An Overview of GDUFA
Introduction to The Office of Generic Drugs (OGD)
The Office of Generic Drugs (OGD) reports directly to the Director of the Center for Drug Evaluation and Research (CDER). The OGD’s mission is to ensure safe, effective, and affordable medicines for the American public.
The OGD helps ensure that human generic drug products are thoroughly tested and shown to meet the statutory standards for approval. The OGD’s work has helped millions of Americans to use quality and affordable generic drug products to treat a wide variety of medical conditions and in turn save the American health care system over $1.6 trillion over the 10-year period from 2005 through 2014. Under the Drug Price Competition and Patent Term Restoration Act of 1984, or Hatch Waxman Act, recent evidence has shown that the OGD has helped save Americans over $254 billion in just in 2014 alone.
This Success Brought New Challenges
Over the last several decades, the generic industry, the number of generic drug applications (known as “Abbreviated New Drug Applications” or “ANDAs”) submitted to FDA for review, and the number of foreign facilities making generic drugs grew substantially. As a result, FDA’s generic drug program became increasingly under-resourced. Its staffing did not keep pace with the growth of the industry.
Because the program could not keep up with its workload, a backlog of submitted ANDAs developed and grew. It overwhelmed the FDA staff and created unpredictability and delay for industry.
What is GDUFA?
The Generic Drug User Fee Amendments (GDUFA) is a recent law passed by Congress as part of the Food and Drug Safety and Innovation Act of 2012. The FDA and generic drug industry developed the proposal for GDUFA. Under GDUFA, industry agreed to pay approximately $300 million in fees each year of the 5-year program. In return, the FDA committed to performance goals. There are a multitude of metrics that apply to GDUFA, and ultimately the end goal is faster window of review for all Abbreviated New Drug Applications (ANDAs). These metrics and commitments have been ramping up over the course of the first 4 years of the program, as illustrated below.
Because of the amount of hiring, restructuring, and catch-up needed, performance goals were set to commence in the later years of the program. The GDUFA performance goals with respect to ANDAs, amendments to ANDAs, and prior approval supplements (PAS) are timeframes by which FDA is to take a “first action” on an application, by either granting an approval or tentative approval, or, if there are deficiencies that prevent approval, identifying those deficiencies to the applicant in a complete response letter or in a refusal to receive4 the application. When deficiencies are identified, industry usually responds by correcting them and resubmitting the application.
Actions on Pre-GDUFA (“Backlog”) Applications
A major commitment of GDUFA was to take a “first action” on 90% of the “backlog” applications, defined as pre-GDUFA applications pending before the Agency on October 1, 2012, by the end of Fiscal Year 2017. As of October 1, 2012, the backlog included 2866 ANDAs and 1873 PASs. The chart above shows that to date, the FDA has completed first actions on 84% of ANDAs and 88% of PASs. And so, FDA is well ahead of schedule in achieving the GDUFA goal to significantly reduce the backlog, and our ultimate goal of eliminating it.
Some of these backlog applications had been pending or in review for a long time prior to GDUFA. At this point in time, as FDA acts on one of the outstanding backlog applications, the “time to approval” of such application will be recorded as, at minimum, 40 months (i.e., we now are three years and four months (40 months) into GDUFA implementation). This helps to explain the often-quoted 42-month approval time, which does not apply to post-GDUFA applications as explained below.
Moreover, the filing backlog for ANDAs has been eliminated. “Filing” is where we evaluate if a drug sponsor’s submitted application is sufficiently complete to permit FDA’s substantive review. In August 2014, we had a filing backlog of over 1,100 applications. Now that backlog is gone. (See chart below).
GDUFA also established goals for our review of PASs. PASs are important because they enable flexibility and improvements for generic drug manufacturing. To date, we have substantially exceeded GDUFA PAS goal of 60% reviewed within 6 months if an inspection is not required and 10 months if an inspection is required.
What are the Outcomes of GDUFA?
2016 marks the 4-year mark of GDUFA being instated, and there has already been considerable progress. To support the growth of GDUFA, the OGD hired roughly 125 new employees in 2015. Additionally, employees were hired across the CDER and FDA to help support the GDUFA program, including employees in the Office of Bioequivalence (OB), Office of Research and Standards (ORS), Office of Regulatory Operations (ORO), and Office of Generic Drug Policy (OGDP).
One of the main goals of GDUFA at the outset was to take “first action” on 90% of applications in backlog (applications submitted prior to the 2012 rollout of GDUFA). The FDA is ahead of schedule in reducing this backlog of several thousand ANDAs and PASs, and by the end of 2015, 84% of ANDAs and 88% of PASs had first actions completed. (See above “Actions on Pre-GDUFA (“Backlog”) Applications”).
A second major focus area has been working through controlled correspondences, which are product development questions that can help companies develop more thoughtful applications. At the end of 2015, the OGD had completed 2,065 controlled correspondences, a record number. (See chart below).
Additionally, another strategic focus of the OGD to achieve GDUFA goals has been improving business processes. There have been several notable improvements thus far, including a new informatics platform, improved review processes, and staff training / professional development.
Another outcome of GDUFA has been the issuance of more tangible guidances and standards. The OGD now has product specific guidance documents (also known as bioequivalence or BE guidances) which serve as recommendations to help facilitate pre-market development and efficient filing of generic drugs. The recommendations include useful information on scientifically and clinical supported methods to go about developing a therapeutically equivalent generic version of the branded / reference listed drug. These BE guidances help clarify the expectations of the OGD for specific products, in hopes of supporting the industry in developing generic alternatives to branded drugs more expeditiously.
As of 2015, there are now more than 1,3000 product specific guidances available to the industry, including the introduction of more nuanced products including complex dosage forms. In addition to issuing BE standards, the OGD publishes regulatory guidances focused on the development and approval process. (See chart below).
An additional goal of the OGD has been more timely and effective communication with the industry. This is being accomplished through an increasing number of forums and webinars.
Finally, as part of GDUFA, the FDA is working with the industry, academics, and the public to develop a list of regulatory science initiatives to further advance generic drug research. This research can provide “new tools to for FDA to evaluate generic drug equivalence and for industry to efficiently develop new generic products in all product categories.” These priority areas for regulatory science research include:
- post-market evaluation of generic drugs
- equivalence of complex drug products
- equivalence of locally acting products
- therapeutic equivalence evaluation and standards
- cross-cutting computational and analytical tools
Generic Drug Approvals on the Rise
2015 has been a record year of generic drug approvals, with the OGD awarding more than 580 approvals and tentative approvals, including 99 in December alone. There is much optimism that this trend will continue in 2016 and future years, all towards the larger goal of bringing safe, effective, and affordable drugs to people as quickly as possible. This is certainly an exciting time to be in the rapid-paced world of generics, with many changes and advancements still on the horizon.
Catawba Research, LLC
Catawba Research, LLC is a full-service contract research organization (CRO) providing clinical management services to pharmaceutical, device, formulation development and biotechnology companies. We focus on what we know best: dermatology, women’s health and ophthalmology.
Catawba Research, LLC is your trusted partner for generic drug development, and is proud to have been a part of dozens of successful ANDA applications including a number of “First-To-File” programs.
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