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/

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."

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 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.

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.

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.

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.

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.

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.

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."

Key Features: Provides botanical descriptions, distribution and pharmacological investigations of notable medicinal and herbal plants used to prevent or treat diabetes. Discusses phytochemical and polyherbal formulations for the management of diabetes and other related complications. Contains reports on antidiabetic plants and their potential uses in drug discovery based on their bioactive molecules.

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.

Aqueous solubility is one of the major challenges in the early stages of drug discovery. One of the most common and effective methods for enhancing solubility is the addition of an organic solvent to the aqueous solution. Along with an introduction to cosolvency models, the Handbook of Solubility Data for Pharmaceuticals provides an extensive database of solubility for pharmaceuticals in mono solvents and binary solvents. Aqueous solubility data can be found in the Handbook of Aqueous Solubility Data by Samuel Yalkowsky and Yan He. Visit www.crcpress.com for more information.

In addition to the experimental efforts to measure the solubility of drugs in mono and mixed solvents, this book discusses the advantages and limitations of a number of mathematical models used to predict the solubility in mono or mixed solvent systems. It covers the pharmaceutical cosolvents and other organic solvents that are used in syntheses, separations, and other pharmaceutical processes. The solutes featured include the available data for official drugs, drug candidates, precursors of drugs, metabolites, and degradation products of pharmaceuticals. The author also presents the solubilities of amino acids since they play an important role in peptide drug properties.

Collecting drug solubilities in various cosolvents, this time-saving handbook includes the mixtures and model constants needed to predict undetermined solubilities. It describes mathematical models that enable data to be derived and provides estimates on how drugs are likely to behave in a given cosolvent. A software program and associated user manual are available on the author s website.

Preclinical Drug Development, Second Edition discusses the broad and complicated realm of preclinical drug development. Topics range from assessment of pharmacology and toxicology to industry trends and regulatory expectations to requirements that support clinical trials. Highlights of the Second Edition include: Pharmacokinetics Modeling and simulation Formulation and routes of administration Toxicity evaluations The assessment of drug absorption and metabolism Interspecies scaling Lead molecule selection and optimization via profiling Screening using in silico and in vitro toxicity evaluations The book also includes case studies on preclinical pharmacokinetic-pharmacodynamic modeling and simulation in drug development, a review of ICH preclinical guidelines, and experimental methods used to study membrane drug transport and metabolism. This guide is a fundamental resource for medicinal chemists, biologists, and other specialists in the drug development sciences.

Recombinant proteins and polypeptides continue to be the most important class of biotechnology-derived agents in today's pharmaceutical industry. Over the past few years, our fundamental understanding of how proteins degrade and how stabilizing agents work has made it possible to approach formulation of protein pharmaceuticals from a much more rational point of view.

This book describes the current level of understanding of protein instability and the strategies for stabilizing proteins under a variety of stressful conditions.

The first contribution describes apolar and polar molecular fossils and, in particular biomarkers, along the lines usually followed in organic chemistry textbooks, and points to their bioprecursors when available. Thus, the apolar compounds are divided in linear and branched alkanes followed by alicyclic compounds and aromatic and heterocyclic molecules, and, in particular, the geoporphyrins. The polar molecular fossils contain as functional groups or constituent units ethers, alcohols, phenols, carbonyl groups, flavonoids, quinones, and acids, or are polymers like kerogen, amber, melanin, proteins, or nucleic acids. The final sections discuss the methodology used and the fundamental processes encountered by the biomolecules described, including diagenesis, catagenesis, and metagenesis. The second contribution covers the distribution of phthalides in nature and the findings in the structural diversity, chemical reactivity, biotransformations, syntheses, and bioactivity of natural and semisynthetic phthalides.

• Describes the endemic plants used in traditional medicine • Includes the chemical and bioactive compounds from desertic medicinal plants • Addresses the analytic techniques to determine chemical and bioactive compounds • Represents an effort to keep the ethnobiological knowledge of communities

During the past decade there have been many changes in the perfumery industry which are not so much due to the discovery and application of new raw materials, but rather to the astronomic increase in the cost of labour required to produce them. This is reflected more particularly in the flower industry, where the cost of collecting the blossoms delivered to the factories has gone up year after year, so much so that most flowers with the possible exception of Mimosa, have reached a cost price which has compelled the perfumer to either reduce his purchases of absolutes and concretes, or alternatively to substitute them from a cheaper source, or even to discontinue their use. This development raises an important and almost insoluble problem for the perfumer, who is faced with the necessity of trying to keep unchanged the bouquet of his fragrances, and moreover, to ensure no loss of strength and diffusiveness. Of course, this problem applies more especially to the adjustment of formulae for established perfumes, because in every new creation the present high cost of raw materials receives imperative con sideration before the formula is approved."

In the late 1980s, it became painfully evident to the pharmaceutical industry that the old paradigm of drug discovery, which involved highly segmented drug - sign and development activities, would not produce an acceptable success rate in the future. Therefore, in the early 1990s a paradigm shift occurred in which drug design and development activities became more highly integrated. This new str- egy required medicinal chemists to design drug candidates with structural f- tures that optimized pharmacological (e. g. , high affinity and specificity for the target receptor), pharmaceutical (e. g. , solubility and chemical stability), bioph- maceutical (e. g. , cell membrane permeability), and metabolic/pharmacokinetic (e. g. , metabolic stability, clearance, and protein binding) properties. Successful implementation of this strategy requires a multidisciplinary team effort, incl- ing scientists from drug design (e. g. , medicinal chemists, cell biologists, en- mologists, pharmacologists) and drug development (e. g. , analytical chemists, pharmaceutical scientists, physiologists, and molecular biologists representing the disciplines of pharmaceutics, biopharmaceutics, and pharmacokinetics/drug metabolism). With this new, highly integrated approach to drug design now widely utilized by the pharmaceutical industry, the editors of this book have provided the sci- tific community with case histories to illustrate the nature of the interdisciplinary interactions necessary to successfully implement this new approach to drug d- covery. In the first chapter, Ralph Hirschmann provides a historical perspective of why this paradigm shift in drug discovery has occurred.

Provides comprehensive coverage of the interpretation of LC MS MS mass spectra of 1300 drugs and pesticides * Provides a general discussion on the fragmentation of even-electron ions (protonated and deprotonated molecules) in both positive-ion and negative-ion modes * This is the reference book for the interpretation of MS MS mass spectra of small organic molecules * Covers related therapeutic classes of compounds such as drugs for cardiovascular diseases, psychotropic compounds, drugs of abuse and designer drugs, antimicrobials, among many others * Covers general fragmentation rule as well as specific fragmentation pathways for many chemical functional groups * Gives an introduction to MS technology, mass spectral terminology, information contained in mass spectra, and to the identification strategies used for different types of unknowns

Examines harmonization of the US Federal Food, Drug, and Cosmetic Act with international regulations as they apply to human drug and device development, research, manufacturing, and marketing. The Second Edition focuses on the new drug approval process, cGMPs, GCPs, quality system compliance, and corresponding documentation requirements. Written in a jargon-free style, it draws information from a wide range of resources. It demystifies the inner workings of the FDA and facilitates an understanding of how it operates with respect to compliance and product approval. FDA Regulatory Affairs: provides a blueprint to the FDA and drug, biologic, and medical device development offers current, real-time information in a simple and concise format contains a chapter highlighting the new drug application (NDA) process discusses FDA inspection processes and enforcement options includes contributions from experts at companies such as Millennium and Genzyme, leading CRO's such as PAREXEL and the Biologics Consulting Group, and the FDA Three all-new chapters cover: clinical trial exemptions advisory committees provisions for fast track

Recent analyses of drug attrition rates reveal that a significant number of drug candidates fail in the later stage of clinical development owing to absorption, distribution, metabolism, elimination (ADME), and toxicity issues. Lead optimization in drug discovery, a process attempting to uncover and correct these defects of drug candidates, is highly beneficial in lowering the cost and time to develop therapeutic drugs by reducing drug candidate failures in development. At present, parallel synthesis combining with high-throughput screening has made it easier to generate highly potent compounds (i. e. , hits). However, to be a potential drug, a hit must have drug-like characteristics in addition to potency, which include optimal physicochemical properties, reasonable ph- macokinetic parameters, and good safety profiles. Therefore, research tools must be available in drug discovery to rapidly screen for compounds with favorable drug-like properties, and thus adequate resources can be directed to projects with high potential. Optimization in Drug Discovery: In Vitro Methods is a compilation of detailed experimental protocols necessary for setting up a variety of assays important in compound evaluation. A total of 25 chapters, contributed by many experts in their research areas, cover a wide spectrum of subjects including physicochemical properties, abso- tion, plasma binding, metabolism, drug interactions, and toxicity. A good pharmacokinetic profile has long been recognized as an imp- tant drug-like characteristic. Pharmacokinetic parameters are affected by many properties of drug molecules such as physicochemical nature, abso- tion, metabolic stability, and so on.

Insights and analysis that challenge current thought on consumer branding theory and strategy Pharmaceutical companies need to go beyond simply relying on strong sales forces and innovative research and development to succeed. Effective branding strategy is essential. PharmaceuticalsWhere's the Brand Logic?: Branding Lessons and Strategy discusses in detail the application of current consumer branding theory to pharmaceutical marketing. This comprehensive book pulls information from fast moving consumer goods (FMCG) research and brand theory and applies it to the pharmaceutical world. It looks at branding on multiple levels within the pharmaceutical industry, including the industry brand, the corporate brand, the franchise brand, and the global and local product brand. Practical strategies are extensively explained and future challenges facing the pharmaceutical industry are explored, all geared to help any pharmaceutical professional to successfully market his or her brand. PharmaceuticalsWhere's the Brand Logic?: Branding Lessons and Strategy may well become a daily reference for anyone in the industry, providing in a single volume a framework for the organization of a brand portfolio for any pharmaceutical company. This unique resource challenges traditional thought about the concept of branding in the pharmaceutical industry, examining several of the most difficult branding theory issues. This helpful guide provides several figures to fully explain data. Topics in PharmaceuticalsWhere's the Brand Logic?: Branding Lessons and Strategy include: what is branding how is branding applied to the FMCG and pharmaceutical industries corporate brandsand how they can be leveraged franchise branding as a business strategy developing and sustaining pharmaceutical brands over time saving the credibility of the pharmaceutical industry changing the pharmaceutical business model to use branding as a strategic tool much, much more PharmaceuticalsWhere's the Brand Logic?: Branding Lessons and Strategy provides the information and tools to help gain the competitive edge in a tough marketplace. This is an invaluable resource for anyone in the global pharmaceutical industry, including marketing personnel, senior management, general managers, strategy groups, and training departments.

In my professional career as a pharmaceutical scientist, I have been involved with severalaspectsofthe drugdevelopmentprocessfrompre-INDto commercialization and, somehow, I usually found myself coming back to a stability-related issue. The stability area seemed to draw my utmost interest because in my day-to-day work, my opportunities involved more than one product, and none of the issues were the same.Eachsituationposedchallengesthatusuallyrequiredanexerciseofjudgment, an understandingof regulations, a knowledgeof science, a graspof compliance, and an appreciation of common practices. Sinceearly2000, Ihavealsobeeninvolvedwithseveraltrainingopportunitiesand I struggled to ?nd good, concise, practical resources, one of which I could just hand to a new scientist who wishes to gain a greater understanding of stability sciences. In addition, I encountered the same questions posted over and over on different stability best practices discussion forums. As a book lover, I also have a good collection of technical books. Unfor- nately, most of the stability related volumes are outdated. Many of these materials are theoretical and do not contain much practical information. I understand that the pharmaceutical industry during this period is quite volatile, and guidelines are changingrapidlywhileregulatoryagenciesareworkingcloselywiththepharmac- tical industryto accommodatethese changes;however, thefundamentalinformation continues to remain quite the same, just as current Good Manufacturing Practices (cGMP) continue to be the standard industry practice. Therefore, I hoped to ass- ble a practical handbook to ?ll this v

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.