When a problem arises with a product regulated by FDA, the Agency can take a number of actions to protect the public health. Initially, the agency works with the manufacturer to correct the problem voluntarily. If that fails, administrative enforcement and legal remedies include asking the manufacturer to recall a product and having federal marshals seize products if a voluntary recall is not done. Drugs can be seized and medical devices can be detained and imports can be stopped at the port of entry until problems are corrected. If warranted, FDA can ask the courts to issue injunctions or prosecute those that deliberately violate the law. When warranted, criminal penalties-including prison sentences-are sought. Ensuring that your company is in compliance at all times in all departments is a never-ending task. Failure to get it right, even once, can mean excessive fines, penalties, or possible debarment. The FDA Administrative Enforcement Manual explores the control of drug research in pharmaceutical, vaccine, biologic, biotechnology, medical device, and cosmeceutical industries. Introducing basic industry techniques, the author explores every day industry problems and presents suggested methods for applying the theory to resolve them. The book covers the ten critical Administrative Enforcement areas, including recalls, application integrity, injunctions, seizures, and more. It supplements these topics with regulations, lawsuit case studies, enforcement information, and reference materials. Offering insight into the impact of FDA enforcement on the national and international pharmaceutical industry, practitioners and industry suppliers, the book provides an understanding of drug development and manufacturing regulations in the United States and shows you what it takes to keep your company in compliance. The only complete, single source available, the FDA Administrative Enforcement Manual draws on the author's experience in the trenches of the pharmaceutical industry with administrative enforcement activities.

Electrochemical Detection in HPLC: Analysis of Drugs and Poisons is the first monograph devoted to the application of this mode of analysis to the assay of exogenous compounds such as drugs in biological fluids and associated areas. The introductory chapters provide information on basic electrochemistry and HPLC-ED, and on trouble-shooting. The specialized area of thiol analysis is also discussed in detail. Salient practical details of published applications of the technique in analytical toxicology and related areas are provided in a standard format. Alternative techniques are suggested throughout. The emphasis is on the analysis of exogenous compounds, although catecholamines and other endogenous species are discussed in so far as they may be used as drugs. The practical nature of this book will make it useful to professionals working in the field. It will also be of benefit to analysts wishing to use HPLC-ED in the analysis of biological samples for analytes not specifically covered in the volume.

In the fast-developing field of nanomedicine, a broad variety of materials have been used for the development of advanced delivery systems for drugs, genes, and diagnostic agents. With the recent breakthroughs in the field, we are witnessing a new age of disease management, which is governed by precise regulation of dosage and delivery. This book presents the advances in the use of metal-based and other nanomaterials for medical imaging, diagnosis, theranostics, and drug delivery. It discusses silver, hybrid gold, and surface-modified magnetic nanoparticles, fluorescent quantum dots, lipid bubbles, and nanobubbles. It provides all available information about these materials and describes in detail their advantages and disadvantages and the areas where they could be utilized successfully. The text also covers topics such as improving bioactivity of poorly soluble actives, cellular and molecular toxicology of nanoparticles, and biofate of nanoemulsions.

With over twenty different official regulatory statements worldwide on Good Manufacturing Practice (GMP) for pharmaceutical, drug, or medicinal products, two stand out as being the most influential and most frequently referenced. Bridging the gap between U.S. regulations and European Good Manufacturing Practice guidelines, Good Pharmaceutical Manufacturing Practice: Rationale and Compliance gleans the most important substance from the U.S. Current Good Manufacturing Practice, parts 210 and 211 (US cGMPs, 2002) and the European Guide to Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use (EU GMP guide, 2002). The author uses his 40+ years of experience in technical management, production, quality assurance, and distribution within the pharmaceutical industry, offering a hands-on guide to better understand and implement optimal pharmaceutical practices. This book also compares the principle requirements of GMP, and explores the reasoning behind these requirements and ways to comply with them. Relevant topics include personnel, documentation, premises and equipment, production, quality control, self-inspection, recalls, and more. This is an essential guidebook for those who wish to expand their pharmaceutical business in any international capacity.

This book examines and evaluates the strategies utilized to design and synthesize pharmaceutically active agents. Significant updates over the last 10 years since the publication of the 1st edition include synthesis of enantiomerically pure isomers, novel chemical methodologies, and new pharmaceutical agents targeted at novel biological endpoints. Written by an experienced successful author, this book meets the needs of a growing community of researchers in pharmaceutical R &D, as well as medical professionals, by providing a useful guide for designing and synthesizing pharmaceutical agents. Additionally, it is a useful text for medicinal chemistry students.

Valuation is a hot topic among life sciences professionals. There is no clear understanding on how to use the different valuation approaches and how to determine input parameters. Some do not value at all, arguing that it is not possible to get realistic and objective numbers out of it. Some claim it to be an art. In the following chapters we will provide the user with a concise val- tion manual, providing transparency and practical insight for all dealing with valuation in life sciences: project and portfolio managers, licensing executives, business developers, technology transfer managers, entrep- neurs, investors, and analysts. The purpose of the book is to explain how to apply discounted cash flow and real options valuation to life sciences p- jects, i.e. to license contracts, patents, and firms. We explain the fun- mentals and the pitfalls with case studies so that the reader is capable of performing the valuations on his own and repeat the theory in the exercises and case studies. The book is structured in five parts: In the first part, the introduction, we discuss the role of the players in the life sciences industry and their p- ticular interests. We describe why valuation is important to them, where they need it, and the current problems to it. The second part deals with the input parameters required for valuation in life sciences, i.e. success rates, costs, peak sales, and timelines.

This authoritative reference presents an up-to-date review of the testing methods, emerging technologies, and analytical systems and procedures used to prevent the microbial contamination of pharmaceutical processes, products, and environments. It identifies new tools for sample analysis and evaluation and the impact of these advancements on the continuous supply and manufacturing of pharmaceutical products. With more than 100 tables and 430 current references, the book contains a detailed analysis of microbial contamination recalls for nonsterile and sterile pharmaceutical products, demonstrating the distribution of microorganisms worldwide and the identification by geographical regions.

As pharmaceutical companies strive to develop safer medicines at a lower cost, they must keep pace with the rapid growth of technology and research methodologies. Defying the misconception of process chemistry as mere scale-up work, Process Chemistry in the Pharmaceutical Industry, Vol. 2: Challenges in an Ever Changing Climate explores novel applications of synthetic, physical, and analytical chemistry in drug discovery and development. It offers an accurate depiction of the most up-to-date process research and development methods applied to synthesis, clinical trials, and commercializing drug candidates. The second installment in this progressive series, this volumereviews the latest breakthroughs to advance process chemistry, including asymmetric synthesis, crystallization, morphology, enzymatic intervention, green chemistry, macromolecules (monoclonal antibodies, biological molecules, polymers), enantioselectivity, organometallic chemistry, process analytical tools, chemical engineering controls, regulatory compliance, and outsourcing/globalization. It explores new approaches to synthetic processes, examines the latest safety methods and experiment design, and suggests realistic solutions to problems encountered in manufacturing and process development. Significant topics include atom economy, ease of synthesis, instrumentation, automization, quality control, cost considerations, green practices, and future trends. Jointly edited by the founder/president of Delphian Pharmaceuticals and the director of Chemical R&D at Pfizer, this book brings together contributions byreputed scientists, technologists, engineers, and professors from leading academic institutions, such as the Imperial College, UK, the University of Tokyo, ETH, Switzerland, the International University at Bermen, Germany, and the University of Connecticut, USA, and from principal pharmaceutical companies that include Merck, Bristol Myers Squibb, Pfizer, Novartis, Eli Lilly, Astrazeneca and DSM.

This set of six volumes provides a systematic and standardized description of 23,033 chemical components isolated from 6,734 medicinal plants, collected from 5,507 books/articles published in Chinese and international journals. A chemical structure with stereo-chemistry bonds is provided for each chemical component, in addition to conventional information, such as Chinese and English names, physical and chemical properties. It includes a name list of medicinal plants from which the chemical component was isolated. Furthermore, abundant pharmacological data for nearly 8,000 chemical components are presented, including experimental method, experimental animal, cell type, quantitative data, as well as control compound data. The seven indexes allow for complete cross-indexing. Regardless whether one searches for the molecular formula of a compound, the pharmacological activity of a compound, or the English name of a plant, the information in the book can be retrieved in multiple ways.

This book is the definitive work on the theory and practice of pharmaceutical tablet and pellet coating. It describes both the practical and theoretical aspects of tablet coating, including the equipment and methods used in laboratory development, scale-up and production systems, More...as well as automation and validation. This book also discusses the problems of conforming to world-wide regulations, and the hazards of environmental pollution.

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.

Specialists drawn from industry, agency and academia explain the role of the various elements in the marketing communications process, and show how a reassessment of the marketing mix can result in a positive response to challenges imposed by a changing commercial environment.

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.

Since 1945, "The Annual Deming Conference on Applied Statistics" has been an important event in the statistics profession. In Clinical Trial Biostatistics and Biopharmaceutical Applications, prominent speakers from past Deming conferences present novel biostatistical methodologies in clinical trials as well as up-to-date biostatistical applications from the pharmaceutical industry. Divided into five sections, the book begins with emerging issues in clinical trial design and analysis, including the roles of modeling and simulation, the pros and cons of randomization procedures, the design of Phase II dose-ranging trials, thorough QT/QTc clinical trials, and assay sensitivity and the constancy assumption in noninferiority trials. The second section examines adaptive designs in drug development, discusses the consequences of group-sequential and adaptive designs, and illustrates group sequential design in R. The third section focuses on oncology clinical trials, covering competing risks, escalation with overdose control (EWOC) dose finding, and interval-censored time-to-event data. In the fourth section, the book describes multiple test problems with applications to adaptive designs, graphical approaches to multiple testing, the estimation of simultaneous confidence intervals for multiple comparisons, and weighted parametric multiple testing methods. The final section discusses the statistical analysis of biomarkers from omics technologies, biomarker strategies applicable to clinical development, and the statistical evaluation of surrogate endpoints. This book clarifies important issues when designing and analyzing clinical trials, including several misunderstood and unresolved challenges. It will help readers choose the right method for their biostatistical application. Each chapter is self-contained with references.

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.

"Provides well-integrated, comprehensive coverage of all the major statistical designs and methods used for animal studies in pharmaceutical research and development. Demonstrates the correct way to interpret the results of animal studies in the risk assessment of biopharmaceutical products and clarifies detailed presentations with real-world examples. "

The most significant changes in isolation technology during the past five years have not been in the technology itself but in its increased acceptance. This acceptance is clearly demonstrated by the series of monographs, guidelines, and standards produced by regulatory bodies to describe best practice in the design and operation of isolators. Thoroughly revised and updated, Isolation Technology: A Practical Guide, Second Edition provides an in-depth overview of new standards and new technology. Here's what's new in the Second Edition: "Descriptions of and comments on new guidelines and standards "Technological advances - such as the new breed of sanitizing gas generators "Updates that reflect current thinking and new information Drawing on his vast experience in this field, the author delineates practical ways to improve product standards, increase operator productivity, efficiency and safety, and cut costs. Carefully designed for easy understanding by readers from multiple fields, the book reviews the how-tos for setting up clean rooms and techniques for maintaining sterility, and includes case studies, resource listings, and numerous photographs. The combination of up-to-date information and the author's clear writing style make this the ideal resource for both experienced and beginning professionals.

From the laboratory to full-scale commercial production, this reference provides a clear and in-depth analysis of bioreactor design and operation and encompasses critical aspects of the biocatalytic manufacturing process. It clarifies principles in reaction and biochemical engineering, synthetic and biotransformation chemistry, and biocell and enzyme kinetics for successful applications of biocatalysis and bioprocess technologies in the food, chiral drug, vitamin, pharmaceutical, and animal feed industries. Studying reactions from small to supramolecules, this reference provides an abundant supply of end-of-chapter problems to sharpen understanding of key concepts presented in the text.

Covering every essential element in the development of chiral products, this reference provides a solid overview of the formulation, biopharmaceutical characteristics, and regulatory issues impacting the production of these pharmaceuticals. It supports researchers as they evaluate the pharmacodynamic, pharmacokinetic, and toxicological characteristics of specific enantiomers and chiral drug compounds and addresses in one convenient reference all the major challenges pertaining to drug chirality that have been neglected in the literature. Chirality in Drug Design and Development collects the latest studies from an interdisciplinary team of experts on chiral drug design.

Discussing a comprehensive range of topics, Advanced Pharmaceutics: Physicochemical Principles reviews all aspects of physical pharmacy. The book explains the basic, mechanistic, and quantitative interpretation skills needed to solve physical pharmacy related problems. The author supplies a strong fundamental background and extensively covers thermodynamics, ionic equilibria, solutions and distribution, surface chemistry and colloids, kinetics, diffusion, and polymer science. He outlines the latest research on diffusion through a membrane and the use of polymers in dosage forms. Packed with formulae and models, the book demonstrates the development of each and then describes the use of those models for a variety of formulation situations. The author's detailed explanation of the evolution of the formulae provides a clear understanding of when and how they are used. This bottom-up approach delineates the evolution of the formulae and gives a clear understanding of when and how they should be used. The book provides an in-depth review and analysis of dosage form design criteria that you can rapidly implement in your day-to-day work.

Designed to enable readers to plan and execute their own audits, this comprehensive guide presents both discussions and practical applications related to establishing a GLP QA unit and performing effective GLP audits. The first section provides the foundation of information needed for designing and initiating a Good Laboratory Practice quality assurance program. Section II contains ready-to-use audit checklists and regulatory references that are in accordance with the most recent regulations. Section III illustrates with examples the document requirements of the Quality Assurance Unit and provides a clear understanding of its function. Section IV comprises the full texts of the relevant standards and regulations along with the Principles of Good Laboratory Practice.

Covering regulatory requirements stipulated by the FDA, this book delineates the organization, planning, verification, and documentation activities and procedural controls required for compliance with worldwide computer systems validation regulations. The author introduces supporting technologies such as encryption and digital signatures and places regulatory compliance within the context of quality assurance. He demonstrates the importance of integrating validation activities into the system lifecycle using a structured top-down approach. He covers practical applications of quality assurance and engineering techniques as they relate to the development of systems fit to meet user and regulatory requirements.

The book on Trends in Quorum Sensing and Quorum Quenching: New Perspectives and Applications focuses on the recent advances in the field of quorum sensing in bacteria and the novel strategies developed for quorum sensing inhibition. The topics covered are multidisciplinary and wide-ranging,and includes quorum sensing phenomenon in pathogenic bacteria, food spoilers, and agriculturally relevant bacteria. The applications of quorum sensing inhibitors such as small molecules, bioactives, natural compounds, and quorum quenching enzymes in controlling bacterial infections in clinical settings, agriculture and aquaculture are discussed. The potential use of quorum quenching enzymes for mitigating biofouling is also covered. Special focus is given to exploring quorum sensing inhibitors from microbes and flora inhabiting biodiversity rich regions including tropical rain forests and marine environments. Key features: Covers the fundamental aspects, the progress and challenges in the field of quorum sensing and quorum quenching Reviews quorum sensing in Gram-positive and Gram-negative bacteria of clinical, agricultural, and industrial relevance Discusses the application and future trends of quorum sensing inhibitors from lab to clinical and environmental settings Provides comprehensive coverage on molecular mechanisms in bacterial signaling

While change control can ensure that developments do not compromise business operations, when dealing with pharmaceuticals manufacturing, change control must also ensure that developments do not compromise regulatory compliance. Pharmaceutical Engineering Change Control, Second Edition gives you the technical and management skills required to successfully and efficiently employ change control procedures.

Lists the necessary steps for meeting compliance requirements during the drug development process. Presents comprehensive approaches for validating analytical methods for pharmaceutical applications. Features key discussions on pre-approval inspections.