Biosimilar

A biosimilar (also known as follow-on biologic or subsequent entry biologic) is a biologic medical product that is almost an identical copy of an original product that is manufactured by a different company. Biosimilars are officially approved versions of original 'innovator' products and can be manufactured when the original product's patent expires. Reference to the innovator product is an integral component of the approval. A biosimilar (also known as follow-on biologic or subsequent entry biologic) is a biologic medical product that is almost an identical copy of an original product that is manufactured by a different company. Biosimilars are officially approved versions of original 'innovator' products and can be manufactured when the original product's patent expires. Reference to the innovator product is an integral component of the approval. Unlike with generic drugs of the more common small-molecule type, biologics generally exhibit high molecular complexity and may be quite sensitive to changes in manufacturing processes. Despite that heterogeneity, all biopharmaceuticals, including biosimilars, must maintain consistent quality and clinical performance throughout their lifecycle. Follow-on manufacturers do not have access to the originator's molecular clone and original cell bank, to the exact fermentation and purification process, or to the active drug substance, but they have access to the commercialized innovator product. Overall, it is harder to ascertain fungibility between generics and innovators among biologics than it is among totally synthesized and semisynthesized drugs. That is why the name 'biosimilar' was coined to differentiate them from small-molecule generics. A simple analogy, often used to explain the difference, is to compare wine with soda pop. It is harder to say objectively that two bottles of wine from two wineries are 'sufficiently interchangeable,' because of differences in yeast strain, weather, and year of grape harvest, than it is to say that two bottles of soda pop of the same flavor coming from two bottling plants are 'sufficiently interchangeable' because they contain the same flavoring powder. Drug-related authorities such as the EU's European Medicines Agency (EMA), the US's Food and Drug Administration (FDA), and the Health Products and Food Branch of Health Canada hold their own guidance on requirements for demonstration of the similar nature of two biological products in terms of safety and efficacy. According to them, analytical studies demonstrate that the biological product is highly similar to the reference product, despite minor differences in clinically inactive components, animal studies (including the assessment of toxicity), and a clinical study or studies (including the assessment of immunogenicity and pharmacokinetics or pharmacodynamics). They are sufficient to demonstrate safety, purity, and potency in one or more appropriate conditions of use for which the reference product is licensed and is intended to be used and for which licensure is sought for the biological product. In case of a monoclonal antibody-containing medicinal product, such as Remsima, extensive physicochemical and biological characterization for it and its reference product Remicade was conducted to demonstrate their highly-similar properties. Therefore, EMA has granted a marketing authorisation for only a few biosimilars since 2006, including a monoclonal antibody, that was recently approved. Meanwhile, on March 6, 2015, the FDA approved the United States's first biosimilar product, the biosimilar of filgrastim called filgrastim-sndz (trade name Zarxio) by Sandoz. The European regulatory authorities led with a specially adapted approval procedure to authorize subsequent versions of previously approved biologics, termed 'similar biological medicinal products', or biosimilars. This procedure is based on a thorough demonstration of 'comparability' of the 'similar' product to an existing approved product. In the United States, the Food and Drug Administration (FDA) held that new legislation was required to enable them to approve biosimilars to those biologics originally approved through the PHS Act pathway. Additional Congressional hearings have been held. On March 17, 2009, the Pathway for Biosimilars Act was introduced in the House. See the Library of Congress website and search H.R. 1548 in 111th Congress Session. Since 2004 the FDA has held a series of public meetings on biosimilars. The FDA gained the authority to approve biosimilars (including interchangeables that are substitutable with their reference product) as part of the Patient Protection and Affordable Care Act signed by President Obama on March 23, 2010. The FDA has previously approved biologic products using comparability, for example, Omnitrope in May 2006, but this like Enoxaparin was also to a reference product, Genotropin, originally approved as a biologic drug under the FD&C Act. On March 6, 2015, Zarxio obtained the first approval of FDA. Sandoz’s Zarxio is biosimilar to Amgen’s Neupogen (filgrastim), which was originally licensed in 1991. This is the first product to be passed under the Biologics Price Competition and Innovation Act of 2009 (BPCI Act), which was passed as part of the Affordable Healthcare Act. But Zarxio was approved as a biosimilar, not as an interchangeable product, the FDA notes. And under the BPCI Act, only a biologic that has been approved as an “interchangeable” may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product. The FDA said its approval of Zarxio is based on review of evidence that included structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamics data, clinical immunogenicity data and other clinical safety and effectiveness data that demonstrates Zarxio is biosimilar to Neupogen. Cloning of human genetic material and development of in vitro biological production systems has allowed the production of virtually any recombinant DNA based biological substance for eventual development of a drug. Monoclonal antibody technology combined with recombinant DNA technology has paved the way for tailor-made and targeted medicines. Gene- and cell-based therapies are emerging as new approaches.