New guidance from the Food and Drug Administration explains what manufacturers must do to qualify their biosimilar medicine as interchangeable with its reference product. Ten years after the Biologics Price Competition and Innovation Act created a pathway for biosimilar approval, the FDA’s guidance now delineates the highest possible level of biosimilarity.
Biosimilars are medicines that closely resemble innovator biologics for conditions such as cancer and arthritis. All biological medicines are complex and can exhibit slight variations even among batches of the same medicine. Even a small difference can impact patients, some of whom see their immune system react as a side effect of treatment with biological medicines. Thus, since the FDA issued draft guidance in 2017, patient advocates have pushed for the highest possible standards in determining interchangeability.
In its final guidance, the FDA reiterates that the similarity between an interchangeable biosimilar and its reference product must be “fingerprint-like.” It also requires manufacturers to perform switching studies to prove that patients do not see harm or reduced efficacy when swapped between the biologic and the interchangeable biosimilar. This is important because it is likely that, once one or more medicines receive this status, patients will be switched among them based on insurer preference.
FDA indicated that the role of the data submitted by a manufacturer seeking interchangeability status is to demonstrate that a biosimilar “can be expected to produce the same clinical result as the reference product in any given patient.” If a manufacturer wants to extrapolate interchangeability status to more than one approved use for a given biosimilar, it must provide scientific justification for doing so.
Interchangeability status means that a biosimilar may be substituted for a prescribed biologic without the physician’s involvement. In practice, the scenario may play out differently; many states have passed laws requiring that a prescribing physician at least be notified when his or her patient has a medicine switched – but only after the switch has occurred.
The FDA has approved 19 biosimilars to date. None has been deemed interchangeable, and only one company has publicly pursued interchangeability status for a biosimilar thus far.