Maui Derm 2016 Highlights: Pre-clinical Characterization of Biosimilars


A. Blauvelt, MD

Before you consider a potentially less-expensive option, you need to understand exactly what you’re getting. A biosimilar product is a biological product that is approved based on a showing that it is highly similar to an FDA-approved biological product, known as a reference product, and has no clinically meaningful differences in terms of safety and effectiveness from the reference product. The wiggle room in the definition of these agents is in terms such as “highly similar” and “clinically meaningful”. What do they actually mean?

The pathway to approval for a biosimilar is very different from that of the originator molecule. Biosimilar development is focused on preclinical evaluation while that for the originator is concentrated on clinical trials.

Biosimilars are reverse engineered from the originator amino acid sequence to derive the DNA sequence. Biosimilars are identical to the originator for amino acid sequence, but that is all. Glycosylation (addition of sugars), protein folding, and other characteristics may be different. Glycosylation is critical since it is a key determinant of protein function and immunogenicity. Is there a risk associated with this? Time will tell.

Manufacturers want the “fingerprint” of the biosimilar to be as close as possible to the originator agent, but there is no criterion for close the match must be. There is a significant “degree of residual uncertainty” about biosimilars. Higher uncertainty will lead to a requirement for more supporting clinical data.