FDA Issues Guidance for Industry on Generic Drug User Fee Amendments of 2012: Q&A

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The U.S. Food and Drug Administration (FDA) recently published its guidance for industry on the Generic Drug User Fee Amendments of 2012 (GDUFA) in a question-and-answer format. This guidance provides answers to anticipated questions regarding GDUFA, specifically on the topics of fees, self-identification of facilities, sites and organizations, review of generic drug submissions, and inspections and compliance, a summary of which is found in the guidance document. A failure to pay a required fee may result in a refusal to receive an Abbreviated New Drug Application (ANDA) or any supplement to an ANDA, or in a drug being deemed misbranded.

Backlog Fee. Each person who owns an original ANDA pending on October 1, 2012 that has not been withdrawn, tentatively approved, or approved by September 28, 2012 will be required to pay a backlog fee. The FDA will determine the backlog fee by dividing $50 million by the number of original ANDAs pending on October 1, 2012. The backlog fee is a one-time fee for each pending original ANDA. To avoid this backlog fee, written notification of a withdrawal of an original ANDA must be received by September 28, 2012. Failure to pay the backlog fee will place the person on a "publicly available arrears list, and FDA will not receive a new ANDA or supplement submitted by that person, or any affiliate . . . of that person."

Drug Master File (DMF) Fee. Only DMFs for a Type II API will incur the one-time DMF fee. The fee is incurred on the date the first generic drug submission references the DMF by initial letter of authorization (if that DMF has not previously been relied upon) on or after October 1, 2012, except for Fiscal Year 2013 when the fee will be due not "earlier than 30 days after publication of the final DMF fee in the Federal Register or 30 days after enactment of an appropriations Act that provides for the collection and obligation of generic drug user fees, whichever is later." The fee is required regardless of whether the DMF has been reviewed prior to GDUFA implementation. The FDA estimates that the DMF fee will be about $43,000. DMF holders, however, may pay the fee prior to any request for a letter of authorization. An ANDA applicant may also pay this fee. A DMF will be "deemed not available for reference” for failure to pay the DMF fee. If such fee is not received within 20 calendar days of notification of failure to pay, any "ANDA referencing the DMF will not be received."

ANDA and Prior Approval Supplement (PAS) Fees. The FDA estimates that the ANDA fee will be about $53,000 and the PAS fee will be about $27,000. These fees are incurred at the time of submission, except for Fiscal Year 2013 when "fees will not be due earlier than 30 days after publication of the ANDA and PAS fees in the Federal Register or 30 days after enactment of an appropriations Act that provides for the collection and obligation of generic drug user fees, whichever is later." If an application is refused for reasons other than failure to pay fees, a partial refund of 75 percent of the fee will be accorded to the applicant. The FDA will not receive any ANDA or PAS if the fee is not paid within 20 calendar days of the due date. Additionally, any active pharmaceutical ingredient (API) manufactured by the applicant will require the payment of a one-time API-related fee for each API. The API-related fee "is a function of the number of APIs referenced in the application and the number of facilities in which those APIs are manufactured. If the ANDA references more than one facility as manufacturing each API, the applicant must pay the API-related fee for each such facility."

Facility Fees. Finished dosage form (FDF) and API facilities fees will be "determined after the self-identification process." Self-identification is required for (1) facilities that manufacture, or intend to manufacture, human generic drug APIs and/or FDFs; (2) sites that package the FDF; (3) sites that are identified in a generic drug submission that subdivide the contents of the primary container/closure system; (4) bioequivalence/bioavailability sites that conduct clinical testing, bioanalytical testing, and/or in vitro testing; and (5) sites that perform testing of one or more attributes/characteristics of the FDF or API. However, "[o]nly facilities that manufacture, or intend to manufacture, generic drug APIs or FDFs, or both, are required to pay facility fees." If a company manufactures such products in different geographic locations, in facilities under the control of multiple management entities, or in separate buildings that are not "within close proximity . . . and are capable of being inspected by the FDA during a single inspection" each facility must be separately identified. Any FDFs or APIs manufactured in a facility that is not self-identified will be deemed misbranded and will violate federal law if shipped in interstate commerce or imported into the U.S. The fees for each identified FDF or API facility will be determined after completion of the self-identification process and, for Fiscal Year 2013, "will be due within 45 days after publication of the final facility fee amounts in the Federal Register, or 30 days after the enactment of an appropriations Act providing for the collection and obligation of generic drug user fees, whichever is later." Thereafter, the annual fee "will be due on the first business day on or after October 1 of each fiscal year, or the first business day after the enactment of an appropriations Act that provides for the collection and obligation of fees." For foreign facilities, the fee "shall not be less than $15,000 and not more than $30,000 higher than the amount of the fee for a domestic facility" and "will be set on the basis of the FDA’s estimate of the average direct cost differential between foreign inspections and domestic inspections." If the facility fee is not paid, "[n]o new generic drug submission referencing the facility will be received," "the facility will be placed on a publicly available arrears list if the fee is not fully paid within 20 days of the due date," and "all FDFs or APIs manufactured in the non-paying facility and all FDFs containing APIs manufactured in such a facility will be deemed misbranded."

Other Fee-Related Issues. The date and time of submission of a generic drug submission or a Type II API DMF will be determined "on the calendar day when the electronic submission arrives at FDA's electronic gateway, except that a submission made on a weekend, Federal holiday, or a day when the FDA office that will review the submission is not otherwise open for business will be deemed to be submitted the next day when that Office is open for business" or, if "submitted in physical media form, the date of submission will be the day it arrives at the appropriate designated FDA document room."

The process for paying GDUFA fees is similar to the procedures for PDUFA and other FDA user fees. The FDA will not invoice any fees, but will require self-identification and payment. The only exemption from these fees are for Positron Emission Tomography drug manufacturers, although they are still required to self-identify. There are no reduced fees available for small businesses. The arrears list for any failure to pay will be available on the FDA's website and will be updated "following each annual facility fee payment deadline" as well as "more frequent updates to reflect payment activity."

If a person inadvertently pays a higher fee than required or claims to have paid a fee in error, that person may submit a written request for the return of the overpayment or erroneous fee within 180 calendar days of such payment.

The FDA has set a public hearing on GDUFA fees for September 21, 2012, from 9:00 a.m. to noon at its facility in Silver Spring, Maryland.

For Further Information

If you have any questions about this Alert, please contact Frederick (Rick) R. Ball, Carolyn A. Alenci, any member of the Pharmaceutical, Pharmacy & Food industry group or the attorney in the firm with whom you are regularly in contact.