Biologic drugs, also known as biologics or biologicals, are produced using living organisms. Various classic biologics, such as the medical human insulin taken by diabetics, have been made by biotechnology processes for some decades. What is relatively new are therapeutic biologics to treat autoimmune diseases and cancer, such as the trade-named monoclonal antibody drugs Remicade (infliximab) and Rituxan (rituximab) used to treat autoimmune diseases. See also: Antibody; Autoimmunity; Biologicals; Biotechnology; Molecular biology; Monoclonal antibodies
Therapeutic biologics, also known as therapeutic proteins, are made by recombinant DNA technology, whereby a gene—a functional DNA sequence encoding a protein—is inserted into living organisms (bacteria, cell, or yeast). Cultures of the cells that produce the therapeutic proteins are cultivated in bioreactors to produce biologics. The process conditions for producing biologics are very exacting, with quality testing each step of the way through isolation, purification, and packaging. Taking a biologic to market is also a complex task that involves preclinical testing to determine how the body absorbs, distributes, metabolizes, and eliminates the drug, as well as studies of the drug’s biochemical and physiologic effects on the body, followed by clinical testing for effectiveness and regulatory approval. See also: Deoxyribonucleic acid (DNA); Gene; Genetic engineering; Protein; Protein engineering; Pharmaceuticals testing; Pharmacy; Quality control
Developing and producing biologics is a costly and risky venture but a rewarding one for the companies that succeed. In 2012, Remicade and Rituxan were the fourth and fifth best-selling drugs. In 2014, sales of biologics worldwide are expected to exceed $125 billion. Biologics are not cheap. Remicade, for example, costs about $20,000–$30,000 per year to treat one patient.
The U.S patents for both Remicade and Rituxan will expire in 2018 and the European patents will expire a few years earlier, which opens the door for the production of cheaper functional equivalents or biosimilar drugs. Unlike generic drugs, biosimilars are not exact chemical copies of their originals. Moreover, because of process variability, no two batches of biologics are exactly the same. As a result, most biologics are manufactured to meet standards that fall within a range of acceptable qualities.
Biosimilars derived from different cell lines and process conditions will have minor structural differences from their biologic originals, and these differences could affect the drugs’ effectiveness and safety. A biosimilar could in principle turn out to be better than the original. Still, the $100 billion unanswered question is whether biosimilars are interchangeable with brand-named biologics and not just functional equivalents of them.
In 2014, the U.S. Food and Drug Administration (FDA) drafted guidelines for the approval of biosimilars. European regulations went into effect in 2005. In June 2013, the European Medicines Agency approved two biosimilars, Remsima and Inflectra, both of which were shown to be similar to Remicade. The FDA gave its first approval for a biosimilar called Zarxio in March 2015. Zarxio is biosimilar to Neupogen (filgrastim), a drug that stimulates the growth of neutrophils, a type of white blood cell that fights bacterial and fungal infections. Neupogen and Zarxio are used to treat patients with abnormally low numbers of neutrophils (neutropenia) resulting from bone marrow transplantation or chemotherapy. See also: Blood; Chemotherapy and other antineoplastic drugs; Infectious disease; Transplantation biology
For now, do not expect the price of biosimilars to lower drug costs as sharply as have generic drugs, which can be 75% cheaper than their brand-name equivalents. The main reason is that the development costs are very high for biosimilars. Celltrion, the manufacturer of Remsima, has said that Remsima will be 30% cheaper than Remicade in Europe when its patent expires.