Biosimilars are often (mistakenly) referred to as being the generic versions of biologics; however, it’s not that simple. For traditional, small molecule drugs a generic is a copy of the brand name drug. All a pharmaceutical company needs to do to replicate it is follow the same manufacturing process to produce a compound that matches the strength, quality, purity and potency of the brand name drug. Conversely, biologics are large molecule drugs that are created by using living cells, meaning it can never be replicated exactly. Instead, the FDA uses the term “biosimilar” to describe a product that is highly similar to a biologic and has no clinically meaningful differences. This distinction is an important one and can impact patients’ treatment choice quite a bit.
Since the drugs aren’t exact copies of one another, there are increased risks when substituting a biologic for a biosimilar. Patients may not respond as well to the biosimilar and then when switched back to the original biologic, also known as the “reference product,” they may have built up an immune response that renders the product ineffective. To address the issue, the FDA created another category of biosimilar called “interchangeable,” meaning the biosimilar and biologic can be substituted without a patient having the aforementioned adverse reactions. It also means that patients can be switched from a reference product to its interchangeable biosimilar by a third-party, like an insurance company or pharmacy benefit manager, without consultation with the patient or prescribing physicians.
Stakeholders have been waiting ever since the 2010 enactment of the Biologics Price Competition and Innovation Act to gain more insight on what exactly qualifies a biologic and its biosimilar as “interchangeable.” Understandably, patient groups have been advocating for stringent interchangeability standards to ensure safety and continuity of care. Some have also began pushing legislation at the state level that would require notification to physicians and record-keeping of such substitutions.
On January 18, the FDA released its draft guidance on demonstrating interchangeability, titled Considerations in Demonstrating Interchangeability with Reference Product. The draft guidance states that studies demonstrating that two biological products are interchangeable would have to include at least two or more switches between the reference product and the biosimilar. The draft guidance also states that the type and amount of data and information needed to demonstrate interchangeability may vary, and encouraged sponsors to be in frequent consultation with FDA on what that may entail.
Many stakeholders were pleased with the strict frameworks outlined in the draft guidance, believing they would ensure that switching patients from a reference product to an interchangeable biosimilar would not adversely impact their care. However, others are concerned that the interchangeability guidance is not clear enough, and that the case-by-case approach that FDA has described may be burdensome and carry the potential to discourage innovation. Comments on the interchangeability guidance are due by March 20, and many hope that stakeholders’ comments will push FDA to provide more clarity on the topic.
A recent executive order aimed at reducing regulatory burden is certain to muddy the waters even more since it’s likely to affect the timing of any final guidance on the issue. Presumably, the FDA will continue to strive to work towards biologic regulatory policy that strikes a balance that promotes both patient safety and innovation.