Optimizing Bioproduction & Processing

Driving Innovation and Speed through Technical and Strategic Transformations

January 18 - 19, 2022 ALL TIMES PST

Current trends toward complex biologics result in unique challenges for both upstream and downstream processes. In CHI’s Optimizing Bioproduction & Processing we will explore strategies that lead to greater productivity when cultivating cells and scaling-up production. Topics include digitalization and automation to accelerate processing, plus novel approaches in downstream and continuous biomanufacturing, across a range of complex modalities.

Tuesday, January 18

1:00 pm Registration (Sapphire West Foyer)
1:30 pm Refreshment Break in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)


Session Room: Sapphire 400

2:00 pm Organizer's Welcome Remarks

Edel O'Regan, Vice President, Production, Cambridge Healthtech Institute

2:05 am

Chairperson's Remarks

James Ware, Director, Purification Development & Tech Transfer, Ligand Pharmaceuticals, Inc.

High Performance Countercurrent Membrane Purification (HPCMP) for Continuous Downstream Processing

Andrew Zydney, PhD, Bayard D. Kunkle Chair & Professor, Chemical Engineering, Pennsylvania State University

This presentation examines a new downstream processing technology, High Performance Countercurrent Membrane Purification (HPCMP), which exploits highly selective diffusive transport across the thin walls of a hollow fiber membrane. Experiments were performed using several model systems. HPCMP achieved greater than 98% product yield for with purification factors >100-fold over 96 hours of continuous operation. These results clearly demonstrate the potential of using HPCMP for protein purification in downstream processing of monoclonal antibodies and other biopharmaceutical products.

2:40 pm

A Novel Protein A-Based Purification Matrix for Mild Purification of Antibodies

Sophia Hober, PhD, Professor, School of Biotechnology, KTH Royal Institute of Technology

Antibodies are widely used affinity molecules in many fields of biological science and their use in therapy is constantly growing. The most common tool used for purification of antibodies is Protein A affinity chromatography, a method that offers high productivity and pure protein product. However, when eluting the captured antibodies from the column, low pH is needed which can be deleterious for certain antibodies and Fc-fusion proteins. We have addressed this issue by protein engineering. Through a combination of selection and directed mutagenesis the behavior of an IgG-binding domain from Protein A was improved resulting in ZCa, that allows for considerably milder elution of the captured antibody, since efficient release can be achieved by merely adding sodium chloride. This results in the release of IgG1 at pH 6 and antibodies of subclasses IgG2 and IgG4 at neutral pH. In contrast to elution at low pH using a commercial Protein A resin, this mild elution has been shown to eliminate the formation of antibody aggregates in the capture step. A tetrameric version of ZCa has demonstrated a binding capacity comparable to commonly used Protein A resins, including exceptional selectivity and recovery. Further, the resin was proved to be highly robust by processing high antibody titers for a great number of cycles in a continuous antibody-production and purification process at pilot scale, rendering high yields. The mild and efficient purification strategy based on ZCa has the potential to enable the development of a broader range of antibodies, which cannot tolerate the current acidic conditions used in antibody capture.

3:10 pm

Osmotic Shock: A Viable Primary Recovery Option for Biopharmaceutical Manufacturing from a Microbial Host

James Ware, Director, Purification Development & Tech Transfer, Ligand Pharmaceuticals, Inc.

Biopharmaceutical manufacturing from a microbial host has many advantages over traditional CHO systems and processing differences in primary recovery provide opportunities to explore alternate techniques that leverage the physical properties of the organism. High titers generated in the Pelican Expression Technology platform are retained within the cell post-fermentation and primary recovery methods can vary depending on the characteristics of the strain and protein stability. We demonstrated that a unique approach using osmotic shock is not only viable for manufacturing but may be a preferential method of protein release.

3:40 pm Refreshment Break in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)


4:30 pm

The Use of a High-Throughput, One-Step Transient-to-Stable Cell Line Generation Process for Accelerated Delivery of Proteins in Early Discovery

Marina Alvi, PhD, Senior Research Scientist, Mammalian Protein Expression, Eli Lilly & Co.

There is a constant need in the pharmaceutical industry to accelerate the production of antibodies and other large molecules in the early stages of R&D. Here we describe a high-throughput cell line generation process that negates the need to perform multiple transfections per expressed protein. Our results show that this process can be applied to a large number of samples with high protein yield and protein quality.

5:00 pm

Continuous Production with E. coli

Gerald Striedner, PhD, Associate Professor, Biotechnology, University of Natural Resources & Life Sciences, Vienna (BOKU), Austria

Genome-integrated as well as growth-decoupled E. coli expression systems enable continuous protein production. Efficient implementation requires suitable process strategies for cultivation and product recovery and purification. The presentation will show two case studies inclusive an economic evaluation with standard fed batch as benchmark.

5:30 pm Close of Day

Wednesday, January 19

7:30 am Registration (Sapphire West Foyer)
8:00 am BuzZ Sessions with Continental Breakfast (Sapphire Foyer)

PepTalk BuzZ Sessions are focused, stimulating discussions in which delegates discuss important and interesting topics related to upstream protein expression and production through downstream scale-up and manufacturing. This is a moderated discussion with brainstorming and interactive problem-solving between scientists from diverse areas who share a common interest in the discussion topic. Continue to check the event website for detailed discussion topics and moderators.

BuzZ Table 7: Buzz Session: Balancing Speed of Development with the Quality of the Product in the Race to an IND Filing

James Ware, Director, Purification Development & Tech Transfer, Ligand Pharmaceuticals, Inc.

Join this buzz session to learn how important balancing speed of development, with the quality of the product, really is, in the race to an IND filing. 

  • Important factors to consider early in development
  • Key considerations for setting the TPP
  • Participation on the product team and at what point in the process
  • When is titer or process yield “good enough” to move forward?
  • Level of focus placed on characterizing process intermediates/impurity clearance
  • Sufficient process understanding to ensure tech transfer success
  • When to consider manufacturability and cost of goods?

BuzZ Table 8: CMC Strategies for Successful Manufacturing of Drugs and Novel Modalities

Brian O'Mara, Associate Director, Downstream Process Development, Ambrx, Inc.

Join this buzz session to learn more about CMC strategies for successful manufacturing of drugs and novel modalities.

  • Internal vs. external manufacturing
  • CDMO selection – Full-service or a la carte – Intermediates (mAb, payload), DS, and DP manufacturing 
  • CDMO relationships
  • Manufacturing of COVID-19 and non-COVID-19 related projects
  • Overseas manufacturing and shipment
  • Novel modalities and capital investment?


Session Room: Sapphire 400

9:00 am

Chairperson's Remarks

Naveenkumar Singh, PhD, Scientist II, Downstream Process Development, Ambrx, Inc.
9:05 am

Production and Purification of Non-mAb Proteins by Platform Processes Using Affinity Tags

Alois Jungbauer, PhD, Professor & Head, Biotechnology, Institute of Bioprocess Science and Engineering, University of Natural Resources and Life Sciences (BOKU)

The conventional His tag often leads to reduced expression level and cleavage is expensive, slow and often the required N-terminus is not achieved. An expression and purification system based on a circular permutated Caspase which generates an authentic N-terminus irrespective of the amino acid is presented.


Protein Tag Technologies

Panel Moderator:
Richard Altman, Field Application Scientist, Life Science Solutions, Thermo Fisher Scientific

Protein fusion tags are indispensable tools used to facilitate protein purification and detection, detect cellular localization of proteins, and improve protein solubility and stability. The following topics will serve as a foundation for an interactive discussion between the panelists and audience. 

  • How do you select an affinity tag?
  • How do you know whether it’s best to cleave the tag or not? 
  • Are there regulations (FDA, EMA) regarding cleaving affinity tags?
  • When does it make sense not to cleave the tag? Are there complications?
  • Is it possible to introduce a universal approach for protein production and purification?​
David W. Wood, PhD, Professor, Chemical & Biomolecular Engineering, The Ohio State University
Dennis Karthaus, MSc, Director, Protein Products & Assays, IBA Lifesciences
John K. Kawooya, PhD, Director, Biologics Optimization and Therapeutic Discovery, Amgen, Inc.
Dominic Esposito, PhD, Director, Protein Sciences, Frederick National Laboratory
Barbara J Kaboord, PhD, Manager, R&D, Thermo Fisher Scientific Inc
10:35 am Coffee Break in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)
11:15 am

Challenges and Solutions for mAb Process Development and Manufacturing

Richard Ding, PhD, Dir Downstream Process Dev & Mfg Operations, DSP PD/MSAT/MFG, Anaptysbio

This presentation will highlight some challenges and effective solutions from early to late stage of mAb development. Some major challenges  related to cell line development, upstream development, downstream development, analytical methods, DS/DP stability are discussed. Effective solutions are assessed and applied.

11:45 am

Hybrid Modeling and Intensified Design of Experiments to Significantly Accelerate Upstream Process Development

Mark Duerkop, CEO, Novasign GmbH, Austria

The cost and required time to conduct reliable process understanding and characterization limits the bioprocess understanding. The talk highlights several upstream showcases in which the combination of hybrid modeling and advanced design space screening methods increased process understanding while simultaneously significantly reduced the required experiments by up to 70%. The chosen model structure also enabled the usage of those models during up-scaling and easy implementation for process monitoring and control.

12:15 pm Session Break
12:55 pm Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
1:25 pm Refreshment Break in the Exhibit Hall and Last Chance for Poster Viewing (Sapphire Ballroom)


2:15 pm

Chairperson's Remarks

Naveenkumar Singh, PhD, Scientist II, Downstream Process Development, Ambrx, Inc.
2:20 pm

Optimizing the Design of Single Pass Tangential Flow Filtration (SPTFF) Processes for Continuous Antibody Purification

Andrew Zydney, PhD, Bayard D. Kunkle Chair & Professor, Chemical Engineering, Pennsylvania State University

Single Pass Tangential Flow Filtration (SPTFF) systems can provide inline concentration of monoclonal antibodies and other biotherapeutics, both to resolve bottlenecks in existing processes and as part of the development of integrated continuous downstream processes. We have developed a model that can be used to optimize the design of SPTFF modules, specifically accounting for the concentration dependence of the antibody viscosity as well as the variation in flow rate and antibody concentration with position. Model simulations and experiments were used to examine the effects of channel width, length, and cassette staging (number of parallel cassettes in each stage) on SPTFF performance for specific process objectives.

2:50 pm

Evolution of a Disruptive Downstream Processing Technology Based on Magnetic Materials

Sonja Berensmeier, PhD, Professor, Bioseparation Engineering Group, Mechanical Engineering, Technical University of Munich

Chromatography has been established as a central step in the purification of proteins, although this is often cost-determining and also has some disadvantages in terms of process engineering. As an alternative, magnetic separation is presented here, in which magnetic nanoparticles serve as a separation phase that can bind the target molecule directly in unclarified cell culture supernatants or cell lysates. In our case, depending on the system, cost-intensive functionalization of the particles can be omitted and a pilot-scale technical implementation is presented.

3:20 pm

Increasing the Dynamic Binding Capacity of Hydrophobic Interaction Chromatography (HIC) Resins Using a Dual Salt System

Dhanesh Gadre, Scientist I, Purification Process Sciences, AstraZeneca

HIC is typically used as a polishing step to remove impurities in a non-platform protein purification process. In select instances, it has been employed as a capture step for novel biotherapeutics. In this work, we demonstrated that combining two kosmotropic salts can increase the DBC on HIC resin significantly compared to single salt systems. We demonstrated this improvement with three different dual salt systems using two model proteins.

3:50 pm

Host Cell Protein Challenges in the Downstream Process Development of Non-Antibody Processes

Naveenkumar Singh, PhD, Scientist II, Downstream Process Development, Ambrx, Inc.

In this case study, host cell protein reduction challenges were encountered with a recombinant protein conjugate expressed in CHO cells. A baseline process using conventional chromatography and filtration techniques was rapidly developed to support toxicology and Phase 1 production. However, HCP levels of 10,000-20,000 ng/mg were measured at the intermediate stage (pre-conjugation) of the process. Here we discuss the systematic approach to reduce HCP levels to within specification using strategies amenable to manufacturing.

4:20 pm

On-Demand and in situ: Continuous Reconstitution of Media and Buffers Directly from Solids

Daniel Komuczki, MMMSc, PhD Candidate, Biotechnology, University of Natural Resources & Life Sciences

The transformation from batch to integrated continuous bioprocessing only “shrinks” the unit-operations while necessary auxiliaries are drastically increased. This leads either to necessarily large hold tanks or high personal costs. To solve this bottleneck, we developed a device for a continuous on-demand reconstitution of media and buffers directly from solids.

4:50 pm Close of Conference