Creating a biosimilar requires skilled scientists to conduct steps in a laboratory that require a high level of precision. Sophisticated analytical tools and methods are used to compare the biosimilar to the reference product on the very fine details of the molecule. In most cases, a robust analytical data package is insufficient for approval without non–clinical and clinical data. The analytical data with the non–clinical and clinical data together comprise the “totality of evidence” for which the level of similarity can be assessed.3-5
Step 1: Transfect living cells with DNA, meaning to insert the genetic “instructions” for each new clone (version of the cell) to produce the amino acid sequence of the biologic.
Step 2: Once several versions of the candidate biologic are created, each by a different clone, scientists evaluate them to identify and select the clone that is most similar to the reference product.
Step 3: The manufacturing process is then developed, and later fine–tuned, to enhance the level of similarity between the biosimilar and the reference product. This process will be the platform for creating an adequate quantity of the biosimilar to supply patients with medicine.
Step 4: Following development of the manufacturing process, non-clinical and clinical testing can occur. Clinical testing often involves two stages:
-A first stage in healthy volunteers or patients to test that the body processes the biologic in the same way as the reference product (ie, pharmacokinetics and pharmacodynamics)
-A second stage in a broader set of patients to test that the biosimilar works with a similar level of efficacy, safety, and immunogenicity as the reference product