Pharmaceutical Process Development: Current Chemical and Engineering Challenges (RSC Drug Discovery, 9) - Hardcover

 
9781849731461: Pharmaceutical Process Development: Current Chemical and Engineering Challenges (RSC Drug Discovery, 9)
Hardcover
ISBN 10: 1849731462 ISBN 13: 9781849731461
Verlag: ROYAL SOCIETY OF CHEMISTRY, 2011

Inhaltsangabe

Pharmaceutical process research and development is an exacting, multidisciplinary effort but a somewhat neglected discipline in the chemical curriculum. This book presents an overview of the many facets of process development and how recent advances in synthetic organic chemistry, process technology and chemical engineering have impacted on the manufacture of pharmaceuticals. In 15 concise chapters the book covers such diverse subjects as route selection and economics, the interface with medicinal chemistry, the impact of green chemistry, safety, the crucial role of physical organic measurements in gaining a deeper understanding of chemical behaviour, the role of the analyst, new tools and innovations in reactor design, purification and separation, solid state chemistry and its role in formulation. The book ends with an assessment of future trends and challenges. The book provides a valuable overview of: both early and late stage chemical development, how safe and scaleable synthetic routes are designed, selected and developed, the importance of the chemical engineering, analytical and manufacturing interfaces, the key enabling technologies, including catalysis and biocatalysis, the importance of the green chemical perspective and solid form issues. The book, written and edited by experts in the field, is a contemporary, holistic treatise, with a logical sequence for process development and mini-case histories within the chapters to bring alive different aspects of the process. It is completely pharmaceutical themed, encompassing all essential aspects, from route and reagent selection to manufacture of the active compound. The book is aimed at both graduates and postgraduates interested in a career in the pharmaceutical industry. It informs them about the breadth of the work carried out in chemical research and development departments, and gives them a feel for the challenges involved in the job. The book is also of value to academics who often understand the drug discovery arena, but have far less appreciation of the drug development area, and are thus unable to advise their students about the relative merits of careers in chemical development versus discovery.

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Über die Autorin bzw. den Autor

Michael T Williams, formerly at Pfizer, now carries out independent consulting work and is an Associate Consultant with Scientific Update, in addition to his work in editing and scientific writing. After completing a BSc Sp Hons in Chemistry at King's College, London, he won a Science and Industry Award giving him a year of industrial experience as a medicinal chemist at ICI Pharmaceuticals, and an earmarked SRC grant. Following his PhD with Prof. Charles Rees at the University of Liverpool, he joined the Chemical Research and Development department of Pfizer. His mid-career responsibilities at Pfizer included the Medicinal Chemistry/Development interface, outsourcing initiatives and technology adoption. In addition to his experience with about 50 early drug candidates, he played a significant role in the late development, filing and commercialization of many agents including ZoloftTM, ViagraTM and RelpaxTM. He rose to become Executive Director and Departmental Head of UK Chemical Research and Development  in 2003 and he also spent a 10 month secondment leading 75 formulators, and helping to build a 40 strong Material Sciences group. John Blacker holds the Chair of Process Chemistry and is Director of the Institute of Process Research and Development, positions held jointly between the School of Chemistry and School of Process Environmental and Materials Engineering at the University of Leeds. Until recently he worked as Research and Development Technical Director at Piramal Healthcare and has been in the fine chemicals industry for over 17 years with predecessor companies Avecia, Zeneca and ICI. Prior to this, he was a post-doctoral fellow with Prof. Sir Alan Fersht at the University of Cambridge; did a PhD and DEA in Chimie Organiques with Prof. Jean-Marie Lehn at the University Louis Pasteur Strasbourg, and a BSc Sp.Hons in Chemistry and Biochemistry at the University of Sheffield. As an industrial chemist, he has made contributions to asymmetric catalysis, pharmaceutical process research and development, with over 80 original research articles, patents and many presentations at international conferences, and was awarded the RSC Process Technology Award in 2006. He is also involved in establishing an Institute of Process Research and Development aimed at bridging the innovation gap and supplying the chemical industry with valuable and competitive new technology.

Von der hinteren Coverseite

Pharmaceutical process research and development is an exacting, multidisciplinary effort but a somewhat neglected discipline in the chemical science curriculum. This book presents an overview of the many facets of process development and how recent advances in synthetic organic chemistry, process technology and chemical engineering have impacted on the manufacture of pharmaceuticals. In fifteen concise chapters the book covers such diverse subjects as route design and selection, the interface with medicinal chemistry, the importance of green chemistry, the design of safe chemical reactions, the crucial role of physical organic measurements in gaining a deeper understanding of chemical behaviour, the role of the analyst, new tools and innovations in reactor design, purification and separation, solid state chemistry and its role in formulation. It ends with an assessment of future trends and challenges. The book is aimed at both graduates and postgraduates interested in a career in the pharmaceutical industry. It informs them about the breadth of the work carried out in chemical research and development departments, and gives them a feel for the challenges involved in the job. The book is also of value to academics who often understand the drug discovery arena, but have far less appreciation of drug development, and are thus unable to advise their students about the relative merits of careers in chemical development versus discovery. Within the pharmaceutical industry the book will be a useful training aid to scientists at an early stage of their careers.

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Pharmaceutical Process Development

Current Chemical and Engineering Challenges

By A. John Blacker, Michael T. Williams

The Royal Society of Chemistry

Copyright © 2011 Royal Society of Chemistry
All rights reserved.
ISBN: 978-1-84973-146-1

Contents

Contributors, xix, 
Chapter 1 Introduction A. John Blacker and Mike T. Williams, 1, 
Chapter 2 Process Research and Development in the Pharmaceutical Industry: Origins, Evolution and Progress Trevor Laird, 15, 
Chapter 3 Active Pharmaceutical Ingredients: Structure and Impact on Synthesis John S. Carey and Dave Laan, 39, 
Chapter 4 Rapid Early Development of Potential Drug Candidates Nicholas M. Thomson, Pieter D. de Koning, Adam T. Gillmore and Yong Tao, 66, 
Chapter 5 Route Design and Selection Mike Butters, 90, 
Chapter 6 The Importance of Green Chemistry in Process Research & Development Peter J. Dunn, 117, 
Chapter 7 Kinetic Approaches for Faster and Efficient Process Development Suju P. Mathew, 138, 
Chapter 8 The Design of Safe Chemical Reactions: It's No Accident David J. Dale, 160, 
Chapter 9 Physicochemical Data Requirements for the Design of Fine Chemical Processes: Acquisition and Application John H. Atherton, 178, 
Chapter 10 Liquid–Liquid Extraction for Process Development in the Pharmaceutical Industry Ian F. McConvey and Paul Nancarrow, 209, 
Chapter 11 Development Enabling Technologies Mike J. Monteith and Mark B. Mitchell, 238, 
Chapter 12 The Analytical Interface and the Impact on Pharmaceutical Process Development Simon Hamilton and Alexis Bertrand, 260, 
Chapter 13 Materials Science: Solid Form Design and Crystallisation Process Development Kevin Roberts, Robert Docherty and Stefan Taylor, 286, 
Chapter 14 Technology Transfer of an Active Pharmaceutical Ingredient Stephen McGhie and Stuart Young, 317, 
Chapter 15 Future Trends and Challenges A. John Blacker and Mike T. Williams, 331, 
Subject Index, 342,


CHAPTER 1

Introduction

A. JOHN BLACKER AND MIKE T. WILLIAMS

1.1 Process Research and Development in Context

Pharmaceutical process research and development (R&D) is a complex, challenging and exciting endeavour that crosses the boundaries between synthetic organic chemistry, process technology and chemical engineering. This book will explore the various aspects of process research and development for small-molecule manufacture that must be brought together to provide sufficient quantities of reliable and cost effective medicines, made with low environmental impact, to make the drug both a success for the company and a safe, affordable and sustainably produced medicine for society.

The pharmaceutical industry has grown inconceivably since early drugs such as aspirin and penicillin were discovered and developed. The growth was first fuelled by post-war increased healthcare requirements in North America, Western Europe and Japan. The undoubted impact of wide access to medicines has been the increase in life expectancy, which has doubled and continues to increase. The growing populations within the economies of Asia and South America are not only starting to benefit from cheaper and more available medicines, but especially in the case of Asia are increasingly responsible for their production. Traditionally poor economies such as Africa are also starting to access cheaper, more widely distributed, medicines which may help alleviate suffering and improve mortality rates. More recently in Western economies there has been an increased demand for medicines to manage lifestyle in areas such as type II diabetes, anti-cholesterolaemics and infertility, and this is similarly expected to continue rising.

The discovery of a drug candidate by medicinal chemistry is the first step in a long journey to the marketplace, and the vast majority of candidates fall by the wayside. The timescale of the overall drug discovery and development process, and the high attrition rate, are illustrated in Figures 1.1 and 1.2. As the drug progresses through clinical trials, the demands for material increase. Not only is drug substance required for clinical trials, but also for analytical, stability, formulation and in vitro studies. Whilst the total amount of drug active required depends upon its activity, effect and physical properties, typical requirements are 1 kg at phase I, 50–100 kg at phase II and at phase III up to 1 tonne. As the drug progresses through the development pipeline, the project team estimates the likely commercial demand profile and ensures that it orders a sizeable contingency to avoid demand outstripping supply. Once launched, the successful drug sees growth in volume that for high-dose drugs (g d-1) may exceed 1000s of tonnes per annum, or for low-dose drugs 100 kg per annum. The period approaching expiry of the main patent sees a significant change in the management of drug supply. Competition from generic producers affects the amount of drug manufactured, partly controlled by their interest in attacking the market and partly by the originating company's strategy. Over the past decade, only about 25 new chemical entities (NCEs) have been approved to enter the global market each year, and the cost of discovering and developing each NCE has been estimated to be in the range of $500–2000 million, depending on the therapeutic area and developing company.

As the drug development programme proceeds, the process R&D group will scale-up new synthetic processes from the laboratory, through to the pilot plant and ultimately into full-scale commercial manufacture, if the programme is successful. In the course of this endeavour, the process R&D group will serve three disparate customers:

• The development process requires escalating quantities of the active pharmaceutical ingredient (API) of the requisite purity for toxicological, clinical and other studies.

• Production requires a synthetic route and a robust manufacturing process to operate if the API is commercialised.

• Regulatory agencies require that the developed process is demonstrated to reproducibly produce the API of the approved high quality, when operated within defined and validated parameters.


1.2 Aims and Scope of the Book

The book is aimed at chemistry, engineering and pharmacy under- and postgraduate students and early to mid career professionals, but may also be of interest to those in allied disciplines such as biologists, medical and business people. To adequately cover the field, the book considers each aspect of process R&D more or less chronologically as it occurs during a project. For example, deciding what equipment will be required for manufacture requires good definition of the chemical process, which in turn necessitates a clearly defined route. The interdependency of each area must be recognised and the book will try to point these out within each chapter. Process R&D expertise resides largely within industry, which is why most of the chapters are authored by currently practicing experts. A number of academic institutions and funding organisations now recognise the need for strategic research and specific training requirements to support the pharmaceutical industry.

This book thus differs from most others that have been published in the area as it is organised to try to walk the reader logically through key aspects of the pharmaceutical chemical R&D process, covering the essential aspects encountered in both early and late stage process development toward...

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Verlag
ROYAL SOCIETY OF CHEMISTRY
Erscheinungsdatum
2011
Sprache
Englisch
ISBN 10 
1849731462
ISBN 13 
9781849731461
Einband
Gebundene Ausgabe
Anzahl der Seiten
354
Herausgeber
Blacker John, Williams Michael T.
Kontakt zum Hersteller
Nicht verfügbar
Verantwortliche Person
Buchbär
info@buchbaer.de

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