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BioRationality: FDA Calls Meeting to Reevaluate the Need for Clinical Efficacy Testing of Biosimilars


Sarfaraz K. Niazi, PhD, flagged an upcoming FDA meeting where stakeholders can make public comment on whether clinical efficacy testing for biosimilars is necessary for regulatory approval.

The evidence-based ideologies demand proof; the liberal epistemologists instead demand a scientific justification. The FDA has decided to take the latter role, calling a meeting on September 12-13, 2023, to hear from stakeholders whether efficacy testing of biosimilars in patients can be waived beyond the current concessions for products with pharmacodynamic markers.

A similar meeting was held last year, but it had a general perspective that resulted in many “general” suggestions. However, now it is the first time that the FDA is ready to listen to why clinical efficacy testing in patients (as opposed to in healthy subjects based on PD markers) may be unnecessary on the scientific grounds of statistical modeling since the anticipated differences are minimal, the study size will demand hundreds of thousand patients to make the study meaningful.

Additionally, the Bayesian theory makes the post-hoc probability almost zero to find a failed investigation. The FDA is now convinced, but it needs to satisfy those who are perpetually against this change, touting the safety and efficacy risks. A simple argument that the developers can present to the FDA is as follows, after completing clinical pharmacological profiling. “Does the FDA find any residual uncertainty?” The FDA must answer. If the answer is yes, then the next question should be, “Is there any clinical efficacy testing in patients that would resolve the residual uncertainty?” It is at this point where you can present the statistical modeling and Bayesian calculations to show that it is impossible.

Once the efficacy testing in patients is removed, it will have the most significant impact on the future of biosimilars since two-thirds of the development cost goes for efficacy testing in patients.

I foresee a deluge of biosimilars entering the market, expanding the choices as so far, only 12 molecules have arrived as biosimilars; 250 more are waiting to be called. But this decision will also impact the unique interchangeability classification of biosimilars; in the European Union and United Kingdom, where biosimilars are interchangeable with the reference product and other biosimilars, unlike in the United States. It takes triple switching and alternating between proving interchangeability only with the reference product. If it is established that clinical efficacy testing in patients cannot discriminate a biosimilar product from its reference product, then the basis of interchangeability falls as well. The FDA is open to this suggestion, as it has given interchangeable status without the switching or alternating to Cimerli (ranibizumab-eqrn), even though initially, the FDA was not in favor of a legislative change to remove the “interchangeable status,” as I had pushed for in the US Senate.

It is a rare opportunity for stakeholders who believe in liberal epistemology requiring scientific evidence, not an evidence-based need for proof, to present this support for this change by sending an email to CDER-BiologicsBiosimilarsInquiries@fda.hhs.gov and also registering for this pivotal event. We need this effort since it is impossible to change the perceptions of diehard believers in seeing proof in patient testing; these may also include prescribers and large developers, who would rather see the cost barrier to development stay high.

I have prepared several discussion points that you may use to support this campaign, and you can get those by emailing me at niazi@niazi.com. I also request associations like the Biosimilars Council to lead in pushing for this change.

After decades of pushing for rationality over beliefs, I am highly optimistic that we are almost there, where we had wanted to be when the biosimilars arrive—to make them affordable. Let us all work together to make it happen.


Niazi, S. (2021). Scientific rationale for waiving clinical efficacy testing of biosimilars. Drug Des Devel Ther. 2021;16:2803-2815. doi:10.2147/DDDT.S378813

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