The FDA has just published a new draft Q&A Guidance document regarding BLA submissions for biosimilar products and interchangeable biosimilar products, as well as recommendations for labeling of interchangeable biosimilar products.  This guidance (Biosimilarity and Interchangeability: Additional Draft Q & As on Biosimilar Development and the BPCI Act is available here) and supplements the two FDA guidances published in December 2018 (Questions and Answers on Biosimilar Development and the BPCI Act and New and Revised Draft Q&As on Biosimilar Development and the BPCI Act [Revision 2]) by providing guidance on Biologics License Applications and product labeling for interchangeable biosimilar products.  At the time of this writing, there is only one BLA for a proposed interchangeable biosimilar product known to be under review at the FDA (Boehringer Ingelheim’s BLA for an Adalimumab to be interchangeable with Abbvie’s Humira®).  However, it is anticipated that additional interchangeability submissions for will be coming in the future (e.g., interchangeable insulins).

Although this new draft guidance document is rather short, it includes some particularly valuable information for those preparing to submit an application for an interchangeable biosimilar product.  A few of the most interesting tidbits (in my mind, anyway) are summarized below.

If your application is intended to support approval for an interchangeable biosimilar product, it is important for this to be stated clearly on the cover letter of your BLA.  Somewhat surprisingly, the guidance informs us that, if you submit a new BLA for an interchangeable biosimilar, the FDA will review the application for biosimilarity and interchangeability separately.  In other words, they will essentially split the review such that, if the data in the BLA will support approval of the product as a biosimilar but not as interchangeable with the reference product, they will issue an approval letter for the biosimilar product and a Complete Response Letter for the interchangeable aspects of the product.  It is not yet clear how the BLA will be split into two submissions, but the fact that the Agency has offered to provide a partial approval in this manner is commendable.  In addition, if you want your BLA to be reviewed only as interchangeable, you must so state on the cover letter “INTERCHANGEABLE-ONLY REVIEW”, in which case the Agency will review it in that light, and, if there are deficiencies, the Agency will outline them in a complete response letter and will not address whether the product could be approved only as a stand-alone biosimilar.

With regard to labeling for an interchangeable biosimilar product, this new draft guidance states that, as is expected for a straight biosimilar product, one should incorporate relevant data and information from the reference product’s label (e.g., safety and efficacy information).  However, the FDA does NOT recommend including data and information from the clinical studies conducted to demonstrate interchangeability with the reference product.

Also, with regards to labeling, it is expected that the package insert for the interchangeable product will include a specific statement on interchangeability.  The format and placement for this interchangeability statement is provided in the draft guidance.  Specifically, the following statement should be placed in the “Highlights of Prescribing Information” section of the label just below the “Initial U.S. Approval” statement:

[Interchangeable Biosimilar’s Prorietary name (interchangeable biosimilar’s proper name) is interchangeable* with [REFERENCE PRODUCT’S PRORIETARY NAME (reference product’s proper name)]

The asterisk is to direct the reader to a footnote regarding the meaning of interchangeability that is to be placed at the end of the “Highlights” section of the package insert.  In the interest of brevity, this footnote is not provided here, but is available in the draft guidance itself.

As this is a draft guidance for industry, it is open for public comment until January 19, 2021.  So, you are encouraged to download the document, read it carefully, and provide feedback to the FDA via the docket at