FDA Proposes Biosimilar and Interchangeable Biological Product User Fee System and Performance Goals

By Kurt R. Karst –      

On December 7, 2011, FDA will publish a Federal Register notice – a prepublication version of which is available here – announcing a December 16th public meeting and comment period (Docket No. FDA-2011-N-0326) to discuss the Agency’s proposed recommendations for a user fee program for biosimilar biological products for Fiscal Years (“FYs”) 2013 through 2017.  The meeting and comment period is required by the Biologics Price Competition and Innovation Act of 2009 (“BPCIA”), which was enacted on March 23, 2010 as part of the Affordable Care Act, and which created, under new section 351(k) of the Public Health Service Act (“PHS Act”), a route to obtain approval of biosimilar and interchangeable versions of a reference product licensed under PHS Act § 351(a).  The December announcement follows a May 2011 notice (see our previous post here) FDA held with public and industry stakeholders regarding the development of a § 351(k) application user fee program for FYs 2013-2017. 

FDA’s notice includes both a discussion of the proposed user fees, and the Agency’s proposed performance goals and procedures for the next five FYs.  Each topic is discussed below.

Proposed User Fees.  FDA proposes the establishment of four types of biosimilars user fees.  Three of the fees – the one-time application fee, and the annual product and establishment fees – are well known to industry and would be set equal to the rates established under the Prescription Drug User Fee Act (“PDUFA”) for a particular FY.  For FY 2012, the PDUFA fees are $1,841,500 (application), $520,100 (establishment), and $98,970 (product) – see our previous post here.  

The big difference for biosimilars is the proposed fourth fee type – the Biosimilar Product Development (“BPD”) fee for products in development.  It is a fee that would initially be due either upon the date of submission of an Investigational New Drug Application (“IND”) pursuant to FDC Act § 505(i) “describing an investigation that FDA determines is intended to support a biosimilar biological application for a product,” or within five days after FDA grants a request for a so-called “BPD Meeting” (discussed below) for a product.  According to the proposal, the initial BDP fee would be equal to 10% of the PDUFA application fee established for a particular FY.  After paying the initial BDP fee, sponsors would pay an annual BPD fee (due on or before October 1st each year) until the sponsor submits a § 351(k) application that is accepted for filing, or until the sponsor discontinues participation in the BPD program for the product.  The cumulative BPD fees paid by a sponsor for a product would be subtracted from the application fee.  Front-loading the fees in this manner, says FDA, will allow the Agency “to generate fee revenue in the near-term and to enable sponsors to have meetings with FDA early in the development of biosimilar biological product candidates.”      

Some other highlights concerning the proposed BPD fees include:

• Only one BPD fee per product will be assessed regardless of the number of proposed indications for the biosimilar product;
• Each person that has submitted an IND before the date of enactment of legislation authorizing the biosimilars user fee program, and that FDA determines is intended to support a § 351(k) application for a product, will be subject to the initial BPD fee;
• An IND sponsor may discontinue participation in the BDP program only after withdrawing the affected IND, and must do so by August 1 of the year of discontinuation to avoid incurring a fee for the next FY;
• A sponsor that has discontinued participation in the BPD program for a product must pay  a reactivation fee equal to twice the initial BPD fee for that fiscal year in order to resume participation in the BPD program for that product;
• Failure to pay the any of the BPD fees (i.e., initial, annual, or reactivation) would result in FDA refusing to grant a BPD Meeting relating to the biosimilar biological product for which the fees are owed.  In addition, “if a sponsor that owes BPD fees submits an IND that FDA determines is intended to support a biosimilar biological product application, FDA would not consider the sponsor’s IND to have been received under [FDC Act § 505(i)(2)].”  For a sponsor with an existing IND, FDA would impose a “financial hold” prohibiting the sponsor from continuing the investigation.  Finally, if a sponsor has failed to pay required BPD fees, then any § 351(k) or supplement submitted by that sponsor “would be considered incomplete and would not be accepted for filing until all fees owed by the sponsor have been paid.”

Proposed Performance Goals and Procedures.  FDA’s notice includes a summary of the proposed performance goals for a number of items, including proprietary name review, major dispute resolution, clinical holds, special protocol assessments, first cycle performance goals, and, as discussed below, review performance goals and meeting management goals.  The full description of FDA’s proposed performance goals and procedures for the biosimilars user fee program are in the draft biosimilars user fee commitment letter that is hot off the presses.

FDA’s proposed review performance goals include goals for biosimilar biological product application submissions and resubmissions, supplements with clinical data, and original manufacturing supplements.  As with the initial iteration of PDUFA, FDA takes a step-wise approach over the first few FYs to reach a goal of 90% for original and resubmitted § 351(k) applications.  This is depicted in the tables below.

Performance Goals for Original and Resubmitted Applications and Supplements

Performance Goals for Original and Resubmitted Supplements

Proposed additions to FDA’s meeting lexicon are five types of meetings related to a sponsor’s biosimilar biological product development program:

• Biosimilar Initial Advisory Meeting – This is an initial assessment meeting limited to a general discussion regarding the feasibility of licensure under PHS Act § 351(k), and general advice on the expected content of the development program if the § 351(k) route is feasible. 
• BPD Type 1 Meeting – Similar to a Type A meeting under PDUFA, this is “a meeting which is necessary for an otherwise stalled drug development program to proceed (e.g. meeting to discuss clinical holds, dispute resolution meeting), a special protocol assessment meeting, or a meeting to address an important safety issue.”
• BPD Type 2 Meeting – This is a meeting for the sponsor and FDA to discuss a specific issue, such as a proposed study design or endpoints, or to discuss questions seeking targeted advice from FDA regarding an ongoing development program.
• BPD Type 3 Meeting – This is an in-depth data review and advice meeting that may include “substantive review of full study reports, FDA advice regarding the similarity between the proposed biosimilar biological product and the reference product, and FDA advice regarding additional studies, including design and analysis.”
• BPD Type 4 Meeting – This is a meeting to discuss the format and content of a § 351(k) application or supplement. 

FDA’s target timeframes for the various meeting types are shown below.  FDA’s performance goals for the meetings begin with 70% in FY2013 and progress to 90% by FY2017.

After the December 16th public meeting, will finalize its user fee and performance goal proposals, revising them as necessary in response to comments or concerns raised at the public meeting and in docket comments.  Under § 7001(f)(1) of the Affordable Care Act, FDA must transmit its recommendations to Congress by January 15, 2012.

Additional Reading:

• PhRMA Statement on Biosimilar User Fees