picture01In January, the United States Food and Drug Administration (FDA) released a draft guidance entitled, “Considerations in Demonstrating Interchangeability” aimed at helping to implement the Biologics Price Competition and Innovation Act of 2009 (BPCIA). This guidance serves to directly address the issue of demonstrating interchangeability of biological products and the standards required to do so. Interestingly, no product has yet been shown to be interchangeable, including the four biosimiliars that have already been approved by the FDA.

As an important aside, biologics are generally large molecule cell-derived therapeutics, a common example of whichwould be a monoclonal antibody therapy. A biosimilar is the “generic” equivalent of a biologic drug. This is analogous to the generic drugs we are now so familiar with. However, biologics are complex and usually produced via complicated cell-based manufacturing procedures. Consequently, with biologics there are two types of these “biosimilar” generics. The first type are generic equivalents that are similar, but not identical. The second type are generic equivalents that are fully interchangeable. It is these fully interchangeable generic equivalents that have been more difficult to define and for which the FDA is seeking to set more stringent standards for their interchangeable substitution at the pharmacy.

The issued guidance provides several recommendations on interchangeability and the data required to establish it, including switching studies and how they should be conducted. Switching studies focus on the actual interchangeability of the potentially interchangeable product and the reference product by ensuring that patients can be safely switched from one treatment to the other two or more times with no change in efficacy, immune response, or safety.

The guidance also focuses on ensuring safety monitoring once the interchangeable has made it to market. The FDA, in this guidance, encourages studies that take place once the drug is on the market to ensure that the safety and efficacy of the interchangeable remain at the same level as those of the reference product.
This guidance is a positive step forward in interpreting and implementing the BPCIA. Although some have argued that interchangeability will be incredibly difficult to prove, this guidance provides an important initial list of requirements and a framework within which both scientists and regulators can function.

– Nicholas Vincent and Anthony D. Sabatelli, PhD, JD

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