Getting Ready for October 1, 2014 – the Reality Check is Coming!

Having previously written about the need for Generic companies to step up the quality of their submissions to avoid refuse-to-receive (RTR) letters as well as avoiding time review penalties for major amendments or multiple minor or unsolicited amendments (here), I must take a moment to perform a reality check on what happens when the Generic Drug User Fee Act’s (GDUFA) metric kick in on applications submitted after October 1, 2014.  As we know, there are no metrics for ANDAs submitted in years one and two of GDUFA; however, years three through five must be looked at with intense scrutiny in light of the good, the bad and the (potentially) ugly aspects of the metrics themselves.

So as we begin the march through year two of GDUFA leading up to year three, what have we seen so far?  First, a tightening of the RTR and amendment requirements with bar set at what one might call a compromise position between what FDA might have wanted and what was ultimately negotiated at the GDUFA table.  There were some indications that the starting point for RTR and application cycle reviews might have been as stringent as not permitting the receipt of an ANDA for any shortcomings or even fewer than is permitted under the new somewhat restrictive guidance.  The second observationrelates to how to treat amendments to ANDA post-receipt.  There was some talk about requiring withdrawal and resubmission of a pending ANDA if any significant changes were made post-receipt (e.g., addition of new API source, addition or change in the manufacturing site of the ANDA product, change in formulation, etc.) However, a more gentle (but not much more) approach was adopted that provided penalties for new amendments to ANDAs in terms of timing (delay) of review and also going as far as taking the ANDA off the GDUFA review clock if the type and limit on the number of amendments is exceeded.  (Again please see previous blog post cited above).

Communications practices have changed dramatically, as those of you who have tried to call OGD may have discovered.   Complete Response Letters (that are supposed to be the norm now) are not always Complete Response Letters but resemble more of the informational request letters one might see from the New Drugs side of the house, in selected instances.  These types of inconsistencies in policy and action leave the industry with many unanswered questions of policy versus substance.

But the process moves on, and we all hope that behind the scenes things are improving.  The number of approvals in November (40) doubled that seen in October (20) and was significant higher that the 26 approved in September (26). But it is still too early to tell if the improvement is real.

Questions of how OGD will deal with the year one and two GDUFA submissions when it must concentrate on meeting its year three and beyond metrics and goals linger.  We still don’t have an answer to that one, albeit OGD’s Acting Director stated at the GPhA Fall Technical Meeting that she anticipated that OGD will strive to meet and or exceed all GDUFA goals.

The reality of some of the GDUFA-mandated review time penalties have not been experienced by the industry yet.  But let me assure you-they are coming.  And when an ANDA is knocked off of the GDUFA goal date because of submission of more than 5 minor amendments, one major amendment or when the firm submits additional CMC information in its request for final approval post -entative Approval and finds that this will set the review clock an additional 4 to 6 or even 12 months away, that is when reality will set in and that is when the screams from the hills will be heard echoing off the OGD buildings.

Again the advice – concentrate on quality, quality, quality, and the final quality of the submissions will be assured.  When the ANDA is originally submitted it should contain all information that will represent the desired manufacturing process and desired product.  Submissions must be clear and concise.  The use of principles imbedded in Quality by Design (QbD) and the question-based review (QbR) format will be imperative to demonstrate that the firm understands its product and the products’ manufacturing space.  Gone will be the days of developing your product on the clock, and those that continue to do so, will end up at the back of the bus.  We are a year and a quarter into GDUFA.  It is time not only to hear the Agency, but to respond to their challenge if you want to be there at the making of the market for any product.

Outside review by a third party may be a valuable addition to internal review.  While it may add costs to the process, it may save significant time in obtaining approval in the long run and we all know that time in the generic market place is money.  Don’t trick yourself into thinking that OGD really has not changed and remember the advice my wife always gives me “Cheap isn’t cheap, cheap is expensive”.