The Uncertain Future of Exclusivity for § 505(b)(2) NDAs

Navigating the Meaning of Conditions of Use, Innovation, and Clinical Benefit under Braeburn
By Ed Allera  - Chairman of The 5059B)(2) Platform

​For decades, several basic concepts have driven drug development.  New drug sponsors first developed and received FDA approval for new chemical entities as immediate release tablets dosed two to three times per day.  These first-in-class drugs were seldom the best, and competitors continued to improve the molecules through basic concepts of organic medicinal chemistry, including beta-blockers, H2 receptor blockers, ACE inhibitors, calcium channel blockers, and statins.  Other companies added clinical benefits to improve patient compliance by extending release times to decrease the number of doses required per day, or by developing new topical patch technologies for easy administration of extended release products having lower toxicity.  Congress recognized the value of these improved clinical benefits when, in 1984, it enacted the Hatch-Waxman Amendments which provided sponsors with three-year exclusivity for such changes made to a new chemical entity that had been approved in a § 505(b)(1) NDA.  This three-year exclusivity applied whether the changes were approved in the form of a § 505(b)(2) NDA or a supplement to the original § 505(b)(1) NDA.
 
Although FDA has never specifically defined “conditions of use,” technologies providing improved clinical benefit have served as the foundation for the conditions of use that have been granted market exclusivity.  Learning about disease mechanisms of action has been the focus of research for decades and, more recently, genetic profiling has become increasingly vital for treating certain patients, such as oncology patients.  This information has, in turn, led to new approaches to treat chronic, severe, and life-threatening diseases.  Patient-specific therapies and dosing has led to improved clinical benefit by improving the technologies, tests, and delivery systems associated with patient care.  The competition among drug sponsors and drug developers has become increasingly fierce.
 
In July 2019, the U.S. District Court for the District of Columbia remanded a case to FDA for clarity on the definition of “conditions of use” with respect to the grant of three-year exclusivity.  The issues in this case (Braeburn Inc. v. FDA) go to the heart of § 505(b)(2) NDA development.  Both FDA and the court struggled to develop a standard for “conditions of use” that was not arbitrary and capricious.  The Center for Drug Evaluation and Research’s Exclusivity Committee argued that it has used an “innovation” standard for determining exclusivity eligibility, after struggling with a number of approaches that focused on product labeling.
 
As part of a continuing trend of skepticism over FDA’s scientific and legal decisions, the court was unwilling to grant extensive deference to the Agency’s decision.  Instead, the court has demanded that FDA establish boundaries for what constitutes a drug product’s “innovation.”  Significantly, FDA has concluded now that, at least in this case, the patient population has no bearing on “innovation.”
 
FDA’s decisions in light of this case are going to be critical to § 505(b)(2) NDAs and their sponsors.  These issues merit further industry discussion, and continued engagement with FDA.  What are your thoughts on the scope of exclusivity for § 505(b)(2) NDAs?  Please send us your comments to meetings@505b2.org or to our Linked In page.
The 505(b)(2) Platform™ is the only non-profit industry organization championing the cause of § 505(b)(2) products and their sponsors.  We are leading the way, actively working with the FDA to develop more appropriate guidelines and other issues.  Become a member of The 505(b)(2) Platform and help ensure the continued value of your development program and currently marketed products.