What is the generic drug applicant program fee? GDUFA III includes a generic drug applicant program fee, which is assessed annually. Each company and its affiliates will be assessed an annual program fee depending on the number of approved ANDAs in their portfolio. To determine the fee amount, there are three tiers of the program fee: Large: 20 or more approved ANDAs; Medium: between 6 and 19 approved ANDAs; Small: 5 or fewer approved ANDAs The term “affiliate” is defined as a business entity that has a relationship with a second business entity if, directly or indirectly, one business entity controls, or has the power to control, the other business entity; or a third-party controls, or has the power to control, both of the business entities. Effective October 1, 2018, generic drug applicants and their affiliates, or an authorized representative, can submit the list of all approved ANDAs via the CDER Direct NextGen Collaboration Portal. Submissions will be for the upcoming fiscal years 2023-2027. To register for an account with the CDER Direct NextGen Collaboration Portal, navigate to https://edm.fda.gov. For more on logging in: CDER Direct NextGen Collaboration Portal FAQs Due to processing times, you might encounter data discrepancies that might have an impact on your portfolio. If you encounter any discrepancies in your portfolio, please update your portfolio in the portal and submit as appropriate. Please note that Withdrawal Requests and Transfers of Ownership must be sent to the official record of the ANDA via the Electronic Submissions Gateway (ESG). When is the program fee due? The program fee is due on October 1 of the fiscal year. If October 1 falls on a weekend, federal holiday, or day when the FDA is otherwise closed, then the fee is due on the following business day. Any ANDA approved after October 1 will be included in the parent company’s portfolio for the following fiscal year. What is the penalty for not paying the program fee? There are three effects if an applicant fails to pay the program fee within 20 calendar days after the due date: (1) The parent company will be placed on a publicly available arrears list. (2) Any ANDA submitted by the applicant or its affiliates will not be received. (3) All drugs marketed pursuant to any ANDA held by such applicant or an affiliate of such applicant shall be deemed misbranded. Are discontinued ANDAs included in the calculation of program fees? Yes, discontinued ANDAs are still considered approved for user fee purposes unless the ANDAs are officially withdrawn. If Company A that has 4 approved ANDAs is affiliated with Company B that has 16 approved ANDAs, can they pay a small and medium fee? Or, must they pay one large fee? Since Company A and B are affiliated, their portfolio includes 20 ANDAs and they, therefore, must pay one large fee. According to 21 U.S.C. § 379j-42(b)(2)(E), if a person has affiliates, a single program fee shall be assessed. If two companies are affiliated, does the parent company have to pay the program fee or can the affiliate pay the fee? Either the parent company or any of the affiliated companies can pay the program fee on behalf of the parent company. When is the deadline for making changes to the approved ANDA list? For FY 2023 through FY 2027, an ANDA shall be deemed not to be approved if the applicant has submitted a request for withdrawal of approval of such ANDA by April 1 of the previous fiscal year. For example, if a company has 6 approved ANDAs and a withdrawal request is submitted for one ANDA before or on April 1, 2022, then the company’s program fee tier would change from medium tier to small tier for FY 2023. For transfers of ownership, consolidations, and other changes to a company’s portfolio, FDA will use the information effective as of October 1 to determine program fee tier. For example, if a company has 6 approved ANDAs and requests a consolidation of 2 ANDAs into 1, but the Office of Generic Drugs does not grant the consolidation request until after October 1, 2022, then the company would remain medium tier for FY 2023. (Total remains 6 ANDAs). For example, if a company with 5 approved ANDAs is determined to be affiliated with another company with 1 approved ANDA, and the date of affiliation is on or prior to October 1, 2022, then the company would be assessed the medium tier fee for FY 2023. If the company had already paid the small tier, then they would need to pay the difference between the medium tier fee and the small tier fee. For other scenarios not listed, please contact CDERCollections@fda.hhs.gov for assistance. When should the industry inform the Agency about their affiliates? By April 1 of each year, each person that owns an ANDA, or a designated affiliate of such person, shall submit, on behalf of the person and the affiliates of such person, to the Agency a list of (1) all approved ANDAs owned by such person, and (2) if any affiliate of such person also owns an ANDA, all affiliates that own any such ANDA and all approved ANDAs owned by any such affiliate. Please submit your responses to the CDER Direct NextGen Collaboration Portal. Are there any drugs or applications excluded from the program fee? The following are excluded from the program fee: Positron emission tomography (PET) drugs, and applications submitted by a State or Federal Government entity for a drug that is not distributed commercially. How does a company pay the program fee? A company can create a program fee cover sheet via the User Fee System and then pay via check, wire transfer, or pay.gov. What if the wrong tier is displayed on the coversheet? Please report any discrepancies via the CDER Direct NextGen Collaboration Portal. Once corrected, the Generic Drug User Fee staff will reach out when the amended cover sheet is available. What are the facility fee types under GDUFA III? There are three types of facility fees: (1) an active pharmaceutical ingredient (API) facility fee; (2) finished dosage form (FDF) facility fee; and (3) Contract Manufacturing Organization (CMO) facility fee. If considered an API/FDF manufacturer or a CMO, a facility owner is required to pay an annual facility fee. Please refer to the GDUFA Fees table above for the exact fee amounts of each facility fee type. Each person who owns a facility that is identified in (1) at least one approved generic drug submission in which the facility is approved to produce one or more APIs, or (2) a Type II API drug master file referenced in at least one approved generic drug submission incurs the API facility fee. Each person who owns a facility that is identified in at least one generic drug submission that is approved to produce one or more FDFs incurs the FDF facility fee. Some FDF facilities may be qualified as CMOs. An annual CMO facility fee is owed by each person who owns an FDF facility that is identified in at least one approved ANDA, where the facility is not identified in an approved ANDA held by the owner of that facility or its affiliates. The CMO facility fee is 24 percent of the amount of the FDF facility fee. A facility owner who qualifies as a CMO will owe the CMO facility fee; no other facility fee amount will be assessed. Is there a difference in fees between foreign and domestic generic drug facilities? Yes. GDUFA III specifies that the amount of the fee for a facility located outside the United States and its territories and possessions shall be $15,000 higher than the amount of the fee for a domestic facility. The basis for this differential is the extra cost incurred by conducting an inspection outside the United States and its territories and possessions. When are facility fees due? Facility fees are incurred annually and 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 providing for the collection of fees for such year. Under what conditions is a facility fee incurred? Under GDUFA III, the owner of a facility incurs a fee when both of the following conditions are met on the facility fee due date: the facility is referenced in an approved generic drug submission; and the facility is engaged in manufacturing or processing an API or FDF A facility does not incur a fee for being referenced only in pending or tentatively approved generic drug submissions under GDUFA III. Do all facilities, sites, and organizations that have to self-identify also have to pay facility fees? No. Self-identification does not, in and of itself, trigger a liability to pay GDUFA facility fees. However, most facilities that self-identify tend to be required to pay an annual facility user fee. These include facilities manufacturing API and/or FDF contained in human generic drugs. Other sites and organizations must self-identify but are not required to pay the annual facility user fee. These include facilities that solely manufacture positron emission tomography (PET) drugs, facilities that are only referenced in applications submitted by State and/or Federal Government entities for drugs that are not distributed commercially, or sites and organizations that only perform testing, repackaging, or relabeling operations. Please note that while repackagers are not required to pay user fees, drug product packagers are, in most cases, subject to FDF or CMO facility fees. This is also the case for drug product labelers and relabelers. Facilities manufacturing for only pending or tentatively approved generic drugs will also perform self-identification. However, these facilities will not incur a GDUFA facility fee if the generic drug is still pending or tentatively approved on the GDUFA facility fee due date. If a facility is first identified in an approved generic drug submission after the due date for payment of the facility fee for a fiscal year, is it required to pay the fee for that fiscal year? No. If a facility is first identified in an approved generic drug submission after the due date for payment of the facility fee for a fiscal year, the facility is not required to pay the fee for that fiscal year. In most cases, the critical question is whether there is a generic drug submission approved on the due date in which the facility is referenced. If the facility is first identified in an approved generic drug submission after the due date, its owner will owe a facility fee on the next due date. For example, if a facility is first identified in an approved abbreviated new drug application on October 15, 2022 (after the fiscal year 2022 due date and during fiscal year 2023), it will start incurring facility fees on the fiscal year 2024 due date (the first business day of October 2023). If a facility is identified in an approved generic drug submission on the due date, and that reference to the facility or the drug submission is later withdrawn, the fee will not be refunded. Is a facility owner required to pay a GDUFA fee if the facility is manufacturing only non-generic APIs or FDFs but is referenced as a fee-incurring operation type in an approved generic drug submission? Yes. Is a facility owner required to pay a GDUFA fee if the facility is referenced as a fee-incurring operation type in an approved generic drug submission but is only manufacturing drugs for the non-US market? Yes. Is a facility that is not currently manufacturing an API or FDF required to pay the applicable facility fees? A facility listed in at least one approved generic drug submission incurs annual facility fees for as long as it is identified in a generic drug submission, even if the facility has not started commercial-scale production of the API or FDF covered by that submission, or if the facility has stopped, temporarily or permanently, the production of that API or FDF. The facility will cease to incur additional fees if it is no longer identified in any generic drug submission or has stopped manufacturing all APIs and FDFs (including both generic and non-generic APIs and FDFs) by the date that the fee is due. Any outstanding fee obligations will, however, remain due. See Section VII.F. of the guidance for industry Assessing User Fees Under the Generic Drug User Fee Amendments of 2022 (GDUFA III guidance) for a description of how a facility can ensure that it is no longer identified in an ANDA. See Section VIII.J. of the GDUFA III guidance for information and instructions on facilities that cease manufacturing. If a facility manufactures both APIs and FDFs for generic drugs, does it incur more than one facility fee? No. Unlike GDUFA I, under GDUFA II and GDUFA III, if a facility is identified in one or more approved generic drug submissions to produce both APIs and FDFs, the facility will only incur the annual FDF fee. Is a facility that manufactures an API excipient mixture or a mixture of two or more APIs used to produce FDFs required to pay an annual FDF facility fee? Generally, manufacturers of API-excipient mixtures are required to pay the annual FDF facility fee. However, GDUFA provides one exception, for fee-paying purposes only, to the definition of FDF as inclusive of in-process materials. GDUFA defines an API-excipient mixture as an API when the mixture is produced because the API is unstable or cannot be transported on its own. In such cases, mixing the API with one or more excipients may prevent the loss of one or more critical quality attributes that allow the API to be made into a finished dosage form. Examples include an API mixed with an antioxidant for chemical stability when the API is prone to oxidative degradation or a highly potent API mixed with a polymer to facilitate safe handling. Additional examples include an API-excipient mixture for physical stability to maintain the API’s amorphous form or an API mixed with a lubricant to prevent agglomeration or solidification of a powder. When claiming this exception, the rationale should be clearly stated and accompanied by supporting information in the DMF or application, as appropriate, for each excipient added for stability purposes. APIs mixed with one or more excipients for commercial convenience only are not considered to fall under this exception to characterization as FDF. Whom does FDA consider as a packager for purposes of GDUFA? If a facility receives product prior to the point in the manufacturing process in which the drug is first packaged in a container/closure system specified in the “How Supplied” section of an approved ANDA and it packages that product into such a container/closure system for the first time, the facility is a packager for the purposes of GDUFA. Every ANDA specifies the forms in which the approved drug product may be distributed in the “How Supplied” section. For example, if a facility receives bulk drugs and packages them into the containers in which they are marketed, that facility is a packager. A facility is also a packager if it receives product in a container/closure specified in the “How Supplied” section of an approved ANDA and applies the FDA-approved prescription package labeling to that product for the first time. Are facilities that manufacture atypical APIs required to pay API facility fees? Facilities that process raw materials used to manufacture human generic drugs are generally required to pay annual facility fees if they supply a product that qualifies as an API as defined in GDUFA. Are packagers required to pay FDF facility fees? Packagers are considered to be manufacturers, regardless of whether that packaging is done pursuant to a contract or by the applicant itself. Such facilities are required to pay annual FDF or CMO facility fees. Repackagers are not required to pay facility fees under GDUFA. Are quality control (QC) testing sites required to pay annual facility fees? No. They are only required to self-identify. Are two locations of the same company required to pay separate facility fees? The answer depends on geography. If the same company’s two locations manufacture a U.S. generic product and they are in different geographic locations, each has to pay an annual facility fee. However, separate buildings within close proximity are considered to be at one geographic location or address if: 1. the activities in them are closely related to the same business enterprise; 2. they are under the supervision of the same local management; and 3. they are capable of being inspected by FDA during a single inspection These are the same criteria used to evaluate whether separate FDA Facility Establishment Identifiers (FEIs) are necessary for multiple facilities (see final guidance for industry Self-Identification of Generic Drug Facilities, Sites, and Organizations). If a firm believes that multiple FEIs have been assigned in error, the firm may request consolidation of the FEIs. Please note that consolidation of FEI numbers is not an appropriate mechanism to address a non-compliant facility. Domestic firms should submit the request to the appropriate FDA District office. Contact information is available at http://www.fda.gov/downloads/ICECI/Inspections/IOM/UCM123522.pdf. Foreign firms should contact FDAGDUFAFEIRequest@fda.hhs.gov. What is the penalty for failure to pay a facility fee? There are several consequences for failure to pay a facility fee: (1) No new ANDA or supplement submitted by the person responsible for paying the fee or that person’s affiliates will be received; (2) No new generic drug submission referencing the facility will be received until the fee is paid; (3) 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 (4) FDA will notify the ANDA applicant of the facility’s failure to satisfy its user fee obligations. Furthermore, all FDFs or APIs manufactured in the non-paying facility and all FDFs containing APIs manufactured in such a facility will be deemed misbranded. This means that it will be a violation of federal law to ship these products in interstate commerce or to import them into the United States. Such violations can result in prosecution of those responsible, injunctions, or seizures of misbranded products. Products misbranded because of failure to pay facility fees are subject to being denied entry into the United States. Additionally, goal dates will not apply to applications that have already been received but list facilities for which facility fees are owed. Please note that the fee is an obligation to the U.S. government, and the failure to pay the fee may result in collection activities by the government pursuant to applicable laws. When will the ANDA filing fee be due? ANDA filing fees will be due on the date the application is deemed submitted. If FDA refuses to receive an ANDA, is there any provision for a partial refund of the application fee? FDA will refund 75% of the application fee for the fiscal year in which the application is deemed submitted. How does the ANDA sponsor receive the 75% refund if FDA has refused to receive the ANDA pursuant to section 505(j)(4) of the FD&C Act? To request a refund, submit an online form at https://userfees.fda.gov/fdarefund/. If you do not submit a refund request, FDA will initiate a refund during its periodic review of outstanding refunds. If such a previously refused application is then resubmitted, will the applicant be required to pay another full fee at the time of resubmission? Yes. When is a response to an RTR letter considered a resubmission? A resubmission of an ANDA is a formal response to a refuse-to-receive (RTR) determination and is submitted to the ANDA refused for receipt. Submission of a dispute of an RTR determination without attempting to remedy the deficiencies (i.e., without resubmitting the ANDA) is not considered a resubmission and is therefore not subject to a new ANDA filing fee. What is the penalty for failure to pay the ANDA filing fee? The application or supplement to an application will be deemed incomplete on the date of submission and will not be received. If an ANDA applicant pays its filing fee more than 20 calendar days after the due date, what will FDA consider as the application’s date of submission? So long as FDA finds that none of the disqualifications outlined in 21 CFR 314.101(d) and (e) apply, the application will be considered submitted as of the date all obligations are satisfied and the payments are received in full. If an ANDA is withdrawn, will FDA issue a refund? Yes, companies are entitled to a 75% refund of the application fee if the application is withdrawn prior to being received. If an ANDA is withdrawn before the filing fee is paid, will the obligation to pay the fee remain? Yes. An ANDA filing fee is incurred upon submission. Once the ANDA is submitted, the applicant is liable for paying that fee. What is a generic drug submission? The phrase generic drug submission refers to an ANDA, an amendment to an ANDA, or a Prior Approval Supplement (PAS) to an ANDA. If a generic drug submission includes API information other than by reference to a DMF, is the applicant required to pay an additional fee? Yes. An applicant is required to pay an API information fee for a generic drug submission that contains information concerning the manufacture of an API at a facility by means other than reference by a letter of authorization to a Type II active pharmaceutical DMF, and for which a fee in the amount equal to the DMF fee has not been previously paid. Similar to the DMF fee, this fee is paid only once. An additional API information fee must be paid for each description, contained in a particular application, of the manufacture of an API by one facility. Therefore, the total amount of the API information fees for a particular application is a function of the number of APIs referenced in the application and the number of facilities in which those APIs are manufactured. The API information fee must be paid for each description of the manufacture of an API by a particular API facility, provided a DMF or API information fee has not already been paid for the manufacture of the same API by the same facility. Because the calculation is potentially confusing, we provide the following two examples. Example One: An applicant (XYZ Corp.) submits an ANDA that, rather than referencing a DMF, describes the manufacture of three APIs at one or more facilities. No previous API information or DMF fee has been paid for the manufacturing of the APIs by these facilities. ProductAPIFacility that has not paid API feeDrug XAlpha1, 2, 3Beta1, 2Gamma1 In this example, XYZ Corp. owes the following API information fee: Fee = (APIs (Alpha + Beta + Gamma) + extra facilities (Alpha 2 + Alpha 3 + Beta 2)) x DMF Fee Amount = (3 APIs + 3 Extra facilities) x DMF Fee Amount = 6 x DMF Fee Amount Example Two: XYZ Corp. then submits a new application for a second product with the following information about API manufacture other than by reference to a DMF: ProductAPIFacilityDrug YAlpha1, 2, 3Beta1, 2Gamma1, 2Delta1 The one-time fee has already been paid for the description of the manufacture of API Alpha at Facility 1, 2, and 3; API Beta at Facility 1 and 2, and API Gamma at Facility 1, so no additional fee is due with respect to these facilities. The applicant owes and API information fee for the following: Fee = (additional API Delta + manufacture of API Gamma at Facility 2) x DMF fee Amount = (1 API + 1 extra facility) x DMF Fee Amount = 2 x DMF Fee Amount Are the references to fees for each API facility in the above example different from the annual fee that each API facility must pay (discussed below)? Yes. The reference to fees for each API facility in the calculation above is meant to replicate the DMF fee required if the information is submitted in a DMF. Annual API facility fees are discussed below and are required for each facility that makes an API for a generic drug, regardless of whether the API is identified in an ANDA or a DMF. When should the application filing fee for a serially submitted ANDA be paid? In some circumstances, ANDA applicants choose to serially submit complete ANDAs in anticipation of a patent being listed for a reference listed drug (RLD) that is protected by new chemical entity (NCE) exclusivity and has no other patents listed. This is done because the ANDA cannot be submitted until the final year of the five-year exclusivity period, and then only if the submitter is challenging the patent. A single payment for multiple submissions of the same ANDA is required. Applicants who choose to serially submit complete ANDAs in anticipation of a patent being listed for a RLD that is protected by NCE exclusivity and has no other patents listed should refrain from remitting their application filing fee until such time as the applicant is instructed by Office of Generic Drugs (OGD) that it has a valid application. Once a patent has been listed and an application can therefore be received for review by OGD, an applicant will have 20 days in which to pay its user fee.
