Making medicinal chemistry more effective—application of Lean Sigma to improve processes, speed and quality

Andersson, Shalini; Armstrong, Alan; Björe, Annika; Bowker, Sue; Chapman, Steve; Davies, R.J.; Donald, Craig S.; Egner, Bryan J.; Elebring, Thomas; Holmqvist, Sara; Inghardt, Tord; Johannesson, Petra; Johansson, Magnus; Johnstone, Craig; Kemmitt, Paul D.; Kihlberg, Jan; Korsgren, Pernilla; Lemurell, Malin; Moore, Jane E.; Pettersson, Jonas; Pointon, Helen; Pontén, Fritiof; Schofield, Paul N.; Selmi, Nidhal; Whittamore, Paul R.O.

doi:10.1016/j.drudis.2009.03.005

Cited by 62 publications

(33 citation statements)

References 10 publications

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“…Most companies start with larger basket of projects in exploratory phase (preclinical) and utilize filtration funnel to rapidly eliminate projects that do not meet pre-established criteria. The efficiency of process and quality of lead generated can be improved by judicious selection of available technologies at various stages of drug discovery such as target ID and/or validation (over expression and knockout), hit generation phase (X-ray crystallography, structure guided drug discovery (SGDD), fragment based, virtual screening, high throughput screening (HTS)) to lead optimization (scaffold hopping, allosteric versus active site modulation, drug pharmacokinetics properties such as absorption, distribution, metabolism and excretion (ADME), selectivity and safety screens) [18][19][20], The projects in lead optimization and clinical phase should always have 'critical killer' experiments with intent to substantiate the 'target product profile' and establish discrimination versus standard of care or competing molecules in clinic. The innovation is crucial in lead generation and for problem solving along the way.…”

Section: Quality Rather Than Quantitymentioning

confidence: 99%

Drug discovery in pharmaceutical industry: productivity challenges and trends

Khanna¹

2012

Drug Discovery Today

373

223

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Section: Quality Rather Than Quantitymentioning

confidence: 99%

Drug discovery in pharmaceutical industry: productivity challenges and trends

Khanna¹

2012

Drug Discovery Today

373

223

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“…The Metrics Champion Consortium, an industry association, has developed standardized performance metrics and supports metric benchmarking for clinical trial improvement. Pharmaceutical research and development teams, clinical laboratories, Institutional Review Boards (IRBs), and research management programs have all discoursed applications of improvement methods to drug discovery, IRB approval, and other processes . Yet such methods are rarely part of public discussions of research, research training program curricula, recommended components within grant applications, or research papers.…”

Section: Why Apply Improvement Methods To Research Processes?mentioning

confidence: 99%

“…Pharmaceutical research and development teams, clinical laboratories, Institutional Review Boards (IRBs), and research management programs have all discoursed applications of improvement methods to drug discovery, IRB approval, and other processes. [14][15][16] Yet such methods are rarely part of public discussions of research, research training program curricula, recommended components within grant applications, or research papers. As academic medical centers' clinical leadership and management are adopting process improvement methods and tools, these approaches have been largely untapped by research teams.…”

Section: Why Apply Improvement Methods To Research Processes?mentioning

confidence: 99%

Applying Process Improvement Methods to Clinical and Translational Research: Conceptual Framework and Case Examples

Daudelin

Selker

Leslie

2015

Clinical Translational Sci

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There is growing appreciation that process improvement holds promise for improving the quality and efficiency across the translational research continuum but frameworks for such programs are not often described. The purpose of this paper is to present a framework and case examples of a Research Process Improvement Program implemented at Tufts CTSI. To promote research process improvement, we developed online training seminars, workshops, and in-person consultation models to describe core process improvement principles and methods, demonstrate the use of improvement tools, and illustrate the application of these methods in case examples. We implemented these methods, as well as relational coordination theory, with junior researchers, pilot funding awardees, our CTRC, and CTSI resource and service providers. The program focuses on capacity building to address common process problems and quality gaps that threaten the efficient, timely and successful completion of clinical and translational studies.

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“…Initiatives like six sigma and lean thinking focus on the improvement of the efficiency of the complete discovery process while maintaining the quality [5,6]. As a result, high-throughput synthesis (combinatorial chemistry), efficient purification procedures or (open access) purity analysis, fast screening of various physicochemical properties and metabolic stability, high-throughput screening technologies for target-ligand screening (IC50 assays) and functional assays have all received tremendous attention [7].…”

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confidence: 99%

MS Applications in Support of Medicinal Chemistry Sciences

Honing¹,

Ingelse²,

Pramanik³

2013

Mass Spectrometry for Drug Discovery and Drug Development

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In the drug discovery process, medicinal chemistry plays a crucial role in the optimal design and synthesis (production) of new chemical entities (NCEs) or new biological entities (NBEs); this is true for a single entity as well as a complete compound library. A key requirement in this field of science is the optimization of both the chemical and the biological properties of these potential drug-like compounds. Important criteria are the design of efficient synthesis routes, the balancing of the physical chemical properties with optimal in vitro and in vivo drug metabolism and pharmacokinetic (DMPK) processes, and a profound understanding of the pharmacodynamics in the appropriate pharmacological models. In the lead optimization stage, an important step is scaling up the synthesis route as needed for the execution of toxicology studies and the screening of suitable drug formulations. In summary, medicinal chemistry support includes participating in a large variety of activities and decision making processes that play a key role in the search for either a "first in class" new drug or a "best in class" new drug [1].These "drug discovery" processes are continuously under pressure, as the research and development (R&D) costs continue to increase and more data are requested before new drug candidates are taken into (pre-)clinical development. Hence, the choice of "targeted" high-throughput screening (HTS) libraries, the process of hit appraisal, and the understanding of target-ligand interactions can be considered the starting points for a new drug discovery program [2]. Next, the main focus is on the discovery of a lead compound; typically, this is a compound showing promising data regarding target affinity, reasonable efficacy in cellular models, good physical chemical parameters (i.e., a "drug-like" compound), and acceptable oral bioavailability in Mass Spectrometry for Drug Discovery and Drug Development, First Edition. Edited by Walter A. Korfmacher.

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Making medicinal chemistry more effective—application of Lean Sigma to improve processes, speed and quality

Cited by 62 publications

References 10 publications

Drug discovery in pharmaceutical industry: productivity challenges and trends

Drug discovery in pharmaceutical industry: productivity challenges and trends

Applying Process Improvement Methods to Clinical and Translational Research: Conceptual Framework and Case Examples

MS Applications in Support of Medicinal Chemistry Sciences

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