Who you Gonna Call . . . . to Resolve a Compliance Status Block on Approval?

By Robert W. Pollock* & Kurt R. Karst –      

If there’s something strange in your neighborhood; Who you gonna call? If there’s something weird, and it don't look good; Who you gonna call? Unfortunately, FDA doesn’t have a Ghostbusters-type unit to call when there’s something strange or weird compliance-wise going on in your neighborhood that’s holding up final ANDA (or 505(b)(2) NDA) approval. (Oh, and you’re welcome for the earworm!)

The GDUFA program has spurred an increase in the number of inspections for generic drug applicants and the establishments identified in those applications. With the increasing number of inspections, comes an increase in Establishment Inspection Reports (“EIRs”) that need to be written by FDA investigators, cleared by their supervisors, and then reviewed and cleared by the Center for Drug Evaluation and Research’s Office of Compliance. As was noted in a recent post on the Lachman Consultants Blog, there appears to be a growing problem in getting timely resolution of compliance-related issues from the time the EIR leaves the field and up until FDA’s computer systems are updated to provide an acceptable finding.

Our firms (Hyman, Phelps & McNamara, P.C. and Lachman Consultant Services, Inc.) have been hearing a rising chorus of complaints about being stuck in what one applicant called the “Compliance Black Hole.” Another company referred to it as the “Endless Summer,” because that company has been trying to figure out when their compliance status will change in the FDA computers after having received no 483 observations on reinspection since March of this year.

Firms note that calls to FDA Regulatory Project Managers (“RMPs”) or Regulatory Business Project Managers yield the same response: “There is nothing we can do until the computer system is updated.” Many of these responses come after the issuance of a Complete Response Letter (“CRL”) stating that the only outstanding issue is resolution of the status of a facility’s compliance. So the firm is stuck in a waiting mode.   Simply calling the Office of Compliance has yielded basically the same result. Clients are telling us that they do not receive return calls (or that they are simply told to sit tight and wait).

Trying to find a sympathetic ear at FDA is also difficult, particularly when a firm is ready to launch but for the final compliance clearance and approval action. In addition, we have heard from firms with potential date-certain launch dates (either day-181 dates or settlement dates) that they were informed by FDA officials that the compliance status of their application remains unresolved in the Agency’s computer system, notwithstanding the fact that the sponsor was informed by an FDA field investigator that there were either no 483 observations following inspection, that a completed EIR was forwarded to CDER finding satisfactory the firm’s responses to inspectional observations, or that an approval recommendation had gone forward. While we recognize we don’t always have the full picture when we hear these types of observations from sponsors, the frequency of occurrence of such complaints is increasing in dramatic fashion. Last week alone, Lachman Consultants received four inquiries about such issues. Each company expressed exasperation in not being able to get an answer other than “You just have to wait!”, and asked the same question: “Who can I call at FDA to discuss the issues?”

There’s no easy answer to that question. Depending on your level of exasperation, you might start at the top of the FDA Office of Compliance food chain, or perhaps at the Office of Process and Facilities, which is in the Office of Pharmaceutical Quality. (Here’s the CDER List of Key Officials in case you need it.)  It’s unclear how many applications are being delayed because they are stuck in the “Compliance Black Hole” . . . probably dozens, and perhaps several score. But, as noted above, a simple call to FDA is unlikely to do the trick in removing a compliance status block on approval. Instead, a sponsor might consider escalating the issue by requesting a meeting with the relevant FDA officials. After all, he who screams the loudest might be more likely to get FDA’s attention.      

* Mr. Pollock is Senior Advisor, Outside Director to the Board, Lachman Consultant Services, Inc., and is an author of the Lachman Consultants Blog.