Return to the Proposed 505(b)(2) and ANDA Proposed Rule

After about a week or so off from reading on in the massive missive of the Proposed Rule, we are back cherry picking tidbits from the document that you may find interesting.  For instance, FDA is codifying the method in which it will notify an ANDA applicant that FDA has refused to receive the ANDA.  Believe it or not, the regulations, as currently written, state that FDA will notify the applicant by telephone of the decision.  We all know that while you might get a call asking for more information before the decision is made, the FDA’s historical practice is to issue a refuse-to-receive letter making the determination.  Therefore, FDA is proposing to amend §314.101(b)(3) to remove the method of notification by which FDA will advise an ANDA applicant that FDA has refused to receive the ANDA under § 314.101(d) or (e) to clarify its method of notification.

Removal of “Delayed Effective Date”

FDA is finally getting around to removing the historical “delayed effective approval” from the regulations.  This change harkens back to the policy prior to the Generic Drugs Scandal in the late 1980’s where FDA would approval an ANDA with a delayed approval date and the applicant could just enter the market after the date specified in the letter, usually based on an unexpired patent or period of market exclusivity associated with the reference drug upon which the ANDA was based.  Because of fraud found in a number of ANDAs, the FDA abandoned Approval Letters with delayed effective approval dates and moved to the Tentative Approval Letter (which notes is not an approval of the application and states the application cannot be marketed until a final approval letter is issued) to give the Agency one last bite at the apple if they find a problem with the data, the requirements change prior to approval, or one or more facilities are no longer in compliance with cGMPs.  In addition, the applicant that has received a Tentative Approval letter is required to update its application with any changes prior to final approval.

No 30-month Stay or Requirement for 45-day Period After Notice if Patent Listed After 505(b)(2) or ANDA Submission

As we all know, if an ANDA or 505(b)(2) is already submitted and the RLD holder lists a new patent in a timely manner, the notification provisions of the Act do apply, but there is no 30-month stay even if the RLD holder or patent holder initiates suit.  FDA is clarifying this position in the Proposed Rule and also making clear that if the application is otherwise acceptable for approval, the Agency can immediately approve the application as there is no 45-day waiting period in this circumstance.

Only One 30-month Stay Available – in Most Cases

The Medicare Modernization Act (MMA) generally limits the 30-month stay for an ANDA or 505(b)(2) applications to one.  This provision was placed into law to avoid the practice of evergreening multiple patent listings over time into multiple 30-month stays.  While patents listed after an ANDA or 505(b)(2) application is submitted will not result in a second 30-month stay, there are instances where a second 30-month stay might arise.

As FDA explains:

“Multiple 30-month stays, however, still may be possible in certain cases. For example, an original 505(b)(2) application or ANDA may contain a paragraph IV certification to a patent that results in a 30-month stay of approval. If the same application also contains a paragraph III certification to a different patent that was submitted to FDA on or after August 18, 2003, and before the 505(b)(2) application or ANDA was submitted, and the applicant subsequently amends the paragraph III certification to a paragraph IV certification, a second 30-month stay would be possible. Two 30-month stays are possible in this example because the challenged patents that gave rise to sequential actions for patent infringement were both submitted to FDA before submission of the original 505(b)(2) application or ANDA. It should be noted that the relevant benchmark for determining whether a patent was submitted by the NDA holder prior to submission of an original 505(b)(2) application or prior to submission of an ANDA later determined to be substantially complete is the date of submission of the patent to FDA and not the date on which the patent information is published in the Orange Book. We note, however, that if the original submission of an ANDA is not determined to be substantially complete (i.e., FDA refuses to receive the ANDA under § 314.101), then the relevant benchmark is the date of the ANDA amendment that results in a subsequent determination that the ANDA is substantially complete.”

Try not to let your head explode, there is more to come on this Proposed Rule, but we are getting close to the end of outlining what we think are some of the more interesting highlights.