Approval Process and Quality of Biosimilars

Peter Kaiser, MD: The approval process for biosimilars is different than [that of] the reference product, and it's certainly very confusing to many who look at the clinical studies. In a reference product, the approach is to prove the safety and efficacy of the drugs, so the majority of the clinical studies are around clinical trials. You need at least 2 positive phase 3 clinical studies for each disease. If you have 2 diseases, that's 4 phase 3 clinical studies. The CMC [Chemistry, Manufacturing, and Controls] and analytical part of the submission is much less important. In contrast, biosimilars flip that on its head because the majority of the regulatory pathways involved in proving that the biosimilar are actually similar to the reference product using analytical studies. In the safety and efficacy study, there only needs to be 1 well-performed clinical study that then is extrapolated to all of the other disease processes. How do you get a drug approved with just 1 clinical study? It's because the majority of the submission, whether it be the FDA [United States Food and Drug Administration] or the EMA [European Medicines Agency], is based on those analytical studies. It's important to understand why it is a biosimilar and not a generic, and largely it's because these biologics—even the reference products—have a difference batch to batch. There is a slight, little glycosylation difference in the batches, and these need to be worked out, so you can't have an identical biologic. You have to have a very similar biologic, and that's where the approval process for biosimilars lies.

When you think of biosimilars, you want to worry about how the manufacturing is performed, and this is very important. It's also why the majority of the regulatory processes are around the analytics and the FDA and the EMA care very much about how these drugs are made. Thus, a very stringent biologic process is required. It's important to understand that it's not like the recipe for the reference product is published on the internet and you just follow that recipe to produce the biologic. In particular, the biosimilar drugs need to be reverse engineered and then manufactured; this is a very time consuming and precise process. The FDA and EMA look very closely at the manufacturing facilities to make sure that they meet all guidelines in terms of safety, cleanliness, sterility, etc, and that's the large part of the regulatory package. As ophthalmologists, we can then be assured when we’re using the biosimilar that the FDA has done the homework for us and evaluated the manufacturing so that these drugs are produced in a similar manner as the reference product.

Transcript edited for clarity