Facilitated, small-group discussions. Interactive participation leads to problem-solving solutions and future collaborations around focused topics.
To see BuzZ Session B discussion table topics (3:45-4:45 pm), please click here.
TABLE 1A Personalizing PepTalk: An Introduction to our Event App
Deborah Shear, Associate Director, Production, Cambridge Healthtech Institute
- Find and install the app
- Search the agenda, posters and exhibit hall
- Build your own schedule
TABLE 2A Label-Free Assays in Biotherapeutic Discovery and Development – The Right Tools for the Right Job
Vishal Kamat, Ph.D., Scientist, Biomolecular HTS Center, Therapeutic Proteins, Regeneron Pharmaceuticals
- Biophysical characterization of proteins
- High-throughput screening of therapeutic antibodies
- Design and development of binding kinetics and epitope binning assays using label-free biosensors
TABLE 3A Cross-Reactive Neutralizing Monoclonal Antibodies (mAbs)
Dimiter S. Dimitrov, Ph.D., Senior Investigator, Protein Interactions Group, National Cancer Institute, NIH
- Need for cross-reactive antibodies – virus neutralization, animal studies
- Methods for enhanced selection of cross-reactive mAbs
- Cross-reactivity versus neutralization potency
TABLE 4A Functional Mapping and Directed Evolution of Protein Interactions Using Combinatorial Libraries and Extensive Mutagenesis
Gertrudis Rojas, Ph.D., Group Leader, Protein Engineering, Systems Biology, Center of Molecular Immunology
- How to improve library design and screening in order to achieve fine functional mapping of protein interactions?
- Are the structural solutions emerging from combinatorial approaches of directed evolution easy to predict/explain on the basis of structural knowledge?
- Epitope mapping based on extensive site-directed mutagenesis of the target antigen vs. screening of random peptide libraries: accuracy or universality?
TABLE 5A The Role of Deep Sequencing in Affinity Reagent Selections
Csaba Kiss, Ph.D., Team Leader, Bioscience Division, Los Alamos National Laboratory
- Various deep sequencing technologies (454, Ion Torrent, MiSeq, Illumina)
- Limitations of the technologies
- How to deal with sequencing errors
- Analyzing the data
TABLE 6A The Role of Fc Receptors in Immunomodulatory mAb Function
Ann White, Ph.D., Senior Research Fellow, University of Southampton, United Kingdom
- Activatory versus inhibitory FcgR engagement
- Optimizing immunomodulatory versus therapeutic function
- Requirements for agents targeting receptors on T cells versus APC
- Treatment of cancer versus infectious disease
- Can efficacy and toxicity be uncoupled?
TABLE 7A Changes in Patent Law: Obtaining Meaningful Protection for Your Invention
John L. Marquardt, Jr., J.D., MBA, Ph.D., Attorney at Law, Marquardt Law
- America Invents Act – changes in the law affect strategies for protecting your intellectual property
- Collaborations – three things you should do before starting a collaborative venture
- Patentable Subject Matter – recent court decisions promote the use of trade secrets
- Your rights as an inventor; negotiating your rights
- European patent law – recent developments
TABLE 8A Next Generation of Antibodies – Bispecific vs. Mixtures
Ivan Horak, M.D., CSO and CMO, Symphogen
- Pros and cons
- Targeting opportunities
- Manufacturing complexities
- Regulatory challenges
TABLE 9A Preclinical Pharmaceutical Target Validation: Is It Possible?
James W. Larrick, M.D., Ph.D., Managing Director and Chief Medical Officer, Velocity Pharmaceutical Development
- What constitutes target validation?
- Predictability of preclinical toxicology
- Reliability of animal models of various diseases
- Go-no-go decisions in therapeutic development
TABLE 10A Solving Manufacturing Issues with (Fusion) Proteins
Stefan Schmidt, Ph.D., Vice President, DSP, Rentschler Biotechnology
- Feed strategies for optimized glycoprofiles
- Strategies for higher titers
- Aggregate removal
- Lack of affinity resins
TABLE 11A Challenges and Solutions for Non-Platform Molecules
Georg Blaser, Ph.D., Group Leader, Applied Protein Services, Lonza Biologics
A significant proportion of novel biotherapeutics cannot be a cultured, purified and analysed in a platform (e.g., antibody) way and require more unique solutions to overcome these challenges. How can challenges be assessed as early as possible in the development/discovery phases? What are they specifically and what could be possible solutions or standardised approaches?
- Post-translational modifications
- Expression/purification challenges
- Expression/purification solutions
TABLE 12A Advantages of Site-Specific Antibody Drug Conjugation Technologies
Aaron K. Sato, Ph.D., Vice President, Research, Sutro Biopharma
- Compare and contrast current technologies for site-specific drug conjugation
- Enzymatic vs. non-natural conjugation chemistries
- Use of multivalent payloads vs. site-specific drug loads
TABLE 13A High-Throughput Stress and Characterization Techniques
Vladimir Razinkov, Ph.D., Principal Scientist, Amgen
- Automation of sample preparation and measurements for formulation development
- Emerging high-throughput characterization methods for critical attributes
- Design of experiment, statistical analysis of high-throughput data
- Prediction models of formulation stability
TABLE 14A Predicting Pharmaceutical Stability from Accelerated Stress Studies and Measurements of Protein Conformational Stability
Mark Brader, Ph.D., Principal Scientist, Biogen Idec
- How useful are thermal unfolding transition (Tm) measurements for formulation stability ranking and prediction?
- Practical utilization and interpretation of data from high-throughput DSF screening methods
- Colloidal stability and conformational stability measurements for formulation screening and prediction
- How useful are forced degradation studies at high temperature for formulation stability prediction and ranking?
TABLE 15A QbD: Where Are We in Drug Product Development?
Steven LaBrenz, Ph.D., Scientific Director, Drug Product Development, Janssen R&D
- Squeezing the tried and true way into a new box?
- Implementation of mathematical modeling in protein formulation is still weak
- Design space as a concept; not targets with variability
TABLE 16A Solid State Protein Stabilization through Formulation and Non-Lyo-Based Process Strategies
Evgenyi Shalaev, Ph.D., FAAPS, Research Investigator, Allergan, Inc.
- Alternate and emerging excipients
- Role of excipient state in defining functionality
- Excipients for oral, parenteral and inhalation delivery
- Formulation strategies for nonclinical applications
TABLE 17A Reconstitution of High-Concentration Freeze-Dried Proteins
Bakul Bhatnagar, Ph.D., Principal Scientist, BioTherapeutics Pharmaceutical Sciences, Pfizer, Inc.
- What attributes should be monitored? Cake surface area, phase behavior of components, cake wetting and hydration, cake displacement, bubbles, effervescence, foam (appearance and height), gel formation, turbidity, viscosity, absorbance of the dissolved phase, dissolution time?
- Reconstitution time: (i) Methodology for the determination of the reconstitution time and definition of the endpoint, (ii) Can strategies based on trial and error for shortening reconstitution times be generalized? (iii) What constitutes a long reconstitution time?
- Reconstitution aids/devices
TABLE 18A High Volume/Viscosity Subcutaneous Drug Delivery – Challenges and Opportunities
Zach Marks, Director of Marketing, West Pharmaceutical Services, Inc.
- How would expanding volume/viscosity constraints affect formulation approaches?
- What are the opportunities and challenges in converting IV to subcutaneous administration?
- What are the key concerns regarding high volume subcutaneous administration?
TABLE 19A Lift Off: Integrated Launch of a New Biotech Company, from Technology to Team to Launch to Exit Plan
Joseph Kittle, Jr., Ph.D., Assistant Professor, Chemistry and Biochemistry, Ohio University and CSO, Molecular Technologies Laboratories, LLC
We will discuss common experiences in early stage companies, aimed at the experienced professional as well as the first-time company founder. MTL/ABV will discuss its integrated approach to forming and launching new companies using our NewCo model. An integrated approach has components that work together to speed up the process, lower costs, capture value and greatly reduce risk. Components include:
- Describing and evaluating technology and IP
- Seed capital and forming a new company, developing a business model that looks ahead to value capture and Exit
- Company setup using a pre-formed management team and a select group of business professionals
- Bringing in a science “tiger team” to do necessary wet lab work in state-of-the-art facilities, to accelerate proof of principle and capture practical IP
- Using a pre-selected group of super angel investors to power product/company development, along with non-dilutive sources of cash to fuel growth
- Providing a path to Exit that includes suitor companies and relationships of trust with investment bankers
TABLE 20A What More Can Be Done for Downstream?
Wei Chen, Ph.D., Managing Director, BioPharmaneer, Inc.
- Relations to upstream
- Cost savings
- Single use
- Alternatives to column chromatography
TABLE 22A Common Issues with Transient Protein Production
Richard Altman, MS, Research Scientist, Alexion Pharmaceuticals
Henry C. Chiou, Ph.D., Senior Product Manager, Life Technologies
Krista Johnson, MSc, Research Scientist, Alexion Pharmaceuticals
Scalable and rapid transient protein production in mammalian cells continues its evolution as an integral part of the biotherapeutic drug discovery process. We will discuss the common issues facing researchers as they try to meet an expanding demand for transiently produced recombinant protein.
- What are the current challenges to transient protein production?
- What elements of transient protein production represent the greatest hope for optimization?
- What scale of expression is most relevant? Is bigger always better?
- HEK293 versus CHO? And the winner is…
- What are the current and potential applications for transiently produced recombinant proteins?
- Purification and characterization of transiently produced protein
TABLE 23A Next-Generation Expression Platforms
Miller Tran, Ph.D., Senior Scientist, Triton Algae Innovations
- Glycosylation of next-generation expression platforms
- Advantages and disadvantages of next-generation expression platforms
- Current and future products based on next-generation expression platforms
- Potential opportunities of alternative expression platforms
TABLE 24A Expression and Affinity Tags for Production of Recombinant Proteins
Alexei Yeliseev, Ph.D., Staff Scientist, Protein Biochemistry, LMBB, National Institutes of Health
- Solubilization tags for production of functional targets in E. coli and other hosts
- Affinity tags for efficient recovery of target proteins from dilute solutions
- Tags for purification of membrane proteins: their usability in detergent micelles
- Methods of tag removal
TABLE 25A Tricks of the Trade: From Protein Purification to X-Ray Crystallography
Vinodh Kurella, Ph.D., Research Fellow, Bioinformatics, Harvard Medical School
- New constructs for maximal protein expression
- Novel methods for endotoxins removal
- Efficient crystallization trials
- In-house vs. synchrotron X-ray generators
- Streamline the process from protein to crystal structure
TABLE 26A Continuous Chromatography for Protein Purification
Andrew L. Zydney, Ph.D., Department Head and Walter L. Robb Family Chair, Chemical Engineering, The Pennsylvania State University
- Critical opportunities and needs
- Technology options and challenges
- Barriers to implementation
TABLE 27A Where Is Downstream Processing Headed? Pre-Packed Columns, Continuous Processing, Alternatives to Protein A, Filtration and the Next Steps
Adam Goldstein, MSc, Principal Engineer, Genentech, Inc.
- Equipment-related failures in processing
- Documentation of extractable profile characterization
- Vendor qualification and/or fitness-for-use criteria definitions
- Scale limitations of pre-packed columns
- Consensus on quality and testing – what to test for and when these tests should occur?
- Greatest areas of need for further development – sensors, integrity testers, 100% leak detection on COAs
TABLE 28A Vendor Qualification, Supplier Agreement and Establishing Quality Standards for Single-Use Implementation
Morten Munk, Vice President, Business Development, Technology Specialist, CMC Biologics
Single-Use Systems (SUS) obviously have a broad range of advantages in biopharmaceutical manufacturing. However, implementation of SUS does also lead to some areas of concern, where the main ones are related to the supplies. The most important concern is probably the increased dependency of the suppliers, their quality system and the different types of technical and quality information end-users need to get from the supplier.
This BuzZ Session will address some of the key concerns:
- What are the key elements in supplier qualification – including supply agreements, audits, requirements to supplier quality systems and requirements to the information package that follows the SUS components?
- Can end users benefit from others’ audits – for example, use RX360?
- What is the best alternative to having dual sourcing for key SUS components?
- E&L – can a common standard be established, and if so, who should be responsible for such a standard?
- Who has the quality responsibility for SUS, that is composed by elements from several suppliers?
TABLE 29A Risk Assessment and Control Strategies for Extractables & Leachables
Ken Wong, Deputy Director, MTech/AP&T, Sanofi Pasteur
- What data and documentation do you request from supplier?
- How do you evaluate supplier data to support the disposable qualification?
- What do you do with supplier data?
- What process or risk assessment do you perform to determine the scope of your leachable study?
- What do you do if the supplier extractables fail your assessment?
- What do you do if the leachable data fail the Safety Concern Threshold?
- Do you have a control strategy in place?
TABLE 30A The Future of Biomanufacturing: Flexible, Compact, Cost-Effective and Modular Facilities
Sadettin S. Ozturk, Ph.D., Head, Process and Analytical Development, MassBiologics
This session will focus on the future of biomanufacturing and discuss the incorporation of disposables and continuous processing to design and operation of new facilities. A panel discussion with active audience participation will outline the drivers for flexible, compact, and modular facilities and presents challenges and obstacles. The questions to be addressed are:
- Do we need to change the manufacturing platform?
- Are we all sold to switch to disposables?
- What is new in continuous processing – didn’t we try it in the 1980s?
- Is continuous downstream processing a pipedream?
TABLE 32A Open Ballroom Manufacturing – Will It Be Accepted by the Industry and Regulators?
John Knighton, MBA, Senior Director, API Large Molecule Technologies & Alliances, Janssen R&D
Open Ballroom Manufacturing has many advantages to facility design and flexibility. This concept still has some discussion points as to approach and industry/regulatory acceptance for commercial manufacturing:
- How Open is Open and what does this really mean?
- What are the validation requirements for equipment and environmental monitoring?
- What is the impact on multiproduct facilities?
- Will this approach be accepted by regulators for commercial manufacturing?
TABLE 33A Site-Specific Modification of Proteins in Display Platforms
Carrie Marshall, Research Assistant, Chemical & Biological Engineering, College of Engineering, University of Wisconsin Madison
- Strategies to chemically modify surface display proteins and antibodies, including biotinylation and click chemistry functionalization
- Methods to specifically release surface displayed proteins to generate soluble proteins
- Value of modification methods for facile integration of proteins engineered via surface display into downstream applications
TABLE 34A Post Formulation Stability Studies: Intracellular Stress Pathways in Antibody-Producing CHO Cells
Stephanie A. Davies, Postgraduate Research Student, Biosciences, The University of Kent
- The “feasibility” of using biomarkers as potential indicators of harvest day as oppose to culture viability
- The possibility of using the intracellular levels of these biomarkers as predictors of downstream antibody stability
- From the work we have done we have identified genes which are up-/down-regulated (with regards to sulture stress), so another area for discussion would be the implications of knocking these genes down in CHO cells to improve recombinant protein stability
TABLE 35A Challenges in High-Throughput Generation and Characterization of Antibody Candidates
Sebastian Schlicker, Project Manager, Biologics, Genedata USA, Inc.
- Impact on novel next-generation antibody formats (e.g., bispecifics but also ADCs)
- Specific challenges arising from cross-technology processes (e.g., phage and hybridoma, B cells)
- Integrated sample management across molecular biology, expression, purification and analytics
- Handover to downstream processes (e.g., cell line development, process development)
- Requirements for integrated workflow systems
TABLE 36A Challenges in Conjugation and Characterization of ADCs
Samadhi Vitharana, Ph.D., Senior Scientist, Core Sciences & Technology, Takeda
- Challenges in conjugating novel linker-payloads
- Strategies to efficiently optimize conjugations
- Different IgG subtypes in conjugations
- Characterization challenges with different ADC platforms/linker-payloads
TABLE 37A Techniques for Large-Scale Purification of Recombinant Proteins
Ellen Brune, Ph.D., CSO, Boston Mountain Biotech
- Resin selection methods
- Optimization of operating conditions
- How important is the initial capture step?
TABLE 38A Challenges and Opportunities in Continuous and Single-Use Downstream Processing of Pharmaceutical Proteins
Boris Napadensky, VP, Engineering, Chromatan Corporation
Value of eliminating need to do cleaning and validation in single-use systems. How does it compare to additional cost of consumables?
Realistic time to "lock-in" purification process. Is it feasible to change the purification process after clinical studies are complete?
Expectations by an end-user on E&L data from a single-use assembly vendor.
Continuous systems tend to use more buffer than batch systems. Could it become a barrier for adoption in clinical and commercial MAB manufacturing?
What is the main cost savings opportunity in MAB purification processes?
TABLE 39A Protein Purification and Recovery Technology – What’s New or Worth Exploring, and What’s Causing More Challenges than Benefits?
Yan-ping Yang, Ph.D., Director, Downstream Purification, Bioprocess Research & Development, Sanofi Pasteur
- Technology for protein purification and recovery has evolved significantly over the last 25 years
- Participants will share their experiences and learning on the various technologies/approaches in their protein purification and recovery experiments
TABLE 40A Strategies for Generation of Protein Complexes for Structural Biophysics
Ian Hunt, Ph.D., Group Leader, Protein Sciences, Novartis
- Why protein complexes?
- What expression system provides the most robust solution for protein complex formation?
- Baculovirus: co-expression vs. co-infection?
- Novel expression systems – what else?
- How to purify and characterize
- How to stabilize – crosslinking and antibodies