Earlier this month, the FDA approved the biosimilar Zarxio (filgrastim-sndz) for sale in the United States.  This approval – the first of its kind under the so-called 351(k) pathway – comes nearly five years after the pathway was created by the Biologics Price Competition and Innovation Act (“BPCIA”).

Prior to the passage of the BPCIA and to this day, another regulatory pathway, the 505(b)(2) pathway, could be used to obtain approval of certain follow-on biologics.  Like the 351(k) pathway, the 505(b)(2) pathway allows the applicant to rely on the safety and effectiveness data of a previously-approved product.  The 505(b)(2) pathway, while largely used to obtain approval of small-molecule drugs, has been used on several occasions to obtain approval of biologics that are similar to the reference product and marketed as biosimilars in Europe.

What is the 505(b)(2) Pathway?

A 505(b)(2) application is an application for approval of different dosage forms, formulations, or combination products of already-approved drugs , but can also be available for approval of biologics that are similar to, and rely on information contained in, a previously-approved New Drug Application (NDA).

The 505(b)(2) pathway is available for a relatively narrow category of biologics – specifically, those that had been approved under an NDA before the BPCIA was signed into law in March 23, 2010 – and it is only available for that narrow category of biologics until March 23, 2020.  See § 7002(e) of the Affordable Care Act (ACA).

But for the biologics that fit into this category, the 505(b)(2) pathway offers a pathway for marketing approval.  Notably, any product approved under the 505(b)(2) pathway will be considered approved under the 351(k) pathway once the ten-year phase-in period is complete.  Id. at § 7002(e)(4).

What are the differences between the 505(b)(2) and 351(k) pathways?

Fundamentally, the 351(k) pathway concerns products that are regulated as biologics under the BPCIA, while the 505(b)(2) pathway concerns products that are regulated as drugs under the Food Drug & Cosmetic Act (FD&C).  The pathways involve vastly different regulatory frameworks.  The table below summarizes some of these differences.

Click here to view the table.

505(b)(2) Example Cases

A number of biologics have been approved under the 505(b)(2) pathway.  Examples of five 505(b)(2) products, all produced by recombinant DNA technology, are discussed in the table below.

Click here to view the table.


The 505(b)(2) pathway offers marketing approval for certain “biosimilars” – at least for the next five years. In addition to a more predictable regulatory pathway, the litigation pathway for 505(b)(2) products is more familiar and predictable as well.