Informa Life Sciences is part of the Knowledge and Networking Division of Informa PLC

This site is operated by a business or businesses owned by Informa PLC and all copyright resides with them. Informa PLC's registered office is 5 Howick Place, London SW1P 1WG. Registered in England and Wales. Number 3099067.

Informa
Key Sessions

Keynote Presentation

8 am 8:15 am (15 mins)

Cell Culture & Upstream Processing

Chairperson’s Opening Remarks

8 am 8:15 am (15 mins)

Recovery & Purification

Chairperson’s Opening Remarks

8 am 8:15 am (15 mins)

Manufacturing Strategy

Chairperson’s Opening Remarks

8 am 8:15 am (15 mins)

Drug Product/Formulations

Chairperson’s Opening Remarks

8 am 8:15 am (15 mins)

Analytical and Quality

Chairperson’s Opening Remarks

8 am 8:15 am (15 mins)

Viral Safety

Chairperson’s Opening Remarks

8:15 am 8:45 am (30 mins)

Cell Culture & Upstream Processing

Case Study of Custom Production Medium Development in Collaboration between Eisai and Thermo Fisher Scientific

The Cell Culture Pilot Plant at Genentech in South San Francisco is a hybrid facility that uses both stainless steel and disposable bioreactors for CHO cell culture in Seed Train, Inoculum Train, and Production stages. In the biotech industry, disposable rocker bioreactors have been used as Seed Train and Inoculum Train operations due to their efficient, cost effectiveness, and small footprint. In 2016, Cell Culture Pilot Plant evaluated a rocker bioreactor for both Seed Train and Inoculum Train processes and found the rocker system did not have a robust pH and dO2 control for continuous Seed Train process that can run for up to 5 months. To address these challenges, Genentech and Thermo Fisher collaborated to modify a 30L Single Use Fermentor bag (SUF) to a 30L Single Use Bioreactor bag (SUB) that matches a traditional 20L stainless steel bioreactor to have ro bust pH and dO2 control. As part of this evaluation, mass transfer and cell culture experiments were performed. The presentation will be focusing on cell culture performance data, ongoing efforts to resolve equipment associated challenges, and expand the use of the 30L SUB in Inoculum Train.

  • Edward Chan - Technical, Cell Culture Pilot Plant, Genetech, Inc
  • Nephi Jones - Manager, Advanced Technology, Research & Development, Thermo Fisher Scientific

8:45 am 9:15 am (30 mins)

Cell Culture & Upstream Processing

Process Optimization and Scale-Up Challenges in the Development of a Large-Scale Chemically-Defined Phase III/Commercial Manufacturing Cell Culture Process

Developing a Phase III/commercial cell culture process can present challenges including optimizing cell culture conditions for maximized productivity while maintaining product quality consistent with the needs of the clinical development program. Development of a phase III/commercial process will be described for a CHO monoclonal antibody product through process optimization and scale-up. A new chemically-defined medium (CDM) formulation was implemented for this process at large scale for the first time. The use of this CDM formulation resulted in highly consistent cell culture performance at both small scale and pilot scale. However, during scale-up for clinical manufacturing, challenges were identified and investigated. Details of this investigation and the process / operational improvements implemented at large scale for Phase III and qualification runs will be presented.

  • Jason Goodrick - Senior Engineer, Late Stage Cell Culture, Genentech, Inc.

9:15 am 9:45 am (30 mins)

Cell Culture & Upstream Processing

Improving Antibody Titers Through Media and Process Improvements, While Maintaining Product Quality Attributes

Rounds of DOE study have led to the selection of the prototype of medium, including basal, feed and feed supplement.  Protein production has improved at bench scales through extensive process optimization, while product quality attributions remains.

8:15 am 8:45 am (30 mins)

Recovery & Purification

A Comprehensive Regeneration Strategy for Protein an Affinity Resin in Monoclonal Antibody (mAb) Purification

Regeneration strategy for Protein A chromatography plays an important role in therapeutical monoclonal antibody (mAb) production. A robust and efficient regeneration procedure ensures product quality, improves resin life time and reduces the cost of the purification processes, particularly for those using expensive protein A resins, such as MabSelect SuRe, which is the most popular Protein A resin used in mAb purification. Microbial killing capability, cleaning efficiency and resin compatibility are the three major aspects to consider in regeneration strategy design. Traditionally, MabSelect SuRe resin is regenerated by 200 mM NaOH and such high NaOH concentration is the leading cause of resin performance loss during the reuse. This work reported a comprehensive strategy, which applying benzyl alcohol with acetic acid, and benzyl alcohol with low concentration N aOH (< ;100 mM) in sequence, to regenerate MabSelect SuRe resin. The new regeneration strategy demonstrated efficient cleaning with improved microbial killing capability and prolonged resin life time. The resin life cycle study demonstrated that the life time of the MabSelect SuRe resin was extended 50% with new strategy.

  • Lu Wang, Ph.D. - Senior Scientist, Purification Development and Operations, CMC Biology, Teva Pharmaceutical Inc.

8:45 am 9:15 am (30 mins)

Recovery & Purification

Multi-target Approach to Affinity Purification of Recombinant Proteins

9:15 am 9:45 am (30 mins)

Recovery & Purification

Functionalized Nanofiber Membranes

Column chromatographic separation of antibodies using protein A conjugated resins has been the industry standard for decades. Advances in resins have been limited to stabilizing the ligand against harsh conditions or incrementally improving the binding capacity. The challenge of using affinity resins continues to be the cycle times and binding capacity with only incremental improvements over time. Bionanoparticles (BNPs), produced by genetically engineered E. coli through a simple fermentation process, are a naturally derived, inexpensive alternative to conventional resins, but which have inherent physical challenges . Embedding protein A, or other ligand displaying BNPs onto the surface of membranes demonstrate the short cycle times of membrane chromatography with increased binding capacity over traditional resins. The resulting increases in recovery efficiency may ena ble single use products for antibody capture.

  • Karl Schilke, Ph.D. - Assistant Professor, Chemical Biological and Environmental Engineering, Oregon State University

8:15 am 9:45 am (90 mins)

Manufacturing Strategy

Manufacturing Optimization/Process Intensification

8:15 am 9:45 am (90 mins)

Drug Product/Formulations

Novel and Adaptive Drug Product Technologies

8:15 am 9:45 am (90 mins)

Analytical and Quality

Analytical Methods for Biosimilars

8:15 am 9:45 am (90 mins)

Viral Safety

Viral Safety Session

9:45 am 10:10 am (25 mins)

Main agenda

Networking Refreshment Break

10:10 am 10:15 am (5 mins)

Cell Culture & Upstream Processing

Chairperson’s Remarks

10:10 am 10:15 am (5 mins)

Recovery & Purification

Chairperson’s Remarks

10:15 am 10:45 am (30 mins)

Cell Culture & Upstream Processing

Scale-Down Model of N-1 Perfusion Seed Bioreactor for High-Throughput Analysis

In the CHO-based monoclonal antibody manufacturing, the N-1 perfusion seed culture was reported to have the capability of supporting high-inoculum seeding in the production bioreactor, thus largely increase the volumetric productivity and shorten the duration for the production phase. However, due to the ineligibility of the small-scale perfusion bioreactors, further process development in N-1 perfusion requires a proper scale-down model to perform perfusion medium optimization, clone selection and other operation optimizations. In our research, we developed a series of scale-down models for N-1 perfusion operation based on shake flasks, cell culture tubes and deep well plates. The operating parameters of those scale-down models were optimized to match the performance in 5L N-1 perfusion bioreactors. Multiple cell lines from different CHO derivatives were tested t o verify the robustness of those scale-down models. The results indicate that the cell growth and viability are comparable between 5L N-1 perfusion and the scale-down models. Meanwhile, the cell quality and health level, estimated by LDH and apoptosis markers, are consistently high during the N-1 seed culture in both 5L N-1 perfusion and scale-down models. Furthermore, we established a workflow to perform the high-throughput DOE for N-1 perfusion culture and subsequent high-inoculum fed-batch production culture. The proof-of-concept workflow shows the adequacy to perform the medium optimization for N-1 perfusion and high-inoculum fed-batch production.

  • Yongqi Wu, Ph.D. - Scientist, Bristol-Myers Squibb

10:45 am 11:15 am (30 mins)

Cell Culture & Upstream Processing

On Demand Nutrient Feed During Automated Cell Culture Process

11:15 am 11:45 am (30 mins)

Cell Culture & Upstream Processing

Session TBA

10:45 am 11:15 am (30 mins)

Recovery & Purification

Removal of CHO Protein - Phospholipase B-Like 2 (PLBL2) During Downstream Processing of Monoclonal Antibodies

Effective removal of host cell proteins (HCPs) and impurities is necessary during mAb manufacturing produced in Chinese Hamster Ovary (CHO) cells. As such, most HCPs and impurities are cleared by rProtein A affinity chromatography, followed by one or two polishing steps in the standard downstream process. A specific HCP present in the cell culture, phospholipase B-like 2 (PLBL2), has been found to degrade a surfactant present in the drug substance formulation, and therefore, clearance during the downstream process is critical to ensure product stability. However, clearance of PLBL2 presents challenges due to a detectability issue using commercial HCP assay kits. We have studied PLBL2 (lipase enzyme) activities, challenges associated with its removal, and evaluated suitability of polishing chromatography during process development. In this presentation, we will d iscuss s imple ways of addressing clearance of PLBL2 during downstream processing of mAb products.

  • Mukesh Mayani, Ph.D. - Scientist II (Process Development), Biologics Process Development, Bristol-Myers Squibb

11:15 am 11:45 am (30 mins)

Recovery & Purification

How Low Can We Go; Application of Multimodal Cation Exchange Chromatography for Reduction of HCP and High Molecular Weight Species for Non-IgG Purification

This talk will highlight the use of a multimodal cation exchange (MMCEX) chromatography column as a polishing step to reduce host cell protein (HCP) and high molecular weight species in a non-IgG production process. The reduction of impurities was achieved by influencing the effects of charge and hydrophobic interactions of the MMCEX chromatography. Specifically, buffer and protein load compositions were studied for its capacity to exploit both CEX and HIC components of the resin ligand during product elution. A high throughput robotic screen was first performed to identify key process parameters and minimize the number of lab scale chromatography experiments. Ultimately, the MMCEX column was implemented as the final chromatography unit operation in the non-IgG purification process to reduce HCP levels approximately 10-fold while maintaining process manufacturability and desired product quality.

  • Zahari Begum - Senior Ressearch Associate, Pharma Technical Development, Purification Development, Genentech, Inc

10:15 am 11:45 am (90 mins)

Manufacturing Strategy

Manufacturing Optimization/Process Intensification

10:15 am 11:45 am (90 mins)

Drug Product/Formulations

Novel and Adaptive Drug Product Technologies

10:15 am 11:45 am (90 mins)

Analytical and Quality

Analytical Methods for Glycan Analysis

10:15 am 11:45 am (90 mins)

Viral Safety

Viral Safety Session

11:50 am 12:20 pm (30 mins)

Main agenda

Concurrent Technology Workshops

12:25 pm 1:40 pm (75 mins)

Main agenda

Luncheon Presentation

1:40 pm 1:45 pm (5 mins)

Cell Culture & Upstream Processing

Chairperson's Remarks

  • Nandu Deorkar, Ph.D. - Vice President, Research and Development, Avantor Performance Materials

1:40 pm 1:45 pm (5 mins)

Recovery & Purification

Chairperson’s Remarks

1:40 pm 1:45 pm (5 mins)

Manufacturing Strategy

Chairperson’s Remarks

1:40 pm 1:45 pm (5 mins)

Drug Product/Formulations

Chairperson’s Remarks

1:40 pm 1:45 pm (5 mins)

Analytical and Quality

Chairperson’s Remarks

1:40 pm 1:45 pm (5 mins)

Viral Safety

Chairperson’s Remarks

1:40 pm 2:10 pm (30 mins)

Recovery & Purification

Purification Process Development for a Light-Sensitive Monoclonal Antibody

Light exposure of biopharmaceuticals may lead to chemical and physical degradation by photooxidation of tryptophan, tyrosine, phenylalanine, and cysteine/cystine. An early photo-stability assessment demonstrated that a mAb had a rapid activity loss when the protein was exposed to white and ultra-violet light. This observation led to challenges for purification process development that included determining the mAb degradation rate in varying process intermediate conditions, determining light exposure control limits to minimize inactive mAb formation, and designing a polishing chromatography step to reduce inactive mAb, formed during processing, to acceptable levels. A photo-stability study of the mAb in process intermediates showed unacceptable degradation rates at room temperature. This result led to a decision to actively minimize light exposure to process material s during the manufacture of all development and clinical materials. Peptide analysis of the isolated inactive mAb revealed that activity loss was caused by the oxidation of two tryptophan residues present at the antigen binding region. Tryptophan oxidation could lead to a localized change is surface hydrophobicity for an impacted protein. This difference in local surface hydrophobicity between the mAb and the oxidized mAb was successfully exploited to separate the two variants using hydrophobic interaction chromatography. The optimized chromatography process delivered active mAb that met design process manufacturing goals for mAb purity and yield. In conclusion, a robust manufacturing process was successfully developed through understanding of protein degradation rates in process intermediates and by applying peptide-level characterization information to guide purification optimization strategy.

  • Nathaniel Macapagal - Scientist I, Purification Process Sciences, MedImmune

1:45 pm 2:15 pm (30 mins)

Cell Culture & Upstream Processing

BPOG Raw Material Risk Assessment Initiative

  • Janeen Skutnik-Wilkinson - Director, Pfizer Limited
  • Chiali Liu, Ph.D. - Principal Scientist, Janssen Supply Chain
  • Duncan Low, Ph.D. - Scientific Executive Director, Operations Technology, Amgen

2:15 pm 2:45 pm (30 mins)

Cell Culture & Upstream Processing

Controlling Variability in Protein Therapeutics by Defining Trace Metal and Carbohydrate Composition in Upstream Process Development

The role of trace metals as cofactors with glycotransferases can be utilized to facilitate uniform carbohydrate attachment by understanding critical media concentrations and using defined media supplements. Here we report current efforts to limit variability by monitoring trace metal composition by using defined media and its resulting effects.  A novel approach to controlling protein heterogeneity using well characterized and defined media to support process development will be described.

  • Brian Beyer, Ph.D. - Global Director, Bioprocessing Applications, Avantor

1:45 pm 3:15 pm (90 mins)

Manufacturing Strategy

Manufacturing Case Studies of Complex Molecules

1:45 pm 3:15 pm (90 mins)

Drug Product/Formulations

Drug Product Process Validation and Control

1:45 pm 3:15 pm (90 mins)

Analytical and Quality

Quality Risk Assesment Throughout the Product Lifecycle

1:45 pm 3:15 pm (90 mins)

Viral Safety

Viral Safety Session

2:10 pm 2:15 pm (5 mins)

Recovery & Purification

Chairperson’s Remarks

2:15 pm 2:45 pm (30 mins)

Recovery & Purification

Flow-Through Versus Bind-And-Elute: An Alternative Strategy for Improved Robustness and Manufacturability for a Challenging Cation Exchange Chromatography

Cation exchange chromatography (CEX) operated in bind-and-elute mode is a common polishing step for removal of aggregates in purification processes of biopharmaceuticals. Depending upon the resolution of the product and the aggregates, the operating ranges for process parameters providing the acceptable clearance can be narrow. This requires tight manufacturing process controls to ensure consistent product quality and process performance. This presentation will show a case study using a monoclonal antibody with cation exchange chromatography operated in flow-through mode, resulting in a more “manufacturing-friendly” purification approach and robust alternative. The flow-through CEX was able to provide high aggregate clearance and step yield, comparable to or better than the bind-and-elute CEX method, over wider ranges of process parameters and with fewer critical process parameters for the control strategy of this step. The presentation will also illustrate advantages of flow-through CEX on manufacturing throughput, raw material consumption, and improved manufacturing process fit over bind-and-elute CEX. Data on process robustness of the flow-through CEX to resin variability versus the bind-elute CEX mode of operation will also be included.

  • Jessica Prentice - Scientist I, Purification Process Sciences, MedImmune

2:45 pm 3:15 pm (30 mins)

Recovery & Purification

Characterization of a Recombinant Enzyme Downstream Process Using Modern DOE Techniques

Process characterization studies are a key component of a Quality by Design (QBD) approach, enabling improved process understanding, determination of critical process parameters (CPP), and definition of the process design space, ensuring that the process is capable of reproducibly generating safe and efficacious product for patients. While a classical design of experiments (DOE) approach is typically used for these studies, there are new statistical and data analytical techniques available that can improve experimental efficiency and better utilize the wealth of data generated from these studies. We demonstrate the potential for these new techniques with a case study of the downstream process characterization of a recombinant enzyme process. Of the four chromatography operations studied, one proved to be a particular challenge. During the initial multivariate screeni ng study, fully 25% of the experiments resulted in extremely low product recovery, indicating that the original process set-point was not robust. Because a new type of screening DOE, a definitive screening design (DSD), was used for this study, we were able to quickly and efficiently identify a new region of the design space for further characterization. Additional experiments were added in this region to support a response surface model, enabling the use of process simulation to identify a robust operating set-point and process design space. Utilization of these new statistical methods greatly improved the efficiency of the characterization of this complex chromatography operation. These techniques, especially the application process simulation for robust process engineering, can become a part of the standard toolbox for future QBD studies.

  • Michael Coolbaugh - Scientist, Sanofi

3:15 pm 3:45 pm (30 mins)

Main agenda

Grand Opening of the BWB Exhibit & Poster Hall and Refreshment Break

3:45 pm 3:50 pm (5 mins)

Main agenda

Chairperson’s Remarks

3:50 pm 4:25 pm (35 mins)

Main agenda

Improving Global Access to Biotherapeutics Through Molecule, Process and Manufacturing Design

This presentation will discuss the application of innovative technologies designed to expand global access to biotherapeutics. These integrated technologies will assist biotherapeutic discovery through the application of molecular design tools to improve candidate molecule developability, improve process design through intensification efforts, and reduce fixed costs associated with manufacturing facility construction and operation through the design of facilities with flexible, low cost features.

  • Dean Pettit, Ph.D. - Chief Scientific Officer and Founding Partner, Just Biotherapeutics

4:25 pm 5 pm (35 mins)

Main agenda

Keynote Presentation

5 pm 7:30 pm (150 mins)

Main agenda

Opening Night Cocktail Reception in the BWB Exhibit & Poster Hall

7:30 pm 10 pm (150 mins)

Main agenda

BWB Awards