GDUFA (Generic Drug User Fee Act): Q&A Session 2 by teleconference

Transcription

1 GDUFA (Generic Drug User Fee Act): Q&A Session 2 by teleconference 11 th December at 2pm GMT, 3pm CET and 9am EST (USA) What is new? GDUFA is in force since October 1, 2012 One-time backlog fee required to pending ANDAs was due no later than November 26, 2012 (this didn t affect DMF holders). Arrears list published DMF fees for FY2013 (Oct2012 Oct 2013) published in the Federal Register were set at $21,340 Self-identification initial deadline was December 3 rd, now extended to December 18 th. 1,700 facilities have self-identified for FY 2013, so far. Draft Guidance about the Initial Completeness Assessment available for comments since October. Facility fee to be published by the FDA at the end of January. 1

2 Most of the following 24 questions were pre-submitted by those on the call. Question Answer 1) Generic API manufacturers have to self-identify with the FDA until 03-December-2012 (now extended to 18-December-2012). What about API intermediates manufacturers? Do they have to selfidentify as well? Per the same deadline? There may be cases that the intermediate manufacturer is not informed of the type of application of the API, i.e. for innovative or for generic drug. 2) A company has filed a DMF for an ANDA between 2008 and October Agreed, the company has to self-identify and pay the self-id fees. If there is a change after October 2012 affecting the DMF, this has to be filed under GDUFA. Does the DMF holder have to pay the full fee for a DMF submission under GDUFA when only a minor part of the DMF is affected, or does the company have to pay a reduced fee or no fee at all as the DMF was already reviewed? 1) If the intermediate doesn t fall into the definition of API, the facility doesn t need to self-identify or to pay facility fees. In case the intermediate falls into the GDUFA definition of API (in italic below), it is important to seek clarity with your customer to know if it is listed in an ANDA. If the intermediate is not considered an API under GDUFA you don t have to be concerned because is out of scope of GDUFA. API as defined in GDUFA includes a substance intended for final crystallization, purification or salt formation or any combination of these activities to become the final API. 2) You don t need to pay for changes to the DMF. Only changes submitted as a Pre Approval Supplement (PAS) need to be paid by the ANDA holder. In the case presented, what triggers DMF payment is when a new Letter of Access to a new customer is issued. You also have the option to pay so that your DMF is listed in the available for reference database. 3) Up to now, DMFs are not approved by FDA. How can a DMF holder see if FDA judged his DMF 3) One of GDUFA review efficiency enhancements makes FDA send a letter to the DMF holder that the DMF doesn t have 2

3 acceptable or if the DMF was reviewed at all? (Provided, the DMF was submitted to FDA after 2007, and no Deficiency Letter was issued by FDA.) open issues once the ANDA is approved or tentatively approved. This an important improvement in the communication to DMF holders but we don t know when it will start. 4) A generic API is manufactured by the DMF holder and then micronized by a contractor identified in the DMF. The DMF holder has self-identified and has paid the fee for the ANDA DMF. Does the micronizing contractor have to self-identify as well? Then, does the micronizing contractor have to pay the self-id fee as well? 4) Micronization or particle reduction in general is not explicitly covered by the API definitions. However if the micronization site is listed in the DMF or ANDA as manufacturers of the API, it needs to self-identify and pay. If you wish you can ask confirmation directly to the FDA by ing: AskGDUFA@fda.hhs.gov 5. Fees for site tax: how much is it for non US manufacturers (we are located in France)? Would these fees be annual or only for years during which we sell product. 6. How payment is managed: will we receive an invoice in order to proceed to payment or will we have to erform it during information record on GDUFA website? 5. As long as your site is listed in an ANDA (submitted or approved) you will have to pay the annual fee. Even if you are not selling, as long as a customer has your company listed as supplier in their ANDA you have to pay. 6. FDA will not issue invoices. You can already pay your DMF by creating a cover sheet in the user fee system. 3

4 7. Is it confirmed that the DMF fee is not due for the ANDAs present in the backlog? I heard that ANDA holders have to pay the fee, but not the DMF holders. 7. That is correct, the backlog is only applicable to ANDAs pending review with the FDA, the DMF fee is not due for those. 8. A Swiss company has submitted in July 2012 a DMF for a generic API including a Letter of Authorization but the sponsor mentioned in this Letter of Authorization has not yet submitted its ANDA. Does this company have to register now as a Letter of Authorization is already provided or can wait until the submission by the sponsor of its ANDA? To date, no other DMF for a generic API has been submitted to the FDA. 9. We have already created the Gdufa Fee Cover Sheet and we have paid DMF Fees for several of our DMFs after October For these DMFs we already had a DMF number assigned by FDA and, therefore, we did not encounter problems when creating the Fee Cover Sheet. In case of new DMFs, however, we will not be able to create the Fee Cover Sheet until a DMF 8. FDA will verify payment of the facility and DMF at the time of ANDA submission. So, you need to have your facility and DMF paid when the ANDA is submitted. We recommend you ask the customer for its planned filing date so that you guarantee the facility and DMF fee is paid when they file. You can already pay the DMF fee of $21,340 to get prepared. This will trigger an initial completeness assessment. The facility fee is not established yet, so you have to wait for January This is correct. You need the DMF number to create a Cover Sheet. The administrative process of assigning the number by the FDA hasn t changed; the DMF is still received by the same administrative group and listed in the DMF database. We are not aware of improvements in the timeline for assigning the DMF number. 4

5 number would have been assigned by FDA. Nowadays it takes about 4 weeks to obtain a DMF number after DMF submission. Is this going to change or we will have to wait these 4 weeks before being able to pay the DMF fee or issue a LoA to the DMF (DMF number is needed)? 10. According to Draft Guidance on Initial Completeness Assessments for Type II API DMFs under Gdufa, new DMFs submitted after October 1, 2012 or old DMFs that have not been reviewed for CMC by FDA after November 30, 2007 will be subject of an initial completeness assessment before entering the FDA Available for Reference public list. Would it be possible for our customers to submit an ANDA referencing one of our DMFs if this DMF is still not listed in the FDA Available for Reference public list? Or the ANDA can only be submitted when that DMF is in the FDA Available for Reference public list. In case of Paragraph IV ANDA submissions this can be critical. 10. The FDA will receive the ANDA is the DMF fee is paid (independently of whether it is in the Available for Reference list). The answer is yes, your customer can file the ANDA even if the DMF doesn t show in the Available For Reference list, as long as the DMF is paid. 11. Which will be the FDA timeline for initial completeness assessments (span of time between the submission of the LoA to DMF and the DMF to be placed in the FDA Available for Reference public list if no Deficiencies are found)? 11. FDA will only start the initial completeness assessment once the DMF is paid. It doesn t matter when you submitted the LoA, but when FDA can confirm it is paid. 5

6 12. Regarding the Self-Identification of API manufacturing sites: Is there a way to verify (on FDA website) that our sites, for which we received a validation message (successful submission), are well integrated in the new GDUFA FDA database? 13. Are there any cases in which a NDA may reference a DMF for a generic application, thus leading to the payment of the GDUFA DMF Fee, or can we consider that all NDAs are excluded? 12. FDA is making available an excel list with the facilities identified to date. Please look into Self Identified Facilities List. 13. All NDAs are excluded. If a NDA references a DMF (of an off-patent drug), it doesn t need to pay the DMF fee. 14. Is it correct that the process of self ID will need to be renewed each year by the API manufactuer and this at its own responsibility without reminder by the FDA? Will there be a relation with the establishment registration renewal? 15. For existing DMFs, fees will only be due when a new LoA is issued or a new generic drug submission referring to the DMF is submitted => no DMF fees due in case of submission of an amendment requiring a PAS to an existing ANDA? In that case, does the DMF need to be fully updated if older than 5 years as required in GDUFA draft GfI on initial assessment of type II API DMF? 14. For the subsequent years, the manufacturers need to submit, update or reconfirm the information annually, on or before June 1. The facility fee due date is October 1 st (when the FDA fiscal year starts) 15. There is no DMF fee due in the case of amendments requiring a PAS (as long as they don t involve a new LoA). Only the ANDA holder that submits a PAS has to pay. If FDA reviewed that DMF at any point after November 30, 2007, then it is considered to have passed the initial completeness assessment and after payment it is automatically included in the available for reference list. If the DMF has not been reviewed after November 30, 2007, then FDA will assign it to a completeness assessment. This doesn t necessarily mean the DMF needs to be updated. If it complies with the checklist provided in the draft guidance about 6

7 16. For existing DMFs, fees will only be due when a new LoA is issued, and upon paying the fee the DMF will be published on a public list. In the case where for an existing DMF no update of the LoA is required, can the API manufacturer decide to pay the fee anyway to have the DMF published on the list? In case so, will the DMF then be assessed by the completeness assessment? Completeness Assessment it doesn t need to be updated. 16. Yes, the API manufacturer can decide to pay for a DMF to have it listed as available to reference. In the event that FDA hasn t reviewed the file after November 2007, then yes it will be subject to a Completeness Assessment. 17. In case of failure to pay, a notification will be sent by the FDA to the applicant, referencing the DMF. Will the DMF holder be notified directly by the FDA as well? 18. If FDA has reviewed the DMF for CMC after Nov 30, 2007, the DMF will be considered to have passed the initial CA without further analysis. However, what is considered as a full review under the completeness assessment? For example, in case a DMF has been amended with a CMC for which only specific CTD sections were updated and no full update of the DMF was submitted? 17. Only the ANDA holder is notified about the failure to pay the DMF or API facility fee. 18. A full review doesn t necessarily imply an updated DMF being submitted. A full review is triggered by a new ANDA submission. If there were no new ANDA submissions after Nov 30, 2007 which triggered a full review, then FDA will assign a reviewer for the initial Completeness Assessment. 19. For API manufacturers, is it confirmed that fees apply to each site, filing of every new DMF, every first LoA? 19. Facility fees are annual and apply to each site. Definitions of same site are available. DMF fee is a one a time fee. You only pay once when the first initial letter after the 1st October 2012 (don t have to pay for every LoA) 7

8 20. When will be published the total amount to be paid? How must we handle each payment? 21. What happens to manufacturers that have not yet accomplished the self-id? 22. Payments in 2013 will be made twice according to the fiscal years? 23. How long in advance shall we pay the fee before filing a new DMF? 20. The DMF was published in the federal register of October 25. The DMF fee is US$ 21, The deadline was extended to Dec 18. If companies fail to selfidentify, all APIs and FDFs using that API will be deemed misbranded. It will be considered a violation to import them into the USA, are subject to be denied entry into the US. 22. This will only happen for the facility fee, because the fee will be published in January and manufacturers have 45 days to pay. Then the facility fee for fiscal year 2014 is due on October 1 st Subsequently is only 1 fee paid per year? 23. You don t need to pay a DMF fee when you file the DMF. The fee is due when the ANDA or PAS is received. However once a company has the DMF number it can pay whenever it wants (even without an ANDA/PAS being submitted). 24. We have heard from customers that a fee should be paid for each Deficiency Letter received, is that true? 24. There are no payments for Deficiency Letters. 8