New Era for Generic Drugs - User fees aim to speed approvals and support inspections. - BioPharm International


New Era for Generic Drugs
User fees aim to speed approvals and support inspections.

BioPharm International
Volume 25, Issue 10, pp. 13-15


Hot-Topic Roundup
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categorized as "incomplete" or were hit with "not approvable" or "complete response" letters years ago, but were not withdrawn by the manufacturer.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 per application.

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 letter issues.

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,
. Read Jill's blogs at


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 (July 17, 2012).

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