BioRationality: FDA Opens Up Biosimilar Inquiries on Reddit

The FDA has opened a portal of inquiry that will be answered by Sarah Yim, MD, director of the FDA’s Office of Therapeutic and Biologics and Biosimilars, on r/medicine at Reddit. There had never been an opportunity like this to hear directly from the agency and in writing. Recently, Yim had answered the following questions [sic]:

• What is your opinion on insurers mandating a switch to biosimilar when patient is stable on the reference drug?
• When the FDA evaluates biosimilars, how much data is required to determine if the product is equally effective for a given indication? For example, Tofidence is approved for arthritis, but not yet for giant cell arteritis; will manufacturers be expected to perform separate trials for each indication? And do we generally expect that biosimilars will perform as well for all of the indications that the reference drug was labeled for (or are there examples you know of where the biosimilar worked for one indication but not another)?
• Why is there still so much pushback regarding interchangeability regarding biosimilars, similar to what we have with generics?
• The lack of clinical studies is the exact reason for patient concern.
• Is there legislation or regulations being worked on to allow interchangeability at the pharmacy level for all existing and future biosimilars approved if immunogenicity has not been found to be a problem?
• When reviewing comparative clinical study (CCS) data, have you (or your colleagues) ever come across a situation where the biosimilar was more efficacious than the reference biologic? I understand that CCS use an equivalence design and if there was a such a situation the biosimilar wouldn't be deemed equivalent but I'm curious what was your (or your departments) response to such a situation.
• Is it possible for a biosimilar manufacturer to trial an approved biosimilar product in a novel indication? I'm guessing it would have to go through the novel integrated delivery network pathway. Would the novel indication appear in the same label or a separate label?
• What is being done to minimize the frustration in having to do another prior authorization after insurance effectively mandates a switch to a biosimilar? I already did a prior authorization for Humira. Why do I need one for Hadlmia/Cyltezo/other adalimumab biosimilars?
• This is going to be a dumb question but can cell or gene therapies ever become generic? The manufacturing and administration process makes me think, No? [FDA answered yes, it is possible]
• So biosimilars use different, but similar cell lines, in their different but similar manufacturing process, to obtain the same "mix" or at least close enough to the same "mix" of the correct molecule? I was always under the impression the "formula/recipe" that was used to make the biosimilar was intellectual property didn't necessarily need to be divulged, and that's why biosimilars had to create their own manufacturing process to come up with the same product, thus why they are called biosimilar and not generic.

Yim answered all these questions and brought much more knowledge, so I recommend stakeholders take this opportunity to ask questions. However, so few questions fail to benefit from this portal. I am encouraging all stakeholders to clear their misconceptions and also encourage the FDA to modify the Biologics Price Competition and Innovation Act guidelines to expedite the approval of biosimilars.I just asked this question:

• Clinical efficacy testing of biosimilars is less sensitive than pharmacokinetic studies and analytical assessments; is this in order? Can the FDA make a scientific statement on this topic?