New Developments in Chemical Engineering for the Production of Drug Substances

Behr, Arno; Brehme, Volker A.; Ewers, Christian L. J.; Gron, Heidi; Kimmel, Thorsten; Küppers, Stephan; Symietz, Ingo

doi:10.1002/elsc.200406127

Cited by 39 publications

(39 citation statements)

References 36 publications

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“…The chains have grown rapidly in recent years due to market rivalry for new, safe and effective drugs with short production times (Behr et al, 2004;Gebauer, Kickuth & Friedli, 2009;Melton, 2005). The market demand for variety in pharmaceutical produce requires greater flexibility, smaller orders and a more varied mix of products within the manufacturing process (Gilmore & Smith, 1996).…”

Section: Research Contextmentioning

confidence: 99%

Job design under lean manufacturing and the quality of working life: a job demands and resources perspective

Cullinane

Bosak

Flood

et al. 2014

The International Journal of Human Resource Management

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ii Declaration I hereby certify that this material, which I now submit for assessment on the programme of study leading to the award of Doctor of Philosophy is entirely my own work, and that I have exercised reasonable care to ensure that the work is original, and does not to the best of my knowledge breach any law of copyright, and has not been taken from the work of others save and to the extent that such work has been cited and acknowledged within the text of my work. Flood. Patrick has provided great support and guidance during the past four years. He was also very influential in my decision to undertake the PhD during my time as a teaching assistant in DCU, and I will always be grateful for that push in the right direction. Over the past four years Janine has become both a wonderful mentor and a great friend. She has acted as my personal coach during this time and continued to build my confidence in my writing, presenting, and analytical skills, particularly when I was feeling insecure. Janine has also been a great advocate of my career and helped me to broaden my skills during my time as a PhD student in terms of teaching, writing and networking. The activities we were involved in together kept me sane and allowed me to maintain balance and perspective on my research. Both supervisors shared their wide international network of colleagues with me during my research which allowed me to meet and work with a number of very influential and interesting people over the years. It was a pleasure to work with you both.I would also like to thank Professor Eva Demerouti (Eindhoven University of Technology) with whom I collaborated with throughout this research. Eva was extremely accommodating when I approached her as an inexperienced and nervous first year student wanting to draw on her time and expertise in the area of engagement and burnout. I am very grateful for all the time, advice and encouragement she provided at our meetings in Utrecht, Eindhoven and during conferences. I also wish to acknowledge the time and effort spent by Eva in reading my work and assisting me with my statistical analysis, which is greatly appreciated. AbstractStudies to date which examine the quality of working life under lean manufacturing have yielded contradictory findings, whereby positive, negative and contingent effects on employee well-being have been demonstrated. A large contributor to these inconsistencies is the absence of an applicable model of job design which captures the complex socio-technical nature of this context. This research proposes and tests a model of job design under lean manufacturing using the Job Demands-Resources framework in order to capture the distinct motivational and health-impairing potential of this context. Cross-sectional data was collected from 200 employees working in a multi-national pharmaceutical manufacturing organisation with extensive lean usage. The findings supported hypotheses relating to the direct and interactive effects of lean-specific resources and demands in the prediction of ...

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Section: Research Contextmentioning

confidence: 99%

Job design under lean manufacturing and the quality of working life: a job demands and resources perspective

Cullinane

Bosak

Flood

et al. 2014

The International Journal of Human Resource Management

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“…replicating small units working in parallel. 1,10,14 However, fluid distribution and parallelization of microscale units is not such a straightforward task as is often claimed, 20 and according to Kockmann et al, 21 it should even be kept as a last option. Furthermore, practical problems such as blockages from solids in suspension still form a main limitation for microreaction technology.…”

Section: Introductionmentioning

confidence: 99%

“…1,2 Fierce competition and increasing time and cost related to drug discovery and development have motivated a change in the business strategy of pharmaceutical companies, increasingly emphasizing cost reduction and shorter time to market. 3,4 These objectives must be met through an improvement of the efficiency and sustainability of all processes related to the discovery, development and long-term manufacturing of drug products.…”

Section: Introductionmentioning

confidence: 99%

“…2 The U.S. Food and Drug Administration (FDA) has also encouraged the adoption of advanced manufacturing and real-time quality-control technologies through the publication of the process analytical technology (PAT) guidance. 9 Several studies have demonstrated the advantages of performing both active pharmaceutical ingredient (API) synthesis [6][7][8]10,11 and drug product formulation 1,4,7,12 in continuous mode. In the context of organic synthesis-based API production, microreactors 8,10,11,13−15 and microseparation 10,16,17 processes have intensively been studied in recent years, providing the basic tools for continuous flow multistep organic synthesis.…”

Section: Introductionmentioning

confidence: 99%

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Monitoring and Control of a Continuous Grignard Reaction for the Synthesis of an Active Pharmaceutical Ingredient Intermediate Using Inline NIR spectroscopy

Padrell

Nielsen

Pedersen

et al. 2012

Org. Process Res. Dev.

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Inline near-infrared (NIR) spectroscopy has been used to monitor a continuous synthesis of an active pharmaceutical ingredient (API) intermediate by a Grignard alkylation reaction. The reaction between a ketone substrate and allylmagnesium chloride may form significant impurities with excess feeding of the Grignard reagent beyond the stoichiometric ratio. On the other hand, limiting this reagent would imply a loss in yield. Therefore, accurate dosing of the two reactants is essential. A feedforward−feedback control loop was conceived in order to maintain the reaction as closely as possible to the stoichiometric ratio, leading the path to full process automation. The feedback control loop relies on NIR transmission measurements performed in a flow cell where, in contrast to labor-intensive offline HPLC analytical methods, the whole reaction product can be scanned in real time without sample dilution. A robust PLS (projection to latent structures) model was developed with a satisfactory standard error of prediction, providing quantification of the ketone substrate in solutions with a high variability of the major solution componentthe alkoxide product. In addition, model performance supervision tools such as the spectral residuals or simple plots of pretreated spectra can assist in the identification of spectral outliers, which in this case could be related to Grignard reagent excess. If the sampling time of the NIR instrument is short enough, manipulating the inputs to the reactor may be used to obtain information about its dynamic behavior. This information is very useful for process control design, assessment of analytical tools and definition of sampling times. In this work, a systematic procedure for chemometric model building is followed, after which a discussion is made on some of the potential applications that can be found when exploiting the fast and rich information provided by NIR spectroscopy.

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“…Die integrierte MiniplantTechnologie, die sich der Miniplant-Technik, Modellierung und Simulation bedient und in der chemischen Verfahrenstechnik Stand der Technik ist, ermöglicht die Untersuchung von verschalteten Verfahrensstufen oder kompletten Prozessen zur beschleunigten Verfahrensentwicklung [1,2] [5], Mustermengen zu produzieren [5], den Einfluss von akkumulierenden Nebenprodukten aufgrund von Rückführungen zu untersuchen [6], die Stabilität der verwendeten Werkstoffe zu prü-fen [7], sind weitere wichtige Anwendungsgebiete von Miniplant-Anlagen. Neben dem Einsatz als Forschungs-und Versuchsanlage können Miniplants für die Kleinmengenproduktion genutzt werden [8]. Bei der Produktion toxischer Stoffe bieten kontinuierliche Miniplant-Anlagen gegenüber absatzweise betriebenen Produktionsanlagen den Vorteil, das Gefahrenpotenzial zu verringern [9].…”

Section: Introductionunclassified

Einsatz und Potenzial der integrierten Miniplant‐Technologie für die Enzymkatalyse

Berendsen

Samorski

2006

Chemie Ingenieur Technik

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New Developments in Chemical Engineering for the Production of Drug Substances

Cited by 39 publications

References 36 publications

Job design under lean manufacturing and the quality of working life: a job demands and resources perspective

Job design under lean manufacturing and the quality of working life: a job demands and resources perspective

Monitoring and Control of a Continuous Grignard Reaction for the Synthesis of an Active Pharmaceutical Ingredient Intermediate Using Inline NIR spectroscopy

Einsatz und Potenzial der integrierten Miniplant‐Technologie für die Enzymkatalyse

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