FDA issued this week a notice in the May 10th Federal Register in which the agency is requesting input from stakeholders and the public on a proposed user-free program for biosimilar and interchangeable biological product (i.e., Sec. 351 (k)) applications. The call for input on biosimilar user fees, a mechanism to fund regulatory review, is another step toward the development of a US regulatory pathway for biosimilars.

The Biologics Price Competition and Innovation (BPCI) Act of 2009, a provision of the Affordable Care Act (Public Law 111–148), created an abbreviated approval pathway for biological products that are demonstrated to be highly similar (i.e., biosimilar) to, or interchangeable with an FDA-licensed biological product, according to FDA in a May 9, 2011, press release. It directs FDA to develop recommendations for a 351(k) user-fee program for fiscal years (FY) 2013 through 2017. The recommendations must be presented to Congress by January 15, 2012.

The proposed biosimilar user-fees program recommends that at least for the initial five-year authorization, biosimilar user fees should remain comparable to those used under the Prescription Drug User Fee Act (PDUFA), the user-fee program now used for pharmaceuticals. FDA, however, noted that since the approval pathway for biosimilar and interechangeable biological products is new, FDA services would be most crucial during the investigational stage prior to the submission of a marketing application, and the proposed user-fee program has some modifications based on this fact.

In the Federal Register notice, the agency said it expects to maintain PDUFA-fee levels for marketing applications, manufacturing establishments, and products. The agency, however, is proposing a 351(k) user-fee structure that would shift payment for FDA review to the earlier stage of development where FDA activities would be in greatest demand and where increased review capacity would be needed.

The proposed 351 (k) user-fee program would consist of several phases. For an application in the premarket phase, there would be a biosimilar product-development fee, paid upon submission of an investigational new drug application and annually thereafter for a biosimilar or interchange product under active development. FDA anticipates that the FY 2013 annual biosimilar product-development fee amount would be on the order of $150,000. There would also be an application fee for each 351(k) marketing application at the time of application submission, which would be equal to a PDUFA original new drug application/biologic license application, less the sum of payments from biosimilar product-development fees. For marketed 351(k) products, there would be annual establishment and product fees set equal to the respective PDUFA fees. FDA anticipates a modest level of funding from these sources because only biosimilar biological products already approved for marketing would be subject to these fees. Comments on the proposed biosimilar user-fee program are due June 9, 2011.

User fees are an inevitable component of a US biosimilar regulatory pathway, particularly in an era of constrained governmental resources. The more significant aspects of a US regulatory pathway for biosimilars, such as the level and extent of clinical-trial testing for establishing bioequivalence and how closely US provisions may align with European provisions, have yet to be finalized. A recent Reuters report indicated that a US guidance on biosimilars will be forthcoming this year, which will a key determinant not only in the regulatory administration of biosimilars, but their market direction.