The abbreviated development program demonstrates biosimilarity through analytical, nonclinical and clinical research, studies and additional studies as needed to address any residual uncertainties.
“Abbreviated” refers to the fact that human clinical trials for biosimilars are smaller and are more highly focused than those typically required for new and novel drugs. The actual amount of data collected to support a new biosimilar is very extensive, but the focus is instead on analytical and functional tests as well as human pharmacokinetic (PK) and pharmacodynamic (PD) studies.
Key Concept 2: Stepwise Evidence Development1
Since no single study demonstrates biosimilarity, a stepwise approach has been outlined by the FDA to generate data and establish any areas of uncertainty between the developing biologic and its reference product.
After each phase of development, differences between the two products are observed.
Next steps are established as to which study or studies will best address any uncertainties.
Key Concept 3: Analytical Similarity Data1
First, the reference biologic is extensively characterized to fully understand the structure, especially the key features that are critical to the clinical response (known as “critical quality attributes”). Evaluations of multiple lots of the reference biologic establish the range for each critical quality attribute.
Once details of the reference biologic are well understood, extensive head-to-head analytical comparisons of the reference biologic and biosimilar are conducted to establish that there are no meaningful differences between the two.
Key Concept 4: Role of Clinical Studies1
To consider a product for biosimilarity, the FDA expects data comparing the product and its reference for PK (PD if relevant) and immunogenicity. If uncertainties remain after all of these steps, the agency expects a comparative clinical study, or studies, in an indication that is sensitive enough to detect any difference that might exist, to confirm that there are no differences in safety or effectiveness between the biosimilar and its reference biologic.
References: 1. US Food and Drug Administration. Christl L. Overview of the regulatory pathway and FDA’s guidance for the development and approval of biosimilar products in the US.