Pharmaceutical Drug Product Development And Process Optimization

Pharmaceutical manufacturers are constantly facing quality crises of drug products, leading to an escalating number of product recalls and rejects. Due to the involvement of multiple factors, the goal of achieving consistent product quality is always a great challenge for pharmaceutical scientists. This volume addresses this challenge by using the Quality by Design (QbD) concept, which was instituted to focus on the systematic development of drug products with predefined objectives to provide enhanced product and process understanding. This volume presents and discusses the vital precepts underlying the efficient, effective, and cost effective development of pharmaceutical drug products. It focuses on the adoption of systematic quality principles of pharmaceutical development, which is imperative in achieving continuous improvement in end-product quality and also leads to reducing cost, time, and effort, while meeting regulatory requirements. The volume covers the important new advances in the development of solid oral dosage forms, modified release oral dosage forms, parenteral dosage forms, semisolid dosage forms, transdermal drug, delivery systems, inhalational dosage forms, ocular drug delivery systems, nanopharmaceutical products, and nanoparticles for oral delivery.

This volume presents and discusses the vital precepts underlying the efficient, effective, and cost-effective development of pharmaceutical drug products. It focuses on the adoption of systematic quality principles of pharmaceutical development.

Optimization of Pharmaceutical Processes presents contributions from leading authorities in the fields of optimization and pharmaceutical manufacturing. Formulated within structured frameworks, practical examples and applications are given as guidance to apply optimization techniques to most aspects of pharmaceutical processes from design, to lab and pilot scale, and finally to manufacturing. The increasing demand for better quality, higher yield, more efficient-optimized and green pharmaceutical processes, indicates that optimal conditions for production must be applied to achieve simplicity, lower costs and superior yield. The application of such methods in the pharmaceutical industry is not trivial. Quality of the final product is of major importance to human health and the need for deep knowledge of the process parameters and the optimization of the processes are imperative. The volume, which includes new methods as well as review contributions will benefit a wide readership including engineers in pharmaceuticals, chemical, biological, to name just a few.

Pharmaceutical product development is a multidisciplinary activity involving extensive efforts in systematic product development and optimization in compliance with regulatory authorities to ensure the quality, efficacy and safety of resulting products. Pharmaceutical Product Development equips the pharmaceutical formulation scientist with extensive and up-to-date knowledge of drug product development and covers all steps from the beginning of product conception to the final packaged form that enters the market and lifecycle management thereof. Applications of core scientific principles for product development are also thoroughly discussed in conjunction with the latest approaches involving design of experiment and quality by design with comprehensive illustrations based on practical case studies of several dosage forms. The book presents pharmaceutical product development information in an easy-to-read mode with simplified theories, case studies and guidelines for students, academicians and professionals in the pharmaceutical industry. It is an invaluable resource and hands-on guide covering managerial, regulatory and practical aspects of pharmaceutical product lifecycle management.

A comprehensive look at existing technologies and processes for continuous manufacturing of pharmaceuticals As rising costs outpace new drug development, the pharmaceutical industry has come under intense pressure to improve the efficiency of its manufacturing processes. Continuous process manufacturing provides a proven solution. Among its many benefits are: minimized waste, energy consumption, and raw material use; the accelerated introduction of new drugs; the use of smaller production facilities with lower building and capital costs; the ability to monitor drug quality on a continuous basis; and enhanced process reliability and flexibility. Continuous Manufacturing of Pharmaceuticals prepares professionals to take advantage of that exciting new approach to improving drug manufacturing efficiency. This book covers key aspects of the continuous manufacturing of pharmaceuticals. The first part provides an overview of key chemical engineering principles and the current regulatory environment. The second covers existing technologies for manufacturing both small-molecule-based products and protein/peptide products. The following section is devoted to process analytical tools for continuously operating manufacturing environments. The final two sections treat the integration of several individual parts of processing into fully operating continuous process systems and summarize state-of-art approaches for innovative new manufacturing principles. Brings together the essential know-how for anyone working in drug manufacturing, as well as chemical, food, and pharmaceutical scientists working on continuous processing Covers chemical engineering principles, regulatory aspects, primary and secondary manufacturing, process analytical technology and quality-by-design Contains contributions from researchers in leading pharmaceutical companies, the FDA, and academic institutions Offers an extremely well-informed look at the most promising future approaches to continuous manufacturing of innovative pharmaceutical products Timely, comprehensive, and authoritative, Continuous Manufacturing of Pharmaceuticals is an important professional resource for researchers in industry and academe working in the fields of pharmaceuticals development and manufacturing.

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.

Very little has been published on optimization of pharmaceutical portfolios. Moreover, most of published literature is coming from the commercial side, where probability of technical success (PoS) is treated as fixed, and not as a consequence of development strategy or design. In this book there is a strong focus on impact of study design on PoS and ultimately on the value of portfolio. Design options that are discussed in different chapters are dose-selection strategies, adaptive design and enrichment. Some development strategies that are discussed are indication sequencing, optimal number of programs and optimal decision criteria. This book includes chapters written by authors with very broad backgrounds including financial, clinical, statistical, decision sciences, commercial and regulatory. Many authors have long held executive positions and have been involved with decision making at a product or at a portfolio level. As such, it is expected that this book will attract a very broad audience, including decision makers in pharmaceutical R&D, commercial and financial departments. The intended audience also includes portfolio planners and managers, statisticians, decision scientists and clinicians. Early chapters describe approaches to portfolio optimization from big Pharma and Venture Capital standpoints. They have stronger focus on finances and processes. Later chapters present selected statistical and decision analysis methods for optimizing drug development programs and portfolios. Some methodological chapters are technical; however, with a few exceptions they require a relatively basic knowledge of statistics by a reader.

As with all of pharmaceutical production, the regulatory environment for the production of therapeutics has been changing as a direct result of the US FDA-initiated Quality by Design (QbD) guidelines and corresponding activities of the International Committee for Harmonization (ICH). Given the rapid growth in the biopharmaceutical area and the complexity of the molecules, the optimum use of which are still being developed, there is a great need for flexible and proactive teams in order to satisfy the regulatory requirements during process development. Process Analytical Technologies (PAT) applied in biopharmaceutical process development and manufacturing have received significant attention in recent years as an enabler to the QbD paradigm. PAT Applied in Biopharmaceutical Process Development and Manufacturing covers technological advances in measurement sciences, data acquisition, monitoring, and control. Technical leaders present real-life case studies in areas including measuring and monitoring raw materials, cell culture, purification, and cleaning and lyophilization processes via advanced PAT. They also explore how data are collected and analyzed using advanced analytical techniques such as multivariate data analysis, monitoring, and control in real-time. Invaluable for experienced practitioners in PAT in biopharmaceuticals, this book is an excellent reference guide for regulatory officials and a vital training aid for students who need to learn the state of the art in this interdisciplinary and exciting area.