This detailed volume brings together leading practitioners in the freeze-drying community to address recent progress, not only in new analytical tools and applications of the data derived in cycle design but also in the manufacturing of lyophilized products in the healthcare sector – whether these be therapeutics, vaccines or diagnostic products - and indeed the equipment to deliver this scale of freeze-drying. Areas of focus include analytical and formulation issues, process monitoring and control, as well as post-lyophilization analysis. Written for the Methods in Pharmacology and Toxicology series, chapters include the type of expert advice that leads to superior results in the lab. Authoritative and practical, Lyophilization of Pharmaceuticals and Biologicals: New Technologies and Approaches serves as an ideal guide for researchers working in or just seeking an update on this rapidly changing field.
A comprehensive source of information about modern drying technologies that uniquely focus on the processing of pharmaceuticals and biologicals Drying technologies are an indispensable production step in the pharmaceutical industry and the knowledge of drying technologies and applications is absolutely essential for current drug product development. This book focuses on the application of various drying technologies to the processing of pharmaceuticals and biologicals. It offers a complete overview of innovative as well as standard drying technologies, and addresses the issues of why drying is required and what the critical considerations are for implementing this process operation during drug product development. Drying Technologies for Biotechnology and Pharmaceutical Applications discusses the state-of-the-art of established drying technologies like freeze- and spray- drying and highlights limitations that need to be overcome to achieve the future state of pharmaceutical manufacturing. The book also describes promising next generation drying technologies, which are currently used in fields outside of pharmaceuticals, and how they can be implemented and adapted for future use in the pharmaceutical industry. In addition, it deals with the generation of synergistic effects (e.g. by applying process analytical technology) and provides an outlook toward future developments. -Presents a full technical overview of well established standard drying methods alongside various other drying technologies, possible improvements, limitations, synergies, and future directions -Outlines different drying technologies from an application-oriented point of view and with consideration of real world challenges in the field of drug product development -Edited by renowned experts from the pharmaceutical industry and assembled by leading experts from industry and academia Drying Technologies for Biotechnology and Pharmaceutical Applications is an important book for pharma engineers, process engineers, chemical engineers, and others who work in related industries.
Thoroughly acquainting the reader with freeze-drying fundamentals, Freeze-Drying/Lyophilization of Pharmaceutical and Biological Products, Second Edition carves practical guidelines from the very latest theoretical research, technologies, and industrial procedures. It delineates the best execution of steps from closure preparation and regulatory control of products to equipment sterilization and process validation. With 13 new chapters providing state-of-the-art information, the book unveils innovations currently advancing the field, including LYOGUARD® packaging for bulk freeze-drying and the irradiation of pharmaceutical and biological products.
Humans have been experimenting with lyophilization, or freeze-drying, as a method to preserve biological structures for over a thousand years. This comprehensive volume, intended for scientists in both academia and industry, covers a wide range of topics relevant to the formulation of peptide and protein drugs in the freeze-dried state.
Recombinant proteins and polypeptides continue to be the most important class of biotechnology-derived agents in today's pharmaceutical industry. Over the past few years, our fundamental understanding of how proteins degrade and how stabilizing agents work has made it possible to approach formulation of protein pharmaceuticals from a much more rational point of view. This book describes the current level of understanding of protein instability and the strategies for stabilizing proteins under a variety of stressful conditions.
The biotechnology/biopharmaceutical sector has tremendously grown which led to the invention of engineered antibodies such as Antibody Drug Conjugates (ADCs), Bispecific T-cell engager (BITES), Dual Variable Domain (DVD) antibodies, and fusion proteins that are currently being used as therapeutic agents for immunology, oncology and other disease conditions. Regulatory agencies have raised the bar for the development and manufacture of antibody-based products, expecting to see the use of Quality by Design (QbD) elements demonstrating an in-depth understanding of product and process based on sound science. Drug delivery systems have become an increasingly important part of the therapy and most biopharmaceuticals for self-administration are being marketed as combination products. A survey of the market indicates that there is a strong need for a new book that will provide “one stop shopping” for the latest information and knowledge of the scientific and engineering advances made over the last few years in the area of biopharmaceutical product development. The new book entitled Development of Biopharmaceutical Drug Device Products is a reference text for scientists and engineers in the biopharmaceutical industry, academia or regulatory agencies. With insightful chapters from experts in the field, this new book reviews first principles, covers recent technological advancements and provides case studies and regulatory strategies relating to the development and manufacture of antibody-based products. It covers topics such as the importance of early preformulation studies during drug discovery to influence molecular selection for development, formulation strategies for new modalities, and the analytical techniques used to characterize them. It also addresses important considerations for later stage development such as the development of robust formulations and processes, including process engineering and modeling of manufacturing unit operations, the design of analytical comparability studies, and characterization of primary containers (pre-filled syringes and vials).Finally, the latter half of the book reviews key considerations to ensure the development and approval of a patient-centered delivery system design. This involves the evolving regulatory framework with perspectives from both the US and EU industry experts, the role of international standards, design control/risk management, human factors and its importance in the product development and regulatory approval process, as well as review of the risk-based approach to bridging between devices used in clinical trials and the to-be-marketed device. Finally, case studies are provided throughout.The typical readership would have biology and/or engineering degrees and would include researchers, scientific leaders, industry specialists and technology developers working in the biopharmaceutical field.
This book provides a detailed account of the most recent developments, challenges and solutions to seamlessly advance and launch a lyophilized biologics or vaccine product, based on diverse modalities, ranging from antibodies (e.g., monoclonal, fused), complex biologics (e.g., antibody drug conjugate, PEGylated proteins), and vaccines (e.g., recombinant-protein based). The authors adeptly guide the reader through all crucial aspects, from biophysical and chemical stability considerations of proteins, analytical methods, advances in controlled ice nucleation and quality-by-design approaches, alternate drying technology, to latest regulatory, packaging and technology transfer considerations to develop a stable, safe and effective therapeutic protein, vaccine and biotechnology products. Lyophilized Biologics and Vaccines: Modality-Based Approaches is composed of four sections with a total of 17 chapters. It serves as a reference to all critical assessments and steps from early pre-formulation stages to product launch: Provides recent understanding of heterogeneity of protein environment and selection of appropriate buffer for stabilization of lyophilized formulations Details the latest developments in instrumental analysis and controlled ice nucleation technology Explains in-depth lyophilized (or dehydrated) formulation strategies considering diverse modalities of biologics and vaccines, including plasmid DNA and lipid-based therapeutics Details an exhaustive update on quality-by-design and process analytical technology approaches, illustrated superbly by case studies and FDA perspective Provides the latest detailed account of alternate drying technologies including spray drying, bulk freeze-drying and crystallization, supported exceptionally by case studies Provides a step-by-step guide through critical considerations during process scale-up, technology transfer, packaging and drug delivery device selection, for a successful lyophilization process validation, regulatory submission and product launch Chapters are written by one or more world-renowned leading authorities from academia, industry or regulatory agencies, whose expertise cover lyophilization of the diverse modalities of biopharmaceuticals. Their contributions are based on the exhaustive review of literature coupled with excellent hands-on experiences in laboratory or GMP setup, making this an exceptional guide to all stages of lyophilized or dehydrated product development.
Freeze-drying, or lyophilization, is a well established technology used in the preservation of numerous pharmaceutical and biological products. This highly effective dehydration method involves the removal of water from frozen materials via the direct sublimation of ice. In recent years, this process has met with many changes, as have the regulatio
Antibody-drug conjugates (ADCs) stand at the verge of a transformation. Scores of clinical programs have yielded only a few regulatory approvals, but a wave of technological innovation now empowers us to overcome past technical challenges. This volume focuses on the next generation of ADCs and the innovations that will enable them. The book inspires the future by integrating the field’s history with novel strategies and cutting-edge technologies. While the book primarily addresses ADCs for solid tumors, the last chapter explores the emerging interest in using ADCs to treat other diseases. The therapeutic rationale of ADCs is strong: to direct small molecules to the desired site of action (and away from normal tissues) by conjugation to antibodies or other targeting moieties. However, the combination of small and large molecules imposes deep complexity to lead optimization, pharmacokinetics, toxicology, analytics and manufacturing. The field has made significant advances in all of these areas by improving target selection, ADC design, manufacturing methods and clinical strategies. These innovations will inspire and educate scientists who are designing next-generation ADCs with the potential to transform the lives of patients.
The definitive guide to the myriad analytical techniques available to scientists involved in biotherapeutics research Analytical Characterization of Biotherapeutics covers all current and emerging analytical tools and techniques used for the characterization of therapeutic proteins and antigen reagents. From basic recombinant antigen and antibody characterization, to complex analyses for increasingly complex molecular designs, the book explores the history of the analysis techniques and offers valuable insights into the most important emerging analytical solutions. In addition, it frames critical questions warranting attention in the design and delivery of a therapeutic protein, exposes analytical challenges that may occur when characterizing these molecules, and presents a number of tested solutions. The first single-volume guide of its kind, Analytical Characterization of Biotherapeutics brings together contributions from scientists at the leading edge of biotherapeutics research and manufacturing. Key topics covered in-depth include the structural characterization of recombinant proteins and antibodies, antibody de novo sequencing, characterization of antibody drug conjugates, characterization of bi-specific or other hybrid molecules, characterization of manufacturing host-cell contaminant proteins, analytical tools for biologics molecular assessment, and more. Each chapter is written by a recognized expert or experts in their field who discuss current and cutting edge approaches to fully characterizing biotherapeutic proteins and antigen reagents Covers the full range of characterization strategies for large molecule based therapeutics Provides an up-to-date account of the latest approaches used for large molecule characterization Chapters cover the background needed to understand the challenges at hand, solutions to characterize these large molecules, and a summary of emerging options for analytical characterization Analytical Characterization of Biotherapeutics is an up-to-date resource for analytical scientists, biologists, and mass spectrometrists involved in the analysis of biomolecules, as well as scientists employed in the pharmaceuticals and biotechnology industries. Graduate students in biology and analytical science, and their instructors will find it to be fascinating and instructive supplementary reading.
