News about GMP/cGMP


FDA: Comments on Draft Biosimilar Interchangeability Guidance

In January 2017, the FDA issued the long-awaited Biosimilar Interchangeability Guidance for public consultation. In this guidance, the Agency details its expectations for demonstrating biosimilar interchangeability.

The deadline for commenting the draft guidance ended on 19 May, with a number of 45 comments being received. Comments came from big pharmaceutical manufacturers like Pfizer, Boehringer Ingelheim, Sandoz, Johnson and Johnson or Genentech or from organisations, e.g the American Society of Clinical Oncology, the Academy of Managed Care Pharmacy, the Combination Products Coalitions or the Biosimilars Forum.

What is the intention of the document?

The guideline gives an overview of important scientific considerations including

  • Data and information needed to support a demonstration of interchangeability
  • Considerations for the design and analysis of a switching study or studies to support a demonstration of interchangeability
  • Recommendations regarding the use of a U.S.-licensed reference product in a switching study or studies
  • Considerations for developing presentations, container closure systems, and delivery device constituent parts for proposed interchangeable products.

The draft guidance so far reflects FDA’s expectation that sponsors will provide data from one or more switching studies to support a demonstration of interchangeability for a proposed product that is intended to be administered more than once. Moreover, FDA’s position that sponsors should use a US-licensed comparator in such studies may present a challenge for sponsors of proposed interchangeable products for which the reference product is subject to a risk evaluation and mitigation strategy (REMS), if that REMS places restrictions on access to the reference product. In addition, FDA asserts that, in some cases, a proposed interchangeable product may need to be licensed first as a biosimilar to enable the sponsor to gather appropriate post-market data before the product can be licensed as an interchangeable.

Some comments:

Most comments concentrate on the issue of "switching studies" and on the lack of clear definitions, e.g. for “fingerprint-like characterization”, “totality of data” or “residual uncertainty”, “switching” or “substitution”.

Another point raised by commenters was the fact that sponsors would have to use a US-licensed reference product in switching studies. This was also commented by the Biosimilar Medicines Group, a sector group of Medicines for Europe. “In order to support global development”, this group stated “that at this point the agreed and now well-established concept of single or global development is being undermined” and that “so far the EU EMA and the US FDA both changed their respective biosimilar medicines guidelines to clarify the reciprocity of a reference product from a foreign source".


The use of a US-licensed reference product, according to Pfizer, “has the potential to create practical challenges with regard to where the study can be conducted”.

In the 29-page commentary by Sandoz it is stated inter alia that interchangeability is a requirement for additional data not a higher standard for the product itself. Furthermore, Sandoz criticizes that the concept of extrapolation is applicable to interchangeable biologics. Regarding indications licensed to a reference product after the approval of an interchangeable biosimilar, Sandoz writes: "In the supplement submission, no new data or information should be required other than that supporting extrapolation and a revised label adopting the new indication(s) and associated supporting information from the reference biologic label."

These are just a few short extracts of some of the comments given to the FDA. It remains to be seen what their impact on the final version of the guidance on biosimilar interchangeability will be. If you are interested in taking a closer look at the comments, please click here.




regulations. gov: Docket Folder

FDA guidance on demonstrating interchangeability with a reference product