Tout sur les médicaments הכל על תרופות كل شيئ عن الأدوية Все о наркотиках 关于药品的一切 డ్రగ్స్ గురించి అన్ని 마약에 관한 모든 것 Όλα για τα Ναρκωτικά Complete Tracking of Drugs Across the World by Dr Anthony Melvin Crasto, Worldpeacepeaker, worlddrugtracker, PH.D (ICT), MUMBAI, INDIA, Worlddrugtracker, Helping millions, 9 million hits on google on all websites, 2.5 lakh connections on all networks, “ALL FOR DRUGS” CATERS TO EDUCATION GLOBALLY, No commercial exploits are done or advertisements added by me. This is a compilation for educational purposes only. P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent
FLOW CHEMISTRY, flow synthesisComments Off on Development and Scale-Up of a Continuous Reaction for Production of an Active Pharmaceutical Ingredient Intermediate
Flow reactor equipment that was used in the piloting of the aldol flow chemistry. (a) The tube-in-shell heat exchangers were used to control stream temperature upstream and downstream of the (b) Y-mixer. Valves and ports on Y-mixer enabled flushing of lines and incorporation of inline thermocouples.
Examples of continuous flow reactions in the laboratory setting are becoming commonplace in pharmaceutical drug substance research. Developing these processes for robust commercialization and identifying the scale-up parameters remains a challenge. An aldol reaction in the formation of an active pharmaceutical ingredient intermediate was developed in flow at the milliliter scale. Research focused on identifying conditions that led to robust and stable operating conditions. Desired reaction performance was achieved in various mixers across reactor scales by identifying conditions that led to similar flow regimes. Conditions from the lab were transferred to the pilot plant to successfully process ∼200 kg of the starting material.
Development and Scale-Up of a Continuous Reaction for Production of an Active Pharmaceutical Ingredient Intermediate
A flow chemistry process for sustainable operations was developed by utilizing THF as a cosolvent to improve the solubility of the reagent degradants. Process robustness was further established by understanding the impact of mixing, residence time, and solvent composition on reaction performance. Identifying a suitable flow regime via the Reynolds number was identified as the scaling parameter for this flow reaction and used to scale the flow reaction from 20 mL/min in the lab to 1.6 L/min in the production environment. A modular flow reactor skid was fabricated for facile integration of flow chemistry components with existing batch equipment and was used to process 200 kg of starting material.
PresentationsComments Off on Reflections on Chirality in the Pharmaceutical Industry: Past, Present and Future Dr. Christopher J. Welch, Distinguished Scientist Process Research & Development Merck Research Laboratories, USA
Reflections on Chirality in the Pharmaceutical Industry: Past, Present and Future Dr. Christopher J. Welch, Distinguished Scientist Process Research & Development Merck Research Laboratories, USA
A PRESENTATION
At Chiral India 2016, New horizons in Drug development, Harnessing the power of Chirality .Organised by chemical weekly at Holiday inn international, Mumbai, India, Nov 8 2016
Christopher J. Welch
Science Lead for Analytical Chemistry
Merck Research Laboratories
Christopher J. Welchis Science Lead for Analytical Chemistry within the Process and Analytical Chemistry area at Merck Research Laboratories in Rahway, NJ. Chris leads the New Technologies Review and Licensing Committee (NT-RLC), the organization that oversees identification, acquisition and evaluation of new technologies of potential value to Merck Research Laboratories. Chris also leads the MRL Postdoctoral Research Fellows Program. He received his BS degrees in Chemistry and Biochemistry from the University of Illinois at Urbana-Champaign in 1982 and a Ph.D. degree in Organic Chemistry (also U of I) in 1992. Dr. Welch has worked in a variety of fields within the chemical industry, including discovery synthesis of agrochemicals (Velsicol-Sandoz), development of reagents for improved immunodiagnostic assays (Abbott Laboratories), and development and commercialization of chromatographic stationary phases, reagents and enantioselective catalysts within a small chemical business environment (Regis Technologies). Since joining Merck in 1999, he has focused on developing and applying improved methods and equipment for purification, synthesis and analysis of pharmaceuticals and intermediates. Dr. Welch has authored more than 230 scientific publications and patents. He is co-founder of the journal, Enantiomer, a current or past member of the editorial advisory boards for the journals, Chirality, Organic & Biomolecular Chemistry, Journal of the Korean Chemical Society, Chemistry World, Chemical & Engineering News and ACS Central Science. Chris is past chair of the ACS Division of Organic Chemistry (ORGN), a member of the Executive Committee for the International Symposia on Chirality, a member of the ACS steering committee for Pacifichem and a member of the PittCon Program Resource Team. Honors and awards include the NJCG Award for Excellence in Chromatography (2004), the PACS Activated Carbon Hall of Fame award (2007), MRL Presidents Award for Environmental Achievement (2009), Microsoft Life Science Innovation Award (2010), Fellow of the American Chemical Society (2010), Fellow of the American Association for the Advancement of Science, AAAS (2013), the Chirality Medal (2015) and the University of Nebraska Industrial Advisory Board Award (2016).
Current responsibilities:
Scientific Lead, Analytical Chemistry
co-chair, New Technologies Review & Licensing Committee (NT-RLC)
co-chair, Merck Research Laboratories Postdoctoral Research Fellows Committee
Previous Positions at Merck:
Science Lead, Global Analytical Chemistry 8/10 – 8/12
Distinguished Senior Investigator, Process Research 7/07 – 8/10
Associate Director. Process Research 1/06 – 6/07
Senior Research Fellow, Process Research 6/03 – 12/05
Research Fellow, Process Research 5/99 – 6/03
– (6 years 11 months)Morton Grove, IL (Chicago area)
– New product development and commercialization (chromatography columns, reagents, enantioselective catalysts)
– Scientific evaluation of custom organic synthesis business
– Set up contract synthesis/preparative chromatographic separation business – first of kind
Honors & Awards
Fellow
American Association for the Advancement of Science (AAAS)
Fellow
American Chemical Society (ACS)
Chirality Medal 2015
Presidential Green Chemistry Award
US Environmental Protection Agency
– for precompetitive collaboration between Merck, Pfizer, Eli Lilly and University of Wisconsin on Aerobic Oxidation Methods for Pharmaceutical Synthesis – co-awardees: Shannon Stahl and Thatcher Root (U. Wisconsin), Joel Hawkins (Pfizer) and Joe Martinelli (Lilly)
Industrial Advisory Board (IAB) Award
University of Nebraska Department of Chemistry
Inaugural IAB award from U. Nebraska recognizing excellence in scientific research in an industry setting
Evaluation of core–shell particle columns for ion-pair reversed-phase liquid chromatography analysis of oligonucleotides, J. Pharm. Biomed. Anal. 72, 25–32, 2013.
Pharmaceutical Industry Practices on Genotoxic Impurities, in Pharmaceutical Industry Practices on Genotoxic Impurities, ed Heewoon Lee, Taylor & Francis, 2013.
Rapid Analysis of Residual Palladium in Pharmaceutical…more
2012 Publications 2012
A Simple Parallel Gas Chromatography Column Screening System, Wes Schafer, Simon E. Hamilton, Zainab Pirzada and Christopher J. Welch, Chirality, 24,1–4, 2012.
Rapid catalyst identification for the synthesis of the pyrimidinone core of HIV integrase inhibitors, A. Bellomo, N. Celebi-Olcum, X. Bu, N. Rivera, R.T. Ruck, C.J. Welch, K.N. Houk, S.D. Dreher, Angew. Chem. Int. Ed., 51 (2012) 1-5
…more
2011 Publications
Application of Ion Mobility Spectrometry in Drug Substance Development, H. Gao, X. Jia, R. Xiang, X. Gong, C. Welch, Analytical Methods, 3, 1828-1837, 2011.
Analytical Method Volume Intensity Index:A Green Chemistry Metric for HPLC Methodology in the Pharmaceutical Industry, R. Hartman, R. Helmy, M. Al-Sayah, C. Welch, Green Chemistry 13, 934-939, 2011.
High-throughput metal screening in pharmaceutical samples by ICP-MS with automated flow injection using a modified HPLC configuration, Tu, Wang, Welch, J. Pharm. Biomed. Anal., 51, 90-95, 2010.
Systematic Evaluation of New Chiral Stationary Phases for Supercritical Fluid Chromatography Using a Standard Racemate Library, Pirzada, Personick, Biba, Gong, Zhou, Schafer, Welch, J. Chromaogr.A,…more
A microtube screening approach affords simple and convenient assessment of the selective adsorption of metal impurities by a variety of different process adsorbents. This approach is helpful in identifying rapid solutions to metal impurity problems in pharmaceutical process research. Several examples illustrating the utility of the approach are presented.
Online Analysis of Flowing Streams Using Microflow HPLC
Welch helped launch Merck’s new postdoctoral research fellowship program.
P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent.
/////////Reflections on Chirality in the Pharmaceutical Industry, Past, Present and Future Dr. Christopher J. Welch, Distinguished Scientist, Process Research & Development, Merck Research Laboratories, USA, presentation
flow synthesisComments Off on Flow Grignard and Lithiation: Screening Tools and Development of Continuous Processes for a Benzyl Alcohol Starting Material
Efficient continuous Grignard and lithiation processes were developed to produce one of the key regulatory starting materials for the production of edivoxetine hydrochoride. For the Grignard process, organometallic reagent formation, Bouveault formylation, reduction, and workup steps were run in continuous stirred tank reactors (CSTRs). The lithiation utilized a hybrid approach where plug flow reactors (PFRs) were used for the metal halogen exchange and Bouveault formylation steps, while the reduction and workup steps were performed in CSTRs. Relative to traditional batch processing, both approaches offer significant advantages. Both processes were high-yielding and produced the product in high purity. The two main processes were directly compared from a number of perspectives including reagent and operational safety, fouling potential, process footprint, need for manual operation, and product yield and purity.
Flow Grignard and Lithiation: Screening Tools and Development of Continuous Processes for a Benzyl Alcohol Starting Material
SYNTHESISComments Off on Development of a Safe and Robust Process for the Large-Scale Preparation of a Vinyl Bromide from a Ketone Using a (PhO)3P/Br2-Derived Reagent
The large-scale synthesis of ethyl 4-bromocyclohex-3-enecarboxyalate, using a mild brominating reagent derived from triphenyl phosphite and bromine, is reported. The development and comparison of both continuous and batch processes are described.
A modified addition sequence was developed based on the knowledge garnered from flow-processing, resulting in a safe and efficient process for the in situ generation of the unstable active reagent and its immediate reaction with the ketone in a batch mode process.
Development of a Safe and Robust Process for the Large-Scale Preparation of a Vinyl Bromide from a Ketone Using a (PhO)3P/Br2-Derived Reagent
† Chemical and Synthetic Development, Biocon Bristol-Myers Squibb Research and Development Center, Biocon Park, Jigani Link Road, Bommasandra IV, Bangalore-560099, India
‡ Chemical and Synthetic Development, Bristol-Myers Squibb, 1 Squibb Drive, New Brunswick, New Jersey 08903, United States
, Christopher H. Marton, Benjamin D. Sherry, Glenn Spencer, Joseph Kukura, and Natalie S. Eyke
