Congress, through the Biologics Price Competition and Innovation Act (BPCI Act) of 2009, created an abbreviated approval pathway for biological products that are demonstrated to be biosimilar to or interchangeable with an Food and Drug Administration-approved biological product. This pathway was established to provide more treatment options, increase patient access, and potentially lower health care costs. Manufacturing these molecules is complex. Biosimilars are not the same as generic drugs and are approved via a distinct pathway.
A biosimilar product has to be shown to have no clinically meaningful differences in terms of safety, purity, and potency to the reference product, except for minor differences in inactive components. This is usually demonstrated through human pharmacokinetic (exposure) and pharmacodynamic (response) studies and an assessment of clinical immunogenicity. Biosimilars may be approved for all or a subset of the approved indications for the reference product.
An interchangeable product is a biosimilar product that meets additional stringent requirements. The manufacturer needs to show that an interchangeable product is expected to produce the same clinical result as the reference product in any given patient. Data need to show the patients can be switched back and forth with no adverse effect. Under law it may be dispensed without notifying the prescriber in some states.
A biosimilar is identified by the four-letter suffix attached to the name to distinguish it from the innovator biologic. Newer innovator biologics also include a four-letter suffix, but ranibizumab, aflibercept and bevacizumab innovators do not. Biosimilars for ophthalmic biologics are anticipated in 2021 in the US. A biosimilar for bevacizumab (bevacizumab-awwb) has been available in US since 2017 and can be repackaged for intravitreal use, but as with the reference product (bevacizumab) it has no approved indication for eye disease.
For an intravitreal-administered biosimilar there will need to be a clinical trial completed for an ophthalmic indication of the FDA’s choosing. A clinical trial is required because reliable ocular pharmacokinetic information cannot be easily obtained and systemic pharmacokinetic information is not relevant to an intravitreally administered product.
The American Academy of Ophthalmology recognizes the societal value of biosimilars for improving care of patients with eye disease. Biosimilars should have sufficient research demonstrating their safety and effectiveness for eye diseases before they are routinely recommended for ophthalmologic use. However, the choice of biologic product — innovator, biosimilar, or interchangeable — should be at the discretion of the treating ophthalmologist and their patient.