- 505(b)(1) – Traditional NDA for pioneer products
- 505(b)(2) – Streamlined approval process for new products with same active moiety as previously approved drug (i.e. a reference listed drug – RLD)
- 505(j) – Abbreviated new drug application (ANDA) (i.e. generic form of an RLD)
There are a number of features that make the 505(b)(2) application process alluring to drug developers, not the least of which are lower costs for development, expedited timelines to approval, and the protection of several years of market exclusivity...
- Proven pediatric safety and effectiveness for formerly adult-only approval
- Alternative formulations or new dosage strengths deemed bioequivalent to the RLD
- Modified release formulations
- Different doses, regimens or dosage forms
They’re not generics, and they’re not completely new. This means that while the differences from the RLD need to be supported with the sponsor’s clinical data for safety and effectiveness (often in as few as a single clinical trial), the fuller safety and efficacy profile of the underlying drug can be submitted from investigations not conducted by the sponsor and “with no right of reference.” These data are derived from:
- Public scientific data from the reference-listed drug
- Previous NDA approvals
- A comprehensive review of the published medical literature
The ability to rely on a well-established safety and efficacy profile as a significant part of the submission can save a drug developer untold amounts of time and cash.
In addition to these savings, Hatch-Waxman provides another extremely attractive advantage for some 505(b)(2) approvals: market exclusivity. Depending on the extent of the differences between the 505(b)(2) drug vs. the reference-listed drug, an approval can (though not always) bring along with it three, five or even seven years of market exclusivity. And this can be extended, in some cases, for 6 months with pediatric studies. Unlike a patent, which can be challenged and found invalid, exclusivity cannot be taken away and the term only starts at approval.
The 505(b)(2) pathway is not available for every follow-on NDA (see here for Guidance for Industry: Applications Covered by Section 505(b)(2)). For this reason it is critically important to establish a dialogue early on with the FDA to determine if 505(b)(2) is a suitable path. But for smaller companies with limited resources and promising innovations on existing drugs, the rewards can be rapid, reasonably-won, and lasting.
First Published in the Life Science Executive Network "Biotech Bulletin" Fall 2015.
[i] Jill Orens, “2014 505(b)(2) NDA Approvals,” The 505(b)(2) Blog, January 17, 2015, http://blog.camargopharma.com/index.php/2015/01/17/2014-505b2-nda-approvals/.