Moving to Risk-Based Inspections

The author discusses the key provisions of GDUFA as they relate to the pharmaceutical supply chain, including parity of inspections between domestic and foreign sites for both finished dosage forms and APIs of generic drugs.
Sep 01, 2012
Volume 2012 Supplement, Issue 5

On Oct. 1, 2012, the Generic Drug User Fee Act (GDUFA), which was signed into law by President Barack Obama on July 9, 2012, goes into effect and provides important changes for generic-drug manufacturers and producers of generic APIs. The law imposes generic-drug user fees, payable by producers of generic finished drugs and APIs, to provide additional funding to FDA to improve the regulatory review process, including inspections for drug-manufacturing facilities, for generic drugs. These measures, which are supported by the generic-drug and fine-chemical industries, are intended to speed the delivery and ensure the quality of generic drugs (1).

Generic-drug user fees

Under the GDUFA, FDA will receive $299 million annually (adjusted for inflation) during the five-year authorization of GDUFA from Oct. 1, 2013 to Sept. 30, 2017 (i.e., fiscal year [FY] 2013 to FY 2017) (2). The user fees required by the GDUFA are:

  • A one-time fee for original abbreviated new drug applications (ANDAs) pending on Oct. 1, 2012 (also known as backlog applications)
  • Annual fees for API and final dosage-form facilities
  • Fees for new ANDAs and prior approval supplements (PASs)
  • A one-time fee for drug master files (DMFs) (1).

Seventy percent of the GDUFA fees will be derived from annual facility fees for facilities producing or pending review to produce APIs or finished dosage forms for a generic-drug application, and approximately 30% of the user fees will be derived from one-time application fees (DMF fees and ANDA and PAS fees). Overall fees were structured to reflect the respective weight in the supply chain, so that 80% of the fees are paid by finished dosage form manufacturers and 20% by API manufacturers. In the first year of the program, $50 million of the total GDUFA user-fee funding will be generated by the one-time backlog fee for ANDAs pending (except for ANDAs that are pending but have received tentative approval) on Oct. 1, 2012. Overall, it is estimated that FDA will receive the funding through approximately 750 ANDAs per year submitted electronically, 750 PASs, 350 newly referenced DMFs per year, and 2000 facilities associated with ANDAs (2).

Major program goals

With the additional funding provided by generic-drug user fees under the GDUFA, FDA is obligated to meet certain performance goals with respect to its regulatory review of generic drugs. The GDUFA outlines goals in five main program areas.

  • Application metrics: By the end of FY 2017, FDA will review and act on 90% of complete electronic ANDAs within 10 months after the date of submission. Certain amended applications may have differing metrics.
  • Backlog metrics: FDA will review and act on 90% of all ANDAs, ANDA amendments, and ANDA PASs of current review status (whether electronic, paper, or hybrid) pending on Oct. 1, 2012, by the end of FY 2017.
  • cGMP inspection metrics: FDA will conduct risk-adjusted biennial cGMP surveillance inspections of generic API and generic finished dosage form manufacturers, with the goal of achieving parity of inspection frequency between foreign and domestic firms in FY 2017.
  • Efficiency enhancements: FDA will implement various efficiency enhancements, which include efforts by industry and FDA to populate and maintain databases as necessary for facilities, fee assessments, efficiency, and other enhancements. FDA also will make DMF- and inspection-based enhancements as well as create a current chemistry manufacturing, and controls (CMC) records database to aid in the efficiency of reviews and inspections.
  • Regulatory science: FDA will continue or begin various regulatory-science initiatives. Some key issues are continuing quality-by-design initiatives for generic drugs, including developing science-based recommendations for product development, raw material, API and process controls, and life-cycle management of complex dosage forms (e.g., orally inhaled drug products and modified-release dosage forms). Another key goal is to develop a risk-based understanding of potential adverse impacts to drug-product quality resulting from changes in API manufacturing and controls. This effort will aid in the ability to predict the potential impact manufacturing changes will have on product quality, so manufacturers can target assessments and controls on high-risk areas and regulators can focus their reviews on these areas (2).

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