Medicinal Chemist Expert in API Chemical Process Development, Manufacturing Process Start-up and API Process Trouble-Shooting

Expertise

• Synthetic organic chemist and small scale chemical process research and development.
• Chemical process research and development for "small molecule" drug substances.
• Guidance for scale-up to provide material for Phases 1 - 3 and manufacturing.
• Pharmaceutical facility start-up troubleshooting.
• Assistance with CMC section of filings.
• Pharmaceutical laboratory process research leading to technology transfer and scale up.
• Design and implementation of practical, cost-saving, processes and procedures.
• Experienced with 12 hands-on manufacturing start-ups of drug substances and intermediates.
• Author of widely-used process chemistry text and experienced instructor of courses on chemical process development.

Experience

Undisclosed Company, Founder, 1997 - Present

• Company formed for consulting and training with pharmaceutical, biotech, and fine chemicals companies.
• Providing efficient development of processes to make drug substances and intermediates to pharmaceutical, biotech and CRO/CMO companies.
• Specific guidance in the preparation of API / CMC regulatory filings, with consideration to process descriptions, specifications, and impurities such as genotoxins.
• Authored and instructed international courses with over 1200 students and over 150 companies in the area of: Practical Process Research and Scale up.

E. R. Squibb & Sons/Bristol-Myers Squibb, New Brunswick NJ, 1979 - 1997

Principal Scientist, Chemical Technology, 1989 - 1997

• Developed and monitored manufacturing processes of key intermediates of captopril (Capoten%uFFFF), $1.5 billion peak annual sales), fosinopril sodium (Monopril%uFFFF), aztreonam (Azactam%uFFFF) and other APIs to ensure optimal product quality and profitability.
• Initiated and introduced simplified process for the manufacture of captopril, resulting in $4 million annual savings by improving productivity and eliminating use and recovery of a solvent.
• Researched alternative pathways to IND candidates (Mitsunobu reaction, PTC-mediated alkylation) for preparation of clinical supplies.
• Served as in-house consultant for pharmaceutical process development.
• Demonstrated in a timely fashion that the processes for the manufacture of aztreonam intermediates could be used to prepare intermediates for drug candidates, thus potentially decreasing development time.
• Expeditiously developed and scaled up new processes (Fischer indolization, chlorination, %u03B2-lactam formation, oxidation, modified Arbuzov reaction, others) for drug candidates. Helped demonstrate process ruggedness in pilot plant.
• Served as resource to BMS chemists and engineers, trained hired chemists in process development, including in-house presentations.
• Assisted BMS Manufacturing, Quality Control, and Technical Registration Resources in identifying impurities, based on process experience.
• Advised BMS Analytical Research and Development on optimizing derivatizations for GC assays.
• Assisted with process optimization to remove trace impurities in drug candidates.
• Authored conception records for alternative processes.
• Managed interdepartmental task force to determine the source and removal of key trace impurities in bulk captopril.
• Advised manufacturing colleagues in Puerto Rico on process alterations to successfully optimize manufacturing operations.
• Generated work on PTC applications and showed that PTC provides a safe effective alternative to the use of NaH / DMF or K2CO3 / DMF for two processes to prepare an API and drug candidate.
• Redeveloped manufacturing process for the manufacture of a fosinopril sodium intermediate, to ensure all batches exceeded specifications.
• Successfully introduced process to manufacturing.
• Responsible for development and successful manufacturing startups of three processes at BMS Ireland facilities.

Group Leader, 1987 - 1989

• Supervised research activity in Chemical Process Technology by evaluating quality and impact of approaches.
• Directed 7 chemists (5 Ph.D.s) in the timely development and startup of processes.
• Chaired Project Team for aztreonam ($155 million annual sales) in an interdisciplinary approach to solving manufacturing problems.
• Introduced an optimized captopril process (productivity improved by 30%) and processes for new fosinopril sodium intermediates.

Senior Research Investigator, 1984 - 1987

• Performed process research and development for new products.
• Responsible for development and successful manufacturing startups of four fosinopril sodium and aztreonam processes at Squibb Ireland facilities. Solved startup problems on the floor.

Research Investigator, 1979 - 1984

• Performed independent research and development on novel, specialized projects.
• Developed and introduced key steps for aztreonam: Lactam formation, oxidation of intermediates, and isolation of aztreonam.
• Simplified manufacturing processes, thus increasing reliability and ultimately profitability.
• Responsible for development and successful manufacturing startups of five aztreonam processes at Squibb facilities in Ireland and Puerto Rico. Solved startup problems on the floor.
• Altered process for nadolol (Corgard%uFFFF, $150 million annual sales) to enable optimal profitability.
• Initiated and developed an aqueous process for nadolol penultimate, which decreased batch time by eliminating a cosolvent.
• Process was later filed with FDA.

McNEIL Pharmaceutical, Spring House, PA, Chemical Research, 1977 - 1979

Post-Doctoral Fellow

• Investigated medicinal and process chemistry of pyrrole acetic acids, and other exploratory research.
• Developed new process for Tolectin%uFFFF intermediate, helping J&J to ward off foreign competition.
• Developed first chemical preparation of a Zomax%uFFFF metabolite, key for NDA filing.

Honors & Publications

Academic and Professional Affiliations

• American Chemical Society, Organic Chemistry Division

Awards

• Received President's Award and Spot Awards in recognition of achievements at E. R. Squibb.

Publications and Patents

• One book: Practical Process
• 13 papers.
• Multiple presentations.
• 6 U.S. patents.

Education

• Ph.D. Medicinal Chemistry, University of Michigan
• B.S. Biology with Chemistry minor, University of Illinois, Champaign, IL