Complete Response Letters Reach 3rd Highest Monthly Total Under GDUFA

February saw the 3rd largest number of Complete Response Letters (CRLS) issued (129) in a single month since the implementation of GDUFA.  Previous highs were 134 in July FY 2015 and 130 reached in November FY 2013. With the review machine gearing up, wouldn’t one expect the number of CRLs to be steadily increasing each month?  Maybe not!  If the information requests (IRs) keep flying out the door along with easily correctable deficiencies (ECDs), then maybe the number of CRLs will remain lower.  Or is that wishful thinking?  That logic would seem to mean that the number of approvals should be soaring.  Well, if you look at the total number of approval actions plus the number of CRLs, the total has actually been going up, and why?  Because the number of monthly approvals has increased in FY 2016!

Take a look at the Activities Report of Generic Drug Program Activity for FY 2015 (here)  and FY 2016 (here) and see for yourself.  You can parse the numbers anyway you want but in total these signs are positive.  The real question is, where does the program need to be before the industry is happy?  I have no answer to that question but have the same hopes as FDA and the rest of the generic pharmaceutical industry.

One thing that does puzzle me is the very low number of requests for post-CRL meetings (teleconferences).  In the first four months of FY 1016, there were only 7 such meeting requests from industry (remember, when looking at the Activities Report, the number is cumulative not per month, and it is believed that the numbers reported are from the beginning of GDUFA).  I guess that industry has a better understanding of the questions in the CRLs than they did at the beginning of GDUFA.  Perhaps that is because they have previously seen most of the questions that eventually appear in a CRL in IRs and ECDs already for the application.  Maybe this is progress.  But remember that CRLs mean another review cycle and review cycles are what cause longer approval times – they are truly the gift that keeps on giving, according to Dr. Uhl.  Sure, we would like to see many more 1st cycle approvals, but when OGD asks for new studies on polymorphs or in use studies, or the generation of additional data and then gives you 10 days to respond, that is basically unrealistic and maybe a CRL should just be issued.   This is something I think that industry and the Office of Generic Drugs (OGD) need to hash out in terms of what makes more sense.  While we don’t want to delay a response to an IR (but know that we can’t meet the deadline even with a reasonable extension), we also don’t want to waste Agency resources in issuing an IR, just to have to issue a CRL 10 or 20 days later.  OGD and industry need to realistically look at ways to further the efficiency of the process and being more realistic in issuing IRs may be one small way to do so.  I think it is time that we talk about it!