The U.S. Food and Drug Administration (FDA) announced this month that it is seeking industry and stakeholder input on the development of a user fee program for biosimilar and interchangeable biological products.1 Written comments must be submitted to the FDA no later than June 9, 2011. In addition to accepting written comments, the agency will be holding public and industry stakeholder meetings. Parties interested in participating in these meetings must submit a notification of interest to the FDA on or before June 3, 2011. The FDA issued a Federal Register notice2 on May 10, 2011, which outlines the agency’s proposals for the new user fee program and includes detailed information about how to submit comments and notices of interest.3

Background: Biosimilars and User Fees

The Biologics Price Competition and Innovation Act of 2009 (BCPI) created section 351(k) of the Public Health Service Act (PHS), which provides for an abbreviated approval pathway for biological products shown to be highly similar (“biosimilar”) to, or interchangeable with, an FDA-licensed reference biological product.4 Under section 351(k) of the PHS, “interchangeable” means that the application contains sufficient information for the FDA to determine that the product is “biosimilar to the reference product” and “can be expected to produce the same clinical result as the reference product in any given patient” (42 U.S.C. § 262(k)(4)(A)). Additionally, “for a biological product that is administered more than once to an individual, the risk in terms of safety or diminished efficacy of alternating or switching between use of the biological product and the reference product [must not be] greater than the risk of using the reference product without such alternating or switching” (42 U.S.C. § 262(k)(4)(B)).  

The BCPI also amended the Federal Food, Drug and Cosmetic Act to make applications submitted under the PHS’s new section 351(k) eligible for user fees. The BCPI directs the FDA to develop recommendations for a biosimilar and interchangeable biological product user free program for section 351(k) applications for fiscal years 2013 through 2017. The FDA’s recommendations on the new user fee program must be submitted to Congress by January 15, 2012.

As it develops recommendations for Congress about the new user fee program, the FDA is required to consult with a range of groups, including scientific and academic experts, healthcare professionals, representatives of patient and consumer advocacy groups, and regulated industry. The FDA’s recent announcement that it is accepting stakeholder input marks the beginning of this process. The FDA will consider comments and other input from such stakeholders as it develops its recommendations about the user fee program, and interested parties should act on this opportunity to inform the FDA’s program development process.

FDA’s Current Thinking on the Biosimilars User Fee Program

The May 10 Federal Register notice outlines the FDA’s current thinking on the new biosimilars user fee program. Specifically, it describes 1) the agency’s principles for developing the program; 2) a proposed structure for the program; and 3) proposed program performance goals. We highlight some of the key provisions of the Federal Register notice below.

  1. Principles for the Development of a Biosimilars User Fee Program

FDA lists the following principles that will guide the development of the new user fee program:

  • Biosimilar and interchangeable biologics represent a critical public health benefit to patients. The FDA needs sufficient review capacity to prevent unnecessary delays in the development and approval of these products.
  • At least for the initial five-year authorization period of the new user fee program, fees for biosimilar and interchangeable biologics should remain comparable to fees for innovator biologics licensed under section 351(a) of the PHS. Review to determine biosimilarity or interchangeability of a 351(k) product is expected, at first, to be as complex, technically demanding and resource intensive as review of traditional biologics license applications.
  • The new user fee program should provide funding to support activities that occur early in the biosimilar and interchangeable product development cycle. Given that the 351(k) approval pathway is new, FDA assistance is most critical during the investigational stage prior to the submission of a marketing application.
  • The 351(k) user fee program should ensure adequate resources for review of biosimilar and interchangeable product applications, so that critical resources for other areas of review are not redirected. Applications for both 351(a) and 351(k) applications need adequate resourcing to ensure the best health outcomes for patients and fairness to all industry sponsors.
  1. Proposal for a Biosimilar User Fee Program

The FDA proposes a user fee program structure that differentiates between premarket products and marketed products. For applications in the premarket phase, the FDA proposes a Biosimilar Product Development Fee that would be paid upon submission of an investigational new drug application and annually thereafter for a biosimilar under active development that is intended for submission in a 351(k) marketing application. The agency also proposes a Marketing Application Fee that would be paid for each submitted 351(k) application. This fee would be set to equal the fee for applications submitted under section 351(a), less the sum of all previously paid annual Biosimilar Product Development Fees for that product.

For marketed biosimilar and interchangeable biologics, the FDA would charge annual Establishment Fees and Product Fees. The Establishment Fee is paid annually for each biosimilar and interchangeable biological product establishment that is listed in an approved 351(k) application. This fee would not apply if the applicant does not manufacture the product in the given fiscal year. The Product Fee is paid annually for each approved biosimilar and interchangeable biological product.  

  1. Proposed Performance Goals for Biosimilar Applications

In its discussion of proposed performance goals, the FDA notes that 351(k) applications fall into two categories. Section 351(k)(7) of the PHS specifies that a 351(k) application may not be submitted until four years after the reference product was first licensed, and the FDA may not make approval of any such application effective until 12 years after the reference product was first licensed. Based on this rule, the first category of 351(k) applications are those submitted 10 or more years after the date that the reference product was first licensed. Such applications would be eligible for effective approval within two years. The second category of applications—those submitted between four and 10 years after the date that the reference product was first licensed—have much longer approval timelines (up to eight years in some cases). Accordingly, the FDA focuses its performance goals on the first category of applications— those filed 10 or more years after the date that the reference product was first licensed.5

In the Federal Register notice, the FDA sets forth detailed year-by-year performance goals for 351(k) applications filed 10 or more years after the date that the reference product was first licensed. Briefly, for fiscal year 2013, the agency initially proposes to review and act on fifty percent of original 351(k) submissions requesting a biosimilarity or interchangeability determination within 10 months of the 60-day filing date. By 2017, the agency proposes to review and act on 90 percent of original 351(k) submissions requesting a biosimilarity or interchangeability determination within 10 months of the 60-day filing date.


The FDA’s Federal Register notice provides considerable insight into the agency’s current thinking on the biosimilar user fee program. Interested parties should review the FDA’s proposals in detail and consider how the proposed approach might affect product development, especially in terms of costs for development and timing for review and approval. The window to submit comments expires on June 9, 2011, so interested parties should act quickly.