The analytical data of a biosimilar is the foundational component to demonstrating a high level of similarity. The key to assessing analytical data is to understand the quality of the assessment:
- Was a comprehensive set of tests conducted so that all relevant biologic activities were tested?
- Were current state-of-the-art testing methods used to ensure a high level of sensitivity in the assessment?
- Was the best process for the assay followed to ensure clear resolution of the comparison of the reference product to the biosimilar?
A comprehensive set of analytical testing needs to test 1. every relevant biological activity that has been identified for the reference product, especially the mechanism or mechanisms of action and 2. each structural component of the molecule such as the amino acid sequence, the attached carbohydrates and the proper molecular folding.
Sensitivity refers to the point at which you can detect something. An analogy for sensitivity of testing can be seen in baking when sugar is added. The amount of sugar added will impact the taste of sweetness. A little sugar sometimes does not result in the taste of sweetness. If an insensitive analytical test is run, lack of similarity may not be detected.
Resolution provides the ability to see the details of a molecule. The difference in the level of resolution in a test can be seen in human weight scales. Older weight scales can closely approximate weight within 2 to 3 pounds. Modern scales can give a precise weight to the first decimal. Both are weight scales, but the level of precision is different. In some circumstances the difference in resolution of the two different tests may not matter, but in some cases the differences may matter to the efficacy of the biosimilar. In general, a more precise test provides greater confidence in the level of similarity of two products.
When the right test is used and the right method applied, the analytical test can give meaningful clarity into the level of similarity of a biosimilar to its reference product. In contrast, tests can also be run, but not provide true insight. The right set of tests that are comprehensive, sensitive and resolving are the critical components to good analytical testing.