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

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.

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.

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.

This book focuses on a diverse range of disciplines, including pharmacy, sociology, social policy, psychology, anthropology, history and health economics, with contributors each bringing a unique perspective and insight into the practice of pharmacy.

The pharmaceutical industry is under increasing pressure to do more with less. Drug discovery, development, and clinical trial costs remain high and are subject to rampant inflation. Ever greater regulatory compliance forces manufacturing costs to rise despite social demands for more affordable health care. Traditional methodologies are failing and the industry needs to find new and innovative approaches for everything it does. Six Sigma in the Pharmaceutical Industry: Understanding, Reducing, and Controlling Variation in Pharmaceuticals and Biologics is the first book to focus on the building blocks of understanding and reducing variation using the Six Sigma method as applied specifically to the pharmaceutical industry. It introduces the fundamentals of Six Sigma, examines control chart theory and practice, and explains the concept of variation management and reduction. Describing the approaches and techniques responsible for their own significant success, the authors provide more than just a set of tools, but the basis of a complete operating philosophy. Allowing other references to cover the structural elements of Six Sigma, this book focuses on core concepts and their implementation to improve the existing products and processes in the pharmaceutical industry. The first half of the book uses simple models and descriptions of practical experiments to lay out a conceptual framework for understanding variation, while the second half introduces control chart theory and practice. Using case studies and statistics, the book illustrates the concepts and explains their application to actual workplace improvements. Designed primarily for the pharmaceutical industry, Six Sigma in the Pharmaceutical Industry: Understanding, Reducing, and Controlling Variation in Pharmaceuticals and Biologics provides the fundamentals of variation management and reduction in sufficient detail to assist in transforming establishe

The aim of this book is to present a range of analytical methods that can be used in formulation design and development and focus on how these systems can be applied to understand formulation components and the dosage form these build. To effectively design and exploit drug delivery systems, the underlying characteristic of a dosage form must be understood--from the characteristics of the individual formulation components, to how they act and interact within the formulation, and finally, to how this formulation responds in different biological environments. To achieve this, there is a wide range of analytical techniques that can be adopted to understand and elucidate the mechanics of drug delivery and drug formulation. Such methods include e.g. spectroscopic analysis, diffractometric analysis, thermal investigations, surface analytical techniques, particle size analysis, rheological techniques, methods to characterize drug stability and release, and biological analysis in appropriate cell and animal models. Whilst each of these methods can encompass a full research area in their own right, formulation scientists must be able to effectively apply these methods to the delivery system they are considering. The information in this book is designed to support researchers in their ability to fully characterize and analyze a range of delivery systems, using an appropriate selection of analytical techniques. Due to its consideration of regulatory approval, this book will also be suitable for industrial researchers both at early stage up to pre-clinical research.

With potentially high specificity and low toxicity, biologicals offer promising alternatives to small-molecule drugs. Peptide therapeutics have again become the focus of innovative drug development efforts backed up by a resurgence of venture funds and small biotechnology companies. What does it take to develop a peptide-based medicine? What are the key challenges and how are they overcome? What are emerging therapeutics for peptide modalities? This book answers these questions with a holistic story from molecules to medicine, combining the themes of design, synthesis and clinical applications of peptide-based therapeutics and biomarkers. Chapters are written and edited by leaders in the field from industry and academia and they cover the pharmacokinetics of peptide therapeutics, attributes necessary for commercially successful metabolic peptides, medicinal chemistry strategies for the design of peptidase-resistant peptide analogues, disease classes for which peptide therapeutic are most relevant, and regulatory issues and guidelines. The critical themes covered provide essential background information on what it takes to develop peptide-based medicine from a chemistry perspective and views on the future of peptide drugs. This book will be a valuable resource not only as a reference book for the researcher engaged in academic and pharmaceutical setting, from basic research to manufacturing and from organic chemistry to biotechnology, but also a valuable resource to graduate students to understand discovery and development process for peptide-based medicine.

Solvent systems are integral to drug development and pharmaceutical technology. This single topic encompasses numerous allied subjects running the gamut from recrystallization solvents to biorelevant media. The goal of this contribution to the AAPS Biotechnology: Pharmaceutical Aspects series is to generate both a practical handbook as well as a reference allowing the reader to make effective decisions concerning the use of solvents and solvent systems. To this end, the monograph was created by inviting recognized experts from a number of fields to author relevant sections. Specifically, 15 chapters have been designed covering the theoretical background of solubility, the effect of ionic equilibria and pH on solubilization, the use of solvents to effect drug substance crystallization and polymorph selection, the use of solvent systems in high throughput screening and early discovery, solvent use in preformulation, the use of solvents in bio-relevant dissolution and permeation experiments, solvents and their use as toxicology vehicles, solubilizing media and excipients in oral and parenteral formulation development, specialized vehicles for protein formulation and solvent systems for topical and pulmonary drug administration. The chapters are organized such that useful decision trees are included together with the scientific underpinning for their application. In addition, trends in the use of solvent systems and a balance of current views make this monograph useful to both the novice and experienced researcher and to scientists at all developmental stages from early discovery to late pharmaceutical operations.

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.

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.

This book is an excursion into the drug development process, from the initial conception in a chemical or molecular biology lab, via tests in isolated cells and animals, to the stage of clinical trials. The human body is a complex ecosystem where little is conclusively known in terms of its response to medication, for both sick and healthy individuals. The considerable degree of uncertainty inherent in health-related research can lead to approval of controversial medicines, particularly in high-stakes scenarios and medical crises. Real-life examples are drawn on here to explain the decision making processes behind the acceptance of new drugs, disproving misconceptions around medicines by delving into the history and current practice of the drug development process.Originally written in Italian, How Medicines are Born helps patients, students, public health officials physicians, healthcare practitioners and biomedical scientists make informed decisions on the benefits and disadvantages of select medicine based on an understanding of the history of drug development.Published in Italian (2014), M D'Incalci & L Vozza, Come Nascono le Medicine; La scienza imperfetta dei farmaci. Bologna: ZanichelliRelated Link(s)

This book is an excursion into the drug development process, from the initial conception in a chemical or molecular biology lab, via tests in isolated cells and animals, to the stage of clinical trials. The human body is a complex ecosystem where little is conclusively known in terms of its response to medication, for both sick and healthy individuals. The considerable degree of uncertainty inherent in health-related research can lead to approval of controversial medicines, particularly in high-stakes scenarios and medical crises. Real-life examples are drawn on here to explain the decision making processes behind the acceptance of new drugs, disproving misconceptions around medicines by delving into the history and current practice of the drug development process.Originally written in Italian, How Medicines are Born helps patients, students, public health officials physicians, healthcare practitioners and biomedical scientists make informed decisions on the benefits and disadvantages of select medicine based on an understanding of the history of drug development.Published in Italian (2014), M D'Incalci & L Vozza, Come Nascono le Medicine; La scienza imperfetta dei farmaci. Bologna: ZanichelliRelated Link(s)

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.

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.

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.

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.

'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.

Explore Important Tools for High-Quality Work in Pharmaceutical Safety Statistical Methods for Drug Safety presents a wide variety of statistical approaches for analyzing pharmacoepidemiologic data. It covers both commonly used techniques, such as proportional reporting ratios for the analysis of spontaneous adverse event reports, and newer approaches, such as the use of marginal structural models for controlling dynamic selection bias in the analysis of large-scale longitudinal observational data. Choose the Right Statistical Approach for Analyzing Your Drug Safety Data The book describes linear and non-linear mixed-effects models, discrete-time survival models, and new approaches to the meta-analysis of rare binary adverse events. It explores research involving the re-analysis of complete longitudinal patient records from randomized clinical trials. The book discusses causal inference models, including propensity score matching, marginal structural models, and differential effects, as well as mixed-effects Poisson regression models for analyzing ecological data, such as county-level adverse event rates. The authors also cover numerous other methods useful for the analysis of within-subject and between-subject variation in adverse events abstracted from large-scale medical claims databases, electronic health records, and additional observational data streams. Advance Statistical Practice in Pharmacoepidemiology Authored by two professors at the forefront of developing new statistical methodologies to address pharmacoepidemiologic problems, this book provides a cohesive compendium of statistical methods that pharmacoepidemiologists can readily use in their work. It also encourages statistical scientists to develop new methods that go beyond the foundation covered in the text.

This book describes seven areas in the field of biotechnology operations as practiced by biopharmaceutical firms and nonprofit institutions. Revisions focus upon changes that have occurred in several areas over the past six years, with emphasis on regulatory, biomanufacturing, clinical and technical information, along with processes and guidlines that have added to the discipline. Examples are increased for new technical fields such as cell and tissue engineering. Further, illustrations or figures are added to each chapter to emphasize particular points.

Biologically Active Small Molecules: Modern Applications and Therapeutic Perspectives focuses on small molecules as active pharmacological agents, their pharmacotherapeutically active properties, new approaches in drug discovery using small molecules, and biopharmaceutic approaches for low molecular weight ligands. Molecules of low mass play a pivotal role in pharmacology because they exhibit multifarious pharmacological effects. Small molecules have become universally popular due to their simple chemistry, easy separation techniques, versatile acceptance for computational studies, large number of places for the substitution of active chemical moieties by well-established synthetic routes with less effort, better quality attributes, and ability to demonstrate numerous biological activities. This book provides a multidisciplinary approach that delivers the most updated knowledge and advances of some newly developed therapeutically active low molecular weight compounds. It includes chapters that present up-to-date and concise content on the classification, structures, chemical syntheses, medicinal chemistry, pharmacology, biochemical pathways, mechanism of actions, side effects, and adverse effects of small molecule drug discovery. The book covers a broad area by highlighting the advances of inter- and multidisciplinary fields of medicine, chemical sciences, and pharmaceuticals. The flowcharts, figures, illustrations, and diagrams provide important information and will be of great interest for readers.

This fully updated second edition reflects the significant changes in process chemistry since the first edition and includes more common process issues such as safety, cost, robustness, and environmental impact. Some areas have made notable progress such as process safety, stereochemistry, new reagents and reagent surrogates. Forty years ago there were few process research and development activities in the pharmaceutical industry, partly due to the simplicity of drug molecules. With increasing structural complexity especially the introduction of chiral centers into drug molecules and stricter regulations, process R&D has become one of the critical departments for pharmaceutical companies. This unique volume now in its second edition is designed to provide readers with an unprecedented strategy and approach which will help chemists and graduate students develop chemical processes in an efficient manner Promotes an industrial mindset concerning safety and commercial viability when developing methods The author discusses development strategies with case studies and experimental procedures Focuses on mechanism-guided process development which provides readers with practical strategies and approaches Addresses more common process issues such as safety, cost, robustness, and environmental impact.

The series Structure and Bonding publishes critical reviews on topics of research concerned with chemical structure and bonding. The scope of the series spans the entire Periodic Table and addresses structure and bonding issues associated with all of the elements. It also focuses attention on new and developing areas of modern structural and theoretical chemistry such as nanostructures, molecular electronics, designed molecular solids, surfaces, metal clusters and supramolecular structures. Physical and spectroscopic techniques used to determine, examine and model structures fall within the purview of Structure and Bonding to the extent that the focus is on the scientific results obtained and not on specialist information concerning the techniques themselves. Issues associated with the development of bonding models and generalizations that illuminate the reactivity pathways and rates of chemical processes are also relevant. The individual volumes in the series are thematic. The goal of each volume is to give the reader, whether at a university or in industry, a comprehensive overview of an area where new insights are emerging that are of interest to a larger scientific audience. Thus each review within the volume critically surveys one aspect of that topic and places it within the context of the volume as a whole. The most significant developments of the last 5 to 10 years should be presented using selected examples to illustrate the principles discussed. A description of the physical basis of the experimental techniques that have been used to provide the primary data may also be appropriate, if it has not been covered in detail elsewhere. The coverage need not be exhaustive in data, but should rather be conceptual, concentrating on the new principles being developed that will allow the reader, who is not a specialist in the area covered, to understand the data presented. Discussion of possible future research directions in the area is welcomed. Review articles for the individual volumes are invited by the volume editors. Readership: research scientists at universities or in industry, graduate students Special offer for all customers who have a standing order to the print version of Structure and Bonding, we offer free access to the electronic volumes of the Series published in the current year via SpringerLink.

Building on the success of the previous editions, the Textbook of Drug Design and Discovery, Fifth Edition, has been thoroughly revised and updated to provide a complete source of information on all facets of drug design and discovery for students of chemistry, pharmacy, pharmacology, biochemistry, and medicine. The information is presented in an up-to-date review form with an underlying and fundamental focus on the educational aspects. Beginning with an introduction to drug design and discovery, the first eight chapters cover molecular recognition, ligand-based drug design, and biostructure-based drug design. The authors also discuss drug-like properties and decision making in medicinal chemistry, chemical biology, natural products in drug discovery, and in vivo imaging in drug discovery. The middle six chapters provide an overview of peptide and protein drug design, prodrugs in drug design and development, and enzyme inhibitors. The authors also go through receptors (structure, function, and pharmacology), ion channels (structure and function), and neurotransmitter transporters (structure, function, and drug binding). The following chapters address important neurotransmitter systems, GABA and glutamic acid receptors and transporter ligands, acetylcholine, histamine, dopamine and serotonin, and opioid and cannabinoid receptors. The book concludes with an examination of neglected diseases, anticancer agents, tyrosine kinase receptors, and antibiotics.

Presents health benefits and medicinal importance of dietary polyphenols having antioxidative effects and their possible preventive role against oxidative stress (OS)-induced chronic human diseases Summarizes latest understanding on the biochemical mechanism(s) involved in the antioxidative action of dietary polyphenols along with their bioavailability, pharmacokinetic, and toxicological considerations Highlights novel approaches of drug discovery from dietary polyphenols through computational screening of bioactive phytochemical components