First Nuvaring Generic Equivalent Filed with a Paragraph IV Certification

Appearing on the FDA’s Paragraph IV database listing on December 3, 2013 is an ANDA filing for Ethinyl Estradiol and Etonogestrel drug-emitting polymeric ring that is used as a contraceptive to prevent pregnancy.  According to product labeling, NuvaRing is made of ethylene vinylacetate copolymers (28% and 9% vinylacetate) and magnesium stearate, and contains 11.7 mg etonogestrel and 2.7 mg ethinyl estradiol.  The dimensions are stated as having an outer diameter of 54 mm and a cross-sectional diameter of 4 mm.

What caught my eye and what it interesting about this product is that it is the first of a kind ANDA for an intravaginal contraceptive product of this nature.  In addition, its posting date (December 3, 2013) and the ANDA submission date listed as June 17, 2013 (see chart below) suggests that either OGD has a very extensive backlog of ANDAs to process, or that this application presented some unique issues of either bioequivalence or chemistry manufacturing and controls that had to be resolved prior to a decision to receive (file) the application.  My guess is that it might be the latter, since OGD has said it was expediting initial completeness and acceptability reviews of ANDAs with Paragraph IV certifications (indicating a challenge to the patent listed for the reference listed drug).

The Orange Book shows a patent expiration date of the only listed patent (5989581) of April 8, 2018.  Further examination of the FDA web page at  (here) shows an October 4, 2013 approval of an efficacy supplement supported with clinical data.  That usually means a period of market exclusivity if the clinical studies were deemed essential for approval.

The approval letter of this supplement states the following:

“This “Prior Approval” supplemental new drug application provides for revisions to the labeling based on the results of two epidemiologic studies that evaluated the risk of venous thromboembolic events (VTEs) associated with use of NuvaRing compared to the risk associated with use of other combination hormonal contraceptives (CHCs).”  

Based on this supplement, new warning/risk information was included in the labeling; however, to date, there is no indication in the Orange Book of any new 3-year period of market exclusivity that would typically be awarded for such a supplement.  It could be that the Orange Book just has not yet been updated.  The next issue is, if exclusivity is awarded, can the new risk information be carved out or will this supplement block ANDA approval for three years from the date of the supplement’s approval?  With ANDA review times being long especially for a first-of-a-kind product and, with either patent litigation or the natural expiration of the patent in 2018, this may be a moot question, unless the patent falls prior to October 4, 2016, three years from the date of the supplemental approval.  Let us keep an eye on this interesting case.

For information on complex drug patent and exclusivity issues or other regulatory questions, please contact Joan Janulis at j.janulis@LachmanConsultants.com