New Paragraph IV Listings – Some Interesting Observations

The FDA’s paragraph IV (PIV) database is designed to give applicants and potential applicants information relative to first-to-file opportunities.  FDA does this for two reasons: 1) it gives applicants assurance that their product is a first-to-file if the acknowledgement date (date acceptable for filing) on their letter from FDA officially receiving their application matches the date of submission in the PIV database.  This has eliminated the many calls to the Office of Generic Drugs (OGD) to find out if their submitted application holds a potential first-to-file seat;  2) the listing also informs potential applicants that at least one ANDA has been submitted with a PIV certification and allows others to decide if they wish to enter the fray and expose themselves to litigation.

FDA finally decided to begin publishing this listing on March 2, 2004.  While it has relieved some of the pressure on FDA relative to inquiries from sponsors, it also generates some interesting reading.

In this list (accessed today here), there are four items I would like to point out.  The first two are that there has been more than one year since submission of the first two listings.  As explained in previous posts, there are a number of reasons for such delays, but when you see first time products for complex dosage forms (in this case, sublingual tablets and a transdermal system), oftentimes the evaluation of whether the bioequivalence information submitted in the ANDA can purport to demonstrate bioequivalence is always a possible cause of delay.  That does not mean that there is a problem with the data but more often  OGD has not yet determined exactly what they are looking for as far as BE studies go.  Sometimes there are complex CMC issues or inactive ingredient issues that must be evaluated and, rarely, sometimes there may be a consult needed outside of OGD.  But, despite these issues, 12 and 14 months seems a bit long for resolution.  It could also be that OGD missed posting the receipt, but that cannot be known until the application is actually approved.

The two other items that caught my eye were the receipt of the Glatiramer Acetate 40mg/mL on February 26, 2014 for a product that was first approved for the innovator on January 28, 2014, and the Hydrocodone Bitartrate submission date of Feb 26, 2014 for an innovator product first approved on October 25, 2013.  What is of interest is the short timelines between NDA approval and ANDA submission.  It is clear that generic companies are attempting to be first-to- file as early as possible to secure a potential 180-day exclusivity period and this desire has firms working well before NDA approval to be ready to test their products as soon as an innovator is approved.

Years ago, an innovator had plenty of time before they had to worry about a challenge to a product with a patent; now, the patent challenge comes (in some cases) only weeks or months after the original NDA is approved.

With the generic industry being as nimble as they appear to be, the pressure on OGD to meet approval or tentative approval for these product in the 40, 36 or 30 month period (depending on when they are submitted) to prevent forfeiture of the exclusivity period becomes even greater especially for unique or complex products.







Asenapine Maleate Sublingual Tablets 5 mg and 10 mg Saphris 8/13/2013
Buprenorphine Transdermal System 5 mcg/hr, 10 mcg/hr, and 20 mcg/hr Butrans 6/6/2013
Calcium Acetate Oral Solution 667 mg/5 mL Phoslyra 12/5/2013
Eltrombopag Olamine Tablets 50 mg and 75 mg Promacta 1/7/2014
Glatiramer Acetate Injection 40 mg/mL, 1 mL pre-filled syringe Copaxone 2/26/2014
Hydrocodone Bitartrate Extended-release Capsules 10 mg, 15 mg, 20 mg, 30 mg, 40 mg, and 50 mg Zohydro ER 2/26/2014
Nicotine Transdermal System 7 mg/24 hrs, 14 mg/24 hrs, and 21 mg/24 hrs Nicoderm CQ 5/30/2014
Tacrolimus Extended-release Capsules 0.5 mg, 1 mg, and 5 mg Astagraf XL 11/15/2013
Topiramate Extended-release Capsules 200 mg Trokendi XR 4/3/2014