Did you ever wonder about the FDA’s requirement than an applicant respond to a complete response letter (CRL) within one year of its issuance as provided for in the regulations at 21 CFR 314.110?  Under this regulation, “an applicant must (1) resubmit its ANDA (i.e., submit all materials needed to fully address all deficiencies identified in the CRL), (2) withdraw its ANDA, or (3) request the opportunity for a hearing.”  Failing to take any of those three options within the prescribed timeframe can be considered by the FDA as a request from the applicant to withdraw its application.

Well, today, the FDA spelled out how to request an extension for response to a CRL if the applicant cannot respond within the regulatory one-year time period.  While I have never known the FDA to deny a request for an extension of time, it appears that the FDA is raising the stakes with this draft guidance titled Failure to Respond to an ANDA Complete Response Letter Within the Regulatory Timeframe.  A copy of the guidance can be found here.

Most of us know that the FDA did not pay too much attention to this regulation until a few years before the first GDUFA legislation was enacted.  Over the course of time, the FDA has become more stringent in watching this one-year deadline and has sent dunner letters in the past.  As noted above, I am not aware of the FDA actually withdrawing an ANDA after a request for extension or even in doing so after multiple requests for extensions.  Previously, these requests were almost always automatic.  Just ask!  Now the Agency is looking behind the kimono and asking firms for reasons why a request for extension is being made and when the applicant plans on responding, and is asking for a description of the circumstances that are preventing the applicant from responding.

The Agency notes that there are circumstances where firms do not respond to a CRL for a number of years.  This often requires the submission of new information, new bioequivalence studies, updates to USP test methods, revised impurity specifications, or changes to the manufacturing process.  This requires extra scarce FDA review resources to assess the changes to application, and oftentimes the original reviewer is no longer there or the period of time is so long that it necessitates rereview of the entire application.  This causes an increase in the number of ANDA review cycles and distorts both the mean and median approval times of ANDAs.  In a phrase, “it makes the OGD’s numbers look bad.”  And I agree with that assessment.  Firms seeking approval of products should pursue product approval with a high degree of diligence.

Now, I am not saying (nor does the guidance) that the FDA will be unreasonable in granting requested extensions, but it basically hints that there will come a time when it may say no.  Not sure if there is great appetite for the FDA to take such regulatory action, but the FDA does set up some reasonable requirements for the extension requests and outlines how, what, and where such requests should be made.  It is like when you were a kid at baseball practice, how many swings at the ball do you get to take before you hit the ball and the next batter gets a chance.

So, don’t worry about making requests, but be diligent in pursuing approval and provide the FDA with a good explanation for any extension request.  And, if you are holding onto the application just because you view it as an asset but have no intent on pursuing approval, let it go.  Or, put another way, don’t hog the bat.