Timely coverage of cleaning validation for the phamaceutical industry, a dynamic area in terms of health-based limits. Author encourages pharmaceutical manufacturers, and particularly upper management, to meet the challenges of the science-based and risk-based approaches to cleaning validation. Draws on the author's vast experience in the field of cleaning validation and hazardous materials Discusses EMA vs. ISPE on Cleaning Limits and revised Risk-MaPP for highly hazardous products in shared facilities Diverse list of topics from protocol limits for yeasts and molds to cleaning validation for homeopathic drug products

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.

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.

This new volume, Promising Drug Molecules of Natural Origin, explores potential beneficial drug substances derived from nature. It presents the general principles, characteristics, evaluation techniques, and applications involved in drug molecules from natural sources, such as plants and marine life. With chapters from renowned experts from around the world, the chapters in this volume address the challenges of standardization of herbal medicines, methods of characterization of natural medicines and phyto-constituents, and quality control methods for herbal medicines. Several chapters in the book focus on the evolution of phyto-constituents in cancer therapeutics, while others deal with applications for other diseases, such as diabetes and neuroinflammatory disorders. The volume also specifically reviews heterocyclic drugs from plants. This volume will be a valuable resource for faculty and advanced students in pharmaceutics as well as researchers, scientists, and industry professionals in medicine and drug development.

Analytical ultracentrifugation (AUC) can supply rich information on the mass, shape, size distribution, solvation, and composition of macromolecules and nanoscopic particles. It also provides a detailed view of their reversible single- or multi-component interactions over a wide range of affinities. Yet this powerful technique has been hard to master in mainstream molecular sciences due to a lack of comprehensive books on the subject. Filling this gap in the literature of biophysical methodology, Basic Principles of Analytical Ultracentrifugation explains the fundamentals in the theory and practice of AUC. The book provides you with up-to-date experimental information to confidently practice AUC. You will understand the basic concepts, full potential, and possible pitfalls of AUC as well as appreciate the current relevance of past work in the field. The book first introduces the basic principles and technical setup of an AUC experiment and briefly describes the optical systems used for detection. It then explores the ultracentrifugation experiment from a macromolecular standpoint, offering a detailed physical picture of the sedimentation process and relevant macromolecular parameters. The authors present important practical aspects for conducting an experiment, including sample preparation, data acquisition and data structure, and the execution of the centrifugal experiment. They also cover instrument calibration and quality control experiments.

Hugo Chavez won re-election in the 2012 Venezuelan presidential election, despite a closer margin between candidates than in previous elections. The results were puzzling for those who believed that Chavez's government had long ago reached its limits, while Chavez's supporters were struck by the growth of the opposition vote. Thus understanding the Venezuelan election of 2012 has proved to be challenging, with various recent studies focused upon it. Luis F. Angosto Ferrandez's book advances two ideas not previously discussed: the relationship between electoral behavior in Venezuela and contemporary Latin American geopolitics, and the way that relationship is projected through the candidates' appeal to narratives that situate Venezuela at the core of a heroic Latin American tradition and of a new regional process of integration. This edited volume first contextualizes and explains the results of the last re-election of Hugo Chavez in terms of its geopolitical conditionings and implications. Contributors tackle Latin American geopolitics by analyzing Venezuelan foreign policy and the country's role in continental projects of supra-national integration. Contributors also examine electoral strategy and tactics in order to show how the two main candidates built their campaign on emotional grounds as much on rational ones. This will be connected to the investigation of new narratives of national identification in contemporary Venezuela and how they may have practical implications in the design of policies addressing issues such as indigenous rights, community media and national security. Compiling state-of-the-art research on Latin American and Venezuelan politics, this book will appeal to academics and professionals who specialize in Latin American studies, international relations, democracy, and indigenous peoples.

Pharmaceutical product development is a multidisciplinary activity involving extensive efforts in systematic product development and optimization in compliance with regulatory authorities to ensure the quality, efficacy and safety of resulting products. Pharmaceutical Product Development equips the pharmaceutical formulation scientist with extensive and up-to-date knowledge of drug product development and covers all steps from the beginning of product conception to the final packaged form that enters the market and lifecycle management thereof. Applications of core scientific principles for product development are also thoroughly discussed in conjunction with the latest approaches involving design of experiment and quality by design with comprehensive illustrations based on practical case studies of several dosage forms. The book presents pharmaceutical product development information in an easy-to-read mode with simplified theories, case studies and guidelines for students, academicians and professionals in the pharmaceutical industry. It is an invaluable resource and hands-on guide covering managerial, regulatory and practical aspects of pharmaceutical product lifecycle management.

This revised publication serves as a handy and current reference for professionals engaged in planning, designing, building, validating and maintaining modern cGMP pharmaceutical manufacturing facilities in the U.S. and internationally. The new edition expands on facility planning, with a focus on the ever-growing need to modify existing legacy facilities, and on current trends in pharmaceutical manufacturing which include strategies for sustainability and LEED building ratings. All chapters have been re-examined with a fresh outlook on current good design practices.

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

Reviews phyto-actives and their targeted action in the management of various cancers Looks at the use of phytochemical-based nano-cosmeceuticals for beautification Explores emerging concepts of vitamins and nanocarriers as nutraceuticals Discusses the advantages of bioactive-loaded nanomedicines over conventional phytotherapies

Applied Biophysics for Drug Discovery is a guide to new techniques and approaches to identifying and characterizing small molecules in early drug discovery. Biophysical methods are reasserting their utility in drug discovery and through a combination of the rise of fragment-based drug discovery and an increased focus on more nuanced characterisation of small molecule binding, these methods are playing an increasing role in discovery campaigns. This text emphasizes practical considerations for selecting and deploying core biophysical method, including but not limited to ITC, SPR, and both ligand-detected and protein-detected NMR. Topics covered include: Design considerations in biophysical-based lead screening Thermodynamic characterization of protein-compound interactions Characterizing targets and screening reagents with HDX-MS Microscale thermophoresis methods (MST) Screening with Weak Affinity Chromatography Methods to assess compound residence time 1D-NMR methods for hit identification Protein-based NMR methods for SAR development Industry case studies integrating multiple biophysical methods This text is ideal for academic investigators and industry scientists planning hit characterization campaigns or designing and optimizing screening strategies.

Planar Chromatography-Mass Spectrometry focuses on a relatively new approach to chemical analysis in general, and to separation science in particular. It is the first book to systemically cover the theoretical background, techniques, instrumentation, and practical applications of planar chromatography-mass spectrometry as a hyphenated tool of analytical chemistry. It also examines the high and as-yet unexploited potential of planar chromatography-mass spectrometry for analytical use in scientific investigations. This book overviews the combination of planar chromatography, a relatively simple and cost-effective separation step for determining complex mixtures of compounds, with mass spectrometry, an efficient, highly instrumental, and relatively expensive technique that enables rapid identification of separated chemical species. It covers electrophoretic-mass spectrometry methods and applications, which are considered planar chromatographic techniques and are increasingly being exploited in proteomic and molecular biology studies as well as for medical diagnostic purposes. It also provides a selection of applications, such as drug control and forensic and food analysis, including more difficult substances such as carbohydrates and lipids. The book advocates growth in using planar chromatography-mass spectrometry in laboratories that have appropriate equipment but have not yet employed the techniques in combination. It also describes the use of a relatively inexpensive commercial system that can be adopted by laboratories currently working without the coupled methodology. Aiming to improve power and efficiency when other analytical methods are inadequate, Planar Chromatography-Mass Spectrometry encourages separation science practitioners in academia and industry to combine the two methods for enhanced results.

Interest in RNA nanotechnology has increased in recent years as recognition of its potential for applications in nanomedicine has grown. Edited by the world's foremost experts in nanomedicine, this comprehensive, state-of-the-art reference details the latest research developments and challenges in the biophysical and single molecule approaches in RNA nanotechnology. In addition, the text also provides in-depth discussions of RNA structure for nanoparticle construction, RNA computation and modeling, single molecule imaging of RNA, RNA nanoparticle assembly, RNA nanoparticles in therapeutics, immunorecognition of RNA nanomaterials, RNA chemistry for nanoparticle synthesis, and conjugation and labeling. Presents the latest research and discoveries in RNA nanotechnology Features contributions from world-class experts in the field Covers RNA nanoparticles in therapeutics Describes self-assembled RNA nanoparticles

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) "

The topics chosen for this volume were selected because they are some of the current development or technological issues facing drug development project teams. They regard the practical considerations for assessment of selected special development populations. For example, they include characterization of drug disposition in pregnant subjects, for measuring arrhythmic potential, for analysis tumor growth modeling, and for disease progression modeling. Practical considerations for metabolite safety testing, transporter assessments, Phase 0 testing, and development and execution of drug interaction programs reflect current regulatory topics meant to address enhancement of both safety assessment and early decision-making during new candidate selection. Important technologies like whole body autoradiography, digital imaging and dried blood spot sample collection methods are introduced, as both have begun to take a more visible role in pharmacokinetic departments throughout the industry.

The volume sheds new light on role of gut dysbiosis in cancer and immunological diseases and their clinical manifestations. Contributions in the volume discuss about the gut microbiota as a therapeutic target and the role of probiotics in its management. The volume explores application of probiotics in the treatment of various cancers viz. colorectal, gastric, lung, and breast cancer and immunological diseases. The volume comprises of chapters from expert contributors organized into various important themes which include, introduction, relationship between gut microbiota and disease condition, mechanisms involved, clinical and in vivo status, conclusion and future directions. This is a highly informative and carefully presented book, providing recent and innovative insight for scholars and researchers with an interest in probiotics and its applications in cancer and immunological diseases.

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.

Over the past two decades the benefits of label-free biosensor analysis have begun to make an impact in the market, and systems are beginning to be used as mainstream research tools in many drug discovery laboratories.

"Label-Free Technologies For Drug Discovery" summarises the latest and emerging developments in label-free detection systems, their underlying technology principles and end-user case studies that reveal the power and limitations of label-free in all areas of drug discovery.

Label-free technologies discussed include SPR, NMR, high-throughput mass spectrometry, resonant waveguide plate-based screening, transmitted-light imaging, isothermal titration calorimetry, optical and impedance cell-based assays and other biophysical methods. The technologies are discussed in relation to their use as screening technologies, high-content technologies, hit finding and hit validation strategies, mode of action and ADME/T, access to difficult target classes, cell-based receptor/ligand interactions particularly orphan receptors, and antibody and small molecule affinity and kinetic analysis.

"Label-Free Technologies For Drug Discovery" is an essential guide to this emerging class of tools for researchers in drug discovery and development, particularly high-throughput screening and compound profiling teams, medicinal chemists, structural biologists, assay developers, ADME/T specialists, and others interested in biomolecular interaction analysis.

Biological and Pharmaceutical Applications of Nanomaterials presents the findings of cutting-edge research activities in the field of nanomaterials, with a particular emphasis on biological and pharmaceutical applications. Divided into four sections-nanomaterials for drug delivery, antimicrobial nanomaterials, nanomaterials in biosensors, and safety of nanomaterials-this book: Covers topics such as stimuli-responsive nanostructured silica matrixes, gold nanoparticles, and liposomes for targeting drug delivery and dental applications Describes the use of nanocarriers and nanoparticles as cancer and peptide therapeutics, the influence of surface characteristics on microbial adhesion, and the latest developments in antimicrobial nanostructured polymers for medical applications Discusses recent advances in nanodiagnostic techniques for infectious agents, chromogenic biosensors for pathogen detection, electrochemical biosensors for detecting DNA damage and genotoxicity, and molecular imaging with quantum dots including surface modifications by polymers for biosensing applications Featuring contributions from field experts and researchers in industry and academia, Biological and Pharmaceutical Applications of Nanomaterials provides state-of-the-art information on nanomaterials and their use in drug delivery, infection control, and biomedicine.

Fundamental Concepts for New Clinical Trialists describes the core scientific concepts of designing, data monitoring, analyzing, and reporting clinical trials as well as the practical aspects of trials not typically discussed in statistical methodology textbooks. The first section of the book provides background information about clinical trials. It defines and compares clinical trials to other types of research studies and discusses clinical trial phases, registration, the protocol document, ethical issues, product development, and regulatory processes. It also includes a special chapter outlining the valuable attributes that statisticians can develop to maximize their contributions to a clinical trial. The second section examines scientific issues faced in each progressive step of a clinical trial. It covers issues in trial design, such as randomization, blinding, control-group selection, endpoint selection, superiority versus noninferiority, and parallel group versus crossover designs; data monitoring; analyses of efficacy, safety, and benefit-risk; and the reporting/publication of clinical trial results. As clinical trials remain the gold standard research studies for evaluating the effects of a medical intervention, newcomers to the field must have a fundamental understanding of the concepts to tackle real-world issues in all stages of trials. Drawing on their experiences in academia and industry, the authors provide a foundation for understanding the fundamental concepts necessary for working in clinical trials.

The biotechnology/biopharmaceutical sector has tremendously grown which led to the invention of engineered antibodies such as Antibody Drug Conjugates (ADCs), Bispecific T-cell engager (BITES), Dual Variable Domain (DVD) antibodies, and fusion proteins that are currently being used as therapeutic agents for immunology, oncology and other disease conditions. Regulatory agencies have raised the bar for the development and manufacture of antibody-based products, expecting to see the use of Quality by Design (QbD) elements demonstrating an in-depth understanding of product and process based on sound science. Drug delivery systems have become an increasingly important part of the therapy and most biopharmaceuticals for self-administration are being marketed as combination products. A survey of the market indicates that there is a strong need for a new book that will provide "one stop shopping" for the latest information and knowledge of the scientific and engineering advances made over the last few years in the area of biopharmaceutical product development. The new book entitled Development of Biopharmaceutical Drug Device Products is a reference text for scientists and engineers in the biopharmaceutical industry, academia or regulatory agencies. With insightful chapters from experts in the field, this new book reviews first principles, covers recent technological advancements and provides case studies and regulatory strategies relating to the development and manufacture of antibody-based products. It covers topics such as the importance of early preformulation studies during drug discovery to influence molecular selection for development, formulation strategies for new modalities, and the analytical techniques used to characterize them. It also addresses important considerations for later stage development such as the development of robust formulations and processes, including process engineering and modeling of manufacturing unit operations, the design of analytical comparability studies, and characterization of primary containers (pre-filled syringes and vials).Finally, the latter half of the book reviews key considerations to ensure the development and approval of a patient-centered delivery system design. This involves the evolving regulatory framework with perspectives from both the US and EU industry experts, the role of international standards, design control/risk management, human factors and its importance in the product development and regulatory approval process, as well as review of the risk-based approach to bridging between devices used in clinical trials and the to-be-marketed device. Finally, case studies are provided throughout.The typical readership would have biology and/or engineering degrees and would include researchers, scientific leaders, industry specialists and technology developers working in the biopharmaceutical field.

The structural complexity and the synthetic challenges facing glycans have historically hampered efforts to study their multifaceted roles and the application of carbohydrates in drug development. However, in very recent years, new synthetic techniques flanked by the growing knowledge about carbohydrate involvement in physiological and pathological states has spurred renewed interest in the chemistry, biology and therapeutic potentialities of carbohydrates. This book offers an overview of key aspects of carbohydrate biology and chemistry that are fundamental for the design of novel therapeutics. The four-part structure of this book introduces these essential components to life, starting from their structure and biological roles and covering analytical methods and synthesis which pave the way for the development of a wide range of therapeutic applications.Leading experts from around the world are brought together to offer their recent research with the ultimate aim of enlightening the reader on the complex yet exciting field of carbohydrate chemistry. Academic and industrial researchers in structural biology, drug discovery and carbohydrate chemistry will find this book an essential guide to the latest research and future potential of medicinal chemistry.

The careful choice of nanoparticles as targets and in drug delivery routes enhances therapeutic efficacy in cancer. Nanoparticle-Based Drug Delivery in Cancer Treatment discusses nanotechnological developments of interfering RNA-based nanoparticles, delivery vehicles, and validated therapeutic RNAi-molecular target interactions and explains the results of clinical and preclinical trials. The book also gives strategies for universal methods of constructing hybrid organic-inorganic nanomaterials that can be widely applied in the biomedical field. Key Features: Reviews recent advances of nanoparticle-mediated siRNA delivery systems and their application in clinical trials for cancer therapy Focuses on material platforms that establish NPs and both localized and controlled gene silencing Emphasizes the most promising systems for clinical application Surveys progress in nanoparticle-based nanomedicine in cancer treatment Describes the most advanced of the nonviral nanocarriers for delivery of oligonucleotides to malignant blood cancer cells This book is a valuable resource for researchers, professors, and students researching drug delivery, gene carriers, cancer therapy, nanotechnology, and nanomaterials.

State-of-the-Art Methods for Drug Safety Assessment Responding to the increased scrutiny of drug safety in recent years, Quantitative Evaluation of Safety in Drug Development: Design, Analysis and Reporting explains design, monitoring, analysis, and reporting issues for both clinical trials and observational studies in biopharmaceutical product development. It presents the latest statistical methods for drug safety assessment. The book's three sections focus on study design, safety monitoring, and data evaluation/analysis. The book addresses key challenges across regulatory agencies, industry, and academia. It discusses quantitative approaches to safety evaluation and risk management in drug development, covering Bayesian methods, effective safety graphics, and risk-benefit evaluation. Written by a team of experienced leaders, this book brings the most advanced knowledge and statistical methods of drug safety to the statistical, clinical, and safety community. It shares best practices and stimulates further research and methodology development in the drug safety area.

Accurate sample size calculation ensures that clinical studies have adequate power to detect clinically meaningful effects. This results in the efficient use of resources and avoids exposing a disproportionate number of patients to experimental treatments caused by an overpowered study. Sample Size Calculations for Clustered and Longitudinal Outcomes in Clinical Research explains how to determine sample size for studies with correlated outcomes, which are widely implemented in medical, epidemiological, and behavioral studies. The book focuses on issues specific to the two types of correlated outcomes: longitudinal and clustered. For clustered studies, the authors provide sample size formulas that accommodate variable cluster sizes and within-cluster correlation. For longitudinal studies, they present sample size formulas to account for within-subject correlation among repeated measurements and various missing data patterns. For multiple levels of clustering, the level at which to perform randomization actually becomes a design parameter. The authors show how this can greatly impact trial administration, analysis, and sample size requirement. Addressing the overarching theme of sample size determination for correlated outcomes, this book provides a useful resource for biostatisticians, clinical investigators, epidemiologists, and social scientists whose research involves trials with correlated outcomes. Each chapter is self-contained so readers can explore topics relevant to their research projects without having to refer to other chapters.