DAY 2, THURSDAY, JUNE 14, 2012
8:30 am Chairperson’s Opening Remarks
Matthew Ravn, Ph.D., Senior Scientist III, GPRD Process R&D, Abbott
» 8:35 KEYNOTE Speaker
Strategies and Innovations Toward the Rapid Development of the Cobicistat Drug Substance
 Richard Yu, Ph.D., Director, Process Development, Gilead Sciences, Inc.
The presentation will highlight the accelerated development of the cobicistat drug substance. The discussion will feature the integration of process research and development plans, innovations, and regulatory strategies taken throughout the lifecycle of the program up to the marketing approval application.
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9:15 Starting Material Designation – "Does It Matter Anymore?”
Sandeep P. Modi, Ph.D., Group Director, CMC Documentation – Pharmaceutical Development, Bristol-Myers Squibb Co.
Starting material(s) are defined in the regulatory submissions to provide the basis for drug substance synthesis. In recent years there has been significant debate on how far back in the synthetic scheme one needs to go to successfully defend starting material designation. We will examine the pros and cons of regulatory starting material(s), and discuss if defending an early intermediate as a starting material for regulatory submission is worth the efforts in the current environment of pharmaceutical regulations.
9:45 Matching Biocatalysts to Chemical Processes
Chris Savile, Ph.D., Associate Director, Business Development Pharma Services, Codexis
Codexis’ CodeEvolverTM protein evolution technology has been used to develop several enzyme classes for the large-scale commercial manufacture of pharmaceutical intermediates. We have now compiled the best enzymes from these evolution programs into screening kits that can be used to rapidly determine the feasibility of biocatalysis and accelerate early phase process development. Our presentation will highlight this technology and some recent results.
10:00 Coffee Break with Poster Viewing
10:30 Addressing Early Process Challenges in the Chemical Development of AG-013958 and PF-04691502
Jay Srirangam, Ph.D., Associate Research Fellow, World Wide Phamraceutical Sciences, Pfizer
Through presenting the chemical development of AG-013958, a VEGF inhibitor and PF-04691502, a Pi3K alpha inhibitor, I will demonstrate how we at Pfizer, La Jolla, have reduced internal efforts and leveraged external CROs to address early process challenges.
11:00 Panel Discussion: Impact of Pharma/CRO Partnerships on Chemical Development
Moderator: Jay Srirangam, Ph.D., Associate Research Fellow, Worldwide Pharmaceutical Sciences, Pfizer
Panelists:
Mahavir Prashad, Ph.D., Head of Chemical Development, Novartis
Antonio Montalban, Ph.D., Director, Chemical R&D, Arena Pharmaceuticals
Richard Yu, Ph.D., Director, Process Development, Gilead Sciences, Inc.
- How are pharma chemical development strategies changing by partnering more with CROs?
- What are the new opportunities for CROs?
- How do they need to adapt?Where are the gaps in the partnerships?
11:30 Breakout Discussion Summaries
Moderators of Breakout Discussion Groups
11:45 Buffet Lunch Provided in the Homestate Cafe (Please Bring Your Ticket)
1:30 pm Chairperson’s Remarks
1:35 Immobilized Transaminases for the Synthesis of Sitagliptin
Matthew Truppo, Ph.D., Associate Director, Process Chemistry, Merck
We have developed an immobilized transaminase capable of running in 100% organic solvent systems that can be recycled. This immobilized transaminase has been used to develop a continuous process for the manufacture of Sitagliptin, enabling significantly less waste, greater productivity, and reduced cost.
2:05 Facile and Practical Synthesis of a Cannabinoid-1 Antagonist
Wen-Chung Shieh, Ph.D., Novartis Leading Scientist, Chemical and Analytical Development, Novartis Pharmaceuticals Corporation
A scalable synthetic strategy of a novel cannabinoid-1 antagonist, starting from a commercially available mandelic acid is described. The key step involves a regio- and stereoselective ring-opening of an aziridium ion by an aniline nucleophile. Employing green chemistry principles, this novel synthesis appears to be highly efficient for the manufacturing of multi-kilogram quantities of an optically-pure active pharmaceutical ingredient.
2:35 Rapid Optimization towards a Practical Kilogram Scale Delivery of the B-Raf Kinase Inhibitor AR00341677 (GDC-0879)
D. David Hennings, Ph.D., Senior Research Investigator, Process Research and Development, Array Biopharma, Inc.
AR00341677 (GDC-0879) was identified during a collaboration between Array BioPharma and Genentech as a potent and selective inhibitor of B-raf kinase. The challenge presented to the process research group was to rapidly prepare over 2 kg of API to support further studies. Although the route used by the discovery chemists was fairly straightforward, there were several issues that needed to be addressed to safely and efficiently prepare the desired product while achieving an acceptable purity profile. The initial optimization and subsequent kilogram scale delivery will be discussed.
3:05 Refreshment Break with Poster Viewing
3:35 Process Development of an Efficient and Scalable Route to the Diamine Core of Cobicistat
Aaron Cullen, Ph.D., Research Scientist II, Process Development, Gilead Sciences, Inc.
This presentation will feature the rapid development of a practical and direct synthesis to the central 1,4-diamine fragment of the PK-enhancer, cobicistat. The assembly of the 1,4-diamine is highlighted by a novel aziridine dimerization to directly construct the diamine core and an N,N-dimethylsulfamoyl protecting group as an essential element for the synthesis. The realization of this route on a manufacturing scale will also be discussed.
4:05 A Scalable AsymmetricSynthesis of a PARP Inhibitor Employing a Memory of Chirality Cyclization
Matthew Ravn, Ph.D., Senior Scientist III, GPRD Process R&D, Abbott
4:35 End of Conference