A new guidance document from the FDA attempts to define in detail when two monoclonal antibodies are the same. It says it will not use this definition for biosimilars, but only for "orphan drugs."
A new guidance document from the US Food and Drug Administration (FDA), Interpreting Sameness of Monoclonal Antibody Products Under the Orphan Drug Regulations, takes the next step in defining when two drugs are considered the same.
Although the Code of Federal Regulations has defined "sameness" for macromolecules such as proteins and nucleic acids, it has never before defined the term for the small-molecule monoclonal antibodies. This definition affects the length of patents for these drugs and therefore, potentially, their cost.
The determination affects the Orphan Drugs Act of 1983, under which many biologics used in rheumatology (particularly for pediatric conditions) have been approved, including adalimumab, anakinra, canakinumab, etanercept, infliximab, and rituximab.
The new document stays that two monoclonal antibodies would be considered the same drug if the amino acid sequences of the hypervariable "complementarity determining" regions (e.g., the antigen binding sites) are either identical or have only "minor" differences. Changes outside these regions, or those due to glycosylation patterns or post-translational modifications, would not "necessarily" cause the products to be classed as different.
The document also foresees the development of therapies based on soluble T-cell receptors, and would apply the same definitions to them.
The Agency states specifically that it "does not intend to apply" these definitions to considerations under the 2009 Biologics Price Competition and Innovation (BPCI) Act governing biosimilars, some of which are available outside the US, often at prices somewhat lower than the index or original drug. Patents granted under the BPCI Act will have terms of 12 years. Those granted under the Orphan Drug Act, enacted to spur creation of treatments for diseases affecting fewer than 200,000 US residents, last for 7 years.
The bottom line, according to Regulatory Focus, a publication of the Regulatory Affairs Professional Society, is that any company that wants to sell a monoclonal antibody that is interpreted as the "same" as a drug approved under the Orphan Drug Act "will have to wait until its 7 years of market-based exclusivity run out before it's eligible to file a biosimilar application."