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Generic Drug User Fee Amendment (GDUFA) and You

By Charles “Chris” Celeste, Director of Regulatory Information and Submissions

FDA expects industry to begin submitting higher-quality applications to facilitate expedited reviews and approvals of generic drugs, agency officials explained at the Generic Drug User Fee Amendment (GDUFA) and You Conference in Lake Buena Vista, FL, March 27-28.

The goal of the meeting — which was hosted by the Office of Small Business and Industry Assistance (SBIA) in FDA’s Center for Drug Evaluation and Research (CDER) and presented by FDA’s Office of Generic Drugs (OGD) — was to update participants on FDA’s current activities and future plans for generic drug reviews.

The purpose of GDUFA was to increase the access of U.S. consumers to generic drugs, to ensure that the drugs are manufactured in compliance with FDA regulations, and to improve FDA’s communication with manufacturers of generic drugs and active pharmaceutical ingredients. In short, the goals are to improve access, safety, and transparency. To achieve these goals, FDA will be using a fee-based program to supplement appropriated Congressional funding.

At the Lake Buena Vista meeting, agency officials provided a reviewer’s perspective of an Abbreviated New Drug Application (ANDA), Drug Master Files (DMFs) and the completeness assessment for type II DMFs. The second day featured GDUFA implementation and policy updates; regulatory science; user fees, arrears lists, appeals and waivers; post approval inspections programs and a review of efficiency enhancements.

In GDUFA-related achievements, the agency has made significant progress in reducing the ANDA review backlog. FDA has hired 291 employees, exceeding the hiring target in the Fiscal Year 2013 goal. It has published criteria for Type II DMFs completeness assessments and refuse-to-receive (RTR) standards and it has posted a list of Type II DMFs that have passed the completeness assessment. And it is establishing a public docket to invite comment on ways to improve the quality of the ANDAs, amendments and supplements.

Here are some of my take-home notes from the meeting:

  • The agency will refuse to receive an ANDA if the number of easily remedied deficiencies is equal to or more than 10 or if a response to the fewer than 10 deficiencies is not received within 10 U.S. business days.
  • ANDAs submitted as a single, continuous, non-bookmarked PDF file will be refused.
  • If an applicant is requesting an expedited review, the cover letter must indicate in boldface “Expedited Review Requested” or “eligible for Expedited Review, GDUFA Year 1 or 2 Cohort.”
  • Upon issuing final guidance, FDA will contact a sponsor of an ANDA containing less than 10 easily remedied deficiencies. A response must be provided within 5 U.S. business days. Day 1 of the 5 U.S. business days will commence the day after notification is provided to the applicant. An ANDA will be refused if the number of easily remedied deficiencies is equal to or more than 10 or if a response to the fewer than 10 deficiencies is not received within 5 U.S. business days.
  • Any deficiencies revealed in the Active Pharmaceutical Ingredient (API) review will be communicated to the applicant. If a response is not received within 5 U.S. business days the ANDA will be refused for receipt.
  • Starting in Cohort Year 3 (FY 2015), which begins October 2, 2014, DMFs must be “Available for Reference” at the time of ANDA submission or they will be Refused to Receive (RTR).
  • Starting in Cohort year 3 the DMF fee should be paid a minimum of 6 months ahead of ANDA submissions to ensure the Completeness Assessment (CA) is done and the DMF is available for reference.
  • FDA is encouraging DMF holders to use a 30 minute teleconference for the first cycle of deficiency letters.
  • The agency is encouraging Type II DMF holders to submit the DMFs in eCTD format. This will aid in the review of the applications.

OGD is issuing the ANDA Filing Checklist on a quarterly basis (March, June, September and December). ANDA applicants should use the checklist as a tool to ensure that their application contains all of the appropriate components.

The agency offered other reference tools for applicants to use when preparing their applications, including Final Guidance for Industry: Providing Regulatory Submissions in Electronic Format – Human Pharmaceutical Applications and Related Submission Using the [electronic Common Technical Document (eCTD)] Specifications; FDA eCTD Table of Contents Headings and Hierarchy; Portable Document Format Specifications: Guidance for Industry M4: The CTD – Quality Questions and Answers/Locations Issues, etc.

FDA will be holding a public meeting on May 16, 2014 to provide an overview of the current status of regulatory science initiatives for generic drugs. The agency wants input from industry, academia, professionals and other interested parties as it develops an annual list of regulatory science initiatives specific to generic drugs. FDA will take the information from the public meeting into account in developing its FY 2015 Regulatory Science Plan. The meeting will be held from 9:00 am to 5:00 pm at FDA’s White Oak Campus. Additional information can be found in the February 26, 2014 Federal Register.

In summary, FDA is working on keeping industry updated on the agency’s activities and trying to provide them with as much information as possible. The agency’s expectation is that industry will begin to submit applications that can be reviewed more efficiently.

EAS has available upon request copies of all the slide presentations for the GDUFA and You 2014 meeting.

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