Vous êtes sur la page 1sur 6

JALE MU"LEH*DD*NO*LU Hightstown, NJ * jm11afa8c@westpost.net * 732.485.

5500 SENIOR CHEMICAL ENGINEER PHARMACEUTICALS * CHEMICAL * HETEROGENEOUS CATALYSIS Utilizes systematic approach and uses first principles for development and imple mentation of processes. Innovative and collaborative. Introduced the first proce ss analytical technologies (PAT) in plant and manufacturing as part of quality b y design (QBD) approach for Bristol-Myers Squibb. Transferred technologies succe ssfully to manufacturing and vendor sites. Demonstrated continuous hydrogenation process for the first time to support PRD for continuous reaction related proce sses. Catalysis background includes Ph.D. on the characterization of silver cata lysts for butadiene oxidation reaction. Lab Process Development & Optimization Kinetic Modeling Pilot Plant, Manufacturing & Technology Transfer Hydrogenation & Gaseous React ions Heterogeneous Catalysis Mechanistic Reaction Studies PAT Application & Implementation GMP/GLP Regulations & Guidelines Statistical Experimental Design Validation & NDA Filing Quality by Design Safety & Hazard Evaluation EDUCATION Ph.D., Chemical Engineering, The Pennsylvania State University, University Park, PA M.S., Chemical Engineering, Middle East Technical University, Ankara, Turkey B.S., Chemical Engineering, Middle East Technical University, Ankara, Turkey PROFESSIONAL EXPERIENCE Bristol-Myers Squibb, Pharmaceutical Research Institute, New Brunswick NJ. 2002 to Present GROUP LEADER, HETEROGENEOUS CATALYSIS GROUP (2008 to Present) SENIOR RESEARCH INVESTIGATOR II, Extended the scope of the group from hydrogenation to heterogeneous catalysis an d took leadership roles as engineering leader for projects and manager as well a s leading a community practice within Bristol-Myers Squibb. Initiated projects i mplemented for the first time in Bristol-Myers Squibb. Initiatives include: ? Leads 3 Engineers for the oncology drug program to optimize reaction, crystall ization, drying, and other unit operations resulting in a robust process and suc cessful plant scale-up. Provides strategic planning support to Project Leader. ? Prepares laboratory for solid-phase peptide synthesis. ? Authors Scope-of-Work and technology transfer documents for outsourcing. Guide s vendors in successful production. Visits vendors? sites to ensure successful p roduction. ? Initiated and demonstrated running hydrogenation reactions in continuous mode. Set-up associated lab. ? Participated in development of gaseous reactions including ammonolysis and hyd roformylation which was being implemented for the first time in PR&D. ? Member of BMS recruitment team. ? Introduced use of heterogeneous catalysts for coupling reactions. ? Participated in technology transfer and execution of validation campaign at th e manufacturing site. ? Developed FTIR methods for process monitoring and control. Transferred technol

ogy of FTIR for in- process controls to manufacturing site.

JALE MU"LEHIDDINO*LU-page two ? Supported preparation of NDA documentation filings. ? Developed and scaled-up hydrogenation processes for toxicology and first in hu man studies. ? Directed work-flow for setting up a 20L hydrogenation reactor in the laborator y including PLC control to enable rapid toxicology and first in human studies. ? Drafted SOPs and WIs for hydrogenation laboratory and equipments. SENIOR RESEARCH INVESTIGATOR I, HYDROGENATION PROCESSES (2005 to 2008) Developed work flow strategy for hydrogenation processes including laboratory de velopment, implementation, and standardization in hydrogenation laboratories. Ma naged 2 Research Scientists. Supervised 2 Post-Doctoral Fellows. Initiatives: ? Team Member for the renovation of the hydrogenation laboratory and pilot plant . Instrumental in creating developed modification proposal. ? Integrated calorimetry, PAT, and modeling for mechanistic and kinetics underst anding of the processes. ? Implemented 3 in-process controls utilizing FTIR for the hydrogenation process as part of QbD including scientific implementation, drafting method, and suitab ility reports following ICH guidelines. Collaborated with QA to determine the re quirements for filing PAT as part of the process. ? Improved process greenness and selectivity by replacing sodium borohydride red uction with gaseous hydrogen. ? Significantly reduced the amount of catalyst used and tedious work-up needs by changing the phase transfer hydrogenation process to gaseous hydrogen for oncol ogy drug program. ? Re-defined process parameters at the vendor site after discovering unexpected levels of impurity. Quickly scaled-up hydrogenation process and successfully gen erated acceptable results. ? Supported technology transfer activities for early and late stage projects. RESEARCH INVESTIGATOR II (2002 to 2005) Initiatives: ? Developed a catalyst for an asymmetric hydrogenation reaction reducing amount of pyrophoric and high- density catalyst for a diabetes drug project. ? Developed and scaled-up hydrogenation process in nitroalkene reduction. Propos ed a significant change in the process to eliminate mass-transfer effect causing low selectivity for HIV drug program. ? Investigated the root cause of leaching problem in one of the hydrogenation pr ocesses. Discovered a new solution which significantly reduced operation time an d resolved leaching issue. Implemented the process successfully in the pilot pla nt for cardiovascular drug program penultimate step. ? Innovated a process which led to robust hydrogenation process. Implemented the process in the pilot plant resulting in successful clinical and non-clinical ca mpaigns for oncology drug final step. AWARDS & HONORS ? NATO Science Fellowship in Chemical Engineering. ? ChE Department Excellence Fund Endowed Graduate Fellowship 2001. ? Chemistry Leadership Award (2007) for the outstanding track of record of excel

lent scientific contributions to multiple projects and creating innovative pract ical solutions to challenging problems. ? 12 Process Research and Development Awards from Bristol-Myers Squibb (addendum ). PUBLICATIONS & PRESENTATIONS Addendum

RESUME ADDENDUM AWARDS & HONORS ? PRD Award in recognition of exemplary teamwork during the development of diabe tes drug. ? PRD Award for leading hydrogenation efforts and solving difficult technical pr oblems for FXA, VEGFR-2 and EVRI projects. ? PRD Award in recognition of outstanding laboratory and pilot plant work for pr e-LTSS and LTSS campaigns of Brivanib alaninate. ? Process Research and Development Star Award for trouble-shooting in Hydrogenat ion reaction in pilot-plant in short time. ? Process Research and Development Star Award for development and superior execu tion of a process utilizing React-IR technology. ? Process Research and Development Star Award for parallel execution in technolo gy transfer and successful scale-up at two vendor locations. ? Process Research and Development Star Award for exceptional collaboration to e nable safe production of product for LTSS. ? Process Research and Development Star Award for exceptional collaboration and expediency in preparation of intermediate for manufacture of diabetes drug. ? Process Research and Development Star Award for innovation and team work which led to a more robust hydrogenation process and successful clinical and non-clin ical campaigns to prepare a cancer drug. ? Process Research and Development Star Award for contributions made towards the process development and successful implementation of the hydrogenation step to prepare the key intermediate in large scale synthesis of HIV AI BU. ? Process Research and Development Star Award in recognition of your outstanding performance and teamwork to support the Apixaban LTSS pilot plant campaign. ? Process Research and Development award for outstanding work in the laboratory, pilot plant and vendor manufacturing sites to support rapid clinical developmen t of BMS-741672. PUBLICATIONS ? Determination of Heavy Metal Concentration in Feed and Permeate Streams of P olymer Enhanced Ultrafiltration Process M?ddino*lu Jale, Uludag Yusuf, Ozbelge, Hilmi Onder, Yilmaz Levent

Talanta 46, 1557-1565, (1998). ? Effect of Operating Parameters on Selective Separation of Heavy Metals from Bi nary Mixtures via Polymer Enhanced Ultrafiltration M?ddino*lu Jale, Uludag Yusuf, Ozbelge, Hilmi Onder, Yilmaz Levent, Journal of Membrane Science, 140, 251-266, (1998). ? CO Adsorption on Supported and Promoted Ag Epoxidation Catalysts M?ddino*lu Jale and Vannice M. Albert Journal of Catalysis, 213, 305-320, (2003). ? Adsorption of NO on Promoted Ag/ *-Al2O3 Catalysts M?ddino*lu Jale and Vannice M. Albert Journal of Catalysis, 217, 442-456, (2003). ? Adsorption of 1,3-Butadiene on Supported and Promoted Silver Catalysts M?ddino*lu Jale and Vannice M. Albert Journal of Catalysis, 222, 214-226, (2004). ? Selective Debenzylation in the Presence of Aromatic Chlorine on Pd/C Catalysts : Effects of Catalyst Types and Reaction Kinetics Wang, Steve S.Y., Li, Jun, TenHussein, Karen, Muslehiddinoglu, Jale, Tummala, Sr inivas, Kiang, San, and Chen, Jiangping, J.P., ? Catalysis of Organic Reactions, Marcel Dekker Inc., Ed. Sowa, J., 2004. ? Kinetics Investigation into the Removal of Carbobenzyloxy Group from Protected Amines via Hydrogenolysis Reaction M?ddino*lu Jale, Lobben Paul, Leung Simon, Spangler Lori, Kiang San, Catalysis Today, 123, 164-170, 2007. ? The Process Development of Ravuconazole; an Efficient Multikilogram Scale Prep aration of an Anti-fungal Agent Jaan Pesti, Chien-Kuang Chen, Lori Spangler, Albert J. DelMonte, Serge Benoit, D erek Berglund, Jeffrey Bien, Paul Brodfuehrer, Yeung Chan, Elisabeth Corbett, Ca rrie Costello, Paul DeMena, Robert P. Discordia, Wendel Doubleday, Zhinong Gao, Stephane Gingras, John Grosso, Oscar Haas, David Kacsur, Chiajen Lai, Simon Leun g, Melanie Miller, Jale Muslehiddinoglu, Nina Nguyen, Jun Qiu, Martina Olzog, Em ily Reiff, Dominique Thoraval, Michael Totleben, Dale Vanyo, Purushotham Vemishe tti, John Wasylak and Chenkou Wei Org. Process Res. Dev. 2009 (13) 716-728. ? Highly Diastereoselective Hydrogenation of Imines by Bimetallic Pd-Cu Heteroge neous Catalyst M?ddino*lu Jale, Jun Li, Srinivas Tummala, Rajendra Desphande Org. Process Res. Dev., 2010, (14) 890-894. ? Flow Reactors (Chapter) M?ddino*lu Jale Green Techniques for Organic Synthesis and Medicinal Chemistry, in preparation. PATENTS ? Process for the preparation of [(1R), 2S]-2-aminopropionic acid-[4-(4-Fluoro2-Methyl-1H-Indol-5-Yloxy)-5-methylpyrolo[2,1-f][1,2,4]Triazin-6-Yloxy]-1-methyl ether ester Crispino Gerard A., Hamedi Mourad, LaPorte Thomas L., Thornton John E., Pesti Ja an A., Xu, Zhongmin, Lobben Paul C., Leahy, David K., M?ddino*lu Jale, Lai Chia jen, Spangler Lori Ann, Discordia Robert U.S. Pat. Appl. Publ. (2007), 15pp. CODEN: USXXCO US 2007249610 A1 2007102 5.

? Process for the preparation of [(1R), 2S]-2-aminopropionic acid-[4-(4-Fluoro2-Methyl-1H-Indol-5-Yloxy)-5-methylpyrolo[2,1-f][1,2,4]Triazin-6-Yloxy]-1-methyl ether ester Crispino Gerard A., Hamedi Mourad, LaPorte Thomas L., Thornton John E., Pesti Ja an A., Xu, Zhongmin, Lobben Paul C., Leahy, David K., M?ddino*lu Jale, Lai Chi ajen, Spangler Lori Ann, Discordia Robert CODEN: USXXCO WO 2007124332 A1 2007. ? Modulators of Chemokine Receptor Activity, Crystalline Forms and Process Yang, M.G., Cherney, R., Eastgate M., Muslehiddinoglu J., Prasad S., Xiao, Z. WO /2008/014381, PCT/US2007/074438. PRESENTATIONS ? Use of in-line FTIR as in-Process Control: Risk Mitigation for Scale-up and C ommercial Manufacturing Jale M?ddino*lu, Shih-Ying Chang, Paul Lobben, Thomas LaPorte, Lori Spangler, Ro bert Wethman, Daniel Wasser,Michael Hrystak, Sushil Srivastava and San Kiang 17th International Process Development Conference, Baltimore, MD, May 2010. ? Development of Efficient and Robust Nitro Reduction Process: Catalyst Selectio n and Thermo-Kinetic Understanding Jale Muslehiddinoglu ,Nicolas Cuniere, Srinivas Tummala, Lucius Rossano North American Catalysis Meeting (NAM), San Francisco, CA, June 2009. ? Application of Catalysis and Process Analytical Tools for the Development and Implementation of Hydrogenation Processes in the Pharmaceutical Industry-A 21st Century Approach Jale Muslehiddinoglu , Paul Lobben, Thomas LaPorte, Lori Spangler, Daniel Fichan a, Shi-Ying Chang, Donald Kientzler, John Venit, Robert Wethman and San Kiang Somer Symposium, Ankara, Turkey, May 2007. ? Development and Execution of a Continuous Process for a High Energy Acid Catal yzed Peroxide Rearrangement Lori Spangler, Mourad Hamedi, Thomas LaPorte, John Thornton, Jaan Pesti, Jale Mu slehiddinoglu, Ioannis Valvis ACS National Meeting, September 2006. ? Kinetic Study of Catalytic Hydrogenation of O-Nitroanisole to O-Anisidine in a Microchannel Reactor Sunitha Tadepalli, Raghu Halder, Adeniyi Lawal, Jale Muslehiddinoglu, Donald Kie ntzler AIChE Spring National Meeting, April 2006. ? Developing and Safe Scale-up of a Grignard Reaction by using FTIR M?ddino*lu Jale, Leung, Simon W., Olzog, Martina, and Pesti Jaan AIChE National Meeting, November 2004. ? Approaches for the Identification of Impurities in Pharmaceutical Development Pathirana, C., Davis, Merril, Lobben, Paul, M?ddino*lu Jale Small Molecule NMR, Colorado, September, 2004. ? Selective Hydrogenation of Nitroalkene reduction on Carbon-Supported Palladiu m, Platinum and Copper-Promoted Palladium Catalysts M?ddino*lu Jale, Tummala, Srinivas, Patel, Sunil, Wang, Steve Y., Leung, Simon W ., and Deshpande, Prashant AIChE National Meeting, November 2003. ? Selective Hydrogenolysis of a Benzyl Group in the presence of an Aromatic Chl

orine over Supported Palladium Catalysts Wang, Steve S.Y., Li, Jun, TenHuisen, Karen, M?ddino*lu Jale, Tummala, Srinivas, Kiang, San, and Chen, Jianping, J.P 18th NAM Meeting, June 2003. ? Selective Debenzylation in the presence of an Aromatic Chlorine on Pd/C Cataly sts:Effects of Catalyst Types and Reaction Kinetics Wang, Steve S.Y., Li, Jun, TenHuisen, Karen, M?ddino*lu Jale, Tummala, Srinivas, Kiang, San, and Chen, Jianping, J.P 20th Conference on Catalysis of Organic Reactions, March 2003. ? Characterization of Cesium- Promoted Silver Catalysts M?ddino*lu Jale, Vannice, M. Albert 18th NAM Meeting, June 2003. ? Characterization of Supported and Promoted Silver Epoxidation Catalysts using CO as a Probe Molecule M?ddino*lu Jale, Vannice, M.Albert Pittsburgh-Cleveland Catalysis Society Meetings, May 2002. ? Adsorption of NO on Silver Catalysts M?ddino*lu Jale, Vannice, M.Albert, Philadelphia Catalysis Meeting, January 2001. ? NO Adsorption on Silver Catalysts M?ddino*lu Jale, Vannice, M. Albert AICHE National Meeting, November 2000. ? NO Adsorption on Silver Catalysts M?ddino*lu Jale, Vannice, M. Albert Pittsburgh-Cleveland Catalysis Society Meetings, May 2000. ? Effect of Operating Parameters on the Selective Separation of Mercury and Cadm ium from Binary Mixtures M?ddino*lu Jale, Ozbelge, Hilmi Onder, Yilmaz Levent, 2nd Turkish National Chemical Engineering Congress, September 9-13, 1996, Istanb ul, Turkey.