Discover the Latest Statistical Approaches for Modeling Exposure-Response Relationships Written by an applied statistician with extensive practical experience in drug development, Exposure-Response Modeling: Methods and Practical Implementation explores a wide range of topics in exposure-response modeling, from traditional pharmacokinetic-pharmacodynamic (PKPD) modeling to other areas in drug development and beyond. It incorporates numerous examples and software programs for implementing novel methods. The book describes using measurement error models to treat sequential modeling, fitting models with exposure and response driven by complex dynamics, and survival analysis with dynamic exposure history. It also covers Bayesian analysis and model-based Bayesian decision analysis, causal inference to eliminate confounding biases, and exposure-response modeling with response-dependent dose/treatment adjustments (dynamic treatment regimes) for personalized medicine and treatment adaptation. Many examples illustrate the use of exposure-response modeling in experimental toxicology, clinical pharmacology, epidemiology, and drug safety. Some examples demonstrate how to solve practical problems while others help with understanding concepts and evaluating the performance of new methods. The provided SAS and R codes enable readers to test the approaches in their own scenarios. Although application oriented, this book also gives a systematic treatment of concepts and methodology. Applied statisticians and modelers can find details on how to implement new approaches. Researchers can find topics for or applications of their work. In addition, students can see how complicated methodology and models are applied to practical situations.

This book details current developments in all natural polymers, with a focus on animal and microbial polysaccharides. The book examines, compares, and contrasts the efficiency of plant and algae based natural polymers in inducing immune reactions. Additionally, the book details the safety and toxicity profiles with respective regulations.

Over the past years, the chem(o)informatics field has further evolved and new application areas have opened up, for example, in the broadly defined area of chemical biology. In Chemoinformatics and Computational Chemical Biology, leading investigators bring together a detailed series of reviews and methods including, among others, system-directed approaches using small molecules, the design of target-focused compound libraries, the study of molecular selectivity, and the systematic analysis of target-ligand interactions. Furthermore, the book delves into similarity methods, machine learning, probabilistic approaches, fragment-based methods, as well as topics that go beyond the current chemoinformatics spectrum, such as knowledge-based modeling of G protein-coupled receptor structures and computational design of siRNA libraries. As a volume in the highly successful Methods in Molecular Biology (TM) series, this collection provides detailed descriptions and implementation advice that are exceedingly relevant for basic researchers and practitioners in this highly interdisciplinary research and development area. Cutting-edge and unambiguous, Chemoinformatics and Computational Chemical Biology serves as an ideal guide for experts and newcomers alike to this vital and dynamic field of study.

This thesis mainly describes the development of a screening process for a mirror-image library of chiral natural products. It demonstrates how, by using mirror-image proteins for the screening of available natural products, unavailable mirror-image isomers of natural products can be screened in a mirror process. Moreover, as mirror-image isomers including target proteins and natural products are mainly prepared by means of chemical synthesis, the screening strategy presented here suggests the importance of organic chemistry. Natural products are commonly used as valuable resources for drug discovery. However, as they are mostly produced as single enantiomeric forms, researchers have tested o nly natural products bearing one stereochemistry available in nature. As natural products and their enantiomers have identical physicochemical properties and different biological activities, mirror-image isomers of natural products are promising candidates for novel medicinal resources. In an effort to identify anticancer agents from the mirror-image library, chemical protein syntheses of some target oncoproteins, MDM2, MDMX and Grb2, and their applications to the chemical array screening process were achieved. In the course of this process the NP843 enantiomer, which is the enantiomer of an -tocopherol derivative, was successfully identified as a novel MDM2-p53 interaction inhibitor. These results clearly show that a mirror-image library of chiral natural products represents an invaluable medicinal resource. Accordingly, the chemistry-based screening strategy described in this thesis will be of great interest to a broad range of chemists involved in natural product, medicinal, and synthetic chemistry.

Bioinformatics and Drug Discovery describes the bioinformatic approaches and techniques employed along the pipeline of drug development from genes to proteins to drugs. The book focuses on gene microarray analysis and techniques for target identification and validation. In addition, clinical applications showing how the analysis can be used for prognostication and diagnosis are described. The second section focuses on protein analysis, including target validation and identification using modern proteomic analysis as well as protein modeling techniques. The third section discusses chemoinformatics, including virtual screening and how to computationally approach chemical space.

Fullerene Collision Reactions provides a comprehensive overview of the state-of-the-art of fullerene collision studies. The book begins with introductory chapters that provide the necessary background in experimental and theoretical techniques. This is followed by experimental results and theoretical calculations covering the wide range of available gas-phase fullerene collision experiments.
Emphasis is placed on gas-phase molecular beam experiments where reaction, fragmentation and charge transfer cross sections have been determined covering collision energy ranges from thermal to MeV. Atomic, ionic, electronic, cluster and surface collisions involving fullerenes are covered in depth accompanied by a clear presentation of the most commonly applied experimental and theoretical techniques.
This book will be an invaluable resource for senior undergraduate students, graduate students and researchers working in the field.

This volume provides readers with the basic principles and fundamentals of extrusion technology and a detailed description of the practical applications of a variety of extrusion processes, including various pharma grade extruders. In addition, the downstream production of films, pellets and tablets, for example, for oral and other delivery routes, are presented and discussed utilizing melt extrusion. This book is the first of its kind that discusses extensively the well-developed science of extrusion technology as applied to pharmaceutical drug product development and manufacturing. By covering a wide range of relevant topics, the text brings together all technical information necessary to develop and market pharmaceutical dosage forms that meet current quality and regulatory requirements. As extrusion technology continues to be refined further, usage of extruder systems and the array of applications will continue to expand, but the core technologies will remain the same.

"Nanotechnology in Dermatology" is the first book of its kind to address all of the important and rapidly growing aspects of nanotechnology as it relates to dermatology. In the last few years there has been an explosion in research and development for products and devices related to nanotechnology, including numerous applications for consumers, physicians, patients, and industry. Applications are underway in medicine and dermatology for the early detection, diagnosis, and targeted therapy of disease, and nanodesigned materials and devices are expected to be faster, smaller, more powerful, more efficient, and more versatile than their traditional counterparts.

Written by experts working in this exciting field, "Nanotechnology in Dermatology" specifically addresses nanotechnology in consumer skin care products, in the diagnosis of skin disease, in the treatment of skin disease, and the overall safety of nanotechnology. The book also discusses future trends of this ever-growing and changing field, providing dermatologists, pharmaceutical companies, and consumer cosmetics companies with a clear understanding of the advantages and challenges of nanotechnology today."

A particular issue for biopharmaceuticals that has not been addressed comprehensively in any book, is the potential of an immune response to the biopharmaceutical product. That is, the human body marks the drug as a foreign body, and develops antibodies against the drug. These antibodies may be relatively harmless, but may also cross-react with the endogenous compound, causing autoimmunogenicity. Recent adverse experiences in Europe with Janssen-Ortho's blockbuster product Eprex has increased the attention towards potential immunogenicity of biopharmaceuticals, above all from the regulatory agencies. This book is intended to give a broad overview of the current state-of-the-art regarding the immune response to biopharmaceuticals. The chapters range from an overview of the immune system and factors that may trigger the immune system, via detection of antibodies and clinical implications, to various case examples and the regulatory view on immunogenicity.

After 13 years there are new areas to discuss and more recent trials to be included. Good clinical practice; evaluation of quality of life; measurement of the benefit: risk comparison; determination of cost- effectiveness and cost utility; stopping rules for trials; meta-analysis and subgroup analysis are all new sections. The references are expanded from 305 to 512 and include the recent advances in trial design, such as the n-of-1 trials and megatrials, and up-to-date examples to illustrate the points made in the 20 chapters.

Drug research and discovery are of critical importance in human health care. Computational approaches for drug lead discovery and optimization have proven successful in many recent research programs. These methods have grown in their effectiveness not only because of improved understanding of the basic science - the biological events and molecular interactions that define a target for therapeutic intervention - but also because of advances in algorithms, representations, and mathematical procedures for studying such processes. This volume surveys some of those advances. A broad landscape of high-profile topics in computer-assisted molecular design (CAMD) directed to drug design are included. Subject areas represented in the volume include receptor-based applications such as binding energy approximations, molecular docking, and de novo design; non-receptor-based applications such as molecular similarity; molecular dynamics simulations; solvation and partitioning of a solute between aqueous and nonpolar media; graph theory; non-linear multidimensional optimization, processing of information obtained from simulation studies, global optimization and search strategies, and performance enhancement through parallel computing.

Transporters in Drug Development examines how membrane transporters can be dealt with in academic-industrial drug discovery and pharmaceutical development as well as from a regulatory perspective. The book describes methods and examples of in vitro characterization of single transporters in the intestines, liver and kidneys as well as characterization of substrate overlap between various transporters. Furthermore, probes and biomarkers are suggested for studies of the transporters' impact on the pharmacokinetics of drug substrates/candidates interacting on transporters. The challenges of translating in vitro observed interaction of transporters into in vivo relevance are explored, and the book highlights perspectives of applying targeted proteomics and mechanistic modeling in this process.

This book is devoted to the graphics of patient data: good graphs enabling straight-forward and intuitive interpretation, efficient creation, and straightforward interpretation. We focus on easy access to graphics of patient data: the intention is to show a large variety of graphs for different phases of drug development, together with a description of what the graph shows, what type of data it uses, and what options there are. The main aim is to provide inspiration in form of a graphics cookbook. Many graphs provide creative ideas about what can be done. The book is not intended to be technical. It introduces general principles of good visualization to make readers understand the concepts, but the main focus is on the creativity and usefulness: readers are enabled to browse through the book to get ideas of how their own data can be analyzed graphically.

For additional information visit Editor s companion website: http: //www.elmo.ch/doc/life-science-graphics/

This book is intended to serve as a resource for analysts in developing and troubleshooting sample preparation methods. These are critical activities in providing accurate and reliable data throughout the lifecycle of a drug product. This book is divided into four parts: * Part One covers dosage form and diluent properties that impact sample preparation of pharmaceutical dosage forms and the importance of sampling considerations in generating data representative of the drug product batch. * Part Two reviews specific sample preparation techniques typically used with pharmaceutical dosage forms. * Part Three discusses sample preparation method development for different types of dosage forms including addressing drug excipient interactions and post extraction considerations, as well as method validation and applying Quality by Design (QbD) principles to sample preparation methods. * Part Four examines additional topics in sample preparation including automation, investigating aberrant potency results, green chemistry considerations for sample preparation and the ideal case where no sample preparation is required for sample analysis.

A one-stop resource for researchers, developers, and post graduate students in pharmaceutical science. This handbook and ready reference provides detailed, but not overloaded information -- presenting the topic without unnecessarily complex formalism. As such, it gives a systematic and coherent overview of disordered materials for pharmaceutical applications, covering fundamental aspects, as well as preparation and characterization techniques for the target-oriented development of drug delivery systems based on disordered crystals and amorphous solids. Special attention is paid to examine the different facets and levels of disorder in their structural and dynamic aspects as well as the effect of disorder on dissolution and stability. Chapters on processing induced disorder and on patenting issues round off the book. As a result the book helps overcoming the challenges of using these materials in the pharmaceutical industry. For pharmaceutical and medicinal chemists, materials scientists, clinical physicists, and pharmaceutical laboratories looking to make better and more potent pharmaceuticals.

In this era of biotechnology there have been many books covering the fundamentals of recombinant DNA technology and protein chemistry. However, not many sources are available for the pharmaceutical develop ment scientist and other personnel responsible for the commercialization of the finished dosage forms of these new biopharmaceuticals and other products from biotechnology. This text will help to fill this gap. Once active biopharmaceutical molecules are candidates for clinical trial investigation and subsequent commercialization, a number of other activities must take place while research and development on these molecules continues. The active ingredient itself must be formulated into a finished dosage form that can be conveniently used by health care professionals and patients. Properties of the biopharmaceutical molecule must be clearly understood so that the appropriate finished product formulation can be developed. Finished product formulation development includes not only the chemical formulation, but also the packaging system, the manufacturing process, and appropriate control strategies to assure such good manufacturing practice attributes as safety, identity, strength, purity, and quality."

This volume serves as a valuable handbook for the development of nanomedicines made of polymer nanoparticles because it provides researchers, students, and entrepreneurs with all the material necessary to begin their own projects in this field. Readers will find protocols to prepare polymer nanoparticles using different methods, since these are based on the variety of experiences that experts encounter in the field. In addition, complex topics such as, the optimal characterization of polymer nanoparticles is discussed, as well as practical guidelines on how to formulate polymer nanoparticles into nanomedicines, and how to modify the properties of nanoparticles to give them the different functionalities required to become an efficient nanomedicine for different clinical applications. The book also discusses the translation of technology from research to practice, considering aspects related to industrialization of preparation and aspects of regulatory and clinical development.

Focused manuscript on the potential use/role of miRNAs in bioprocessing, specifically the production of complex proteins in mammalian cells. With that in mind I propose a draft list of topics/chapters along the following lines: Intro on CHO/bioprocessing/engineering challenges to set scene, Genomic organization, biogenesis and mode of action, Identifying miRNA targets: Computational prediction, transcriptomics, proteomices, UTR analysis, etc., miRNA expression in Chinese Hamster Ovary cells, miRNAs as engineering targets: pathway manipulation to impact bioprocess phenotypes, miRNAs as biomarkers, Detection methods: Northern, PCR, hybridization arrays, Next Gen Seq, Manipulation of expression in cultured cells: Transient/stable disregulation, Knockout.

This book provides a unique and up-to-date insight into the biopharmaceutical industry. Largely written by industrial authors, its scope is multidisciplinary, rendering it an ideal reference source for students undertaking advanced undergraduate or postgraduate courses in biotechnology, pharmaceutical science, biochemistry, or medicine.

Pharmaceutical Biotechnology is a unique compilation of reviews addressing frontiers in biologicals as a rich source for innovative medicines. This book fulfills the needs of a broad community of scientists interested in biologicals from diverse perspectives-basic research, biotechnology, protein engineering, protein delivery, medicines, pharmaceuticals and vaccinology. The diverse topics range from advanced biotechnologies aimed to introduce novel, potent engineered vaccines of unprecedented efficacy and safety for a wide scope of human diseases to natural products, small peptides and polypeptides engineered for discrete prophylaxis and therapeutic purposes. Modern biologicals promise to dramatically expand the scope of preventive medicine beyond the infectious disease arena into broad applications in immune and cancer treatment, as exemplified by anti-EGFR receptors antibodies for the treatment of breast cancer. The exponential growth in biologicals such as engineered proteins and vaccines has been boosted by unprecedented scientific breakthroughs made in the past decades culminating in an in-depth fundamental understanding of the scientific underpinnings of immune mechanisms together with knowledge of protein and peptide scaffolds that can be deliberately manipulated. This has in turn led to new strategies and processes. Deciphering the human, mammalian and numerous pathogens' genomes provides opportunities that never before have been available-identification of discrete antigens (genomes and antigenomes) that lend themselves to considerably improved antigens and monoclonal antibodies, which with more sophisticated engineered adjuvants and agonists of pattern recognition receptors present in immune cells, deliver unprecedented safety and efficacy. Technological development such a nanobiotechnologies (dendrimers, nanobodies and fullerenes), biological particles (viral-like particles and bacterial ghosts) and innovative vectors (replication-competent attenuated, replication-incompetent recombinant and defective helper-dependent vectors) fulfill a broad range of cutting-edge research, drug discovery and delivery applications. Most recent examples of breakthrough biologicals include the human papilloma virus vaccine (HPV, prevention of women genital cancer) and the multivalent Pneumoccocal vaccines, which has virtually eradicated in some populations a most prevalent bacterial ear infection (i.e., otitis media). It is expected that in the years to come similar success will be obtained in the development of vaccines for diseases which still represent major threats for human health, such as AIDS, as well as for the generation of improved vaccines against diseases like pandemic flu for which vaccines are currently available. Furthermore, advances in comparative immunology and innate immunity revealed opportunities for innovative strategies for ever smaller biologicals and vaccines derived from species such as llama and sharks, which carry tremendous potential for innovative biologicals already in development stages in many pharmaceutical companies. Such recent discoveries and knowledge exploitations hold the promise for breakthrough biologicals, with the coming decade. Finally, this book caters to individuals not directly engaged in the pharmaceutical drug discovery process via a chapter outlining discovery, preclinical development, clinical development and translational medicine issues that are critical the drug development process. The authors and editors hope that this compilation of reviews will help readers rapidly and completely update knowledge and understanding of the frontiers in pharmaceutical biotechnologies.

Biopharmaceutical medicines, the newest class of therapeutics, are quite heterogeneous and include a range of molecules such as proteins, peptides, vaccines and nucleic acids, with use in virtually all therapeutic fields (e.g. cancer and infectious diseases, vaccination, metabolic dysfunctions) and diagnostics. This edited book gives a concise and up-to-date overview of the biological features justifying the use of different human mucosa as delivery routes for biopharmaceuticals, the technological strategies that have been followed so far regarding the optimization of mucosal potentialities as well as the challenges that arise with the advent of new biopharmaceutical drugs and alternative means of administration. Following a brief introduction, the first section addresses general aspects of the biology of mucosal tissues and their unique aspects toward beneficial or deleterious interaction with biopharmaceuticals and their delivery systems. The second part reviews the different delivery strategies that have recently been investigated for different mucosal sites. The third section describes the development and clinical applications of drug delivery systems and products enclosing biopharmaceuticals for mucosal delivery, with a focus on the most successful case studies of recent years. The last section briefly centers on relevant aspects of the regulatory, toxicological and market issues of mucosal delivery of biopharmaceuticals. Scientists and researchers in the fields of drug delivery, material science, biomedical science and bioengineering as well as professionals, regulators and policy makers in the pharmaceutical, biotechnology and healthcare industries will find in this book an important compendium of fundamental concepts and practical tools for their daily research and activities.

This unique book is the only one to discuss various new techniques developed to enhance the application of nanoparticulate drug delivery systems using surface modification of nanoparticles. The understanding of the surface characteristics nano-particles is growing significantly with the advent of new analytical techniques. Polymer chemistry is contributing to the development of many new versatile polymers which have abilities to accommodate many different, very reactive chemical groups, and can be used as a diagnostic tool, for better targeting, for more effective therapeutic results as well as for reducing the toxic and side effects of the drugs. Surface modification of such polymeric nanoparticles has been found by many scientists to enhance the application of nanoparticles and also allows the nano particles to carry specific drug molecule and disease /tumor specific antibodies which refine and improve drug delivery. Surface Modification of Nanoparticles for Targeted Drug Delivery is a collection essential information with various applications of surface modification of nanoparticles and their disease specific applications for therapeutic purposes.

Only four short decades ago, the control of insect pests by means of chemicals was in its early infancy. The pioneers in the area consisted largely of a group of dedicated applied entomologists working to the best of their abilities with a very limited arsenal of chemicals that included inorganics (arsenicals, fluorides, etc.), some botanicals (nicotine), and a few synthetic organics (dinitro-o-cresol, organothiocyanates). Much of the early research was devoted to solving practical problems associated with the formulation and application of the few existing materials, and although the discovery of new types of insecticidal chemicals was undoubtedly a pipe dream in the minds of some, little or no basic research effort was expended in this direction. The discovery of the insecticidal properties of DDT by Paul Miiller in 1939 has to be viewed as the event which marked the birth of modern insecticide chemistry and which has served as the cornerstone for its subse quent developement. DDT clearly demonstrated for the first time the dramatic potential of synthetic organic chemicals for insect control and provided the initial stimulus which has caused insecticide chemistry to become a field not only of immense agricultural and public health importance but also one that has had remarkable and unforseeable repercussions in broad areas of the physical, biological, and social sciences. Indeed, there can be few other synthetic chemicals which will be judged in history to have had such a broad and telling impact on mankind as has DDT."

This three-volume set of Pharmaceutical Dosage Forms: Parenteral Medications is an authoritative, comprehensive reference work on the formulation and manufacture of parenteral dosage forms, effectively balancing theoretical considerations with the practical aspects of their development. As such, it is recommended for scientists and engineers in the pharmaceutical industry and academia, and will also serve as an excellent reference and training tool for regulatory scientists and quality assurance professionals.

First published in 1984 (as two volumes) and then last revised in 1993 (when it grew to three volumes), this latest revision will address the plethora of changes in the science and considerable advances in the technology associated with these products and routes of administration. The third edition of this book maintains the features that made the last edition so popular but comprises several brand new chapters, revisions to all other chapters, as well as high quality illustrations.

Volume one presents:

A historical perspective of injectable drug therapy, common routes of administration, and biopharmaceutics of NCEs and NBEs.

An in-depth discussion on the preformulation and formulation of small and large molecules, including ophthalmic dosage forms.

A presentation of parenteral primary packaging options - glass and plastic containers, as well as elastomeric closures.

A definitive chapter on container-closure integrity.

New chapters on solubility and solubilization, formulation of depot delivery systems and biophysical/biochemical characterization of proteins.

Volume two presents:

Chapters on aseptic facility design, environmental monitoring, and cleanroom operations.

A comprehensive chapter on pharmaceutical water systems.

A discussion of quality attributes of sterile dosage forms, including particulate matter, endotoxin, and sterility testing.

A detailed chapter on processing of parenteral drug products (SVPs and LVPs).

Presentations on widely used sterilization technologies steam, gas / chemical, radiation, filtration and dry heat.

An in-depth chapter on lyophilization.

Volume three presents:

An in-depth discussion of regulatory requirements, quality assurance, risk assessment and mitigation, and extractables/leachables.

Specific chapters on parenteral administrations devices, injection site pain assessment, and parenteral product specifications and stability testing.

Forward-thinking discussions on the future of parenteral product manufacturing, and siRNA delivery systems.

New chapters covering recent developments in the areas of visual inspection, quality by design (QbD), process analytical technology (PAT) and rapid microbiological methods (RMM ), and validation of drug product manufacturing process.