Book Review pubs.acs.org/OPRD
Right First Time in Fine-Chemical Process Scale-Up: Avoiding ScaleUp Problems: The Key to Rapid Success allowing a phenomenological understanding of what chemists used to call a “black” art. Other product isolation techniques such as distillation, extraction, and filtration provide a very useful end to the chapter. The 240 case studies in chapter four are perhaps the most useful and unique aspect of the book. The half-page examples are drawn from both in-house and others’ experiences, and all are referenced. Each example is logically presented and has a reaction scheme, description of the lab-process, evaluation of the problem and development work undertaken, a description of the pilot- or plant-scale process, and a review of the learning points. To give an idea, one randomly selected and paraphrased example is: (S)-phenylglycine was reacted with acetoacetate; in the lab the reagents were heated, the solvent partially removed, and after cooling gave a crystalline product; repeated at 1 M3 pilot-scale, the process worked fine, whilst at 12 M3 plant-scale no crystallisation occurred, and the product could not be isolated; after review it was determined that the longer reaction time allowed more impurities caused by a change in pH due to K2CO3, and the impurities prevented crystallisation; when the carbonate was replaced with KOH, degradation was avoided, and the batch successfully crystallised. Chapter five summarises in numerous tables the learning points from all of the examples to help draw conclusions by identifying common primary causes in a system called ALICE (Analysis Like Interactive Concurrent Evaluation). For example, Table 1 summarises the cause, solution, and review, whilst Table 2 has examples relating to yield, selectivity, quality, or safety. Table 3 summarises the scale-up issues, e.g. mass transfer, mixing, etc., whilst Table 4 describes each type of (multi)phase from the 240 systems. There are many more tables that evaluate the data in different ways. The result is a fascinating dissection of most process problems that occur in process development and scale-up. These will be appreciated by anyone involved in process development or manufacture, and would make an interesting publication in their own right. Having presented the evidence and dissected the results, the author in the final chapter poses the logical question “Could the Surprises Have Been Avoided?” To support an affirmative answer, the author provides a comprehensive checklist with pointers to each page and chapter dealing with the issue. Finally, there is a good discussion of the main problem areas identified, such as operational time, heat transfer, procedures in lab down-scale to help evaluate different phase combinations and unit operations. Similar to a Lewis Carroll novel, the book closes with “ALICE’s Dream for the Future” in which the author considers the impact of future developments in highthroughput methods and multistep continuous processes, such as those being developed for producing artemisinin. A useful index is included.
Right First time in Fine-Chemical Process Scale-Up: Avoiding Scale-Up Problems: The Key to Rapid Success, Lumburtus A. Hulshof. Scientific Update LLP: Mayfield, U.K., 2013. 483 + xii pp. £99.50. ISBN: 978-0-9533994-1-3.
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his is the latest in a recent series of books about process research and development but is the first to specifically address Fine Chemicals. It is clear from first seeing and leafing through the book that it is a labour of love: size is A4; number of pages is 483; language is enthusiastic; exemplar case studies covered equal 240; and there is a quirky front cover. This makes it fantastic reading, to dip into rather as a guide to consult, rather than as an educational text to read cover to cover. The book will be of interest to new and experienced practitioners in the wider pharma and agro-, fine-, and speciality chemical industries rather than to students, although the latter group may find it useful to provide examples to use in coursework or in Ph.D. studies. The author is clearly an expert, with insight gained over many years working in the industry. He has a deep working appreciation not only of the chemistry, physical science, and engineering but also of their interplay, which is crucial in successful scale-up - right first time. Chapter one explains the industry’s background, covering important commercial, chemical, and engineering concepts. At times the descriptions are colloquial, and this adds to the sense of its being a narrated story, with actions louder than words, rather than an academic perfection. The chapter introduces economic, safety, environmental, efficiency, and productivity concepts that underpin process development activities. There are numerous examples, lots of tables, graphs, and figures, with 132 supporting references that illustrate well the discussion. The second chapter discusses the challenges in process development. To start with the critical chemist−chemical engineer interface is recognised. Ways in which they can work together are elucidated along with potential misunderstandings and misconceptions such as terms, measurement, and molecular- vs macroscopic-scale thinking. Again a multitude of figures and schemes provide good visualisation of the concepts that are explained in detail, such as design of experiments (DOE), screening, reactor mode, and microwave technology. The tables and graphs show comparisons of the different process variables for a number of exemplar reactions. Chapter three focuses on the challenges in process scale-up with in-depth discussion of multiphase systems, the cause of most problems. There are many examples of surface area to volume problems associated with heat and mass transfer explained along with mixing and temporal effects. Methods and equipment used in large-scale fermentations are also described. Measurement and modelling of systems are described clearly in a way comprehensible to non-engineers. Furthermore, there are subchapters with good examples on chemical and physical kinetics and thermodynamics relating to both reactivity and crystallisation that will be recognised by most practitioners. This latter subject is presented in more detail along with drying, © XXXX American Chemical Society
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dx.doi.org/10.1021/op400176g | Org. Process Res. Dev. XXXX, XXX, XXX−XXX
Organic Process Research & Development
Book Review
Overall, this book is a work of art. It covers an enormous scope and most importantly discusses lots of examples of problems, potential solutions, and their avoidance in the first place. Right First Time in Fine-Chemical Process Scale-Up is a good title for an excellent book that should be in every process chemist’s and engineer’s library.
John Blacker
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Institute of Process R&D, University of Leeds, U.K.
AUTHOR INFORMATION
Notes
The authors declare no competing financial interest.
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dx.doi.org/10.1021/op400176g | Org. Process Res. Dev. XXXX, XXX, XXX−XXX
