Cambridge Healthtech Institute’s 4th Annual

Advances in Purification & Recovery

New Materials, Technologies and Processes for Novel Products

August 15-16, 2018


New and emerging molecules coming down the pipeline bring a new set of challenges to the downstream team. Now, not only do they have to meet higher upstream titers, they have to come up with strategies to purify these novel and unconventional formats. Biopharm companies are thus increasingly looking to process intensification methods including high throughput, automation, mechanistic modeling and integrated manufacturing strategies to meet these challenges while improving productivity and reducing cost.

At CHI’s 4th Annual Advances in Purification & Recovery conference, scientist will share their pursuit of new materials, technologies and approaches to enhance productivity and reduce bottlenecks, and highlight strategies and best practices in downstream purification of novel, non-platform products from bispecific antibodies, cell and gene therapies, to viral vaccines and microbial-expressed proteins.


Final Agenda

Wednesday, August 15

7:00 am Registration Open and Morning Coffee

PROCESS INTENSIFICATION - MODELLING, HIGH THROUGHPUT METHODS AND PROCESS CONTROLS

8:05 Chairperson’s Remarks

David W. Wood, PhD, Professor, Chemical and Biomolecular Engineering, Ohio State University


8:15 KEYNOTE PRESENTATION: Advanced Modelling of Process Chromatography Combining CFD with Mass Transfer Models

Alois_Jungbauer_2Alois Jungbauer, PhD, Professor, Biotechnology, University of Natural Resources and Life Sciences, Vienna and Austrian Centre of Industrial Biotechnology

For a complete description of process chromatography, the packing of the column including the extra column space and the mass transfer must be considered. This is only possible when the convective flow is described by CFD and the diffusion into the pores by mass transfer models. An example will be given for scale up from 1 ml column to 65 L columns. Methods to implement it in process development will be discussed.

9:00 Feedback Control System for mAb Downstream Purification

Lizy_Kaiyan_TangLizy Kaiyan Tang, MSc, Senior Scientist, MMD, BVA, PAT, Merck

A feedback control system for monoclonal anitbody downstream purification established by liquid chromatography the analyzer, prep scale chromatography the purification system and PAT software the brain. This talk will illustrate how this system enables real time product quality control as well as its extended applications.


9:30 Implementation of Design Space Strategy to Control Product Quality During Large Scale Purification of Therapeutic Proteins

Ionela_IliescuIonela Iliescu, Msc, Scientist I, Technical Development, Biogen

Design Space/QbD strategy offers great flexibility in dealing with adsorbent lot variability in commercial scale manufacturing. The information contained in the chromatography certificate of analysis may not be sufficient to evaluate adsorbent lot performance for a specific process and product separation. This presentation will describe the development of a chromatography step with a control strategy which accounts for adsorbent lot to lot variability, the regulatory considerations, and the activities required to implement it in manufacturing.

10:00 Coffee Break in the Exhibit Hall with Poster Viewing

10:45 Modular Buffer Mixing for Automated Membrane Protein Purification Using AkTA Avant

Jonas_LeeJonas Lee, PhD, Scientist, Protein Technologies, Amgen

Transmembrane proteins are important targets in therapeutics discovery. Yet they are difficult to express and purify due to its exposed hydrophobic regions requiring complex buffer formulation that needs to be screened. I will present various automated high-throughput methods to screen for best solubilizing conditions for membrane proteins followed by modular buffer mixing capability of AkTA Avant to purify multiple membrane proteins in different buffer conditions automatically.

11:15 Qualification and Use of Statistically Equivalent Scale-Down Models for Continuous Process Improvement

Zhi_LiZhi Li, PhD, Scientist, Manufacturing Science & Technology, Bristol-Myers Squibb

Scale-down models are routinely used during process design and characterization. It is important to develop scale-down models that are statistically equivalent to large scale manufacturing. With paired data from the two scales, statistical equivalence can be examined using the Two-One-Sided Test (TOST) with appropriately justified equivalence threshold. These models are used to enhance process understanding, investigate deviations, and conduct continuous process improvement.

11:45 New Depletion Technology for Mid-Stream and Downstream Purification Operation

Rousset_FabienFabien Rousset, PhD, Head, Bioseparations, Business Unit, DAICEL/Chiral Technologies Europe

Due to increased levels of process-related impurities, midstream operations are limited and challenging. Depletion performances for HCP, DNA, and other target mABs are improved with this new SU flexible technology thanks to several removal mechanisms. Classic technologies can be combined into a single-step unit, which operates pre-protein A. This enhances process safety and overall purification platform performances.

12:15 pm Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:00 Session Break

NON-PLATFORM DOWNSTREAM PROCESSES FOR EMERGING PRODUCTS

1:45 Chairperson’s Remarks

Alois Jungbauer, PhD, Professor, Biotechnology, University of Natural Resources and Life Sciences, Vienna and Austrian Centre of Industrial Biotechnology

1:50 ProTIA: Challenges with Isolation and Purification of a Novel, XTENylated Bispecific T Cell Engager Therapeutic

Ulrich_ErnestUlrich Ernst, COO & Senior Vice President, Technical Operations, AMunix Operating, Inc.

Amunix has created a bispecific T cell engager platform in a pro-drug delivery format that overcomes current, on-target/off-tumor challenges related to conventional antibody constructs. Challenges to manufacturing and scale up of the molecule have been successfully overcome by a priori selection and incorporation of affinity domains into the molecule design. Data and results are presented demonstrating how these design features have been successfully utilized to enable efficient high throughput screening, process development and scale up to GMP requirements.

2:20 Purification Methods for Higher Throughput Generation of Bispecific Antibodies

Adam_ZwolakAdam Zwolak, PhD, Senior Scientist, Biologics Discovery, Janssen R&D

BsAbs comprised of mutant and wild-type IgG subunits can be efficiently separated from contaminating parental mAbs by differential protein A elution starting from either a) purified parental mAbs, b) in-supernatant crossed parental mAbs, or c) co-transfected mAbs. We show that the Q311R mutation confers enhanced FcRn interaction in vitro, and Abs harboring either the Q311R or TLQ mutations have serum half-lives as long as wild-type human IgG1. Together, the results lead to a method for high-throughput generation of BsAbs suitable for in vivo studies.

2:50 A Practical Self-Cleaving Tag Platform for Initial Capture of Complex Glycoproteins

David_WoodDavid W. Wood, PhD, Professor, Chemical and Biomolecular Engineering, Ohio State University

We present our latest work on a split-intein system for the capture and purification of complex glycoproteins. This system is based on a capture resin, which immobilizes the tagged target while generating a cleavage-competent complex to release the tagless and traceless target after purification. This presentation will detail new information on the performance of the system with various targets, and provides guidance on predicting and enhancing cleavage performance in laboratory and manufacturing settings.

3:20 Challenges in Purifying Influenza Virus-Like Particles

Christina_PeixotoCristina Peixoto, Head, Downstream Process, Animal Cell Technology, iBET Instituto de Biologia Experimental Tecnologica

Here we describe the establishment of an improved DSP unit train platform, adapted from virus particles to influenza VLPs, using pseudo-affinity sulfated cellulose membrane adsorbers (SCMA). Using this SCMA platform for influenza virus particles purification, we were able to speed up the process by decreasing the number of DSP steps, to improve the scale-up and to reduce costs due to the removal of other chromatographic steps.

3:50 Refreshment Break in the Exhibit Hall with Poster Viewing


4:45 Plenary Keynote Session

The Next 10 Years: Looking Ahead to Next-Gen Bioprocessing

4:45 pm Chairperson’s Remarks

John Sterling, Editor in Chief, Genetic Engineering & Biotechnology News (GEN)

 

Murray_Jerry4:50 Digital Transformation to Advance Next-Generation Biomanufacturing through Data Integration and Analytics

Jerry Murry, PhD, Senior Vice President, Process Development, Amgen

Hundreds of millions of data points are currently generated through the development and execution of biopharmaceutical processes. It is expected that the volume and complexity of biomanufacturing data is set to grow exponentially as developers and manufacturers integrate novel sensors, smart materials, process analytical technologies and process automation into laboratories and manufacturing plants. This presentation will describe the value associated with a comprehensive digital strategy incorporating a structured data integration and analytics platform inclusive of AI, predictive modeling and visualization, and how digital transformation can advance next-generation biomanufacturing.

5:20 Driving Change in Biomanufacturing through Innovation in Processes, Technologies and Operations

Eliana Clark, PhD, Vice President, International Manufacturing Operations, Biogen

A critical step in meeting the demand of biologic production worldwide involves implementing disruptive manufacturing technologies, processes and capabilities. This talk will use Biogen’s new manufacturing site in Switzerland, due to go online in 2019, as an example to demonstrate the new processes, operational models and technologies being adopted to drive value through innovation and deliver new medicines in areas such as Alzheimer’s.

5:50 End-to-End Solutions Considering New Trends in Biomanufacturing

Guillaume Plane, MSc, MBA, Manager, Global Development, Biodevelopment Solutions, MilliporeSigma

The presentation will get into the current state of biomanufacturing, from DNA to market approval, considering the way a key supplier can support drug makers to the fullest, thanks to a deep understanding of the trends that could affect our industry in the midterm, including growth of the pipelines, strengthening of regulations, and acceleration of timelines, for development as well as for the set-up of capabilities. Some thoughts and ideas will be proposed to consider commercial manufacturing with single-use equipment.

6:25 Close of Plenary Keynote Session

6:25 10th Anniversary Champagne Reception in the Exhibit Hall with Poster Viewing

7:30 End of Day

Thursday, August 16

8:00 am Registration Open and Morning Coffee

NEW MATERIALS, TECHNOLOGIES AND APPROACHES

8:25 Chairperson’s Remarks

Andrew Kim, PhD, Senior Scientist, Global MSAT, Sanofi

8:30 A Universal Platform for Protein Purification (UPPP) by Liquid Chromatography

Xindu_GengXindu Geng, PhD, Professor, Separation Science and Technology, Northwest University, Suzhou, China

A universal platform for protein purification (UPPP) by multiple dimensional liquid chromatography (mD-LC) which is suitable for ultrafast purification with simultaneously high resolution of proteins is established. All assisted operations in mD-LC, such as desalting, buffer exchange, re-concentration of target proteins, etc., can now be done in a closed and positive pressure system. Target proteins can be quantitatively transferred from previous separation mode to subsequent mode, greatly increasing mass recovery, separation speed, reproducibility, and sample loading.

9:00 Continuous Virus Inactivation Process Using A Novel Packed-Bed Reactor

Martins_DuarteDuarte L. Martins, PhD Student, Lab of Protein Technology and Downstream Processing, Dept of Biotechnology, University of Natural Resources and Life Sciences Vienna

Continuous virus inactivation has been overlooked while the biopharm industry moves towards continuous integrated processing. A novel continuous virus inactivation setup, which has several advantages over other approaches, will be presented. This talk will focus on ta case study in which solvent/detergent treatment was employed for continuous inactivation of two-industry-standard virus models (X-MuLV and BVDV). Control experiments will be presented showing that the continuous setup is as effective as the batch incubation. 

9:30 Sponsored Presentation (Opportunity Available)

10:00 Coffee Break in the Exhibit Hall with Poster Viewing

10:45 Enhanced Affinity Capacity via Novel Utilization of Hydrophobic Interactions

Keith Selvitelli, Senior Associate Scientist, Process Biochemistry, Biogen

Protein-ligand binding/interaction presents a delicate balance between charges on the ligand and the conserved residues on the molecule. To examine the effects and dependence of salt type and salt concentration on capacity and recovery from novel/custom affinity chromatography step, protein-ligand binding kinetics were studied. Preliminary results provided evidence for enhanced retention resulting in better resin bed capacity utilization, higher loading capacities, improved yields, smaller bed volumes and a general reduction in cost of goods.

11:15 High Concentration Ultrafiltration Challenges in Manufacturing Platform

Mahsa_HadidiMahsa Hadidi, PhD, Process Engineer III, Global MSAT Process Sciences, Sanofi Genzyme

Ultrafiltration is the most commonly used method for concentration and diafiltration of nearly all recombinant therapeutic proteins. However, there are unique challenges in applying this technique to obtain very high target concentration that is needed for monoclonal antibody (mAb) formulations. This work is a case study discussing challenges in a manufacturing platform and the approach towards easy-to-implement resolutions to overcome these difficulties.

11:45 Mechanisms of mAb Viral Filtration Improvement by Nylon Prefilters

Vitali_StanevichVitali Stanevich, PhD, Process Development Scientist, Janssen Pharmaceuticals

We found that nylon membranes significantly improved mass throughput during mAb viral filtration step in comparison to target conditions. The Definitive Screening Design (DSD) experiment showed ionic nature of impurity removal and protection. In particular, nylon prefilters showed themselves as weak-anion exchangers, where mass-throughput directly correlated with pH and reversely with conductivity. Our findings can contribute to optimization of cost, increased throughput, and reduction of development time when using a nylon membrane as a prefilter.

12:15 pm Enjoy Lunch on Your Own

1:15 Dessert Refreshment Break in the Exhibit Hall with Last Chance for Poster Viewing

1:55 End of Conference


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