In the US, biopharmaceutical innovators have 12 years of patent protection for biologic medicines, at which point it becomes possible for biosimilar and biobetter sponsors to market similar therapeutic protein products.
The FDA has published the scientific consideration for demonstrating biosimilarity to a reference product, which provides insight how they will evaluate biosimilar biological products.
In order to establish the biosimilarity of a therapeutic drug candidate to the original innovator molecule, both proteins must be exhaustively structurally characterized for a number of criteria—all covered in International Council for Harmonization guidelines ICH Q5E and ICH Q6B.
Thermo Fisher Scientific has proven workflows and capabilities to support all recommended protein structural analyses for biosimilar development:
|Critical quality attribute||Solution|
|Primary amino acid sequence||Our new, robust peptide mapping workflow gives you 100% sequence coverage.|
|Protein variation||Simple, standardized peptide mapping can be used to easily monitor for protein deamidation and oxidation.|
|Glycosylation post translational modifications||Determine modifications to amino acids with sugar moieties (glycosylation) with our advanced workflows for intact glycoforms, released glycans, glycopeptides, monosaccharides, and sialic acids.|
|Protein heterogeneity||Find our range of buffers, column chemistries, and UHPLC instrumentation to meet the needs for robust charge variant profiling of biopharmaceuticals.|
|Process and product-related impurities||Easily discover the identity and quantity of host cell proteins with our HCP analysis workflow.|
|Protein aggregation||Get the latest innovations in size exclusion chromatography (SEC) for high-resolution separation of monoclonal antibodies (mAb) and their aggregates.|
|Higher order structure||Discover how Orbitrap-based mass spectrometry can enable insight into protein folding and protein-protein interactions.|
|Intentional chemical modifications||Learn how to effectively monitor PEGylation sites and characteristics.|
BioPharma Finder integrated software is a complete solution for intact protein characterization and peptide mapping.
A key step to proving biosimilarity is to establish glycosylation patterns, because variations in glycosylation can affect the efficacy and safety of therapeutic proteins, influencing their biological activity, serum half-life, and immunogenicity. Monosaccharides, including sialic acid composition analysis can detect variations in glycosylation, and support quality control for process development and manufacturing procedures. As a result, proteins are routinely analyzed to determine their monosaccharides and sialic acids amount and identity.