Using time-to-event analysis methodology requires careful definition of the event, censored observation, provision of adequate follow-up, number of events, and independence or "noninformativeness" of the censoring mechanisms relative to the event. Design and Analysis of Clinical Trials with Time-to-Event Endpoints provides a thorough presentation of the design, monitoring, analysis, and interpretation of clinical trials in which time-to-event is of critical interest. After reviewing time-to-event endpoint methodology, clinical trial issues, and the design and monitoring of clinical trials, the book focuses on inferential analysis methods, including parametric, semiparametric, categorical, and Bayesian methods; an alternative to the Cox model for small samples; and estimation and testing for change in hazard. It then presents descriptive and graphical methods useful in the analysis of time-to-event endpoints. The next several chapters explore a variety of clinical trials, from analgesic, antibiotic, and antiviral trials to cardiovascular and cancer prevention, prostate cancer, astrocytoma brain tumor, and chronic myelogonous leukemia trials. The book then covers areas of drug development, medical practice, and safety assessment. It concludes with the design and analysis of clinical trials of animals required by the FDA for new drug applications. Drawing on the expert contributors' experiences working in biomedical research and clinical drug development, this comprehensive resource covers an array of time-to-event methods and explores an assortment of real-world applications.

An eminent scientist talks about the pharmaceutical industry, biotechnology and the future of drug research. In the course of our busy, technologically-driven lives, it is taken for granted that we respond to minor fluctuations in our health by taking pills -- pills for headache and for toothache; sleeping pills and tranquilizers; pills to lower fever, quiet coughs, and clear the sinuses; medicines to reduce appetite; preparations to relieve heartburn; and many more. In the war against serious disease, medicines are an indispensable weapon in the physician's arsenal: they save lives, or at least prolong them and make them more bearable. Despite the important role that pharmaceuticals play in our lives, few of us know where medicines come from or how the pharmaceutical industry discovers and develops new drugs. Jurgen Drews, an acclaimed leader in the pharmaceutical industry, tells the fascinating story of drug discovery and development from his years of successfully leading internatnional research teams at Hoffman-LaRoche. Drews traces the history of modern drug development from pharmacies, chemical companies, and individual entrepeneurs in Switzerland, Germany and the U.S. to the mega-corporations that dot the landscape of Europe, Japan and America. He describes the process by which new drugs are tested and brought to market, including a provacative look at how AIDS activism stimulated the approval process in the US. Drews' commentary on the role of clinical trials -- the time involved and their cost -- is sobering testimony to the complexity of bringing innovation to the marketplace. In the final two chapters of "In Quest of Tomorrow's Medicines", Drews offers an important and critical analysis of research in the the pharmaceutical industry, pointing to strategies that work and management practices that impede progress. Drews' comments on the impact that the growing relationship between the biotechnology industry and university-sponsored research will have ont he pharmaceutical industry makes provocative reading for pharmaceutical researchers, managers and investors. "In Quest of Tomorrow's Medicines" in written in clear, thoughtful language for people in the pharmaceutical and biotechnology industries, as well as policy makers, industry analysts and observers.

FDA Regulatory Affairs is a roadmap to prescription drug, biologics, and medical device development in the United States. Written in plain English, the concise and jargon-free text demystifies the inner workings of the US Food and Drug Administration (FDA) and facilitates an understanding of how the agency operates with respect to compliance and product approval, including clinical trial exemptions, fast track status, advisory committee procedures, and more. The Third Edition of this highly successful publication: Examines the harmonization of the US Federal Food, Drug, and Cosmetic Act with international regulations on human drug, biologics and device development, research, manufacturing, and marketing Includes contributions from experts at organizations such as the FDA, National Institutes of Health (NIH), and PAREXEL Focuses on the new drug application (NDA) process, cGMPs, GCPs, quality system compliance, and corresponding documentation requirements Provides updates to the FDA Safety and Innovation Act (FDASIA), incorporating pediatric guidelines and follow-on biologics regulations from the 2012 Prescription Drug User Fee Act (PDUFA) V Explains current FDA inspection processes, enforcement options, and how to handle FDA meetings and required submissions Co-edited by an industry leader (Mantus) and a respected academic (Pisano), FDA Regulatory Affairs, Third Edition delivers a compilation of the selected US laws and regulations as well as a straightforward commentary on the FDA product approval process that's broadly useful to both business and academia.

In a living body, a variety of molecules are working in a concerted manner to maintain its life, and to carry forward the genetic information from generation to generation. A key word to understand such processes is "water," which plays an essential role in life phenomena. This book sheds light on life phenomena, which are woven by biomolecules as warp and water as weft, by means of statistical mechanics of molecular liquids, the RISM and 3D-RISM theories, both in equilibrium and non-equilibrium. A considerable number of pages are devoted to basics of mathematics and physics, so that students who have not majored in physics may be able to study the book by themselves. The book will also be helpful to those scientists seeking better tools for the computer-aided-drug-discovery. Explains basics of the statistical mechanics of molecular liquids, or RISM and 3D-RISM theories, and its application to water. Provides outline of the generalized Langevin theory and the linear response theory, and its application to dynamics of water. Applies the theories to functions of biomolecular systems. Applies the theories to the computer aided drug design. Provides a perspective for future development of the method.

Bioprocess Engineering for a Green Environment examines numerous bioprocesses that are crucial to our day-to-day life, specifically the major issues surrounding the production of energy relating to biofuels and waste management. The nuance of this discussion is reflected by the text's chapter breakdown, providing the reader with a fulsome investigation of the energy sector; the importance of third-generation fuels; and the application of micro- and macroalgae for the production of biofuels. The book also provides a detailed exploration of biocatalysts and their application to the food industry; bioplastics production; conversion of agrowaste into polysaccharides; as well as the importance of biotechnology in bio-processing. Numerous industries discharge massive amounts of effluents into our rivers, seas, and air systems. As such, two chapters are dedicated to the treatment of various pollutants through biological operation with hopes of achieving a cleaner, greener, environment. This book represents the most comprehensive study of bioprocessing-and its various applications to the environment-available on the market today. It was furthermore written with various researchers in mind, ranging from undergraduate and graduate students looking to enhance their knowledge of the topics presented to scholars and engineers interested in the bioprocessing field, as well as members of industry and policy-makers. Provides a comprehensive overview of bioprocesses that apply to day-to-day living. Is learner-centered, providing detailed diagrams for easy understanding. Explores the importance of biocatalysts and their applications to the food industry, as well as bioplastics production. Examines the unique capabilities of bioprocess engineering and its ability to treat various pollutants. .

Medical device regulation in Asia has gained more importance than ever. Governments and regulatory bodies across the region have put in place new regulatory systems or refined the existing ones. A registered product requires a lot of technical documentation to prove its efficacy, safety, and quality. A smooth and successful registration process demands soft skills for dealing with various key stakeholders in the government, testing centers, and hospitals and among doctors. This handbook covers medical device regulatory systems in different countries, ISO standards for medical devices, clinical trial and regulatory requirements, and documentation for application. It is the first to cover the medical device regulatory affairs in Asia. Each chapter provides substantial background materials relevant to the particular area to have a better understanding of regulatory affairs.

This book discusses fabrication of functionalized gold nanoparticles (GNPs) and multifunctional nanocomposites, their optical properties, and applications in biological studies. This is the very first book of its kind to comprehensively discuss published data on in vitro and in vivo biodistribution, toxicity, and uptake of GNP by mammalian cells providing a systematization of data over the GNP types and parameters, their surface functionalization, animal and cell models. As distinct from other related books, Gold Nanoparticles in Biomedical Applications discusses the immunological properties of GNPs and summarizes their applications as an antigen carrier and adjuvant in immunization for the preparation of antibodies in vivo. Although the potential of GNPs in nanobiotechnology has been recognized for the past decade, new insights into the unique properties of multifunctional nanostructures have recently emerged. With these developments in mind, this book unites ground breaking experimental data with a discussion of hybrid nanoparticle systems that combine different nanomaterials to create multifunctional structures. These novel hybrids constitute the material basis of theranostics, bringing together the advanced properties of functionalized GNPs and composites into a single multifunctional nanostructure with simultaneous diagnostic and therapeutic functions. Such nanohybrids can be physically and chemically tailored for a particular organ, disease, and patient thus making personalized medicine available.

The field of ethics in science aims to improve the way the audience perceives science, and this unique workbook discusses the areas of ethics and scientific misconduct. It provides assessments and exercises for learners to work through in groups or alone. Completion of the workbook but especially the assessment and tests will earn the learner a certificate for scientific misconduct training compiled by the author, and the certificate is available from the author's own website. This volume is a companion to the author's published volume, Ethics in Science: Ethical Misconduct in Scientific Research, Second Edition and will appeal to undergraduates, graduates and even high school students. Features: A unique training workbook in ethics and good conduct, easliy accessible and user friendly Unlike books in this area which mostly cover the theoretical foundations of ethics in science, here the author provides a practical workbook and ancillaries Case studies and a PowerPoint presentation are provided and readers will receive a certificate of completion There is a wealth of instructor resources available from the homepage A knowledge of scientific misconduct is of utmost importance in an era of mass higher education

Molecular farming is a biotechnological approach that includes the genetic adjustment of agricultural products to create proteins and chemicals for profitable and pharmaceutical purposes. Plant molecular farming describes the manufacture of recombinant proteins and other biologically active product in plants. This approach depends on a genetic transformation of plants that can be accomplished by the methods of stable gene transfer, such as gene transfer to nuclei and chloroplasts, and unstable transfer methods like viral vectors. The requirement for recombinant proteins in terms of quality, quantity, and diversity is increasing exponentially This demand is traditionally met by recombinant protein construction technologies and the engineering of orthodox expression systems based on bacteria or mammalian cell cultures. However, majority of developing countries cannot afford the high costs of medicine derived from such existing methods. Hence, we need to produce not only the new drugs but also the cheaper versions of those already present in the market. Plant molecular farming is considered as a cost-effective technology that has grown and advanced tremendously over the past two decades. This book summarizes the advances and challenges of plant molecular farming for all those who are working on or have an interest in this rapidly emerging area of research.

Who wins the race to turn molecules into medicines? How much does it cost? What factors influence the choice of synthetic routes and reaction mechanisms? How can pharmaceutical companies protect their discoveries? In From Bench to Market, Walter Cabri and Romano Di Fabio chart the process of industrial chemical synthesis, from the first discovery of a molecule to its entry in the marketplace as a drug. Using real case histories of drug development from several therapeutic areas, they discuss all aspects related to the process research for bulk production, including comparison between different synthetic routes, key methodologies and reaction mechanisms, costs, patent competition, and crystalline forms.

Mass Spectrometry in Drug Discovery summarizes the theory, instrumentation, techniques, and application of mass spectrometry and atmospheric pressure ionization to screening, evaluating, and improving the performance and quality of drug candidates. It provides time- and cost-efficient approaches for the generation and analysis of effective pharmaceuticals, covers advances in combinatorial chemistry, molecular biology, bioanalysis automation, and computing, and demonstrates the use of mass spectrometry in the assessment of disease states, drug targets, and potential drug agents.

Specification of Drug Substances and Products: Development and Validation of Analytical Methods, Second Edition, presents a comprehensive and critical analysis of the requirements and approaches to setting specifications for new pharmaceutical products, with an emphasis on phase-appropriate development, validation of analytical methods, and their application in practice. This thoroughly revised second edition covers topics not covered or not substantially covered in the first edition, including method development and validation in the clinical phase, method transfer, process analytical technology, analytical life cycle management, special challenges with generic drugs, genotoxic impurities, topical products, nasal sprays and inhalation products, and biotechnology products. The book's authors have been carefully selected as former members of the ICH Expert Working Groups charged with developing the ICH guidelines, and/or subject-matter experts in the industry, academia and in government laboratories.

Pharmaceutical packaging requires a greater knowledge of materials and a greater intensity of testing than most other packed products, not to mention a sound knowledge of pharmaceutical products and an understanding of regulatory requirements. Structured to meet the needs of the global market, this volume provides an assessment of a wide range of issues. It covers the entire supply chain from conversion of raw materials into packaging materials and then assembled into product packs. Integrating information from many drug delivery systems, the author discusses testing and evaluation and emphasizes traceability and the need to for additional safeguards.

This volume contains the proceedings of the Ninth Meeting of the "International Study Group for Tryptophan Research" (lSTRY), held at the University of Hamburg, Germany, from October 10 to 14, 1998. At this meeting the recent developments in the field of tryptophan research were presented by leading researchers from all over the world in 81 oral and 48 poster contri butions. Research on tryptophan and its derivatives provides an inexhaustible subject. At the conference we tried to compose a multifacetted picture of the recent investiga tions through contributions from the major disciplines involved. Thus, we tried to strike a balance between basic research topics and clinical, nutritional or industrial applica tions. We offered workshops on tryptophan (in sleep and mood), melatonjn, IDO-acti vation and the eosinophilia-myalgia syndrome (EMS) as a platform for intensive discussion for the participants. In these proceedings many contributions are multidisciplinary and have practical or theoretical implications for different research fields. Hence, we have organized this volume in nine main chapters according to basic disciplines and subjects. We are aware that this classification is artificial, but we hope that it is the best compromise for contributors and readers."

Natural products play an integral and ongoing role in promoting numerous aspects of scientific advancement, and many aspects of basic research programs are intimately related to natural products. The significance, therefore, of the Studies in Natural Product Chemistry series, edited by Professor Atta-ur-Rahman, cannot be overestimated. This volume, in accordance with previous volumes, presents us with cutting-edge contributions of great importance.

Drug Discovery Targeting Drug-Resistant Bacteria explores the status and possible future of developments in fighting drug-resistant bacteria. The book covers the majority of microbial diseases and the drugs targeting them. In addition, it discusses the potential targeting strategies and innovative approaches to address drug resistance. It brings together academic and industrial experts working on discovering and developing drugs targeting drug-resistant (DR) bacterial pathogens. New drugs active against drug-resistant pathogens are discussed, along with new strategies being used to discover molecules acting via new modes of action. In addition, alternative therapies such as peptides and phages are included. Pharmaceutical scientists, microbiologists, medical professionals, pathologists, researchers in the field of drug discovery, infectious diseases and microbial drug discovery both in academia and in industrial settings will find this book helpful.

This volume focuses on the potential use of probiotics in treating metabolic disorders such as diabetes mellitus, metabolic acidosis, and gut dysbiosis. Chapters draw an association between gut microbiota and its diversity with metabolic diseases like diabetes, obesity, related liver and gut disorders; gut-brain axis; increased inflammation, and a compromised immune system resulting from these manifestations and scope of intervention with probiotics. Special attention is laid on describing the mechanisms of action of such beneficial effects of probiotic administration. The ability of probiotics to decrease metabolic endotoxemia by restoring the disrupted intestinal mucosal barrier is also included. The volume is a comprehensive compilation describing the scope and application of probiotic and prebiotic therapy in treating metabolic disorders. Readers will discover how probiotics are not just confined to the microbiology industry but are showing promising results in the medical and pharmaceutical sectors.

Nanotechnology Based Approaches for Tuberculosis Treatment discusses multiple nanotechnology-based approaches that may help overcome persisting limitations of conventional and traditional treatments. The book summarizes the types of nano drugs, their synthesis, formulation, characterization and applications, along with the most important administration routes. It also explores recent advances and achievements regarding therapeutic efficacy and provides possible future applications in this field. It will be a useful resource for investigators, pharmaceutical researchers, innovators and scientists working on technology advancements in the areas of targeted therapies, nano scale imaging systems, and diagnostic modalities in tuberculosis.

We're all familiar with the idea that plant-derived chemicals can have an impact on the functioning of the human brain. Most of us reach for a cup of coffee or tea in the morning, many of us occasionally eat some chocolate, some smoke a cigarette or take an herbal supplement, and some people use illicit drugs. We know a great deal about the mechanisms by which the psychoactive components of these various products have their effects on human brain function, but the question of why they have these effects has been almost totally ignored. This book sets out to describe not only how, in terms of pharmacology or psychopharmacology, but more importantly why plant- and fungus-derived chemicals have their effects on the human brain. The answer to this last question resides, in part, with the terrestrial world's two dominant life forms, the plants and the insects, and the many ecological roles the 'secondary metabolite' plant chemicals are trying to play; for instance, defending the plant against insect herbivores whilst attracting insect pollinators. The answer also resides in the intersecting genetic heritage of mammals, plants, and insects and the surprising biological similarities between the three taxa. In particular it revolves around the close correspondence between the brains of insects and humans, and the intercellular signaling pathways shared by plants and humans. Plants and the Human Brain describes and discusses both how and why phytochemicals affect brain function with respect to the three main groups of secondary metabolites: the alkaloids, which provide us with caffeine, a host of poisons, a handful of hallucinogens, and most drugs of abuse (e.g. morphine, cocaine, DMT, LSD, and nicotine); the phenolics, including polyphenols, which constitute a significant and beneficial part of our natural diet; and the terpenes, a group of multifunctional compounds which provide us with the active components of cannabis and a multitude of herbal extracts such as ginseng, ginkgo and valerian.

Biopharmaceuticals are emerging as frontline medicines to combat several life-threatening and chronic diseases. However, such medicines are expensive to develop and produce on a commercial scale, contributing to rising healthcare costs. Developability of Biotherapeutics: Computational Approaches describes applications of computational and molecular modeling techniques that improve the overall process of discovery and development by removing empiricism. The concept of developability involves making rational choices at the pre-clinical stages of biopharmaceutical drug development that could positively impact clinical outcomes. The book also addresses a general lack of awareness of the many different contributions that computation can make to biopharmaceutical drug development. This informative and practical reference is a valuable resource for professionals engaged in industrial research and development, scientists working with regulatory agencies, and pharmacy, medicine, and life science students and educators. It focuses primarily on the developability of monoclonal antibody candidates, but the principles described can also be extended to other modalities such as recombinant proteins, fusion proteins, antibody drug conjugates and vaccines. The book is organized into two sections. The first discusses principles and applications of computational approaches toward discovering and developing biopharmaceutical drugs. The second presents best practices in developability assessments of early-stage biopharmaceutical drug candidates. In addition to raising awareness of the promise of computational research, this book also discusses solutions required to improve the success rate of translating biologic drug candidates into products available in the clinic. As such, it is a rich source of information on current principles and practices as well as a starting point for finding innovative applications of computation towards biopharmaceutical drug development.

This first ever coverage of the pharmacokinetic and pharmacodynamic characteristics of biopharmaceuticals meets the need for a comprehensive book in this field. It spans all topics from lead identification right up to final-stage clinical trials.

Following an introduction to the role of PK and PD in the development of biotech drugs, the book goes on to cover the basics, including the pharmacokinetics of peptides, monoclonal antibodies, antisense oligonucleotides, as well as viral and non-viral gene delivery vectors. The second section discusses such challenges and opportunities as pulmonary delivery of proteins and peptides, and the delivery of oligonucleotides. The final section considers the integration of PK and PD concepts into the biotech drug development plan, taking as case studies the preclinical and clinical drug development of tasidotin, as well as the examples of cetuximab and pegfilgrastim.

The result is vital reading for all pharmaceutical researchers.

Contents:
Part 1 Identifying the issues: control of microbial contamination in cosmetics, toiletries and non-sterile pharmaceuticals; hazards associated with the microbiological contamination of cosmetics, toiletries and pharmaceuticals. Part 2 Control in manufacture: microbiological control of raw materials; control of microbial contamination during manufacture. Part 3 Control through preservation: natural and physical preservative systems; the effect of container materials and multiple phase formulation components on the activity of antimicrobial agents; formulation aspects of the preservation of skin and hair products; preservation of solid oral dosage forms; development of preservative systems; microbial resistance to preservative systems; safety evaluation of preservatives. Part 4 Microbiological control - methods and standards: preservative efficacy testing of pharmaceuticals, cosmetics and toiletries and its limitations; challenge tests and their predictive ability; new methodology for microbial quality assurance; microbial contamination of manufactured products - official and unofficial limits.

D ring the past ten ears or so, there has been an increasing n mber of p blications describing ario s aspects of oligon cleotide chemistr and the application of oligon cleotides in basic, as ell as applied science. More recentl , ario s oligon cleotide conj gates nthesi ed that are c rrentl being st died for their ha e been s potential diagnostic and therape tic applications. With the introd- tion of ne oligon cleotide conj gates, anal tical methods for the anal sis of these oligon cleotides are also being de eloped and op- mi ed. The present ol me, Protocols for Oligon cleotide Con- gates: S nthesis and Anal tical Techniq es, is designed to bring readers p-to-date on the protocols for the s nthesis of ario s oli- gates and on all the important techniq es for the n cleotide conj nthetic oligon cleotides and their analogs. The s- anal sis of s thetic chemistrof man of these oligon cleotides and their ario s analogs has been co ered in a companion ol me entitledProtocols for Oligon cleotides and Analogs: S nthesis and Properties. The first chapter ofProtocols for Oligon cleotide Conj gates- scribes the protecting gro ps in oligon cleotide s nthesis.

Pharmaceutical Applications of Dendrimers explores the applications of dendrimers in the solubilization of hydrophobic active ingredients, drug delivery, gene delivery, imaging, diagnosis and photodynamic therapy. The book discusses the diagnostic applications of dendrimers, including their use as MRI contrast agents and in the imaging of diseased areas. In addition, the anti-inflammatory, antimicrobial and antiviral properties of PPI and PAMAM are also covered, along with a discussion on photosensitizers, such as rose Bengal and protoporphyrin IX that have been delivered using PAMAM and PPI dendrimers for the treatment of cancer. This book is an important research reference for those who want to learn more about the development of dendrimer-based solutions for drug delivery.

This groundbreaking, multidisciplinary work is one of the first books to cover Nanotheragnostics, the new developmental edge of nanomedicine. Through a collection of authoritative chapters, the book reports on nanoscopic therapeutic systems that incorporate therapeutic agents, molecular targeting, and diagnostic imaging capabilities. An invaluable reference for researchers in materials science, bioengineering, pharmacy, biotechnology, and nanotechnology, this volume features four main parts on biomedical nanomaterials, advanced nanomedicine, nanotheragnostics, and nanoscaffolds technology.