FDA Issues New Biosimilars Guidance Documents, Proposed Rule

December 21, 2018

Biosimilars Team

In the interest of taking “additional new steps” to “[promote] more competition when it comes to biosimilar products,” the Food and Drug Administration (FDA) has issued four new guidance documents and a proposed rule. The guidance documents and proposed rule were announced by FDA Commissioner Scott Gottlieb, MD, in a statement released on December 11.

Question and Answer Guidances

Two of the guidance documents provide answers to common questions from prospective applicants and other interested parties regarding the Biologics Price Competition and Innovation Act of 2009 (BPCI Act). They are companion documents—one draft guidance and one final guidance—intended to offer greater clarity on scientific and regulatory considerations for the development of biosimilar and interchangeable products. The FDA issues each question (e.g., “Can a proposed biosimilar product have a formulation that is different from the reference product?”) and associated answer in draft form in the draft guidance document, receives comments on the draft Q&A, and, as appropriate, moves the Q&A to the final guidance document, after reviewing comments and incorporating suggested changes to the Q&A, when appropriate.

The newly issued final guidance document “Questions and Answers on Biosimilar Development and the BPCI Act” is a revision of “Biosimilars: Questions and Answers Regarding Implementation of the Biologics Price Competition and Innovation Act of 2009,” which was issued in April 2015. The draft guidance document “New and Revised Draft Q&As on Biosimilar Development and the BPCI Act (Revision 2)” is a revision of “Biosimilars: Additional Questions and Answers Regarding Implementation of the Biologics Price Competition and Innovation Act of 2009”; the previous version was issued in May 2015.

Electronic or written comments on the draft guidance are being accepted through February 11, 2019.

“Deemed to Be a License” Guidances

The other two guidance documents describe how—starting on March 23, 2020—the FDA will transition certain biological products currently approved as drugs under the Food, Drug, and Cosmetic (FD&C) Act to be licensed as biologics under the Public Health Service (PHS) Act. The final guidance titled “Interpretation of the ‘Deemed to be a License’ Provision of the Biologics Price Competition and Innovation Act of 2009” and the draft guidance titled “The ‘Deemed to be a License’ Provision of the BPCI Act: Questions and Answers” discuss how certain biological products such as insulin and human growth hormone will be removed from the Orange Book and transitioned to the Purple Book, and pending NDA supplements will be converted to pending BLA supplements. Deeming the transition “a watershed moment for insulin products,” Gottlieb explained that this transition “will enable, for the first time, products that are biosimilar to, or interchangeable with, [biological] products to come to market.”

Electronic or written comments on the draft guidance are being accepted through February 11, 2019.

Proposed Rule

The proposed rule “Definition of the Term ‘Biological Product’” is intended to clarify the statutory framework under which biological products are regulated. The BPCI Act amended the definition of biological product in section 351(i) of the PHS Act to include a “protein (except any chemically synthesized polypeptide).” Under the proposed rule, the term protein would mean any alpha amino acid polymer with a specific, defined sequence that is greater than 40 amino acids in size. A chemically synthesized polypeptide would mean any alpha amino acid polymer that is made entirely by chemical synthesis and is greater than 40 amino acids but less than 100 amino acids in size. Formalizing these interpretations would reduce regulatory uncertainty over whether certain products are regulated as drugs or biological products.

Electronic or written comments on the proposed rule are being accepted through February 25, 2019.