  • A robust toolbox of polishing technologies enabling a fully flow through polishing platform
  • How implementation of next generation processing can positively impact facility fit limitations

Aug. | 2016

• Presenter: Dr. Mikhail Kozlov, Senior Marketing Manager, MilliporeSigma
• Abstract

  According to market research, DNA and RNA therapeutics are growing at 12% CAGR and expected to reach $1.2 billion by 2020. This webinar reviews the current dynamics in the RNA therapeutics/vaccines market and focuses on process development and manufacturing strategies.
  
  By watching this webinar, you will know more about:

  • The differences between small-interfering RNA (siRNA), RNA interference (RNAi), microRNA (miRNA), and messenger RNA (mRNA).
  • The general production processes for these platforms.
  • The challenges encountered during process development and production and the strategies to overcome them.

June | 2016

• Presenter: André Kiesewetter, Applications Engineer, Merck KGaA, Darmstadt, Germany
• Abstract

  Chromatographic process development is a challenge. Defining an optimal process requires the testing of many different resins under various operating conditions such as buffers, load and gradients.

  Three basic techniques for resin testing are commonly available:

  • Resin slurry plates (batch incubation)
  • Micropipette tips
  • Miniature chromatography columns (MCCs)

  Even though the batch assay is considered the most simple, flexible and fastest way for resin screening, it only provides limited information on the resolution of impurities, yield and purity under column operation conditions. Same for the micropipette tips working in batch-mode and presenting very limited capabilities to mimic real column operation conditions.

  High-throughput technology like miniature chromatography columns however represents a reliable resin screening tool which applies the packed bed principle and flow conditions of conventional chromatography but on a microliter scale. Complex separations are possible and close resemblance between data from the MCC and lab scale format can be achieved. However, the implementation of a MCC based screening platform on a liquid handling system (LHS) and the identification of appropriate parameter settings represent a challenging task which requires users to have multidisciplinary knowledge in the areas of automation, liquid handling, data processing and application of chromatography scale down theories.

  Watching this webinar, you will learn:

  • Principles of common resin screening formats and its application areas
  • Fundamental aspects of scale down
  • How to implement pseudo-linear gradient elution for resin screening using miniature columns
  • How to avoid pitfalls of liquid handling
  • Which MCC applications are feasible

June | 2016

• Presenters:
  
  • Dr. Michael Schulte, Head of Chromatography R&D, Merck KGaA, Darmstadt, Germany
  • Michaela Oberle, R&D Project Leader and Specialist for Thin Layer Chromatography, Advanced Analytics, Merck KGaA, Darmstadt, Germany
• Abstract

  A revival for the development of new drug molecules from plants or other biological sources has been observed, certainly fostered by the 2015 Nobel Prize for Medicine granted for the development of the antimalarial drug artemisinin, which has been extracted from the plant Artemisia annua and purified by preparative chromatography.
  
  Analytical Thin Layer (TLC) and Preparative Liquid Chromatography (Prep LC) work together hand-in-hand in the area of natural products by first identifying new lead compounds, and later on isolating them in sufficient quantities from plants or biological sources. With TLC and Prep LC sorbents coming from the same production process, this path is easy and straight forward as selectivity is the same for both separation methods hence enabling an easy method transfer (up-scale).

  Join us for this webinar as we will focus on:

  • Using TLC for lead substance identification in combination with on-plate activity screening
  • Structure elucidation using direct TLC/MS-coupling
  • Transfer to and scale-up on Prep LC

  Learn how:

  • Thin Layer Chromatography shows you which compound to isolate
  • To use the parameter from TLC for direct transfer to Prep LC
  • A method for maximum throughput is optimized in Prep LC

April | 2016

• Presenters:
  
  • Prof. Dr. Christian Frech, Head of the Institute for Biochemistry, Mannheim University of Applied Sciences, Germany
  • Dr. Michael Schulte, Purification R&D, Merck KGaA, Darmstadt, Germany
• Abstract

  Ion-exchange chromatography is typically using gradients of increasing salt concentration at a constant pH-value for elution. This technical approach is widely used at process scale in the biopharmaceutical industry since decades. With the appearance of novel products drug molecules such as bispecific antibodies, antibody fragments as well as charge variants of proteins, high resolution process chromatography is needed for more efficient separations of closely related impurities from the main biological drug molecules.
  
  The combination of two gradient modes, i.e. changing pH and salt concentration simultaneously, is providing a much higher separation efficiency and larger process flexibility. With such combined gradients, different operation modes can be realized: pH and salt gradient slopes in parallel, but also pH and salt gradient slopes in opposite directions. Underlying the theory of the "Linear Gradient Elution", this approach allows to optimize process conditions at small scale, which can easily be scaled up.

  Watching this webinar, you will learn:

  • How to apply the theory of the Linear Gradient Elution
  • How to screen the best separation conditions with dual gradients
  • How to transfer the separation to large-scale process conditions
  • Why the importance of the separation of charge variants is steadily increasing

March | 2016

• Presenters:
  
  • Paul Beckett, Ph.D., Technology Consultant, Purification, MilliporeSigma
  • Romas Skudas, Ph.D., Senior Scientist R&D, Purification, MilliporeSigma
• Abstract

  Bind/elute chromatography steps are challenging to implement in continuous processes due to the step wise load/wash/elute/clean cycle used. Multiple columns are therefore utilised to provide a continuous elution stream but these are complex to install and control. Flow through methods are therefore far more conducive to continuous process operation.
  
  Depth filters are overwhelmingly used in flow through modes in current bioprocesses already, purifying by a mixture of size exclusion and adsorptive mechanisms. The adsorptive capabilities of modern depth filter materials, with complex binding mechanisms to diatomaceous earth or activated carbon, are often underestimated and effective removal of soluble process contaminants can be achieved with this technology.
  
  Flow through chromatography can be used for highly effective purification based on the novel implementation of combination technologies working in a continuous fashion. These combination technologies use orthogonal binding mechanisms to remove a broad spectrum of impurities.
  
  Join us as we explore case studies on effective separation of host cell proteins (HCPs), antibody fragments and low molecular weight substances from solutions containing monoclonal antibodies. Monoclonal antibody recoveries of >85% and HCP reduction to <10ppm suggest that this platform can be adapted to standard and new purification templates whilst maintaining critical product quality attributes and achieving economically efficient biopharmaceutical molecule purification.

Feb. | 2016

• Presenter: Herbert Lutz, Principal Consulting Engineer, MilliporeSigma
• Abstract

  Ease of administration and high dose applications are driving the bioprocessing industry to formulate higher concentration biotherapeutics. Formulation by ultrafiltration may be limited in reaching these concentrations due to high pressures caused by high viscosities. The performance of a new PES cassette is described that meets this challenge and allows the use of high caustic concentrations for cleaning and sanitization. Viscosity modifying excipients are also shown to be complementary to the use of the new cassette.

Feb. | 2016

• Presenter: Jacqueline Hollands Ignacio, Corporate Responsibility Programs Manager, MilliporeSigma
• Abstract (US Program Only)

  As the biopharmaceutical industry increases the adoption of single-use manufacturing products, the issue of recycling becomes a challenge. Disposal and recycling the plastics from these products is a challenging task due to many factors.
  
  We have teamed up with a recycling partner, Triumvirate Environmental in order to take a new approach to recycling this challenging waste stream. This unique and innovative process allows for safe and fully traceable recycling of single-use products.
  
  Join us to learn how you can how your site may be able to take advantage of this new program.

Jan. | 2016

• Presenter: Kenneth Muzykewicz, Director of Membrane Process and Technology, MilliporeSigma
• 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

Dec. | 2015

• Presenter: Dr. Paul Beckett, Technology Consultant, MilliporeSigma
• Abstract

  Continuous bioprocessing is generating considerable excitement in the biopharma industry as it promises to increase efficiency, decrease equipment footprint, reduce underused plant capacity and, ultimately, lower cost of goods. Standard batch tangential flow filtration (TFF) processes are not well aligned with the continuous processing paradigm. The requirement of a retentate loop and large independent tanks, in addition to the highly discrete nature of batch concentration and diafiltration, means that the continuously flowing homogenous product stream is not possible. However, it is feasible to replace some of the batch TFF steps with a single-pass TFF equivalent, which is fully aligned with the needs of a continuous process.
  
  This webinar will explore:
  
  

  • How single-pass TFF works and which bioprocess applications it is most suited for, whether standard or continuous in nature.
  • Industrial data and case studies will be presented, along with operational guidance on the implementation and optimization of single-pass TFF into your process.

Nov. | 2015

• Presenter: Dr. Michael Schulte, Purification R&D, Cation Exchange and New Surfaces, MilliporeSigma
• Abstract

  Shifting peaks? Insufficient resolution? Low purity and yield? – When facing troubles in preparative HPLC a variety of different effects can be the underlying reason. In this webinar, Michael Schulte will provide you with key guidelines from his 20+ years of experience in preparative HPLC to effectively apply troubleshooting and hence to solve your HPLC challenges.
  
  Join us for this part II webinar as we will focus on:
  
  

  • Stationary phase conditioning and cleaning in normal as well as reversed phase mode
  • Challenges arising from low feed solubilities
  • Design and maintenance issues related to preparative columns and systems

  and learn how:

  • Thin Layer Chromatography can show you what´s typically not visible
  • You can virtually elongate your column
  • A slight shift in pH can massively influence the separation

Sept. | 2015

• Presenter: Dr. Michael Schulte, Purification R&D, Cation Exchange and New Surfaces, MilliporeSigma
• Abstract

  Normal phase and reversed phase chromatography is often used as a final polishing step for the purification of recombinant proteins, therapeutic peptides and small molecule APIs and is also a recommended method for purity checking and protein mapping.
  
  Join us for this webinar as we discuss basic principles of HPLC. Learn the difference between analytical and preparative chromatography and how to best scale-up your process. Critical key parameters that need to be taken into consideration for building an efficient purification process will be presented. Approaches for process optimization (e.g. through the increase of efficiency and selectivity) will also be addressed. Hear more on phase screening, method optimization, process development and troubleshooting during this interactive webinar.
  
  Who should attend?
  Newcomers and experienced chromatographers and researchers active in the field of Normal Phase and Reversed Phase Chromatography.

Aug. | 2015

• Presenter: Dr. Paul Beckett, Technology Consultant, Purification, MilliporeSigma
• Abstract

  Tangential flow filtration (TFF) operations are an integral part of bioprocessing operations for clarification, concentration, diafiltration and formulation processes. If these processes occur immediately prior to final formulation, there are no subsequent purification steps, making validation of the TFF cassette’s quality extremely important.
  
  In early-phase clinical manufacturing, operation and cleaning procedures are not yet optimized and biopharmaceutical companies may decide not to reuse and store TFF cassettes. For mid- to late-stage clinical manufacturing, cassette reuse and storage is more common resulting in the need for qualification reducing the risk of compromising finished product quality. Full reuse and storage qualification is required in final stage clinical manufacturing as well as full-scale production.
  
  As manufacturers experience the drive to file for product manufacturing, the complete qualification of cassette reuse, lifetime and storage may be overlooked. Increased levels of regulatory scrutiny surrounding product quality and purity may identify any shortcomings in TFF cassette qualification.
  
  This webinar investigates the operational requirements and risks of TFF cassette storage and reuse. In addition, it outlines a validation plan for these operations within a manufacturing environment and illustrates how this plan complies with the latest industry and regulatory guidance.

May | 2015

• Presenters: Prof. Dr. Christian Frech, Head of the Institute for Biochemistry, Mannheim University of Applied Sciences, Germany and Dr. Lothar Jacob, Product Manager for Ion Exchange Chromatography, Process Solutions, MilliporeSigma
• Abstract

  During the downstream processing of monoclonal antibodies (mAbs), ion exchange chromatography (IEX) is a very crucial purification tool. It is mostly utilized as post-protein A and/or polishing step. Within both types of ion exchange chromatography - cation exchange (CEX) and anion exchange (AEX) - the optimization of operating parameters can enhance the entire purification scheme. Antibody aggregate removal can be significantly improved through CEX if the monomeric forms elutes before the aggregates come off the column. Choosing the right elution condition is key for efficiently separating host cell proteins (HCPs) as well. The main contribution of anion exchange (AEX) chromatography is efficient DNA and virus removal, in many applications in a flow-through mode. However, also CEX can contribute to additional process safety with regard to virus removal even in bind-elute mode. Key factors influencing the separation of mAbs on ion exchange chromatographic columns as well as case studies will be presented during this webinar.

April | 2015

• Presenter: Michael Payne, Senior Technical Biosafety Consultant, MilliporeSigma
• Abstract

  Tangential flow filtration (TFF) is widely used in biopharmaceutical processes from upstream such as cell or viral harvesting and purification, to downstream such as protein concentration and diafiltration, as well as in final formulation. Today’s biopharmaceutical industry is under pressure from regulatory organizations to be able to meet increasing levels of compliance, and from pharmaceutical buying advocates and the financial community to show better operating economics. We will explore the role that quality by design (QbD) plays in meeting the challenges of these pressures while being able to ensure that final product quality is maintained or improved. The use of QbD tools and approaches will be applied to the drug product development process, the scale-up and to the manufacturing process. The identification and interrelationship of critical process parameters (CPPs), critical product quality attributes (CQAs), target product profiles (TPPs) and the use of risk assessment will be shown to help ensure that process parameters are maintained within the desired range to ensure product quality and reliable process operation. The webinar will offer fundamental practical information on the use of QbD in critical processes using ultrafiltration technology to meet risk and quality based reviews.

March | 2015

• Presenter: Alex Xenopoulos, Principal Research Scientist, MilliporeSigma
• Abstract

  Virus-like particles (VLPs) represent an appealing model for vaccine development, as they resemble native viruses but are not infectious. FDA has already approved VLP vaccines against hepatitis B and human papilloma virus, while clinical studies on others are in progress. VLPs can be produced in various cell culture systems and production is frequently done using baculovirus-infected insect cells systems. These systems can result in good production yields but purification requires particular attention. The key impurity that needs to be removed is the baculovirus itself, with a size not dissimilar from the VLP product. Furthermore, VLPs are particularly sensitive and require gentle production, harvesting and purification techniques.
  
  In this webinar we will describe how hepatitis C VLP vaccine candidates were successfully produced and purified. Disposable bioreactors were used with good results to allow flexibility in process development and manufacturing. Multiple clarification options were explored, focusing on depth filtration, an attractive option with low capital investment. Concentration using ultrafiltration membranes was optimized and final purification was done using anion exchange chromatography resins. Extensive chromatographic optimization was done and can be used to guide the selection of the particular approach for purification.
  
  Join us to learn more about process development and the choices made to improve yield and purification factor for this important class of vaccine candidates.

Oct. | 2014

• Presenter: Herb Lutz, Principal Consulting Engineer, MilliporeSigma
• Abstract

  The need for ease-of-use and high dosage is driving the use of administration through pre-filled syringes. Ultrafiltration systems are used for formulation and may be challenged to deliver the high viscosities needed. This webinar highlights the potential limitations of current systems and cassettes and introduces a new high viscosity cassette that can overcome these limitations.

April | 2014

• Presenters: Claire Scanlan, Process Development Scientist, MilliporeSigma and Jeffrey Shumway, Associate Director, Sales Development, MilliporeSigma
• Abstract

  Monoclonal Antibodies (mAbs) have been of great focus in the biotechnology industry for the past few decades. In recent years, the focus has shifted towards development of “next generation” biologic therapeutics and manufacturing platforms. This shift is being driven by the need to develop more efficient and cost effective processes, reduce side effects and increase specificity to enhance efficacy.
  
  Antibody fragments (Fabs) are one example of these next generation biologics and are emerging as credible alternatives to the widely accepted mAbs. These fragments can be produced using more economical expression systems (e.g. microbial), while retaining the target specificity of a mAb. Other Fab advantages include elimination of non-specific binding between the Fc portions of antibodies and the Fc receptor on cells, and the ability to engineer the Fab region for improved specificity and therapeutic efficiency.
  
  The downstream purification of Fabs poses some processing challenges including clarification (microbial lysates can be difficult to clarify), chromatography separation (with no affinity for Protein A, alternate resins such as mixed mode or IEX have to be evaluated), and formulation or ultrafiltration (these molecules are fairly small and require tighter TFF filters which can impact process times and fluid properties). Product solubility and stability can also be a challenge at times.
  
  This interactive presentation provides an overview of the next generation biologic’s platforms and describes the Fab purification process and challenges. We also discuss strategies that can help overcome the challenges associated with the downstream purification of Fabs.

March | 2014

• Presenter: Nanying Bian, Ph.D., Principal Scientist, Chromatography R&D, MilliporeSigma
• Abstract

  Protein A affinity chromatography plays a critical role in the downstream purification processes of antibodies and other Fc-containing molecules due to its specificity and efficiency in the removal of soluble impurities from clarified cell culture. However, the relatively high cost of Protein A resins also drives the need to optimize this purification step and maximize resin performance and lifetime. Additionally, with new antibodies and Fc-containing molecules being developed for better pharmacokinetics and specificity, the commonly established one-step elution Protein A capture regimen might be under-utilizing Protein A’s purification potential, especially in the presence of antibody variants. Please join us and learn more about the productivity and Cost of Goods (COGs) calculation of Protein A affinity chromatography resin at production scale. You will learn about strategies to lower COGs by employing best practices in extending the life time of Protein A affinity chromatography resin. Additionally, the aggregate removal ability of Protein A affinity chromatography resin under pH gradient elution conditions will be discussed.

Feb. | 2014

• Presenters: Prof. Dr. Christian Frech, Head of the Institute for Biochemistry, University of Applied Sciences, Mannheim, Germany and Dr. Lothar Jacob, Ion Exchange Chromatography, Product Manager, MilliporeSigma, Darmstadt, Germany
• Abstract

  Once a target protein has been identified to become a potential drug, the purification process has to yield an even higher quantity of proteins for further studies. While it is critical to maintain the product’s purity and to fulfill all requirements in terms of quality, the purification processes have to be scaled up – usually from the mg-level up to the kg scale. The easiest way of efficiently scaling-up chromatography operations is to change the column dimensions by keeping the height of the gel bed constant while increasing the column diameter.
  
  Join us as we present current model-based rational approaches to easily and efficiently scale-up chromatography processes. Hear about common challenges encountered during this process transfer and learn more about basic scale-up rules and industry recommendations making your process development and scale-up project successful.

Jan. | 2014

• Presenter: Eric Youssef, European Plasma Market Director, Process Solutions, MilliporeSigma
• Abstract

  The plasma industry is looking for process improvements to develop new formulations and dosages with higher concentration for subcutaneous administration, such as for Immunoglobulin. However, process improvements are very challenging and pose a number of process limitations. High concentrations are difficult to manage during the final UF/DF step of the process. High concentrations also create offsets of excipient concentrations from target specifications, and can impact the rheology of the product, making it more viscous and therefore more difficult to process. This presentation will describe the best practices in UF/DF high concentration processes, explain the mitigation strategies to overcome formulation challenges, and evaluate the latest ultrafiltration technologies for concentrating high concentrations of immunoglobulins.

Dec. | 2013

• Presenters: Tommaso Ronconi, Food & Beverage Development Specialist and Ramón Pérez Campoy, Food & Beverage Technology Expert
• Abstract

  What if you could optimize wine clarification using less energy and resources, while protecting the wine quality parameters?
  From harvest to barrel, every step of the production process influences the quality of the final wine product. This webinar will present an alternative to typical tangential flow filtration and diatomaceous earth methods for wine clarification. By attending this online event, you will have a better understanding of how a closed processing system avoids wine oxidation, protects organoleptic properties, and provides a more sustainable approach for the environment. Material covered in this discussion will include data from a recent customer study of our Millchilling® Normal Flow filtration System.

Nov. | 2013

• Presenters: Prof. Dr. Christian Frech, Head of the Institute for Biochemistry, University of Applied Sciences, Mannheim, Germany and Dr. Lothar Jacob, Ion Exchange Chromatography, Product Manager, MilliporeSigma, Darmstadt, Germany
• Abstract

  Based on recent advances in biotechnology, the introduction of protein and peptide drugs is growing rapidly. Nearly all applications require a high purity. Thus, efficient chromatographic column separations are necessary. The most important technique is ion exchange chromatography (IEX). This technique results in high purities combined with high recoveries while the operational costs are rather moderate. In addition, for ion exchange steps, scale-up can be done efficiently from laboratory to production. Join us as we discuss the basic principles of ion exchange chromatography. Learn how to set up the right separation protocol and hear more about critical parameters of this chromatography step.

Nov. | 2013

• Presenter: Frank Appel, Senior Manager Europe Vaccines Segments, MilliporeSigma
• Abstract

  The production of viral vaccines at commercial scale requires large quantities of viruses as an antigenic source. There are different production platforms suitable for viral replication - mammalian, avian and insect cells. Host cell residuals in the final product - nucleic acid in particular - create a significant concern due to a potential transfer and integration into the living cell’s genetic material, potentially leading to various harmful effects including cancer. Health authorities and regulatory bodies continue to increase safety standards for the manufacturing products providing stringent guidelines on removal of residual nucleic acid from vaccine processes. Several physicochemical methods exist to reduce nucleic acid during the manufacturing processes. Please join us to learn more about recent advances in efficiently removing nucleic acids from vaccine processes. The webinar will highlight diverse methods such as enzymatic degradation with endonucleases or ultrafiltration/diafiltration and chromatography to easily reduce nucleic acid contaminants from your vaccine manufacturing process.

Oct. | 2013

• Presenter: David Bohonak, Ph.D., Senior Applications Engineer, MilliporeSigma
• Abstract

  This webinar discusses how to evaluate retentate recycle tank performance and how an active retentate mixing step can best enable optimum performance of protein concentration / diafiltration in single-use systems. By watching this webinar you will learn:
  
  

  • How to properly determine the mixing efficiency of your UF/DF system
  • Differences in performance between tanks using active or passive agitation
  • The consequences of insufficient retentate mixing

June | 2013

• Presenter: Dr. Romas Skudas, Senior Scientist, Process Purification Downstream Technologies, MilliporeSigma
• Abstract

  Are increases in upstream expression levels also putting pressure on your downstream operations? Do you need a solution that not only increases productivity of your overall process, but does it without sacrificing process robustness? This webinar discusses increasing your productivity up to 4-20x through applying the principle of continuous chromatography. During this webinar, you will learn about the advantages of continuous chromatography not only for bind and elute applications (e.g. affinity and ion-exchange chromatography), but also in challenging polishing applications such as reversed phase chromatography. We highlight experimental data confirming significant increases in productivity, reduced buffer consumption as well as enhanced resin utilization without impacting critical product quality attributes. Hear how these features enable continuous chromatography to be easily adapted to standard purification templates, but also potentially make disposable chromatography a reality.

June | 2013

• Presenter: Frédéric Sengler & Simone Klein, Field Marketing Specialists Tangential Flow Filtration, MilliporeSigma
• Abstract

  Many factors contribute to a TFF system design; this webinar explains how to optimize the TFF process parameters to achieve superior product quality, consistent and high product yield, high concentration, and reproducible process flux and time.

Sept. | 2011

• Presenter: Sal Giglia, Principal Applications Engineer, MilliporeSigma
• Abstract

  The traditional method for sizing normal flow filters operating in series has been shown to be inefficient and inadequate in applications where filter sizing is flow rate dependant. For filters operating in series at constant inlet pressure, each filter in the filtration train operates and generally fouls at different rates. Filter sizing models that do not account for the effect of flow rate on the rate of filter fouling will not properly simulate serial filtration behavior. As a result, filter train sizing estimates can be skewed and unbalanced between the initial filter and the final filter, leading to lower than expected serial filtration performance.
  
  Join us as we share best practices for optimal filter sizing using a model and method that improves the accuracy of sizing membrane filters operated in series. In addition, we will demonstrate how to use this model for rapid and efficient optimization of prefilter to final filter area ratios.