Due to their complex nature, biologics are produced by cells and later purified to make a therapeutic. However, different cells will produce slightly different biologics. To identify the cell that will produce a biologic most similar to the reference product, thousands of cells lines are evaluated. In depth scientific analysis of both the cell-produced biologics in comparison to the reference product is then conducted to select the best cell, referred to as the clone, to produce the biosimilar.
In order to select the best clone to produce a biosimilar, scientists must match, as closely as possible, the critical quality attributes and, most importantly, the biological function of the reference product. The match of critical quality attributes and biological function gives confidence that the biosimilar will have similar efficacy and safety to the reference product. To best match these attributes, hundreds to thousands of cells are evaluated using an extensive screening process to identify the one that will produce a biosimilar of the highest functional similarity. This screening process demands constant comparison to the reference product and follows four basic steps: candidate clone evaluation, transfection and amplification, clone selection, and product and process optimization. When each of these steps is completed, the end result can lead to a high-quality biosimilar.
See an example of an analytical test scientists use to identify a clone with the highest level of biosimilarity to a reference product.
Example Output from An Analytical Test of Critical Quality Attributes (CQA)
Above is an example of an analysis of two biosimilar clone candidates vs. a reference product. The lines represent results from an analytical test of glycans. The line from biosimilar clone 1 follows the same height pattern as the reference product, showing a high level of similarity. The line from biosimilar clone 2 is higher at several points indicating several glycan differences. Because of these differences, this clone would not be considered for future development.