FDA Guidance for Industry

As the biosimilars marketplace matures, EU and US regulatory agencies are beginning to align around regulatory guidelines for development of biosimilars, which is beneficial for the entire industry. 

FDA Guidance for IndustryCurrently, there are few differences between regulatory guidelines from the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). Both regulatory agencies have similar requirements for sourcing of the reference product for analytical, non-clinical (in vitro and/or in vivo), as well as Phase I comparability studies. Both agencies require the reference product to be sourced from the country/region of interest – i.e., for a biosimilar product to be approved in the US, it has to be sourced from the US, even though the product may have the same name as the one being marketed in the EU. 

Once the bridge demonstrating similiarity between the EU and US product is built, both regulatory agencies will allow the reference product for Phase III study to come from either region. This is a new update in the recent draft guidance that was recently released by the EMA.

However, the two regulatory bodies are not completely in sync. The primary difference between FDA and EMA guidelines for biosimilars is that interchangeability may be allowed in the US unlike the EU. 

To be declared interchangeable by the FDA, a biosimilar is “expected to produce the same clinical result as the reference product in any given patient.” The safety and efficacy risks cannot be greater than using the reference product without switching. Basically, the FDA expects to see no increase in risk in terms of reduction in efficacy or increase in safety concerns between the two products upon multiple alternating or switching cycles. 

Interchangeability assessment in the EU is left up to the member states. EMA does not have the legal authority to make this assessment.

Also, FDA has a requirement for a transition study in order to garner approval as a biosimilar product in the US. This is one time transition for patients who are on the reference product to be switched to the biosimilar product in development to show that there are no increases safety events between the pre- and post- switch population. A transition study is not required by EMA. 

There are also differences around pediatric study requirements. In the US, if a product is approved as a biosimilar the sponsor has to address whether or not pediatric studies are needed and whether they can be conducted post-approval. If the product is interchangeable by the FDA, then pediatric studies are not required. In the EU, pediatric studies are not required.

Topics in this blog post: Biosimilars, EMA, EU, FDA