The Ying and Yang – CRLs vs IRs ECDs and Approvals


As they say, “you learn something new every day”!  Perhaps I knew this all along but I had my suspicions confirmed yesterday.  So what is it that I learned?  That Complete Response Letters (CRLs) (remember those letters where FDA was going to respond all at once with Division level review and you were not going to get any more discipline specific letters?) are a harbinger of “approval issues that are too great to resolve through other means”.  Yes, that’s right, expect a CRL if issues are complex or too vexing to permit approval.

Now what about Information Requests (IRs) and Easily Correctible Deficiency (ECDs) letters?  Well, OGD has listened to the industry, and has recognized that the New Drugs model of real time review and communication relative to issues regarding the application may work better in driving the application towards approval.  Thus, the IRs and ECDs are more like mini discipline-specific reviews that will allow the ANDA application to continue moving through the system and hopefully towards approval faster.  These correspondences also give the industry time to response to outstanding issues earlier in the review process and will benefit the firms overall, especially if other disciplines that have not yet completed their reviews find no problems in the submission.  Thus, it gives the industry a leg up in the timing department.

Doesn’t this sound like the Office of Generic Drugs (OGD) of old?  Well, yes to some extent, but now that the coordination efforts are more honed, hopefully the process will run smoother with defined review and response times that are associated with the IRs and ECDs.

In looking at some new statistics, it is becoming more clear that the reason the numbers of approvals are slowly creeping up while the number of CRLs has appeared to lag is that the body of effort expended by OGD to keep the application on track for approval rather than a CRL has maybe not been as obvious to industry.  In addition, confusion about what an IR and ECD actually represent has baffled many on the industry side.  Now we know that you may get an IR or ECD from each of the disciplines, so don’t think that because you get an ECD or IR from the quality group, that your labeling, micro, bioequivalence or compliance status is acceptable.  You may get multiple “interim” request for information.

Just to give you an idea of the workload that may have been diverted from issuance of CRLs in FY 2015, OGD issued 4276 IRs and ECDs in FY 2015 through August 31 (September figures are not yet in) and about 1000 CRLs.   Thus much of the effort that goes into issuance of approvals and CRLs have been shifted “temporarily” to real time issuance of IRs and ECDs.  OGD believes that this will translate into a larger number of approvals and thus a lower need to issue CRLs.

I know that this might be a bit obtuse and recognize that you may be skeptical before the approval numbers really shoot up, but when you think about it,  it makes perfect sense.  The New Drugs folks have about an 85% first cycle approval rate using a similar system, whereas OGD has less than a 3% first cycle approval rate.  Let’s take a look at how that number fares in FY 2016.  Please remind me if I forget! Oh and yes – get those IR and ECD responses back into OGD quickly!