The first authoritative overview of past and current strategies for successful drug development by analog generation, this unique resource spans all important drug classes and all major therapeutic fields, including histamine antagonists, ACE inhibitors, beta blockers, opioids, quinolone antibiotics, steroids and anticancer platinum compounds.

Of the 19 analog classes presented in detail, 9 are described by the scientists who discoverd them.

The book includes a table of the most successful drug analogs as based on the IMS ranking and compares them in terms of chemical structure, mode of action and patentability.

A comprehensive treatise on the hot working of aluminum and its alloys, Hot Deformation and Processing of Aluminum Alloys details the possible microstructural developments that can occur with hot deformation of various alloys, as well as the kind of mechanical properties that can be anticipated. The authors take great care to explain and differentiate hot working in the context of other elevated temperature phenomena, such as creep, superplasticity, cold working, and annealing. They also pay particular attention to the fundamental mechanisms of aluminum plasticity at hot working temperatures. Using extensive analysis derived from polarized light optical microscopy (POM), transmission electron microscopy (TEM), x-ray diffraction (XRD) scanning electron-microscopy with electron backscatter imaging (SEM-EBSD), and orientation imaging microscopy (OIM), the authors examine those microstructures that evolve in torsion, compression, extrusion, and rolling. Further microstructural analysis leads to detailed explanations of dynamic recovery (DRV), static recovery (SRV), discontinuous dynamic recrystallization (dDRX), discontinuous static recrystallization (dSRX), grain defining dynamic recovery (gDRV) (formerly geometric dynamic recrystallization, or gDRX), and continuous dynamic recrystallization involving both a single phase (cDRX/1-phase) and multiple phases (cDRX/2-phase). A companion to other works that focus on modeling, manufacturing involving plastic and superplastic deformation, and control of texture and phase transformations, this book provides thorough explanations of microstructural development to lay the foundation for further study of the mechanisms of thermomechanical processes and their application.

Written by internationally acclaimed experts in the economics of innovation, this volume examines how the biotechnology and pharmaceutical sector is affected by the dynamics of innovation, institutions, and public policy. It contributes both theoretically and empirically to the increasingly influential Schumpetarian framework in industrial economics, which places innovation at the centre of the analysis of competition. Both quantitative and qualitative studies are included, and this varied perspective adds to the richness of the volume's insights. The contributors explore different ideas regarding the historical evolution of technology in the sector, and how firms and industry structure have co-evolved with innovation dynamics. Important policy questions are considered regarding the future of innovation in this sector and its impact on the economy.

This is the first book that comprehensively and systematically describes the new technology of hydrophilic interaction liquid chromatography (HILIC). Hydrophilic interaction chromatography is a separation technique suitable for polar and hydrophilic compounds and orthogonal to reversed phase liquid chromatography. From small organic molecules to proteins, the text explores the many applications of HILIC in the analytical field. Winner of the President's Award for Excellence, the author explains how HILIC can significantly improve analytical throughput by shortening sample preparation procedure, which is one of the bottlenecks for drug discovery and development in the pharmaceutical industry.

A major new work on all aspects of water, the most used raw material ingredient in the pharmaceutical and biotechnology industries used as an excipient in pharmaceutical formulations, as a cleaning agent, and as a separately packaged product diluent.

Drawing on the author s extensive field experience with more than 400 pharmaceutical and related water purification systems, the text s numerous case studies illuminate the best and worst of water system design and operation.

The expanded Second Edition also includes new chapters that discuss:

• passivation and electropolishing
• rouging
• ozone systems and accessories
• USP purified water and water for injection
• individual component process and instrumentation diagram (P&IDs) with control interface
• documentation and specification requirements
• systems installation, start-up, and commissioning

Vitamin C may offer significant therapeutic benefits in the treatment of cancer. This book includes chapters by a group of leading scientific researchers documenting the ways cancer can be affected by high doses of ascorbate. After an initial chapter providing a historical perspective, subsequent chapters focus on cancer cell death, reprogramming of somatic cells, recent case studies, and other ways vitamin C can improve outcomes of therapy. Features Includes chapters from a team of leading international scholars Reviews the history of beneficial uses of vitamin C in the treatment of cancer Summarizes recent case studies Discusses how vitamin C may synergistically affect other cancer treatment methods

Vitamin C holds a unique place in scientific and cultural history. In this book, a group of leading scientific researchers describe new insights into the myriad ways vitamin C is employed during normal physiological functioning. In addition, the text provides an extensive overview of the following: the rationale for utilizing vitamin C in the clinic, updates on recent uses of vitamin C in cancer treatment through high-dose intravenous therapies, the role vitamin C plays in the treatment of sepsis and infectious disease, management of the ways vitamin C can improve stem cell differentiation, as well as vitamin C use in other important health situations. Features Includes chapters from a team of leading international scholars Reviews the history and recent research on the functions, benefits, and uses of vitamin C Focuses special attention on the way vitamin C can be used in the treatment of cancers Discusses how vitamin C can be employed against infectious disease

Colloidal drug delivery systems present a range of therapeutic benefits in the treatment of a number of challenging conditions, allowing researchers to cross barriers that have previously prevented efficient treatment while offering improved and more targeted absorption. Summarizing recent research in the field, Colloids in Drug Delivery assembles the work of 65 of the world's leading colloid scientists who examine the full spectrum of this rapidly emerging science, from pure to applied, most of it drawn from their own experience and research. The book begins by examining the basics of surfactant and polymer surface activity and self-assembly, the various types of structures formed by such compounds, and their use in drug delivery and biotechnology. It examines the development of controlled and targeted delivery systems by utilizing the various properties of colloids before moving on to discuss various applications and fields of research. Topics discussed include: The use of hard, soft, and macromolecular colloidal drug delivery systems formed by surfactants, polymers, proteins, and lipids Recent advances in procolloidal systems, self-emulsifying drug delivery systems, and aerosol applications to pharmaceutical drug delivery Colloidal nanocarriers for imaging applications and the treatment of dental and periodontal diseases Classification and application of colloidal drug delivery systems in tumor targeting The use of colloids for improved nasal, ocular, vaginal, oral, buccal, gastrointestinal, and colon drug delivery Examining topics necessary to the critical evaluation of a drug candidate's potential for delivery, the book also describes the preparation, classification, interfacial activity, surface modifications and influence on particle characteristics, drug delivery, and drug targeting. Each chapter in this expansive volume explains why a particular system is used for the intended application, how it is made, and how it behaves. All those concerned with the research, development, and manufacture of drugs will find this a valuable reference, offering a wealth of research upon which they can build.

The development of suitable assays, the integration of appropriate technology, and the effective management of the essential infrastructure are all critical to the success of any high- throughput screening (HTS) endeavor. However, few scientists have the multidisciplinary experience needed to control all aspects of an HTS drug discovery project. A Practical Guide to Assay Development and High-Throughput Screening in Drug Discovery integrates the experience of diverse experts who offer fundamental and practical guidance across numerous situations. The book first discusses assay developments for important target classes such as protein kinases and phosphatases, proteases, nuclear receptors, G protein-coupled receptors, ion channels, and heat shock proteins. It next examines assay developments for cell viability, apoptosis, and infectious diseases. The contributors explore the application of emerging technologies and systems, including image-based high content screening, RNA interference, and primary cells. Finally, they discuss the essential components of the integrated HTS process, such as screening automation, compound library management, the screening of natural products from botanical sources, and screening informatics. Designed to motivate researchers to bring further advances to the field, this volume provides practical guidance on how to initiate, validate, optimize, and manage a bioassay intended to screen large collections of compounds. Drawing on the knowledge from experts actively involved in assay development and HTS, this is a resource that is both comprehensive and focused.

Useful Statistical Approaches for Addressing Multiplicity Issues Includes practical examples from recent trials Bringing together leading statisticians, scientists, and clinicians from the pharmaceutical industry, academia, and regulatory agencies, Multiple Testing Problems in Pharmaceutical Statistics explores the rapidly growing area of multiple comparison research with an emphasis on pharmaceutical applications. In each chapter, the expert contributors describe important multiplicity problems encountered in pre-clinical and clinical trial settings. The book begins with a broad introduction from a regulatory perspective to different types of multiplicity problems that commonly arise in confirmatory controlled clinical trials, before giving an overview of the concepts, principles, and procedures of multiple testing. It then presents statistical methods for analyzing clinical dose response studies that compare several dose levels with a control as well as statistical methods for analyzing multiple endpoints in clinical trials. After covering gatekeeping procedures for testing hierarchically ordered hypotheses, the book discusses statistical approaches for the design and analysis of adaptive designs and related confirmatory hypothesis testing problems. The final chapter focuses on the design of pharmacogenomic studies based on established statistical principles. It also describes the analysis of data collected in these studies, taking into account the numerous multiplicity issues that occur. This volume explains how to solve critical issues in multiple testing encountered in pre-clinical and clinical trial applications. It presents the necessary statistical methodology, along with examples and software code to show how to use the methods in practice.

Since the advent of cDNA microarrays, oligonucleotide array technology, and gene chip analysis, genomics has revolutionized the entire field of biomedical research. A byproduct of this revolution, toxicogenomics is a fast-rising star within toxicological analysis. Gathering together leading authors and scientists at the forefront of the field, An Introduction to Toxicogenomics provides a comprehensive overview of this new discipline. With a focus on toxicology, it introduces the basic principles of microarray/oligonucleotide array-based genomic analysis and explains how it fits into the field of biomedical research. These discussions provide an overview to the actual mechanics of the analyses themselves and offer insights on handling and quality control. Then the book features an important section on the basics of data analysis and clustering methods such as genetic algorithms. Finally, it covers the application of expression profiling in the field of toxicology and addresses the two fundamental types of analysis in detail, with sections dedicated to both mechanistic and predictive studies. Although toxicogenomics promises fast, efficient techniques and information-rich data, much of its potential remains untapped. An Introduction to Toxicogenomics consolidates the concepts underlying the field to provide a solid foundation from which to begin your research endeavors.

The development of suitable assays, the integration of appropriate technology, and the effective management of the essential infrastructure are all critical to the success of any high-throughput screening (HTS) endeavor. However, few scientists have the multidisciplinary experience needed to control all aspects of an HTS drug discovery project. A Practical Guide to Assay Development and High-Throughput Screening in Drug Discovery integrates the experience of diverse experts who offer fundamental and practical guidance across numerous situations. The book first discusses assay developments for important target classes such as protein kinases and phosphatases, proteases, nuclear receptors, G protein-coupled receptors, ion channels, and heat shock proteins. It next examines assay developments for cell viability, apoptosis, and infectious diseases. The contributors explore the application of emerging technologies and systems, including image-based high content screening, RNA interference, and primary cells. Finally, they discuss the essential components of the integrated HTS process, such as screening automation, compound library management, the screening of natural products from botanical sources, and screening informatics. Designed to motivate researchers to bring further advances to the field, this volume provides practical guidance on how to initiate, validate, optimize, and manage a bioassay intended to screen large collections of compounds. Drawing on the knowledge from experts actively involved in assay development and HTS, this is a resource that is both comprehensive and focused.

A must-have reference for any researcher or scientist interested in cutaneous protective mechanisms, this guide provides expertly researched chapters on every aspect of stratum corneum structure, function, and development, as well as detailed sections on barrier-repair strategies and the role of barrier function in diseases such as atopic dermatitis, psoriasis, and ichthyosis.

All too often, the words "computer validation" strike terror into the hearts of those new to the process and may even cause those familiar with it to tremble. Validating Pharmaceutical Systems: Good Computer Practice in Life Science Manufacturing delineates GCP, GLP, and GMP regulatory requirements and provides guidance from seasoned practitioners on how to fulfill them. John Andrews and his team tackle the perceived complexities surrounding the validation of a wide variety of automated systems. Sprinkled with case studies and real-life examples, the book offers a step-by-step review of topics such as planning, design, auditing, risk management, and specification. The in-depth, by example coverage demystifies the challenges of manufacturing execution systems(MES), laboratory information management systems(LIMS), and network qualification. The first section examines the different levels of automated systems used throughout the drug development, manufacture, and delivery lifecycle, using the GAMP 4 lifecycle approach to their validation. The second section uncovers some real-life applications of GAMP 4 to different areas of the regulations such as GLP, GCP, GMP, and GDP. The book explores some of the latest thinking on computer validation and reflects changes that have occurred in the industry since the early days of validation. The contributors are a deliberate blend of those who have faced the problems of the 1990s and the Y2K controversies and those who have more recently arrived on the scene and made an impact on the perception of validation of automated systems across the field of GxP. They do more than show you how to do the right thing; they show you how to do the right thing in compliance with regulations.

Using clear and practical examples, Polymorphism in Pharmaceutical Solids, Second Edition presents a complete examination of polymorphic behavior in pharmaceutical development.
Ideal for pharmaceutical development scientists and graduate students in pharmaceutical science, this updated edition includes:
NEW CHAPTERS - on the latest developments and methods in the field that give pharmaceutical development scientists the up-to-date information they need to successfully implement new drug development techniques and methods
EXPERT EDITORSHIP - from Dr. Harry G. Brittain, whose vast experience and knowledge of the pharmaceutical industry provides readers with the authoritative advice they need and trust
COMPREHENSIVE CONTENT - that includes information appropriate for all levels of expertise in the field, from experienced pharmaceutical scientists to graduate students in physical pharmacy
200 HIGH QUALITY ILLUSTRATIONS - that present readers with a visual blueprint to the methods and techniques involved in polymorphism and solvatomorphism

Written especially for the pharmaceutical industry professional, this book addresses each part of the life-cycle of engineering change control. It covers issues in the EU and US and describes the operational requirements and responsibilities that ensure change controls are effectively applied and recorded. Providing guidance on how to demonstrate that a change control system is working, the book includes chapters on computer validation, customization of the change process to each project's needs, and case histories and anecdotes illustrate key points and provide a basis for change control training. It gives readers a toolbox for ensuring that adequate controls are implemented.

One of the biggest computer validation challenges facing pharmaceutical manufacturers is the large corporate system. This book provides practical information and advice on good IT practice and validation principles. Written by experts, it includes case studies on EDMSs, EAM systems, LIMSs, and MRP II systems.

A Single Source on Parallel Synthesis for Lead Optimization The end of the previous millennium saw an explosion in the application of parallel synthesis techniques for making compounds for high-throughput screening. Over time, it became clear that more thought in the design phase of library development is necessary to generate high quality hits. More recently, the use of parallel synthesis techniques has shifted to applications beyond screening collections. Exploring the nuances of this technology, High-Throughput Lead Optimization in Drug Discovery describes the application of parallel synthesis to lead optimization and the design and synthesis of targeted libraries. Examine Case Studies that Cover a Range of Different Biological Targets Featuring real-world examples and contributions from well-known scientists, the book explores the shift to conducting parallel lead optimization in-house while outsourcing most of the screening libraries synthesis. It includes more than 15 case studies that encompass a range of biological targets for application in different therapeutic areas. The text contains examples of solid and solution-phase techniques for the synthesis of directed libraries. The chapter authors explain the design principles they used to direct the choice of templates and diversity elements. Speed Up Drug Discovery and the Hit-to-Lead Process Focusing on the application of combinatorial chemistry to medicinal chemistry, this volume compiles a series of optimization projects that give you a snapshot of successes and challenges in the use of parallel synthesis for lead optimization. It explores how this technology, when applied to library design, can speed up drug discovery.

The introduction of combinatorial chemistry technology has increased the amount of compounds generated in a year from 50 to 2000. Conventional analytical approaches simply cannot keep up. These circumstances have caused drug discovery to take on the shape of a bottleneck, like traffic through a toll booth. In order to break the bottleneck, a corresponding revolutionary improvement to the conventional methodology must happen.

Liposome Technology, Volume III: Interactions of Liposomes with the Biological Milieu, Third Edition, is a comprehensively updated and expanded new edition of a classic text in the field. Including step-by-step technical details, Volume III describes technologies for yielding liposomes that can function in a targeted fashion, and highlights methods for studying the interaction of liposomes within the biological environment to be applied in the detection, therapy, or prevention of disease. This source also offers critical discussions of the methodologies of each technology described so that readers can examine the benefits and limitations and compare it to other approaches.

Safety pharmacology is the evaluation and study of the pharmacological effects of a potential drug that are unrelated to the desired therapeutic effect. These effects often present a hazard-particularly in individuals with compromised or limited organ system functions. Safety Pharmacology in Pharmaceutical Development: Approval and Post Marketing Surveillance, Second Edition covers safety pharmacology from the regulatory requirements down to the studies that must be done to justify them. Using the author's more than 30 years of direct experience, the book incorporates tricks and practical insights for making studies work and understanding why they fail. The second edition includes current regulations, including USFDA and those from Europe and Japan. Presenting a clear description of what is needed and why for supporting drug development, the book focuses on updated test methods, interpretation, and science. It covers the core and supplemental batteries of test procedures and how to do them and provides an overview of available facilities and contract organizations for performing studies.

Adaptive clinical trial designs, unlike traditional fixed clinical trial designs, enable modification of studies in response to the data generated in the course of the trial. This often results in studies that are substantially faster, more efficient, and more powerful. Recent developments in web-based real-time data entry and advances in statistical methods have made adaptive clinical trials much more popular because they have become both more practical and attractive. However, there is paucity of resources that explain the mathematical framework and the practical considerations for adaptive designs without the use of highly technical statistical jargon. Suitable for readers in academia, industry, and government involved in drug development, Adaptive and Flexible Clinical Trials is the first book that comprehensively explains all essential aspects of adaptive clinical trials. Written in an easy-to-understand style aimed at clinicians and other non-statisticians, this book focuses not on the statistical details, but rather on the application of statistical concepts for adaptive clinical trials. Utilizing concrete examples, the book thoroughly explains the design, conduct, and analysis of adaptive and flexible clinical trials, allowing readers to select and design the appropriate trial designs from a conceptual perspective. From basic theory to real-life practical issues, it covers all aspects of adaptive and flexible clinical trials, including regulatory issues, interim analysis, adaptive dosing, and sequential designs.

Providing more than just a comprehensive history, critical vocabulary, insightful compilation of motivations, and clear explanation of the state-of-the-art of modern clinical trial simulation, this book supplies a rigorous framework for employing simulation as an experiment, according to a predefined simulation plan, that reflects good simulation practices. The book discusses how to clinical trial designs according to their probability for success, techniques to define distributions of virtual subjects' characteristics, methods to determine the sensitivity of the trial design, and the population relationship between dosing schedules and patient response.

A True Insider's Guide to the Field - Then and Now Until now, there has not been a book that effectively addresses the historical basis of protein discovery. Featuring contributions from a distinguished international panel of experts, Protein Discovery Technologies elucidates the principles, techniques, strategies, and broad range of applications of protein discovery by documenting the often untold stories and personal accounts of the contributors' past scientific achievements. Incorporates Short, Personal Discovery Vignettes Rather than an exhaustive field analysis, this globally pertinent resource presents in-depth discussions of various methods for protein discovery, including bioinformatics, interaction cloning, protein purification, phage display, non-primate models, and chemical targeting. It also explores biological themes through the examination of cell death, angiogenesis, hemostasis, development, signal transduction, transcriptional control, cell cycle control, neurobiology, and quality control. This readily accessible resource discusses an array of interesting topics, including: Tumor necrosis factors The origin of interferon as an angiogenesis inhibitor In vivo combinatorial mapping of vascular zip codes Extracellular matrix degradome as regulators of angiogenesis and tumor growth A matricellular protein prototype The use of RING finger proteins as E3 Ubiquitin Ligases Whereas most books tend to be more specialized, this book contains a broad view of the protein discoveries in many different fields, making Protein Discovery Technologies a valuable reference for today's researchers, both the new and more seasoned, who are seeking a newfound perspective or a deeper understanding of this exciting field.

Addressing issues at the forefront of interest for the Clinical Trial Materials Professional (CTMP), this Second Edition highlights the most critical concepts related to the planning, manufacturing, packaging, labeling, distribution, reconciliation, and quality and regulatory control of clinical trial materials-offering an authoritative selection of chapters on the current and evolving state of clinical supplies operations by esteemed researchers and consultants in industry.