Target Discovery and Validation

Helps engineers and scientists assess and manage uncertainty at all stages of experimentation and validation of simulations Fully updated from its previous edition, Experimentation, Validation, and Uncertainty Analysis for Engineers, Fourth Edition includes expanded coverage and new examples of applying the Monte Carlo Method (MCM) in performing uncertainty analyses. Presenting the current, internationally accepted methodology from ISO, ANSI, and ASME standards for propagating uncertainties using both the MCM and the Taylor Series Method (TSM), it provides a logical approach to experimentation and validation through the application of uncertainty analysis in the planning, design, construction, debugging, execution, data analysis, and reporting phases of experimental and validation programs. It also illustrates how to use a spreadsheet approach to apply the MCM and the TSM, based on the authors’ experience in applying uncertainty analysis in complex, large-scale testing of real engineering systems. Experimentation, Validation, and Uncertainty Analysis for Engineers, Fourth Edition includes examples throughout, contains end of chapter problems, and is accompanied by the authors’ website www.uncertainty-analysis.com. Guides readers through all aspects of experimentation, validation, and uncertainty analysis Emphasizes the use of the Monte Carlo Method in performing uncertainty analysis Includes complete new examples throughout Features workable problems at the end of chapters Experimentation, Validation, and Uncertainty Analysis for Engineers, Fourth Edition is an ideal text and guide for researchers, engineers, and graduate and senior undergraduate students in engineering and science disciplines. Knowledge of the material in this Fourth Edition is a must for those involved in executing or managing experimental programs or validating models and simulations.

Validation describes the procedures used to analyze pharmaceutical products so that the data generated will comply with the requirements of regulatory bodies of the US, Canada, Europe and Japan. Calibration of Instruments describes the process of fixing, checking or correcting the graduations of instruments so that they comply with those regulatory bodies. This book provides a thorough explanation of both the fundamental and practical aspects of biopharmaceutical and bioanalytical methods validation. It teaches the proper procedures for using the tools and analysis methods in a regulated lab setting. Readers will learn the appropriate procedures for calibration of laboratory instrumentation and validation of analytical methods of analysis. These procedures must be executed properly in all regulated laboratories, including pharmaceutical and biopharmaceutical laboratories, clinical testing laboratories (hospitals, medical offices) and in food and cosmetic testing laboratories.

Systems' Verification Validation and Testing (VVT) are carried out throughout systems' lifetimes. Notably, quality-cost expended on performing VVT activities and correcting system defects consumes about half of the overall engineering cost. Verification, Validation and Testing of Engineered Systems provides a comprehensive compendium of VVT activities and corresponding VVT methods for implementation throughout the entire lifecycle of an engineered system. In addition, the book strives to alleviate the fundamental testing conundrum, namely: What should be tested? How should one test? When should one test? And, when should one stop testing? In other words, how should one select a VVT strategy and how it be optimized? The book is organized in three parts: The first part provides introductory material about systems and VVT concepts. This part presents a comprehensive explanation of the role of VVT in the process of engineered systems (Chapter-1). The second part describes 40 systems' development VVT activities (Chapter-2) and 27 systems' post-development activities (Chapter-3). Corresponding to these activities, this part also describes 17 non-testing systems' VVT methods (Chapter-4) and 33 testing systems' methods (Chapter-5). The third part of the book describes ways to model systems’ quality cost, time and risk (Chapter-6), as well as ways to acquire quality data and optimize the VVT strategy in the face of funding, time and other resource limitations as well as different business objectives (Chapter-7). Finally, this part describes the methodology used to validate the quality model along with a case study describing a system’s quality improvements (Chapter-8). Fundamentally, this book is written with two categories of audience in mind. The first category is composed of VVT practitioners, including Systems, Test, Production and Maintenance engineers as well as first and second line managers. The second category is composed of students and faculties of Systems, Electrical, Aerospace, Mechanical and Industrial Engineering schools. This book may be fully covered in two to three graduate level semesters; although parts of the book may be covered in one semester. University instructors will most likely use the book to provide engineering students with knowledge about VVT, as well as to give students an introduction to formal modeling and optimization of VVT strategy.

Built on a decade of experience with novel molecular diagnostics, this practice-oriented guide shows how to cope with validation issues during all stages of biomarker development, from the first clinical studies to the eventual commercialization of a new diagnostic test.

Practical approaches to ensure that analytical methods and instruments meet GMP standards and requirements Complementing the authors' first book, Analytical Method Validation and Instrument Performance Verification, this new volume provides coverage of more advanced topics, focusing on additional and supplemental methods, instruments, and electronic systems that are used in pharmaceutical, biopharmaceutical, and clinical testing. Readers will gain new and valuable insights that enable them to avoid common pitfalls in order to seamlessly conduct analytical method validation as well as instrument operation qualification and performance verification. Part 1, Method Validation, begins with an overview of the book's risk-based approach to phase appropriate validation and instrument qualification; it then focuses on the strategies and requirements for early phase drug development, including validation of specific techniques and functions such as process analytical technology, cleaning validation, and validation of laboratory information management systems Part 2, Instrument Performance Verification, explores the underlying principles and techniques for verifying instrument performance—coverage includes analytical instruments that are increasingly important to the pharmaceutical industry, such as NIR spectrometers and particle size analyzers—and offers readers a variety of alternative approaches for the successful verification of instrument performance based on the needs of their labs At the end of each chapter, the authors examine important practical problems and share their solutions. All the methods covered in this book follow Good Analytical Practices (GAP) to ensure that reliable data are generated in compliance with current Good Manufacturing Practices (cGMP). Analysts, scientists, engineers, technologists, and technical managers should turn to this book to ensure that analytical methods and instruments are accurate and meet GMP standards and requirements.

When using numerical simulation to make a decision, how can its reliability be determined? What are the common pitfalls and mistakes when assessing the trustworthiness of computed information, and how can they be avoided? Whenever numerical simulation is employed in connection with engineering decision-making, there is an implied expectation of reliability: one cannot base decisions on computed information without believing that information is reliable enough to support those decisions. Using mathematical models to show the reliability of computer-generated information is an essential part of any modelling effort. Giving users of finite element analysis (FEA) software an introduction to verification and validation procedures, this book thoroughly covers the fundamentals of assuring reliability in numerical simulation. The renowned authors systematically guide readers through the basic theory and algorithmic structure of the finite element method, using helpful examples and exercises throughout. Delivers the tools needed to have a working knowledge of the finite element method Illustrates the concepts and procedures of verification and validation Explains the process of conceptualization supported by virtual experimentation Describes the convergence characteristics of the h-, p- and hp-methods Covers the hierarchic view of mathematical models and finite element spaces Uses examples and exercises which illustrate the techniques and procedures of quality assurance Ideal for mechanical and structural engineering students, practicing engineers and applied mathematicians Includes parameter-controlled examples of solved problems in a companion website (www.wiley.com/go/szabo)

A practical approach to enhancing quality in software models using UML Version 2.0 «Despite its increasing usage, many companies are not taking the best advantage of UML and, occasionally, individuals have experienced frustration in applying its standards. Perhaps this is because they have not yet read this book!» -From the Foreword by Prof. Brian Henderson-Sellers This book presents a practical checklist approach to enhancing the quality of software models created with the Unified Modeling Language (UML) Version 2.0. The foundation for quality is set by the discussion on the nature and creation of UML models. This is followed by a demonstration of how to apply verification and validation checks to these models with three foci: syntactical correctness, semantic meaningfulness, and aesthetic symmetry. The quality work is carried out within three distinct yet related modeling spaces: * Model of problem space (MOPS) * Model of solution space (MOSS) * Model of background space (MOBS) Readers can then choose a specific quality approach according to their roles in their projects. Verification and validation checks are also organized according to these three modeling spaces, making it easier for the reader to focus on the appropriate diagrams and quality checks corresponding to their modeling space. In addition, a major element of this publication is the Strengths, Weaknesses, Objectives, and Traps (SWOT) analysis. This analysis is performed on each UML diagram, enabling readers to fully comprehend these diagrams, their advantages and limitations, and the way in which they can be used in practical projects for modeling. A consistent case study of the Lucky Insurance System is provided throughout the chapters to illustrate the creation of good quality UML diagrams, followed by application of quality checks to them. With its emphasis on quality in UML-based projects, this book is an essential resource for all quality professionals, including quality analysts, process consultants, quality managers, test designers, and testers.

This second edition of a global bestseller has been completely redesigned and extensively rewritten to take into account the new Quality by Design (QbD) and lifecycle concepts in pharmaceutical manufacturing. As in the first edition, the fundamental requirements for analytical method validation are covered, but the second edition describes how these are applied systematically throughout the entire analytical lifecycle. QbD principles require adoption of a systematic approach to development and validation that begin with predefined objectives. For analytical methods these predefined objectives are established as an Analytical Target Profile (ATP). The book chapters are aligned with recently introduced standards and guidelines for manufacturing processes validation and follow the three stages of the analytical lifecycle: Method Design, Method Performance Qualification, and Continued Method Performance Verification. Case studies and examples from the pharmaceutical industry illustrate the concepts and guidelines presented, and the standards and regulations from the US (FDA), European (EMA) and global (ICH) regulatory authorities are considered throughout. The undisputed gold standard in the field.

A consolidated and comprehensive reference on ligand-binding assays Ligand-binding assays (LBAs) stand as the cornerstone of support for definition of the pharmaco-kinetics and toxicokinetics of macromolecules, an area of burgeoning interest in the pharmaceutical industry. Yet, outside of the Crystal City Conference proceedings, little guidance has been available for LBA validation, particularly for assays used to support macromolecule drug development. Ligand-Binding Assays: Development, Validation, and Implementation in the Drug Development Arena answers that growing need, serving as a reference text discussing critical aspects of the development, validation, and implementation of ligand-binding assays in the drug development field. Ligand-Binding Assays covers essential topics related to ligand-binding assays, from pharmacokinetic studies, the development of LBAs, assay validation, statistical LBA aspects, and regulatory aspects, to software for LBAs and robotics and other emerging methodologies for LBAs. Highlights include: A general discussion of challenges and proven approaches in the development of ligand-binding assays More detailed examination of characteristics of these assays when applied to support of pharmacokinetic and toxicokinetic studies of compounds at different stages in the discovery or development timeline A concise, but detailed, discussion of validation of ligand-binding assays for macromolecules A practical approach to «fit-for-purpose» validation of assays for biomarkers, those molecules receiving increased attention as potentially demonstrating that the target chosen in discovery is being modulated by the candidate therapeutic, both in nonclinical and clinical studies Written by a team of world-recognized authorities in the field, Ligand-Binding Assays provides key information to a broad range of practitioners, both in the pharmaceutical and allied industries and in related contract research organizations and academic laboratories and, perhaps, even in the field of diagnostics and clinical chemistry.

Validation of Communications Systems with SDL provides a clear practical guide to validating, by simulation, a telecom system modelled in SDL. SDL, the Specification and Description Language standardised by the International Telecommunication Union (ITU-T), is used to specify and develop complex systems such as GSM, GPRS, UMTS, IEEE 802.11 or Hiperlan. Since the downturn in the telecom industry, validating a system before its implementation has become mandatory to reduce costs. This volume guides you step by step through the validation of a simplified protocol layer, from interactive simulation to proof of properties using reachability analysis combined with observers. Every step is explained, using the two main SDL tools commercially available: ObjectGeode™ and Tau SDL™ Suite, both from Telelogic. Contents: Short tutorial on SDL Presentation of the protocol layer case study Interactive simulation, MSC generation Scripting, automatic non-regression Auto matic validation against MSC, HMSC, etc. Random simulation Exhaustive and bit-state simulation Errors detected and not detected by simulation Other simulator features This book offers you the opportunity to: Learn expert validation techniques and tips Master advanced simulation features of Telelogic ObjectGeode™ and Tau SDL Suite™ Practice 156 hands-on exercises with solutions. The SDL models and scripts used in the exercises can be downloaded from the Web.