FDA has published new draft guidance for industry titled “Biosimilarity and Interchangeability: Additional Draft Q&As on Biosimilar Development and the BPCI Act.” 

The draft guidance supplements two prior documents concerning biosimilar interchangeability published in December 2018.[1]  This new guidance, in particular, has some useful information for prospective applicants who seek licensure of an “interchangeable” biosimilar product. 

The BPCI Act created an abbreviated licensure pathway under § 351(k) of the Public Health Service Act (PHS Act) for biological products shown to be “biosimilar” to, or “interchangeable” with, an FDA-licensed biological reference product.  Specifically, an applicant who seeks to demonstrate “interchangeability” needs to show “biosimilarity” plus the additional requirements under § 351(k)(4) of the PHS Act.  In turn, interchangeable products may be substituted for the reference product without the intervention of the prescribing healthcare provider.  See PHS Act § 351(i)(3).

FDA’s recent guidance addresses a situation where a BLA submitted under § 351(k) for “interchangeability” does not contain data and information sufficient to support licensure of the product as an interchangeable biosimilar, but does contain data and information sufficient to support licensure as a biosimilar.  In this circumstance, some applicants may still want their product to receive licensure for biosimilarity.

The draft guidance states that “FDA intends to split the application for administrative purposes,” which would allow FDA to take separate actions.  Draft Guidance at 5.  FDA could license the product as a biosimilar product and convey in a complete response letter any deficiencies in the application for licensure as an interchangeable biosimilar.  Id.  FDA could later decide interchangeability upon submission of supplemental data and information.  Id.

However, if the BLA applicant does not want FDA to make a determination on biosimilarity, the draft guidance explains that the applicant may indicate that the review is only for interchangeability.  Id.  In this situation, an FDA complete response letter may still include deficiencies pertaining to a demonstration of biosimilarity (because it is a condition required for interchangeability), but it would not address whether the application was sufficient to support a demonstration of licensure as a biosimilar product alone.  Id.

Another question the draft guidance seeks to address is what happens if a § 351(a) BLA holder of a licensed biological product would like to show that the same product is biosimilar to, or interchangeable with, another licensed biological product, i.e., another reference product.

The draft guidance explains that the § 351(a) BLA holder would need to submit an original application for licensure under § 351(k) with data and information showing biosimilarity to, or interchangeability with, a reference product.  Id. at 6.  However, the applicant may use relevant data and information from the applicant’s own § 351(a) BLA.  Id. at 7.  The § 351(a) BLA holder does not need to seek revocation of its § 351(a) license in order to proceed with the § 351(k) application.  Id.  In addition, the § 351(a) BLA holder may continue to market its product while the § 351(k) application is pending and even after it receives licensure under § 351(k).  Id.

Finally, with respect to the labeling of interchangeable biosimilars, the draft guidance recommends that relevant data and information, including safety and efficacy data, from the reference product labeling should be included.  Id.  While the labeling should include a statement of interchangeability with the reference product (id. at 9), FDA advises against including data and information that demonstrates interchangeability.  Id at 7.  Further, it may be appropriate for interchangeable biosimilar labeling to deviate from that of the reference product to the extent an applicant sought licensure for fewer than all of the reference product’s licensed conditions of use.  Id. at 8.

FDA intends to provide any additional recommendations for interchangeable biosimilar labeling in future guidance.  Id. at 9.