When, in a given clinical setting, one medicine is substituted with another that is equivalent, it is referred to as interchangeability. This can be done on the initiative or with the agreement of the prescriber.
The Science
Interchanging medication
Extrapolation
Since biosimilars match their reference product in terms of quality, safety, and efficacy, a specific biosimilar can be used interchangeability with its reference product. As part of the approval process, therapeutic equivalence would have been demonstrated to allow for adoption of the same dosing instructions (also termed posology).1,4
Once a biosimilar has been approved for use and has passed the rigorous regulatory requirements called for, it may also be approved for further indications (i.e., other conditions) for which initial studies were not conducted based on the principles of extrapolation. In other words, if there is sufficient evidence to demonstrate biosimilarity for at least one of the reference product’s indications, then it is possible to use data and information to scientifically justify approval for other conditions that were not specifically studied initially, but for which the reference product has received approval. This process of extrapolation thus allows for the approval or registration of a biosimilar for use in a condition held by the reference product, but which the biosimilar manufacturer did not directly study in clinical trials during the development process.2,4
Extrapolation: A scientific and regulatory principle
After biosimilarity is determined, extrapolation enables potential licensure of a biosimilar across indications approved for the reference biologic.
Scientific justification is required in each indication not studied clinically
Biosimilar extrapolation occurs from the reference biologic to the biosimilar, when scientifically justified, based on all available data – not from the indication(s) studied with the biosimilar to other indications
Non-automatic
It is important to bear in mind that extrapolation does not follow automatically, but that it must be supported by scientific justification based on knowledge of the mechanism(s) of action, pharmacokinetic and pharmacodynamic characteristics, efficacy and safety, and immunogenicity of the biosimilar and reference products in question.2
Key FDA considerations for extrapolation
Mechanism of action
Experience with the reference biologic can help define the mechanism of action (MA) and functional moieties in each indication
PK and Biodistribution
PD measures may provide important MO information
Immunogenecity
Differences that may exist in each patient population
Expected toxicities
Differences that may exist in each indication and patient population
