Is Biosimilar Insulin Available?
In December 2015, the Food and Drug Administration (FDA) approved the long-acting human insulin analog Basaglar (insulin glargine injection). Basaglar is similar to the insulin glargine injection Lantus, and the approval of Basaglar relied in part on the FDA’s finding of safety and effectiveness for Lantus. In Europe, the analogous product is considered to be a biosimilar. In the United States, Basaglar is not approved as a biosimilar product—the FDA refers to it as a “follow-on” insulin. So what’s up?
The answer lies in a quirk of biological product approval. The term “biological product” is defined in the Public Health Service (PHS) Act as a “virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, or analogous product… applicable to the prevention, treatment, or cure of a disease or condition of human beings.” Various FDA regulations and policies have interpreted the definition to include immunoglobulin products, products containing cells or microorganisms, and most protein products. Biological products are licensed (i.e., approved) under section 351 of the PHS Act.
Many therapeutic biological products also meet the definition of “drugs” under the Federal Food, Drug, and Cosmetic (FDC) Act; in fact, they are considered to be a subset of drugs. Drugs are approved under section 505 of the FDC Act.
Historically, some natural source protein products have been regulated as drugs under the FDC Act, not biological products under the PHS Act. Insulin is one of those products. When human insulin (Humulin) was approved as the world’s first recombinant DNA drug product in 1982, it was approved under the FDC Act. This dichotomy continues today, with some proteins licensed under the PHS Act and some—notably hormones such as insulin and human growth hormones—approved under the FDC Act.
What does all this mean for “biosimilar” insulin? The Biologics Price Competition and Innovation Act (BCPIA) created an abbreviated licensure pathway for biosimilar products under the PHS Act. Biosimilars must have the same mechanism of action, route of administration, dosage form, and strength as the original reference biological product. However, no insulin products are licensed under the PHS Act, so no reference products exist. According to current statutory definitions, it is not possible to have a biosimilar insulin in the United States. “Generic” insulin also is not possible, because insulin is not a conventional small-molecule chemical drug.
It is possible for manufacturers to develop insulin products that are similar to previously approved products, through an abbreviated approval pathway under section 505(b)(2) of the FDC Act. This pathway gives the FDA the authority to approve new products based in part on the agency’s findings of safety and efficacy for the previously approved product. When these new products are biologics, the FDA refers to them as follow-on biologics. They are listed in the “Orange Book” of approved drug products with therapeutic equivalence evaluations.
Much of this confusion is set to clear up in 2020. As of March 23, 2020, an approved application for a biological product under section 505 of the FDC Act “shall be deemed to be a license for the biological product under section 351 of the PHS Act.”