The aim of this unique volume is to help medical researchers design clinical trials to improve survival, remission duration, or time to recurrence of disease. Written in a user-friendly step-by-step format, this work enables the researcher-with no background in statistics-to determine sample size and write statistical considerations for their protocols. It provides critical language which can help with FDA submissions and/or research grants. It also provides the mathematical justification of the material at a level consistent with one year of undergraduate mathematical statistics. It presents survival analysis methods at a more elementary level than any known text. Filled with tables, figures, plus an extensive appendix, this one-of-a-kind reference is an absolute must for all clinical researchers and biostatisticians.

In Silico Drug Discovery and Design: Theory, Methods, Challenges, and Applications provides a comprehensive, unified, and in-depth overview of the current methodological strategies in computer-aided drug discovery and design. Its main aims are to introduce the theoretical framework and algorithms, discuss the range of validity, strengths and limitations of each methodology, and present applications to real world problems in the drug discovery arena. Special emphasis has been given to the emerging and most pressing methodological challenges in in silico drug discovery and design. The book assumes a basic knowledge of physical principles and molecular modeling. Particular attention has been paid to outline the underlying physico-chemical foundation of the methods described, thus providing the necessary background to avoid a "black-box" approach. In each self-contained chapter, this is presented together with the latest developments and applications, and the challenges that lie ahead. Assembling a unique team of experts to weigh in on the most important issues influencing modern computational drug discovery and design, this book constitutes both a desktop reference to academic and industrial researchers in the field, and a textbook for students in the area of molecular modeling and drug discovery. Comprised of 18 chapters and divided into three parts, this book: Provides a comprehensive, unified, and in-depth overview of the current methodological strategies in computer-aided drug discovery and design Outlines the underlying physico-chemical foundation of the methods described Presents several applications of computational methods to real world problems in the drug design field Helps to avoid a "black-box" approach to in silico drug discovery Constitutes an actual textbook for students in the area of molecular modeling and drug discovery Gives the reader the adequate background to face the current challenges of the field In Silico Drug Discovery and Design: Theory, Methods, Challenges, and Applications describes the theoretical framework, methods, practical applications and case examples relevant to computer-aided drug lead discovery and design. This text will surely aid in understanding the underlying physical foundation of computational tools and their range of application, thus facilitating the interpretation of simulation results.

This open access book presents a unique collection of practical examples from the field of pharma business management and research. It covers a wide range of topics such as: 'Brexit and its Impact on pharmaceutical Law - Implications for Global Pharma Companies', 'Implementation of Measures and Sustainable Actions to Improve Employee's Engagement', 'Global Medical Clinical and Regulatory Affairs (GMCRA)', and 'A Quality Management System for R&D Project and Portfolio Management in a Pharmaceutical Company'. The chapters are summaries of master's theses by "high potential" Pharma MBA students from the Goethe Business School, Frankfurt/Main, Germany, with 8-10 years of work experience and are based on scientific know-how and real-world experience. The authors applied their interdisciplinary knowledge gained in 22 months of studies in the MBA program to selected practical themes drawn from their daily business.

What'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 in the biopharmaceutical industry, this volume examines the science, technology, finance, legality, ethics, and politics of biosimilar drugs. It considers strategic planning elements that include an overall understanding of the history and the current status of the art and science of biosimilars, and it provides detailed descriptions of the legal, regulatory, and commercial characteristics. The book also presents a global strategy on how to build, take to market, and manage the next generation of biosimilars throughout their life cycle.

With contributions from leading experts, this book is the first to focus solely on addressing the problems and reviewing the strategies currently being used to improve the delivery of antisense nucleic acids. Important delivery issues, such as improving biological stability, improving cell-specific targeting and cellular uptake, manipulating subcellular distribution and producing liposomal delivery systems for antisense agents are comprehensively covered in this volume. This book links review-type articles with contributions that contain exciting never-before-published data on the cellular delivery of oligonucleotides. It stimulates reading for both established researchers and newcomers to the antisense field.

This is the first book that comprehensively and systematically describes the new technology of hydrophilic interaction liquid chromatography (HILIC). Hydrophilic interaction chromatography is a separation technique suitable for polar and hydrophilic compounds and orthogonal to reversed phase liquid chromatography. From small organic molecules to proteins, the text explores the many applications of HILIC in the analytical field. Winner of the President's Award for Excellence, the author explains how HILIC can significantly improve analytical throughput by shortening sample preparation procedure, which is one of the bottlenecks for drug discovery and development in the pharmaceutical industry.

The activity of many biopharmaceutical polymers is dependent on conformation, and the next several years will see increased interest in the conformational analysis of these polymers resulting from the development of biosimilar or "follow-on" biological products. While a wide variety of approaches to analysis exists, finding the most viable ones would be much easier with a consolidated reference that details the benefits and cost of each approach, with an emphasis on real results and real products. Explores the Growing Role of Conformational Analysis in Comparing Generic Biopharmaceuticals Approaches to the Conformational Analysis of Biopharmaceuticals gathers the most useful techniques and methods into a single volume, putting the greatest emphasis on those approaches that have proven the most fruitful. Rather than cover specific uses of techniques in detail, this book provides commercial biotechnologists and researchers with the information and references they need to make good choices about the technology they choose to use. With a large number of references that direct readers to primary source material, it includes studies drawn from the gamut of current literature, covering physical methods, such as differential scanning calorimetry, light scanning, and analytical ultracentrifugation. It also addresses chemical methods, such as hydrogen-deuterium exchange and trace labeling, along with infrared, ultraviolet, and Raman spectroscopy. Written by Roger Lundblad, a true pioneer in protein science, this volume supplies the necessary information researchers need to access when deciding on the most cost-effective approach, including: Comparability of biopharmaceuticals Characterization of follow-on biologics Quality attributes of protein biopharmaceuticals Confrontational analysis of biopharmaceutical products With a clear focus on relevant commercial biotechnology, this book belongs on the shelves of those serious researchers who are paving the way for the next generation of biopharmaceutical polymers.

Meta-regulation presents itself as a progressive policy approach that can manage complexity and conflicting objectives better than traditional command and control regulation. It does this by 'harnessing' markets and enlisting a broad range of stakeholders to reach a more inclusive view of the public interest that a self-regulating business can then respond to. Based on a seventeen year study of the Australian energy industry, and via the lens of Niklas Luhmann's systems theory, Meta-Regulation in Practice argues that normative meta-regulatory theory relies on questionable assumptions of stakeholder morality and rationality. Meta-regulation in practice appears to be most challenged in a complex and contested environment; the very environment it is supposed to serve best. Contending that scholarship must prioritise an understanding of communicative possibilities in practice, this book will be of interest to undergraduate and postgraduate students, as well as postdoctoral researchers interested in subjects such as business regulation, systems theory and corporate social responsibility. Please visit meta-regulation.com for more insightful information on meta-regulation and Meta-Regulation in Practice.

The development of new drugs is very complex, costly and risky. Its success is highly dependent on an intense collaboration and interaction between many departments within the drug development organization, external investigators and service providers, in constant dialogue with regulatory authorities, payers, academic experts, clinicians and patient organizations. Within the different phases of the drug life cycle, drug development is by far the most crucial part for the initial and continued success of a drug on the market.

This book offers an introduction to the field of drug development with a clear overview of the different processes that lead to a successful new medicine and of the regulatory pathways that are used to launch a new drug that are both safe and efficacious.

"This is the most comprehensive and detailed book on drug development I have ever read and I feel that it is likely to become a staple of drug development courses, such as those taught at Masters Level in my own University.... I think in the light of increasing integration of company and academic approaches to drug development both sides can read this book.. (and, therefore)... this book could not be more timely. "

"Professor Mike Coleman, University of Aston., UK ( from his review of the final manuscript) "

"In Vitro" Methods in Pharmaceutical Research provides a comprehensive guide to laboratory techniques for evaluating "in vitro" organ toxicity using cellular models. Step-by-step practical tips on how to perform and interpret assays for drug metabolism and toxicity assessment are provided, along with a comparison of different techniques available. It is a welcome addition to the literature at a time when interest is growing in cellular "in vitro" models for toxicology and pharmacology studies.
Key Features
* Meets the continuing demand for information in this field
* Compares "In Vitro" techniques with other methods
* Describes cell-culture methods used to investigate toxicity in cells derived from different organs
* Includes contributions by leading experts in the field

Although batch processing has existed for a long time, designing these processes and unit operations has been considered an onerous task that required computational efforts. Design of these processes is made more complex because of the time dependent nature of the process and the allowable flexibility. More often than not, every unit encounters optimal control problems. Therefore, traditional design books have not covered batch processing in detail. Filling this void, Batch Processing: Modeling and Design describes various unit operations in batch and bio-processing as well as design methods for these units. Topics include: Batch distillation operating modes and configurations Batch absorption operations based on the solubility difference Batch adsorption based on differential affinity of various soluble molecules to solid absorbents Batch chromatography for measuring a wide variety of thermodynamic, kinetic, and physico-chemical properties Batch crystallization where a phase is used to find the supersaturation at which point material crystallizes Batch drying that stresses the phase diagram of water to describe this operation Batch filtration using a porous medium or screen to separate solids from liquids Batch centrifugation where centrifugal force is used for separation Batch processes are widely used in pharmaceutical, food, and specialty chemicals where high value, low volume products are manufactured. Recent developments in bio-based manufacturing also favor batch processes because feed variations can be easily handled in batch processes. Further, the emerging area of nanomaterials manufacturing currently uses batch processes as they are low volume, high energy intensive processes. With examples, case studies, and more than 100 homework problems, this book describes the unit operations in batch and bioprocessing and gives students a thorough grounding in the numerical methods necessary to solve these design problems.

Advances in genomics and combinatorial chemistry during the past two decades inspired innovative technologies and changes in the discovery and pre-clinical development paradigm with the goal of accelerating the process of bringing therapeutic drugs to market. Written by William Kisaalita, one of the foremost experts in this field, 3D Cell-Based Biosensors in Drug Discovery Programs: Microtissue Engineering for High Throughput Screening provides the latest information - from theory to practice - on challenges and opportunities for incorporating 3D cell-based biosensors or assays in drug discovery programs. The book supplies a historical perspective and defines the problem 3D cultures can solve. It also discusses how genomics and combinatorial chemistry have changed the way drug are discovered and presents data from the literature to underscore the less-than-desirable pharmaceutical industry performance under the new paradigm. The author uses results from his lab and those of other investigators to show how 3D micro environments create cell culture models that more closely reflect normal in vivo-like cell morphology and function. He makes a case for validated biomarkers for three-dimensionality in vitro and discusses the advantages and disadvantages of promising tools in the search of these biomarkers. The book concludes with case studies of drugs that were abandoned late in the discovery process, which would have been discarded early if tested with 3D cultures. Dr. Kisaalita presents evidence in support of embracing 3D cell-based systems for widespread use in drug discovery programs. He goes to the root of the issue, establishing the 3D cell-based biosensor physiological relevance by comparing 2D and 3D culture from genomic to functional levels. He then assembles the bioengineering principles behind successful 3D cell-based biosensor systems. Kisaalita also addresses the challenges and opportunities for incorporating 3D cell-based biosensors or cultures in current discovery and pre-clinical development programs. This book makes the case for widespread adoption of 3D cell-based systems, rendering their 2D counterparts, in the words of Dr. Kisaalita "quaint, if not archaic" in the near future.

Now that prohibitions against stem cell research are relaxing, it is time for the field to move forward with the advances that promise to eliminate so much human suffering. However, it would be naive to ignore the fact that regenerative medicines pose a whole new set of challenges to an industry sector that for decades has geared itself to the development and delivery of traditional pharmaceuticals. Still, significant strides are being made. Unique in its focus, The Delivery of Regenerative Medicines and Their Impact on Healthcare delves into material not included in other books. Edited by Dr. Catherine Prescott and Professor Dame Julia Polak, two of the most respected authorities in stem cell research and the business of regenerative medicine, this text presents original firsthand accounts of experts from around the globe. Professor Polak starts by summarizing the progress made and the challenges currently facing the field both as a science and an emerging industry. This is followed by topics relevant to regulators, insurers, and investors as well as pharmaceutical and biotech researchers. Offering innovative insight on topics rarely covered, this volume: Details various innovative investment models Offers a detailed overview of cell-based products and therapeutic stem cell technologies Examines concerns over safeguarding intellectual property Looks at evolving regulations in the U.S. and Europe Discusses insurance and risk management and the establishment of reimbursement parameters This book reaches out to inform a wide audience across government, industry, and academia. It goes beyond the usual discussions to help invigorate the dialogue and present solutions that must occur at the crossroads of technology and commerce for regenerative medicines to realize their promise.

One of the main problems concerning therapeutic tools for the treatment of parasitic diseases, including leishmaniasis, is that some field parasites are naturally resistant to the classical drugs; additionally, current therapies may select parasites prone to be resistant to the applied drugs. These features are (at least partially) responsible for the disappointing persistence of the disease and resultant deaths worldwide. This book provides a comprehensive view of the pathology of the disease itself, and of parasitic drug resistance, its molecular basis, consequences and possible treatments. Scientists both from academic fields and from the industry involved in biomedical research and drug design, will find in this book a valuable and fundamental guide that conveys the knowledge needed to understand and to improve the success in combating this disease worldwide.

There is a clear need for innovative technologies to improve the delivery of therapeutic and diagnostic agents in the body. Recent breakthroughs in nanomedicine are now making it possible to deliver drugs and therapeutic proteins to local areas of disease or tumors to maximize clinical benefit while limiting unwanted side effects. Nanomedicine in Drug Delivery gives an overview of aspects of nanomedicine to help readers design and develop novel drug delivery systems and devices that build on nanoscale technologies. Featuring contributions by leading researchers from around the world, the book examines: The integration of nanoparticles with therapeutic agents The synthesis and characterization of nanoencapsulated drug particles Targeted pulmonary nanomedicine delivery using inhalation aerosols The use of biological systems-bacteria, cells, viruses, and virus-like particles-as carriers to deliver nanoparticles Nanodermatology and the role of nanotechnology in the diagnosis and treatment of skin disease Nanoparticles for the delivery of small molecules, such as for gene and vaccine delivery The use of nanotechnologies to modulate and modify wound healing Nanoparticles in bioimaging, including magnetic resonance, computed tomography, and molecular imaging Nanoparticles to enhance the efficiency of existing anticancer drugs The development of nanoparticle formulations Nanoparticles for ocular drug delivery Nanoparticle toxicity, including routes of exposure and mechanisms of toxicity The use of animal and cellular models in nanoparticles safety studies With its practical focus on the design, synthesis, and application of nanomedicine in drug delivery, this book is a valuable resource for clinical researchers and anyone working to tackle the challenges of delivering drugs in a more targeted and efficient manner. It explores a wide range of promising approaches for the diagnosis and treatment of diseases using cutting-edge nanotechnologies.

Clinical Trial Optimization Using R explores a unified and broadly applicable framework for optimizing decision making and strategy selection in clinical development, through a series of examples and case studies. It provides the clinical researcher with a powerful evaluation paradigm, as well as supportive R tools, to evaluate and select among simultaneous competing designs or analysis options. It is applicable broadly to statisticians and other quantitative clinical trialists, who have an interest in optimizing clinical trials, clinical trial programs, or associated analytics and decision making. This book presents in depth the Clinical Scenario Evaluation (CSE) framework, and discusses optimization strategies, including the quantitative assessment of tradeoffs. A variety of common development challenges are evaluated as case studies, and used to show how this framework both simplifies and optimizes strategy selection. Specific settings include optimizing adaptive designs, multiplicity and subgroup analysis strategies, and overall development decision-making criteria around Go/No-Go. After this book, the reader will be equipped to extend the CSE framework to their particular development challenges as well.

The GLP regulations have been enacted since 1978 and are currently under a proposed FDA amendment to revise terminology and accommodate other changes relating to advances in technology related to the industry. This book provides a unique opportunity to access interpretation of the 21CFR58 regulatory requirements from leading industry experts with a vast knowledge and expertise in their fields. The approach used takes the regulations, provides interpretations and references to examples and regulatory actions. Data integrity and the use of electronic systems in compliance with 21CFR11 Electronic Records: Electronic Signatures are also discussed. * Unique volume covering FDA inspections of GLP facilities * Provides a detailed interpretation of GLP Regulations * Presents the latest on electronic data management in GLP * Describes GLP and computer systems validation * Can be referenced repeatedly in supporting daily hands on implementation of the CFR requirements

When a biological drug patent expires, alternative biosimilar products are developed. The development of biosimilar products is complicated and involves numerous considerations and steps. The assessment of biosimilarity and interchangeability is also complicated and difficult. Biosimilar Drug Product Development presents current issues for the development of biosimilars and gives detailed reviews of its various stages and contributing factors as well as relevant regulatory pathways and pre- and post-approval issues.

Biologically active natural products and their substructures have long been valuable starting points for medicinal chemistry and drug discovery. This new volume explores biologically active natural products and their use in microbial technologies and as phyto-pharmaceuticals in drug development. It presents detailed scientific principles and recent research on applications of nanotechnology in diagnostics and drug delivery. Topics include pharmacotherapeutically active proteins and peptides; the biotechnological potential of hydrogen-oxidizing bacteria; synthesis and production; synthetic colorants, pigments, dyes, and lakes; and more. The use of various plants is discussed in several chapters, including Artemisia, Asteraceae, Abutilon indicum, Prosopis juliflora, Acacia arabica, Aloe barbadensis, Tabermontana divaricate Linn., among others. With the information presented in Biologically Active Natural Products: Microbial Technologies and Phyto-Pharmaceuticals in Drug Development, scientists, faculty, and graduate students will gain a unique insight into nanotechnology and natural pharmaceuticals today with practical implementation in various industrial sectors.

Colloidal drug delivery systems present a range of therapeutic benefits in the treatment of a number of challenging conditions, allowing researchers to cross barriers that have previously prevented efficient treatment while offering improved and more targeted absorption. Summarizing recent research in the field, Colloids in Drug Delivery assembles the work of 65 of the world's leading colloid scientists who examine the full spectrum of this rapidly emerging science, from pure to applied, most of it drawn from their own experience and research. The book begins by examining the basics of surfactant and polymer surface activity and self-assembly, the various types of structures formed by such compounds, and their use in drug delivery and biotechnology. It examines the development of controlled and targeted delivery systems by utilizing the various properties of colloids before moving on to discuss various applications and fields of research. Topics discussed include: The use of hard, soft, and macromolecular colloidal drug delivery systems formed by surfactants, polymers, proteins, and lipids Recent advances in procolloidal systems, self-emulsifying drug delivery systems, and aerosol applications to pharmaceutical drug delivery Colloidal nanocarriers for imaging applications and the treatment of dental and periodontal diseases Classification and application of colloidal drug delivery systems in tumor targeting The use of colloids for improved nasal, ocular, vaginal, oral, buccal, gastrointestinal, and colon drug delivery Examining topics necessary to the critical evaluation of a drug candidate's potential for delivery, the book also describes the preparation, classification, interfacial activity, surface modifications and influence on particle characteristics, drug delivery, and drug targeting. Each chapter in this expansive volume explains why a particular system is used for the intended application, how it is made, and how it behaves. All those concerned with the research, development, and manufacture of drugs will find this a valuable reference, offering a wealth of research upon which they can build.

This important new book provides the fundamental understanding of the peptide and protein drug delivery systems with a special focus on their nanotechnology applications. Addressing an increasing interest in peptide and protein drug delivery systems in both academic and industrial circles worldwide, this book fills the need for a comprehensive review and assessment of conventional and nonconventional routes of administration.

The Science and Business of Drug Discovery is written for those who want to learn about the biopharmaceutical industry and its products whatever their level of technical knowledge. Its aim is to demystify the jargon used in drug development, but in a way that avoids over simplification and the resulting loss of key information. Each of the twenty chapters is illustrated with figures and tables which clarify some of the more technical points being made. Also included is a drug discovery case history which draws the relevant material together into a single chapter. In recognizing that it is difficult to navigate through the many external resources dealing with drug development, the book has been written to guide the reader towards the most appropriate information sources, including those listed in the two appendices. The following topics are covered: Different types of drugs: from small molecules to stem cells Background to chemistry of small and large molecules Historical background to drug discovery, pharmacology and biotechnology The drug discovery pipeline: from target discovery to marketed medicine Commercial aspects of drug discovery Challenges to the biopharmaceutical industry and its responses Material of specific interest to technology transfer executives, recruiters and pharmaceutical translators

'Cannabinoids' is a broad term covering a group of natural products from Cannabis sativa, one of which locks on to specific receptors - protein molecules on the surface of cells - known as cannabinoid receptors. Over the past decades scientists have found that cannabinoid receptors and their endogenous ligands, the endocannabinoids, are involved in a vast array of physiological functions, including helping to control brain activity, energy metabolism, heart function, the immune system and even reproduction. In Cannabinoids, Vincenzo Di Marzo has assembled contributions from international experts to provide the definitive guide to what continues to be a rapidly developing research field. After an introductory historical chapter, the book continues by looking at the biochemical, genetic and molecular elements of cannabinoids, followed by chapters covering their role in health and disease. The final chapter outlines the need for a new nomenclature to reflect the complex and multi-disciplinary nature of this area.

The 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 covers the characterization and possible properties of metallonutraceuticals. It also examines bioavailability and drug interactions, and therapeutic applications of nanometals including use as imaging agents, in cancer diagnosis and treatment, as antibacterials and antivirals, in ocular disease, and in neurodegenerative diseases. The book explores the use of metals in traditional Chinese medicine, potential applications for metalloenzymes, the use of nanosilver in nutraceuticals, and the potential of gold nanoparticles as a drug delivery system. In addition, it addresses intellectual property rights and regulatory considerations regarding metallonutraceuticals. Using an interdisciplinary approach, this user-friendly text provides a knowledge base and inspiration for new research in this exciting field.

Get Up to Speed on Many Types of Adaptive Designs Since the publication of the first edition, there have been remarkable advances in the methodology and application of adaptive trials. Incorporating many of these new developments, Adaptive Design Theory and Implementation Using SAS and R, Second Edition offers a detailed framework to understand the use of various adaptive design methods in clinical trials. New to the Second Edition Twelve new chapters covering blinded and semi-blinded sample size reestimation design, pick-the-winners design, biomarker-informed adaptive design, Bayesian designs, adaptive multiregional trial design, SAS and R for group sequential design, and much more More analytical methods for K-stage adaptive designs, multiple-endpoint adaptive design, survival modeling, and adaptive treatment switching New material on sequential parallel designs with rerandomization and the skeleton approach in adaptive dose-escalation trials Twenty new SAS macros and R functions Enhanced end-of-chapter problems that give readers hands-on practice addressing issues encountered in designing real-life adaptive trials Covering even more adaptive designs, this book provides biostatisticians, clinical scientists, and regulatory reviewers with up-to-date details on this innovative area in pharmaceutical research and development. Practitioners will be able to improve the efficiency of their trial design, thereby reducing the time and cost of drug development.