Cambridge Healthtech Instituteの第9回年次会議
Advances in Purification & Recovery
2023年8月16 - 17日、EDT（米国東部標準時）
Registration and Morning Coffee7:30 am
DOWNSTREAM PROCESS INNOVATIONS FOR COMPLEX & EMERGING BIOLOGICS
KEYNOTE PRESENTATION: Platform Approaches for a Diverse Pipeline: Engineering Ways of Working for Robust Separations
Kevin P. Brower, PhD, Global Head, Purification Process Development, Sanofi
Modality diversity and variable separation challenges have become increasingly prevalent in the portfolios in biotechnology. Despite this complexity, timeline and resource pressures remain. In this presentation, we describe Sanofi’s purification platform approaches, including separation science, establishment of work packages, and application of novel engineering technologies in high-throughput and integrated continuous biomanufacturing to meet the challenge of our diverse pipeline of mAbs, multi-specifics, antibody-drug conjugates, and therapeutic proteins.
Downstream Processing of Allogeneic iNK and iT Cell Therapy
Christopher Deborde, PhD, Process Development Engineer, Century Therapeutics
Allogeneic iPSC-derived iNK and iT cell therapies have shown encouraging preclinical and clinical promise. These therapies have the potential to treat a wide range of indications and provide a limitless source of readily available doses to numerous patients. As therapeutic technologies progress, the requirement for the development to adequately support clinical-to-commercial scale production becomes more critical. To that end, this presentation will highlight the downstream processing, purification, and drug product formulation strategies that meet the requirements of both patients and cell therapy manufacturers.
Identifying and Remediating Root Cause of Particle Formation in Drug Product Presentations
Sponsored Presentation (Opportunity Available)9:45 am
Coffee Break in the Exhibit Hall with Poster Viewing10:00 am
Capillary-Channeled Polymer Fibers: A Singular Platform for the Purification of Diverse Vector Types
R. Kenneth Marcus, PhD, Professor, Chemistry, Biosystems Research Complex, Clemson University
This laboratory has developed a novel family of polymer fiber stationary phases to affect the isolation and purification of exosomes using a hydrophobic interaction chromatography elution scheme. Here we will demonstrate the breadth of applicability of the approach, extending it to further sources of exosomes including bovine milk and plants. The same method has now been applied to lentiviruses and adeno-associated viruses (AAVs) and lipid nanoparticle (LNP) vectors as well. The ability to affect separations across this group of vector species, using the same process platform and protocol is seen as a tremendous advantage on the research and clinical scales.
AAV Purification: History, Current Practices, Challenges, and Solutions
Richard Ding, PhD, Head, Purification Process Development, Gene Therapy, Biogen
This presentation will cover the following areas:
- AAV purification historry: density gradient centrifugation to chromatography
- Current practices: process design, efficiency, capability, scalability, consistency, yield to cost reduction
- Challenges & solutions: process- and product-related impurity removal such as empty capsid and aggregates
Overcoming Supply Chain Challenges for Various Filters Used in Commercial Biologics Downstream Manufacturing
Elizabeth Pontius, BSc, Associate Engineer/Scientist, MSAT, Bristol Myers Squibb Co.
Filtration is an essential component in biologics downstream manufacturing. The COVID pandemic has caused a global supply shortage in filters used in various downstream processing steps. To ensure manufacturing continuity and uninterrupted delivery to patients, innovative solutions are needed to overcome these challenges. Alternative filter evaluations and sizing studies have been performed to mitigate stockout risks for several filters used in commercial biologics manufacturing.
Jungmin Oh, Development Manager, Bioprocessing Research, Avantor
Downstream purification of antibodies encounters issue of optimization and scale-up when different complex molecules are considered for multiple chromatographic steps. In this session, we will review common challenges faced during the affinity step of DSP and discuss the troubleshooting practices and methodologies to optimize the process through screening of different resins and additives. The case studies will include different types of antibodies including fragment antibodies where the process is initially developed in the lab scale and 100X scale up was achieved successfully.
Refreshment Break in the Exhibit Hall with Poster Viewing12:40 pm
DOWNSTREAM PROCESS INNOVATIONS FOR COMPLEX & EMERGING BIOLOGICS (CONT.)
Developing High-Productivity Mixed-Mode CHT Chromatography Purification Step for Complex Biologics
Evaluating the Impacts of Dual Salts and Organic Modifiers on Purification of Antisense Oligonucleotide via Anion Exchange Chromatography
Armin Delavari, PhD, Scientist II, Technical Development, Biogen
Antisense oligonucleotides are short single strand modified RNA/DNA sequences that are designed to treat genetic disorders by eliminating target mRNAs via specific binding. The safety and efficacy of these therapeutics can be affected by their purities, and therefore, a robust purification process is required. In this study, we explored novel approaches to enhance impurity clearance using anion exchange chromatography polishing step using dual salt systems and organic modifiers.
Refreshment Break in the Exhibit Hall with Poster Viewing3:00 pm
PLENARY KEYNOTE: LEADING TO TOMORROW'S ADVANCES
Current and Future Trends in Biomanufacturing of New Modalities
Konstantin B. Konstantinov, PhD, CTO, Codiak Biosciences
Using exosomes as an example, this presentation examines the current and future trends in biomanufacturing, and the technologies needed to manufacture emerging modalities at scale. Traditional biomanufacturing methods do not provide the industrialized, commercially scalable, highly efficient and reproducible manufacturing process essential for this new class of biotherapeutics- so we built it from the ground up.
The Digitalization of Biomanufacturing
Richard D. Braatz, PhD, Edwin R. Gilliland Professor, Chemical Engineering, Massachusetts Institute of Technology
A fully instrumented testbed is described for the end-to-end integrated and continuous manufacturing of monoclonal antibodies. The testbed consists of parallel bioreactors, simulated moving bed chromatography systems for capture and polishing, bespoke viral inactivation, and a MAST auto-sampling system. Experimental results are compared with a digital twin for continuous runs lasting 30 to 60 days each, which include variations in metabolites and glycosylation profiles in designed experiments. The increased consistency in the glycosylation profile of the monoclonal antibodies being produced is quantified when going from batch to semi-batch to perfusion mode, and when moving from start-up to quasi-steady conditions.
Networking Reception in the Exhibit Hall with Poster Viewing5:00 pm
Close of Day6:00 pm
Registration and Morning Coffee7:30 am
ADVANCES IN TOOLS, MATERIALS, AND TECHNOLOGIES FOR NEXT-GEN PURIFICATION PLATFORMS
Computational Modeling of Protein A Resin Slurry in a Mixing Tank
Chadakarn Sirasitthichoke, PhD, Process Engineer, MS&T Process Analytics and Engineering, Bristol Myers Squibb Co.
Protein separation is an important purification step in a biopharmaceutical downstream process. Prior to column packing, homogenous resin slurry is necessity for optimal column packing and effective chromatographic purification. Agitation speed, packing buffer, and resin solid percentage are key factors to achieve the homogeneity. In this study, computational fluid dynamics (CFD) is used as a tool to guide those operating parameters for slurry suspension in a stirred tank and thus providing a more consistent column packing process. The result of this work can be applied to predict optimal slurry tank parameters for other types of resin.
High-Resolution 3D Imaging to Visualize and Characterize 3D-Printed Chromatography Columns
Thomas F. Johnson, PhD, Senior Research Fellow, Biochemical Engineering, University College London
3D design and printing bioprocessing structures enables the chemical and physical characteristics of downstream media to be specifically tailored to the product of interest, particularly important due to the emerging popularity of advanced modalities. In this study we apply high resolution imaging to view multiple length scales analogous to packed bed chromatography that informs the design of next-generation DSP materials.
Coffee Break in the Exhibit Hall with Poster Viewing9:00 am
Subject matter experts sit down 1:1 with our moderator to discuss and share their personal bioprocessing experiences, insights, and advice. The real “pay it forward” atmosphere provides biopharma leaders with unique opportunities to leverage and apply their expertise to make better technology, process, and business decisions, and, ultimately, to accelerate success. Dedicated networking within the session allows all attendees to follow up and dive deeper into conversation.
Viral Clearance Capability of Biotechnology Product Manufacturing Process: IND Viral Clearance Database Case Study
Opeyemi Ajayi, PhD, Research Analyst, CDER/OPQ/QBP, FDA
Clearance of endogenous and adventitious viruses is an important consideration for any mammalian cell-derived biotechnology product. Process changes in the investigational phase may impact clearance capabilities depending on the applied unit operations and parameters. Data from an in-house database created to evaluate these process parameters and their impact on clearance will be presented.
How to Leverage Risk-based Approaches, Process Knowledge, and Appropriate Strategies for the Design of Process-Relevant Impurity Clearance Challenge Studies
Raj Prabu Vijayakumar Saraswathi, Principal Scientist, Biologics Process Dev, Alkermes Inc
This talk focuses on designing a process relevant impurity clearance challenge studies. We used risk-based approach to identify process-related impurities that warranted impurity clearance challenge studies, and applied three different strategies to design the studies: upstream worst case material, column overloading approach and by-pass approach. Data generated will be used to set acceptance criteria wihtin the process control strategy.
Sponsored Presentation (Opportunity Available)11:30 am
Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own12:00 pm
Refreshment Break in the Exhibit Hall & Last Chance for Poster Viewing12:30 pm
OPTIMIZING DOWNSTREAM PROCESSING FOR AAVs
Advanced AEX Platform for AAV Enrichment
Yonatan Abune, Principal Research Associate and Engineer, CMC, Vedere Bio II
In this investigation, we employed AEX chromatography to simultaneously enrich full AAV capsid and eliminate endotoxin from the final drug product. By optimizing the column conditions, we achieved a high level of AAV capsid purity, as well as a significant reduction in endotoxin levels. This strategy offers a promising solution for the production of safe and effective AAV-based therapeutics.
Lessons Learned: A Case Study in the Downstream Optimization of an AAV5 Production Process
Ashton Lavoie, PhD, Associate Director, Downstream Process Development, BridgeBio Gene Therapy
Manufacturing strategies and progress towards platform processes for adeno-associated virus (AAV) production have seen substantial advancement in support of the impressive clinical success for this modality. This presentation will provide a case study for the development of a robust, high yield downstream process for the production of AAV serotype 5. Key findings will be discussed in addition to pitfalls and challenges in this development work.
Using High-Throughput Techniques to Improve Downstream Process Development for AAV
Arjun Bhadouria, PhD, Scientist, Purification Process Development, Genomic Medicine Unit CMC, Sanofi
High throughput purification development has become an integral part of purification development by providing an order of magnitude reduction in material and time requirement. It can be especially valuable since material limitations are often a challenge for AAVs. An initial screening of several process operating parameters using small amounts of material can be performed to narrow down the development space to focus on and further optimize the process. Here we discuss the various high throughput approaches utilized in Sanofi for developing several downstream unit operations including clarification, affinity chromatography, polishing AEX chromatography, etc.
Networking Refreshment Break2:40 pm
Studying AAV Capsid Aggregation in Complex Matrix of Clarified Lysate
Yulia Ivanova, PhD, Principal Scientist, Bioprocess R&D, Pfizer Inc.
Recovery out of harvest is the least understood step in downstream purification of AAV vectors. Complexity of lysed cell culture coupled to relatively low protein concentration of AAV product makes it very difficult to analytically investigate this process space. Here we evaluate the ability of dynamic light scattering (DLS) to serve as analytical characterization tool that would allow to investigate AAV capsid aggregation in a complex matrix of clarified harvest.
Plasmid Purification Process Development for Gene Therapy Applications
Close of Summit4:25 pm