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Key Sessions

Sara Radcliffe

California Life Sciences State of the Industry 2018: A look at the trends and influences driving the life sciences industry in California for 2018 and beyond

California Life Sciences Association (CLSA)

Jason Bock, PhD

Achieving Efficiency through a Comprehensive Approach to Facility, Organization and Process Design

Teva Pharmaceuticals

7:30am - 8:00am

Registration and Coffee

8:00am - 8:05am
Chairperson's Opening Remarks

Chairperson's Opening Remarks

  • Shawn Liu, PhD - Chief Scientist & Department Head, Bayer Healthcare LLC
Showing of Streams
9:10am - 9:40am

Networking Refreshment Break

Showing of Streams
Showing of Streams
12:15pm - 12:20pm
Close of Conference - See you in 2019!

Close of Conference - See you in 2019!

7:30am - 8:00am 30 mins
Registration and Coffee
8:00am - 8:05am 5 mins
Chairperson's Opening Remarks
  • Shawn Liu, PhD - Chief Scientist & Department Head, Bayer Healthcare LLC
8:40am - 9:10am 30 mins
Keynote Presentations
Achieving Efficiency through a Comprehensive Approach to Facility, Organization and Process Design
  • Jason Bock, PhD - Vice President, Biologics CMC, Teva Pharmaceuticals
more
9:10am - 9:40am 30 mins
Networking Refreshment Break
9:40am - 9:45am 5 mins
Single-Use: Case Studies and Innovations
Chairperson's Remarks
  • Susan Dexter - Managing Director, Latham BioPharm Group
more
9:40am - 9:45am 5 mins
Early Stage Process Development: Process Intensification and Integration
Chairperson's Remarks
  • Ashley Hesslein, PhD - Associate Director in Biological Development, Bayer Healthcare LLC
more
9:40am - 9:45am 5 mins
Late Stage Process Development: Raw Materials
Chairperson's Remarks
  • Matthew Luther - Development Associate II, Late Stage Purification Development, Alexion
more
9:40am - 9:45am 5 mins
Commercial Manufacturing: Quality Assurance
Chairperson's Remarks
  • Tiffany Rau, PhD - Senior Consultant, BioProcess Technology Consultants, Inc.
more
9:45am - 10:15am 30 mins
Single-Use: Case Studies and Innovations
Large Scale Single Use Bulk Drug Substance Freeze and Thaw Platform
  • Jeffrey Johnson - Director and New Technology Lead, Global Engineering Solutions, Merck & Co., Inc.
more
9:45am - 10:15am 30 mins
Early Stage Process Development: Process Intensification and Integration
Process Development to Minimize a Light-Chain Mispaired Variant in a Bispecific Antibody
  • Ambrose Williams, PhD - Scientist, Genentech
more

Asymmetric bispecific antibodies comprised of different light and heavy chains are ideally suited for certain therapeutic mechanisms where monovalent crosslinking of targets is desired, such as immune cell recruitment to tumors. Developing these molecules as single-cell bispecific formats also brings convenience to bioprocess design, but increases the repertoire of chain-mispairing product-related variants. Minimizing these variants can be important to patient safety, but is challenging due to the similarity of these variants to the target molecule. A case study is presented of a bispecific design prone to LC-mispairing. This talk will focus on the rapid development of a downstream process through high-throughput chromatography screening coupled with mass spec analysis and molecular dynamics. The resulting strategy allows for identification and elimination of unique product related variants.

9:45am - 10:15am 30 mins
Late Stage Process Development: Raw Materials
Improved Characterization of Animal Serum for use in Cell Culture
  • Rosemary Versteegen, PhD - CEO, International Serum Industry Association
more

This presentation will provide an update on the development and implementation of the Industry wide date base for testing of bonnie serum for geographic origin based on trace element analysis. Recent studies which have led to improved, more specific specifications for determining whether serum is fetal or new born in origin will also be reviewed in detail.

9:45am - 10:15am 30 mins
Commercial Manufacturing: Quality Assurance
A contamination control and prevention program at an aging facility
  • Yuval Shimoni, PhD - Principal Engineer, Bayer Healthcare
more

An approach to enhancing and/or establishing a contamination control program will be presented. We will open with an introduction of current regulatory expectations and industry best practices. We will then describe the process of assessing current contamination control and prevention practices in a fully integrated (aging) manufacturing facility (warehouse, API (active pharmaceutical ingredient) and FP (final product) manufacturing/ fill-finish, as well as QC testing labs and environmental monitoring); emphasis will be given to risk prioritization of identified vulnerabilities. We will end with actions to minimize the risk of contamination incidences (excursions) as well as the potential for false positives while minimizing the disruptive impact of mitigating activities (e.g., preventive measures, training, cleaning and sanitization enhancements etc.) on routine commercial operations.

10:15am - 10:45am 30 mins
Single-Use: Case Studies and Innovations
In Process Monitoring in Single-Use Manufacturing of Dendritic Cells
  • Shashi Murthy, PhD - Professor of Chemical Engineering & Sherman Center Director, Northeastern University
more

This presentation will describe a new perfusion-based single use system for the manufacturing of patient-specific, therapeutic dendritic cells and, as a case study, detail the incorporation of sensors and monitoring instrumentation to achieve monitoring of key process parameters.

10:15am - 10:45am 30 mins
Early Stage Process Development: Process Intensification and Integration
Scale-Down High Throughput ambr® 250 Perfusion Development
  • Nathan Bandow, PhD - Postdoctoral Fellow, Continuous Manufacturing Skill Center, Sanofi
more

Recent interest in high-intensity perfusion processes for biologics manufacturing has increased the demand for a small-scale high throughput perfusion system. Developed in collaboration with Sartorius, the ambr® 250 prototype perfusion system has produced results comparable to 10L bench-scale bioreactors and promises to become an invaluable tool for perfusion-specific medium development, clone selection and process development.

10:15am - 10:50am 35 mins
Late Stage Process Development: Raw Materials
Young Scientists Awards Presented by 3M - - Chairpersons Opening Remarks: Innovation Management - A Perspective from Regeneron Pharmaceuticals Process Development
  • Andrew Tustian, Ph.D. - Associate Director, Regeneron Pharmaceuticals & 3M Representative
more

Session Tracks: New technologies in bioprocess development

Accelerating bioprocess development through innovation

Industry Perspective: The industry overview centered on providing industry’s perspective on,

  • Speed to clinic - technologies to enable fast timelines to clinic
  • Enabling breakthrough therapy timelines
  • Flexible manufacturing - faster changeover, more agile shifting between demands
  • Minimizing manufacturing cost
  • Personalized medicines - technologies to enable truly personalized treatments

 

10.15 AM Chairperson’s Opening Remarks: Andrew Tustian, Regeneron Pharmaceuticals
‘Innovation Management: A Perspective from Regeneron Pharmaceuticals Process Development’


Award Selection Committee

  • Andrew Tustian, Regeneron Pharmaceuticals –Chair
  • Peter Watler, Chief Technical Officer, Coherus Biosciences
  • Steven Hager, Senior Account Director, Business Development, Catalent Pharma Solutions
10:15am - 10:45am 30 mins
Commercial Manufacturing: Quality Assurance
Global Particle Library for Drug Product Inspection
  • Matthew Hammond, Ph.D. - Process Development Senior Scientist, Amgen
more
10:45am - 11:15am 30 mins
Single-Use: Case Studies and Innovations
Comparison of USP <665> and BPOG Protocols for Extractables Studies of SUS Components
  • Raymond Colton, MBA - Founder, VR Analytical
more

The extent of testing for extractables from biopharmaceutical contact materials currently not defined by any published guidance. The two approaches being considered are provided by USP in a draft chapter <665> and by the BioPhorum Operations Group (BPOG) in its Extractables Protocol. Among the considerations described in these documents are the recommended solvents and extraction periods for an extractables study. While both guidelines share some of the same recommendations for these considerations, they differ in the total number of solvents recommended and in the lengths of the extraction periods. In particular, BPOG recommends testing at a higher pH compared to USP <665> and BPOG recommends testing with a high ionic strength solvent (5M NaCl). To investigate the effect of pH and ionic strength, we conducted an extractable analysis of three gamma irradiated test articles used in single use systems: a polyether sulfone filter, a tubing set, and a biocontainer bag. We tested at increasing pH and ionic strength in order to evaluate if the importance of these variables. The results of these analyses shows where each approach does or does not have merit and how the materials of construction of the test article should be a consideration in the choice of solvents.

10:45am - 11:15am 30 mins
Early Stage Process Development: Process Intensification and Integration
Developability Assessment Of Therapeutic Proteins – An Overview & A Case Study
  • Duc Nguyen, PhD - Group Head, Novartis
more
10:45am - 11:15am 30 mins
Commercial Manufacturing: Quality Assurance
Unresolved Ambiguities in the Biologics Price Competition and Innovation Act (BPCIA) of 2010 Continue to Challenge Drug Product Sponsors
  • Verne Luckow, PhD, JD - Attorney-at-Law, The Intellectual Property Law Office
more
10:50am - 11:10am 20 mins
Late Stage Process Development: Raw Materials
Novel low shear bioreactor for the scalable production of human mesenchymal stem cells
  • Andrew Burns, MSc. - Student, Keck Graduate Institute
more

Human Mesenchymal Stem Cells (hMSCs) are multipotent stem cells with the capacity to proliferate ex-vivo, making them a suitable therapeutic candidate in regenerative medicine. However, a reliable and scalable production system for hMSCs is needed to achieve the estimated billion cells needed for successful hMSC therapies. hMSC expansion is currently achieved through adherent 2D static culture methods, which are labor intensive and have limited control over culture conditions, resulting in impurities and low yields. We are currently investigating a novel low shear 3D culture system for controlled high-density production of hMSCs. We have assessed compatibility of these cells on viable scaffolds and are developing a scale down model bioreactor for characterization. To validate and better understand the system we combine traditional benchwork with Computational Fluid Dynamic (CFD) modeling. This in-silico testing allows for rapid testing and optimization of parameters, such as oxygen transport and shear, to support high cell density hMSC production.

11:15am - 11:45am 30 mins
Single-Use: Case Studies and Innovations
Feedback on Single-Use Manufacturing and a New Approach for Scale Transfer
  • Christophe Martin - USP Production Manager, MilliporeSigma
more

Single use production equipment are used at Merck Biodevelopment (Martillac, France) since 2011. In 2015, manufacturing capacity was increased after the creation of new suites dedicated to production with single use equipment, at 2KL scale. The aim of this presentation is to share a feedback after 2 years using these large scale single use systems. This presentation will discuss the benefits offered by these systems from an organizational/plant management perspective. We’ll also discuss a new USP scale-up strategy, and an improvement of CO2 stripping strategy.

11:15am - 11:45am 30 mins
Early Stage Process Development: High Throughput Development and Monitoring
Coupling of the Ambr 250 with Robocolumns for Upstream/Downstream Screening
  • Ashley Hesslein, PhD - Associate Director in Biological Development, Bayer Healthcare LLC
more

Upstream and downstream development groups have increased technical sophistication, efficiencies, and throughput using AMBR bioreactors and miniaturized columns. However, these technologies have often been confined to upstream or downstream workflows. Here we present a combined process flow which maximizes data at early development stages (clone selection) and late stages (Process Characterization).

Authors: Ashley Hesslein, Ryan Zolyomi, Yu-Hsi Chang, Justin Grahek, Patrick Trogdon, Yi Liu, Hendri Tjandra

11:15am - 11:35am 20 mins
Young Scientists Awards - Presented by 3M
Biologics Development, Isolation & Purification
  • Ryan Zolyomi, Ph.D. - Scientist, Bayer
more

The implementation of a platform purification process for therapeutic monoclonal antibody (MAb) products is highly desirable because it allows for rapid and cost-effective process development. A platform process often includes a viral filtration (VF) unit operation in order to provide sufficient viral clearance by the end of the manufacturing process. Virus filter performance, as characterized by flux (LMH) and loading density (kg antibody/m2), was found to be inconsistent for a therapeutic MAb despite feed material being processed by a similar platform purification process. The product exhibited a severe flux decay and low throughput in spite of containing negligible HCP, DNA, and aggregate content. 

One root cause could be batch-to-batch variation in cell culture conditions resulting in variable product quality attributes; charge variants, glycosylation patterns, and hydrophobicity. Alternatively, operational parameters such as source and mode of flowrate, pH and conductivity could impact VF performance. A design of experiments (DOE) study was performed to investigate whether pH, ionic strength, protein concentration, and mode of operations could alleviate poor filter performance. Filtration performance outputs such flux decay, product-related impurity and step yield were monitored. Additional investigation implicated impurities from cell culture clarification to impact the performance of viral filtration. Optimization of the various operating conditions led to the development of a robust viral filtration unit operation that fits within the platform purification process to consistently and robustly manufacture clinical materials.

11:15am - 11:45am 30 mins
Commercial Manufacturing: Cost-Modeling
Leveraging Process Simulation Models at Different Phases of Development and Commercialization
  • Rick Stock, PhD - Consultant, BioProcess Technology Consultants, Inc.
more

The right tools and processes are needed to ensure that biologics developers and manufacturers deliver the product to the patients in the “best” way possible. Robust simulation packages from cradle to grave of a product is one way to de-risk challenges and improve likelihood of success in the manufacturing suite. It is equally important that the production simulation models are designed to be flexible and/are updated as the product goes through the different stages of development to enable better decision making at every step with regards to how and where to manufacture the life improving and saving therapeutic. In this presentation, we explore important concepts for handling cost data generated using commercially available modeling tools to simulate the manufacturing of a “typical” monoclonal antibody product. We will illustrate several important concepts, through theoretical case studies such as optimizing suite capacity base on theoretical demand, supporting the decision to manufacture in-house versus outsourcing to a CMO and estimating the impact on scale of different manufacturing process. - - Tiffany D Rau, Ph.D. BioProcess Technology Consultants corresponding author.

11:35am - 11:55am 20 mins
Young Scientists Awards - Presented by 3M
Computational fluid dynamic modeling of alternating tangential flow filtration for perfusion cell culture
  • Flaka Radoniqi, MSc. - Student, Keck Graduate Institute
more

Alternating tangential flow (ATF) filtration has been successfully adopted as a low shear cell separation device in many perfusion-based processes. The reverse flow per cycle is used to minimize fouling compared to tangential flow filtration (TFF). Currently, modeling of the ATF system is based on empirically derived formulas, leading to oversimplification of model parameters. In this study, a validated porous CFD model was used to predict localized fluid behavior and pressure profile in the ATF membrane using water and supernatant solution. The results gave a numerical evidence of starling flow phenomena that has been claimed, but not proved for the current operating parameters. Cross flow velocity was shown to significantly affect the localized flux distribution; higher crossflow rates lead to an increased localized permeate flux as well as irreversible and reversible fouling resistance. The small average permeate flow rates values used in perfusion bioreactor membranes lead to approximately half membrane utilization during pressurized and exhaust phases of one ATF cycle. These preliminary CFD results suggest that local flux and resistance distribution would aid in better understanding on fouling of membranes in ATF perfusion based system.

11:45am - 12:15pm 30 mins
Single-Use: Case Studies and Innovations
Technology transfer and scale up of a late clinical stage biotherapeutic to a nearly completely single-use manufacturing facility (a case study)
  • Kishan Rao, MS - Associate Director Clinical Technical Services, Alexion
more
11:45am - 12:15pm 30 mins
Early Stage Process Development: High Throughput Development and Monitoring
High Throughput Tangential Flow Filtration for Formulation Robustness
  • Anthony Portolesi - Technical Development Research Associate, Genentech Inc.
more

A multi-channel, high throughput TFF system, which could surpass the limitations of the conventional, single-channel TFF system is being developed by Sartorius in collaboration with several biotech companies. Our findings show that the careful selection of system components and process parameters is crucial for the development of a TFF system suitable for use in formulation robustness studies.  


Anthony Portolesi1, Zephania Kwong Glover1, Debbie O’Connor2, William Man2, John Lazzareschi2, Judy Hsii2, John Betts3

1 Late Stage Pharmaceutical Development, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080

2 Purification Development, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080

3 Sartorius-Stedim Biotech Group, York Way, Royston,  Herts, SG8 5WY, UK

11:45am - 12:15pm 30 mins
Commercial Manufacturing: Cost-Modeling
Will the Cost of Manufacturing be the Death of Your New Therapy?
  • Jennifer Chain, PhD - Science Officer, Oklahoma Blood Institute
more

In the cell and gene therapy sector there is no shortage of new ideas for the development of cell mediated therapies. During the discovery and proof of concept phase, free money from the NIH, universities and foundations provide a safety net allowing laboratory base observations to be evaluated in a first in human application. After success is measured and reported, large sums of capital are invested into moving the therapy through the development pipeline with the vision of becoming the next “big drug”. Reliance on scaling the methods used in the laboratory have proven to not yield therapies that the market is prepared to embrace. To survive and flourish, our industry has to identify new pathways to accomplish the critical steps in preparation and manufacturing. Leveraging the existing infrastructure of the haematopoietic stem cell industry may be just what the doctor ordered.

11:55am - 12:10pm 15 mins
Young Scientists Awards - Presented by 3M
Award committee deliberates on the session and nominates a winner
  • Russ Grove, Ph.D. - Executive Director, Coherus Biosciences
  • Steven Hager, Ph.D. - Senior Account Director, Catalent Pharma Solutions
  • Andrew Tustian, Ph.D. - Associate Director, Regeneron Pharmaceuticals & 3M Representative
more
12:10pm - 12:15pm 5 mins
Young Scientists Awards - Presented by 3M
Presentation of Young Scientist Award Winner - Chair & 3M Representative
  • Andrew Tustian, Ph.D. - Associate Director, Regeneron Pharmaceuticals & 3M Representative
more
12:15pm - 12:20pm 5 mins
Close of Conference - See you in 2019!