Preclinical Safety Evaluation Of Biopharmaceuticals

Translational Medicine: Optimizing Preclinical Safety Evaluation of Biopharmaceuticals provides scientists responsible for the translation of novel biopharmaceuticals into clinical trials with a better understanding of how to navigate the obstacles that keep innovative medical research discoveries from becoming new therapies or even making it to clinical trials. The book includes sections on protein-based therapeutics, modified proteins, oligonucleotide-based therapies, monoclonal antibodies, antibody–drug conjugates, gene and cell-based therapies, gene-modified cell-based therapies, combination products, and therapeutic vaccines. Best practices are defined for efficient discovery research to facilitate a science-based, efficient, and predictive preclinical development program to ensure clinical efficacy and safety. Key Features: Defines best practices for leveraging of discovery research to facilitate a development program Includes general principles, animal models, biomarkers, preclinical toxicology testing paradigms, and practical applications Discusses rare diseases Discusses "What-Why-When-How" highlighting different considerations based upon product attributes. Includes special considerations for rare diseases About the Editors Joy A. Cavagnaro is an internationally recognized expert in preclinical development and regulatory strategy with an emphasis on genetic medicines.. Her 40-year career spans academia, government (FDA), and the CRO and biotech industries. She was awarded the 2019 Arnold J Lehman Award from the Society of Toxicology for introducing the concept of science-based, case-by-case approach to preclinical safety evaluation, which became the foundation of ICH S6. She currently serves on scientific advisory boards for advocacy groups and companies and consults and lectures in the area of preclinical development of novel therapies. Mary Ellen Cosenza is a regulatory toxicology consultant with over 30 years of senior leadership experience in the biopharmaceutical industry in the U.S., Europe, and emerging markets. She has held leadership position in both the American College of Toxicology (ACT) and the International Union of Toxicology (IUTOX) and is also an adjunct assistant professor at the University of Southern California where she teaches graduate-level courses in toxicology and regulation of biologics.

"The goal is to provide a comprehensive reference book for the preclinicaldiscovery and development scientist whose responsibilities span target identification, lead candidate selection, pharmacokinetics, pharmacology, and toxicology, and for regulatory scientists whose responsibilities include the evaluation of novel therapies." —From the Afterword by Anthony D. Dayan Proper preclinical safety evaluation can improve the predictive value, lessen the time and cost of launching new biopharmaceuticals, and speed potentially lifesaving drugs to market. This guide covers topics ranging from lead candidate selection to establishing proof of concept and toxicity testing to the selection of the first human doses. With chapters contributed by experts in their specific areas, Preclinical Safety Evaluation of Biopharmaceuticals: A Science-Based Approach to Facilitating Clinical Trials: Includes an overview of biopharmaceuticals with information on regulation and methods of production Discusses the principles of ICH S6 and their implementation in the U.S., Europe, and Japan Covers current practices in preclinical development and includes a comparison of safety assessments for small molecules with those for biopharmaceuticals Addresses all aspects of the preclinical evaluation process, including: the selection of relevant species; safety/toxicity endpoints; specific considerations based upon class; and practical considerations in the design, implementation, and analysis of biopharmaceuticals Covers transitioning from preclinical development to clinical trials This is a hands-on, straightforward reference for professionals involved in preclinical drug development, including scientists, toxicologists, project managers, consultants, and regulatory personnel.

Considerable investment has been made by both pharmaceutical and biotechnology companies in pharmaceutical products of biotechnology. However, because relatively few of these products have been marketed, lack of relevant experience means that uncertainty still surrounds the most appropriate strategy for their safety evaluation. The 13th CMR International Workshop, held in February 1997, provided the opportunity for regulatory authority and industry experts from Europe, Japan and the USA to share their experiences of designing safety evaluation programmes for specific product classes: colony stimulating factors, growth factors, hormones, interferons, interleukins, monoclonal antibodies for therapeutic use, and gene therapy products. Participants worked together to recommend those studies that should be considered for such safety evaluation, and those that may be unnecessary. These recommendations subsequently made a valuable contribution to the ICH guideline `Safety Studies for Biotechnological Products', which was finalised at ICH 4 in Brussels in July 1997. The Workshop proceedings not only describe the recommendations but also provide the reader with an appreciation of the science behind safety evaluation strategies used by experts, the influence of different regulatory systems on these strategies, and the type of data required by both toxicologists and clinicians before they have sufficient confidence to administer pharmaceutical products of biotechnology to humans.

This book aims to provide scientists involved in the translation of novel biopharmaceuticals into clinical trials a better understanding of how best to navigate the valley of death. The goal is to define best practices for efficient leveraging of discovery research to facilitate a science-based, rational, efficient and predictive preclinical development program to ensure clinical efficacy and safety."

Drug Discovery and Evaluation has become a more and more difficult, expensive and time-consuming process. The effect of a new compound has to be detected by in vitro and in vivo methods of pharmacology. The activity spectrum and the potency compared to existing drugs have to be determined. As these processes can be divided up stepwise we have designed a book series "Drug Discovery and Evaluation" in the form of a recommendation document. The methods to detect drug targets are described in the first volume of this series "Pharmacological Assays" comprising classical methods as well as new technologies. Before going to man, the most suitable compound has to be selected by pharmacokinetic studies and experiments in toxicology. These preclinical methods are described in the second volume „Safety and Pharmacokinetic Assays". Only then are first studies in human beings allowed. Special rules are established for Phase I studies. Clinical pharmacokinetics are performed in parallel with human studies on tolerability and therapeutic effects. Special studies according to various populations and different therapeutic indications are necessary. These items are covered in the third volume: „Methods in Clinical Pharmacology".

New edition of succesful standard reference book for thepharmaceutical industry and pharmaceutical physicians! The Textbook of Pharmaceutical Medicine is the coursebookfor the Diploma in Pharmaceutical Medicine, and is used as astandard reference throughout the pharmaceutical industry. The newedition includes greater coverage of good clinical practice, acompletely revised statistics chapter, and more on safety. Coversthe course information for the Diploma in PharmaceuticalMedicine Fully updated, with new authors Greater coverage of good clinical practice and safety New chapters on regulation of medical devices in Europe andregulation of therapeutic products in Australia

This book illustrates, in a comprehensive manner, the most current areas of importance to Safety Pharmacology, a burgeoning unique pharmacological discipline with important ties to academia, industry and regulatory authorities. It provides readers with a definitive collection of topics containing essential information on the latest industry guidelines and overviews current and breakthrough topics in both functional and molecular pharmacology. An additional novelty of the book is that it constitutes academic, pharmaceutical and biotechnology perspectives for Safety Pharmacology issues. Each chapter is written by an expert in the area and includes not only a fundamental background regarding the topic but also detailed descriptions of currently accepted, validated models and methods as well as innovative methodologies used in drug discovery.

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. Features, Focuses on the quantitative evaluation of safety of biopharmaceutical products, Covers several Bayesian approaches, including a meta-experimental design for evaluating cardiovascular risk, adaptive trials for drug safety, and network meta-analysis for safety evaluation, Explains why a DMC safety report differs from a safety report written at the end of the trial, Describes the safety surveillance and signal detection process, Discusses the observational medical outcomes partnership (OMOP), Addresses regulatory issues in the meta-analysis of safety data, Presents safety evaluation and quantitative approaches during preclinical and early phases of drug development, 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. Book jacket.