United States: FDA's First Major Action On Establishing User Fees For Biosimilar Applications Under PHSA 351(K)

On 9 May 2011, the Food and Drug Administration (FDA) issued a request for comments on the agency's proposed options for a user fee program for biosimilar and interchangeable biological applications for fiscal years 2013-17, which is required by the Biologics Price Competition and Innovation Act of 2009 (BPCIA).¹ The BPCIA established an abbreviated regulatory pathway for the approval of biosimilar and interchangeable biologics under the Public Health Service Act (PHSA), section 351(k). Under the new notice, the agency is requesting input on its proposed principles, structure, and performance goals for a section 351(k) user fee program. Comments are due by 9 June 2011. Notification of interest to participate in public stakeholder meetings is due by 3 June 2011.

Proposed principles

FDA's proposed guiding principles to develop a "fair and adequate initial user fee program" for section 351(k) applications are, briefly:

• The need to ensure sufficient review capacity and resources for section 351(k) applications.
• The need to support activities that occur early in the section 351(k) product life cycle, including advice and oversight during the product development and investigational phases.
• The need to ensure that oversight of biosimilars will not draw resources away from agency activities on innovative biologics, and vice versa.
• The need to maintain some level of comparability between section 351(k) and section 351(a) user fees.

Proposed user fee structure

FDA proposes that because resource allocation will be similar between review of section 351(k) and section 351(a) applications, the user fees should be the same. Thus, biosimilar applicants would pay the same user fee and annual product and establishment licensing fees as applicants for new biologics under section 351(a).

FDA's proposed structure includes two pre-market phase fees—a Biosimilar Product Development Fee and an Application Fee. It also includes two fees for marketed applications—Establishment Fees and Product Fees.

Essentially, the agency is proposing a structure under which user fees for biosimilar and interchangeable biologics applications will be front-loaded, with payments beginning with the submission of an IND for a product to be developed under the section 351(k) pathway. A sponsor of a potential biosimilar would, for example, pay an annual fee (i.e., a "Biosimilar Product Development Fee") for every year until the sponsor submits a section 351(k) marketing application. At that time, the total sum of fees paid under the Biosimilar Product Development Fee will be subtracted from the amount due for the Application Fee. Thus biosimilar sponsors will not pay more than sponsors of new biologics; they will just pay fees earlier.

Table 1 - FDA proposed section 351(k) user fee program

Proposed performance goals

For purposes of establishing performance goals, FDA is seeking to account for the 12-year exclusivity period applicable to innovative biological substances and, in particular, the idea that biosimilar applications may be submitted many years before they could indeed be marketed. The agency wants to avoid a "hurry up and wait" system in which it promptly reviews applications that will then have to sit idle for extended periods.

Thus, FDA is proposing to distinguish between section 351(k) applications that are submitted at least 10 years after the first licensure of the reference product—where most of the exclusivity will have already run—and applications that are submitted earlier in the original marketing period for the pioneer. The first category of products can be approved within two years or less, depending on the relevant filing dates, and performance goals similar to those for section 351(a) may be appropriate.

The agency appears uncertain, however, of how to set performance goals for applications received more than two years prior to the expiration of the innovator's exclusivity period. The BPCIA allows for submission of applications as early as four years after first licensure of the reference product but prevents approval until 12 years after first licensure. The agency is concerned that significant quality attributes and manufacturing changes could occur during this period—up to eight years—that would require re-review of the application closer to the time of approval.

As for performance goals, the agency proposes phasing in the goals over a five-year period. Beginning in FY 2013, 50 per cent of reviews would be expected to be completed (to first action) within 10 months of the 60-day filing date, and within six months for a resubmission. Each year the percentage target would increase 10 per cent so that by FY 2017, the agency's goal would be complete 90 per cent of its reviews meeting the specified timelines.

FDA has asked for input on the above principles, structure, and goals. The agency has also asked for input on how to factor into its performance goals the sponsor's readiness for inspection. Overall, the agency has expressed interest in whether there are any other factors unique to the section 351(k) pathway that should be considered. For example, one interesting issue not identified in the agency's notice is the relationship between deferral of the review of certain applications where substantial exclusivity time remains, and the provisions under section 351(k) that allow for early patent litigation. Will the agency's proposal to defer certain reviews encourage the filing of weak or placeholder applications intended primarily to trigger patent litigation?

Footnotes

1. Federal Register notice, Docket number FDA-2011-N-0326

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