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Tracing back through history, one observes that the treatment of human disease, while always multimodal, has been strongly influenced, and even dominated, by select therapeutic strategies for discrete periods of time. Examples include the use of herbs to treat disease in prehistoric times (herbalism), bloodletting and humorism (starting around 500 years before the Christian era), germ theory, and chemotherapy (in the eighteenth and nineteenth centuries). Although the use of chemicals for medicine may be traced back to Paracelsus in the sixteenth century, pharmacotherapy with small molecule drugs (SMDs) did not dominate medicine until the twentieth century. At present, early in the twenty‐first century, thousands of SMDs are in use as treatments for virtually all human diseases and conditions, including infectious disease, cardiovascular disease, mental health, pain, diabetes, and cancer.

The use of antibodies to treat disease may be traced to the 1890s, with the application of antisera to treat and prevent toxicity relating to diphtheria. Exogenous insulin was first used to treat diabetes in 1922, and human, recombinant insulin became available for therapeutic use in 1978. Building on these successes, and through advancements in the fields of protein chemistry, immunology, and molecular biology, we may now be entering a new phase where biological drugs, including peptides, proteins (e.g. antibodies), nucleic acid therapeutics (siRNA, antisense oligonucleotides, etc.), and cell therapies (T‐cells, viruses, bacteriophages, etc.) emerge as dominant treatments for human disease.

At the time of writing this text in 2020, biologics account for more than 50% of new therapeutic entities under development at many major pharmaceutical companies, and monoclonal antibodies (mAbs) may be considered as the largest drug class (with ~75 mAbs approved for therapeutic use). Five of the current top 10 selling drugs are mAbs, including the top selling drug (adalimumab).

Relative to SMD, biologic drugs are often more selective in their actions, which translates to an improved ratio of beneficial effects relative to unwanted toxicity. However, biologics are much larger, and much more complex, than typical SMDs. An average mAb is associated with a molecular weight of ~150 000 Da, more than 30‐times the average molecular weight of SMDs. Additionally, most biological drugs are not chemically synthesized, but are produced by biological systems (e.g. cells grown in bioreactors) that are subject to biological variability. Consequently, biological drugs may be most appropriately considered as complex distributions of molecular entities, rather than as unique chemical compositions. Variability exists within and between preparations of a biologic with regard to post‐translational modifications (e.g. the extent and nature of glycosylation and sialylation), chemical modifications (e.g. deamidation and oxidation of labile functional groups), presence of aggregates, and the presence of host cell proteins (i.e. proteins relating to the cells used for production of the biologic). These and other product variables have been associated with significant effects on the pharmacokinetics, pharmacodynamics, and safety of the biologic product. As such, pharmacists, physicians, and other healthcare professionals have been faced with uncertainties regarding the safety and utility of preparations of biologics that are marketed as being “biosimilar” to an innovator biologic, or preparations that are developed as being superior to an innovator product (i.e. “biobetter”).

This text is extremely timely in that it addresses many fundamental scientific, clinical, and regulatory issues relating to innovator biologics, biosimilars, and biobetters, through a thoughtful and detailed collection of 16 chapters. The text, which has been expertly compiled and edited by Dr. Iqbal Ramzan, provides discussion of the major classes of biological drugs, clear presentation of the terminology and nomenclature of the field, review of approved biosimilar and biobetter drugs, biophysical concepts and key biophysical analytical tests, pharmacokinetics, pharmacogenomics, pharmacovigilance, and pharmacoeconomics. The work provides a practical and clinical perspective to the use of biologics and biobetters, including consideration of controversial topics such as the interchangeability of innovator and biosimilar products. This book will serve as an excellent primer for all pharmacists and clinicians as we move forward into what may become a new era of medicine, an era dominated by the use of biological drugs.

Joseph P. Balthasar

University at Buffalo, Buffalo NY USA