蛋白質精製的放大與製造

5月 1日 (四)

8:00 am - 5:00pm Registration Open

ALTERNATIVE SYSTEMS

8:30am Chairperson's Remarks

8:35 Recombinant Expression and Purification of the Hepatitis C Envelope Protein E1 in the Yeast Hansenula polymorpha
Joost Haelewyn, Ph.D., Purification Manager, Biologics, GENimmune NV
The methylotrophic yeast Hansenula polymorpha was used as a production system for the hepatitis C virus (HCV) envelope protein E1, a potentially relevant protein in the context of HCV treatment or prophylaxis. But while recombinant, core-glycosylated E1 accumulates intracellularly in yeast endoplasmic reticulum, the hydrophobic nature of E1, and its tendency to spontaneously form aggregates complicate the purification process. We therefore developed a strategy to overcome these challenges and established a first-generation production process whereby batches of E1 drug substance were produced according to cGMP standards to support toxicity studies and clinical trials (phase 1 and 2). During clinical trials, the production process was further improved and optimized at the process-development scale, which resulted in a fully scalable second-generation production process with a 10-fold higher overall E1 yield. Various cGMP-related issues were also resolved.

9:05 Producing Recombinant Proteins and Antibodies in the Chloroplasts of Microalgae
Peter B. Heifetz, Ph.D., Chief Scientific Officer, Rincon Pharmaceuticals, Inc.
Rincon's AlgRx platform utilizes the unique features of the plastid (chloroplast) organelle of eukaryotic microalgae to manufacture recombinant proteins. Recombinant proteins expressed from genes introduced into the plastid genome via homologous targeting are
tassembled with high fidelity into their native, disulfide-bonded eukaryotic conformations. Once synthesized, these proteins do not interact metabolically with cellular components outside the organelle and thus are functionally insulted allowing the accumulation of typically difficult-to-express molecules. This strategy of combining the most advantageous aspects of microbial fermentation and eukaryotic cell culture has thus far allowed us to produce a variety of therapeutic proteins including a range of antibody formats from scFv's to complete human IgGs and chimeric receptor fusions.

9:35 Glyco-Engineering in Moss and Production of Optimized Antibodies
Gilbert Gorr, Ph.D., Chief Scientific Officer, greenovation Biotech GmbH
Glyco-engineered mosses are suitable hosts for the production of biopharmaceuticals. Long-term cultivation of mosses can be performed in a robust, flexible and sustainable manner in photobioreactors. Furthermore, moss-produced antibodies - lacking fucose residues on its N-glycans - have been shown to be superior when compared to its parental counterparts. These data together with additional features like genetic stability of transgenic moss strains will be presented and discussed.

10:05 Coffee Break in the Exhibit Hall

MANAGING THE MANUFACTURING PROCESS

10:50 The Business & Science of Technology Transfer: A Case Study
Geoffrey Hodge, Ph.D., Vice President, Process Development and Technology, Xcellerex, Inc.
Technology transfer is a complex process involving elements of business and project management as well as good science. This presentation will discuss the role of each of these functional areas in order to ensure a clearly understood technology transfer from client to CMO and a successful scale-up of processes from bench to pilot and manufacturing scale. Case studies and examples of successes and potential pitfalls will be reviewed.

11:20 Creating a State-of-the-Art Facility for Protein-Based Biopharmaceuticals Using Modular Technology – Design Considerations, Project Execution and Examples
Pär Almhem, President, Pharmadule, Inc.
Bill Smith, President, Wes-Tech, LLC, formerly VP of Engineering, Eli Lilly and Co.
Modular technology has proven to be a viable and increasingly popular alternative for designing and building facilities for the production of biological drug products. This presentation illustrates the benefits and challenges of using modular construction, design considerations for a biopharmaceutical production facility, and execution of the modular project. It will include examples from completed and ongoing projects.

11:50 End of Protein Scale-Up & Manufacturing conference