Pharmaceutical chemistry and technology Books

Book SynopsisAcute toxicology testing constitutes the first line of defense against potentially dangerous chemicals. This book provides a detailed presentation of protocols for each of the common designs, reviews their development and objectives, discusses the types of data they generate, and examines the current status of alternative test designs and models. For each test, applicable U.S. and international guidelines are also presented, and the formulation and selection of vehicles, dosages, and test animals are addressed.

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Book SynopsisIn this book we present recent studies that have been carried out on some widely used medicinal plants. The need for new and alternative treatments stem from the lack of efficiency of existing remedies for certain illnesses. We have compiled information that may be useful to researchers in their quest to develop new drugs.Table of ContentsPart 1: Ethnobotany 1. The Genus Aloysia Paláu (Verbenaceae) in Argentina. A Paradigm in Ethnobotany 2. Ethnobotany of Medicinal and Sacred Plants with Ethnopharmacological Potential from Southwestern Colombia 3. Ethnobotanical Uses and Potential Pharmaceutical Applications of the Cactaceae Family 4. Traditional Use of Plants in Mexico for the Treatment of Diabetes: An Ethnopharmacological Review and Scientific Evaluations 5. Limits and Risks of Plants Valorization in Morocco Associated with Their Vernacular Names 6. Resilience of Mapuche Health System and the Influence of COVID-19 Part 2: Traditional Knowledge of Useful Plants 7. Medicinal Use of the Plants of the Atacama Desert 8. Local Botanical Knowledge of Plants Associated with Andean and Chinese Traditions in the Metropolitan Area of Buenos Aires (Argentina): An Urban Ethnobotany Study 9. Traditional Uses, Phytochemistry, and Pharmacology of Mopane (Colophospermum mopane) in Southern African Countries 10. Traditional Medicine of the Kichwa of the Upper Napo 11. Traditional Practices Regarding the Use of Botanicals to Treat Bovine Haemonchosis in Pakistan

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Book SynopsisThis revised and updated new edition of a best-selling text remains a fast and convenient overview of the clinical trials in gynecologic cancer treatment, outlining the evidence base of treatment decisions in uterine, ovarian, cervical, and vulvar cancers, and gestational trophoblastic neoplasia. Residents and fellows will find this book an indispensable reference, while practitioners will welcome it as a clarification of the evidence base for treatment options. *Gives a convenient summary of trials in gynecologic oncology *Supplies an invaluable revision primer for those undertaking certification *Provides a uniquely up-to-date resourceTable of ContentsPreface to the second edition1. Uterine Malignancies. 1.1. Endometrial Carcinoma. 1.1.1. Studies addressing surgical treatment. 1.1.1.1. Lymph node assessment 1.1.2. Studies addressing adjuvant therapy. 1.1.2.1. Radiation. 1.1.2.2. Chemoradiation. 1.1.2.3. Chemotherapy. 1.1.3. Studies addressing treatment of recurrent endometrial carcinoma. 1.1.3.1. Hormonal therapy. 1.1.3.2. Chemotherapy. 1.1.3.3. Targeted therapy. 1.1.3.4. Immunotherapy. 1.2. Uterine Carcinosarcoma. 1.2.1. Studies addressing prognosticators. 1.2.2. Studies addressing adjuvant treatment. 1.2.3. Studies addressing treatment of advanced/ recurrent uterine carcinosarcoma. 1.3. Uterine Leiomyosarcoma. 1.3.1. Studies addressing adjuvant treatment of early stage uterine leiomyosarcoma. 1.3.2. Studies addressing treatment of advanced uterine leiomyosarcoma. 1.4. References.2. Ovarian Malignancies. 2.1. Epithelial ovarian cancer (EOC). 2.1.1. Studies addressing upfront surgery. 2.1.2. Studies addressing adjuvant therapy. 2.1.3. Studies addressing intraperitoneal chemotherapy. 2.1.4. Studies addressing first line maintenance treatment. 2.1.5. Studies addressing neoadjuvant therapy. 2.1.6. Studies addressing prediction of debulking. 2.1.7. Studies addressing time point of treatment of recurrence. 2.1.8. Studies addressing treatment of recurrent ovarian cancer, platinum-sensitive. 2.1.8.1. Chemotherapy and targeted therapy. 2.1.8.2. Secondary debulking surgery. 2.1.9. Studies addressing treatment of recurrent ovarian cancer, platinum-resistant. 2.1.9.1. Chemotherapy and targeted therapy. 2.1.9.2. Immunotherapy. 2.2. Low grade serous ovarian cancer. 2.3. Mucinous epithelial ovarian cancer (mEOC). 2.4. Ovarian Germ Cell Tumors (GCT). 2.5. Ovarian Sex Cord-Stromal Tumors (SCT). 2.6. References.3. Cervical Cancer. 3.1. Studies addressing surgical treatment. 3.2. Studies addressing adjuvant therapy. 3.3. Studies addressing primary chemoradiation therapy. 3.4. Studies addressing treatment of recurrent or metastatic cervical cancer. 3.4.1. Chemotherapy and targeted therapy. 3.4.2. Immunotherapy. 3.5. References.4. Vulvar Cancer. 4.1. Studies addressing surgical treatment. 4.1.1. Groin lymph nodes. 4.2. Studies addressing advanced vulvar cancer. 4.2.1. Chemoradiation. 4.2.2. Immunotherapy. 4.3. References.5. Gestational Trophoblastic Neoplasia (GTN). 5.1. Studies addressing surgical treatment. 5.2. Studies addressing chemotherapy in low-risk GTN. 5.3. Studies addressing (chemo)therapy in high-risk GTN. 5.4. References.6. Glossary. Index.

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Book SynopsisThe use of medicinal plants in herbal and modern medicine has gained popularity over the last few decades due to consumers taking more natural approaches to medicine. Aquatic medicinal plants are rich in bioactive compounds and demonstrate various commercial, nutraceutical, and biological applications. Aquatic Medicinal Plants offers the reader a wealth of information on uses of bioactive components of these plants, along with crucial references, and explains their traditional uses, phytochemistry, and pharmacological properties.Features Provides information on aquatic and semiaquatic medicinal plants and their uses globally. Discusses phytochemical components with the known active constituents and their pharmaceutical applications. This volume in the Exploring Medicinal Plants series is appropriate for scientists, experts, and consultants associated with the exploration of aquatic medicinal plant usage.  This book is an essenTable of ContentsMedicinal Importance of Nelumbo nucifera. Traditional Uses, Important Phytochemical, and Therapeutic Profile of Persicaria hydropiper. Ethnobotanical, Phytochemistry, and Pharmacological Activity of Marsilea minuta. Traditional Uses, Phytochemistry, and Pharmacological Properties of Hedychium coronarium. Pharmacognostical Phytochemical, and Ethnomedicinal Properties of Enhydra fluctuans. Medicinal Uses and Pharmacological Properties of Acorus calamus. Medicinal properties of Rotula aquatic. Traditional Uses and Pharmacological Profile of Sphaeranthus indicus. Phytochemistry and Medicinal Uses of Pistia stratiotes. Biological Activity and Medicinal Uses of Arundo donax. Sagittaria sagittifolia. Phytochemistry and Pharmaceutical Application of Laurencia obtuse: A Red Seaweed. Phytochemical and Therapeutic Properties of Didemnum genus. Brown Algae (Phaeophyta) Source of Different Phytochemical and their Medicinal Application. Phytochemistry and Bioactivity of Green Algae (Chlorophyta). Chemical Composition and Biological Activity of Red Algae (Rhodophyta).

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Book SynopsisSince the early 2000s, there has been increasing interest within the pharmaceutical industry in the application of Bayesian methods at various stages of the research, development, manufacturing, and health economic evaluation of new health care interventions. In 2010, the first Applied Bayesian Biostatistics conference was held, with the primary objective to stimulate the practical implementation of Bayesian statistics, and to promote the added-value for accelerating the discovery and the delivery of new cures to patients.This book is a synthesis of the conferences and debates, providing an overview of Bayesian methods applied to nearly all stages of research and development, from early discovery to portfolio management. It highlights the value associated with sharing a vision with the regulatory authorities, academia, and pharmaceutical industry, with a view to setting up a common strategy for the appropriate use of Bayesian statistics for the benefit of patients. TheTrade Review"The book is full of interesting real examples across the chapters, which not only makes the reading fun but also demonstrates the practical usefulness of Bayesian methods in pharmaceutical research. In synthesis, this is a very well written book, which can be used as self-learning material or as a main reference for experts and practitioners."- Pablo Emilio Verde, International Society for Clinical Biostatistics, 72, 2021Table of ContentsI Introductory part Chapter 1: Bayesian Background Chapter 2: FDA Regulatory Acceptance of Bayesian StatisticsChapter 3: Bayesian Tail Probabilities for Decision Making II Clinical development Chapter 4: Clinical Development in the Light of Bayesian Statistics Chapter 5: Prior ElicitationChapter 6: Use of Historical Data Chapter 7: Dose Ranging Studies and Dose Determination Chapter 8: Bayesian Adaptive Designs in Drug Development Chapter 9: Bayesian Methods for Longitudinal Data with MissingnessChapter 10: Survival Analysis and Censored Data Chapter 11: Benefit of Bayesian Clustering of Longitudinal Data: Study of Cognitive Decline for Precision Medicine Chapter 12: Bayesian Frameworks for Rare Disease Clinical Development Programs Chapter 13: Bayesian Hierarchical Models for Data Extrapolation and Analysis in Pediatric Disease Clinical Trials III Post-marketing Chapter 14: Bayesian Methods for Meta-AnalysisChapter 15: Economic Evaluation and Cost-Effectiveness of Health Care InterventionsChapter 16: Bayesian Modeling for Economic Evaluation Using "Real World Evidence"Chapter 17: Bayesian Benefit-Risk Evaluation in Pharmaceutical Research IV Product development and manufacturing Chapter 18: Product Development and Manufacturing Chapter 19: Process Development and Validation Chapter 20: Analytical Method and Assay Chapter 21: Bayesian Methods for the Design and Analysis of Stability Studies Chapter 22: Content Uniformity Testing Chapter 23: Bayesian methods for in vitro dissolution drug testing and similarity comparisons Chapter 24: Bayesian Statistics for Manufacturing V Additional topics Chapter 25: Bayesian Statistical Methodology in the Medical Device Industry Chapter 26: Program and Portfolio Decision-Making

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Book SynopsisMedicinal and aromatic plants are beneficial to human health. Plant-derived molecules possess biological activities that can be used to prevent many infectious diseases and metabolic disorders. Ethnobotany and Ethnopharmacology of Medicinal and Aromatic Plants summarizes techniques and methods used to study the biological activities of plant-derived extracts and compounds to study ethnobotanical and ethnopharmacological features of medicinal and aromatic plants.This book: Includes computational approaches to study the pharmacological properties of biomolecules in medicinal and aromatic plants. Details methods in ethnopharmacology including chromatographical and analytical techniques. Demonstrates trends in sustainable use and management of medicinal and aromatic plants. Features information on databases and tools used in computational phytochemistry for drug designing and discovery. Elucidates the importance of phytocTable of ContentsChapter 1: Introduction to Medicinal and Aromatic Plants: Diversity, Biogeographic Distribution and Conservation Status. Chapter 2: Botanical Bases of Medicinal and Aromatic Plants. Chapter 3: Trends in Sustainable Use and Management of Medicinal and Aromatic Plants: Utilization and Development. Chapter 4: Threatened and Endangered Medicinal and Aromatic Plants. Chapter 5: Ethnobotany, Ethnopharmacology, and Traditional Uses of Medicinal and Aromatic Plants. Chapter 6: Wild Edible Medicinal and Aromatic Plants in Ancient Traditions. Chapter 7: Ethnopharmacology and Ethnopharmacognosy: Current Perspectives and Future Prospects. Chapter 8: Phytochemistry and Biosynthesis of Phytochemicals. Chapter 9: Phytochemicals as Immunomodulators, Nutraceuticals, and Pharma Food. Chapter 10: Phytochemotaxonomy: Role of Phytochemicals in Plant Classification: Chapter 11: Biological Roles and Mechanism of Phytochemicals in Disease Prevention and Treatment. Chapter 12: Metabolomics of Medicinal and Aromatic Plants. Chapter 13: Methods in Ethnopharmacology: Phytochemical Extraction, Isolation, and Detection Techniques. Chapter 14: Chromatographic Techniques in Phytochemistry and Analytical Techniques in Elemental Profiling. Chapter 15: NMR-based Metabolomics and Hyphenated NMR Techniques. Chapter 16 Animal Models in Phytopharmacology and Toxicological Testing of Plant Products. Chapter 17: Computational Phytochemistry in Drug Discovery: Databases and Tools. Chapter 18: Nanoformulations and Herbal Drug Development. Chapter 19: Novel Phytochemicals Targeting the Signaling Pathways of Anticancer Stem Cell: A Novel Approach Against Cancer. Chapter 20: Evolving Challenges and Opportunities in Plant-based Drug Discovery and Development. Index.

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Book SynopsisHerbal Treatment of Anxiety: Clinical Studies in Western, Chinese and Ayurvedic Traditions explains the nature and types of anxiety, its neurobiology, the pathophysiology that exacerbates and perpetuates it, and the psychopharmacology of the chemical agents that relieve its manifestations. Throughout the text are discussions of Western, Chinese and Ayurvedic herbal treatments that have been clinically shown to be effective in relieving anxiety. The book also features a scientific discussion of the use of herbs and essential oils in aromatherapy and the mechanisms by which they may work. The book concludes by providing bases upon which herbs can be chosen to treat the anxiety of patients according to their individual needs.Additional features include: Examines the increasingly popular subject of the use of herbs as a natural alternative treatment and provides a much-needed scientific basis for treatments often considered as merely folk medicine. Discusses the psychoactive phytochemicals contained in herbs. Includes a chapter discussing the nature and mechanisms of action of adaptogens. Adds to the armamentarium of anxiolytics for providers who have become reluctant to prescribe benzodiazepines as treatment of anxiety, particularly in the context of the opiate crisis. Gives an introduction to herbal treatments of traditional Chinese and Ayurvedic medicine. Offers practical advice on initiating and managing herbal treatments. Herbal Treatment of Anxiety is a valuable reference for psychiatrists, psychiatric nurse practitioners, primary care providers, naturopathic doctors and therapists interested in the most current scientific information on the effects of herbal treatments of anxiety disorders.

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Book SynopsisCombination products are therapeutic and diagnostic products that combine drugs, devices, and/or biological products. According to the US Food and Drug Administration (FDA), âœa combination product is one composed of any combination of a drug and a device; a biological product and a device; a drug and a biological product; or a drug, device and a biological product.â Examples include prefilled syringes, pen injectors, autoinjectors, inhalers, transdermal delivery systems, drug-eluting stents, and kits containing drug administration devices co-packaged with drugs and/or biological products. This handbook provides the most up-to-date information on the development of combination products, from the technology involved to successful delivery to market. The authors present important and up-to-the-minute pre- and post-market reviews of international combination product regulations, guidance, considerations, and best practices.This handbook: Brings clarity of understanding for global combination products guidance and regulations Reviews the current state-of-the-art considerations and best practices spanning the combination product lifecycle, pre-market through post-market Reviews medical product classification and assignment issues faced by global regulatory authorities and industry The editor is a recognized international Combination Products and Medical Device expert with over 35 years of industry experience and has an outstanding team of contributors. Endorsed by AAMI â Association for the Advancement of Medical Instrumentation.

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Book SynopsisCovering all major arthropods of medical importance worldwide, this award-winning resource has established itself as a standard reference for almost 25 years. With the globilization of commerce and the world becoming more intimately connected through the everyday ease of travel, unknown arthropod species are being increasingly encountered. This means access to up-to-date, authoritative information in medical entomology has never been more important. Now in its seventh edition, this book maintains its well-acclaimed status as the ultimate easy-to-use guide to identify disease-carrying arthropods, the common signs and symptoms of vector-borne diseases, and the current recommended procedures for treatment. Includes an in-depth chapter with diagnostic aids to help physicians to recognize and accurately diagnose arthropod-related diseases and conditions more easilyUpdates all chapters with the latest medical and scientific findings, including Zika virus, red meat allergyTrade ReviewPraise for the previous edition "The sixth edition continues the previous tradition, in that the information provided is practical and presented in a format optimal for use on an as-needed basis. The addition of color photographs throughout the text (and not just an insert) is a major plus. Additional clinical case histories enliven the text. General guidelines to treatment of conditions resulting from exposure to arthropods and appropriate references to detailed material are also provided. Another aspect, the ‘Bug Coach’ CD-ROM, provides over 100 line drawings, figures, and photos in three sections: (1) arthropods, (2) arthropod-induced diseases and conditions, and (3) an identification guide. The CD also now includes a few brief instructional videos. … This text has come of age at a time when it is needed most. It will especially be valued by health care providers who find themselves in unknown territory, both geographically and medically."—Richard D. deShazo, M.D., University of Mississippi Medical Center Table of ContentsPart I Pathological Conditions Caused by Arthropods and Principles of Their Treatment 1 Principles of Treatment for Arthropod Bites, Stings, and Other Exposure 2 Allergy to Arthropods 3 Stings 4 Bites 5 Blistering, Dermatitis, and Urticaria from Contact with Arthropods 6 Myiasis (Invasion of Human Tissues by Fly Larvae) 7 Delusions of Parasitosis (Imaginary Insect or Mite Infestations) PART II Identification of Arthropods and the Diseases They Cause 8 Identification of Medically Important Arthropods 9 Clinician’s Guide to Common Arthropod Bites and Stings PART III Arthropods of Medical Importance 10 Ants 11 Bees 12 Beetles 13 Bugs (The True Bugs) 14 Caterpillars (Urticating) 15 Centipedes 16 Cockroaches 17 Earwigs 18 Fleas 19 Flies (Biting) 20 Flies (Nonbiting) 21 Flies (That Might Cause Myiasis) 22 Lice 23 Millipedes 24 Mites 25 Mosquitoes 26 Moths (Species Whose Scales or Hairs Cause Irritation) 27 Pentastomes (Tongue Worms) 28 Scorpions 29 Spiders 30 Ticks 31 Wasps (Yellowjackets, Hornets, and Paper Wasps) PART IV Personal Protection Measures against Arthropods 32 Pros and Cons of Insect Repellents 33 Arthropod-Specific Personal Protection Techniques

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Book SynopsisDiabetes is a chronic condition associated with metabolic disorder. Persons suffering from diabetes have shown accelerated levels of blood sugar which often harms the heart, blood vessels, eyes, kidneys, and nerves. Over the past few decades, the prevalence of diabetes has been progressively increasing. Synthetic drugs are used to treat diabetic patients to help control the disorder, but it is shown that numerous medicinal plants and herbal drugs are widely used in several traditional systems of medicine to prevent and treat diabetes. They are reported to produce beneficial effects in combating diabetes and alleviating diabetes-related complications. These plants contain phtyonutrients and phytoconstituents demonstrating protective or disease preventive properties. In many developing countries, herbal drugs are recommended by traditional practitioners for diabetes treatment because the use of synthetic drugs is not affordable.Key Features:ProvidesTable of ContentsSection A - Introduction to Diabetes: An Overview. Medicinal and Herbal Plants-Based Phytochemicals Associated with Antidiabetic Response. Antidiabetic Medicinal and Herbal Plants and their Mechanisms of Action. Section B - Antidiabetic Medicinal and Herbal Plants. Babul (Acacia arabica). Bael (Aegle marmelose). Church steeples (Agrimonia eupatoria). Onion (Allium cepa). Garlic (Allium sativum). Ghrita kumara (Aloe vera). Bitterweed (Andrographis paniculata). Sugar apple (Annona squamosa). Neem (Azadirachta indica). Orchid tree (Bauhinia variegata). Red spiderling (Boerhaavia diffusa). Ash gourd (Benincasa hispida). Beetroot (Beta vulgaris). Fever nut (Caesalpinia bonducella). Bitter apple (Citrullus colocynthis). Ivy gourd (Coccinia indica). Eucalyptus (Eucalyptus globules). Banyan tree (Ficus benghalenesis). Gurmar (Gymnema sylvestre). Gurhal (Hibiscus rosa-sinesis). Sweet potato (Ipomoea batatas). Purging nut (Jatropha curcas). Mango (Mangifera indica). Karela (Momordica charantia). Mulberry (Morus alba). Kiwach (Mucuna pruriens). Black cumin (Nigella sativa). Tulsi (Ocimum sanctum). Guava (Psidium guajava). Bisasar (Pterocarpus marsupium). Anar (Punica granatum). Jamun (Syzygium cumini). Giloy (Tinospora cordifolia). Methi (Trigonella foenum-graecum). Bitter leaf (Vernonia amygdalina). Chinese date (Zizyphus spina-christi).

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Book SynopsisThis volume in the popular series, Drugs and the Pharmaceutical Sciences, begins with the history of cancer treatment, carcinogens, and molecular mechanisms involved in cancer pathogenesis. It incudes conventional and advanced cancer therapies ranging from oral and parenteral preparations to advanced fabricated systems such as nanoparticles, liposomes, antibodies, aptamers, poly(amidoamine) and photodynamic therapies. The preparation and mechanisms of molecular targeting of cancer are presented and the authors focus on a diverse audience including undergraduates and research students.Features Timely coverage of changes in process control technology for the phamaceutical industry, a dynamic area in terms of products and manufacturing processes Provides an update on the unique requirements of these industries and how they differ from others, for example the microelectronics or specialized chemicals industries Draws on the author''s vaTable of Contents History of Cancer Therapies Cancer and Carcinogens Causes of Death from Cancer Passive Targeting Cancer Active Targeting Strategies Conventional Cancer Therapies Oral Anticancer Therapies Parenteral Anticancer Therapies Advanced Cancer Therapies The Advent of Micro and Nano-spheres for Cancer Treatment The Emergence of Liposomes in Cancer Therapy Niosomes-Based Anticancer Therapies Solid Lipid Nanoparticles-Based Anticancer Therapies Mesoporous Nanoparticles-Based Anticancer Therapies Antibody-Based Cancer Therapies Aptamer-Based Anticancer Therapies Polyamidoamines-Based Anticancer Therapies Photodynamic Therapies for Cancer Treatment

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Book SynopsisMedical Affairs is one of the three strategic pillars of the pharmaceutical and MedTech industries, but while clear career paths exist for Commercial and Research and Development, there is no formal training structure for Medical Affairs professionals. Medical and scientific expertise is a prerequisite for entry into the function, and many people transitioning into Medical Affairs have advanced degrees such as PhD, MD, or PharmD. However, these clinical/scientific experts may not be especially well-versed in aspects of industry such as the drug development lifecycle, crossfunctional collaborations within industry, and digital tools that are transforming the ways Medical Affairs generates and disseminates knowledge. This primer for aspiring and early-career Medical Affairs professionals equips readers with the baseline skills and understanding to excel across roles.Features:Defines the purpose and value of Medical Affairs and provides clear career Table of ContentsSECTION 1: MEDICAL AFFAIRS IN THE PHARMACEUTICAL AND MEDTECH INDUSTRIES Chapter 1 What Is Medical Affairs? Chapter 2 Groups and Structure of Medical Affairs Chapter 3 Medical Affairs Collaborations Across the Drug/Device Development Lifecycle Chapter 4 Measuring the Impact of Medical Affairs Chapter 5 Medical Affairs Careers SECTION 2: THE PRACTICE OF MEDICAL AFFAIRS Chapter 6 Medical Strategy and Launch Excellence Chapter 7 Evidence Generation and Real-World Evidence Chapter 8 Medical Communications Chapter 9 External Education Chapter 10 Field Medical Chapter 11 Insights Chapter 12 Medical Information Chapter 13 Patient Centricity Chapter 14 Medical Operations Chapter 15 Digital Strategy Chapter 16 Compliance Chapter 17 Rare Disease and Gene Therapy Chapter 18 Medical Affairs in MedTech

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Book SynopsisThe management of clinical data, from its collection during a trial to its extraction for analysis, has become critical in preparing a regulatory submission and obtaining approval to market a treatment. Groundbreaking on its initial publication nearly 14 years ago, and evolving with the field in each iteration since then, this latest volume includes revisions to all chapters to reflect the recent updates to ICH E6, good clinical practices, electronic data capture, and interactive response technologies. Keeping the coverage practical, the author focuses on the most critical information that impacts clinical trial conduct, providing a full end-to-end overview for clinical data managers.Features:Provides an introduction and background information for the spectrum of clinical data management tasks.                            &nbsp

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Book SynopsisLeadership in the Pharmaceutical Industry focuses on leadership in pharmaceutical organisations at three levels: individual, team, and organisational. At the individual level, it covers leadership basics, theories, types of leaders, differences between leader and manager, leadership traits and skills, and systems thinking. At the team level, it explores leadership styles, the leader's interaction with the team, and employee motivation, including the use of intrinsic motivational factors. At the organisational level, it examines the leader's role in creating and maintaining organisational culture, forming and implementing organisational strategy, and managing organisational changes.The book also addresses the specifics of the pharmaceutical industry, including the types and characteristics of innovations and the ethics of leader behaviour, emphasising the importance of ethical leadership. Notably, leadership issues are illustrated with practical cases featuring prominent leaders such as Paul Janssen, Daniel Vasella, Charles Walgreen III, John C. Martin, Roy Vagelos, Albert Bourla, Kiran Mazumdar-Shaw, and Filya Zhebrovska. These leaders were or are involved in creating, manufacturing, and providing patients with pharmaceutical products.The book is designed to benefit readers from various business sectors, with the primary audience being academics, students, and individuals interested in leadership in the pharmaceutical industry.

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Book SynopsisAn authoritative reference that contains the most up-to-date information knowledge, approaches, and applications of lipid crystals Crystallization of Lipids is a comprehensive resource that offers the most current and emerging knowledge, techniques and applications of lipid crystals. With contributions from noted experts in the field, the text covers the basic research of polymorphic structures, molecular interactions, nucleation and crystal growth and crystal network formation of lipid crystals which comprise main functional materials employed in food, cosmetic and pharmaceutical industry. The authors highlight trans-fat alternative and saturated-fat reduction technology to lipid crystallization. These two issues are the most significant challenges in the edible-application technology of lipids, and a key solution is lipid crystallization. The text focuses on the crystallization processes of lipids under various external influences of thermal flucTable of ContentsPreface xiii List of Contributors xv 1 Introduction: Relationships of Structures, Properties, and Functionality 1 Kiyotaka Sato 1.1 Introduction 1 1.2 Lipid Species 1 1.2.1 Hydrocarbons 1 1.2.2 Fatty Acids 2 1.2.3 Alcohols and Waxes 4 1.2.4 Acylglycerols 4 1.3 Physical States and the Functionality of Lipid Products 5 1.4 Formation Processes of Lipid Crystals 7 1.5 Polymorphism 9 1.6 Aging and Deterioration 11 1.7 Trans‐Fat Alternative and Saturated‐Fat Reduction Technology 13 References 15 2 Polymorphism of Lipid Crystals 17 Kiyotaka Sato 2.1 Introduction 17 2.2 Thermal Behavior of Polymorphic Transformations 17 2.3 Molecular Properties 20 2.3.1 Subcell and Chain‐Length Structures 20 2.3.2 Conformation of Hydrocarbon Chains 24 2.3.3 Glycerol Conformations 25 2.3.4 Polytypism 26 2.4 Fatty Acids 27 2.4.1 Saturated Fatty Acids 27 2.4.2 Unsaturated Fatty Acids 32 2.5 Monoacylglycerols and Diacylglycerols 37 2.5.1 Crystal/Molecular Structures 37 2.5.2 Polymorphic Behavior 39 2.6 Triacylglycerols (TAGs) 41 2.6.1 Crystal/Molecular Structures 42 2.6.2 Polymorphic Behavior 46 2.7 Conclusions 54 References 54 3 Molecular Interactions and Mixing Phase Behavior of Lipid Crystals 61 Eckhard Floeter, Michaela Haeupler, and Kiyotaka Sato 3.1 Introduction 61 3.2 Thermodynamic Considerations 63 3.2.1 Framework for Engineering Calculations 63 3.2.2 Phase Behavior of Co‐Crystallizing Components 66 3.2.3 Governing Principles for Phase Boundaries 70 3.3 Effects of Molecular Structures on the Phase Behavior 70 3.3.1 Aliphatic Chain‐Chain Interactions: n‐Alkanes 71 3.3.2 Mixtures of Fatty Acids 72 3.3.3 Mixtures of Partial Glyceride Fatty‐Acid Esters 81 3.3.4 Mixtures of TAGs 82 3.4 Mixing Behavior of TAGs in Natural and Interesterified Fats 92 3.4.1 Cocoa Butter 93 3.4.2 Palm Oil 94 3.4.3 Coconut Oil 95 3.4.4 Milk Fat 95 3.4.5 Interesterified Fats 96 3.5 Crystallization Properties 97 3.6 Conclusions 98 References 100 4 Fundamental Aspects of Crystallization of Lipids 105 Hironori Hondoh, Satoru Ueno, and Kiyotaka Sato 4.1 Introduction 105 4.2 Physical and Structural Properties of Lipid Liquids 105 4.2.1 Preheating Effects 106 4.2.2 Liquid Phases of Triacylglycerols 109 4.3 Driving Forces for Crystallization 112 4.4 Nucleation 114 4.4.1 Homogeneous versus Heterogeneous 114 4.4.2 Polymorph‐Dependent Nucleation Kinetics 118 4.4.3 Secondary Nucleation 121 4.4.4 Crystal Seeding 122 4.5 Kinetics of Crystal Growth 125 4.5.1 Mechanism of Crystal Growth 125 4.5.2 Crystal Growth Rate 127 4.5.3 Polymorph‐Dependent Growth Rate 129 4.5.4 Spherulite 130 4.5.5 Epitaxial Growth 132 4.5.6 Morphology of Crystals 133 4.6 Conclusions 135 Acknowledgment 136 References 136 5 Supramolecular Assembly of Fat Crystal Networks from the Nanoscale to the Mesoscale 143 Fernanda Peyronel, Nuria C. Acevedo, David A. Pink, and Alejandro G. Marangoni 5.1 Introduction 143 5.2 Cryo‐TEM 144 5.2.1 Challenges Associated with the Microscopic Observation of Fat Microstructure 144 5.2.2 Sample Preparation for Cryo‐TEM 145 5.2.3 Nanoscale Structure Characterization 146 5.2.4 Effects of External Fields on Fat Nanostructure 148 5.3 Physical Interactions, Models, and Mathematical Methods 154 5.3.1 Models in General 155 5.3.2 Coarse‐Grained Interactions: Nano‐ to Mesoscale 156 5.3.3 Models Using Spheres 157 5.3.4 Introduction to Modeling the Statics and Dynamics of Aggregates 157 5.3.5 Static Structure Functions 158 5.3.6 Application 1: CNP Aggregation. Tristearin Solids in Triolein Oil 158 5.3.7 Application 2: Complex Oils. Tristearin Solids in Complex Oils 161 5.3.8 Application 3: Nanoscale Phase Separation in Edible Oils 162 5.4 Ultra Small Angle X‐Ray Scattering (USAXS) 164 5.4.1 Principles of X‐Ray Scattering 164 5.4.2 USAXS Instrumentation at the APS 167 5.4.3 Sample Preparation 168 5.4.4 Unified Fit and Guinier‐Porod Models 168 5.4.5 Experimental Results 170 5.5 Concluding Remarks 174 Acknowledgments 175 References 175 6 Effects of Dynamic Temperature Variations on Microstructure and Polymorphic Behavior of Lipid Systems 183 Laura Bayés‐García, Teresa Calvet, and Miquel À. Cuevas‐Diarte 6.1 Introduction 183 6.2 Influence on the Polymorphic Behavior in Bulk State 183 6.2.1 Single Tag Components 183 6.2.2 Binary Mixtures of TAGs 189 6.3 Colloidal Dispersion States 193 6.3.1 Emulsions 193 6.3.2 Organogels 196 6.4 Role of Thermal Treatments on End Food Products Properties 198 6.4.1 Milk Fats 198 6.4.2 Other Dairy Products 199 6.4.3 Cocoa Butter 200 6.4.4 Vegetable Fats 204 6.5 Conclusions 206 References 207 7 Lipid Crystal Networks Structured under Shear Flow 211 Farnaz Maleky and Gianfranco Mazzanti 7.1 Introduction 211 7.2 Overview of the Formation of Fat Crystals 212 7.3 Temperature Gradients and Optimal Supercooling 213 7.4 Basic Concepts on Shear Flow 214 7.5 Fat Crystallization under Shear 216 7.5.1 Shear Affects Polymorphic Transformations 216 7.5.2 Crystalline Orientation Induced by Shear Flow 219 7.5.3 Shear Affects Fat Structural Properties at the Micro‐ and Nano‐Length Scales 224 7.5.4 Physicochemical Properties of Sheared Fat Matrices 227 7.5.5 Effects of Shear Flow on Mass Transfer Dynamics of Crystallizing and Crystallized Materials 231 7.6 Concluding Remarks 233 References 234 8 Tailoring Lipid Crystal Networks with High‐Intensity Ultrasound 241 Yubin Ye, Peter R. Birkin, and Silvana Martini 8.1 Introduction 241 8.2 Fundamentals of Sonication 242 8.2.1 Acoustic Driving Force 242 8.2.2 Acoustic Cell Characteristics 243 8.2.3 Cavitation 244 8.2.4 Experimental Conditions 245 8.3 Tailoring Lipid Crystal Networks 246 8.3.1 Crystallization Kinetics 246 8.3.2 Inferential Mechanism 249 8.3.3 Postsonication Changes 250 8.4 Practical Considerations 255 8.4.1 Oxidation 255 8.4.2 Scale Up 257 8.4.3 Combination with Other Processing Methods 258 8.5 Conclusions and Future Research 258 References 259 9 Effects of Foreign and Indigenous Minor Components 263 Kevin W. Smith and Kiyotaka Sato 9.1 Introduction 263 9.2 Basic Understanding 264 9.3 Effects of Foreign Components 265 9.3.1 Emulsifiers 265 9.3.2 Indigenous Minor Components 276 9.4 Other Additives 276 9.5 Conclusions 278 References 279 10 Crystallization Properties of Milk Fats 283 Christelle Lopez 10.1 Introduction 283 10.2 Milk Fat: A Wide Diversity of Fatty Acids and Triacylglycerols (TAGs) 284 10.3 Crystallization Properties of Bovine Anhydrous Milk Fat (AMF) 285 10.3.1 Thermal Properties 285 10.3.2 Effect of Cooling Rate on AMF Crystals 286 10.3.3 Effect of Shear on AMF Crystals 295 10.3.4 Effect of Minor Lipid Compounds 295 10.4 Crystallization of TAGs in Bovine Milk Fat Globules and Emulsion Droplets 296 10.4.1 Effect of Cooling Rate and Tempering 298 10.4.2 Effect of the Size of Milk Fat Globules and Lipid Droplets 304 10.5 Crystallization Properties of Milk Fat in Dairy Products 306 10.6 Tag Compositions Affecting Crystallization Properties of Milk Fat 308 10.6.1 Technological Process: Dry Fractionation 308 10.6.2 Dietary Manipulations 312 10.6.3 Milk Fat from Various Mammal Species 315 10.7 Liquid Tag Phase 316 10.8 Conclusions 317 References 318 11 Crystallization Behavior of Sunflower Oil–Based Fats for Edible Applications 323 Maria L. Herrera and Silvana Martini 11.1 Introduction 323 11.2 High Stearic High Oleic Sunflower Oil 324 11.2.1 Fractionation of HSHO‐SFO 324 11.2.2 Crystallization Behavior 326 11.2.3 Polymorphic Behavior 329 11.3 Blends of Sunflower Oil and Milk Fat 337 11.3.1 Chemical Composition 340 11.3.2 Physical Properties 340 11.3.3 Addition of Palmitic Sucrose Ester 344 11.4 HSHO‐Based CBE 347 11.5 Conclusions 348 References 348 12 Physical Properties of Organogels Developed with Selected Low‐Molecular‐Weight Gelators 353 Jorge F. Toro‐Vazquez, Flor Alvarez‐Mitre, and Miriam Charó‐Alonso 12.1 Introduction 353 12.2 Basic Aspects of LMOGs: From Molecular Architecture to Functional Assemblies 355 12.3 Why Developing Organogels with Vegetable Oils? 356 12.3.1 Vegetable Oils as Solvent in the Development of Organogels with LMOGs 357 12.3.2 Relationship between Molecular Structure of LMOGs and Physical Properties of Organogels 367 12.4 Organogels of Candelilla Wax 373 12.4.1 Rheological Properties of Candelilla Wax Organogels Developed Applying Shear Rate 373 12.4.2 Applications of Candelilla Wax Organogels 377 12.5 Conclusions 377 References 379 13 Formation and Properties of Biopolymer‐Based Oleogels 385 Ashok R. Patel 13.1 Introduction 385 13.2 Formation of Polymer‐Based Oleogels 386 13.2.1 Polymer Oleogelation through Direct Methods 387 13.2.2 Polymer Oleogelation through Indirect Methods 389 13.3 Properties of Polymer‐Based Oleogels 393 13.3.1 Mechanical Properties 393 13.3.2 Temperature Sensitivity 394 13.3.3 Stability in Presence of Water 397 13.4 Potential Applications of Polymer‐Based Oleogels 397 13.4.1 Replacement of Beef Fat in Frankfurters 397 13.4.2 Heat‐Resistant Chocolates 397 13.4.3 Polymer Oleogels as Alternative to Full‐Fat Shortenings 397 13.4.4 Bakery Applications of Ethyl Cellulose Oleogels 398 13.5 Conclusions: Opportunities and Challenges 398 Acknowledgments 401 References 402 14 Lipid Crystallization in Water‐in‐Oil Emulsions 405 Nicole L. Green and Dérick Rousseau 14.1 Introduction 405 14.2 Basics of Emulsion Properties 406 14.3 Emulsifier Effects on W/O Emulsions 408 14.3.1 Mono‐ and Diacylglycerols (E471) 409 14.3.2 Sucrose Fatty‐Acid Esters (E473) 411 14.3.3 Lecithins (E322) 412 14.3.4 Sorbitan Esters and Polyesters (E491‐E496) 413 14.3.5 Polyglycerol Esters (E475 – E476) 415 14.4 Stabilization Modes of W/O Emulsions 415 14.4.1 Pickering Stabilization 416 14.4.2 Network Stabilization 420 14.4.3 Combined Pickering and Network Stabilization 421 14.5 Conclusions 423 References 424 15 Crystallization of Lipids in Oil‐in‐Water Emulsion States 431 John N. Coupland 15.1 The Basic Concepts 431 15.2 Surface Nucleation 432 15.3 Polymorphic Transitions in Droplets 436 15.4 Morphology of Crystalline Droplets 437 15.5 Colloidal Stability of Crystalline Droplets 439 15.6 Conclusions 442 References 443 16 Lipid Crystals and Microstructures in Animal Meat Tissues 447 Michiyo Motoyama, Genya Watanabe, and Keisuke Sasaki 16.1 Introduction 447 16.2 Depot Fat and Crystalline State 448 16.2.1 Adipose Tissue 448 16.2.2 Triacylglycerol (TAG) Compositions of Animal Fats 449 16.3 Fat Crystals and Quality of Porcine Adipose Tissue 450 16.3.1 Polymorphism of Extracted Porcine Fat Crystals 450 16.3.2 Fat Crystals and Macroscopic Meat Quality 454 16.3.3 Application to Actual Meat and Meat Products 455 16.4 Crystal Microstructures in Adipose Tissues 460 16.5 Concluding Remarks 462 Acknowledgments 462 References 462 17 Conventional and New Techniques to Monitor Lipid Crystallization 465 Annelien Rigolle, Koen Van Den Abeele, and Imogen Foubert 17.1 Introduction: What Would Be a Perfect Technique? 465 17.2 Conventional Techniques (and Advances Made) 466 17.2.1 Pulsed Nuclear Magnetic Resonance 466 17.2.2 Differential Scanning Calorimetry 469 17.2.3 X‐Ray Diffraction 472 17.2.4 Rheology 474 17.2.5 Microscopy 476 17.3 “New” Techniques with Potential for Online Monitoring 478 17.3.1 Ultrasonic Techniques 478 17.3.2 Laser Backscattering 484 17.3.3 Near‐Infrared and Raman Spectroscopy 485 17.4 Conclusions 485 Acknowledgments 486 References 487 Index 493

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Book SynopsisPhysiologically Based Pharmacokinetic (PBPK) Modeling and Simulations The first book dedicated to the emerging field of physiologically based pharmacokinetic modeling (PBPK) Now in its second edition, Physiologically Based Pharmacokinetic (PBPK) Modelling and Simulations: Principles, Methods, and Applications in the Pharma Industry remains the premier reference book throughout the rapidly growing PBPK user community. Using clear and concise language, author Sheila Annie Peters connects theory with practice as she explores the vast potential of PBPK modeling for improving drug discovery and development. This fully updated new edition covers key developments in the field of PBPK modelling and simulations that have emerged in recent years. A brand-new section provides case studies in different application areas of PBPK modelling, including drug-drug interaction, genetic polymorphism, renal impairment, and pediatric extrapolation. Additional chapters address Table of ContentsPreface xix Acknowledgements xxi About the companion xxiii Section I. Principles, Methods, andBackground Information 1 1 A Review of Pharmacokinetic and Pharmacodynamic Principles 3 1.1 Introduction 4 1.2 Pharmacokinetic Principles 4 1.2.1 Routes of Drug Administration 4 1.2.2 Intravenous Bolus 4 1.2.3 Plasma Protein Binding and Blood–Plasma Ratio 9 1.2.4 Hepatic, Renal, and Biliary Clearances 12 1.2.5 Extravascular (Subcutaneous, Intramuscular, and Per Oral) Absorption 16 1.2.6 Absorption from Solid Dosage Forms 20 1.2.7 Role of Transporters in ADME 22 1.2.8 Linear and Non-Linear Pharmacokinetics 24 1.2.9 Intravenous Infusion, Repeated Dosing, Steady State Kinetics, and Accumulation 25 1.2.10 Active Metabolite and Prodrug Kinetics 28 1.3 Pharmacokinetic Variability 32 1.4 Pharmacokinetics Optimization in Drug Discovery 34 1.5 Pharmacodynamic Principles 34 1.5.1 Pharmacological Targets and Drug Action 35 1.5.2 Functional Adaptation Processes 39 1.5.3 Biomarkers, Surrogate Endpoints, and Clinical Endpoints 41 Keywords 47 References 48 2 A Review of Drug–Drug Interactions 51 2.1 Introduction 51 2.2 Drug Interactions Mediated by Enzymes and Transporters at Various Sites 54 2.3 Factors Affecting DDI 54 2.4 In Vitro Methods to Evaluate Drug–Drug Interactions 56 2.4.1 Candidate Drug as a Potential Perpetrator 57 2.4.2 Candidate Drug as a Potential Victim of Inhibition 58 2.5 Sources of Uncertainty 59 2.6 Therapeutic Protein–Drug Interaction 59 References 61 3 Modeling Pharmacokinetics, Pharmacodynamics, And Drug Interactions 65 3.1 Introduction 66 3.2 Modeling Pharmacokinetics 66 3.2.1 Compartmental Modeling of Linear and Nonlinear Pharmacokinetics (Enzyme and/or Transporter Capacity Limitation as Well as Target-Mediated Drug Disposition) 67 3.2.2 Population Pharmacokinetics 76 3.3 Pharmacokinetics/Pharmacodynamics and PK/Efficacy (Exposure/ Response) Modeling 80 3.3.1 PK/PD Models for Direct Effect: Sigmoid Emax Model 84 3.3.2 PK/PD Models for Direct Effect: Classical Receptor Theory 86 3.3.3 PK/PD Models Accommodating Delayed Pharmacological Response 89 3.3.4 PK/PD Models Accommodating Functional Adaptation Leading to Nonlinearity in Pharmacological Response with Respect to Time 96 3.3.5 PK/Efficacy Modeling 97 3.3.6 Translation of PK/PD and PK/Efficacy Modeling to Human 100 3.3.7 Average, Minimum, and Maximum Steady-State Concentrations 104 3.3.8 Estimation of Biologically Effective Dose in Human 107 3.3.9 Therapeutic Window 109 3.3.10 Static Models for Drug Interactions 109 3.4 Physiologically Based Pharmacokinetic (PBPK) Modeling and Its Integration with Pharmacodynamics and Efficacy Models 112 3.4.1 PK Modeling Compartmental vs PBPK 112 3.4.2 PK Variability: Population PK (popPK) Modeling vs PBPK 114 3.4.3 Integration of PBPK with PD, Quantitative Systems Pharmacology (QSP) Models or Quantitative Systems Toxicologyand Safety (QSTS) 114 3.4.4 PBPK Models to Evaluate Drug–Drug Interactions 115 3.4.5 DDI Risk Assessment with PBPK vs Static Models 118 Keywords 123 References 125 4 Physiological Model For Absorption 129 4.1 Introduction 130 4.2 Drug Absorption and Gut Bioavailability 130 4.2.1 Solubility and Dissolution Rate 130 4.2.2 Permeability: Transcellular, Paracellular, and Carrier-Mediated Pathways 136 4.2.3 Barriers to Membrane Transport – Luminal Degradation, Efflux, and Gut Metabolism 138 4.3 Factors Affecting Drug Absorption and Gut Bioavailability 140 4.3.1 Physiological Factors Affecting Oral Drug Absorption and Species Differences in Physiology 140 4.3.2 Compound-Dependent Factors 144 4.3.3 Formulation-Dependent Factors 144 4.4 In Silico Predictions of Passive Permeability and Solubility 147 4.4.1 In Silico Models for Permeability 147 4.4.2 In Silico Models for Solubility 147 4.5 Measurement of Permeability, Solubility, Luminal Stability, Efflux, Intestinal Metabolism 148 4.5.1 In Vitro, In Situ, and In Vivo Models for Effective Permeability 148 4.5.2 Measurement of Thermodynamic or Equilibrium Solubility 153 4.5.3 Luminal Stability 154 4.5.4 Efflux 154 4.5.5 In Vitro Models for Gut Metabolism and Estimation of Fraction Escaping Gut Metabolism 155 4.6 Absorption Modeling 156 Keywords 162 References 163 5 Physiological Model For Distribution 169 5.1 Introduction 170 5.2 Factors Affecting Tissue Distribution of Xenobiotics 170 5.2.1 Physiological Factors and Species Differences in Physiology 171 5.2.2 Compound-Dependent Factors 176 5.3 In Silico Models of Tissue Partition Coefficients 176 5.4 Measurement of Parameters Representing the Rate and Extent of Tissue Distribution 181 5.4.1 Assessment of Rate and Extent of Brain Penetration 181 5.5 Physiological Model for Drug Distribution 186 5.6 Drug Concentrations at the Site of Action 187 Keywords 189 References 189 6 Physiological Models For Drug Metabolism And Excretion 193 6.1 Introduction 193 6.2 Factors Affecting Drug Metabolism and Excretion of Xenobiotics 194 6.3 Models for Hepatobiliary and Renal Excretion 197 6.3.1 In Silico Models 197 6.3.2 In Vitro Models for Hepatic Metabolism 197 6.3.3 In Vitro Models for Transporters 200 6.4 Physiological Models 203 6.4.1 Hepato-Biliary Elimination of Parent Drug and Metabolites 205 6.4.2 Renal Excretion 208 References 211 7 Generic Whole-Body Physiologically Based Pharmacokinetic Modeling 217 7.1 Introduction 217 7.2 Structure of a Generic Physiologically-Based Pharmacokinetic (PBPK) Model 218 7.3 Somatic Compartments 220 7.3.1 Lungs (LU) 220 7.3.2 Arterial Blood (ART) 220 7.3.3 Venous Blood (VEN) 220 7.3.4 Stomach (ST) 220 7.3.5 Gut (GU) 220 7.4 Model Assumptions 221 7.5 PBPK Software 221 References 223 8 Pbpk Modeling Of Biotherapeutics 225 8.1 Introduction 226 8.2 Therapeutic Proteins 226 8.2.1 Peptides and Proteins 226 8.2.2 Antibodies and Antibody-Based Therapies 227 8.3 Pharmacokinetics of Therapeutic Proteins 234 8.3.1 Absorption 234 8.3.2 Renal Elimination 235 8.3.3 Immunogenicity 235 8.3.4 PEGylation 239 8.3.5 Transport by Convective and Transcytotic Extravasation 239 8.3.6 Catabolic Elimination (Proteolysis) 239 8.3.7 FcRn-Mediated Protection of IgGs Against Catabolism in FcRn-Rich Cells 241 8.3.8 Distribution and lymphatic elimination 242 8.3.9 Target-Mediated Drug Disposition and Receptor-Mediated Endocytosis 243 8.4 PBPK Modeling of Monoclonal Antibodies 244 8.4.1 Full PBPK Model for Monoclonal Antibodies 244 8.4.2 Minimal PBPK Model for Monoclonal Antibodies 253 8.5 Applications of PBPK Modeling of Monoclonal Antibodies 253 8.5.1 Pharmacokinetic Scaling 253 8.5.2 PBPK Integration with Pharmacodynamics of Monoclonal Antibodies 255 Keywords 156 References 258 9 Uncertainty And Population Variability 263 9.1 Introduction 264 9.2 Distinguishing Uncertainty and Variability 264 9.3 Sources of Uncertainty in Drug-related Parameters 264 9.4 Sources of Variability in System Parameters 266 9.5 Handling Population Variability 269 9.5.1 A POSTERIORI and A PRIORI Approaches to Handling Population Variability 269 9.5.2 Correlations Between Parameters 271 9.6 Uncertainty and Sensitivity Analysis 272 9.6.1 Local Sensitivity Analysis (One-at-a-time (OAT) and Derivative-based Methods) 272 9.6.2 Parameter Interactions and Global Sensitivity Analysis (GSA) 275 9.6.3 Global Sensitivity Analysis for Correlated Parameters (cGSA) 278 9.6.4 Applications of Sensitivity Analysis for PBPK Models 280 9.6.5 Limitations of Global Sensitivity Analysis 281 9.7 Uncertainty and Population Variability in Clinical Efficacy and Safety 282 Keywords 285 References 285 10 Nonclinical, Clinical, and Model-Informed Drug Development 293 10.1 Introduction: An Overview of Different Phases of Drug Development 294 10.2 Nonclinical Development 295 10.2.1 Preclinical Pharmacology, PK/PD Modeling, and Human Dose Prediction 297 10.2.2 Safety and Toxicology Studies 297 10.2.3 Studies with Radiolabeled Compound 298 10.3 Clinical Pharmacology Studies 302 10.3.1 First-in-Human, Single, and Multiple Ascending Dose Studies 302 10.3.2 Biopharmaceutics – Absolute Oral Bioavailability and Bioequivalence Study 304 10.3.3 Food Effect Study 304 10.3.4 Organ (Hepatic and Renal) Impairment Study 305 10.3.5 Pediatric Assessment 306 10.3.6 Mass Balance Study 307 10.3.7 Drug Interaction Study 307 10.3.8 Pharmacogenomics Study 308 10.3.9 Thorough QT (TQT) and Concentration QT (C-QT) Study 308 10.3.10 Immunogenicity Assays and Comparability Study for Biologics 309 10.3.11 Drug Labelling 309 10.4 Clinical Development in Oncology 310 10.5 Fast Track Routes to Address Unmet Medical Need in the Treatment of Serious Conditions 311 10.6 Model-Informed Drug Development 312 10.7 Physiologically Based Pharmacokinetic Models Complementing Clinical Pharmacology Studies 314 10.8 PBPK in Oncology 315 Regulatory Guidelines 316 References 319 Section II. Applications In The Pharmaceutical Industry 323 11 Overview Of Pbpk Applications 325 11.1 Introduction 325 11.2 PBPK Applications for Internal Decisions 326 11.3 PBPK Applications for Regulatory Filing 328 11.4 PBPK Modeling and Simulations Along the Value Chain 332 References 335 12 Applications Of Hypothesis Generation And Testing With Pbpk Models 337 12.1 Introduction 338 12.2 Hypothesis Generation and Testing with PBPK Models 338 12.2.1 Parameter Estimation from Intravenous Pharmacokinetic Profiles 338 12.2.2 Simulation of Oral PK Profile 341 12.2.3 Sensitivity Analysis 342 12.2.4 Verification of Hypotheses 346 12.2.5 Auto-inhibition of Drug-Metabolizing Enzymes, Uptake and Efflux Transporters 347 12.3 Hypothesis Generation and Testing Along the Value Chain 348 12.4 Conclusions 351 References 351 13 Applications of Physiologically Based Pharmacokinetic Models Integrated With Drug Effect Models (Pbpk/Pd) 353 13.1 Introduction: Integration of PBPK with Drug Effect Models 354 13.2 Dosing in Specific Populations 355 13.3 PBPK/PD for Bottom-Up Prediction of Inter-Patient Variability in Drug Response 357 13.4 PBPK/PD for Predicting the Inter-Patient Variability in Response to Prodrugs and Active Metabolites 358 13.5 PBPK/PD When Systemic Concentrations are not the Driver forDrug Response 359 13.5.1 Pre-Systemic Drug Target 359 13.5.2 Effect-Site Drug Concentration Different from Systemic Concentration 360 13.6 PBPK/PD for Monoclonal Antibodies 362 13.7 PBPK Models Linked to Quantitative Systems Pharmacology and Toxicology Models 363 13.7.1 PBPK–QST Models to Predict Drug-Induced Liver Injury 363 13.7.2 PBPK–QST Models to Predict Drug-Induced Cardiotoxicity 367 13.8 Conclusions 371 References 371 14 Pbpk Modeling and Simulations to Evaluate Clinical Drug-Drug Interactions 375 14.1 Introduction 376 14.2 Clinical DDI Studies and Modeling Approaches to Address Key Questions Related to Drug–Drug Interactions 376 14.2.1 Dedicated Clinical DDI Studies 378 14.2.2 Investigation of Phenotypic Effects for NMEs Predominantly Cleared by Polymorphic Enzyme or Transporter 379 14.2.3 Prospective Nested DDI Study 380 14.2.4 Cocktail DDI Study 381 14.2.5 PBPK Modeling and Simulations 381 14.2.6 Claims Relating to Results of DDI Studies 381 14.2.7 Impact on Label 382 14.3 PBPK Modeling of Different Types of Drug Interactions 382 14.3.1 PBPK Modeling Strategy: New Molecular Entity as Victim of CYP-Based Drug Interactions 382 14.3.2 PBPK Modeling Strategy: New Molecular Entity as Perpetrator of CYP-Based Drug Interactions 383 14.3.3 Non-CYP Based Drug Interactions 384 14.3.4 Transporter-Mediated Drug Interactions 385 14.4 DDI Predictions with PBPK Modeling and Simulations in Clinical Drug Development and Regulatory Submissions 387 14.4.1 DDI Predictions Along the Value Chain (Figure 14.5) 387 14.4.2 Possible Regulatory Outcomes, Based on the Predictions from a Verified and Validated PBPK Model 389 14.4.3 Regulatory Acceptance of PBPK Analyses Included in Regulatory Submissions 390 14.4.4 Predictive Performance of PBPK Models 391 14.5 Comparison of DDI Prediction Using Static and Dynamic Models 392 14.6 Conclusions 393 References 394 15 Dose Extrapolation Across Populations (Healthy Adult Caucasian To Pediatric, Pregnant Women, Different Ethnicities, Geriatric, Smokers And Obese Populations) 397 15.1 Introduction 398 15.2 PBPK Modeling Strategy for Dose Extrapolation to Specific Populations 398 15.3 Potential Benefits of PBPK Modeling for Dose Extrapolations to Specific Populations 399 15.4 Dose Extrapolations to Specific populations 404 15.4.1 Pediatric Starting Dose Selection 404 15.4.2 Pregnancy 406 15.4.3 Ethnicity – Japanese Population 407 15.4.4 Geriatric Population 408 15.4.5 Obese 409 15.4.6 Smokers 410 15.5 Conclusions 410 References 411 16 Dose Extrapolation Across Populations: Healthy Adult To Hepatic And Renal Impairment Populations 417 16.1 Introduction 418 16.2 Pathophysiological Changes in Organ Impairment 419 16.2.1 Hepatic Impairment 419 16.2.2 Renal Impairment 420 16.3 PBPK Modeling Strategy: Model Development, Verification, Validation, and Application 420 16.4 Benefits of Applying Validated PBPK Models to Organ-Impaired Populations 421 16.4.1 Enhancing Regulatory Confidence in the Application of PBPK Modeling for the Prediction of Exposure in the Organ-Impaired Population 421 16.4.2 Contribution of PBPK to the Totality of Evidence in Evaluating the Effect of Renal Impairment on Drug Exposure to Inform Labelling 424 16.5 Conclusions 425 References 426 17 Absorption-Related Applications Of Pbpk Modeling 429 17.1 Introduction 429 17.2 In Vitro – In Vivo Disconnect, Parameter Non-Identifiability and the Importance of Identifying Factors Limiting Absorption Through a Deconvolution of the Mechanisms Contributing to Gut Bioavailability 431 17.3 Non-Regulatory Internal Applications of PBPK Modeling and Simulations 433 17.3.1 Prediction of Fraction Absorbed 433 17.3.2 Oral Formulation Development 433 17.4 Regulatory Applications of PBPK Modeling and Simulations 438 17.4.1 Food–Drug Interactions 438 17.4.2 Interactions of a Poorly Soluble Weak Base with Acid Reducing Agents (ARAs) 444 17.4.3 In Vitro – In Vivo Correlations (IVIVCs) to Serve as Surrogate for Bioequivalence Testing (Case Study 12) 445 17.4.4 Biowaivers Based on Virtual Bioequivalence 449 17.4.5 Virtual Bioequivalence of Locally Acting Products (LAPs) 450 17.5 Conclusions 450 References 452 18 Regulatory Guidelines On The Reporting Of Physiologically Based Pharmacokinetic (Pbpk) Modeling Analysis 457 18.1 Introduction 457 18.2 Food and Drug Administration (FDA) Guidelines 458 18.3 European Medicines Agency (EMA) Guidelines 459 18.4 Comparison of FDA and EMA Guidelines 461 18.5 Risk-Informed Evidentiary Framework to Assess PBPK Model Credibility 463 18.6 Drug Model Verification of Locally Acting Products (LAPs) 464 References 466 19 Resolving The Challenges To Establishing Confidence In Pbpk Models 469 19.1 Introduction 470 19.2 Requirements for Developing Mechanistically Credible PBPK Models for the Three Broad Categories of Applications 470 19.3 Challenges to Developing Mechanistically Credible PBPK Models and Consequences 473 19.3.1 Model Building 473 19.3.2 Model Verification of Predicted Exposure and Validation of Predictive Performance 476 19.4 Resolving the Challenges to Developing Mechanistically Credible PBPK Models 476 19.5 Totality of Evidence 478 19.6 Conclusions 480 References 481 20 Epilogue 483 20.1 PBPK Modeling Successes 483 20.2 Challenges 484 20.2.1 Drug Model Parameterization 484 20.2.2 Knowledge Gaps in Physiological Parameters 485 20.2.3 Prospective Validation of Prediction Performance 485 20.3 Meeting the Challenges 485 20.4 Future Directions for PBPK Modeling 486 References 488 Section III. Case Studies Of Pbpk Applications In The Pharmaceutical Industry 491 Case Study 1 Hypothesis Testing (Solubility) 493 Case Study 2 Hypothesis Testing (Gastric Emptying) 499 Case Study 3 Hypothesis Testing (Intestinal Loss) 505 Case Study 4 Pbpk/Pd 509 Case Study 5 Drug–Drug Interaction (Inhibition) 515 Case Study 6 Drug–Drug Interaction (Induction) 521 Case Study 7 Genetic Polymorphism 527 Case Study 8 Pediatric Extrapolation 535 Case Study 9 Pregnancy 541 Case Study 10 Hepatic Impairment 547 Case Study 11 Renal Impairment 555 Case Study 12 Absorption – Ivivc 561 Appendices 567 Index 579

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Book SynopsisBioanalytical Aspects in Biological Therapeutics Deepen your understanding of how critical data are generated from bioanalysis In Bioanalytical Aspects in Biological Therapeutics, a team of renowned chemists, immunologists, and biologists delivers a timely and practical exploration of the diverse scientific and technical literature on the bioanalytical investigation of current biotherapeutics under development. The book discusses the challenges and considerations for bioanalytical support, covering a wide range of central topics in the field, including overview and basic immunology for testing of biological therapeutics, pharmacokinetic aspects, clinical immunogenicity prediction and testing, biomarker testing, biotransformation assessment for biologics, statistical aspects of bioanalytical testing, regulatory expectations, and more. Drug development and analysis professionals will learn how critical data are generated from bioanalysis and how proven tools and methods are applied to thTable of ContentsPreface viiXiaohui Xu and Weifeng Xu Foreword ixBinodh DeSilva Acknowledgments xiii About the Editors xv List of Contributors xvii 1 Overview of the Development of Biotherapeutics and the Role of Bioanalytical Sciences 1Robert Dodge 2 Basic Immunology for Bioanalytical Testing of Biotherapeutics 23Kang Chen and Weifeng Xu 3 Platform and Instrument Considerations in Bioanalytical Testing 51Dominic Warrino and Franklin Spriggs 4 Pharmacokinetic Assays 67Tong-Yuan Yang and Eric Wakshull 5 Recent Progress in Biomarker Bioanalysis and Target Engagement Assessment 87Yan G. Ni, Lindsay E. King and Carmen Fernández-Metzler 6 Immunogenicity Risk Assessment for Biotherapeutics 141Jochem Gokemeijer 7 Bioanalytical Strategy to Support Clinical Immunogenicity Assessment: Anti-drug Antibodies 159Ying Wang and Michael Luong 8 Bioanalytical Scheme for Antidrug Neutralizing Antibody Assays 185Weifeng Xu, Bonnie Wu and Jim McNally 9 Critical Reagents in Bioanalysis 209Yang Xu, Agostinho Gomes Rocha, Shannon Chilewski, Krisna C. Duong-Ly, Kun Yang and Jonathan Haulenbeek 10 Statistical Aspects of Bioanalytical Testing 239Arkady M. Gershteyn and Mark Ma 11 Bioanalytical Aspects in Biological Therapeutics: Biotransformation 277Wenying Jian, Cong Wei and Jinping Gan 12 New Modalities: Multidomain Therapeutics and Gene Therapy Programs 309Kelly Colletti and Mark Ma 13 Regulatory Aspects for Assay Development, Validation, and Sample Analysis 327Amy Lavelle and Megan Wiberg Index 355

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Book SynopsisMarket access is the fourth hurdle in the drug development process and the primary driver for global income of any new drug. Without a strategy in place for pricing, showing value for effectiveness and an understanding of the target purchasers' needs, the drug will fail to reach its intended market value. Introduction to Market Access for Pharmaceuticals is based on an accredited course in this area, taken from the European Market Access University Diploma (EMAUD), and is affiliated with Aix Marseille University.Key Features:The first guide to market access for pharmaceuticals based on tested teaching materialsAddresses both pharmaceutical and vaccine productsIncludes case studies and scenariosCovers market access consdierations for Western Europe, the USA, Japan and ChinaExplains the impact the changing healthcare market will have on your productTable of ContentsChapter 1: Health as a GoodChapter 2: Decision-Making in Public HealthChapter 3: Definition and ConceptsChapter 4: HTA Decision Analysis frameworkChapter 5: Early HTA AdviceChapter 6: Overview of Market Access AgreementsChapter 7: External Reference PricingChapter 8: Gap between Payers and RegulatorsChapter 9: Early Access ProgramsChapter 10: Market Access of Orphan DrugsChapter 11: Market Access of Vaccines in Developed CountriesChapter 12: FranceChapter 13: GermanyChapter 14: ItalyChapter 15: SpainChapter 16: SwedenChapter 17: United KingdomChapter 18: The United StatesChapter 19: JapanChapter 20: China

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Book SynopsisA Practical Guide to Managing Clinical Trials is a basic, comprehensive guide to conducting clinical trials. Designed for individuals working in research site operations, this user-friendly reference guides the reader through each step of the clinical trial process from site selection, to site set-up, subject recruitment, study visits, and to study close-out. Topics include staff roles/responsibilities/training, budget and contract review and management, subject study visits, data and document management, event reporting, research ethics, audits and inspections, consent processes, IRB, FDA regulations, and good clinical practices. Each chapter concludes with a review of key points and knowledge application.Unique to this book is A View from India, a chapter-by-chapter comparison of clinical trial practices in India versus the U.S. Throughout the book and in Chapter 10, readers will glimpse some of the challenges and opportunities in the emerging and Trade Review'"A Practical Guide to Managing Clinical Trials" provides a good introduction to the basics of clinical research for investigators, study coordinators, and other site personnel. The clear writing makes the book a quick read.' – Norman M. Goldfarb for Journal of Clinical Research Best Practices, Vol. 13, No. 12, December 2017.'"A Practical Guide to Managing Clinical Trials" provides a good introduction to the basics of clinical research for investigators, study coordinators, and other site personnel. The clear writing makes the book a quick read.' – Norman M. Goldfarb for Journal of Clinical Research Best Practices, Vol. 13, No. 12, December 2017.Table of ContentsChapter 1: Rules, Roles and ResponsibilitiesChapter 2: Products, Protocols, and Pre-trial PreparationChapter 3: Sponsor, Site and Study Start-upChapter 4: Enticement, Enrollment, and Engagement: The Informed Consent ProcessChapter 5: From Enrollment to Final VisitChapter 6: Collaborating for Compliance and Quality Data – Monitoring and AuditsChapter 7: Building BudgetsChapter 8: Contracts, Clauses and Closing the DealChapter 9: US Clinical Trials – Additional TopicsChapter 10: Clinical Research and India

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Book SynopsisOligonucleotides represent one of the most significant pharmaceutical breakthroughs in recent years, showing great promise as diagnostic and therapeutic agents for malignant tumors, cardiovascular disease, diabetes, viral infections, and many other degenerative disorders. The Handbook of Analysis of Oligonucleotides and Related Products is an essential reference manual on the practical application of modern and emerging analytical techniques for the analysis of this unique class of compounds. A strong collaboration among thirty leading analytical scientists from around the world, the book provides readers with a comprehensive overview of the most commonly used analytical techniques and their advantages and limitations in assuring the identity, purity, quality, and strength of an oligonucleotide intended for therapeutic use.Topics discussed include: Strategies for enzymatic or chemical degradation of chemically modified oligonucleotides toTrade ReviewThis is a unique resource for guiding the analysis of oligonucleotide-based drug products. No other single source provides such a comprehensive overview of the necessary analytical techniques that assess the qualitative characteristics of oligonucleotides intended for pharmaceutical use.—Rachel R Chennault, Ph.D.(American College of Clinical Pharmacy), in Doody's Notes Table of ContentsPurity Analysis and Impurities Determination by Reversed-Phase High- Performance Liquid Chromatography. Purity Analysis and Impurities Determination by AEX-HPLC. Purity Analysis and Molecular Weight Determination by Size Exclusion HPLC Analysis. Analysis of Oligonucleotides by Liquid Chromatography—Mass Spectrometry. Sequence Determination and Confirmation by MS/M S and MALDI-TOF. Tm Analysis of Oligonucleotides. Purity and Content Analysis of Oligonucleotides by Capillary Gel Electrophoresis. Bioanalysis of Therapeutic Oligonucleotides Using Hybridization-Based Immunoassay Techniques. Oligonucleotide Assay and Potency. Microbial Analysis: Endotoxin Testing. Analysis of Residual Solvents by Head Space Gas Chromatography. Determination of Extinction Coefficient. Structural Determination by NMR. Infrared Analysis of Oligonucleotides. Stability Indicating Methods for Oligonucleotide Products. Analysis by Hydrophilic Interaction Chromatography. Determination of Base Composition. Analysis of Metals in Oligonucleotides. Regulatory Considerations for the Development of Oligonucleotide Therapeutics.

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Book SynopsisUsing 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 Trade Review… One of the strengths of the book is the collection, discussion and illustration of the many diverse time-to-event problems that may occur in practice. … this publication provides a comprehensive overview of classical and emerging ideas in the analysis of time-to-event problems. Written by experts in their area, the book has a wealth of references in each topic should the reader wish to learn about or extend their understanding of individual concepts or analysis methods. It is a worthwhile book to have in the library for anyone working in designing, conducting, analysing or interpreting studies with time-to-event outcomes.—Australian & New Zealand Journal of Statistics, 2011Table of ContentsOverview of Time-to-Event Endpoint Methodology. Design (and Monitoring) of Clinical Trials with Time-to-Event Endpoints. Overview of Time-to-Event Parametric Methods. Overview of Semiparametric Inferential Methods for Time-to-Event Endpoints. Overview of Inferential Methods for Categorical Time-to-Event Data. Overview of Bayesian Inferential Methods Including Time-to-Event Endpoints. An Efficient Alternative to the Cox Model for Small Time-to-Event Trials. Estimation and Testing for Change in Hazard for Time-to-Event Endpoints. Overview of Descriptive and Graphical Methods for Time-to-Event Data. Design and Analysis of Analgesic Trials. Design and Analysis of Analgesic Trials with Paired Time-to-Event Endpoints. Time-to-Event Endpoint Methods in Antibiotic Trials. Design and Analysis of Cardiovascular Prevention Trials. Design and Analysis of Antiviral Trials. Cure Rate Models with Applications to Melanoma and Prostate Cancer Data. Parametric Likelihoods for Multiple Nonfatal Competing Risks and Death, with Application to Cancer Data. Design, Summarization, Analysis, and Interpretation of Cancer Prevention Trials. LASSO Method in Variable Selection for Right-Censored Time-to-Event Data with Application to Astrocytoma Brain Tumor and Chronic Myelogenous Leukemia. Selecting Optimal Treatments Based on Predictive Factors. Application of Time-to-Event Methods in the Assessment of Safety in Clinical Trials. Design and Analysis of Chronic Carcinogenicity Studies of Pharmaceuticals in Rodents. Design and Analysis of Time-to-Tumor Response in Animal Studies: A Bayesian Perspective. Index.

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Book SynopsisThis book covers the essentials of drug delivery research and provides a unique forum for scientific experimental methods that are exclusively focused by the in-vitro, ex-vivo, and in-vivo methodologies of drug delivery research and felicitates translational research. The book includes recent and novel approaches in evaluation methods of transdermal, nasal, ocular, oral and intraoral, gastro-retentive, colon-targeted, and brain-targeted drug delivery systems. Providing up to date and comprehensive information, this text is invaluable to students, teachers, scientists, and others employed in the field of drug delivery. Table of Contents1. In-Vitro and In-Vivo Tools in Emerging Drug Delivery Scenario: Challenges and Updates 2. Intraoral and Peroral Drug Delivery Systems 3. Transdermal Drug Delivery Systems 4. Nasal and Pulmonary Drug Delivery Systems 5. Ocular Drug Delivery Systems 6. Gastroretentive Drug Delivery Systems 7. Colon Targeted Drug Delivery Systems 8. Brain Targeted Drug Delivery Systems 9. Parenteral Drug Delivery Systems Appendix: Characterization Parameter and Common Characterization Tools

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Book SynopsisWhat's the Deal with Biosimilars?Biosimilars are gaining momentum as new protein therapeutic candidates that can help fill a vital need in the healthcare industry. The biological drugs are produced by recombinant DNA technology that allows for large-scale production and an overall reduction time in costs and development. Part of a two-volume set that covers varying aspects of biosimilars, Biosimilars and Interchangeable Biologics: Strategic Elements explores the strategic planning side of biosimilar drugs and targets issues surrounding biosimilars that are linked to legal matters. This includes principal patents and intellectual property, regulatory pathways, and concerns about affordability on a global scale. It addresses the complexity of biosimilar products, and it discusses the utilization of biosimilars and related biological drugs in expanding world markets.Of specific interest to practitioners, researchers, and scientists Table of ContentsIntroduction to Biosimilar and Interchangeable Products. Intellectual Property Issues for Biosimilars. European Regulatory Guidance. EMA-Approved Biosimilars. FDA Regulatory Guidance. ROW Regulatory Guidance. US Commercialization. Global Commercialization. Quality and Lifecycle Management.

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Book SynopsisCompletely revised text that reflects to emergent trends and cutting-edge advances in pharmaceutical biotechnology, this Third Edition provides a well-balanced framework for understanding every major aspect of pharmaceutical biotechnology, including drug development, production, dosage forms, administration, and therapeutic developments. New chapters cover evolving areas regarding biopharmaceuticals, including oligonucleotides, siRNA and various monoclonal antibodies, immunogenicity, gene therapy, and the regulatory issues factoring into the biopharmaceutical approval processTable of ContentsMolecular Biotechnology. Biophysical and Biochemical Analysis of Recombinant Protein Structure and Analysis of Proteins. Production and Downstream Processing of Biotech Products. Formulation of Biotech Products, Including Biopharmaceutical Considerations. Pharmacokinetics and Pharmacodynamics of Peptide and Protein Drugs. Immunogenicity. Genomics, Proteomics and Additional Biotechnology-related Techniques. Gene Therapy. Oligonucleotides and siRNA. Hematopoetic Growth Factors. Interferons and Interleukins. Insulins. Growth Hormones. Recombinant Thrombolytics and Coagulation Factors. General Considerations of Monoclonal Antibodies. Monoclonal Antibodies in Oncology. Monoclonal Antibodies in Transplantation. Monoclonal Antibodies in Anti-inflammatory Therapy. Recombinant Human Deoxyribonuclease. Follicle-stimulating Hormone. Vaccines. Dispensing Biotechnology Products. Economic Considerations in Medical Biotechnology. Regulatory Issues and Drug Product Approval for Biopharmaceuticals

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Book SynopsisNovel drug delivery technologies strive to bypass challenging biological layers to elicit desired pharmacological activity. The skin, one of our key defensive barriers, allows certain topically applied substances and toxins to pass. The dermatokinetics of a drug determines the efficacy of treatment of skin disorders.Presenting the first comprehensive reference on this important area of research, Dermatokinetics of Therapeutic Agents includes a general overview of the theoretical as well as practical aspects of dermatokinetics and addresses the impact of a drug delivery system on the dermatokinetics of drugs. Chapters and illustrations cover introductory aspects and the significance, methods, and models used in dermatokinetic studies of therapeutic agents.Topics include: Theoretical Models for Dermatokinetics of Therapeutic Agents Drug Delivery Approaches to Modulate Dermatokinetics of DrugsTable of ContentsIntroduction to Dermatokinetics. Theoretical Models for Dermatokinetics of Therapeutic Agents. Drug Delivery Approaches to Modulate Dermatokinetics of Drugs. Conventional Methods of Cutaneous Drug Sampling. Cutaneous Microdialysis. Sampling Substrates by Skin Permeablization. Spectroscopic Techniques in Dermatokinetics Studies. Dermatokinetics of Gene Therapeutics. Regulatory Perspective of Dermatokinetic Studies.

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Book SynopsisThe nutritional and medicinal value of metals, such as zinc, calcium, and iron, has been known in traditional medicine for a long time. Other metals, such as silver and gold, may also have therapeutic and health benefits. Ancient medicines have long incorporated their use in the treatment of diseases, and they have also more recently been explored for treatment in allopathic medicine, birthing the concept of metallonutraceuticals. The challenge of using metals in the human body is to find forms that are safe and effective.Handbook of Metallonutraceuticals presents basic concepts related to the nutritional and therapeutic use of metals, product development strategies, and some ideas ready to be applied for condition-specific metallonutraceuticals. The book begins with an overview of the nutraceuticals field and the need for metallonutraceuticals. It considers the roles of various metals in metabolism, reviews the ethnopharmacology and ethnomedicine of metals, and coverTable of ContentsConcept, Definition, and Need for Metallonutraceuticals. Roles of Metals in Metabolism. Ethnopharmacology and Ethnomedicine of Metals. Characterization of Metallonutraceuticals. Characterization Bioavailability and Drug Interactions of Metallonutraceuticals. Therapeutic Applications of Nanometals. Metallonanotherapeutics for Neurodegenerative Diseases. Nanometals and Complexes in Cancer Diagnosis and Therapy. Application of Metals in Traditional Chinese Medicine. Metalloenzymes: Relevance in Biological Systems and Potential Applications. Application of Nanosilver in Nutraceuticals. Regulatory Pathways and Intellectual Property Rights for Metallonutraceuticals. Gold Nanoparticles: A Promising Nanometallic Drug Delivery System with Many Therapeutic Applications. Index.

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Book SynopsisMaintaining a practical perspective, Bioequivalence and Statistics in Clinical Pharmacology, Second Edition explores statistics used in day-to-day clinical pharmacology work. The book is a starting point for those involved in such research and covers the methods needed to design, analyze, and interpret bioequivalence trials; explores when, how, and why these studies are performed as part of drug development; and demonstrates the methods using real world examples. Drawing on knowledge gained directly from working in the pharmaceutical industry, the authors set the stage by describing the general role of statistics. Once the foundation of clinical pharmacology drug development, regulatory applications, and the design and analysis of bioequivalence trials are established, including recent regulatory changes in design and analysis and in particular sample-size adaptation, they move on to related topics in clinical pharmacology involving the use of cross-over Trade Review"The two authors are well-respected statisticians with numerous publications in BE and broad pharmaceutical industry experience. … The book is written in plain language and statistics is presented with minimum mathematical proof, which makes it a great introduction and reference for statisticians and clinical pharmacologists. With case studies and associated SAS and R codes included in the book and website, both statisticians and clinical pharmacologists will find this book helpful in understanding the context to use a method and implementing the ready-to-use codes. Particularly, each chapter begins with an interesting real-life story of the authors working as statisticians in the pharmaceutical industry, which makes the reading delightful. …In summary, Bioequivalence and Statistics in Clinical Pharmacology, Second Edition, provides an update on regulatory recommendations, statistical methods, and applications in clinical pharmacology and BE studies to support drug product development. With its inclusion of SAS and R codes, this book will be a valuable reference for pharmaceutical scientists, statisticians, and regulators working in these areas."—Wangjie Sun and Wenlei Jiang, US Food and Drug Administration, in Journal of the American Statistical Association, January 2018"This book is a second edition of the authors’ take on the concepts and methods in the analysis and design of bioequivalence studies, supported by references to regulation authorities’ guidelines ... The authors are working in the pharmaceutical industry and therefore bring a view from the inside compared to the other reference work in the field by academics … Throughout the book, different examples with data and codes are provided both showing and not showing bioequivalence to facilitate the learning process. … To conclude, this book covers efficiently the statistical methods of bioequivalence testing and their many applications in clinical pharmacology. Furthermore, the dense reference list provides a helpful guide for the reader to go in deeper details on topics of interest."—Julie Bertrand, Faculté de Médecine Bichat, IAME, in Journal of Biopharmaceutical Statistics, May 2017"The first edition of Bioequivalence and Statistics in Clinical Pharmacology was a classic text book for researchers and statisticians in the field of clinical pharmacology and pharmaceutical industry. This new second edition is a timely update with the inclusion of new areas such as adaptive bioequivalence trials, scaled average bioequivalence testing, and vaccine trials. This is one of few books in the literature with the focus on statistical issues in clinical pharmacology and bioequivalence. The topics it covers are critical for understanding the pharmacology of an investigational drug, and are becoming increasingly important in the era of precision medicine. The book is just as well structured as the first edition, in an accessible, thorough, and clear manner. Case studies and associated SAS code included in the book are extremely helpful. In summary, the book is a most welcome addition to the collection of pharmaceutic statisticians and researchers in clinical pharmacology." —Liang Fang, Director of Biostatistics, Gilead Sciences Inc."Bioequivalence and Statistics in Clinical Pharmacology, Second Edition, provides readers with a statistical background of bioequivalence and presents several special topics in clinical pharmacology. This second edition contains updated and extended discussions of these topics and includes new chapters on adaptive bioequivalence studies, scaled average bioequivalence, and vaccine trials. The book’s presentation is comprehensive and clear, and is complimented by numerous illustrations, examples, and computer programs with data analyses. Scientists and practitioners working in industry, regulatory authorities, and academia will find this book useful, interesting, and enjoyable due to the delightful and instructive stories featured in the introductions of each chapter, the various important and relevant topics covered by these chapters, and the informative and practical technical appendices."—Laszlo Endrenyi, Professor Emeritus, University of TorontoPraise for the First Edition:"… the book provides a good introduction to common uses of statistics in early phases of the drug development process by using a good mix of technical detail, intuitive understanding and factual knowledge. … personal accounts together with the numerous real data examples which are accompanied by SAS code for analysis and the opportunity to download the data to gain first-hand experience are the best features of the book. … the authors did a fine job in providing an introduction to statistics in the early stages of the drug development process. The availability of real example data allows the reader to engage himself easily in the topic and the long experience of the authors ensures that many different aspects of pharmacological studies are discussed."—Thomas Jaki, Lancaster University, Journal of the Royal Statistical Society, Series A, 2010"I really enjoyed reading this book. Each chapter includes an excellent introduction based on Scott Patterson's experience working as a biometrician. This will especially be of interest to young statisticians starting their career in the pharmaceutical industry. Therefore, I strongly recommend this book to all pharmaceutical statisticians to learn more of the challenging statistical problems being generated in drug development. In addition, the presented material provides a springboard for all scientists from academia who are looking to do research in this area of medical applications."—Dieter Haushcke, Biometrics, September, 2006"The authors formulate bioequivalence exhaustively and clearly. … Given the background of the authors, they constitute a key piece of social information in understanding the context in which clinical pharmacology research develops within the pharmaceutical industry."—Journal of Biopharmaceutical Statistics"The two authors are well-respected statisticians with numerous publications in BE and broad pharmaceutical industry experience. … The book is written in plain language and statistics is presented with minimum mathematical proof, which makes it a great introduction and reference for statisticians and clinical pharmacologists. With case studies and associated SAS and R codes included in the book and website, both statisticians and clinical pharmacologists will find this book helpful in understanding the context to use a method and implementing the ready-to-use codes. Particularly, each chapter begins with an interesting real-life story of the authors working as statisticians in the pharmaceutical industry, which makes the reading delightful. …In summary, Bioequivalence and Statistics in Clinical Pharmacology, Second Edition, provides an update on regulatory recommendations, statistical methods, and applications in clinical pharmacology and BE studies to support drug product development. With its inclusion of SAS and R codes, this book will be a valuable reference for pharmaceutical scientists, statisticians, and regulators working in these areas."—Wangjie Sun and Wenlei Jiang, US Food and Drug Administration, in Journal of the American Statistical Association, January 2018"This book is a second edition of the authors’ take on the concepts and methods in the analysis and design of bioequivalence studies, supported by references to regulation authorities’ guidelines ... The authors are working in the pharmaceutical industry and therefore bring a view from the inside compared to the other reference work in the field by academics … Throughout the book, different examples with data and codes are provided both showing and not showing bioequivalence to facilitate the learning process. … To conclude, this book covers efficiently the statistical methods of bioequivalence testing and their many applications in clinical pharmacology. Furthermore, the dense reference list provides a helpful guide for the reader to go in deeper details on topics of interest."—Julie Bertrand, Faculté de Médecine Bichat, IAME, in Journal of Biopharmaceutical Statistics, May 2017"The first edition of Bioequivalence and Statistics in Clinical Pharmacology was a classic text book for researchers and statisticians in the field of clinical pharmacology and pharmaceutical industry. This new second edition is a timely update with the inclusion of new areas such as adaptive bioequivalence trials, scaled average bioequivalence testing, and vaccine trials. This is one of few books in the literature with the focus on statistical issues in clinical pharmacology and bioequivalence. The topics it covers are critical for understanding the pharmacology of an investigational drug, and are becoming increasingly important in the era of precision medicine. The book is just as well structured as the first edition, in an accessible, thorough, and clear manner. Case studies and associated SAS code included in the book are extremely helpful. In summary, the book is a most welcome addition to the collection of pharmaceutic statisticians and researchers in clinical pharmacology." —Liang Fang, Director of Biostatistics, Gilead Sciences Inc."Bioequivalence and Statistics in Clinical Pharmacology, Second Edition, provides readers with a statistical background of bioequivalence and presents several special topics in clinical pharmacology. This second edition contains updated and extended discussions of these topics and includes new chapters on adaptive bioequivalence studies, scaled average bioequivalence, and vaccine trials. The book’s presentation is comprehensive and clear, and is complimented by numerous illustrations, examples, and computer programs with data analyses. Scientists and practitioners working in industry, regulatory authorities, and academia will find this book useful, interesting, and enjoyable due to the delightful and instructive stories featured in the introductions of each chapter, the various important and relevant topics covered by these chapters, and the informative and practical technical appendices."—Laszlo Endrenyi, Professor Emeritus, University of TorontoPraise for the First Edition:"… the book provides a good introduction to common uses of statistics in early phases of the drug development process by using a good mix of technical detail, intuitive understanding and factual knowledge. … personal accounts together with the numerous real data examples which are accompanied by SAS code for analysis and the opportunity to download the data to gain first-hand experience are the best features of the book. … the authors did a fine job in providing an introduction to statistics in the early stages of the drug development process. The availability of real example data allows the reader to engage himself easily in the topic and the long experience of the authors ensures that many different aspects of pharmacological studies are discussed."—Thomas Jaki, Lancaster University, Journal of the Royal Statistical Society, Series A, 2010"I really enjoyed reading this book. Each chapter includes an excellent introduction based on Scott Patterson's experience working as a biometrician. This will especially be of interest to young statisticians starting their career in the pharmaceutical industry. Therefore, I strongly recommend this book to all pharmaceutical statisticians to learn more of the challenging statistical problems being generated in drug development. In addition, the presented material provides a springboard for all scientists from academia who are looking to do research in this area of medical applications."—Dieter Haushcke, Biometrics, September, 2006"The authors formulate bioequivalence exhaustively and clearly. … Given the background of the authors, they constitute a key piece of social information in understanding the context in which clinical pharmacology research develops within the pharmaceutical industry."—Journal of Biopharmaceutical StatisticsTable of ContentsBioequivalence & Biopharmaceutical DevelopmentDrug Development and Clinical PharmacologyAims of This BookBiopharmaceutical DevelopmentClinical PharmacologyStatistics in Clinical PharmacologyStructure of the BookHistory and Regulation of BioequivalenceWhen and How BE Studies Are PerformedWhy Are BE Studies Performed?Deciding When Formulations Are BioequivalentPotential Issues with TOST BioequivalentCurrent International RegulationSome Practical NotesTesting for Average BioequivalenceBackgroundLinear Model for 2 x 2 DataApplying the TOST ProcedureCarry-over, Sequence, and Interaction EffectsChecking Assumptions Made about the Linear ModelPower and Sample Size for ABE in the 2 x 2 DesignExample Where Test and Reference Are Not ABENonparametric AnalysisBE Studies with More Than Two PeriodsBackgroundThree-period DesignsWithin-subject VariabilityRobust Analyses for Three Period DesignsFour-period DesignsDesignes with More Than Two TreatmentsAdjusting for Multiple TestingNonparametric Analyses of TmaxTechnical appendix: EfficiencyTables of DataSpecial Topics in BioequivalenceDealing with Special BE ChallengesRestricted Maximum Likelihood ModellingFailing BE and the DER AssessmentSimulationData-based SimulationCarry-overOptimal DesignsDetermining Trial SizeWhat Outliers Are and How to Handle Their DataBayesian BE AssessmentAdaptive Bioequivalence TrialsBackgroundTwo-stage design for testing for ABETOST using the standard combination testExample of using the standard combination testThe maximum combination testExample of using the maximum combination testConditional errors and conditional powerAlgorithm for sample size re-estimationOperating characteristicsConclusionsTechniccal Appendix: R codeScaled Average Bioequivalence TestingBackgroundScaled Average Bioequivalence in EuropeScaled Average Bioequivalence in USADiscussion and CautionsClinical PharmacologyClinical Pharmacology Safety StudiesBackgroundFirst-time-in-humansSub-chronic Dosing StudiesFood-Effect Assessment and DDIsDose-ProportionalityTechnical AppendixQTcBackgroundModelling of QTc DataInterpreting the QTc Modelling FindingsDesign of a Thorough QTc Study in the FutureClinical Pharmacology Efficacy StudiesBackgroundSub-chronic DosingPhase IIa and the Proof of ConceptPopulation PharmacokineticsPopulation and PharmacokineticsAbsolute and Relative BioavailabilityAge and Gender Pharmacokinetic StudiesEthnicityLiver DiseaseKidney DiseaseTechnical Appendix Vaccines & Epilogue Vaccine TrialsBrief Introduction to Vaccine Research and DevelopmentPhase I Vaccine StudiesProof of Concept and Phase IILot ConsistencyConcomitant VaccinationCross-over Trials in VaccinesEpilogue BibliographyIndex

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Book SynopsisSince 1945, The Annual Deming Conference on Applied Statistics has been an important event in the statistics profession. In Clinical Trial Biostatistics and Biopharmaceutical Applications, prominent speakers from past Deming conferences present novel biostatistical methodologies in clinical trials as well as up-to-date biostatistical applications from the pharmaceutical industry.Divided into five sections, the book begins with emerging issues in clinical trial design and analysis, including the roles of modeling and simulation, the pros and cons of randomization procedures, the design of Phase II dose-ranging trials, thorough QT/QTc clinical trials, and assay sensitivity and the constancy assumption in noninferiority trials. The second section examines adaptive designs in drug development, discusses the consequences of group-sequential and adaptive designs, and illustrates group sequential design in R. The third section focuses on oncology clinical triTrade Review"This book of timely, self-contained chapters covers a wide range of current methods and unresolved challenges in clinical trial statistical methods and will prove to be an essential guide for biostatisticians who work in this field."—Dirk F. Moore, Journal of Biopharmaceutical Statistics". . . the contributed chapters in this collection are clearly written, easily digestible, and well-referenced. The book is a useful resource for the clinical trialist interested in obtaining a quick overview of standard practices and current methodological development for a specific biostatistical application, or a worthwhile read for the researcher seeking to familiarize him or herself with a diversity of emerging topics in clinical trials.—Megan T. Smith, University of California, IrvineTable of ContentsEmerging Issues in Clinical Trial Design and Analysis. Adaptive Clinical Trials. Clinical Trials in Oncology. Multiple Comparisons in Clinical Trials. Clinical Trials in the Genomic Era. Index.

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Book SynopsisAs the generic pharmaceutical industry continues to grow and thrive, so does the need to conduct adequate, efficient bioequivalence studies. In recent years, there have been significant changes to the statistical models for evaluating bioequivalence. In addition, advances in the analytical technology used to detect drug and metabolite levels have made bioequivalence testing more complex. The second edition of Handbook of Bioequivalence Testing has been completely updated to include the most current information available, including new findings in drug delivery and dosage form design and revised worldwide regulatory requirements.New topics include: A historical perspective on generic pharmaceuticals New guidelines governing submissions related to bioequivalency studies, along with therapeutic code classifications Models of noninferiority Biosimilarity of large molecule drugs Bioequivalence of complementary andTrade Review"This handbook offers a complete description of every aspect of bioequivalence testing … [It] is an essential, one-of-a-kind resource for anyone interested in bioequivalence. There are no other books that compile so many aspects in one place."—Jennifer L. Colon, PharmD, Temple University School of Pharmacy, in Doody’s Review Service Table of ContentsHistorical Perspective on Generic Pharmaceuticals. Physicochemical Basis of Bioequivalence Testing. Drug Delivery Factors. Pharmacokinetic/Pharmacodynamic (PK/PD) Modeling. Bioequivalence Testing Rationale and Principles. Bioequivalence Waivers. Statistical Evaluation of Bioequivalence Data. Regulatory Inspection Process. Fed Bioequivalence Studies. Topical Drugs. Bioequivalence of Nasal Products. Bioequivalence of Complementary and Alternate Medicines. Bioequivalence of Biosimilar Products. Bioequivalence Testing: The US Perspective. Bioequivalence Testing: European Perspective. Bioequivalence Testing: The ROW Perspective. Bioequivalence Testing Protocols. Bioequivalence Documentation. Good Laboratory Practices. Bioanalytical Method Validation. Good Clinical Practice. Computer and Software Validation. Outsourcing and Monitoring of Bioequivalence Studies. Epilogue: Future of Bioequivalence Testing. Appendix A: Glossary of Terms. Appendix B: Dissolution Testing Requirements for US FDA Submission. Bibliography. Index.

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Book SynopsisAdverse Drug Interactions: A Handbook for Prescribers assists clinicians by providing key information on potential adverse effects that can result from prescribing two or more drugs for simultaneous use. Interactions that are likely to give rise to life-threatening conditions, and which must therefore be completely avoided, are clearly highlighted. Less threatening but nonetheless important interactions necessitating practical measures, such as frequent monitoring and advice to patients, are also discussed.Presented in a user-friendly format, the book is organised by drug class and provides a brief summary of the mechanism underlying a particular interaction, alternative drugs lacking the same reactions that may be considered, and instructions for monitoring patients when adverse effects occur. All interactions listed in the previous edition have been reviewed and updated using the latest information available. The clinical reality of tTrade Review“There is much to commend. There are useful preliminary sections on the complexity of drug–drug interactions and the emerging role of electronic decision support systems… I was particularly pleased to see the inclusion of interactions with herbal and common over-the-counter medications, alcohol, ‘classic’ recreational drugs, vitamins and minerals, and key food groups.”—Daniel Marks, University College London Hospital, London, British Journal of Hospital MedicineTable of ContentsDrugs Acting on the Cardiovascular System. Drugs Acting on the Central Nervous System. Anticancer and Immunomodulating Drugs. Anticoagulants. Antidiabetic Drugs. Other Endocrine Drugs. Analgesics. Musculoskeletal Drugs. Anesthetic Drugs: General. Drugs to Treat Infections. Drugs Acting on the Gastrointestinal Tract. Respiratory Drugs. Metabolic Drugs. Obstetrics and Gynecology. Drugs Used to Treat the Urinary System. Drugs of Abuse. Miscellaneous. Over-the-Counter/Online Drugs, Traditional and Herbal Remedies. Appendices.

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Book SynopsisGood Manufacturing Practice (GMP) ensures medicinal products are produced consistently and controlled to the quality standards appropriate for their intended use and as required by product specifications or marketing authorization. Annex 11 details the European Medicines Agency (EMA) GMP requirements for computer systems.The purpose of Annex 11 is to provide the EMA healthcare industry with consistent criteria for effective implementation, control, and use of computer systems. EU Annex 11 Guide to Computer Validation Compliance for the Worldwide Health Agency GMP supplies practical information to facilitate compliance with computer system GMP requirements, while highlighting and integrating the Annex 11 guidelines into the computer compliance program.The ideas presented in this book are based on the author's 25 years of experience with computer validation in the healthcare industry with various computer systems development, maintenance, and quality functiTable of ContentsIntroduction. SLC, Computer Validation, and Annex 11. Annex 11 Principles. Risk Management. Personnel. Suppliers and Service Providers. Validation. Data. Accuracy Checks. Data Storage. Printouts. Audit Trails—Ensuring Data Integrity. Change and Configuration Management. Periodic Evaluation: Independent Review to Ensure Continued Validation of Computerized Systems. Security. Incident Management. Electronic Signatures: Electronic Signing Requirements. Batch Certification and Release. Business Continuity. Archiving. SLC Documentation. Relevant Procedural Controls. Maintaining the Validated State in Computer Systems. Annex 11 and the Cloud. EU GMP Chapter 4–Documentation and Annex 11. Annex 11 and Electronic Records Integrity. Annex 11 and 21 CFR Part 11: Comparisons for International Compliance.

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Book SynopsisThe recent introduction of nanomedicines in the drug therapy arena is revolutionizing the management of severe diseases. The key advance in the field is the optimization of the biological fate of drug molecules, thus improving the therapeutic effect while keeping to a very minimum the associated toxicity. Volume one of this book series, Nanoplatforms in Drug Delivery, established the basic aspects in the development of drug-loaded nanoplatforms, the so-called nanomedicines or nanodrugs, focusing on representative materials and strategies used in their formulation. Taking advantage of the advanced conceptualizations on nanomedicine engineering that were described in volume one, volume two, Nano-Engineering Strategies and Nanomedicines against Severe Diseases, analyzes in depth special features related to the formulation of nanoplatforms for oral, dental, topical and transdermal, pulmonary and nasal, ocular and otic, vaginal, and brain drug delivery Table of ContentsPreface to the Book Series. Preface to Volume 2. Emerging Technologies of Polymers for Nanomedicine Applications. Nanotechnology for Oral Drug Delivery and Targeting. Nanoparticulate Systems for Dental Drug Delivery. Nanotechnology for Topical and Transdermal Drug Delivery and Targeting. Nanotechnology for Pulmonary and Nasal Drug Delivery. Lipid Nanoplatforms for Pulmonary Drug Delivery. Nanotechnology for Ocular and Otic Drug Delivery and Targeting. Nanotechnology for Vaginal Drug Delivery and Targeting. Potential Nanocarriers for Brain Drug Delivery. Nanomaterials and Cancer Therapy. Nanomedicine in Cardiovascular Disease. Nano(Neuro)Medicinal Interventions for Neurodegenerative Disorders: a Meta-Analysis of Concurrent Challenges and Strategic Solutions. Nanomedicines against Infectious Diseases. Nanomedicines against Chronic Inflammatory Diseases. Nanomedicine Biopharmaceuticals for Metabolic Diseases. Nanotechnology in Gene Knockdown and miRNA Replacement in Vivo. Nanotheranostics.

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Book SynopsisThe premise of Quality by Design (QbD) is that the quality of the pharmaceutical product should be based upon a thorough understanding of both the product and the manufacturing process. This state-of-the-art book provides a single source of information on emerging statistical approaches to QbD and risk-based pharmaceutical development. A comprehensive resource, it combines in-depth explanations of advanced statistical methods with real-life case studies that illustrate practical applications of these methods in QbD implementation. Table of ContentsBACKGROUND. Introduction. ANALYTICAL METHOD. Statistical Methods for Analytical Procedure Development, Validation and Transfer. Parallelism Testing of Bioassay. Validation of Assay Linearity. ROCESS DEVELOPMENT. Residual Host Cell DNA Risk Assessment. Statistical Evaluations of Viral Clearance. Pre-filtration Bio-burden Testing. Process Validation and Verification. MANUFACTURING. Specifications.

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