Biosimilars Of Monoclonal Antibodies

Addressing a significant need by describing the science and process involved to develop biosimilars of monoclonal antibody (mAb) drugs, this book covers all aspects of biosimilar development: preclinical, clinical, regulatory, manufacturing. • Guides readers through the complex landscape involved with developing biosimilar versions of monoclonal antibody (mAb) drugs • Features flow charts, tables, and figures that clearly illustrate processes and makes the book comprehensible and accessible • Includes a review of FDA-approved mAb drugs as a quick reference to facts and useful information • Examines new technologies and strategies for improving biosimilar mAbs

Monoclonal antibodies (mAbs) are naturally occurring complex biomolecules. New engineering methods have turned mAbs into a leading therapeutic modality for addressing immunotherapeutic challenges and led to the rise of mAbs as the dominant class of protein therapeutics. mAbs have already demonstrated a great potential in developing safe and reliable treatments for complex diseases and creating more affordable healthcare alternatives. Developing mAbs into well-characterized antibody therapeutics that meet regulatory expectations, however, is extremely challenging. Obstacles to overcome include the determination and development of physiochemical characteristics such as aggregation, fragmentation, charge variants, identity, carbohydrate structure, and higher-order structure (HOS). This book dives deep into mAbs structure and the array of physiochemical testing and characterization methods that need to be developed and validated to establish a mAb as a therapeutic molecule. The main focus of this book is on physiochemical aspects, including the importance of establishing quality attributes such as glycosylation, primary sequence, purity, and HOS and elucidating the structure of new antibody formats by mass spectrometry. Each of the aforementioned quality attributes has been discussed in detail; this will help scientists in researching and developing biopharmaceuticals and biosimilars to find practical solutions to physicochemical testing and characterization. Describes the spectrum of analytical tests and characterization methods necessary for developing and releasing mAb batches Details antibody heterogeneity in terms of size, charge, and carbohydrate content Gives special focus to the structural analysis of mAbs, including mass spectrometry analysis Presents the basic structure of mAbs with clarity and rigor Addresses regulatory guidelines - including ICH Q6B - in relation to quality attributes Lays out characterization and development case studies including biosimilars and new antibody formats

Biologics have revolutionized – and are revolutionizing – the treatment of many serious disorders. The evidence acquired from more than 10 years of clinical experience, with more than 50 biosimilar drugs and more than 700 million patient-days' exposure in Europe, shows that approved biosimilars can be used as safely and effectively as originator biologics. Yet concerns persist about biosimilars – particularly in curative cancer treatment, where they are relatively recent therapeutic options. 'Fast Facts: Biosimilars in Hematology and Oncology' provides a concise overview of emerging global practice in this fast-moving area together with practical information on adding biosimilars to a formulary and switching patients. Contents: • Biologics and the need for biosimilars • Why do we need biosimilars? • How is the quality of biosimilar medicines assured? • Legal issues • Switching, interchangeability and extrapolation • Safety and pharmacovigilant • Global issues • Formulary considerations: pharmacy issues • Formulary considerations: supportive care biosimilars • Formulary considerations: therapeutic anti-cancer biosimilars • Communication and awareness

This long overdue title provides a comprehensive, up-to-date, state-of-the art review of approved biologic therapies, with coverage of mechanisms of action, Indications for therapy, immunogenicity and a detailed examination of adverse effects and safety of the many and diverse therapeutic agents presented in a total of 13 chapters. It is predicted that by 2016, biologics will make up half of the world's 20 top-selling drugs and by 2018, biologic medicine sales will account for almost half of the world's 100 biggest selling drugs. Recombinant proteins dominate the growing list of the more than 200 approved biotherapeutic agents with targeted antibodies, fusion proteins and receptors; cytokines; hormones; enzymes; proteins involved in blood-clotting, homeostasis and thrombosis; vaccines; botulinum neurotoxins; and, more recently, biosimilar preparations, comprising the majority of approved biologics. Written with clinicians, other health care professionals, and researchers in mind, Safety of Biologics Therapy examines, in a single volume, the full range of issues surrounding the safety of approved biologic therapies. A good understanding of the risks and safety issues of modern biologics therapy is increasingly being demanded of all those connected with their development, handling, prescribing, administration and subsequent patient management. In addition to being of great value to clinicians in all branches of medicine, and to nurses, pharmacists and researchers, this book will prove invaluable for students taking undergraduate and graduate courses in the above disciplines and in the biomedical sciences.

Therapeutic Monoclonal Antibodies: From Lot Release to Stability Testing is a highly topical resource on a subject of interest for scientists and researchers working on monoclonal antibodies' characterization, release testing, stability testing and similarity assessments of monoclonal antibodies in the biopharmaceutical industry. Monoclonal antibodies (mAbs) are large, extremely complex and dynamic biomolecules, so it can be challenging to develop well-characterized therapeutic antibodies that meet regulatory expectations that are also in-line with commercialized standards for different drug markets. Lot release testing and understanding the stability of the mAb over a period of time, and in different environmental conditions, is an indispensable aspect of mAb physicochemical characterization. This book covers the process, including extensive analysis that starts with quantifying the purity attribute to glycan profiling and identifying the mAb primary structure. The book has a primary purpose of focusing on both Lot release testing and stability testing of monoclonal antibodies (subjects not covered in any great detail in other books). Discusses, in detail, the Lot release methods for both drug substance and drug product, along with their importance in process sample analysis Gives specific attention to general characteristics tests, such as pH determination, osmolality, sub-visible particle count, appearance and visible tests, and regulatory/pharmacopeial guidelines Includes different kinds of stability testing (real time, accelerated and stressed) and their importance and determinations on product shelf life Presents regulatory guidelines on ICH Q2R1, ICHQ6B and ICHQ5C, which are discussed along with analytical method validation, monoclonal antibodies physicochemical characterization and stability testing Provides different characterization methods and validation and development case studies of monoclonal antibodies, including biosimilars and innovators

A comprehensive primer and reference, this book provides pharmacists and health practitioners the relevant science and policy concepts behind biologics, biosimilars, and biobetters from a practical and clinical perspective. Explains what pharmacists need to discuss the equivalence, efficacy, safety, and risks of biosimilars with physicians, health practitioners, and patients about Guides regulators on pragmatic approaches to dealing with these drugs in the context of rapidly evolving scientific and clinical evidence Balances scientific information on complex drugs with practical information, such as a checklist for pharmacists

Biopharmaceutical medicinal products (biologics) represent a huge financial market. Thus upon patent protection expiry of the innovator (reference) biologic there is interest from industry to gain a portion of this market by launching a 'similar' biologic at a reduced development cost, thus boosting potential gains. The EMA responded to this desire and lead the guidance process with industry on the topic of biosimilars. Based on the experience gained with biosimilars in the past, the EMA started to introduce a second generation series of guidance documents, which take into account the past, current and possibly future challenges of biosimilars. Those proposals were evaluated by EMA and partially incorporated into new guidance documents. This work highlights the challenges and risks associated with biosimilar submissions for large and complex bio-molecules such antibodies. Results: There are unaddressed questions for the regulator with regard to the unsolved dynamic of heterogeneity and variations of the quality profile, which have potential implications on safety and efficacy. This is neglected and not taken into account seriously enough by the stakeholders. Solution: Further, the only (in my view) progressive way to deal with such foreseeable situations from the biosimilar developer’s point of view is to incorporate a design space.

The purpose of this book is to give a concise introduction to development and analysis of pharmaceutical biologics for those in the pharmaceutical industry who are switching focus from small molecules to biologics processing, analysis, and delivery. In order to maintain a limited focus, Introduction to Biologic and Biosimilar Product Development and Analysis, will deal only with peptides, proteins and monoclonal antibodies.