Eden Biodesign ebook Monoclonal Antibody Production: Building the Platform

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1 Eden Biodesign ebook Monoclonal Antibody Production: Building the Platform CHAPTER 1: Overview CHAPTER 2: Challenges CHAPTER 3: Purification Methodology CHAPTER 4: Results CHAPTER 5: About Eden Biodesign

2 Eden Biodesign has developed a purification methodology for the clinical production of an IgG4 monoclonal antibody. Learn more.

3 Chapter 1 Overview A soaring increase in the biopharmaceutical drug product pipeline due to more applied focus and identification of potential drug candidates has escalated the pressure within the biopharmaceutical industry to increase manufacturing capacity and to maximize potential from existing facilities. According to recent estimates, the global biopharmaceutical market is worth upwards of $75 Billion, with an expected growth rate of 12 percent per annum, with monoclonal antibodies accounting for a significant proportion of this market. Eden Biodesign has developed a purification methodology for the clinical production of monoclonal antibodies, with a view to the production of a robust and scalable platform antibody purification methodology. Read on to learn more about how Eden Biodesign is helping to overcome many of the technical obstacles and accelerate monoclonal antibody production with this platform approach.

4 Chapter 2 Challenges Historically, the major production bottleneck in monoclonal antibody production has been fermentation capacity. The industry has responded by producing ever higher yields using both new and novel expression systems, developing and optimizing new and existing growth media, and increasing cell densities. All have gone a long way towards increasing the productivity of the upstream fermentation processes, with the best examples of optimized monoclonal antibody fermentation achieving yields in the region in excess of 5 g/l. Theses advancements have meant that, over the past few years, an increasing emphasis has been placed on downstream purification processes, with low titre fermentations quickly becoming a thing of the past. Alongside the increase in yield, in process impurities have also increased, mainly due to more complex growth media and increased cell densities with lower cell viabilities. This introduces elevated levels of host cell proteins, lipids and nucleic acids into the process, offering a greater challenge to the purification process with harvest and clarification issues and column and chromatography resin limitations.

5 Chapter 3 Purification Methodology Monoclonal antibody production typically follows the following production processes: Step 1: Fermentation Step 2: Harvest & Clarification Step 3: Protein A Chromatography Step 4: Low ph Viral Inactivation Step 5: Cation Exchange Chromatography Step 6: Anion Exchange Chromatography Step 7: Concentration & Buffer Exchange Step 8: Viral Reduction Filtration Step 9: Bioburden Reduction

6 These steps can be complex and costly with the most significant limitation and cost being the Protein A Chromatography column. Eden Biodesign has developed a purification methodology for the clinical production of an IgG4 monoclonal antibody that offers several solutions to current antibody production challenges, including: High Throughput Processing Achieved with resins with high operational flow rates and increased dynamic binding capacities reducing batch time. Disposable Technology With the advantage of reducing cleaning validation requirements and plant turn-around times both of which offering significant cost benefits for a multi-product production facility.

7 Chapter 4 Results The objective was the development of an antibody purification process for the production of an IgG4 monoclonal antibody produced from a CHO cell line utilizing cell expression technology in a stirred tank bioreactor format using chemically defined growth media. Eden started with direct clarification of the bioreactor using Depth Filtration to remove gross cellular debris with fully disposable options. Eden then selected a panel of resins (Protein A, Cation and Anion Exchange) and performed a full resin screening followed by further process optimization of selected candidates. Once developed and optimized, Eden then applied the purification process at 2 L bioreactor scale, with a view to subsequent 20 L then 200 L verification batches. The purification process achieved was a robust, scalable process suitable for clinical manufacture with the ability to produce product of an extremely high degree of purity.

8 Analytical Results of this study include: ANALYSIS TECHNIQUE RESULT Endotoxin LAL <0.5 EU/mL DNA qpcr <16 pg/ml Purity (SEC) SEC 100% Host Cell Protein ELISA In Development Recovery ELISA In Development Because of the promising nature of these results, work is being conducted to further refine this antibody purification process.

9 Chapter 5 About Eden Biodesign As an established international biopharmaceutical development and manufacturing services provider, Eden Biodesign understands the required technical and regulatory issues involved in accelerating novel vaccine products into and through clinical development. Eden Biodesign offers the most scientifically advanced development and manufacturing services to biotech clients across Europe, the USA, Asia, Africa and Australia. We understand the challenges facing vaccine developers worldwide. We begin with the end in mind, helping you develop valuable biopharmaceutical medicines through the application of good science, right from day one.

10 Clients turn to Eden Biodesign for: Consultancy: Eden provides global CMC support, regulatory services, training, strategic insights and clinical logistics support. Process Design & Development: Eden specializes in helping our clients develop well defined, robust, scalable and reproducible processes, that are both commercially viable and regulatory compliant. cgmp Manufacturing Expertise: Eden offers cgmp manufacturing services for every significant biopharmaceutical production technology mammalian, microbial and viral. World Class Facilities: Our world-class facilities provide the full range of services required to take novel biopharmaceuticals and vaccines from proof of concept through to cgmp manufacturing for clinical trials.

11 Eden Biodesign Headquarters Eden Biodesign Ltd. NBC Estuary Banks Estuary Commerce Park Speke Road Liverpool, UK L24 8RB In the U.S. Eden Biodesign, Inc. Eden Biodesign, Inc Meridian Parkway Suite 300 Durham NC USA Visit Our Website