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The US Biosimilars Pathway: Key Questions

In 2015, FDA issued a number of final guidance documents for biosimilars.  But many fundamental questions remain unsettled and the industry awaits FDA’s guidance on labeling of biosimilars, the requirements for interchangeability, and naming, among others.  There is much ahead for the US biosimilars pathway in 2016.

In April 2015, FDA released three final guidances for biosimilars, including one in Q&A format titled “Biosimilars: Questions and Answers Regarding Implementation of the Biologics Price Competition and Innovation Act of 2009.”  This Q&A document finalized a draft guidance issued in 2012, but omitted questions on several important topics that had appeared in the earlier draft, including a Q&A on the determination of interchangeability, signaling that FDA’s views are still developing in this important area.  Those omitted questions, along with several new ones, appeared in a new draft guidance released in May, “Biosimilars: Additional Questions and Answers Regarding Implementation of the Biologics Price Competition and Innovation Act of 2009.”  FDA’s draft guidance states, as it did in February 2012, that “[a]t this time, it would be difficult as a scientific matter for a prospective biosimilar applicant to establish interchangeability in an original 351(k) application given the statutory standard for interchangeability and the sequential nature of that assessment.”

In April 2015, FDA also issued a final guidance titled, “Scientific Considerations in Demonstrating Biosimilarity to a Reference Product.”  That guidance drew criticism for eliminating labeling information to distinguish the biosimilar product from its reference product, such as identifying the product as a biosimilar.

Industry is pressing for guidance to address both labeling and interchangeability.  The label for Sandoz’s Zarxio, the first and only US biosimilar to be approved under the biosimilar pathway, does not state that Zarxio was approved as a biosimilar of Neupogen, nor does it state that Zarxio is not interchangeable with Neupogen.  Both of these issues raised concerns, and in June 2015 AbbVie, an innovator company, filed a citizen petition stating FDA’s approach to labeling was inconsistent with the Biologics Price Competition and Innovation Act of 2009 (BPCIA) and misleading.  BIO and PhRMA also recently filed a citizen petition urging FDA to require labeling that distinguishes a biosimilar product from its reference product including identifying that it is a biosimilar and stating that the biosimilar has not been approved as interchangeable with the reference product if there has been no such approval.  They also ask FDA to promptly issue a labeling guidance document.

In addition, AbbVie filed a citizen petition requesting FDA establish a standard for interchangeability determinations under the BPCIA.  AbbVie asked FDA to require that applicants seeking interchangeability determinations meet the statutory “Safety Standards for Determining Interchangeability” with respect to each indication.  AbbVie also requested that FDA clarify that the statutory standards for interchangeability differ “in both kind and scope” from the standards for biosimilarity.  Finally, AbbVie asked FDA to hold a Part 15 hearing to seek public input on interchangeability standards.  FDA intends to provide guidance on the requirements for interchangeability and labeling this year.

The naming of biosimilars is another important and unsettled issue.  In August 2015, FDA released draft guidance for naming biosimilars.  It proposed to add on distinguishable meaningless suffixes, consisting of four random letters, to the nonproprietary name of the reference product for both biosimilars and reference biologics.  After critical comments from both innovator companies and biosimilar makers alike, however, FDA may reconsider its approach and use distinguishable meaningful suffixes instead, such as those that identify the manufacturer of the biologic.  FDA took this approach in its placeholder name for Sandoz’s Zarxio, filgrastim-sndz, prior to the issuance of its draft guidance.  Sandoz had suggested filgrastim-sndz as the nonproprietary name for its biosimilar to FDA.  Based on industry comments, it is also likely that the naming scheme used for biosimilars products will be applied to the naming of interchangeable products as well.

With additional biosimilars expected to be approved this year, FDA’s guidance on labeling, naming and interchangeability (though no biosimilar maker has sought to qualify as an interchangeable product yet) is particularly important.

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