FDA Gets the Ball Rolling on Biosimilar/Interchangeable Biological Product User Fee Program; Proposal Gives a Hat Tip to PDUFA While Acknowledging the Nascent State of the Industry

By Kurt R. Karst –      

On May 9th, FDA announced the May 10th publication of a Federal Register notice proposing and requesting comment on the structure of a user fee program for applications for biosimilar and interchangeable biological products submitted under section 351(k) of the Public Health Service Act (“PHS Act”), which was created with the March 23, 2010 enactment of the Biologics Price Competition and Innovation Act of 2009 (“BPCIA”) (under Title VII of the Affordable Care Act).  Section 7001(f)(1) of the Affordable Care Act directs FDA to meet with a range of groups, to develop recommendations for a user fee program for 351(k) applications for Fiscal Years 2013 through 2017, and to submit recommendations to Congress by January 15, 2012. 

Before getting into the meat of FDA’s proposal, the Agency sets the stage by noting that  “[d]eveloping a user fee program for 351(k) applications presents unique challenges as compared to other medical product user fee programs.”  After all, FDA says, when PDUFA “was first implemented in FY 1993, the biopharmaceutical industry was relatively mature.”  In contrast, “given that the biosimilar and interchangeable biological product approval pathway did not exist prior to March 2010, the biosimilar and interchangeable biological product market is just forming.”  Thus, while “the PDUFA program is a useful model, FDA believes that a user fee program for 351(k) applications will need to include different elements to ensure an equitable program that generates adequate revenue.”

FDA also describes a set of four “key principles to support the development of a fair and adequate initial user fee program,” which are based on stakeholder comments to FDA and the Agency’s “prior experience with elements that foster strong and successful user fee programs.”  Those four “key principles” are:

(1)  “FDA needs sufficient review capacity to prevent unnecessary delays in the development and approval of [biosimilar and interchangeable biological] products;”

(2)  “At least for the initial 5-year authorization of the 351(k) user fee program, 351(k) user fees should remain comparable to 351(a) user fees [under PDUFA];”

(3)  “The 351(k) user fee program should provide funding to support activities that occur early in the biosimilar and interchangeable product development cycle;” and

(4)  “The 351(k) user fee program should ensure adequate resources for the review of 351(k) applications, so that critical resources for 351(a) review are not redirected from innovator drug review to biosimilar products.”

With that background in place, FDA launches into the Agency’s proposed user fees and performance goals for Fiscal Years 2013 through 2017. 

FDA proposes four different types of fees – two in the pre-351(k) market approval phase and two in the marketed 351(k) phase.  The two proposed pre-351(k) market approval phase user fees are:

(1)  A “Biosimilar Product Development Fee” of $150,000 that would “support the ongoing scientific, technical, and other regulatory activities associated with 351(k) biosimilar development, including milestone meetings and the application data reviews required to provide advice for the next steps in development.”  This fee would be paid upon the submission of an IND and annually thereafter “for a biosimilar or interchangeable product (molecule) under active development that is intended for submission in a single 351(k) marketing application.”  Failure to pay the fee “would result in the IND being placed on Full Clinical Hold;” and

(2) A “351(k) Marketing Application Fee” that would be paid for each submitted 351(k) marketing application, and that “would be set equal to a 351(a) marketing application fee [under PDUFA], less the sum of all of the previously paid annual Biosimilar Product Development fees associated with the biosimilar product that is the subject of the 351(k) application.

The two proposed marketed 351(k) phase user fees are the annual Establishment and Product Fees the drug industry is familiar with under PDUFA and that would be set equal to those PDUFA fees established annually by FDA.  The table below from FDA’s Federal Register notice captures each of the four proposed fees.

With respect to performance goals for Fiscal Years 2013 through 2017, FDA proposes that 351(k) applications be categorized into two types as a result of the exclusivity provisions at PHS Act § 351(k)(7).  Under PHS Act § 351(k)(7), a 351(k) application cannot be submitted to FDA until 4 years after the reference product was first licensed under section 351(a) and cannot be approved until 12 years after the reference product was first licensed (or 4.5 years and 12.5 years with pediatric exclusivity).

In Category 1 are “applications that are submitted 10 or more years after the date of first licensure of the reference product” and that “would be eligible for approval in 2 years or less, depending on the relevant filing dates.”  For this category, FDA proposes phased-in performance goals akin to those hammered out for PDUFA I.  Specifically, FDA proposes that beginning in Fiscal Year 2013, 50% of both original biosimilar and interchangeable 351(k) applications be reviewed and acted on within 10 months of the 60-day filing date, and 50% of biosimilar and interchangeable 351(k) application resubmissions in response to a complete response action be acted on within 6 months of receipt.  In Fiscal Years 2014-2017, the 50% figures from 2013 would go up to 60%, 70%, 80%, and 90%, respectively, while the 10-month (original) and 6-month (resubmission) review timeframes would remain static. 

In Category 2 are “applications submitted between 4 and 10 years after the date of first licensure of the reference product” and that “would not be eligible for approval for more than 2 years and perhaps for as long as 8 years.”  For this category, FDA says that the Agency “is concerned about committing resources to meet performance goals that might ready an application for approval years before it could be approved, necessitating updating of the application, new reviews, and new inspections of facilities shortly before the application becomes eligible for approval,” and therefore, instead of proposing performance goals, FDA is soliciting public comment on establishing performance goals for 351(k) applications in this category of applications, and specifically on three questions:

(1) “What factors should the Agency consider in determining appropriate performance goals for 351(k) applications that are filed earlier than 2 years prior to the date on which a 351(k) application would be eligible for approval (i.e., 12 years after the date of first licensure of the reference product)?”

(2) “How should the performance goals take into account readiness for inspection?”

(3) “What other factors relating to the unique characteristics of the 351(k) approval pathway should the Agency consider when setting performance goals for 351(k) applications?”

Not knowing exactly which companies comprise the regulated industry and acknowledging that not all public stakeholders have necessarily notified FDA of their interests, FDA implores interested parties to notify the Agency of their interest so that they can be included in the user fee recommmendation process.  Information on contacting FDA is included in the Agency’s Federal Register notice.