By Kevin E. Noonan --
Much has been written about the biosimilar approval pathway contained in the Biologics Price Competition and Innovation Act of 2009 (BPCIA). While the substantive provisions are still being worked out, one mundane and practical detail is how the government will pay for erecting and maintaining the regulatory edifice mandated under the biosimilars law. As with much of what the FDA does, this will be done by user fees, and determining the extent of these fees is currently being hashed out in Congress.
On Friday, the Senate considered several amendments and passed its version of the user fee provisions, S. 3187. Relevant to the BPCIA is TITLE IV: User Fees for Biosimilar Drugs, which contains several provisions related to various aspects of the nascent biosimilars regime. These include specifically Section 402, which sets forth amendments to the Food, Drug and Cosmetics Act as follows:
• For the "initial biosimilar biological product development fee," a fee that can be charged for an "initial meeting" with the FDA (744H(a)(1)(A)(ii)), or a "clinical protocol for an IND 'protocol' (under FCDA 505(i))" (744H(a)(1)(A)(iii));
• An "annual biosimilar biological product development fee" for maintaining the application (744H(a)(1)(B)); and
• Provisions for discontinuing payment (744H(a)(1)(C)) and reactivating payments (744H(a)(1)(D)) depending on status of application (withdrawn or resubmitted).
The bill also authorizes the FDA to refuse to meet with or receive IND from any applicant that has not timely paid the required fee (744H(a)(1)(E)), and provides for no refunds (744H(a)(1)(F)(i)), waivers, exemptions or reductions (744H(a)(1)(F)(ii)).
Further and different fees are assessed for filing the biosimilars application itself from which can be deducted the "cumulative amount" of any of the initial meeting, IND protocol or reinstatement fees previously paid. 744H(a)(2)(A)(i). There is a 50% discount of the application fee "for which clinical data (other than comparative bioavailability studies) with respect to safety or effectiveness are not required." 744H(a)(2)(A)(ii)). However, the same 50% fee will be charged for a supplement that submits clinical data for safety or effectiveness is required (having the same exemption for bioavailability studies). 744H(a)(2)(A)(iii).
Once approved, the successful biosimilar applicant will be assessed a "biosimilar biological product establishment fee" (744H(a)(3)(A)) for each "establishment" that manufactures an approved biologic drug; the fee is annual (744H(a)(3)(B)). The successful applicant is also assessed a "biosimilar biologic product fee" (744H(a)(4)(A)).
After setting forth what fees are to be charged, the bill sets forth the extent of the fees (744H(b)(1)(A)): generally the same as the fees for conventional drug products, but the initial meeting and product development fees are 10% of the fees charged under section 736(c)(4) for applications per Section 736(a)(1)(A)(i).
However, the total amount of fees charged for a fiscal year under this section may not exceed the total amount for such fiscal year of the costs of resources allocated for the process for the review of biosimilar biological product applications, pursuant to Section 744H(b)(2), indicating that Congress does not wish biosilimar applicants to become a "cash cow" for the agency. In addition, there is a waiver of the fee for the first biosimilar application filed by a "small business" (Section 744H(c)(1)), where a "small business" is defined as:
[A]n entity that has fewer than 500 employees, including employees of affiliates, and does not have a drug product that has been approved under a human drug application (as defined in section 735) or a biosimilar biological product application (as defined in section 744G(4)) and introduced or delivered for introduction into interstate commerce.
The bill also includes an amendment introduced by Senator Tom Coburn, M.D. of Oklahoma. The amendment, No. 2131 entitled "Independent Assessment Of The Drug And Biologic Application Review Process," reads:
SEC. 723. INDEPENDENT ASSESSMENT.
(a) IN GENERAL.—The Secretary shall contract with a private, independent consulting firm capable of performing the technical analysis, management assessment, and program evaluation tasks required to conduct a comprehensive assessment of the process for the review of drug applications under subsections (b) and (j) of section 505 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355(b), (j)) and subsections (a) and (k) of section 351 of the Public Health Service Act (42 U.S.C. 262(a), (k)). The assessment shall address the premarket review process of drugs by the Food and Drug Administration, using an assessment framework that draws from appropriate quality system standards, including management responsibility, documents controls and records management, and corrective and preventive action.
(b) PARTICIPATION.—Representatives of the Food and Drug Administration and manufacturers of drugs subject to user fees under part 2 of subchapter C of chapter VII of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 379g et seq.) shall participate in a comprehensive assessment of the process for the review of drug applications under section 505 of the Federal Food, Drug, and Cosmetic Act and section 351 of the Public Health Service Act. The assessment shall be conducted in phases.
The bill further provides that the first contract under this provision of the law be awarded "not later than March 31, 2013" and the agency must publish a "written assessment" "no later than February 1, 2016. (Section 723(c)). The findings of each such independent assessment must be published ("not later than six months after the contract is a awarded") and the "[f]inal comprehensive findings and recommendations" published "not later than 1 year after the contract is awarded. " (Section 723(d)(1)). The content of these assessments is also specified in the bill (Section 723(e)):
(1) Identification of process improvements and best practices for conducting predictable, efficient, and consistent premarket reviews that meet regulatory review standards.
(2) Analysis of elements of the review process that consume or save time to facilitate a more efficient process," that includes—
(A) consideration of root causes for inefficiencies that may affect review performance and total time to decision;
(B) recommended actions to correct any failures to meet user fee program goals; and
(C) consideration of the impact of combination products on the review process.
(3) Assessment of methods and controls of the Food and Drug Administration for collecting and reporting information on premarket review process resource use and performance.
(4) Assessment of effectiveness of the reviewer training program of the Food and Drug Administration.
(5) Recommendations for ongoing periodic assessments and any additional, more detailed or focused assessments.
The Secretary is mandated to "analyze" these recommendations and "incorporate" the recommendations into its practices "as appropriate." (Section 723(f)). The bill also directs the agency to include "the results of the assessment in a Good Review Management Practices guidance document, which shall include initial and ongoing training of Food and Drug Administration staff, and periodic audits of compliance with the guidance."
In his comments when introducing the bill, Senator Coburn stated that the amendment "came out of study of the [General Accounting Office's] findings" on the FDA's performance. He cited the GAO's study as finding "an irregular pattern of performance review at the FDA" and said that this amendment was intended as a "management tool" to "evaluate individual employees." "Timeliness" appears to be the impetus for the amendment, as well as better ways to assess timeliness. "The idea is not to push drugs out that shouldn't be approved," the Senator reassured his colleagues. But consistent with the goals of providing user fees in the first place, the Senator urged that the amendment be included in the bill because it was consistent with those aims, stating that fears that the amendment's provisions would result in a regime where unsafe drugs were approved was not realistic because the GAO's recommendations contained provisions relating to "inappropriate pressure" that could be brought to bear by users on the agency. He praised (backhandedly) the agency and the way it performs its duties, saying they "do an awfully good job" but that "they are just awfully slow at it."
The amendments sunset on October 1, 2017 and are effective at the later of October 1, 2012 or on the date of enactment of the amendments into law.
The House version of the bill, H.R.5651, is reportedly ready for a floor vote in the near future.