Biosimilar Development

Biosimilar development is a highly skilled, multi-step process and requires extensive understanding of the reference product.

Manufacturers of biosimilars execute two paths simultaneously – one to understand the reference product and the second for creating, selecting and making the biosimilar. These paths intersect each other as data from the reference product is continuously compared to the biosimilar throughout its development process.


Understanding a Reference Product
To understand how a reference product works to treat patients, scientists review the literature published in peer reviewed medical journals on both the diseases and the reference product. Additionally, they acquire the reference product and use sophisticated analytical tests to characterize the medicine. More specifically, they look to identify the critical quality attributes, meaning the very fine details of the molecule, that provide the function that allows the medicine to treat patients.
Creating and producing a biosimilar
Creating a biosimilar requires skilled scientists to conduct steps in a laboratory that require a high level of precision. The first step in developing a biosimilar is to 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. Once thousands of versions of the biologic are created, each by a different clone, scientists evaluate them to identify the clone that is most similar to the reference product. Once that clone has been selected, the manufacturing process is developed to enhance the level of similarity between the biosimilar and the reference product. This process will also be the platform for creating a large enough quantity of the biosimilar to supply patients with medicine. Once this process has been defined, non-clinical and clinical testing can occur. Clinical testing of biosimilars 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 (i.e., pharmacokinetics and pharmacodynamics) and a second stage in patients to test that the biosimilar works with a similar level of efficacy and safety as a reference product.
Comparison of the reference product and the biosimilar throughout
Through each step of developing, selecting and making the biosimilar, the biosimilar is compared to the reference product to ensure that a high level of similarity is maintained throughout the process. The comparison to the reference product is made through both analytical testing (tests conducted in a lab) and clinical testing (tests conducted in patients). Sophisticated analytical tools and methods are used to compare the biosimilar to the reference product on the very fine details of the molecule. Analytical tools have made great advancements over time, but are still insufficient in predicting certainty of activity or safety reactions in patients. Because of this, in most cases, a robust analytical data package is insufficient for approval without clinical data, but provides the foundation to justify abbreviated clinical testing for a biosimilar. The analytical data with the clinical data together comprise the “totality of evidence” for which the level of similarity can be assessed. 

Biosimilar Development Process

Glossary