Quality by Design for Biopharmaceuticals

Quality by Design reflects the research and applied training conducted at Dartmouth Medical School under the leadership of Gene Nelson, Paul Batalden, and Marjorie Godfrey. The book includes the research results of high-performing clinical microsystems, illustrative case studies that highlight individual clinical programs, guiding principles that are easily applied, and tools, techniques, and methods that can be adapted by clinical practices and interdisciplinary clinical teams. The authors describe how to develop microsystems that can attain peak performance through active engagement of interdisciplinary teams in learning and applying improvement science and measurement; explore the essence of leadership for clinical Microsystems; show what mid-level leaders can do to enable peak performance at the front lines of care; outline the design and redesign of services and planning care to match patient needs with services offered; examine the issue of safety; describe the vital role of data in creating a rich and useful information environment; provide a core curriculum that can build microsystems’ capability, provide excellent care, promote a positive work environment, and contribute to the larger organization. Ancillary materials for use in classroom teaching, training, or coaching are available at https://clinicalmicrosystem.org/

A practical guide to Quality by Design for pharmaceutical product development Pharmaceutical Quality by Design: A Practical Approach outlines a new and proven approach to pharmaceutical product development which is now being rolled out across the pharmaceutical industry internationally. Written by experts in the field, the text explores the QbD approach to product development. This innovative approach is based on the application of product and process understanding underpinned by a systematic methodology which can enable pharmaceutical companies to ensure that quality is built into the product. Familiarity with Quality by Design is essential for scientists working in the pharmaceutical industry. The authors take a practical approach and put the focus on the industrial aspects of the new QbD approach to pharmaceutical product development and manufacturing. The text covers quality risk management tools and analysis, applications of QbD to analytical methods, regulatory aspects, quality systems and knowledge management. In addition, the book explores the development and manufacture of drug substance and product, design of experiments, the role of excipients, multivariate analysis, and include several examples of applications of QbD in actual practice. This important resource: Covers the essential information about Quality by Design (QbD) that is at the heart of modern pharmaceutical development Puts the focus on the industrial aspects of the new QbD approach Includes several illustrative examples of applications of QbD in practice Offers advanced specialist topics that can be systematically applied to industry Pharmaceutical Quality by Design offers a guide to the principles and application of Quality by Design (QbD), the holistic approach to manufacturing that offers a complete understanding of the manufacturing processes involved, in order to yield consistent and high quality products.

Covers a widespread view of Quality by Design (QbD) encompassing the many stages involved in the development of a new drug product. The book provides a broad view of Quality by Design (QbD) and shows how QbD concepts and analysis facilitate the development and manufacture of high quality products. QbD is seen as a framework for building process understanding, for implementing robust and effective manufacturing processes and provides the underpinnings for a science-based regulation of the pharmaceutical industry. Edited by the three renowned researchers in the field, Comprehensive Quality by Design for Pharmaceutical Product Development and Manufacture guides pharmaceutical engineers and scientists involved in product and process development, as well as teachers, on how to utilize QbD practices and applications effectively while complying with government regulations. The material is divided into three main sections: the first six chapters address the role of key technologies, including process modeling, process analytical technology, automated process control and statistical methodology in supporting QbD and establishing the associated design space. The second section consisting of seven chapters present a range of thoroughly developed case studies in which the tools and methodologies discussed in the first section are used to support specific drug substance and drug-product QbD related developments. The last section discussed the needs for integrated tools and reviews the status of information technology tools available for systematic data and knowledge management to support QbD and related activities. Highlights Demonstrates Quality by Design (QbD) concepts through concrete detailed industrial case studies involving of the use of best practices and assessment of regulatory implications Chapters are devoted to applications of QbD methodology in three main processing sectors—drug substance process development, oral drug product manufacture, parenteral product processing, and solid-liquid processing Reviews the spectrum of process model types and their relevance, the range of state-of-the-art real-time monitoring tools and chemometrics, and alternative automatic process control strategies and methods for both batch and continuous processes The role of the design space is demonstrated through specific examples and the importance of understanding the risk management aspects of design space definition is highlighted Comprehensive Quality by Design for Pharmaceutical Product Development and Manufacture is an ideal book for practitioners, researchers, and graduate students involved in the development, research, or studying of a new drug and its associated manufacturing process.

The state of the art in biopharmaceutical FUSION PROTEIN DESIGN Fusion proteins belong to the most lucrative biotech drugs—with Enbrel® being one of the best-selling biologics worldwide. Enbrel® represents a milestone of modern therapies just as Humulin®, the first therapeutic recombinant protein for human use, approved by the FDA in 1982 and Orthoclone® the first monoclonal antibody reaching the market in 1986. These first generation molecules were soon followed by a plethora of recombinant copies of natural human proteins, and in 1998, the first de novo designed fusion protein was launched. Fusion Protein Technologies for Biopharmaceuticals examines the state of the art in developing fusion proteins for biopharmaceuticals, shedding light on the immense potential inherent in fusion protein design and functionality. A wide pantheon of international scientists and researchers deliver a comprehensive and complete overview of therapeutic fusion proteins, combining the success stories of marketed drugs with the dynamic preclinical and clinical research into novel drugs designed for as yet unmet medical needs. The book covers the major types of fusion proteins—receptor-traps, immunotoxins, Fc-fusions and peptibodies—while also detailing the approaches for developing, delivering, and improving the stability of fusion proteins. The main body of the book contains three large sections that address issues key to this specialty: strategies for extending the plasma half life, the design of toxic proteins, and utilizing fusion proteins for ultra specific targeting. The book concludes with novel concepts in this field, including examples of highly relevant multifunctional antibodies. Detailing the innovative science, commercial realities, and brilliant potential of fusion protein therapeutics, Fusion Protein Technologies for Biopharmaceuticals is a must for pharmaceutical scientists, biochemists, medicinal chemists, molecular biologists, pharmacologists, and genetic engineers interested in determining the shape of innovation in the world of biopharmaceuticals.

The latest edition of this highly acclaimed textbook, provides a comprehensive and up-to-date overview of the science and medical applications of biopharmaceutical products. Biopharmaceuticals refers to pharmaceutical substances derived from biological sources, and increasingly, it is synonymous with 'newer' pharmaceutical substances derived from genetic engineering or hybridoma technology. This superbly written review of the important areas of investigation in the field, covers drug production, plus the biochemical and molecular mechanisms of action together with the biotechnology of major biopharmaceutical types on the market or currently under development. There is also additional material reflecting both the technical advances in the area and detailed information on key topics such as the influence of genomics on drug discovery.

Written for industrial and academic researchers and development scientists in the life sciences industry, Bioprocessing Technology for Production of Biopharmaceuticals and Bioproducts is a guide to the tools, approaches, and useful developments in bioprocessing. This important guide: • Summarizes state-of-the-art bioprocessing methods and reviews applications in life science industries • Includes illustrative case studies that review six milestone bio-products • Discuses a wide selection of host strain types and disruptive bioprocess technologies

Chitosan is a linear polysaccharide commercially produced by the deacetylation of chitin. It is non-toxic, biodegradable, biocompatible, and acts as a bioadhesive with otherwise unstable biomolecules – making it a valuable component in the formulation of biopharmaceutical drugs. Chitosan-Based Systems for Biopharmaceuticals provides an extensive overview of the application of chitosan and its derivatives in the development and optimisation of biopharmaceuticals. The book is divided in four different parts. Part I discusses general aspects of chitosan and its derivatives, with particular emphasis on issues related to the development of biopharmaceutical chitosan-based systems. Part II deals with the use of chitosan and derivatives in the formulation and delivery of biopharmaceuticals, and focuses on the synergistic effects between chitosan and this particular subset of pharmaceuticals. Part III discusses specific applications of chitosan and its derivatives for biopharmaceutical use. Finally, Part IV presents diverse viewpoints on different issues such as regulatory, manufacturing and toxicological requirements of chitosan and its derivatives related to the development of biopharmaceutical products, as well as their patent status, and clinical application and potential. Topics covered include: chemical and technological advances in chitins and chitosans useful for the formulation of biopharmaceuticals physical properties of chitosan and derivatives in sol and gel states absorption promotion properties of chitosan and derivatives biocompatibility and biodegradation of chitosan and derivatives biological and pharmacological activity of chitosan and derivatives biological, chemical and physical compatibility of chitosan and biopharmaceuticals approaches for functional modification or crosslinking of chitosan use of chitosan and derivatives in conventional biopharmaceutical dosage forms manufacture techniques of chitosan-based microparticles and nanoparticles for biopharmaceuticals chitosan and derivatives for biopharmaceutical use: mucoadhesive properties chitosan-based systems for mucosal delivery of biopharmaceuticals chitosan-based delivery systems for mucosal vaccination chitosan-based nanoparticulates for oral delivery of biopharmaceuticals chitosan-based systems for ocular delivery of biopharmaceuticals chemical modification of chitosan for delivery of DNA and siRNA target-specific chitosan-based nanoparticle systems for nucleic acid delivery functional PEGylated chitosan systems for biopharmaceuticals stimuli-sensitive chitosan-based systems for biopharmaceuticals chitosan copolymers for biopharmaceuticals application of chitosan for anti-cancer biopharmaceutical delivery chitosan-based biopharmaceuticals scaffolds in tissue engineering and regenerative medicine wound healing properties of chitosan and its use in wound dressing biopharmaceuticals toxicological properties of chitosan and derivatives for biopharmaceutical applications regulatory status of chitosan and derivatives patentability and intellectual property issues quality control and good manufacturing practice preclinical and clinical use of chitosan and derivatives for biopharmaceuticals Chitosan-Based Systems for Biopharmaceuticals is an important compendium of fundamental concepts, practical tools and applications of chitosan-based biopharmaceuticals for researchers in academia and industry working in drug formulation and delivery, biopharmaceuticals, medicinal chemistry, pharmacy, bioengineering and new materials development.

Everyone involved in a building project wants to achieve a better building but design quality means different things to clients, users, architects, cost consultants and contractors. Negotiating design priorities is an important part of the development process. The Design Quality Manual helps give an objective evaluation of the qualitative aspects of design. Matrices with five defined levels of quality have been developed that cover the key areas of architecture, environmental engineering, user comfort conditions, whole-life costs, detail design and user satisfaction. These can be scored by a visual survey and professional judgement and then augmented by scientific measurement where possible (e.g. temperature, lighting and sound levels). The resultant scores allow comparisons in terms of overall and specific aspects of building performance and design quality. The Manual covers schools, hospitals and housing and offers a set of criteria by which to judge a broad range of design values; it focuses the design team on the needs of the end user and on the overall building performance.

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.

Praise for the Second Edition «As a comprehensive statistics reference book for quality improvement, it certainly is one of the best books available.» —Technometrics This new edition continues to provide the most current, proven statistical methods for quality control and quality improvement The use of quantitative methods offers numerous benefits in the fields of industry and business, both through identifying existing trouble spots and alerting management and technical personnel to potential problems. Statistical Methods for Quality Improvement, Third Edition guides readers through a broad range of tools and techniques that make it possible to quickly identify and resolve both current and potential trouble spots within almost any manufacturing or nonmanufacturing process. The book provides detailed coverage of the application of control charts, while also exploring critical topics such as regression, design of experiments, and Taguchi methods. In this new edition, the author continues to explain how to combine the many statistical methods explored in the book in order to optimize quality control and improvement. The book has been thoroughly revised and updated to reflect the latest research and practices in statistical methods and quality control, and new features include: Updated coverage of control charts, with newly added tools The latest research on the monitoring of linear profiles and other types of profiles Sections on generalized likelihood ratio charts and the effects of parameter estimation on the properties of CUSUM and EWMA procedures New discussions on design of experiments that include conditional effects and fraction of design space plots New material on Lean Six Sigma and Six Sigma programs and training Incorporating the latest software applications, the author has added coverage on how to use Minitab software to obtain probability limits for attribute charts. new exercises have been added throughout the book, allowing readers to put the latest statistical methods into practice. Updated references are also provided, shedding light on the current literature and providing resources for further study of the topic. Statistical Methods for Quality Improvement, Third Edition is an excellent book for courses on quality control and design of experiments at the upper-undergraduate and graduate levels. the book also serves as a valuable reference for practicing statisticians, engineers, and physical scientists interested in statistical quality improvement.