BPI Analytical and Quality Summit 
Event Information
Document Title
Agenda
| Pre-Conference Workshops Monday, June 2, 2008 | PRE-CONFERENCE WORKSHOPS | DAY ONE | DAY TWO | DAY THREE | | ||||
| Workshop A: The Principles and Application of Design of Experiments in Bioprocessing - A Hands-On Course | ||||
| 7:30 | Registration and Networking Coffee | |||
| 8:20 | Workshop Leader's Opening Remarks Martin Kane, MS, CRE, Senior Manager, Process Statistics, Human Genome Sciences, Inc. | |||
| 8:30 | Introduction to DOE Concepts, Steps and Analysis Design of Experiments (DOEs) are tests or series of tests in which purposeful changes are made to the input variables of a process or system so that we may observe, learn, and identify the reasons for changes in the output response(s). This extended presentation provides an introduction to design of experiments with demonstrations of how they are set up and analyzed. This is an entry point into the other talks that follow in this morning's session. Martin Kane, MS, CRE, Senior Manager, Process Statistics, Human Genome Sciences, Inc. | |||
| 9:30 | An Overview of Computer-Aided Workflow for DOE in Bioprocessing Bioprocessing projects are complex, often requiring much experimentation to learn about key process variables and to optimize settings. Modern computer hardware and software tools make the design, analysis, and exploitation of experiments in realistic settings more productive. Learn how recent developments enable you to extract more information, with more confidence and less effort. Mark Bailey, Statistical Services Specialist, SAS Institute, Inc. | |||
| 10:00 | Networking Coffee Break | |||
| 10:30 | Small Group Problem Solving Exercise Delegates will be divided into small workgroups to share input on hypothetical exercises that use the concepts presented in the earlier part of the workshop. Then, representatives of each group will share their approaches and lessons learned, allowing the audience to hear different approaches to the exercises. | |||
| 11:15 |
The physiochemical conditions used in the process development of biopharmaceutics often affect the target product's quality, formulation, and stability. A focus on the effect of physiochemical conditions on the product can result in a robust process and stable formulation. DOE screening and optimization design is an organized approach to determine the optimum process and formulation parameters of the target product with minimum time and cost. Wasfi Al-Azzam, Ph.D., Senior Process Development Scientist, Formulation and Delivery, Talecris Biotherapeutics | |||
| 11:40 |
Abstract to come. Guillermo Miroquesada, Ph.D., Senior Research Scientist, Bioprocess Research and Development, Eli Lilly and Company | |||
| 12:05 | Lunch on Your Own | |||
| Workshop B: Oligomerization and High Molecular Weight Species Determination - Understanding and Meeting Current Regulatory Requirements | ||||
| 7:30 | Registration and Networking Coffee | |||
| 8:20 | Workshop Leader's Opening Remarks Yin Luo, Ph.D. Principal Research Scientist III, Characterization & Analytical Development, Wyeth BioPharma | |||
| 8:30 | Overview of Regulatory Considerations for Product Aggregates Abstract to come. Nadine M. Ritter, Ph.D., Senior CMC Consultant, Biologics Consulting Group, Inc. | |||
| 9:00 | The Capabilities and Limitations of Analytical Ultracentrifugation in the Biopharmaceutical Drug Development Process This presentation focuses on the integration of analytical ultracentrifugation (AUC) into the biopharmaceutical development process to help accelerate the successful discovery and development of biopharmaceutical drugs. Examples that illustrate these points and highlight the capabilities and limitation of AUC analysis are presented. Steven A. Berkowitz, Ph.D., Principal Scientist, Analytical Development, Biogen Idec, Inc. | |||
| 9:30 |
Dynamic light scattering (DLS) is an established technique for biomolecule characterization. Typical applications are determining protein size and thermal stability, aggregation and solubility behavior, and screening for compound aggregates. Using high-throughput DLS, a multitude of sample conditions, such as buffer compositions, concentrations, and time and temperature stability can be screened automatically using disposable microwell plates. Case studies for protein solubility and aggregation are presented. Sigrid C. Kuebler, Ph.D., Application Scientist, Wyatt Technology Corporation | |||
| 10:00 | Networking Coffee Break | |||
| 10:30 |
Light scattering either in batch mode or in conjunction with size exclusion chromatography is widely used for determination of molar mass and size distribution. This presentation discusses capabilities and limitations of light scattering applications with emphasis on detection and quantitation of high molecular weight aggregates in protein samples. The application of light scattering for characterization of morphology of protein aggregates is presented. Ewa Folta-Stogniew, Ph.D., Director of Biophysics Resource of W.M. Keck Biotechnology Resource Laboratory, Yale University School of Medicine | |||
| 11:00 | The Use of Electrospray Differential Mobility Analysis (ES-DMA) for Aggregate Determination The presentation describes a new method to detect the degree of protein flocculation, electrospray-differential mobility analysis (ES-DMA), also known as gas-phase electrophoretic mobility molecular analysis (GEMMA). ES-DMA uses electrospray to convey proteins, protein aggregates and self-assembled protein structures into the gas phase. Differential mobility analysis then separates the proteins based on their charge-to-drag ratio, after which particles of a specific size are counted with a condensation particle counter. Leonard F. Pease III, Chemical and Materials Engineer, Process Measurements Division, National Institute of Standards and Technology | |||
| 11:30 | Panel Discussion with Workshop Speakers | |||
| 12:00 | Lunch on Your Own | |||
| Workshop C: Best Practices for Working with Contract Organizations for Analytical Support | ||||
| 7:30 | Registration and Networking Coffee | |||
| 8:20 | Workshop Leader's Opening Remarks Svetlana Bergelson, Ph.D., Principal Scientist, Analytical Development, Biogen Idec, Inc. | |||
| 8:30 | Strategies for Internal and External Assay Transfers Development of multiple protein products on shortened timelines dictates rapid assay development and transfer of the assays to internal and external testing groups. Smooth transfer of the assays becomes increasingly important to prevent delays in testing support and batch release. This presentation provides an overview of an assay transfer process and covers common challenges such as transfer timelines, instrumentation compatibility, analyst training, reagent transfer, and assay transfer documentation. Svetlana Bergelson, Ph.D., Principal Scientist, Analytical Development, Biogen Idec, Inc. | |||
| 9:00 | The Outsourcing Decision: Which Assays and Methodologies are Best to be Outsourced and Which Should be Developed Internally? The importance of analytical testing to biopharmaceutical manufacturing cannot be overemphasized. At all stages of development and production analytical results impact processing decisions and product quality. Decisions about outsourcing analytics are critical and selection of a testing facility is as important as selection of a manufacturing facility. This presentation discusses the general approach to decisions on outsourcing of testing as well as concerns on outsourcing specific methods and the potential impact on your product. Sheila G. Magil, Ph.D., Consultant, BioProcess Technology Consultants, Inc. | |||
| 9:30 | Outsourcing Analytical Activities in Support of Formulation Development to Contract Support Organizations Abstract to come. Robert Troutman, Senior Analyst, External Services, Merck & Co. | |||
| 10:00 | Networking Coffee Break | |||
| 10:30 | Enabling Strategies for Outsourcing Development Activities In the competitive pharmaceutical environment, sponsors employ outsourcing to streamline the drug development process and more rapidly progress products into the clinic. This presentation provides guidelines for the best practices to employ when selecting and working with contract development organizations to ensure successful execution of a development program. Core areas covered include general strategies for outsourcing as well as topics specifically related to outsourcing for small to mid-size biotech versus large pharma. Alex Tracy, Ph.D., Senior Director, Biopharmaceutics, KBI Biopharma | |||
| 11:00 |
Biologic-based therapeutics are typically complex molecules that require analytical techniques above and beyond those required for traditional small molecule-based therapeutics. Because of this greater complexity, significantly more characterization is required for both drug substances and drug products in Investigational New Drug Applications. This presentation provides a broad regulatory overview of the analytical techniques and characterization data required for initial clinical trials and provides some example case studies. Scott Burian, Ph.D., Associate Director of Pharmaceutical Development, Cato Research | |||
| 11:30 | Panel Discussion with Workshop Speakers | |||
| 12:00 | Lunch on Your Own | |||
| Main Conference - Day One Monday, June 2, 2008 | PRE-CONFERENCE WORKSHOPS | DAY ONE | DAY TWO | DAY THREE | | ||||
| Method Validation | ||||
| 1:20 | Chairperson's Remarks K.C. Cheng, Ph.D., MBA, Associate Director, Analytical Development, Medarex, Inc. | |||
| Keynote Presentation | ||||
| 1:30 | Interdependence of Product Characterization, Analytical Method Validation, and Comparability Assessment Development and validation of accurate and reproducible analytical methods to monitor product identity, purity, and potency and the characterization of key product variants and impurities are important responsibilities for the analytical scientist. A comprehensive knowledge of the product variants and product-related impurities is required to demonstrate product comparability upon manufacturing process change or site transfer. This presentation explores the interdependence of product characterization, method validation, and product comparability. Chulani Karunatilake, Ph.D., Director, Analytical Sciences, Amgen, Inc. | |||
| The Validation Lifecycle - Phase-Appropriate Methods and Planning | ||||
| 2:15 | Proceedings of the PDA Task Force Team for Analytical Method Validation for Commercial Products This presentation summarizes the proceedings of a task force initiative to implement a new guidance document for analytical method validation (AMV). An international team with delegates representing both industry and regulatory bodies is working on new draft for this guidance, which is sponsored by the Parenteral Drug Association (PDA). Once finalized and approved (at the end of 2008), this guidance will include all elements of best analytical method validation practices for chemical and biochemical test methods. Stephan Krause, Ph.D., Director, Quality Control, Favrille, Inc. | |||
| 2:45 |
With the recent trend of shortened development timelines for protein therapeutics, analytical support and method development must keep pace with process development, adapting to these accelerated timelines. The characterization and analytical package must provide a comprehensive assessment of product safety, efficacy and quality while being rapidly implemented. A case study illustrates the strategy Wyeth BioPharma has followed regarding analytical support and characterization of protein therapeutic candidates from pre-development to Phase I in an accelerated development environment. Thomas J. Porter, Ph.D., Director, Characterization and Analytical Development, Wyeth Biopharma | |||
| 3:15 | Networking Coffee Break, Opening of Exhibit and Poster Hall | |||
| 4:00 |
A comprehensive development, validation, and qualification program is described using an ELISA developed by AppTec as an example. In general, assay development activity typically follows a standardized approach for generating a "validation-ready" ELISA. Following the development phase, the ELISA is validated using the sponsor's test article following ICH guidelines. Additional activities are discussed, including post-validation qualifications and assay transfers. Diana M. Colleluori, Ph.D., Associate Director, Quality Control and Analytical, AppTec, Inc. | |||
| 4:30 | Development of a cIEF Method to Support Process Characterization Free-solution imaged capillary isoelectric focusing (cIEF) is a powerful tool to quantitatively monitor protein charge heterogenetity using direct detection of charged isoforms at 280nm. It offers many benefits, including high reproducibility and utility in measuring product quality attributes during process optimization. This presentation discusses cIEF assay development and validation, and the use of this assay as a tool for process development of a glycosylated recombinant therapeutic protein. Jamie Bailey, Principal Research Associate, Bioanalytical Development, Genzyme Corporation | |||
| Technology Workshop | ||||
| 5:00 |  Using Differential Scanning Calorimetry to Optimize Purification Process DevelopmentBiopharmaceutical process development can be costly and problematic. The ultimate goal is to maximize purified product by the most cost effective, reproducible and robust route. Since batch failures can have major economic consequences, a thorough understanding of protein stability throughout the development pathway, from research through clinical development to commercial manufacturing is fundamental to drug commercialization. This workshop focuses on the utility of Differential Scanning Calorimetry, a stability-indicating technique, to guide the development of purification processes. Eric L. Reese Ph.D., Director, Business Development, Biotherapeutic Products, MicroCal LLC | |||
| 5:30 | End of Day One Sessions | |||
| Biophysical Analysis | ||||
| 1:20 | Chairperson's Remarks Sandeep Kumar, Ph.D., Principal Scientist, Pharmaceutical Sciences, Pfizer Global Biologics | |||
| Keynote Presentation | ||||
| 1:30 | New Methods for Characterization of Protein Aggregation The talk presents protein case studies and newly developed analytical methods to analyze protein aggregation in formulations in conditions as near as possible to those in which the drug is applied in vivo. These "tailor-made" analytical methods are adapted to the necessities of the protein formulation rather than to the needs of the analytical techniques. Tudor Arvinte, Ph.D., Professor, Department of Pharmaceutics and. Biopharmaceutics, School of Pharmacy, University of Geneva, Switzerland | |||
| Problem Solving Using Biophysical Analysis | ||||
| 2:15 | The Practical Application of DSC for Preformulation and Characterization Studies Abstract to come. Alex Tracy, Ph.D., Director, Biopharmaceutical Development, KBI Biopharma | |||
| 2:45 | Biophysical Characterization of Therapeutic Proteins Liquid biotech formulations are currently of great interest. Protein aggregation represents one of the key hurdles in formulation development and its mechanisms are often not fully understood. This presentation describes approaches to characterize therapeutic protein drugs in terms of biophysical properties (e.g. surface charge, self-association). Potential implications for aggregation and formulation development are discussed. Stefan Fischer, Ph.D., Research Scientist, Formulation R&D Biologics, F. Hoffmann-La Roche Ltd., Switzerland | |||
| 3:15 | Networking Coffee Break, Opening of Exhibit and Poster Hall | |||
| 4:00 |
Product variants of a recombinant IgG have been identified, including: pyroglutamate formation at the N-termini of light chain, removal of heavy chain C-terminal lysine, and cleavage of heavy chain. Characterization of these variants as "Product-Related Substances" (properties comparable to those of the desired product with respect to activity, efficacy, and safety) or Product-Related Impurities (properties comparable to those of the desired product with respect to activity, efficacy, and safety) are discussed. Mark D. Moody, Ph.D., Senior Director, Quality Control and Formulation, Merrimack Pharmaceuticals | |||
| 4:30 | The Application of Nanodrop Technology in the Analysis of Therapeutic Protein Concentration - A Comparative Study The process development and manufacturing of therapeutic Biopharmaceuticals requires continuous assessment of product concentration. Standard UV spectrophotometers are used which have limited dynamic range and thus require sample dilution prior to measurement. NanoDrop technology was most useful in generating protein concentration rapidly relative to the standard bench top spectrophotometer. Nanodrop data were compared with empirical data and those generated using standard spectrometer technique. The study demonstrated the capability, potential and limitations of Nanodrop. Nesredin A Mussa Ph.D., Analytical Development Lead, Manufacturing Technical Services, Lonza Biologics | |||
| Technology Workshop | ||||
| 5:00 | Using Differential Scanning Calorimetry to Optimize Purification Process Development Biopharmaceutical process development can be costly and problematic. The ultimate goal is to maximize purified product by the most cost effective, reproducible and robust route. Since batch failures can have major economic consequences, a thorough understanding of protein stability throughout the development pathway, from research through clinical development to commercial manufacturing is fundamental to drug commercialization. This workshop focuses on the utility of Differential Scanning Calorimetry, a stability-indicating technique, to guide the development of purification processes. Eric L. Reese Ph.D., Director, Business Development, Biotherapeutic Products, MicroCal LLC | |||
| 5:30 | End of Day One Sessions | |||
| Process Characterization | ||||
| 1:20 | Chairperson's Remarks Sheila G. Magil, Ph.D., Consultant, BioProcess Technology Consultants, Inc. | |||
| Keynote Presentation | ||||
| 1:30 | Quality by Design in Biotechnology: Why and How? The development of a stable, capable and commercially viable biotechnology process requires careful long-term planning and integration of key activities throughout all stages of product cycle development. Decisions that are made early on in clinical development in terms of molecule selection, understanding of critical quality attributes, and process development along with clinical manufacturing can have significant impact on the commercial process capability and product profile definition. The role and approaches that QbD can play in enabling an integrated development program are discussed. Gail Burnett, Ph.D., Senior Director of Quality Bioanalytical Development, Genentech, Inc. | |||
| Automation and Platforming of Process Development and Control | ||||
| 2:15 | High Throughput Methods for Accelerating Bioprocess Development Abstract to come. Judy Chou, Ph.D., Group Leader, Oceanside Process Research and Development, Genentech, Inc. | |||
| 2:45 |
Cell culture development of an antibody entails evaluation and optimization of process parameters that allow the identification of critical parameters impacting product quality. A case study involving antibody cell line development using XOMA's proprietary CHO expression system and cell culture process is presented showing the investigation of changes to antibody characteristics as a function of process parameter variations in scale up, temperature, base addition, seeding, feeds, medium modification and production cell days. Abdul Wajid, Ph.D., Senior Director, Process Sciences, XOMA (US) LLC | |||
| 3:15 | Networking Coffee Break, Opening of Exhibit and Poster Hall | |||
| 4:00 |
Techniques for miniaturizing purification processes can accelerate development by enabling parallel experimentation and automation. Two examples are shown illustrating their use in bioprocess development. In the first example, a multi-step chromatographic purification was used to define fermentation process performance. In the second example, the operating boundaries for the ion-exchange chromatography of a monoclonal antibody were defined. Marc Wenger, Senior Research Biochemist, Merck & Co., Inc. | |||
| 4:30 | Determining Design Requirements for Tailored Automated Autologous Vaccine Production to Achieve Marketable Costs The commercial viability of single patient tailored therapeutic products are strongly affected by processing costs. Autologous vaccine therapies employ patient-derived specific materials. Therefore, the design requirements for the system and practical strategies employed to meet them are critical. A case study describing the process of evaluating and selecting a novel unit operation employing single-use devices demonstrates the opportunities that technology creates while addressing the clinical process needs. Ian Fitzpatrick M.Eng.Sci, Manager Manufacturing Innovation, Invetech, Pty. | |||
| Technology Workshop | ||||
| 5:00 | Using Differential Scanning Calorimetry to Optimize Purification Process Development Biopharmaceutical process development can be costly and problematic. The ultimate goal is to maximize purified product by the most cost effective, reproducible and robust route. Since batch failures can have major economic consequences, a thorough understanding of protein stability throughout the development pathway, from research through clinical development to commercial manufacturing is fundamental to drug commercialization. This workshop focuses on the utility of Differential Scanning Calorimetry, a stability-indicating technique, to guide the development of purification processes. Eric L. Reese Ph.D., Director, Business Development, Biotherapeutic Products, MicroCal LLC | |||
| 5:30 | End of Day One Sessions | |||
| Main Conference - Day Two Tuesday, June 3, 2008 | PRE-CONFERENCE WORKSHOPS | DAY ONE | DAY TWO | DAY THREE | | ||||
| 7:30 | Networking Coffee in Exhibit Hall | |||
| Method Validation | ||||
| 8:10 | Chairperson's Remarks Stephan Krause, Ph.D., Director, Quality Control, Favrille, Inc. | |||
| Keynote Presentation | ||||
| 8:15 | Applying Quality by Design Principles to Assay Development and Validation Abstract to come. Dieter Schmalzing, Ph.D., Associate Director, Genentech, Inc. | |||
| Problem-Solving Case Studies | ||||
| 9:00 | Implementation and Qualification of Platform Methods for Release Testing of Clinical Drug Substance and Drug Product The accelerated pace of new protein therapeutics entering first-in-man trials have necessitated streamlining of drug development, including assay transfer and qualification. A set of methods has been developed that can be applied without further development to new products. Additionally, a standard set of procedures has been developed to transfer and qualify those methods. Robert Kitchen, Senior Research Scientist II, Wyeth BioPharma | |||
| 9:30 | Analytical Validation of a Carbohydrate Profiling Method for a Monoclonal Antibody by Capillary Electrophoresis: Lessons Learned Due to the complexity of the CE carbohydrate profiling method, there exists significant challenges in performing a comprehensive analytical validation study. This presentation focuses on practical considerations on design of relevant experiments, selection of appropriate acceptance criteria, and the interpretation of validation data. The regulatory perspectives and lessons learned during the method validation are also discussed. Suhe Chen, Ph.D., Section Head, Analytical Development, Human Genome Sciences, Inc. | |||
| 10:00 | Networking Refreshments, Exhibit and Poster Viewing | |||
| 10:45 | Design and Implementation of an Improved Analytical Method Transfer Process Failed analytical method transfers consume time, resources and money resulting from rework activities and can significantly delay project timelines, release of material and regulatory submissions. In order to assure successful transfers and sustainable performance of analytical methodology in a QCL environment, we have undertaken a comprehensive root cause analysis for failed method transfers. This presentation describes a new process designed to ensure successful installation of analytical methodology. Sarah Demmon, Research Scientist, Bioproduct Pharmaceutical Development, Eli Lilly and Company | |||
| New Regulatory Requirements for Method Validation | ||||
| 11:15 | Validation of Peptide Maps - A New Challenge Having a better understanding of antibodies is not only to fulfill the regulatory requirements, but also provides better quality control of drugs before they are given to patients. Among analytical assays, the peptide map serves as a unique way to answer many questions related to quality and stability issues. However, it is a challenge to validate this method. Some experiences are shared in this talk in validating this assay during early and late phases of drug development. K.C. Cheng, Ph.D., MBA, Associate Director, Analytical Development, Medarex, Inc. | |||
| 11:45 | Networking Luncheon, Exhibit and Poster Viewing | |||
| 1:10 | Chairperson's Remarks Dieter Schmalzing, Ph.D., Associate Director, Genentech, Inc. | |||
| Bioassay Development and Validation | ||||
| 1:15 |
The application of Design of Experiments (DOE) as a practical tool in developing and validating bioassays is demonstrated in this case study. For example, the use of DOE to evaluate method robustness during pre-validation experiments is useful when developing the validation protocol and establishing acceptance criteria. David J. Cirelli, Scientist II, Wyeth BioPharma | |||
| 1:45 | Challenges in the Transfer of Potency Methods The transfer of potency methods to production sites, partners, or to contract manufacturing organizations (CMOs) can be particularly challenging due to the reliance of these methods on analyst technique, critical equipment and/or reagents and the use of cell cultures. This presentation discusses the challenges and lessons learned from the transfer process. Max Tejada. Ph.D., Scientist, Biological Technologies, Genentech, Inc. | |||
| 2:15 | One Statistician's View of Effective Ways to Satisfy the Forthcoming New USP Guidelines on Bioassay Validation Abstract to come. David Lansky, Ph.D., President, Precision Bioassay | |||
| 2:45 | Networking Refreshments, Last Chance for Exhibit and Poster Viewing | |||
| Analytical Method Transfers | ||||
| 3:30 |
Pre-defined action and contingency plans are essential to the successful intra or inter corporate transfer of bioassay methods Two examples of processes developed for bioassay method transfer are presented. The first is a titer assay transferred to a CMO for the development and scale-up of a pre-IND bioreactor production process. The second example is the transfer of a qualified cell-based potency bioassay from development to Quality Control for lot release and ongoing stability testing. Brian Lentrichia, Ph.D., Associate Director, Shire Human Genetic Therapies | |||
| 4:00 |
Cell-based bioassays are complex analytical methods with multiple factors contributing to the results. Validation of such complex assays is thus not a trivial exercise. The validation protocol should contain parameters and acceptance criteria which have been derived both from a bioassay and a statistical perspective. We present here a case study for bioassay validation for Protein X and subsequent method transfer to a global site. Anindita Sen, Ph.D., Senior Research Scientist, Eli Lilly and Company | |||
| 4:30 | End of Day Two Sessions | |||
| Biophysical Analysis | ||||
| 8:10 | Chairperson's Remarks Sathish Hasige, Ph.D., Scientist II, Formulation Development, Process Biochemistry, MedImmune, Inc. | |||
| Keynote Presentation | ||||
| 8:15 | The Application of Novel Biophysical Methods for Drug Development Biophysical methods have been widely used in the process of drug development in biotech industry. These methods have provided critical product information about structure, function, quality and impurity. This presentation provides an overview of recent progress in biophysical methods, in particular, a focus on analytical ultracentrifugation, field flow fractionation and image based methods. Examples are presented to address the issues of implementing these methods for product analysis and characterization. Jun Liu, Ph.D., Senior Scientist, Genentech, Inc. | |||
| Characterization of High Concentration Protein Products | ||||
| 9:00 |
Understanding opalescence requires characterization of non-covalent interactions that occur at high protein concentrations. In most cases, the results obtained from analysis at low concentration cannot be extrapolated to high concentrations, especially when reversible self associating systems are involved. This presentation discusses techniques such as viscometry, membrane osmometry and light scattering to measure colloidal properties of a therapeutic mAb in the 1-100 g/L concentration range to understand opalescence in an IgG1 antibody. Sathish Hasige Ph.D., Scientist II, Formulation Development, Process Biochemistry, MedImmune, Inc. | |||
| 9:30 | Protein Interactions at High Concentrations Studied by Small Angle X-ray Scattering and Rheometry Highly viscous protein formulations pose challenges in manufacturing, reconstitution, and drug delivery. Using small angle x-ray scattering and rheometry, we have studied the intermolecular interaction in high concentration protein formulations. The strength and the site of intermolecular interactions that give rise to increased viscosity were determined. The impact of excipients on intermolecular interactions and thus on solution viscosity is discussed. Sonoko Kanai, Ph.D., Post Doctoral Research Fellow, Late Stage Pharmaceutical Device and Development, Genentech, Inc. | |||
| 10:00 | Networking Refreshments, Exhibit and Poster Viewing | |||
| Computational Characterization | ||||
| 10:45 | Identification of Potential Markers for Physical and Chemical Instabilities in Biologics Using Sequence and Structure Information Biologics can degrade in several ways. Using the available sequence and structural information on biologics, one can make educated guesses about their degradation pathways. This information may be used by early formulation development teams to assess the complexity of the task ahead. This talk is delivered with the help of two examples of intact antibodies whose crystal structures are publicly available from the protein data bank (PDB). Sandeep Kumar, Ph.D., Principal Scientist, Pharmaceutical Sciences, Pfizer Global Biologics | |||
| 11:15 | Rational Design of Proteins with Increased Stability Using Computational Biophysics We developed a computational approach that allows engineering proteins with enhanced stability by rational redesign of protein surface. An outline of the design protocol and rationale is presented. In addition, several examples providing experimental validation for these protein design approaches are given. George Makhatadze, Ph.D., Professor, Rensselaer Polytechnic Institute | |||
| 11:45 | Networking Luncheon, Exhibit and Poster Viewing | |||
| 1:10 | Chairperson's Remarks Dingjiang Liu, Ph.D., Principal Scientist, Department of Protein Formulation, Amgen, Inc. | |||
| Biophysical Analysis in Formulation Development | ||||
| 1:15 | Stability and Structure Changes as a Consequence of Methionine Oxidation of IgG1 Fc Region To gain an understanding of the effect of methionine oxidation on the structure and stability of the human IgG1 Fc, we characterized the fully oxidized Fc using biophysical and bioanalytical methods. Results showed the methionine oxidation resulted in changes in the structure and stability of the Fc. These findings are directly applicable to Fc containing protein therapeutics such as MAbs and Fc-fusion proteins; therefore it is critical to monitor and control methionine oxidation during manufacturing and storage. Dingjiang Liu, Ph.D., Principal Scientist, Department of Protein Formulation, Amgen, Inc. | |||
| 1:45 |
Throughout MAb development, a knowledge base is assembled that describes the physical-chemical properties of the protein molecule. One key aspect of this is building an understanding of the primary degradation pathways including fragmentation and aggregation. A case study demonstrates how results achieved using PAGE and SEC can be extended by incorporation of Capillary Electrophoresis and Sedimentation Velocity analysis. Results obtained with different monoclonal antibodies are compared and contrasted. W. Blaine Stine Ph.D., Associate Research Investigator, Protein Analytics, Abbott Bioresearch Center | |||
| 2:15 | The Diversity in Structure, Function and Mechanisms of Aggregates in Therapeutic Monoclonal Antibodies and Fc Fusion Proteins The structures and functions of HMW species from monoclonal antibodies and Fc fusion proteins have been characterized using biochemical and biophysical methodologies. The mechanisms of aggregation include covalent bonding, reversible self-association, and stable domain exchange. The impact of these aggregation forms on the antigen/ligand-binding and the FcγR-binding are discussed. Yin Luo, Ph.D., Principal Research Scientist III, Characterization & Analytical Development, Wyeth BioPharma | |||
| 2:45 | Networking Refreshments, Last Chance for Exhibit and Poster Viewing | |||
| Evaluating the Stability of Macromolecules | ||||
| 3:30 | Investigation of Therapeutic Protein Instabilities at Low Temperatures Proteins can exhibit markedly different solution behavior and degradation products under refrigerated storage condition than those predicted by accelerated stability studies done at elevated temperatures. This talk focuses on how biophysical analyses, particularly spectroscopy and thermodynamics, can be used to investigate and address potential protein instability at low temperature and its relation to real-time refrigerated stability studies. Rob Simler, Ph.D., Staff Scientist, BioFormulations Development, Genzyme Corporation | |||
| 4:00 | Differential Scanning Calorimetry (DSC) to Evaluate Molecular Stability of Biologics Apart from the midpoint transition temperature (Tm), energetics obtained from DSC (changes in enthalpy, entropy and heat capacity) for biologics that undergo reversible transitions can provide useful information about conformation, cooperativity, and molecular association. DSC is also being widely used to monitor the structural states of nucleic acids. Particular emphasis is given to dissect the energetics associated with non-reversible systems, distinguishing the independent domain transitions, and the thermodynamics of DNA transition and unfolding. Sandeep Kumar, Ph.D., Principal Scientist, Pharmaceutical Sciences, Pfizer Global Biologics | |||
| 4:30 | End of Day Two Sessions | |||
| Process Characterization | ||||
| 8:10 | Chairperson's Remarks Hanne Bak, Ph.D., Staff Engineer, Purification Development, Regeneron Pharmaceuticals | |||
| Keynote Presentation | ||||
| 8:15 | Application of QbD for Development and Manufacturing of a BioPharamaceutical Quality by Design is an important initiative in the biotechnology industry which is intended to provide a thorough understanding of the molecule and the process. This presentation addresses the various components of QbD such as design space, process analytical technology (PAT), definition of critical product attributes, etc. In addition, methods developed for screening of raw materials are also discussed. Rohin Mhatre, Ph.D., Director, Bioprocess Development, Biogen Idec, Inc. | |||
| Process Characterization and Control Recovery and Purification | ||||
| 9:00 |
Solid liquid separation or clarification is the first step in the purification of biological molecules. The clarification is often performed by disc stack centrifugation followed by depth filtration, or depth filtration alone. This case study describes what happened when changing to depth filtration only, and how traditional means of evaluating filtrate clarity does not always describe what you get. Hanne Bak, Ph.D., Staff Engineer, Purification Development, Regeneron Pharmaceuticals | |||
| 9:30 | Obtaining a Constant Product by Applying a Physical Model to an Enzymatic Reaction Step In situations where the starting material of a process step inevitably has a certain variance, a fixed process will yield a varying product. In order to produce a constant product, the process can be varied according to the starting material using a physical / mathematical model combined with at-line analysis, which describes the reaction. This provides a powerful tool for predicting performance and understanding the process. Janus Krarup, MSc, Principal Scientist, Novo Nordisk A/S, Denmark | |||
| 10:00 | Networking Refreshments, Exhibit and Poster Viewing | |||
| Process Characterization and Control Formulation and Fill/Finish | ||||
| 10:45 | Impact of the Fill-Finish Process on Protein Degradation and Shelf Life Implications An important consideration in the development of a protein therapeutic is an evaluation of the impact of processing conditions on chemical, physical, and long-term stability. Fill-finish processes may cause protein degradation due to a variety of external factors. This presentation describes various examples of characterization studies aimed to understand the impact of formulation and processing conditions on protein degradation and relation to overall product shelf life. Angela W. Blake-Haskins, Ph.D., Senior Scientist I, Drug Product Sciences, Human Genome Sciences, Inc. | |||
| 11:15 |
Abstract to come. Adrienne L. Williams, Manager, Biotech Technical Group, West Pharmaceutical Services | |||
| 11:45 | Networking Luncheon, Exhibit and Poster Viewing | |||
| 1:10 | Chairperson's Remarks Itzcoatl A. Pla, Ph.D., Associate Research Investigator, Abbott Bioresearch Center | |||
| Process Characterization and Control Cell Culture and Fermentation | ||||
| 1:15 |
Abstract to come. Itzcoatl A. Pla, Ph.D., Associate Research Investigator, Abbott Bioresearch Center | |||
| 1:45 | Development and Characterization of High-Density Batch, Fed-Batch, and XDTM Production Processes using the PER.C6® Human Cell Line This talk focuses on recent advances in the development of three different platform cell culture processes for the production of monoclonal antibody using the PER.C6® human cell line. Using mostly off-the-shelf commercial media and additives, final titers of approximately 2 g/L, 6 g/L, and 13 g/L have been demonstrated in batch, fed-batch and XDTM processes, respectively. A comparison of these three platform processes with respect to operation and control characteristics is presented. John H. Chon, Ph.D., Director, Upstream Process Development, Percivia | |||
| Data Management | ||||
| 2:15 | Advanced Chemometric Tools - From Data to Knowledge to Increasing Process Understanding and Control Key to understanding the underlying rationale and design of a manufacturing processes is that the 'design' transferred to manufacturing should be demonstrably 'fit' for its intended use. The availability, quality and validity of process development data from early process definition through to formal process characterization studies and ultimately from commercial production are crucial. This presentation reviews how advanced chemometric methods are successfully exploited to aid process development and increase process understanding and control. Bo Kara, Director, Science and Technology, Avecia Biologics Ltd., United Kingdom | |||
| 2:45 | Process Characterization and Control Session Ends for the Day; Networking Refreshments, Last Chance for Exhibit and Poster Viewing | |||
| Main Conference - Day Three Wednesday, June 4, 2008 | PRE-CONFERENCE WORKSHOPS | DAY ONE | DAY TWO | DAY THREE | | ||||
| Method Validation | ||||
| Biophysical Analysis | ||||
| Case Studies of Advanced Analytical Methods | ||||
| 8:20 | Chairperson's Remarks Stephen Raso, Ph.D., Principal Research Scientist, Analytical Biochemistry and Biophysics, Wyeth BioPharma | |||
| 8:30 |
Abstract to come. Stephen Raso, Ph.D., Principal Research Scientist, Analytical Biochemistry and Biophysics, Wyeth BioPharma | |||
| 9:00 | Models for a Priori Identification of Proteotypic Mass Spectrometry Peptides and Proteins The standard approach to identifying peptides based on high resolution mass spectrometry compares mass and elution time to a database of peptides. These models of peptide identification assume that peptides and proteins are equally likely to be identified. However, significant improvements, in respect to computation and accuracy, can be achieved by searching for only peptides/proteins that are detectable (proteotypic) by high resolution mass spectrometry. Bobbie-Jo Webb-Robertson, Ph.D., Senior Research Scientist, Pacific Northwest National Laboratory | |||
| Characterization of Complex Biologics | ||||
| 9:30 | Characterization of Protein Conjugates Analysis and formulation of protein conjugates is challenging due to the effect of the small molecule that is linked to the protein. Additional modes of degradation (relative to recombinant proteins) attributable to the small molecule and the conjugate as a whole also need to be monitored. This presentation highlights the unique challenges associated with this emerging class of product and the approaches to overcome these challenges. Rajesh Krishnamurthy, Ph.D., Director, Analytical and Pharmaceutical Sciences, ImmunoGen, Inc. | |||
| 10:00 | Networking Refreshment Break | |||
| 10:30 | Characterization of a Fc Fusion Protein and its Degradants by LC/MS Fc fusion proteins are composed of the Fc fragment from a human IgG1 antibody and two active proteins attached to the terminus of the Fc. The degradation products of a Fc fusion protein have been identified and quantified at intact, limited proteolysis, and peptide mapping levels using various LC/MS techniques. Da Ren, Ph.D., Senior Scientist, Department of Pharmaceutics, Amgen, Inc. | |||
| 11:00 | Modes of Action of HuMax-EGFr (mAb 2F8, zalutumumab) Zalutumumab (HuMax-EGFr), a human IgG1 antibody targeting the Epidermal Growth Factor receptor (EGFr), was found to have two mechanisms of action in cancer therapy. First, it blocks tumor growth by arresting EGFr in an inactive conformation which results in inhibition of signaling. Second, at relatively low dose, potent antitumor effects were observed in mice, which are likely based on the engagement of immune effector mechanisms, in particular ADCC. Jeroen Lammerts van Bueren, Ph.D., Scientist, Research & Technology, Genmab B.V., The Netherlands | |||
| 11:30 | Track Ends; Process Characterization and Control Session Continues | |||
| 12:00 | End of Conference | |||
| Process Characterization | ||||
| 8:20 | Chairperson's Remarks Cenk Undey, Ph.D., Principal Engineer, Process Development, Process and Systems Analysis, Amgen, Inc. | |||
| Developing Design Space and Control Space | ||||
| 8:30 | Are We There Yet? An Industrial Perspective of Evolution from Postmortem Data Analysis towards Real-Time Multivariate Monitoring and Control of Biologics Manufacturing Processes Batch biopharmaceutical processes that are typically comprised of a series of unit procedures operated in batch mode to produce therapeutic proteins have complex reaction mechanisms and non-linear, time-variant process dynamics that make their modeling, monitoring and control challenging. Multivariate methods provide very efficient means of analyzing abundant and complex data generated by these processes as well as helping to set up very effective means of monitoring and control. This presentation covers the current state-of-the-art, provides real-world examples and summarizes potential future directions. Cenk Undey, Ph.D., Principal Engineer, Process Development, Process and Systems Analysis, Amgen, Inc. | |||
| 9:00 |
Typically, quality specifications are set by statistical descriptors from clinical lots. For example, standard deviations or ranges provide a basis for setting specification limits. This method is only appropriate when a quality space can be described by a convex-like space. The interactions among parameters often violate this assumption. This presentation provides a case study to demonstrate this deficiency and how to overcome it. Mike Su, Ph.D., Manager, BioPharma Technology Group, Bayer Corporate and Business Services LLC | |||
| 9:30 |
Stryker Biotech's OP-1® Implant is a combination product regulated by the FDA's CDRH division. Within the Office of Compliance, renewed emphasis is being placed on statistical evaluation of process validation data to demonstrate that a process is capable of producing the desired product. This case study demonstrates how this assurance was provided post validation by additional analysis of existing data. Margaret Worden, Director of Manufacturing Sciences, Stryker Biotech | |||
| 10:00 | Networking Refreshment Break | |||
| Case Studies of Process Characterization and Control | ||||
| 10:30 |
Biogen Idec has been using MSPC (Multivariate Statistical Process Control) systems for commercial campaigns for past several years. This case study summarizes the challenges and benefits that were faced, and the pro and cons of the system implementation. In addition, the presentation describes how the system is integrated with the existing deviation, batch record and process validation systems, among others. Seongkyu Yoon, Ph.D., Manager, Manufacturing Sciences, Biogen Idec, Inc. | |||
| 11:00 | Applying Structural and Stability Information in the Development of Protein Manufacturing Processes: A Biophysical Approach At Diosynth, we have the privilege of developing comprehensive manufacturing processes for a variety of protein molecules that have distinct structural and stability characteristics. During process development, biophysical assays, such as dynamic light scattering, calorimetry, circular dichroism and fluorescence are routinely used to gain understanding of the effects of process variables on protein stability. This presentation reviews several case studies highlighting the utility of these methods in the development of robust and cost-effective manufacturing strategies. Katherine E. Bowers, Ph.D., Scientist II, Analytical and Formulation Development, Diosynth Biotechnology, a part of Schering-Plough | |||
| 11:30 |
At ImmunoGen, we develop anticancer therapeutics consisting of a potent cell killing agent (derivative of maytansine) conjugated to a tumor-targeting antibody. The process for immunoconjugate production is key to ensure critical and key product quality attributes are met. Here we present a case study on process development and control, aiming for a robust process that achieves essential product quality. Yong Wang, Ph.D., Scientist, Process Science & Engineering, ImmunoGen, Inc. | |||
| 12:00 | End of Conference | |||
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