The FDA, now now EMA, emphasize analytical similarity as the pivotal step to minimize residual uncertainty, but creating a plan to demonstrate fingerprint-like similarity has been difficult because of improper use of testing methods, testing protocol, statistical modeling and the knowledge of the variability within and between lots. I have addressed this issue in my several books including the Biosimilars and Interchangeable Biologics: Tactical Issues (https://www.niazi.com/handbooks-and-technical-books) but now I have invented a new method that makes fingerprint-like similarity testing possible. This should help bringing biosimilars faster to market by assuring least residual uncertainty in the early phases of development. What will make biosimilars accessible (available and affordable) is a mindset that supports FDA thinking on scientific approaches that the Agency has demonstrated repeatedly; the ball is in the court of developers to give FDA reasons to approve biosimilars without lengthy, expensive clinical trials. I will be happy to provide more information and details to anyone wishing to examine their approach.
While the concept of non-inferiority testing has been applied to clinical trials, this concept is yet to be applied to analytical similarity testing; the testing protocols as shared by FDA in reviewing three biosimilars, filgrastim, insulin glargine and bevacizumab show a more conventional approach to demonstrate similarity, not non-inferiority. The CQAs for the latter are different than those used of demonstrating similarity.
My inventions include methods to demonstrate difference through a process of thermodynamic extrapolation. I have shared the novelty aspect as well as the non-inferiority trial designs with regulatory agencies and they have all encouraged this approach. I will soon be filing a CP to enforce these new technology and the proposed approach. Being able to demonstrate non-inferiority is a double-edge sword; biosimilar developers can use it to show fingerprint-like similarity but the LBP companies can use these methods to show lack of similarity as well, whether it is clinically meaningful or not.
I am strong that urging the scientific community in the biologics arena to come up with better tests to allow FDA to approve products without requiring phase 3 studies in those cases where these studies can take long time to complete and add to the cost of biosimilar development.