Project managers in drug development are the driving force behind the coordination of efforts. This book provides a practical reference for project managers in the pharmaceutical and biotech drug development industry, with the goal of assisting in creating an efficient and effective team structure and environment. The text details the role of project managers at each stage of drug development, the key interfaces that the PM will need to work closely with, and essential tools of the trade including frequently used techniques and methodologies. This book is useful for both entry-level and advanced-level PMs, as well as non-project managers from other functions. Features Includes authors' recent experience with improved tactics and technologies/software at various stages of drug development. Provides the most up-to-date and best practices, techniques, and methodologies in project management. Details the role of the PM at each stage of drug development, including working with the key interfaces throughout the process. Diverse audience including nonproject managers in clinical development, clinical operations, regulatory affairs, medical affairs, clinical pharmacology, and biostatistics. Provides templates and timelines for critical paths from development to commercialization and has potential as a textbook on relevant courses.

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 studies the production of indole alkaloids in the important medicinal plant Catharanthus roseus (L.) G. Don, commonly known as periwinkle. The anticancer alkaloids, viz. vinblastine and vincristine, are mainly present in the leaves of C. roseus and inhibit the growth of cancer cells by hindering the formation of mitotic apparatus during cell division. Further, vinblastine helps increase the chance of surviving childhood leukemia while vincristine is used to treat Hodgkin's disease. Great efforts have been made to produce these alkaloids at a large scale by the culture of plant cells. In view of this worldwide demand for commercial use, this book explores how to maximize the production of anticancer alkaloids from C. roseus. This reference book will be helpful for research students, teachers, ethnobotanists, pharmacologists and herbal growers who have a strong interest in this anticancer medicinal plant of paramount importance.

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 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.

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.

Chronic inflammation is one of the major pathological bases manifesting the development of gastric cancers, hepatitis and hepatocellular carcinoma, cervical cancer, ulcerative colitis and colorectal cancer [1]. Microbial infections, viral infections and autoimmune responses can lead to chronic inflammation-associated cancer formation. Human herpesviruses, such as human cytomegalovirus (HCMV) and Kaposi sarcoma herpesvirus (KSHV) are known to be associated with tumorigenesis and tumor progression. HCMV infection potentiates malignancies of colon cancer and malignant glioma [2,3]. KSHV was initially discovered from Kaposi's sarcoma lesion of an AIDS patient [4]. It was subsequently discovered that KSHV contributed to the pathogenesis of KS, primary effusion lymphoma [5] and lymphoproliferative disorder multicentric Castleman's disease. Emerging evidence shows that herpesvirus infection interferes or inhibits host cell immune defense and maintains a tumor-promoting microenvironment by expressing virulent homologues of host cell proteins that disturb normal cell cycle progression and leads to apoptosis of the host cells. For example, cellular growth and transformation are induced by viral-encoded homologues of cytokines, chemokines or chemokine receptors [6]. The constitutive expression of viral chemokine GPCRs triggers prolonged activation of G protein signaling and eventually becomes the major inputs for chronic leukocyte infiltration and cancer development. GPCRs can serve as proto-oncogenes since overexpression of various wild type GPCRs can transform cells in the presence of their specific ligands. Mutations on GPCRs may result in constitutive signaling and oncogenesis [7]. Naturally occurring mutations in GPCRs have been identified in human tumors [8,9].

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 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.

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."

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

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.

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.

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.

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

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.

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.

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

Nanophytomedicine is a field that involves the application of nanomedicine-based systems to phytotherapy and phytopharmacology. This book assesses the clinical successes and failures of nanophytomedicine and also highlights emerging concepts in this field. The content is divided into three sections, the first of which describes core issues in the pharmaceuticals industry in connection with the successes, failures and prospects of nanophytomedicine. The second section highlights recent advances in phytomedicine formulation development based on nanotechnology approaches, while also discussing a variety of nanocarrier systems for the successful delivery of phytomedicines. Focusing on the clinical perspective, the third section addresses the current clinical status of nanophytomedicine as a single drug therapy or combinatorial drug therapy, pharmacovigilance, pharmacokinetics, drug interactions and toxicological profiles, while also providing concluding remarks on recent experimental findings, and considering ethical issues & regulatory challenges in nanophytomedicine. Given its scope, the book offers a valuable guide for early career researchers, young scientists, master level students, academics and industrial scientists working in various healthcare fields, e.g. the pharmaceutical and biological sciences, life sciences, biotechnology, biomedical engineering, and nanobiotechnology.