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Jul 20

FDASIA, Part 1: The “UFAs”

On 09 July 2012, the Food and Drug Administration Safety and Innovation Act (FDASIA, otherwise known as PDUFA V) was signed into law.  In a 4-part series, we will cover the major changes in FDASIA as follows:

Today, we start with the User Fee Amendments (UFAs), two of which are renewals (PDUFA and MDUFA) and two of which are brand new (GDUFA and BsUFA).

PRESCRIPTION DRUG USER FEE AMMENDMENTS ACT (PDUFA)

PDUFA was initially enacted in 1992.  It mandated that manufacturers of new drugs pay a fee for submitting a New Drug Application (NDA).  The subsequent increase in revenue was intended to be used to reduce the time of FDA review of NDAs.  PDUFA was very successful and was reauthorized in 1997, 2002, 2007, and now, in 2012.  There are several changes in the 2012 version that are summarized below.

FEES

  • Establishment and product fees are now “due on the later of 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 and obligation of fees for such fiscal year.”
  • Prescription drug products are not subject to a product user fee if the product is the same as another NDA or ANDA (Abbreviated NDA) approved product AND the other NDA or ANDA approved product is not listed in the discontinued section of the Orange Book

GOALS

  • A new review model for NDAs and BLAs (Biologic License Applications) including the following:
    • A”strongly encouraged” presubmission meeting to agree on content of a complete application and to have early discussions on REMS.  If there is no presubmission meeting or other agreement in place between the sponsor and the FDA, the NDA or BLA application should be complete at the time of submission.
    • A mid-cycle communication to provide a status update of the application review to the sponsor
    • A late-cycle meeting for the FDA and the sponsor to discuss the status of the review
    • Pre-IND and other Type C meetings will no longer automatically be granted, and instead of granting a meeting, the FDA can provide a written response within 60 days of a Pre-IND meeting request
    • New review timelines are based on the FILING date of an NDA.  These timelines are intended to ensure that standard NDA/BLA reviews take place within 12 months and priority NDA/BLA reviews take place in 8 months from the application submission.
    • Major NDA or BLA amendments that are submitted AT ANY TIME during the review cycle may extend the goal date by 3 months (for an original application, efficacy supplement, or resubmission) or 2 months (for a manufacturing supplement)

MEDICAL DEVICE USER FEE AMMENDMENTS ACT (MDUFA)

MDUFA was initially enacted in 2002 and was reauthorized 2007.  Changes in FDASIA include the following:

FEES

  • MDUFA fees apply to ANY establishment “engaged in the manufacture, preparation, propagation, compounding, or processing of a device” (not just to manufacturers, reprocessors, and specifications developers).
  • PMA fees are increased to $248,000 in Fiscal Year (FY) 2013 and will increase to $268,443 by FY 2017
  • 510k fees are 2% of PMA fees per FY
  • Establishment fees are $2,575 in FY 2013 and will increase to $3,872 by FY 2017
  • MDUFA fees can be waived if it is in the interest of public health

GOALS

  • If the FDA issues a deficiency letter, a telephone or email hold, or an information request, the communication will be based on a review of the entire application
  • For original PMAs, supplements, and premarket report applications, review goals are as follows:
    • 15 calendar days  – communication of the filing of the application
    • 45 calendar days (from receipt of application) – communication of application filing status
    • 90 calendar days (from filing date of application) – communication of Substantive Interaction identifying any major deficiencies in the application)
    • 180 FDA Days – communication of MDUFA decision if advisory panel input is not required
    • 320 FDA Days – communication of MDUFA decision if advisory panel input is required
  • For 501(k) submissions, review goals are as follows:
    • 15 calendar days – communication if submission is accepted for review
    • 60 calendar days (from filing date of application) – communication of Substantive Interaction
    • 90 FDA Days – communication of MDUFA decision

GENERIC DRUG USER FEE AMMENDMENTS ACT (GDUFA)

GDUFA is the first of two new UFAs in FDASIA, and it establishes user fees for manufacturers of generic drugs.    Similar to the other UFAs, GDUFA is intended to increase revenue to the FDA to reduce the review and approval times of generic drugs.  GDUFA includes the following:

 FEES

  • Original ANDA fee (amount for FY 2013 amount not yet determined)
  • Prior Approval Supplement (PAS) fee (½ the ANDA fee)
  • Type II Drug Master File (DMF) fee to be paid by each person owning a Type II Active Pharmaceutical Ingredient (API) DMF that is referenced in a generic drug submission on or after 01 Oct 2012.  This is a 1-time fee due no later than when the referencing ANDA is submitted (amount not yet determined).
  • Annual facility fee paid by both Finished Dosage Form and API manufacturers (amount not yet determined)
  • ANDA backlog fee for FY 2013 for ANDAs pending on 01 Oct 2012 (fee will be $50 million divided by the number of ANDAs in the backlog).

GOALS

  • “Expedited review” of ANDAs in FY 2013 and FY 2014; 15 month review of 60% of submissions in FY 2015 and 75% in FY 2016; and 10 month review of 90% of submissions in FY 2017
  • Review and act on 90% of all ANDAs and ANDA PASs that are pending on 01 Oct 2012 by end of FY 2017
  • Biennial cGMP inspections of domestic and foreign generic API and FDF manufacturers
  • Rolling review of ANDAs and DMFs
  • Complete review and response letters for ANDAs and DMFs
  • First cycle deficiency meetings for ANDAs and DMFs

BIOLOGICS USER FEE AMMENDMENTS ACT (BsUFA)

BsUFAs are new user fees for biosimilars, which are generic versions of biologically manufactured products.  With the recent passage of the Patient Protection and Affordable Care Act, there is now a mechanism in place for the review and approval of biosimilar applications as defined by the Biologics Price Competition and Innovation Act (BPCIA).

FEES

  • One-time application fee (equal to PDUFA application fee if new clinical data is required, or ½ PDUFA application fee if only comparative bioavailability studies are required)
  • Annual product and establishment fee (equal to PDUFA establishment fee)
  • Supplement fee (equal to ½ PDUFA application fee)
  • Biosimilars Biological Product (BBPD) fee (10% of PDUFA application fee), due with the IND submission or within 5 days of a request for a BBPD meeting, whichever is earlier
  • Backlog fee (10% of PDUFA application fee) for biosimilar INDs submitted before 09 Jul 2012, due 07 Sept 2012 or within 5 days of a request for a BBPD meeting, whichever is earlier
  • Annual BBPD fee beginning the FY after the initial BBPD fee was paid (10% of PDUFA application fee).  This fee is required annually until the application is accepted, discontinued, or withdrawn
  • Reactivation fee (20% of PDUFA application fee)
  • Product fee for each biosimilar product that is approved (equal to PDUFA product fee)
  • Fees may be waived for “the first BBP application that a small business or its affiliate submits” (must be submitted within 180 days after the fee is due)

GOALS

  • Review:
    • 10 month review of 70% of original submissions in FY 2013 to increase to 90% by FY 2017
    • 6 month review of 70% of resubmitted applications in FY 2013 to increase to 90% by FY 2017
  • Meetings:
    • Biosimilar Initial Advisory Meeting (feasibility advice; 90% to be granted within 21 days and to take place within 90 days of request)
    • BBPD Type 1 Meeting (similar to PDUFA Type A for clinical holds; 90% to be granted within 14 days and to take place within 30 days of request)
    • BBPD Type 2 Meeting (for sponsor and FDA to discuss specific issue; 90% to be granted within 21 days and to take place within 75 days of request)
    • BBPD Type 3 Meeting (substantive review and advice; 90% to be granted within 21 days and to take place within 120 days of request)
    • BBPD Type 4 Meeting: (discuss format and content of biosimilar application; 90% to be granted within 21 days and to take place within 60 days of request)
    • Proprietary name review within 180 days if submitted during development and within 90 days if submitted with product application
    • Response within 45 days  to special protocol assessments
    • Response within 30 days of receipt  sponsor’s complete response regarding a clinical hold