By Kurt R. Karst –
Anyone from the United States who has visited a foreign city – like São Paulo, Brazil or Mumbai, India – knows immediately upon exiting the sealed environment of their aircraft that they are no longer in the United States. There’s an indescribable smell to the air. It permeates everything. After a few weeks though, the smell loses its force and seems to go away. Of course, it doesn’t really go away (which you realize upon returning home and opening up your suitcase), you just become accustomed to it. And you begin to wonder what newcomers and visitors are complaining about. A similar smell appears to be permeating Rockville, Maryland, and, more specifically, the suite of buildings on Standish Place where the Office of Generic Drugs (“OGD”) is located. Those of us who visit the OGD campus can smell the change in the air, though others who have grown accustomed to the smell may not.
Over the past several months we’ve noticed and heard about small, but significant changes in the way OGD has traditionally operated. Consider, for example, a recent article penned by Bob Pollock on the Lachman Consultants Blog. In his August 19th post, Bob provides a useful snapshot of ANDA approval times for June. Bob would have liked to provide information on July ANDA approvals, but he couldn’t. “[W]e understand that OGD has temporarily stopped releasing its monthly statistics,” says Bob. “Hopefully, that will be resolved soon because these numbers are the only concrete view that the industry has into OGD’s performance. This certainly is one piece of information that makes transparency seem alive and well and, now, at least for the short term, that piece of information is not available.”
Then, earlier this week, FDA released a new Manual of Policies and Procedures (“MAPP”) – MAPP 5200.3 – titled “Responding to Industry Inquiries with respect to Abbreviated New Drug Applications in the Office of Generic Drugs.” The stated purpose of the MAPP is to “clarify[y] the general principles for handling inquiries with respect to abbreviated new drug applications (ANDAs) from the authorized representative for an applicant with an ANDA submission (the authorized inquirer) by Regulatory Project Management (RPM) staff in [OGD].” The MAPP is specifically tied to implementation of the Generic Drug User Fee Amendments of 2012 (“GDUFA”), stating:
The Center for Drug Evaluation and Research (CDER) believes it is important to timely respond to industry inquiries. Historically, OGD staff responded to a range of informal, ad hoc inquiries from industry regarding the status of ANDAs. In order to systematically improve the predictability and timeliness of the ANDA review process, however, industry and FDA negotiated the Generic Drug User Fee Amendment (GDUFA). GDUFA was enacted by Congress and became effective as of October 1, 2012. Pursuant to GDUFA, OGD implemented certain agreed-upon premarket review efficiency enhancements, such as complete response letters, and also committed to achieve certain agreed-upon application and backlog metric goals. As OGD works to fulfill its GDUFA performance obligations, industry has an interest in clarity regarding the process for handling inquiries going forward.
After stating that the generic drug industry is responsible for designating “a single individual” to communicate with OGD and must “make all inquiries through that authorized inquirer,” the MAPP goes on to lay our various procedures. For example:
- Reviewers, team leaders, discipline specific project managers, deputies, division directors, other OGD management or OGD immediate office staff should refer all inquiries from the authorized inquirer on the status of an ANDA or related submissions to the RPM for that ANDA.
- RPMs should not provide dates or time lines for when reviews will be completed, when letters will be issued, or when other actions will be taken. Because workload and competing priorities affect action times, time lines are especially difficult to predict and should not be provided.
- RPM should try to understand the reasoning behind the status inquiry. The underlying principle identified by the authorized inquirer may reveal valuable information to aid FDA in providing a timely review to address a public health need (e.g., patent expiration date, drug shortage). If the justification does reveal previously unknown information, the RPM will communicate this to OGD management and the review team.
It wasn’t long after the posting of MAPP 5200.3 that we began to receive phone calls and emails expressing shock, anger, and frustration. We started to feel like a therapist for the generic drug industry. “In return for collecting hundreds of millions of $ in GDUFA fees, OGD is now restricting inquiries to only the Regulatory Project Manager, who will not provide any specific information regarding timing or content of reviews. To add insult, INDUSTRY is supposed to inform OGD as to WHY THEY NEED THIS INFORMATION!,” read one email. “This is so obviously a self-serving bureaucratic attempt to hide continuing disastrous performance by OGD, I have started calling it The Dog Ate My DAARTS Log MAPP of 2013,” continued the email, referring to the Document Archiving, Reporting and Regulatory Tracking System FDA uses to track applications. Another comment we received said that the “transparency that has taken place is like the transparency of a brick wall!” Some other comments we received we cannot post here – we’re only a PG-rated blog.
So what’s going on? We call it “UFAization”: the process by which an FDA component, after the enactment of a User Fee Act, becomes focused on so-called process enhancements to meet goals and commitments at the expense (both literally and figuratively) of those who are subject to such user fees. (Ok, maybe it’s not a term that will appear in the Oxford English Dictionary, but it’s better than “twerk!”). While other FDA components have likely undergone similar changes though the years as User Fee Acts have been enacted and implemented, OGD – and the generic drug industry – has a character all its own. Asking the generic drug industry to change its character is kind of like asking a tiger to change his stripes.
GDUFA and the accompanying Performance Goals and Procedures FDA and the generic drug industry hammered out and agreed to have three key aims:
Safety – Ensure that industry participants, foreign or domestic, who participate in the U.S. generic drug system are held to consistent high quality standards and are inspected biennially, using a risk-based approach, with foreign and domestic parity.
Access – Expedite the availability of low cost, high quality generic drugs by bringing greater predictability to the review times for abbreviated new drug applications, amendments and supplements, increasing predictability and timeliness in the review process.
Transparency – Enhance FDA’s ability to protect Americans in the complex global supply environment by requiring the identification of facilities involved in the manufacture of generic drugs and associated active pharmaceutical ingredients, and improving FDA’s communications and feedback with industry in order to expedite product access.
What some in the generic drug industry appear to be saying with their criticism of recent changes at OGD is that these changes are not merely growing pains as a result of GDUFA implementation, but that FDA is not meeting the key aims of GDUFA, or worse, that the Agency is reneging on some aspects of them. We’re certain that we’re not the only outlet for folks to vent their concerns. The Generic Pharmaceutical Association ("GPhA") is probably getting an earful from its members. Whether or not the generic drug industry will simply become accustomed to the unusual smell these changes seem to be creating, or whether there will be a call to action, remains to be seen. A couple of upcoming events – the GPhA/FDA Fall Technical Conference and a House Energy and Commerce Committee hearing on FDA's implementation of FDASIA – might be good venues at which to raise concerns.
- Bob Pollock, The MaPP to Nowhere (Sept. 26, 2013)