Surfactants in Biopharmaceutical Development addresses the progress, challenges and opportunities for surfactant research specific to pharmaceutical development, providing a broad range of important surfactant-related topics as they relate directly to the biopharmaceutical process. Chapters address fundamental topics, like mechanisms of protein stabilization by surfactants, the latest, state-of-the-art technology and methods to illustrate the practical application to biopharmaceutical development, forward-looking chapters on control strategies and novel surfactants, with a special focus on current regulatory aspects of paramount importance for biopharmaceutical companies and regulators. It has been widely recognized that surfactants provide protection to therapeutic proteins against interfacial stresses. Despite the fact that the very mechanism of protein stabilization by surfactants has not been completely understood, surfactants are universally regarded as critical functional excipients by the industry and by regulators. Describes the current state of research on surfactants in the context of biopharmaceutical development, drawing upon contributions from international experts across industry, academia, and regulators Addresses the opportunities and challenges associated with surfactants in biologic drug development Provides a defining resource for practitioners in the biopharmaceutical industry, regulators and academics by summarizing the latest knowledge of surfactants in biopharmaceutical development in one comprehensive volume

Nonionic Surfactants, Sugar-Based Surfactants, Alkylpolyglucosides, Protein Formulations

It is now twelve years since Solubilization by Surface-Active Agents appeared. Since the publication of that monograph the subject has expanded rapidly as the unique potential of surfactants has become known to a wider circle of scientists. In a recent review Menger (Accounts of Chemical Research, 12 (1979) 111) estimated that since 1970 there have been over 2800 publications on micelles and micellization alone. The topic of catalysis in micellar media was in an early stage of development in 1968 but the growth in this subject has given rise to an excellent textbook by Fendler and Fendler. We have felt for some time that a revision of Solubilization by Surface-Active Agents was overdue. The book has been out of print for some time. Owing to pressure of other work, Professor P. H. Elworthy and Dr C. B. Macfarlane were unable to undertake the work of revision but while working together on an undergraduate textbook the present authors decided to set to work, realizing both the impossibility of producing a comprehensive textbook and the need to alter the scope of the book. Micellar solubilization occurs over a relatively small surfactant concentration range; because of this and because the phenomenon is never observed in isolation, we have extended the text to include surface activity, emulsions and suspensions and, as our emphasis is on formulation of medicinal products, to the of the toxicology of surface-active agents.

As the pharmaceutical industry shifts from small molecule drug to biologic drug development, new and unique formulation needs emerge. Issues relating to shelf-stability of biologic formulations remain a key challenge to new drug development for both the developed and developing world. N-myristoyl phenylalanine Jeffamine M1000 diamide (FM1000) is a new experimental surfactant that has been developed for stabilizing biopharmaceuticals. FM1000 exhibits an order of magnitude faster interfacial dynamics than conventional formulation excipients, leading to improved agitation stability. A three-fold drop in IgG aggregation rate was observed for IgG formulated with FM1000 compared to control surfactant formulations. In a study of abatacept aggregation, FM1000 minimized the monomer loss both in glass vials and in IV bags, even out-performing Poloxamer 188, the incumbent technology. FM1000 also reduced subvisible particle formation in a cetuximab model formulation. Coupling aggregation performance with fundamental surfactant interfacial dynamics and behavior will help better understand the underlying mechanisms of protein (de)stabilization, enabling the development of higher stability formulations.

This authoritative volume provides a contemporary view on the latest research in molecules with optimal drug-like properties. It is a valuable source to access current best practices as well as new research techniques and strategies. Written by leading scientists in their fields, the text consists of fourteen chapters with an underlying theme of early collaborative opportunities between pharmaceutical and discovery sciences. The book explores the practical realities of performing physical pharmaceutical and biopharmaceutical research in the context of drug discovery with short timelines and low compound availability. Chapters cover strategies and tactics to enable discovery as well as predictive approaches to establish, understand and communicate risks in early development. It also examines the detection, characterization, and assessment of risks on the solid state properties of advanced discovery and early development candidates, highlighting the link between solid state properties and critical development parameters such as solubility and stability. Final chapters center on techniques to improve molecular solubilization and prevent precipitation, with particularly emphasis on linking physiochemical properties of molecules to formulation selection in preclinical and clinical settings.