Formulation Strategies for Protein Therapeutics
Event Information
Document Title
Agenda
| Pre-Conference Workshop Tuesday, September 23, 2008 | PRE-CONFERENCE WORKSHOP | DAY ONE | DAY TWO | DAY THREE | | ||||||
| Developing Formulations for Pre-Filled Syringe-Based Products - From Early Development to Commercialization | ||||||
| 7:30 | Registration and Networking Coffee | |||||
| 8:20 | Chairperson's Opening Remarks Thomas M. Spitznagel, Ph.D., Executive Director, Pharmaceutical Sciences and Global Project Management, Human Genome Sciences, Inc. | |||||
| 8:30 | Integration of Key Milestones and Deliverables for a Pre-Filled Syringe or Device Development Project into a Global Project Timeline Developing a dosage form that includes either a pre-filled syringe or a delivery device requires careful integration into the overall program timeline. This talk highlights the key milestones that are needed to ensure a smooth integration of the development activities into the clinical and regulatory timelines. Examples from both early and late-stage programs are used to illustrate the critical hurdles as a program moves from clinical to commercialization. Thomas M. Spitznagel, Ph.D., Executive Director, Pharmaceutical Sciences and Global Project Management, Human Genome Sciences, Inc. | |||||
| 9:00 |
Determining the compatibility between the drug product and the pre-filled syringe system should be evaluated early in development. Extractables and leachables is an important part of these early development and compatibility studies. The presentation includes: a) a screening study with different pre-filled syringes and buffer systems; b) a leachables study for a protein product packaged in pre-filled syringe; and c) a leachables study for a biosimilar packaged in a pre-filled nozzle. Jennifer L. Riter, Director, Analytical and Technical Services, West Pharmaceutical Services | |||||
| 9:30 |
Rapid growth and increased competition in the biotechnology industry are driving the need to differentiate among products. One way to differentiate is to improve drug delivery by automating the delivery of injectable drugs. Product presentation forms, evolving from vial to pre-filled syringe then to pre-filled syringe in an auto-injector, is a response to a competitive marketplace. Adding a device component to a drug product poses many development, quality and regulatory challenges. There are operational and commercial issues related to launching the injectable combination products. Some of these issues are discussed in this presentation. Robin Hwang, Ph.D., Scientific Director, Amgen | |||||
| 10:00 | Networking Refreshment Break | |||||
| 10:30 | Commercialization Challenges for Pre-filled Syringe Products Demand for pre-filled syringe products is expected to increase in the foreseeable future. This talk focuses on challenges related to ensuring successful scale-up and commercialization of pre-filled syringe products. The presentation also discusses timing of key development activities and experience related to late stage development. Strategies recently employed during the development of vaccine products are included. David J. Geer, Ph.D., Senior Development Engineer, Sterile and Liquids Commercialization, Merck and Co., Inc. | |||||
| 11:00 |
Abstract to come. Carl "Charlie" Hitscherich Jr., Ph.D., Senior Manager, Biogen Idec | |||||
| 11:30 | Regulatory Considerations in Formulation Development for Syringes Abstract to come. Dov H. Pluznik, Ph.D., Microbiologist, Division of Therapeutic Proteins, United States Food and Drug Administration | |||||
| 12:00 | Workshop Ends; Lunch on Your Own | |||||
| Main Conference - Day One Tuesday, September 23, 2008 | PRE-CONFERENCE WORKSHOP | DAY ONE | DAY TWO | DAY THREE | | ||||||
| 1:20 | Chairperson's Opening Remarks Steven Bishop, Ph.D., Associate Director, Formulation Sciences, MedImmune, Inc. | |||||
| Keynote Presentation | ||||||
| 1:30 | Integrating Market Drivers in Drug Product Development and Lifecycle Management With the emerging importance of protein therapeutics in the healthcare marketplace, the role of commercial positioning during drug development has become increasingly critical. Throughout the lifecycle of a given protein therapeutic, understanding how and when to implement formulation or configurational changes is difficult. Strategic incorporation of commercial drivers throughout clinical formulation development, along with a rational approach to product improvements beyond launch, should be the foundation of a robust product lifecycle. Anthony B. Barry, Ph.D., Principal Research Scientist, Drug Product Development, Wyeth BioPharma | |||||
| Measuring and Predicting Protein Aggregation | ||||||
| 2:15 |
Proteins are subjected to a large number of processes that could impact their stability. Purification, viral inactivation, diafiltration/concentration, and lyophilization can all lead to protein degradation during both development and scale-up. Multi-angle laser light scattering in-line with size exclusion chromatography was used to better characterize the nature of a large oligomer that appeared during the scale-up of a tangential flow filtration (TFF) step for a monoclonal antibody. Nicholas Guziewicz, Senior Research Associate, Genzyme Corporation | |||||
| 2:45 | The Impact of Excipient Selection on Aggregation Abstract to come. Tom Leach, Ph.D., Scientist II, Process Biochemistry & Formulation Sciences, MedImmune, Inc. | |||||
| 3:15 | Growth of Glucagon Fibrils of Different Morphologies Many aspects of protein degradation by fibrillation remain poorly understood. We present data on the concentration dependence of glucagon fibrillation. Glucagon fibrils formed at low concentration are coiled when visualized by electron microscopy, while high concentration gives straight fibrils. Cross-seeding experiments clarify this difference, by showing that the coiled fibrils are unable to grow at high peptide concentrations. Microstructural investigations indicate that the distinct morphologies also have different arrangements of the peptides within the fibrils. Christian Rischel, Ph.D., Senior Scientist, Protein Structure and Biophysics, Novo Nordisk A/S, Denmark | |||||
| 3:45 | Networking Refreshment Break | |||||
| Improving the Stability of Protein Therapeutics | ||||||
| 4:15 |
Protein molecules can be very difficult to formulate as stable therapeutics, especially in a ready-to-use liquid dosage form. This presentation uses a case study to highlight the issues faced during protein formulation and some approaches to mitigate them. Advait Badkar, Ph.D., Group Leader & Principal Scientist, Pharmaceutical R&D, Global Biologics, Pfizer Inc | |||||
| 4:45 |
In this study, forced degradation studies or stress testing was performed on a monoclonal antibody (mAb) to challenge the capability and suitability of the stability-indicating methods. The selection of the specific stress conditions was based on preformulation, manufacturing and stability data. Analysis of the stressed samples confirmed that the proposed stability-indicating methods were able to detect stress-induced degradation products in the samples. Jesper Davidsen, Ph.D., Formulation Manager, Genmab A/S, The Netherlands | |||||
| Technology Workshop | ||||||
| 5:15 |
Among biopharmaceutical companies, there is considerable divergence in the extent of accelerated stability data deemed appropriate to support formulation development during preclinical and phase 1 clinical development. There are obvious considerations for development timelines/milestones and the resources required for such studies, as well as debate around the predictive value of accelerated stability for protein therapeutics. This case study compares conservative and aggressive approaches utilized with different proteins to illustrate the advantages and disadvantages of each. Tim Kelly, Ph.D., Vice President, Biopharmaceutical Development, KBI Biopharma, Inc. | |||||
| 5:45 | Networking Cocktail Reception; Opening of BioProcess International™ Exhibit and Poster Hall Sponsored by  | |||||
| Main Conference - Day Two Wednesday, September 24, 2008 | PRE-CONFERENCE WORKSHOP | DAY ONE | DAY TWO | DAY THREE | | ||||||
| 7:30 | Networking Coffee | |||||
| 8:00 | Chairperson's Opening Remarks Siddharth J. Advant, Ph.D., Principal & Head, West Coast Office, Tunnell Consulting | |||||
| Applying Quality by Design to Formulation and Process Development | ||||||
| Keynote Presentation | ||||||
| 8:05 | Identifying Critical Product Attributes and Developing the Design Space for Protein Formulations The current trend towards applying the principles of Quality by Design to therapeutic proteins is influencing the way lead drug candidates are selected and how formulations are developed. Considerations are now being given to stability and manufacturability of protein drug candidates as they are engineered within discovery research and the scope of formulation development now includes studies to understand design space. Although all of the pieces are not yet in place to fully execute Quality by Design, some progress has been made in many of the related areas. Joseph Phillips, Ph.D., Executive Director, Formulation and Analytical Development, Amgen | |||||
| Panel Discussion | ||||||
| 8:45 | The QbD Pioneers: Perspectives from Companies that have Implemented Quality by Design Concepts in Formulation Development
Panelists: David J. Geer, Ph.D., Senior Development Engineer, Sterile and Liquids Commercialization, Merck and Co., Inc.; Angela Kantor, Principal Research Scientist II, Protein Formulation Development, Wyeth Biopharma; Carol F. Kirchhoff, Ph.D., Senior Principal Scientist, Pfizer, Inc.; Niles Ron, Ph.D., MBA, Associate Director, Formulation and Fill-Finish, Seattle Genetics, Inc.; Ping Yeh, Ph.D., Director, Protein Pharmaceutical Development, Biogen Idec, Inc. | |||||
| 9:45 | Networking Refreshment Break in BioProcess International™ Exhibit and Poster Hall | |||||
| Advancing Formulation Development for High Concentration Protein Products | ||||||
| 10:30 |
Apparent solubilities of mAbs were measured using a PEG precipitation method. The response of the apparent solubility to changes in conditions such as pH, temperature, salt and sucrose was well within expectation of empirical observations. The method has been demonstrated in application to high throughput screening to achieve high efficiency and reduce the amount of protein required for solubility studies. This approach may be useful in detecting protein candidates with potentially difficult solubility characteristics for developing high protein concentration formulations. Li Li, Ph.D., Senior Research Scientist II, Wyeth BioPharma | |||||
| 11:00 |
Abstract to come. Merrill Goldenberg, Ph.D., Senior Principal Scientist, Amgen | |||||
| 11:30 | Biophysical Characterization of High Concentration Protein Formulations Highly viscous protein formulations pose challenges in manufacturing, reconstitution, and drug delivery. This presentation focuses on the application of biophysical tools to characterize protein-protein and protein-excipient interactions in high concentration protein formulations. In particular, rheometry and adaptation of analytical tools for high concentration formulation development are discussed. Sonoko Kanai, Ph.D., Lab Head, F. Hoffmann-La Roche Ltd., Switzerland | |||||
| 12:00 | Technology Workshop IBC's Technology Workshops offer supplier and service companies the opportunity to present product and service offers directly to the audience at the conference. For more information on presenting a technology workshop at this meeting, please contact Kristen Schott at (508) 614-1239 or kschott@ibcusa.com. | |||||
| 12:30 | Networking Luncheon in BioProcess International™ Exhibit and Poster Hall | |||||
| 2:10 | Chairperson's Opening Remarks Anthony B. Barry, Ph.D., Principal Research Scientist, Drug Product Development, Wyeth BioPharma | |||||
| 2:15 |
Abstract to come. Osigwe Esue, Ph.D., Engineer II, Early Stage Pharmaceutical Development, Genentech, Inc. | |||||
| 2:45 |
Commercial scale manufacturing of therapeutic antibody products can expose the protein solution to a variety of stresses. The use of relevant laboratory stress models can help to establish process robustness and explore the design space for high concentration antibody formulations. These studies can also identify potential mechanisms for loss of chemical and physical stability, and demonstrate whether the analytical toolkit employed is appropriate and truly stability indicating. Examples from multiple lab models and antibody molecules are presented. Thomas J. Nikolai, Director, Biologics, Parenteral Products, Manufacturing Science & Technology, Global Pharmaceutical Operations, Abbott Laboratories | |||||
| Special Presentation | ||||||
| 3:15 | The Role of Formulation Development in Biologics Patent Protection Formulation development provides innovators with new opportunities for patent protection that can offset the loss of early patents covering biological actives. Clinical trials and even post-marketing R&D can continue to produce new inventions, such as new methods of treatment, mechanisms of action, packaging, delivery profiles, dosing ranges, and combination products and therapies, that are patentable over the innovator's own earlier patents, and which can extend the patent life cycle. Timothy J. Shea, Jr., Director, Sterne, Kessler, Goldstein & Fox P.L.L.C. | |||||
| 3:45 | Networking Refreshment Break in BioProcess International™ Exhibit and Poster Hall | |||||
| Small Group Scientific Exchange Discussions | ||||||
| 4:15 | A Best Practices Exchange for Formulation Scientists This year, our popular Scientific Exchange session will focus on an exchange of best practices among formulation scientists from industry companies of different size and scope. Each 15-20 person group will have a facilitator, and the hour-long interactive discussion will focus on the following topics:
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| 5:15 | Panel Discussion with Representatives of Each Roundtable Following the small group breakout sessions, a member of each group will join an interactive panel to discuss the most important best practices outlined in the sessions. | |||||
| 5:45 | Networking Cocktail Reception in BioProcess International™ Exhibit and Poster Hall | |||||
| Main Conference - Day Three Thursday, September 25, 2008 | PRE-CONFERENCE WORKSHOP | DAY ONE | DAY TWO | DAY THREE | | ||||||
| 7:30 | Networking Coffee | |||||
| 8:40 | Chairperson's Opening Remarks Tapan Das, Ph.D., Senior Principal Scientist, Pfizer Inc | |||||
| 8:45 |
Drug products generally begin with formulations that have undergone little or no product-specific development. The formulation then evolves between clinical phases or even within a clinical phase. A case study is presented in which a non-optimized formulation was used to initiate clinical trials. Product instability under frozen conditions led to reformulation. The formulation further evolved into a freeze-dried product, and it was further optimized to reflect changes in clinical configuration. Process changes to the lyophilization cycle paralleled the formulation/drug concentration and configuration changes. James Colandene, Ph.D., Associate Director, Drug Product Sciences, Pharmaceutical Sciences, Human Genome Sciences, Inc. | |||||
| Predictive Methods for Formulation Development | ||||||
| 9:30 | Differential Scanning Calorimetry (DSC), a Powerful Predictive Method for Formulation Screening Studies The stability of a protein is critically dependent on its folding conformation. Monitoring the changes of folding conformation of a protein under various formulation conditions provides predictive power for formulation development. Formulation stability trends at elevated temperatures suggest an excellent correlation between DSC's predictive capacity and the propensity of protein to aggregate, particularly on pH dependence. Correlations between biophysical techniques and analytical techniques are also presented. Robert Yi-Te Chou, Ph. D., Scientist, Amgen | |||||
| 10:00 | Application and Advancement of Biophysical Analysis in the Formulation Development of Protein Therapeutics This presentation discusses a variety of biophysical analyses of two mAbs that have very different pH dependent thermal stabilities. The presentation includes, (i) pH and excipient dependent conformational transition and the relation between structure and stability; (ii) calculated stability based upon reversible and irreversible transitions; (iii) the importance of pre-transitional thermal reversibility (PTR) and minimum destructive temperature (Td); and (iv) shelf-life and apparent intrinsic protein activity. Haripada Maity, Ph.D., Senior Scientist, Formulation Development, ImClone Systems Incorporated | |||||
| 10:30 | Networking Refreshment Break in Meeting Room | |||||
| Formulation Development for Lyophilized Products | ||||||
| 11:00 |
Formulation development for a lyophilized product is an interplay between the optimization of stabilizing excipients, choice of primary package and lyophilization conditions. This presentation highlights how the formulation development of a conjugated protein in a dual chamber syringe was impacted by each factor. Specific examples include the impact of moving from vial to dual chamber syringe on the following: product stability, excipient optimization, quality attributes, lyophilization cycle development and overall project timeline. Susan W. H. Martin, Ph.D., Principal Scientist, Global Biologics-Pharmaceutical Sciences, Pfizer Inc | |||||
| 11:30 |
The common practice in defining the pH of a lyophilized formulation for proteins is first to identify the optimal pH through screening studies in solutions. In most cases, this optimal solution pH can also be the optimal pH for the stability of a lyophilized formulation. However, there are some exceptions when the mechanism of degradation is different. This case study discusses the difference in the optimal pH for a liquid versus a lyophilized formulation of a glycoprotein. Gaozhong Zhu, Ph.D., Senior Scientist II, Pharmaceutical & Analytical Development, Shire Human Genetic Therapies, Inc. | |||||
| 12:00 |
Formulation development is often limited by time and material. Design of Experiments (DOE) is a valuable tool for solving this challenging exercise with the efficiency of statistical methods. In this case study, a robust freeze-dried formulation for a monoclonal antibody was developed by screening excipients and stabilizers and optimizing their concentrations in consideration of protein concentration. Arvind Srivastava, Ph.D., Associate Director, Formulation Development, ImClone Systems Incorporated | |||||
| 12:30 | Networking Luncheon in BioProcess International™ Exhibit and Poster Hall | |||||
| 1:55 | Chairperson's Opening Remarks David D. Hile, Ph.D., Senior Scientist, Formulation Development, Stryker Biotech | |||||
| 2:00 | Formulation of Self-Administered Microneedle Patches for Influenza Vaccines To facilitate self-administration of seasonal and pandemic influenza vaccines, we are developing microneedle patches coated with vaccine. The effect of coating formulation was investigated to improve coating efficiency, antigen stability and immunogenic response to the vaccine. Mice vaccinated by antigen-coated microneedles with optimized formulations developed strong antibody responses and were fully protected from challenge with a fatal dose of influenza virus. Therefore, appropriately formulated microneedles have the potential to provide a useful vaccine delivery technology. Yeu Chun Kim, Ph.D., Postdoctoral Fellow, School of Chemical and Biomolecular Engineering, Georgia Institute of Technology | |||||
| 2:30 | Prediction of New Protein Formulation Stability using Meta-Analysis Stability trend estimates for new lyophilized protein formulations were desired a priori in order to design appropriate experiments. In order to leverage available data, a meta-analysis was performed with existing stability data on related formulations. Stability indicating characteristics, specifically aggregation, oxidation, and activity, were modeled as a function of percent carbohydrate in the formulation, protein concentration, storage temperature, and time. The analysis identified significant factors affecting stability and provided insight into formulation selection and experimental study design. David D. Hile, Ph.D., Senior Scientist, Formulation Development, Stryker Biotech | |||||
| Formulation Development for Novel Proteins | ||||||
| 3:00 | Early-Stage Formulation Development of a Mimetic Fusion Protein Drug Product Abstract to come. Adam Dinerman, Ph.D., Assistant Director, Formulation Development, Centocor, Inc. | |||||
| 3:30 | Networking Refreshment Break in BioProcess International™ Exhibit and Poster Hall; Final Opportunity for Exhibit and Poster Viewing | |||||
| 4:00 |
Abstract to come. Michiel Lodder, Ph.D., Director, Business Development, OctoPlus Inc. | |||||
| 4:30 |
A development platform was established to rapidly advance HSA fusion proteins from development to the clinic. While many aspects of this approach are successful due to the biochemical dominance of the large albumin moiety over the entire fusion protein, particular care must be taken in formulation, where the fusion partner may define primary degradation pathways or the disease indication may influence formulation development. Jason Bock, Ph.D., Director, Pharmaceutical Development, Teva Biopharmaceuticals, USA (formerly CoGenesys, Inc.) | |||||
| 5:00 | Conference Ends | |||||
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