There are more than 500 biopharmaceuticals on the market, including more than 200 therapeutic proteins, making biologics the fastest growing sector in the biopharmaceutical market. These products include more than 40 monoclonal antibodies, for indications ranging from treatment or mitigation of various types of cancer to rheumatoid arthritis. The clinical application of these therapeutic peptides and proteins is limited by several problems, such as lack of physical and chemical stability or the lack of desirable attributes for adequate absorption or distribution. Thus, as these therapeutic peptides and proteins are made available, it will be essential to formulate these drugs into safe, stable, and efficacious delivery systems. The pharmaceutical scientist involved in this effort needs to call upon the knowledge of several disciplines, such as pharmaceutics, medicinal chemistry, biochemistry, microbiology, and chemical engineering and needs to keep abreast with the latest research in the published literature. Therapeutic Peptides and Proteins: Formulation, Processing, and Delivery Systems, Third Edition provides a comprehensive overview of the field for scientists in industry and academia and for students, while also providing practical information on the challenges facing the formulation and delivery aspects of these unique macromolecules. In particular, the book: Explains how recombinant DNA techniques now allow us to produce therapeutic proteins in a commercially viable form Discusses the physical and chemical pathways of peptide and protein degradation Includes a detailed discussion of protein formulation and lyophilization Overviews the pharmacokinetic aspects of therapeutic peptides and proteins and discusses controlled delivery systems for parenteral administration, including microsphere formulations Discusses research progress on oral, transdermal, mucosal, and topical delivery systems discusses transdermal and topical delivery

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

This book introduces the principles and practices of modern medicinal chemistry and covers all aspects of drug discovery from the initial lead to final development. It teaches how to convert a lead compound into a potential drug and provides recent case histories as examples of successes. Medicinal Chemistry is unique in dealing with the subject in such a practical way and is the only book currently available to bring together all areas of the subject in one volume. This breadth of coverage is supplemented by references to specialist monographs and reviews, where the reader can find more detail on specific topics of interest if required. Medicinal Chemistry is essential reading for students studying medicinal chemistry, as it provides a grounding in all the required disciplines and subjects. It will also be of great interest to chemists, biochemists and pharmacologists either already working in or contemplating a career in the pharmaceutical and allied industries.

The biopharmaceutical industry has entered an era of unprecedented change and challenge, characterized by increasing pricing pressures, rising rates of attrition in the product development lifecycle, and decreasing scientific innovation. The most successful products are losing patent protection, and pipelines have been unable to fill the gap. This book explores the evolving definition of innovation in therapeutic product development and begins to examine its effects on the life sciences R&D industry. Historically, scientific innovation alone was sufficient to maintain ROI and deliver on unmet medical needs. However, with many forces now conspiring to increase pressures on the commoditization of drug development, industry support for truly novel, often high-risk development has eroded. This calls for a drastic redefinition of what "innovation" is. While innovation in the pharmaceutical R&D industry has historically been applied to major advances in therapy and unmet medical needs, we now need to see innovation increasingly defined in terms of financial, marketing (e.g. branded generics and emerging markets), pharmacoeconomic, and operational innovation. In this book, contributors drawn from the executive ranks of clinical development practitioners and stakeholders-from biopharmaceutical companies, clinical research organizations, academia, the financial community, and the patient perspective-have all come together to provide their expertise and visions. Their goal is to start a dialogue about ways to radically improve therapeutics development and get more and better medicines to the patients who need them, as fast as possible, in the most cost-efficient manner.

A great deal of confusion and uncertainty over genotoxic impurity (GTI) identification, assessment, and control exists in the pharmaceutical industry today. Pharmaceutical Industry Practices on Genotoxic Impurities strives to facilitate scientific and systematic consensus on GTI management by presenting rationales, strategies, methods, interpretations, practices, and case studies from the pharmaceutical industry. Featuring the contributions of industry leaders from nine major pharmaceutical companies, this authoritative text: Explores the safety, quality, and regulatory aspects of GTIs Provides an overview of the latest FDA and EMEA guidelines Explains the how and why of various GTI control tactics and practices Describes genotoxicity evaluation, acceptable exposure calculation, and analytical methods for testing Includes real-life examples of GTI control in drug substance and drug product development processes Containing case studies from large and small pharmaceutical firms in multiple geographical regions, Pharmaceutical Industry Practices on Genotoxic Impurities supplies an overview of-and a current framework for-GTI control in the pharmaceutical industry, demonstrating how proper management of GTIs can occur with the appropriate guidance, a firm grasp of the practical implications, and effective information sharing between disciplines.

Forage crops include several species of grasses and legumes that are widely used as animal fodder in the form of hay, pasturage and silage, as well as for turf and erosion control. Some forage grasses are also being considered for bio-energy generation. In this book leading researchers review the latest advances in molecular genetics and genomics; they also examine the success of breeding programs for forage grasses and legume species. The book will be useful for students and young researchers with an interest in forage, turf and bio-energy crops improvements.

Stroke remains one of the major causes of death and long-term disability worldwide. Currently, the only approved therapy for the acute treatment of this disease is thrombolysis, a strategy that can only be applied to a small percentage of patients due to its narrow therapeutic window. Unfortunately, during the last years numerous promising drugs that showed neuroprotection in the experimental setting failed to translate into the clinic because of their toxicity or lack of efficacy. Researchers in the field now face the crucial need to develop effective stroke therapies and successfully translate novel strategies into the clinical setting. Rational Basis for Clinical Translation in Stroke Therapy presents the most recent promising preclinical approaches and the most updated clinical evidence for treating stroke patients. By bringing together the experience of accomplished stroke researchers and clinicians, the book is a useful tool for improving the treatment and management of stroke patients. The book describes current approaches for the management of stroke patients including thrombolysis and mechanical recanalization procedures as well as other clinically relevant topics such as diagnosis, imaging, risk factors, and prevention. Also described are emerging interventions based on the use of stem cells, botulinum toxin, and antidepressants which complement emergency stroke treatment and conventional rehabilitation procedures. Clinical approaches are integrated with the most promising therapeutic opportunities based on targeting the immune system, hypothermia, and postconditioning. The book also covers issues related to the improvement of R&D strategies in stroke therapeutics, aimed at the implementation of preclinical approaches with stroke model guidelines and at the optimization of clinical trial design. This volume is a reference for all those interested in the rational development of novel stroke therapeutics.

An examination of the widespread application of nano materials in biology, medicine, and pharmaceuticals and the accompanying safety concerns, Bio-interactions of Nano Materials addresses the issues related to toxicity and safety of nano materials and nano systems. It covers the interactions in biological systems and presents various tools and methods used to evaluate the nano toxicity and nano safety issues. Written by leading scientists, the book focuses on the bio-interaction of nano materials, covering various techniques and tests which have been developed to evaluate the toxicity of materials at the nano level. The book highlights the challenges of bio-interactions of nano materials and possible solutions to those challenges. It addresses the assessment and characterization of nano systems in bio-environments, toxicity and bio-sensing devices for toxicity assessment, carbon nano tubes and pulmonary toxicity, and nano toxicity of solid lipid nanoparticles. It also discusses nano safety concerns and solutions, including the effects of nano particles on different organs and regulatory implications of nano materials. These particles may be used to encapsulate drugs, recognize biological markers, or visualize body tissues among many other possibilities, all enabling their widespread application in biology, medicine, and pharmaceutics. Indeed, these nano materials may have beneficial effects that have not even been imagined. This book gives you an understanding of the safety issues, how to assess for them, and how to mitigate them to move forward in research and development of new applications for nano materials.

Building on its best-selling predecessors, Basic Statistics and Pharmaceutical Statistical Applications, Third Edition covers statistical topics most relevant to those in the pharmaceutical industry and pharmacy practice. It focuses on the fundamentals required to understand descriptive and inferential statistics for problem solving. Incorporating new material in virtually every chapter, this third edition now provides information on software applications to assist with evaluating data. New to the Third Edition Use of Excel (R) and Minitab (R) for performing statistical analysis Discussions of nonprobability sampling procedures, determining if data is normally distributed, evaluation of covariances, and testing for precision equivalence Expanded sections on regression analysis, chi square tests, tests for trends with ordinal data, and tests related to survival statistics Additional nonparametric procedures, including the one-sided sign test, Wilcoxon signed-ranks test, and Mood's median test With the help of flow charts and tables, the author dispels some of the anxiety associated with using basic statistical tests in the pharmacy profession and helps readers correctly interpret their results using statistical software. Through the text's worked-out examples, readers better understand how the mathematics works, the logic behind many of the equations, and the tests' outcomes.

Written by an author with more than 40 years of teaching experience in the field, Experiments in Pharmaceutical Chemistry, Second Edition responds to a critical classroom need for material on directed laboratory investigations in biological and pharmaceutical chemistry. This new edition supplies 75 experiments, expanding the range of topics to 22 major areas of pharmaceutical chemistry. These include biochemical groups, botanical classes important to pharmacy, and major drug classifications:

• Carbohydrates
• Lipids
• Proteins
• Enzymes
• Inorganics
• Vitamins
• Steroids
• Plant Acids
• Flavonoids
• Alkaloids
• Tannins
• Resins
• Glycosides
• Gums
• Balsams
• Volatile Oils
• Analgesics
• Anesthetics
• Sulfa Drugs (Sulfonamides)
• Psychotropic Drugs
• Antibiotics
• Nucleic Acids

Sections contain introductions to basic concepts underlying the fields addressed and a specific bibliography relating to each field. Each experiment provides detailed instructions in a user-friendly format, and can be carried out, in most cases, without the need for expensive instrumentation. This comprehensive laboratory manual offers much-needed instructional material for teaching laboratory classes in pharmaceutical chemistry. The breadth of subject matter covered provides a variety of choices for structuring a laboratory course.

"Development of novel vaccines" gives an overview of the tasks in basic research leading to the final product -- the vaccine and its applications, belonging to the most complex biologics in the pharmaceutical field. Distinct from most textbooks in the vaccine arena, the current issue focuses on the translational aspect, namely, how research results can be transformed into life-saving medical interventions. Each chapter of the book deals with one important paradigm for the development of novel vaccines, along the value chain towards the final vaccine, and furthermore, with the inevitable tools required for this process. Contributions are prepared by teams of scientists, all of whom are experts in the field, most of them anchored in biomedical organizations devoted to translational culture, thereby lighting the certain topics from different views. This volume is a must read for researchers engaged in vaccine development and who really want to see their research results to become a product.

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

Many practitioners in the pharmaceutical industry are still largely unfamiliar with benefit-risk assessment, despite its growing prominence in drug development and commercialization. Helping to alleviate this knowledge gap, Benefit-Risk Assessment in Pharmaceutical Research and Development provides a succinct overview of the key considerations relevant to benefit-risk assessment across the pharmaceutical R&D spectrum, from early clinical development to late-stage development to regulatory review to post-launch assessment. The book first presents interpretations of benefit and risk in the context of a molecule moving from preclinical evaluation into its early testing in humans. It next considers benefit and risk characterization and assessment during a molecule's journey from its clinical evaluation in humans through its submission to regulators for marketing approval. Throughout these sections, the book offers insight into the role of benefit-risk assessment in heightening understanding among key stakeholders by shaping questions and guiding discussions among scientists, physicians, developers, and regulatory agencies. The book also focuses on a molecule's entry into the marketplace as a drug available for consumption by people. It explores the role of benefit-risk assessment as the relevance of carefully collected clinical efficacy and safety metrics fades in the wake of real-world use and evidence of effectiveness and safety. Bringing together the expertise of 15 contributors from academia and the industry, this book offers an easy-to-read guide to the various facets of benefit-risk assessment in the major stages of pharmaceutical R&D. Suitable for those in both technical and managerial roles, it enables readers to communicate more effectively across their development chain as well as rationally and thoughtfully embed benefit-risk assessment into their R&D processes.

Theory of Drug Development presents a formal quantitative framework for understanding drug development that goes beyond simply describing the properties of the statistics in individual studies. It examines the drug development process from the perspectives of drug companies and regulatory agencies. By quantifying various ideas underlying drug development, the book shows how to systematically address problems, such as: Sizing a phase 2 trial and choosing the range of p-values that will trigger a follow-up phase 3 trial Deciding whether a drug should receive marketing approval based on its phase 2/3 development program and recent experience with other drugs in the same clinical area Determining the impact of adaptive designs on the quality of drugs that receive marketing approval Designing a phase 3 pivotal study that permits the data-driven adjustment of the treatment effect estimate Knowing when enough information has been gathered to show that a drug improves the survival time for the whole patient population Drawing on his extensive work as a statistician in the pharmaceutical industry, the author focuses on the efficient development of drugs and the quantification of evidence in drug development. He provides a rationale for underpowered phase 2 trials based on the notion of efficiency, which leads to the identification of an admissible family of phase 2 designs. He also develops a framework for evaluating the strength of evidence generated by clinical trials. This approach is based on the ratio of power to type 1 error and transcends typical Bayesian and frequentist statistical analyses.

By guiding in the application of techniques and tools for predicting ADMET outcomes in drug candidates, Predictive ADMET offers a road map for drug discovery scientists to generate effective and safe drugs for unmet medical needs. Featuring case studies and lessons learned from real drug discovery and development, the text: helps users diagnose ADMET problems; presents appropriate recommendations; introduces the current clinical practice for drug discovery and development; and consolidates the tools and models to intelligently integrate existing in silico, in vitro and in vivo ADMET data.

Presenting authoritative and engaging articles on all aspects of drug development, dosage, manufacturing, and regulation, this Third Edition enables the pharmaceutical specialist and novice alike to keep abreast of developments in this rapidly evolving and highly competitive field. A dependable reference tool and constant companion for years to come, the Third Edition will offer completely new entries that cover critical issues in the field such as the impact of genomics, biotechnology, and implants on drug discovery, targeting, delivery, and formulation. In addition, it will address new regulatory issues, such as the changes in advertising regulations, and emerging FDA procedures.

This book is an accessible resource offering practical information not found in more database-oriented resources. The first chapter lists acronyms with definitions, and a glossary of terms and subjects used in biochemistry, molecular biology, biotechnology, proteomics, genomics, and systems biology. There follows chapters on chemicals employed in biochemistry and molecular biology, complete with properties and structure drawings. Researchers will find this book to be a valuable tool that will save them time, as well as provide essential links to the roots of their science. Key selling features: Contains an extensive list of commonly used acronyms with definitions Offers a highly readable glossary for systems and techniques Provides comprehensive information for the validation of biotechnology assays and manufacturing processes Includes a list of Log P values, water solubility, and molecular weight for selected chemicals Gives a detailed listing of protease inhibitors and cocktails, as well as a list of buffers

The aim and scope of this book is to highlight the sources, isolation, characterization and applications of bioactive compounds from the marine environment and to discuss how marine bioactive compounds represent a major market application in food and other industries. It discusses sustainable marine resources of macroalgal origin and gives examples of bioactive compounds isolated from these and other resources, including marine by-product and fisheries waste streams. In addition, it looks at the importance of correct taxonomic characterization.

This title includes a number of Open Access chapters. Pharmaceutical technology deals with the discovery, production, processing, and safe and effective delivery of medications to patients. Technologies involved include computer modeling for research, bioengineering for research instrumentation, processes and methods for increasing production, and computing technology and biosystematics for the management and analysis of data. This new book covers a wide range of important topics on today's pharmaceutical technology, such as in vitro drug release and controlled drug delivery, the use of nanotechnology in pharmaceuticals, quantum dot imaging, assessment and efficacy of pharmaceuticals, and much more.

The neurosciences have been an especially difficult field for drug discovery. Because of the huge complexity of the nervous system and poor understanding of most psychiatric and neurological diseases, most drugs currently available are the result of chance observations rather than a truly comprehensive approach. However, this situation has begun to change. Enormous progress in molecular biology has yielded breakthrough discoveries of the causes of nervous system diseases, opening the door for better-targeted and entirely novel therapies.
Reflecting these recent advances, Drug Discovery for Nervous System Diseases presents the latest techniques and approaches for drug discovery, organizing them according to diseases rather than classes of drugs or drug targets, as past books have done. Written with optimistic anticipation of great progress still to come, this text provides both a guide to present realities and a look to future possibilities in this burgeoning field.
Coverage in Drug Discovery for Nervous System Diseases includes:
* Fundamentals of drug discovery-receptors, target selection, and drug development
* Schizophrenia
* Depression
* Anxiety disorders
* Alzheimer's disease
* Parkinson's disease
* Ischemic stroke, brain, and spinal cord injury
* Other neurodegenerative diseases
* Sleep disorders
* Epilepsy
* Pain
This practical handbook features a uniform presentation for each chapter, with a brief description of existing drugs leading to recent molecular biological and genetic findings, translational research and the interface to clinical trials, and finally an outlook on future drug targets. Rich illustrations-schematic diagrams and tables-provide a dynamic visual experience throughout the text.
A unique and up-to-date guide to a field currently undergoing a major growth spurt, Drug Discovery for Nervous System Diseases offers both practitioners and advanced students an unparalleled resource.

Dietary Supplement GMP is a one-stop "how-to" road map to the final dietary supplement GMP regulations recently issued by the FDA covering the manufacture, packaging, and holding of dietary supplement products. The recent regulations, outlining broad goals, intentionally avoid specifics to allow for future technological advances-leaving implementation to the discretion of each firm. Given this latitude and flexibility, this new resource is an essential source of workable and practical suggestions on ways the industry can best meet the goals. Based on broad experience with GMP compliance techniques worked out over the years in the food, drug, and medical device industries, it is a must-have guide for all DS companies, especially the many smaller firms for whom this is new territory. Dietary Supplement GMP provides: a practical guide in easy to understand language to help navigate through the requirements for systems covering process and quality control suggestions and practical recommendations on "how-to" achieve full compliance explanation of the FDA's role regarding inspection, enforcement, recall/seizure of products and prosecution Dietary Supplement Good Manufacturing Practices (GMP) covers: Personnel Plants and Grounds Equipment and Utensils Sanitation of Buildings and Equipment Quality Assurance and Laboratory Operations The Quality Control Unit Production and Process Controls

Recent advances in immunology and biology have opened new horizons in cancer therapy, included in the expanding array of cancer treatment options, which are immunotherapies, or cancer vaccines, for both solid and blood borne cancers. Cancer Vaccines: Challenges and Opportunities in Translation is the first text in the field to bring immunotherapy treatments from the laboratory trial to the bedside for the practicing oncologist. Cancer Vaccines: Challenges and Opportunities in Translation: * Critically analyzes the most promising classes of investigational immunotherapies, integrating their scientific rationale and clinical potential * Discusses "theranostics" as pertaining to immunotherapy, i.e., using molecular diagnostics to identify patients that would most likely benefit from a therapy * Presents the new paradigm of biomarker guided R&D and clinical development in immunotherapy of cancer * Reviews bottlenecks in translational process of immunotherapies and offers strategies to resolve them

Finally - a book that covers all aspects of the illicit use of cocaine, amphetamines, ecstasy and/or designer drugs such as GHB, written by two experts in their field. The use of these drugs remains a continuous threat in health and medical care delivery, and this book will be an essential asset to the physician who may have to face the evaluation of patients whose use of these drugs compromises an effective treatment plan for other health issues.

The book has been conceived to fill the void in existing physician reference materials, and provides a comprehensive review of the theoretical knowledge and scope of pharmacotherapy in individuals who are hooked on a psychoactive substance.

While detailed scientific information is obtainable in other major articles, the book's straightforward format and style, along with its illustrations, will make for easy reading as emphasis is put on information specifically related to drugs that occur most abused in today s society. The information provided is based on clinical practice rather than pure experimental data, which will give the physician more effective tools useful in their daily practice. Many mechanisms of action of abuse are described in detail and references are provided to direct the reader to further sources for additional information.

As a special feature, the book incorporates uncluttered tables and charts, which result in immediate clarification of the mode of action on the central nervous system and the reason for misuse, thus avoiding usual long and fatiguing text in common reference books. The book aims to give the reader a clear and concise plan on what to do when being faced with an overdose situation.

A well-organized Table of Contents rapidly leads the reader from general pharmacological issues to the specific overdose syndrome and its management. Additionally, significant emphasis is placed on the practical do's and don ts for physicians, with special reference to the predictive signs of aberrant drug-related behavior and the identification of the drug diverter by using urine drug screening. "

The third edition of Pharmaceutical Process Scale-Up deals with the theory and practice of scale-up in the pharmaceutical industry. This thoroughly revised edition reflects the rapid changes in the field and includes: New material on tableting scale-up and compaction. Regulatory appendices that cover FDA and EU Guidelines. New chapters on risk evaluation and validation as related to scale-up. Practical advice on scale-up solutions from world renowned experts in the field. Pharmaceutical Process Scale-Up, Third Edition will provide an excellent insight in to the practical aspects of the process scale-up and will be an invaluable source of information on batch enlargement techniques for formulators, process engineers, validation specialists and quality assurance personnel, as well as production managers. It will also provide interesting reading material for anyone involved in Process Analytical Technology (PAT), technology transfer and product globalization.

Written to help companies comply with GMP, GLP, and validation requirements imposed by the FDA and regulatory bodies worldwide, Quality Control Training Manual: Comprehensive Training Guide for API, Finished Pharmaceutical and Biotechnologies Laboratories presents cost-effective training courses that cover how to apply advances in the life sciences to produce commercially viable biotech products and services in terms of quality, safety, and efficacy. This book and its accompanying downloadable resources comprise detailed text, summaries, test papers, and answers to test papers, providing an administrative solution for management. Provides the FDA, Health Canada, WHO, and EMEA guidelines directly applicable to pharmaceutical laboratory-related issues Offers generic formats and styles that can be customized to any organization and help management build quality into routine operations to comply with regulatory requirements Contains ready-to-use training courses that supply a good source of training material for experienced and inexperienced practitioners in the biotechnology/biopharmaceutical industries Includes downloadable resources with downloadable training courses that can be adopted and directly customized to a particular organization Supplies ready-to-use test papers that allow end users to record all raw data up to the issuance of the attached certificate The biotechnology/bioscience industries are regulated worldwide to be in compliance with cGMP and GLP principles, with particular focus on safety issues. Each company must create a definite training matrix of its employees. The training procedures in this book enable end users to understand the principles and elements of manufacturing techniques and provide documentation language ranging from the generic to the specific. The training courses on the downloadable resources supply valuable tools for developing training matrices to achieve FDA, Health Canada, EMEA, MHRA UK, WHO, and GLP compliance.