FDA issues new guidances to advance biosimilars

In its ongoing efforts to advance new policies that are aimed at promoting more competition for biosimilar products, the Food and Drug Administration last week issued four new guidance documents.

Noting that the Biosimilars Action Plan that the agency released last July advances the FDA’s ongoing implementation of the Biologics Price Competition and Innovation Act, or BPCIA, FDA commissioner Scott Gottlieb said the agency will focus attention on potentially anti-competitive practices when it comes to biosimilar drugs.

“We’re issuing notice of how the FDA will – upon request – review study protocols submitted by biosimilar applicants to assess whether their protocols contain comparable safety protections to those in the REMS for the reference product they’re trying to reference. If requested, the FDA will issue a letter to the reference product holder informing them that comparable protections exist, and that the FDA won’t consider it to be a violation of the branded drug company’s REMS to provide the biosimilar sponsor with a sufficient quantity of the reference product to perform testing necessary to support its biosimilar application,” Gottlieb said.

The FDA will evaluate how it can make it easier for biosimilar manufacturers to use reference products from outside the U.S., where prices may be cheaper and reference products more accessible.

“We’re also releasing today two critical guidance documents that describe how the agency plans to implement Congress’ direction that we transition certain biological products currently approved as drugs under the FD&C Act to be licensed as biologics under the PHSA. Transitioning these drugs to the PHSA will let them to be treated as biologics under that law. And that means opening them up to competition through the biosimilars pathway. This includes insulin, which has been historically regulated as a drug and not a biologic,” said Gottlieb.

Begining in March 2020, the approved marketing applications for the small subset of “biological products” such as insulin and human growth hormone will be deemed to be biologics licenses under section 351 of the PHSA.

"We’ve shaped these policies to implement the intent of Congress, and to make sure a few things happen. First, that the anti-evergreening provisions under the biosimilars legislation – meant to prevent sponsors from being able to game the exclusivity provisions to forestall biosimilar entry – will apply to these newly deemed products, including insulin," Gottlieb said.

Emphasizing that the FDA wants to make sure that as these drugs transition to the biologics pathway, they don’t receive additional exclusivities that they aren’t entitled to, Gottlieb said,"They don’t get to start benefiting from the 12 years of exclusivity that the law grants to newly licensed biologics, just because these drugs – some of which were approved decades ago – are being treated as biologics for the first time. Once their patents have lapsed, and certain previously awarded exclusivities like orphan drug protection, have run their course, these products can be open to brisk competition from biosimilars."

Pointing out that the transition of biological products currently regulated as drugs to being regulated as biologics will enable, for the first time, products that are biosimilar to, or interchangeable with, these products to come to market, Gottlieb said, "This is a watershed moment for insulin products, which millions of American take each day to maintain stable blood glucose."

The final guidance provides recommendations to sponsors of proposed biological products that are intended for submission in a New Drug Application (NDA) that may not receive final approval under the drug pathway of the FD&C Act by March 2020 to carefully consider how they can align their development plans to account for the transition provisions of the new biologics pathway.

Biological products that have been approved under section 505 of the FD&C Act will be removed from the FDA’s Orange Book on March 23, 2020, based on the agency’s position that these products are no longer “listed drugs.” That means that a follow-on applicant won’t be able to rely upon these NDAs for approval. They have to go down the biosimilars path after the transition. Products approved in NDAs that are deemed to be Biologics License Applications (BLAs) will be included in the Purple Book, which lists biologics licensed by the FDA under the PHSA.

The final guidance also describes the FDA’s plans for supplements to approved NDAs that are pending under the FD&C Act on March 23, 2020. "We intend to administratively convert these pending NDA supplements to pending BLA supplements under the PHS Act. We’re doing this to minimize possible disruption caused by the transition provisions of the BPCIA and provide clarity and certainty to application holders who seek to make changes to their products close to the transition date," Gottlieb said.