“A key difference between the EU and the U.S. biosimilars markets is how they address interchangeability,” Dr. Worthing says. “The EMA does not decide whether a drug is interchangeable with its reference product but rather leaves that decision—and thus, whether a pharmacy can substitute biosimilars automatically—to specific member nations. In the U.S., the FDA has proposed a separate approval process for interchangeable biosimilars that will require switching studies.”
“Biosimilars are not ‘knock-offs’ of their reference products. They are reverse engineered, designed and produced to be as close to the reference product as might be another batch of the reference product,” Dr. Kay says. The evidence so far seems to indicate that interchangeability would be reasonable because biosimilars are so similar to their reference product.
“A big question is how safe it will be to switch from the originator to a biosimilar,” Dr. Cohen says. “You will have nonmedical switching, in which the insurance company will say [a biologic] is not on their formulary or it’s a tier 3 drug, so you must use a biosimilar. I don’t think that will be an issue. We have multiple data that allow for a single switch, and there’s no issue.”
The ACR “strongly supports the FDA’s proposal to require manufacturers use robust switching studies to determine whether alternating between a biosimilar and its reference product impacts the safety or efficacy of the drug. Such studies are vital to achieve a clear understanding of what patients are likely to experience with changing formularies in a multi-payer, multi-state, and ever-changing market. These data should be open and accessible for outside investigators to analyze, and should be made clearly available to prescribing doctors in the interchangeable drug’s label via text or hyperlink. Further, we urge the FDA to consider requiring manufacturers to submit updated and standardized pharmacovigilance data as a prerequisite to certain post-market labeling changes.”
Dr. Cohen heard a colleague in Europe speculate whether psychologically, patients feel that a drug that is cheaper to use is not as effective as the more expensive counterpart. It’s also common for biologics to undergo very minor manufacturing changes as each batch is produced; although that has not been shown to change the effectiveness of the medication.
Another area of concern is extrapolation of indications, which the European report notes is an approach that has been used over the past decade.1 “If a biosimilar is highly similar to its reference product and has comparable safety and efficacy in one therapeutic indication, safety and efficacy data may be extrapolated to other indications for which the reference medicine is approved,” according to the report. By adhering to this concept, fewer clinical trials are needed to allow use of the biosimilar to be expanded to other disease states.