June 2, 2011
7:30 am Registration and Morning Coffee
8:30 am Chairperson’s Opening Remarks
Neal G. Anderson, Principal, Anderson’s Process Solutions
8:40 Stereoselective Synthesis of a Chiral Phosphoramidate Nucleotide Prodrug: Process Synthesis of the Anti-HCV Agent PSI-7977
Bruce Ross, Ph.D., Director, Process Research, Pharmasset
PSI-7977 is a single phosphoramidate isomer prodrug of 2’-deoxy-2’-a-fluoro-2’-b-C-methyl-uridine monophosphate. PSI-7977 is currently in Phase IIb clinical trials for the treatment of Hepatitis C infection. The process synthesis of the nucleoside as well as the development of the chiral synthesis of the phosphoramidate moiety will be described.
9:10 Process Development Towards Efficient Production of a Macrocyclic HCV Protease Inhibitor
Matthew M. Ravn, Ph.D., Senior Scientist III, Process Chemistry, Global Pharmaceutical R&D, Abbott Laboratories
Abbott is working in partnership with Enanta Pharmaceuticals on developing the next generation of HCV protease inhibitors. This talk will discuss the enabling and second generation syntheses of a macrocyclic HCV protease inhibitor.
9:40 The Process Development of a Nucleotide Reverse Transcriptase Inhibitor GS–9131
Brandon Brown, Ph.D., Senior Research Scientist, Process R&D, Gilead
This presentation will cover the early process development of the clinical candidate GS–9131. The development of a scalable process included the stereoselective synthesis of a fluoro–nucleoside and the production of a diasteromerically pure phosphonamidate prodrug moiety. The convergent synthetic approach was able to support a multi–kilogram scale production of GS–9131.
10:10 Opening Coffee Break with Exhibit and Poster Viewing
10:55 Process Research and Development of a p38 Inhibitor
Robert Milburn, Ph.D., Scientist, Chemical Process R&D, Amgen
This talk will cover the development of a pyrazolopyridinone-based p38 MAP kinase inhibitor. The synthesis was refined and optimized to provide kilogram quantities without chromatography. Key steps include a selective N-methylation and a high-yielding Suzuki reaction. In situ Raman spectroscopy was leveraged to monitor and understand the complex physicochemical properties of the final product.
Sponsored by
11:25 Novel & Cost-Effective Membrane Based Process Technologies for Sustainable API Synthesis, Separation, and PurificationManish Goel, Founder & CTO, i3 Nanotec LLC
The explosive growth of pharmaceutical production has been accompanied by a tremendous environmental cost. i3 Nanotec’s membrane and membrane-conventional hybrid processes and systems enable cost-effective, safe, and energy efficient API manufacturing, while simultaneously improving green process efficiency metrics significantly. This presentation will cover pervaporation (PV), vapor permeation (VP), gas permeation (GP), and hydraulic permeation (MF, UF, NF, & RO) membrane process technologies. Case studies for key membrane applications – non-thermal API concentration & purification, solvent exchange, solvent drying, solvent–methanol separation, spent HPLC solvent reprocessing, and solvent vapor recovery are also included.
11:55 Scale-Up Syntheses of Drug Candidates: A Case History of Two CCK1 Receptor Antagonists 
Neelakandha Mani, Ph.D., Senior Director, Process Research & Development, Johnson & Johnson
Cholecystokinin 1 (CCK 1) receptor antagonists are potential therapeutic agents in the treatment of a number of gastrointestinal or pancreatic disorders such as irritable bowel syndrome, nonulcer dyspepsia, biliary colic, chronic constipation and pancreatic cancer. Design of concise and practical routes for the stereoselective synthesis of two CCK1 receptor antagonists compounds will be discussed.
12:10 pm Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own
1:40 Chairperson’s Remarks
Mahavir Prashad, Ph.D., Head of Chemical Development Unit US, Novartis Pharmaceuticals Corporation
1:45 Managing CROs to Provide API from Pre-Clinical through Commercial
Scott M. Duncan, Ph.D., Senior Manager, API Development & Process Chemistry, Alkermes, Inc.
2:15 Panel Discussion with CROs
Moderator: Robert Hughes, Ph.D., Scientist II, Chemical Development, Vertex
Panelists:
Manish Goel, Founder & CTO, i3 Nanotec LLC
Simon Hickling, Ph.D., Director of Business Development, Codexis
John Roosenberg, Ph.D., Section Head, Chemical Development, AMRI
- Managing relationships
- Communicating changes
- Overseas v. domestic
Sponsored by
2:45 Enzyme Optimization for Generating Process-ready Biocatalysts:Cliff Veighey, Associate Director, Chemical Technology, CodexisCustom biocatalysts are now readily generated using CodeEvolverTM technologies. I will discuss the application of these technologies for developing large scale manufacturing processes for pharmaceutical products such as atorvastatin and sitagliptin.
3:00 Networking Refreshment Break with Exhibit and Poster Viewing
3:30 Rethinking the Routes to Scale-Up: Escitalopram
Peter J. Harrington, Ph.D., Better Pharma Processes, LLC
There is a need to inform the public that not all generic drugs are manufactured by the same process and that the different processes may have dramatically different environmental impacts. Two global forces are at odds today - the push for “greener” processes and the push for lower drug prices. This talk presents detailed discussions of the published process chemistry of escitalopram, one of the ten top-selling small molecule drugs in the US in 2007-2008, and highlights criteria used to arrive at a “best process” for manufacturing this blockbuster drug.
4:00 The Control of Genotoxic Impurities – A Collaborative Effort
Michelle Kenyon, Principal Scientist, Pfizer Global Research and DevelopmentDrug Safety R&D, Genetic Toxicology
This talk will highlight the practical aspects of scientific collaboration between experts in toxicology and process chemistry that are critical to the appropriate management of genotoxic impurities. A general framework for how toxicology experts use structure-based assessments to identify pharmaceutical impurities with genotoxic potential will be reviewed. The application of this information by chemistry experts to guide management and control of genotoxic impurities to ensure patient safety will also be discussed. Case examples will be presented to highlight the utility of this approach.
4:30 Breakout Roundtable Discussions
Attendees, once they are at the meeting, join one of the small group discussions listed below. It's a relaxed and informative way to meet and learn from colleagues with similar interests.
Topic 1: Going with Flow
Moderator: Teresa Makowski, Senior Scientist, Chemistry Technology Group --API, Global R&D, Pfizer
Implementing on scale – What are the challenges and experiences (analytical, capital investment, validation, internal vs external flow implementation, etc)
How to achieve a cultural change within process research (transition from batch thinking to flow thinking)
Best opportunities to have impact on process chemistry (early phase vs. late phase development) – benefits at early and late phase and how to bridge the gap if the benefits are different
Topic 2: Barriers to scale-up of microwave-assisted reactions
Moderator: Nicholas E. Leadbeater, Ph.D., Professor, Department of Chemistry, University of Connecticut
What are the hurdles I have to overcome to be able to scale up a reaction using microwave heating?
When using microwave heating, what chemistries are scalable and what chemistry are not?
What technology is out there for scaling up reactions using microwave heating and is it safe?
Are there other approaches I can take?
Topic 3: Best Practices for Outsourcing Process Chemistry
Moderator: Jay Srirangam, Ph.D., Associate Research Fellow, La Jolla Laboratories, Pfizer Global R&D
Topic 4: Incorporating Biocatalysis
Moderator(s): Matthew Truppo, Ph.D., Senior Scientist, Process Chemistry, Merck
Gjalt Huisman, Ph.D., VP, Product Planning Pharmaceuticals, Codexis, Inc.
When to start evolution of an enzyme
When to start considering biocatalysis
Where is continuous processing with biocatalysis appropriate
5:30-6:30 Networking Reception with Exhibit and Poster Viewing