Identifying current tools, techniques, and approaches for the evaluation of laboratory operations, this reference reviews the latest regulatory standards and auditing practices to test laboratory safety, quality, and performance.

Dosage Form Design Parameters, Volume I, examines the history and current state of the field within the pharmaceutical sciences, presenting key developments. Content includes drug development issues, the scale up of formulations, regulatory issues, intellectual property, solid state properties and polymorphism. Written by experts in the field, this volume in the Advances in Pharmaceutical Product Development and Research series deepens our understanding of dosage form design parameters. Chapters delve into a particular aspect of this fundamental field, covering principles, methodologies and the technologies employed by pharmaceutical scientists. In addition, the book contains a comprehensive examination suitable for researchers and advanced students working in pharmaceuticals, cosmetics, biotechnology and related industries.

Specifically geared to personnel in the pharmaceutical and biotechnology industries, this book describes the basics and challenges of oral bioavailability one of the most significant hurdles in drug discovery and development. Describes approaches to assess pharmacokinetics and how drug efflux and uptake transporters impact oral bioavailability Helps readers reduce the failure rate of drug candidates when transitioning from the bench to the clinic during development Explains how preclinical animal models used in preclinical testing and in vitro tools translate to humans, which is an underappreciated and complicated area of drug development Includes chapters about pharmacokinetic modelling, the Biopharmaceutics Drug Disposition Classification System (BDDCS), and the Extended Clearance Classification System (ECCS) Has tutorials for applying strategies to medicinal chemistry practices of drug discovery/development

This authoritative volume examines the major laws, regulations and guidelines related to pharmaceutical product development in China. With a focus on patent, clinical and registration strategies, the book helps Western companies introduce their clinical drugs to the Chinese market, determine a strategic path and bridge the gap for regulatory and legal differences between China and the Western world. For a better understanding of the drug registration process, it explores the differences between the China Food and Drug Administration (CFDA)-including its regulations and registration procedures-and those of the Western world. The volume discusses disparities between China's application requirements compared to Western standards to make it easier for companies to prepare their application packages. It also provides detailed commentary on CFDA guidelines in reference to clinical trial (IND) and market application (NDA) requirements. Overall, this book offers guidance for Western companies aspiring to expand into China's pharmaceutical market in hopes that they may gain a fundamental understanding of its rules and complexities in order to ensure a smooth transition and prevent future issues.

Through this monograph, the pharmaceutical chemist gets familiar with the possibilities electroanalytical methods offer for validated analyses of drug compounds and pharmaceuticals. The presentation focuses on the techniques most frequently used in practical applications, particularly voltammetry and polarography. The authors present the information in such a way that the reader can judge whether the application of such techniques offers advantages for solving a particular analytical problem. Basics of individual electroanalytical techniques are outlined using as simple language as possible, with a minimum of mathematical apparatus. For each electroanalytical technique, the physical and chemical processes as well as the instrumentation are described. The authors also cover procedures for the identification of electroactive groups and the chemical and electrochemical processes involved. Understanding the principles of such processes is essential for finding optimum analytical conditions in the most reliable way. Added to this is the validation of such analytical procedures. A particularly valuable feature of this book are extensive tables listing numerous validated examples of practical applications. Various Indices according to the drug type, the electroactive group and the type of method as well as a subject and author index are also provided for easy reference.

This book provides a detailed account of the most recent developments, challenges and solutions to seamlessly advance and launch a lyophilized biologics or vaccine product, based on diverse modalities, ranging from antibodies (e.g., monoclonal, fused), complex biologics (e.g., antibody drug conjugate, PEGylated proteins), and vaccines (e.g., recombinant-protein based). The authors adeptly guide the reader through all crucial aspects, from biophysical and chemical stability considerations of proteins, analytical methods, advances in controlled ice nucleation and quality-by-design approaches, alternate drying technology, to latest regulatory, packaging and technology transfer considerations to develop a stable, safe and effective therapeutic protein, vaccine and biotechnology products. Lyophilized Biologics and Vaccines: Modality-Based Approaches is composed of four sections with a total of 17 chapters. It serves as a reference to all critical assessments and steps from early pre-formulation stages to product launch: Provides recent understanding of heterogeneity of protein environment and selection of appropriate buffer for stabilization of lyophilized formulations Details the latest developments in instrumental analysis and controlled ice nucleation technology Explains in-depth lyophilized (or dehydrated) formulation strategies considering diverse modalities of biologics and vaccines, including plasmid DNA and lipid-based therapeutics Details an exhaustive update on quality-by-design and process analytical technology approaches, illustrated superbly by case studies and FDA perspective Provides the latest detailed account of alternate drying technologies including spray drying, bulk freeze-drying and crystallization, supported exceptionally by case studies Provides a step-by-step guide through critical considerations during process scale-up, technology transfer, packaging and drug delivery device selection, for a successful lyophilization process validation, regulatory submission and product launch Chapters are written by one or more world-renowned leading authorities from academia, industry or regulatory agencies, whose expertise cover lyophilization of the diverse modalities of biopharmaceuticals. Their contributions are based on the exhaustive review of literature coupled with excellent hands-on experiences in laboratory or GMP setup, making this an exceptional guide to all stages of lyophilized or dehydrated product development.

In this book, clinicians and basic scientists from USA, India, and other countries discuss the rationales and clinical experiences with targeted approaches to treat, prevent, or manage cancer. Cancer is a hyperproliferative disorder that is regulated by multiple genes and multiple cell signaling pathways. Genomics, proteomics, and metabolomics have revealed that dysregulation of dozens of genes and their products occur in any given cell type that ultimately leads to cancer. These discoveries are providing unprecedented opportunities to tackle cancer by multi-faceted approaches that target these underpinnings. This book emphasizes a multi-targeted approach to treating cancer, the focus of the 5th International Conference on Translational Cancer Research that was held in Vigyan Bhawan, Delhi (India) from Feb 6-9, 2014.

Medicinal chemistry is both science and art. The science of medicinal chemistry offers mankind one of its best hopes for improving the quality of life. The art of medicinal chemistry continues to challenge its practitioners with the need for both intuition and experience to discover new drugs. Hence sharing the experience of drug research is uniquely beneficial to the field of medicinal chemistry. Drug research requires interdisciplinary team-work at the interface between chemistry, biology and medicine. Therefore, the topic-related series Topics in Medicinal Chemistry covers all relevant aspects of drug research, e.g. pathobiochemistry of diseases, identification and validation of (emerging) drug targets, structural biology, drugability of targets, drug design approaches, chemogenomics, synthetic chemistry including combinatorial methods, bioorganic chemistry, natural compounds, high-throughput screening, pharmacological in vitro and in vivo investigations, drug-receptor interactions on the molecular level, structure-activity relationships, drug absorption, distribution, metabolism, elimination, toxicology and pharmacogenomics. In general, special volumes are edited by well known guest editors.

This volume offers a comprehensive guide on the theory and practice of amorphous solid dispersions (ASD) for handling challenges associated with poorly soluble drugs. In twenty-three inclusive chapters, the book examines thermodynamics and kinetics of the amorphous state and amorphous solid dispersions, ASD technologies, excipients for stabilizing amorphous solid dispersions such as polymers, and ASD manufacturing technologies, including spray drying, hot melt extrusion, fluid bed layering and solvent-controlled micro-precipitation technology (MBP). Each technology is illustrated by specific case studies. In addition, dedicated sections cover analytical tools and technologies for characterization of amorphous solid dispersions, the prediction of long-term stability, and the development of suitable dissolution methods and regulatory aspects. The book also highlights future technologies on the horizon, such as supercritical fluid processing, mesoporous silica, KinetiSol (R), and the use of non-salt-forming organic acids and amino acids for the stabilization of amorphous systems. Amorphous Solid Dispersions: Theory and Practice is a valuable reference to pharmaceutical scientists interested in developing bioavailable and therapeutically effective formulations of poorly soluble molecules in order to advance these technologies and develop better medicines for the future.

Natural products and functional/medical foods are now widely acknowledged as having an effect on the microbiome of the intestine, which in turn influences the outcome of certain disease. This book reviews the impact and effects of natural products and functional/medical foods (nutritional programming) on disease management, specifically focusing on diseases related to 1) Inflammation and Immunity, 2) Cancer, COPD and Cachexia, 3) Allergy and 4) Brain Neuro/Immune. Hippocrates said "let medicine be thy food and food be thy medicine". While most of us are familiar with Hippocrates famous words, we admit that in recent times, the disciplines of pharma and nutrition have evolved separately. Today, with the ever growing burden of diseases in modern society, we see a convergence of the two in relation to specific disease prevention and treatment. This re-discovered common ground between the complementary values of pharma and nutrition can be conceptualized in the term pharma-nutrition. Various chapters in the book review the aspects of molecular characteristics of food ingredients towards clinical effectiveness and relevance.

This detailed volume addresses key issues and subtle nuances involved in developing hydrophilic matrix tablets as an approach to oral controlled release. It brings together information from more than five decades of research and development on hydrophilic matrix tablets and provides perspective on contemporary issues. Twelve comprehensive chapters explore a variety of topics including polymers (hypromellose, natural polysaccharides and polyethylene oxide) and their utilization in hydrophilic matrices, critical interactions impacting tablet performance, in vitro physical and imaging techniques, and microenvironmental pH control and mixed polymer approaches, among others. In one collective volume, Hydrophilic Matrix Tablets for Oral Controlled Release provides a single source of current knowledge, including sections of previously unpublished data. It is an important resource for industrial and academic scientists investigating and developing these oral controlled release formulations.

Drug Delivery Systems, Second Edition expands upon the previous edition with current, detailed methods and technologies to further study drug delivery. With new chapters on nanobiotechnology techniques, experimental methods and the clinical use for the intrathecal delivery of analgesics. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Drug Delivery Systems, Second Edition will be useful for pharmaceutical scientists as well as well as physicians both in the academic institutions and in the industry.

The complexity of biological systems has intrigued scientists from many disciplines and has given birth to the highly influential field of systems biology wherein a wide array of mathematical techniques, such as flux balance analysis, and technology platforms, such as next generation sequencing, is used to understand, elucidate, and predict the functions of complex biological systems.  More recently, the field of synthetic biology, i.e., de novo engineering of biological systems, has emerged. Scientists from various fields are focusing on how to render this engineering process more predictable, reliable, scalable, affordable, and easy.  Systems and control theory is a branch of engineering and applied sciences that rigorously deals with the complexities and uncertainties of interconnected systems with the objective of characterising fundamental systemic properties such as stability, robustness, communication capacity, and other performance metrics. Systems and control theory also strives to offer concepts and methods that facilitate the design of systems with rigorous guarantees on these properties. Over the last 100 years, it has made stellar theoretical and technological contributions in diverse fields such as aerospace, telecommunication, storage, automotive, power systems, and others. Can it have, or evolve to have, a similar impact in biology? The chapters in this book demonstrate that, indeed, systems and control theoretic concepts and techniques can have a significant impact in systems and synthetic biology.  Volume I provides a panoramic view that illustrates the potential of such mathematical methods in systems and synthetic biology.  Recent advances in systems and synthetic biology have clearly demonstrated the benefits of a rigorous and systematic approach rooted in the principles of systems and control theory - not only does it lead to exciting insights and discoveries but it also reduces the inordinately lengthy trial-and-error process of wet-lab experimentation, thereby facilitating significant savings in human and financial resources.  In Volume I, some of the leading researchers in the field of systems and synthetic biology demonstrate how systems and control theoretic concepts and techniques can be useful, or should evolve to be useful, in order to understand how biological systems function.  As the eminent computer scientist Donald Knuth put it, "biology easily has 500 years of exciting problems to work on". This edited book presents but a small fraction of those for the benefit of (1) systems and control theorists interested in molecular and cellular biology and (2) biologists interested in rigorous modelling, analysis and control of biological systems.

The world is beset by a pandemic of obesity and type 2 diabetes and the need for new drugs is startlingly clear; recent years have seen a huge increase in research activity to fill this gap. The development of new drugs for diabetes and obesity must be founded upon a sound appreciation of the pathophysiology of these common disorders. The dual defects of insulin resistance and impaired insulin secretion are fundamental to the pathogenesis and progression of obesity-associated type 2 diabetes. There is a need to explain how new drugs can counter insulin resistance and insulin deficiency to a broad range of professionals, from clinical scientists active in early (and later) phase drug development to specialist physicians and increasingly primary care doctors who must tailor drug regimens to the individual patient. Clinical research methods for measuring insulin action and insulin secretion have become well-established in proof-of-mechanism studies; however, selection of the best techniques is by no means straightforward. The purpose of the book is to aid the selection of the most appropriate techniques for assessing insulin action, insulin secretion and body composition in humans (with particular reference to new drugs) in phase 1 and 2 studies and aid the understanding of drug effects and non-drug treatment strategies on key biochemical-hormonal defects of obesity and type 2 diabetes. The book will assume a working knowledge of human physiology relating to glucose metabolism and will be of interest to biomedical scientists, pharmacologists, academics involved in metabolic research and clinicians practicing in these specialties.

This authoritative volume provides a contemporary view on the latest research in molecules with optimal drug-like properties. It is a valuable source to access current best practices as well as new research techniques and strategies. Written by leading scientists in their fields, the text consists of fourteen chapters with an underlying theme of early collaborative opportunities between pharmaceutical and discovery sciences. The book explores the practical realities of performing physical pharmaceutical and biopharmaceutical research in the context of drug discovery with short timelines and low compound availability. Chapters cover strategies and tactics to enable discovery as well as predictive approaches to establish, understand and communicate risks in early development. It also examines the detection, characterization, and assessment of risks on the solid state properties of advanced discovery and early development candidates, highlighting the link between solid state properties and critical development parameters such as solubility and stability. Final chapters center on techniques to improve molecular solubilization and prevent precipitation, with particularly emphasis on linking physiochemical properties of molecules to formulation selection in preclinical and clinical settings.

Achieving operational excellence is a challenge for the pharmaceutical industry, with many companies setting successful examples time and again. This book presents such leading practices for managing operational excellence throughout the pharmaceutical industry. Based on the St.Gallen OPEX Model the authors describe the current status of OPEX and the future challenges that have to be dealt with. The ample theoretical background is complemented hand-in-hand by case studies contributed by authors from leading pharmaceutical companies.​

In his thesis, Kiyoun Lee describes his studies into tandem and organocatalytic oxa-conjugate addition reactions for the synthesis of complex tetrahydropyrans (THP). Readers gain insight into the new methods Lee employs for the synthesis of biologically interesting natural products including (+)-leucascandrolide A, (+)-dactylolide, and (±)diospongin A. The reactions Lee investigates are applicable to a broad range of substrates and proceed with excellent stereoselectivity. Moreover, the methodologies allow the synthesis of a wide range of THP-containing compounds. The development of reactions, such as those discussed by Lee, has the potential to impact natural product synthesis, pharmaceutical development and chemical biology.

The octanol-water partition coefficient is a laboratory-measured property of a substance. It provides a thermodynamic measure of the tendency of the substance to prefer a non-aqueous or oily milieu rather than water (i.e. its hydrophilic/lipophilic balance). Partition coefficients are used extensively in medicinal chemistry, drug design, ecotoxicology and environmental chemistry. The partition coefficient is recognized by governmental and international agencies (U.S. Environmental Protection Agency, OECD) as a physical property of organic pollutants equal in importance to vapour pressure, water solubility and toxicity. Octanol-Water Partition Coefficients is a comprehensive and up-to-date survey of the thermodynamics of partitioning and of the octanol-water pair. In addition, all current methods of measurement are reviewed, strengths and weaknesses are noted and recommendations for particular applications are given. Current methods of calculation of partition coefficients are similarly surveyed and described. Five of the most popular computerized methods are tested for predictive accuracy for drugs, pollutants, aminoacids, etc. The book will be of interest not only to solution chemists, but to any chemists who use partition coefficients. It provides a thorough understanding of the fundamentals and offers clear guidance on the choice of methods of measurement and calculation. Contents: Introduction, Thermodynamics and Extrathermodynamics of Partitioning, Experimental Methods of Measurement, Discussion of Measurement Methods, Methods of Calculating Partitioning Coefficients, Discussion of LogKow Predictive Methods The Wiley Series in Solution Chemistry fills the increasing need to present authoritative, comprehensive and fully up-to-date accounts of the many aspects of solution chemistry. Internationally recognized experts from research or teaching institutions in various countries are invited to contribute to the series.

The development of innovative drugs is becoming more difficult while relying on empirical approaches. This inspired all major pharmaceutical companies to pursue alternative model-based paradigms. The key question is: How to find innovative compounds and, subsequently, appropriate dosage regimens? Written from the industry perspective and based on many years of experience, this book offers: - Concepts for creation of drug-disease models, introduced and supplemented with extensive MATLAB programs - Guidance for exploration and modification of these programs to enhance the understanding of key principles - Usage of differential equations to pharmacokinetic, pharmacodynamic and (patho-) physiologic problems thereby acknowledging their dynamic nature - A range of topics from single exponential decay to adaptive dosing, from single subject exploration to clinical trial simulation, and from empirical to mechanistic disease modeling. Students with an undergraduate mathematical background or equivalent education, interest in life sciences and skills in a high-level programming language such as MATLAB, are encouraged to engage in model-based pharmaceutical research and development.

This book presents the fundamentals and applications of Matrix Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-ToF-MS) technique. It highlights the basic principles, the history of invention as well as the mechanism of ionization and mass determination using this technique. It describes the fundamental principles and methods for MALDI spectra interpretation and determination of exact chemical structures from experimental data. This book guides the reader through the interpretation of MALDI data where complex macromolecular spectra are simplified in order to present the major principles behind data interpretation. In addition, each chapter describes how MALDI-ToF-MS analysis provides necessary understanding of the copolymer systems that have been designed for specialized biomedical applications.

Modern Strategy for Preclinical Pharmaceutical R&D Towards the Virtual Research Company David Cavalla Arachnova Ltd, Cambridge, UK With contributions from: John Flack AMRAD Corporation, Richmond, Australia and Richard Jennings Wolfson Industrial Liaison Office, University of Cambridge, UK The twentieth century has been a great success for modern medicine, and has resulted in the generation of a plethora of drugs to treat most common illnesses. However, in the light of increasing regulatory demands, spiralling costs and diminishing commercial returns, the question of how, when, where and whether to conduct pharmaceutical R&D has profound implications, and not just for those within the pharmaceutical industry. Modern Strategy for Preclinical Pharmaceutical R&D gets to the heart of the debate that surrounds this topic and asks the questions: Can the economies of scale of large multinational pharmaceutical companies adequately compensate for the loss of creative individualism that is essential for the process of drug discovery and development? Might technological experts provide better services to a number of clients rather than work within a single large infrastructure where confidentiality is paramount and synergy of multi-disciplinary operation readily possible? What are the long-term prospects for the latest alternatives to large pharmaceutical R&D companies? In response to these and other dilemmas, the authors define the processes involved in drug R&D, explore the advantages and disadvantages of collaborative methods of drug research, and examine the roles that academia, CROs, small 'biotechnology' companies and 'research boutiques', and possibly even the 'virtual research company'might play as contractors and collaborators. Without a doubt, Modern Strategy for Preclinical Pharmaceutical R&D is essential reading for all those interested in making sense of the confusion that surrounds today's pharmaceutical industry.

This comprehensive text presents a rigorous framework from within which regulators can respond strategically to the claim by the pharmaceutical industry that lower drug prices today lead to a loss for the population's future health due to less innovation. It starts with a critical review of the empirical evidence of the return to consumers on their ongoing investment into high drug prices in order to increase future innovation. The implicit, critical and unrealistic assumption inherent in these studies is identified, namely that the health budget can be expanded to purchase drugs at higher prices without an opportunity cost, for example, the foregone benefits of alternative investments in health care infrastructure. Price effectiveness analysis (PEA), is introduced. PEA informs the question of how the innovative surplus from the new drug should be allocated between the manufacturer and the consumer so as to optimise society's welfare. The method allows the decisions by the regulator and the firm to be analysed jointly by specifying the firm's production and revenue functions in terms of the clinical innovation of a new drug; the incremental effect used in the summary metric of cost effectiveness analysis. An economic value of innovation that takes into account opportunity cost under conditions of economic efficiency in the health system is proposed: the health shadow price. The limitations of the non-strategic methods that currently inform the highly contested new drug subsidy game are presented and the relative strengths of PEA are demonstrated. Health technology assessment quantifies both the clinical innovation of a new drug and its financial impact on the health system. Cost effectiveness analysis tests the relationship between the incremental cost and incremental effect of a new drug for target patients, at a given price. PEA tests the relationship between the price of a new drug and the health of the whole population, now and into the future. It achieves this by taking into account current inefficiency in both resource allocation and the displacement process, and the relationship between price and future innovation.

The development of new CNS drugs is notoriously difficult. Drugs must reach CNS target sites for action and these sites are protected by a number of barriers, the most important being the blood -brain barrier (BBB). Many factors are therefore critical to consider for CNS drug delivery, e.g. active/passive transport across the BBB, intra-brain distribution, and central/systemic pharmacokinetics, to name a few. Neurological disease and trauma conditions add further complexity because CNS barriers, drug distribution and pharmacokinetics are dynamic and often changed by disease/trauma. Knowledge of all these factors and their interplay in different conditions is of utmost importance for proper CNS drug development and disease treatment. In recent years much information has become available for a better understanding of the many factors important for CNS drug delivery and how they interact to affect drug action. This book describes small and large drug delivery to the brain with an emphasis on the physiology of the BBB and the principles and concepts for drug delivery across the BBB and distribution within the brain. It contains methods descriptions for studying drug delivery, routes and approaches of administering drugs into the brain, the influence of disease, and drug industry perspectives. Therewith, it contributes to an in-depth understanding of the interplay between brain (patho)-physiology and drug characteristics. Furthermore, the content is designed to be both cutting-edge and educational, so that the book can be used in high-level training of academic and industry scientists with full references to original publications.

One of the most promising new approaches for the prevention of HIV transmission, particularly for developing countries, involves topical, self-administered products known as microbicides. The development of microbicides is a long and complicated process, and this volume provides an overview of all the critical areas, from the selection of appropriate candidate molecules and their formulation, preclinical and clinical testing for safety and efficacy, strategies for product registration and finally, issues associated with product launch, distribution and access. The book will prove valuable to both those working in the field and all others who are interested in learning more about this product class, which has the potential to significantly impact the future of this devastating epidemic.

The series Structure and Bonding publishes critical reviews on topics of research concerned with chemical structure and bonding. The scope of the series spans the entire Periodic Table and addresses structure and bonding issues associated with all of the elements. It also focuses attention on new and developing areas of modern structural and theoretical chemistry such as nanostructures, molecular electronics, designed molecular solids, surfaces, metal clusters and supramolecular structures. Physical and spectroscopic techniques used to determine, examine and model structures fall within the purview of Structure and Bonding to the extent that the focus is on the scientific results obtained and not on specialist information concerning the techniques themselves. Issues associated with the development of bonding models and generalizations that illuminate the reactivity pathways and rates of chemical processes are also relevant. The individual volumes in the series are thematic. The goal of each volume is to give the reader, whether at a university or in industry, a comprehensive overview of an area where new insights are emerging that are of interest to a larger scientific audience. Thus each review within the volume critically surveys one aspect of that topic and places it within the context of the volume as a whole. The most significant developments of the last 5 to 10 years should be presented using selected examples to illustrate the principles discussed. A description of the physical basis of the experimental techniques that have been used to provide the primary data may also be appropriate, if it has not been covered in detail elsewhere. The coverage need not be exhaustive in data, but should rather be conceptual, concentrating on the new principles being developed that will allow the reader, who is not a specialist in the area covered, to understand the data presented. Discussion of possible future research directions in the area is welcomed. Review articles for the individual volumes are invited by the volume editors. Readership: research scientists at universities or in industry, graduate students Special offer For all customers who have a standing order to the print version of Structure and Bonding, we offer free access to the electronic volumes of the Series published in the current year via SpringerLink.