Inhaled Pharmaceutical Product Development Perspectives: Challenges and Opportunities describes methods and procedures for consideration when developing inhaled pharmaceuticals, while commenting on product development strategies and their suitability to support regulatory submission. It bridges the gap between the aspirations of scientists invested in new technology development and the requirements that must be met for any new product. The book brings together emerging analytical and inhalation technologies, providing perspectives that illuminate formulation and device design, development, regulatory compliance, and practice. Focusing on underlying scientific and technical principles known to be acceptable from the current regulatory perspective, this monograph will remain useful as a high-level guide to inhaled product development for the foreseeable future.

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.

The 2012 International Conference on Applied Biotechnology (ICAB 2012) was held in Tianjin, China on October 18-19, 2012. It provides not only a platform for domestic and foreign researchers to exchange their ideas and experiences with the application-oriented research of biotechnology, but also an opportunity to promote the development and prosperity of the biotechnology industry. The proceedings of ICAB 2012 mainly focus on the world's latest scientific research and techniques in applied biotechnology, including Industrial Microbial Technology, Food Biotechnology, Pharmaceutical Biotechnology, Environmental Biotechnology, Marine Biotechnology, Agricultural Biotechnology, Biological Materials and Bio-energy Technology, Advances in Biotechnology, and Future Trends in Biotechnology. These proceedings are intended for scientists and researchers engaging in applied biotechnology. Professor Pingkai Ouyang is the President of the Nanjing University of Technology, China. Professor Tongcun Zhang is the Director of the Key Laboratory of Industrial Fermentation Microbiology of the Ministry of Education at the College of Bioengineering, Tianjin University of Science and Technology, China. Dr. Samuel Kaplan is a Professor at the Department of Microbiology & Molecular Genetics at the University of Texas at Houston Medical School, Houston, Texas, USA. Dr. Bill Skarnes is a Professor at Wellcome Trust Sanger Institute, United Kingdom.

Volume III of this manual provides an overview of the analytical investigation of 23 additional Chinese Herbal Drugs, which are most commonly used in Traditional Chinese Medicine. Together with Volumes I and II this current volume represents the most comprehensive overview to analytical studies of those herbal drugs. The quality proof of the investigation meets the standard of the European Drug Regulatory Authority. The authors refer to the bioactive constituents, pharmacological and biological activities of all single herbal drugs, as well as their therapeutic applications. Analytical methods applied are described in detail.

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.

Volumes are organized topically and provide a comprehensive discussion of developments in the respective field over the past 3-5 years. The series also discusses new discoveries and applications. Special volumes are dedicated to selected topics which focus on new biotechnological products and new processes for their synthesis and purification. In general, special volumes are edited by well-known guest editors. The series editor and publisher will however always be pleased to receive suggestions and supplementary information. Manuscripts are accepted in English.

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.

This volume focuses on current evidence-based pharmacological treatments of various forms of pulmonary hypertension and provides a comprehensive review of the latest developments in this area. The first part of the book covers the definition, classification, pathophysiology, pathology, biomarkers and animal models of the disease, thus laying the conceptual basis for what follows. The middle section provides an overview of the established therapies, such as calcium channel blockers, prostanoids, endothelin receptor antagonists, phosphodiesterase-5 inhibitors and inhaled nitric oxide. The last section explores novel pathways and emerging therapeutic approaches including soluble guanylate cyclase stimulators, Rho-kinase inhibitors, inhibitors of serotonin receptors and transporters, peptide growth factors, vasoactive peptides, modulators of redox equilibrium and cyclic nucleotide homeostasis, as well as immunosuppressive and anti-proliferative agents. Particular attention is given to the clinical applications of these experimental therapies, that are on the horizon. The book thus spans the continuum from basic science to clinical applications.

This book highlights the challenges facing quality assurance/quality control (QA/QC) in today's biopharmaceutical environment and presents the strategic importance and value generated by QA/QC for their involvement in control of manufacturing. It will put into perspective the need for a graded approach to QA/QC from early clinical trials through market approval. Since the first edition published in 2004, there have been more than 50 new regulatory guidances released by the Food and Drug Administration (FDA), European Medicines Agency (EMA) and ICH that affect the CMC regulatory compliance of biopharmaceuticals; also the application of biosimilars has been developed in Europe and is under development in the USA. The revised update will be broadened to include not only biopharmaceuticals (biotech drugs) but also other biologics (vaccines, cell therapy, plasma-derived proteins, etc.)

Examples from various organs and diseases illustrate the potential benefit obtained when both therapeutic approaches are combined with delivery strategies. Representing the combined effort of several leading international research and clinical experts, this book, Emerging Trends in Cell and Gene Therapy, provides a complete account on and brings into sharp focus current trends and state-of-the-art in important areas at the interface of cell- and gene-based therapies. This book addresses the current fragmented understanding regarding these two research areas and fills the vast unmet educational need and interest of both students and researchers in academia and industry. Main features of the book: * Biological aspects of stem cell sources, differentiation and engineering. * Application of microfluidics to study stem cell dynamics * Potential clinical application of stem cells and gene therapy to specific human disease. * Utilization of biomaterials and stem cells in regenerative medicine with particular emphasis on spinal cord repair, ligament and bone tissue engineering. * Biomimetic multiscale topography for cell alignment.

Satya P. Gupta's Hydroxamics Acids is the first book to compile invited articles written by international experts on the class of compounds hydroxamic acids. Found to possess a wide spectrum of biological activities, the hydroxamic acids are of interest to theoretical and experimental chemists who can study and make use of them in drug design and development. Chapters in this book provide a diverse and comprehensive coverage of this compound class and consequently this publication is a valuable resource for researchers in chemical, pharmaceutical and biological sciences.

The author successfully developed novel anti-HIV PD 404182 derivatives that exhibited submicromolar inhibitory activity against both HIV-1 and HIV-2. His thesis is in three parts. The first part expounds efficient methods for the synthesis of tricyclic heterocycles related to PD 404182 based on the sp2-carbon−heteroatom bond formations. Starting from arene or haloarene, C-O, C-N, or C-S bonds were formed by simply changing the reactants. These synthetic methods provide powerful approaches for the divergent preparation of pyrimido-benzoxazine, -quinazoline, or -benzothiazine derivatives. The second part explains SAR studies of PD 404182 for the development of anti-HIV agents. Through optimization studies of the central 1,3-thiazin-2-imine core, the benzene and cyclic amidine ring parts, 3-fold more potent inhibitors were obtained compared with the lead compound. The author also reveals by a time-of-drug-addition experiment that PD 404182 derivatives impaired HIV replication at the binding or fusion stage. The third part of the thesis elucidates the development of photoaffinity probes for the target identification of PD 404182. By the photolabeling experiment of HIV-1-infected H9 cells using these probes, the author detected proteins specifically bound to PD 404182. These new anti-HIV agents may be promising agents for anti-HIV therapy because their mechanisms of action differ from those of the currently approved anti-HIV agents.

Presents Practical Applications of Mass Spectrometry for Protein Analysis and Covers Their Impact on Accelerating Drug Discovery and Development * Covers both qualitative and quantitative aspects of Mass Spectrometry protein analysis in drug discovery * Principles, Instrumentation, Technologies topics include MS of peptides, proteins, and ADCs , instrumentation in protein analysis, nanospray technology in MS protein analysis, and automation in MS protein analysis * Details emerging areas from drug monitoring to patient care such as Identification and validation of biomarkers for cancer, targeted MS approaches for biomarker validation, biomarker discovery, and regulatory perspectives * Brings together the most current advances in the mass spectrometry technology and related method in protein analysis

This book presents a detailed overview of the development of new viral vector-based vaccines before discussing two major applications: preventive vaccines for infectious diseases and therapeutic cancer vaccines. Viral vector-based vaccines hold a great potential for development into successful pharmaceutical products and several examples at the advanced pre-clinical or clinical stage are presented. Nevertheless, the most efforts were focused on novel and very innovative technologies for new generation of vector-based vaccines. Furthermore, specific topics such as delivery and adjuvant and protection strategies for cell-mediated-based vaccines are presented. Given its scope, the book is a "must read" for all those involved in vaccine development, both in academia and industrial vaccine development.

First introduced to biomedical research in 1980, the term biomarker has taken on a life of its own in recent years and has come to mean a number of things. In biomedical science, biomarker has evolved to most commonly mean a characteristic that can be used either as a diagnostic or a prognostic, but most significantly as a screening indicator for pathologies that tend to be somewhat silent prior to overt clinical display. Applying scientific rigor, as well as a disciplined approach to nomenclature, Roger Lundblad's Development and Application of Biomarkers rationalizes the current enthusiasm for biomarkers with the use of well-established clinical laboratory analytes in clinical medicine. Highly respected for his work as both a classical protein scientist and as a pioneer in proteomics, Dr. Lundblad catalogs various biomarkers recognized in clinical medicine and, where possible, matches the expectations for advances in screening technologies with the realities of statistical analysis. More specifically, this important reference: Details an extensive list of biomarkers for various stages of a number of cancer types including ovarian, pancreatic, prostate, and breast cancer Looks at how proteomics is used for the discovery and validation of biomarkers Explores the use of microarray technology, ultra-high performance liquid chromatography, and computational bioinformatic approaches for the discovery and use of biomarkers Examines the use of cells and cell fragments as more complex biomarkers Organizes a host of significant biomarkers and essential research by type and use in a series of readily accessible tables Throughout this volume, Dr. Lundblad encourages consideration of biomarkers more as a concept than as laboratory analytes, emphasizing the relation between the discovery of a biomarker and the biology underlying its production. Ultimately, it is a thorough understanding of that underlying biology that will lead to the development of assays that are robust and reproducible, as well as clinically significant.

Transgenic plants present enormous potential to become one of the most cost-effective and safe systems for large-scale production of proteins for industrial, pharmaceutical, veterinary, and agricultural uses. Over the past decade, much progress has been made with respect to the development of vaccines, antibodies, and other therapeutic proteins. Biopharmaceuticals in Plants: Toward the Next Century of Medicine provides a comprehensive survey of all major aspects of the development and production of plant-made biopharmaceuticals. Accompanied by an exhaustive list of references to facilitate further study, this critical volume: Describes the theory and practice of modern plant transformation techniques with respect to nuclear and plastic genomes Outlines the steps involved in the generation of transgenic plants Discusses the engineering of plant virus expression vectors for transient expression of vaccine proteins and other therapeutics in plant tissue Addresses the significant role of glycosylation in the production of plant-made mammalian proteins Investigates the basis of mucosal immunity using plant-based oral vaccines Examines the scale-up of plant-derived vaccine and therapeutic proteins in entire crops or in large batch cell suspension cultures Explores the development of clinical trials utilizing plant-derived biopharmaceutical proteins Evaluates risks and biosafety concerns regarding plant-derived pharmaceuticals The book concludes with a discussion of the future of plant-based vaccines and other therapeutic proteins with respect to commercial viability and as a tool to improve global public health. Far-reaching in its scope, this text is a baseline reference that students and researchers in a broad range of fields such as medicine, plant science, biotechnology, crop science, natural products chemistry, and engineering will consult regularly. It will also serve as a useful tool for individuals and companies seeking to invest in this dynamic area.

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 author has summarized a decade of teaching combinatorial chemistry into this timely brief. The solid phase synthesis of unnatural heterocyclic alpha-amino acids is illustrated by practical examples starting from the ABCs of peptide synthesis explored in chapter one. Chapter two is concerned with the solid phase synthesis which is shown on various techniques - BillBoard, tea-bag, and Lantern devices, and demonstrated on heterocyclic examples and protocols. In the third chapter the tools for accelerating chemical synthesis - solid phase and liquid phase - are reviewed. Here the techniques of parallel refluxing (including microwave and flow technique) and parallel separation (filtration, centrifugation, evaporation, and chromatography) are described. In the chapters 4 and 5 the author goes on to describe how the liquid phase synthesis of heterocycles (reductive amination and Ugi reaction of heterocycles) is illustrated with the use of semi-automated protocols. Finally, the design of combinatorial libraries of heterocycles is reviewed including the original author's findings.

In recent years, emerging trends in the design and development of drug products have indicated ever greater need for integrated characterization of excipients and in-depth understanding of their roles in drug delivery applications. This book presents a concise summary of relevant scientific and mechanistic information that can aid the use of excipients in formulation design and drug delivery applications. Each chapter is contributed by chosen experts in their respective fields, which affords truly in-depth perspective into a spectrum of excipient-focused topics. This book captures current subjects of interest - with the most up to date research updates - in the field of pharmaceutical excipients. This includes areas of interest to the biopharmaceutical industry users, students, educators, excipient manufacturers, and regulatory bodies alike.

The rise of bio- and nano-technology in the last decades has led to the emergence of a new and unique type of medicine known as non-biological complex drugs (NBCDs). This book illustrates the challenges associated with NBCD development, as well as the complexity of assessing the effects of manufacturing changes on innovator and follow-on batches of NBCDs. It also touches upon proven marketing authorization requirements for biosimilars that could be effective in evaluating follow-on NBCDs, including a demonstration of control over the manufacturing process and a need for detailed physico-chemical characterization and (pre)clinical tests. This book is meant to be used for years to come as a standard reference work for the development of NBCDs. Moreover, this book aims to stimulate discussions and further our thinking to ensure that decisions regarding the approval of complex drugs are made with relevant scientific data on the table.

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.

Nanofiber Composite Materials for Biomedical Applications presents new developments and recent advances in nanofiber-reinforced composite materials and their use in biomedical applications, including biomaterial developments, drug delivery, tissue engineering, and regenerative medicine. Unlike more conventional titles on composite materials, this book covers the most innovative new developments in nanofiber-based composites, including polymers, ceramics, and metals, with particular emphasis on their preparation and characterization methodology. Selected case studies illustrate new developments in clinical and preclinical use, making the information critical for the development of new medical materials and systems for use in human health care, and for the exploration of new design spaces based on these nanofibers. This book is essential reading for those working in biomedical science and engineering, materials science, nanoscience, biomedical nanotechnology, and biotechnology.

This comprehensive reference provides an in-depth discussion on state-of-the-art regulatory science in bioequivalence. In sixteen chapters, the volume explores a broad range of topics pertaining to bioequivalence, including its origin and principles, statistical considerations, food effect studies, conditions for waivers of bioequivalence studies, Biopharmaceutics Classification Systems, Biopharmaceutics Drug Disposition Classification System, bioequivalence modeling/simulation and best practices in bioanalysis. It also discusses bioequivalence studies with pharmacodynamic and clinical endpoints as well as bioequivalence approaches for highly variable drugs, narrow therapeutic index drugs, liposomes, locally acting gastrointestinal drug products, topical products and nasal and inhalation products. FDA Bioequivalence Standards is written by FDA regulatory scientists who develop regulatory policies and conduct regulatory assessment of bioequivalence. As such, both practical case studies and fundamental science are highlighted in these chapters. The book is a valuable resource for scientists who work in the pharmaceutical industry, regulatory agencies and academia as well as undergraduate and graduate students looking to expand their knowledge about bioequivalence standards.

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.

Until the 1990s, it was generally accepted that medicines were first developed for adults and their use in children was investigated later, if at all. One of the main tasks of hospital pharmacies was the manufacturing of child-appropriate formulations in a more or less makeshift way. The first change came in 1997 with U.S. legislation that rewarded manufacturers to do voluntary pediatric research. Ten years later, the European Union passed legislation that required manufacturers to discuss all pediatric aspects, including formulations, with the regulatory authorities as a condition of starting the registration procedure. In consequence, manufacturers must now cover all age groups, including the youngest ones. So far, pediatric formulations were more a focus for academic researchers. Through the changed regulatory environment, there is now a sudden high commercial demand for age-appropriate formulations. This book begins by highlighting the anatomical, physiological and developmental differences between adults and children of different ages. It goes on to review the existing technologies and attempts to draw a roadmap to better, innovative formulations, in particular for oral administration. The regulatory, clinical, ethical and pharmaceutical framework is also addressed.