This volume provides a complete update of all the materials in prior volumes on the subject (including current directories to testing labs and other support establishments worldwide), while adding substantial new material on the following topics: * The history of CROs, including snapshots of CROs and a genealogy chart making clear where they came from and where they went. * Study directors and principal investigators. * The nuts and bolts of study performance. * Electronic reporting requirements - SEND and eCTD (required for NDA, BLA, ANDA, and IND submissions). * Consultants and their roles. * An expanded examination of common problems and their solutions. This book boasts complete directories to the global universe of operating labs - where they are, how to contact them, and what they do (including special capabilities). Additionally, checklists for qualifying labs and manufacturing facilities - and for auditing studies and projects at such facilities - are included. It is directed at those in industry (specifically directed at those working for companies using CRO services) but will also be of interest to scientists or administrators working in research organizations themselves. In this case, the contents of this new work are essential to the target reader because the work, regulations, and actors (CROs) have evolved and changed at a rapid pace in the 10 years since the earlier volume that the author published. Likewise, the companies using these services have come to all be almost completely dependent on outsourcing. The earlier texts remain the only source of their kind (paper or electronic) on the field and the only noncommercial guide to the global industry and this volume provides a complete update.

The last 10 years have seen a seismic shift in therapeutic product development and testing. In both the pharmaceutical (both small and large molecule) and medical device sectors, the vast majority of testing and evaluation of products is not performed within innovator companies, but rather has been outsourced to a growing universe of commercial organizations. The authors both have more than 30 years experience in this field, and both have worked within innovator companies, for CROs, and as consultants in the field. "Contract Research and Development Organizations: Their Role in Global Product Development" has been crafted by these authors to provide a how to guide for all aspects of working with CROs in selecting, working with and ensuring the best possible desirable outcome of having the R&D function, or substantial parts of it, outsourced. It uses as the exemplary case nonclinical safety assessment, biocompatibility and efficacy testing which are to be performed to select the best possible candidate compound, device or formulation and then moving the resulting regulated therapeutic medical product into and through the development process and to marketing approval. But also covered are the contract synthesis of drug substances and corresponding manufacture of biologics and manufacture of products, formulation development, clinical evaluation, regulatory and document preparation support, and use of consultants.

Included in the volume are an exhaustive listing of those CROs in the (drug and device) safety evaluation sector and their contact information and capabilities, and extensive similar listing for the other types of contract service providers. Also included are guidances on how to monitor ongoing work at contract facilities and audit check lists for GLP, GMP and GCP facilities. These listings are international in scope, and a specific chapter addresses working with some of the newer international CROs. "

The inspiration for this text was the 1988 volume by Alder and Zbinden, written before the ICH harmonization process for drug safety evaluation (or its ISO analog for device biocompatibility evaluation) had been initiated or come to force. Since then, much has changed in both the world and practice of medicine and the regulation of drugs. The intent of this volume is to provide similar guidance as to what nonclinical safety assessment tests need to be performed to move a drug into man, through development and to market approved (this intent was subsequently extended to cover the closely related medical device biotechnology, and combination product fields) in a concise, abbreviated manner for all the major world market countries.

While the safety assessment ("biocompatibility") of medical devices has been focused on issues of local tissue tolerance (irritation, sensitization, cytotoxicity) and selected quantal effects (genotoxicity and acute lethality) since first being regulated in the late 1950s, this has changed as devices assumed a much more important role in healthcare and became more complex in both composition and in their design and operation. Add to this that devices now frequently serve as delivery systems for drugs, and that drugs may be combined with devices to improve device performance, and the problems of ensuring patient safety with devices has become significantly more complex. A part of this, requirements for ensuring safety (once based on use of previously acceptable materials - largely polymers and metals) have come to requiring determining which chemical entities are potentially released from a device into patients (and how much is released). Then an appropriate and relevant (yet also conservative) risk assessment must be performed for each identified chemical structure. The challenges inherent in meeting the current requirements are multifold, and this text seeks to identify, understand, and solve all of them. * Identify and verify the most appropriate available data. * As in most cases such data is for a different route of exposure, transform it for use in assessing exposure by the route of interest. * As the duration (and rate) of exposure to moieties released from a device are most frequently different (longer) than what available data speaks to, transformation across tissue is required. * As innate and adaptive immune responses are a central part of device/patient interaction, assessing potential risks on this basis are required. * Incorporating assessments for special populations such as neonates. * Use of (Q)SAR (Quantitative Structure Activity Relationships) modeling in assessments. * Performance and presentation of integrative assessments covering all potential biologic risks. Appendices will contain summarized available biocompatibility data for commonly used device materials (polymers and metals) and safety assessments on the frequently seen moieties in extractions from devices.

This practical book provides toxicologists with essential information on the regulations that govern their jobs and products. Regulatory Toxicology, Third Edition is an up-to-date guide to required safety assessment for the entire range of man-made marketed products. Individual chapters written by experts with extensive experience in the field address requirements not only for human pharmaceuticals and medical devices (for which there are available guidances), but for the full range of man-made products. New in this edition are three chapters addressing Safety Data Sheet Preparation, Regulatory Requirements for GMOs, and Regulatory Requirements for Tobacco and Marijuana. The major administrative divisions for regulatory agencies and their main responsibilities are also detailed, as are the basic filing documents the agencies require. Coverage includes food additives, dietary supplements, cosmetics, over-the-counter drugs, personal care and consumer products, agriculture and GMO products, industrial chemicals, air and drinking water regulations and the special cases of California's Proposition 65, requirements for safety data sheets, and oversight regulations. Both US and international requirements are clearly presented and referenced. In one volume, those who have regulatory responsibility in companies, lawyers, educators, and those selling these materials in the marketplace can learn about regulatory requirements and how to meet them.

Contents:
1. Introduction 2. The Pharmaceutical Development Process 3. The Medical Device Development Process 4. Functions and Types of CRO's (referencing function listings in appendices) 5. Selection of CRO 6. Pricing and Cost 7. Monitoring Work 8. Common Problems and their Solutions

If we will ever achieve Paul Ehrlich's "magic bullet," that is, a molecule which goes with high selectivity to the therapeutic target site, does what it needs to do, and is subsequently cleared from the body, the practice of safety assessment will have to change. Nonclinical Drug Administration: Formulations, Routes and Regimens for Solving Drug Delivery Problems in Animal Model Systems seeks to address a trio of objectives that, though separate, are linked and central to biomedical science and, ultimately, medicine. Rather seeing these as separate "silos," those working in nonclinical safety assessment will have to view these three in an integrated manner and to regularly and thoughtfully incorporate new information and technology. The trio of objectives this book explores are: first, to present how to deliver more of a drug product systemically to facilitate the regulatory need for evaluating safety and efficacy in animal species (at elevated exposure levels) prior to advancing the drug to human testing; second is to achieve better tolerance to therapeutics administration in test animals and humans which achieves objectives 1 and 3; and third, to explore ways to improve on therapeutic target receptor delivery performance, therefore improving both clinical pharmacodynamics bioavailability and specificity. The book's ten chapters assemble the basic concepts, principles and hypotheses involved in quantitative receptor and chronological organism interaction dynamics central to the successful development of new therapeutics which depend on systemic administration to achieve desired therapeutic goals and in so doing avoid outcomes which limit, marginalize, or preclude the therapeutic use of so many molecules.

The inspiration for this text was the 1988 volume by Alder and Zbinden, written before the ICH harmonization process for drug safety evaluation (or its ISO analog for device biocompatibility evaluation) had been initiated or come to force. Since then, much has changed in both the world and practice of medicine and the regulation of drugs. The intent of this volume is to provide similar guidance as to what nonclinical safety assessment tests need to be performed to move a drug into man, through development and to market approved (this intent was subsequently extended to cover the closely related medical device biotechnology, and combination product fields) in a concise, abbreviated manner for all the major world market countries.

Safety pharmacology is the evaluation and study of the pharmacological effects of a potential drug that are unrelated to the desired therapeutic effect. These effects often present a hazard-particularly in individuals with compromised or limited organ system functions. Safety Pharmacology in Pharmaceutical Development: Approval and Post Marketing Surveillance, Second Edition covers safety pharmacology from the regulatory requirements down to the studies that must be done to justify them. Using the author's more than 30 years of direct experience, the book incorporates tricks and practical insights for making studies work and understanding why they fail. The second edition includes current regulations, including USFDA and those from Europe and Japan. Presenting a clear description of what is needed and why for supporting drug development, the book focuses on updated test methods, interpretation, and science. It covers the core and supplemental batteries of test procedures and how to do them and provides an overview of available facilities and contract organizations for performing studies.

Capturing the growth of the global medical device market in recent years, this practical new guide is essential for all who are responsible for ensuring safety in the use and manufacture of medical devices. It has been extensively updated to reflect significant advances, incorporating combination products and helpful case examples of current real-life problems in the field. The Third Edition explores these key current trends: global device markets continually advancing technology the increasing harmonization of device safety regulation worldwide Each aspect of safety evaluation is considered in terms of International Standards Organization (ISO), US Food and Drug Administration (FDA), European Union (EU), and Japanese Ministry of Health and Welfare (MHW) perspectives. In addition, the book reflects the role of the continuing growth of technology in the incorporation of science, particularly in the areas of immunotoxicology and toxicokinetics.

This volume provides a complete update of all the materials in prior volumes on the subject (including current directories to testing labs and other support establishments worldwide), while adding substantial new material on the following topics: * The history of CROs, including snapshots of CROs and a genealogy chart making clear where they came from and where they went. * Study directors and principal investigators. * The nuts and bolts of study performance. * Electronic reporting requirements - SEND and eCTD (required for NDA, BLA, ANDA, and IND submissions). * Consultants and their roles. * An expanded examination of common problems and their solutions. This book boasts complete directories to the global universe of operating labs - where they are, how to contact them, and what they do (including special capabilities). Additionally, checklists for qualifying labs and manufacturing facilities - and for auditing studies and projects at such facilities - are included. It is directed at those in industry (specifically directed at those working for companies using CRO services) but will also be of interest to scientists or administrators working in research organizations themselves. In this case, the contents of this new work are essential to the target reader because the work, regulations, and actors (CROs) have evolved and changed at a rapid pace in the 10 years since the earlier volume that the author published. Likewise, the companies using these services have come to all be almost completely dependent on outsourcing. The earlier texts remain the only source of their kind (paper or electronic) on the field and the only noncommercial guide to the global industry and this volume provides a complete update.

While the safety assessment ("biocompatibility") of medical devices has been focused on issues of local tissue tolerance (irritation, sensitization, cytotoxicity) and selected quantal effects (genotoxicity and acute lethality) since first being regulated in the late 1950s, this has changed as devices assumed a much more important role in healthcare and became more complex in both composition and in their design and operation. Add to this that devices now frequently serve as delivery systems for drugs, and that drugs may be combined with devices to improve device performance, and the problems of ensuring patient safety with devices has become significantly more complex. A part of this, requirements for ensuring safety (once based on use of previously acceptable materials - largely polymers and metals) have come to requiring determining which chemical entities are potentially released from a device into patients (and how much is released). Then an appropriate and relevant (yet also conservative) risk assessment must be performed for each identified chemical structure. The challenges inherent in meeting the current requirements are multifold, and this text seeks to identify, understand, and solve all of them. * Identify and verify the most appropriate available data. * As in most cases such data is for a different route of exposure, transform it for use in assessing exposure by the route of interest. * As the duration (and rate) of exposure to moieties released from a device are most frequently different (longer) than what available data speaks to, transformation across tissue is required. * As innate and adaptive immune responses are a central part of device/patient interaction, assessing potential risks on this basis are required. * Incorporating assessments for special populations such as neonates. * Use of (Q)SAR (Quantitative Structure Activity Relationships) modeling in assessments. * Performance and presentation of integrative assessments covering all potential biologic risks. Appendices will contain summarized available biocompatibility data for commonly used device materials (polymers and metals) and safety assessments on the frequently seen moieties in extractions from devices.

The last 10 years have seen a seismic shift in therapeutic product development and testing. In both the pharmaceutical (both small and large molecule) and medical device sectors, the vast majority of testing and evaluation of products is not performed within innovator companies, but rather has been outsourced to a growing universe of commercial organizations. The authors both have more than 30 years experience in this field, and both have worked within innovator companies, for CROs, and as consultants in the field. Contract Research and Development Organizations: Their Role in Global Product Development has been crafted by these authors to provide a how to guide for all aspects of working with CROs in selecting, working with and ensuring the best possible desirable outcome of having the R&D function, or substantial parts of it, outsourced. It uses as the exemplary case nonclinical safety assessment, biocompatibility and efficacy testing which are to be performed to select the best possible candidate compound, device or formulation and then moving the resulting regulated therapeutic medical product into and through the development process and to marketing approval. But also covered are the contract synthesis of drug substances and corresponding manufacture of biologics and manufacture of products, formulation development, clinical evaluation, regulatory and document preparation support, and use of consultants. Included in the volume are an exhaustive listing of those CROs in the (drug and device) safety evaluation sector and their contact information and capabilities, and extensive similar listing for the other types of contract service providers. Also included are guidances on how to monitor ongoing work at contract facilities and audit check lists for GLP, GMP and GCP facilities. These listings are international in scope, and a specific chapter addresses working with some of the newer international CROs.

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

Toxicology of the Gastrointestinal Tract focuses on the specifics of the mechanisms and adverse effects of xenobiotic agents and pharmaceuticals on the structure and function of the GI tract. The book focuses on a number of specific areas of intestinal research. Beginning with the well-recognized and major functions of nutrient absorption and its role as a protective barrier, the text elaborates on the expanding body of knowledge that relates to the intestines as a major metabolic and immunologic organ involved in the synthesis and degradation of both natural and foreign substances. It includes an overview of the function and dysfunction of the human absorptive process and the effects of microbial flora on these processes, as well as specific classes of toxicants that target the GI tract. The international panel of contributors presents a critical appraisal of the interactions of chemicals and drugs with the gastrointestinal system and the experimental methods and regions of research on which to focus future efforts.

Providing a complete and multidisciplinary overview of the gastrointestinal system both in health and as it is involved in the toxicity of exogenous agents, Toxicology of the Gastrointestinal Tract brings together the current and growing knowledge of this critical organ system in a single volume.