CUTTING THE BACKLOG
FDA's Office of Generic Drugs (OGD) also will collect a one-time ANDA backlog fee this year on pending ANDAs, which will generate
an expected $50 million to support the processing of almost 3000 ANDAs currently in the application queue. Many of these applications
are categorized as "incomplete" or were hit with "not approvable" or "complete response" letters years ago, but were not withdrawn
by the manufacturer. The initiative aims to clear out 90% of the ANDAs and amendments in the backlog by 2017.
FDA would like to whittle down the backlog before launching the GDUFA backlog program and announced in June that it plans
to cancel backlogged applications that have not involved any communication with the sponsor since 1991. An August Federal Register notice further encourages manufacturers to withdraw backlogged applications that they no longer wish to pursue (3). The agency
calculated that if 2000 applications remain in the backlog (of the 3000 pending in August), the backlog fee would be $25,000
FDA also promises to meet a range of GDUFA performance goals outlined in a commitment letter to manufacturers that is structured
similarly to programs that have been in place for brand drugs for 20 years (4). Under a phased-in approach, FDA will "review
and act on" 60% of ANDA submissions within 15 months by the third year of the program; the timeframe tightens in year five
to review of 90% of submissions within 10 months. ANDA evaluation will take longer if a manufacturer files major amendments
during the review process, and OGD will not accept an ANDA until the application fee is paid, a situation that could be important
in determining which generic firm is "first to file."
OGD will strive to clarify review decisions by issuing complete response letters and DMF "completeness assessments," instituting
rolling reviews, and holding first cycle deficiency meetings with sponsors. If minor problems crop up during a review, OGD
staff will try to inform sponsors of "easily correctable deficiencies" that can be remedied quickly. OGD reviewers expect
that issues raised in complete response letters will be addressed initially through teleconferences with the agency; eventually
GDUFA will provide time and resources for sponsors to meet with OGD reviewers in person to discuss specific complete response
Sponsors still may file applications on paper, but FDA does not have to meet user-fee performance goals unless the ANDA is
filed electronically, a process that FDA expects will become universal in the near future. FDA would like to see continued
improvement in the quality of applications to reduce the frequent back-and-forth questioning that routinely delays approvals.
OGD has been encouraging generic-drug makers to adopt quality-by-design (QbD) approaches by issuing sample pharmaceutical
development reports with QbD principles for both immediate-release and modified-release solid oral dosage forms. The agency
recently updated its Question-Based Review system to incorporate QbD models and has tightened initial criteria for filing
ANDAs to discourage incomplete submissions. OGD has established a central system to track the progress and status of each
application as it moves through the review process, and a broader OGD quality management system aims to clearly document procedures
to provide more consistency across review divisions. Some of the GDUFA revenues also will support development of further guidance
and research to facilitate development of more complex generic products, such as anti-epileptic drugs and inhaled products.
FDA held a public meeting in September to review with manufacturers these and other program implementation issues. GDUFA policies
also were a prime topic at the PDA/FDA Joint Regulatory Conference on September 11, 2012 in Baltimore and at the fall technical
conference on Oct. 2–3 sponsored by the Generic Pharmaceutical Association.
Implementing GDUFA will involve a significant expansion in OGD staff on all levels, along with extensive training for new
hires and expanded IT systems. To provide the broader management structure needed to oversee this more complex generic drug
program, CDER director Janet Woodcock recently announced plans to elevate OGD to a "super office" with other offices reporting
to it. Instead of being part of CDER's Office of Pharmaceutical Science (OPS), OGD will be a parallel umbrella organization,
similar to CDER's Office of New Drugs and Office of Compliance. New OGD director Greg Geba will head the super OGD, reporting
directly to Woodcock and better positioned to work with CDER's Office of Executive Programs on GDUFA implementation.
The larger plan is to replace OPS with a new Office of Pharmaceutical Quality (OPQ), which will be responsible for overseeing
drug quality throughout the product lifecycle. The new OPQ will absorb certain OPS functions as well as some activities performed
by the Office of Manufacturing and Product Quality in the Office of Compliance. And, when we went to press, there was considerable
anxiety that Congress would fail to enact an FDA appropriations bill by Oct. 1, which is needed for the agency to collect
any 2013 user fees. Hopefully, that impass will be remedied by the time you read this report.
Jill Wechsler is BioPharm International's Washington editor, Chevy Chase, MD, 301.656.4634, email@example.com
. Read Jill's blogs at http://www.pharmtech.com.
1. FDA, Guidance for Industry: Generic Drug User Fee Amendments of 2012, Questions & Answers (FDA, Rockville, MD, August 2012).
2. FDA, Guidance for Industry: Self-Identification of Generic Drug Facilities, Sites and Organizations (FDA, Rockville, MD, August 2012).
3. Federal Register Vol. 77, No. 166 (August 27, 2012).
4. FDA, Human Generic Drug Performance Goals and Procedures, Fiscal Years 2013 through 2017, posted at http://www.fda.gov/ (July 17, 2012).