Concepción Jiménez-González

Expanding GSK's solvent selection guide – embedding sustainability into solvent selection starting at medicinal chemistry

Solvents make a large contribution to the environmental impact of manufacturing processes of active pharmaceutical ingredients (API), as well as playing an important role in other chemical industries, with millions of tons used and disposed of each year. GlaxoSmithKline (GSK) has previously reported on the both the development of a GSK solvent selection guide and the incorporation of solvent life cycle inventory and assessment information. The GSK solvent selection guide has been further enhanced by: • Revising the assessments of factors that impact process safety, separating reactivity from fire and explosion rankings. • More than doubling the number of solvents in the guide, to a total of 110 from the initial 47. • Adding a customised solvent selection guide appropriate for medicinal chemistry and analytical laboratories. The new GSK solvent selection guide enables GSK scientists to objectively assess solvents and determine whether existing or new solvents brought to market as ‘greener’ alternatives truly represent a more sustainable choice or whether they are just addressing a single issue associated with sustainability.

Method for selection of solvents for promotion of organic reactions

A method to select appropriate green solvents for the promotion of a class of organic reactions has been developed. The method combines knowledge from industrial practice and physical insights with computer-aided property estimation tools for selection/design of solvents. In particular, it employs estimates of thermodynamic properties to generate a knowledge base of reaction, solvent and environment related properties that directly or indirectly influence the rate and/or conversion of a given reaction. Solvents are selected using a rules-based procedure where the estimated reaction-solvent properties and the solvent-environmental properties guide the decision making process. The current method is applicable only to organic reactions occurring in the liquid phase. Another gas or solid phase, which may or may not be at equilibrium with the reacting liquid phase, may also be present. The objective of this method is to produce, for a given reaction, a short list of chemicals that could be considered as potential solvents, to evaluate their performance in the reacting system, and, based on this, to rank them according to a scoring system. Several examples of application are given to illustrate the main features and steps of the method.

Bioprocesses: Modeling needs for process evaluation and sustainability assessment

The next generation of process engineers will face a new set of challenges, with the need to devise new bioprocesses, with high selectivity for pharmaceutical manufacture, and for lower value chemicals manufacture based on renewable feedstocks. In this paper the current and predicted future roles of process system engineering and life cycle inventory and assessment in the design, development and improvement of sustainable bioprocesses are explored. The existing process systems engineering software tools will prove essential to assist this work. However, the existing tools will also require further development such that they can also be used to evaluate processes against sustainability metrics, as well as economics as an integral part of assessments. Finally, property models will also be required based on compounds not currently present in existing databases. It is clear that many new opportunities for process systems engineering will be forthcoming in the area of integrated bioprocesses.

Solvents in organic synthesis : Replacement and multi-step reaction systems

Abstract The solvent selection methodology developed earlier by Gani et al. [Gani, R., Jimenez-Gonzalez, C., & Constable, D. J. C. (2005). Method for selection of solvents for promotion of organic reactions. Computers and Chemical Engineering , 29 , 1661–1676] has been extended to handle multi-step reaction systems as well as solvent substitution for specific reaction steps for existing processing systems. The problems were formulated based on the methodology guidelines, and solved using ICAS software tool [ICAS Documentation. (2003). Internal report . CAPEC, Department of Chemical Engineering, Technical University of Denmark]. Highly promising results were obtained, either in accordance with results previously published in the literature, or with industrial process data. This shows that the methodology has potential for application to complex reaction schemes as well as on the problems of solvent replacement.

The evolution of life cycle assessment in pharmaceutical and chemical applications – a perspective

This paper provides a broad strokes perspective on the evolution for the application of Life Cycle Assessment (LCA) within the pharmaceutical and chemical industries. This focus is mainly on the challenges faced to produce the needed inventory data and using the resulting LCA output in decision making, which are the backbone of any LCA estimation and practical application in industry. It also provides some of the insights the authors have derived over the last two decades of work in this area, and proposes a series of development needs within life cycle assessment as it becomes more integrated into decision-making in industry.

Systematic Selection of Green Solvents for Organic Reacting Systems

The solvent selection methodology developed earlier by Gani et al. (Comp. Chem. Eng., 2005) has been extended to handle multi-step reaction systems. The solvent selection problem was formulated based on the methodology guidelines, and solved using ICAS software tool. A list with solvent candidates is generated so that it can be further investigated experimentally. Comments and clarifications from chemists have been incorporated into the problem formulations to clarify the role of the solvents in the chemistry and potential reactivity issues. Highly promising results were obtained, in accordance with Industrial process data.

How do you select the “greenest” technology? Development of guidance for the pharmaceutical industry

There is widespread interest in government and industry in green chemistry and green technology. For truly “green” processes to be developed, scientists must take a concurrent, integrated approach that considers chemistry and technology. While it is vital to understand those things traditionally considered in technology selection such as operational, quality, and cost differences, it is equally vital to understand the associated environmental and safety issues that are inherent to the chosen technology. This is a major challenge and there is a clear need for guidance in this area. This paper proposes the concept of a “Clean/Green Technology Guide” as an expert system that would provide scientists and engineers with comparative environmental and safety performance information on available technologies for commonly performed unit operations in the pharmaceutical industry. At this stage, the framework has been developed to demonstrate the concept, using a metric set based on the concepts of sustainable development. This framework is used to evaluate the alternatives on a case-scenario basis, and will compare traditional and emerging technologies. A life-cycle approach is also used in the evaluation of the alternatives. This approach is illustrated by comparing batch, mini-, and microreactors.

Energy optimization during early drug development and the relationship with environmental burdens

Process development in the pharmaceutical industry is oriented to several key objectives, like yield or purity; and energy usage is normally given only a secondary consideration. On the other hand, there is a growing interest to give a greater weight to environmental factors as an integral part of the decision-making process at the Research and Development (R&D) stages of design for drug manufacturing. Therefore, there is a need to assess the energy usage throughout the development stage, to be able to quantify the changes in the development phases and evaluate the total environmental benefits due to energy optimization. In the present work, energy life cycle information is developed to provide environmental input into process selection and development within the pharmaceutical industry. The evaluation and comparison of energy requirements and energy-related emissions at various stages of the development process for a pharmaceutical product was conducted. It was found that the main optimization in energy usage for this specific system takes place during the pilot scale stage in the process developments (about 70% energy reduction). The reductions in energy usage are translated in even higher reduction of total energy-related emissions (for the full-scale processes, around 80%). It could be clearly seen that energy optimization in the early stages of process design translates into a lower level of emissions related to the use of energy.

Chapter 18 Technology assessment for a more sustainable enterprise: The GSK experience

Publisher Summary This chapter discusses the Glaxo Smith Khnes (GSK) experience for technology assessment for a more sustainable enterprise. One aspect of GSK Environment, Health and Safety (EHS) vision for environmental sustainability is to champion the research and implementation of increasingly sustainable technologies and processes. While developing and implementing these programs, it became increasingly clear that the greatest short to medium term gains toward more sustainable practices would be realized at the interface of chemistry and technology. While GSK Corporate EHS had developed considerable understanding of fundamental pharmaceutical industry chemistry and chemical processing approaches to more sustainable practices, there was a lack of understanding about the materials and energy efficiency implications related to technology selection. As a result, a Green Technology Guide (GTG) is developed for technologies and unit operations of interest to the pharmaceutical industry. The Guide is developed as a module of the existing Web-based Green Chemistry Guide, and was designed to provide scientists and engineers with comparative assessments of unit operations from a sustainability perspective.