Last week, the U.S. Food and Drug Administration published the Biosimilar Biological Product Reauthorization Performance Goals and Procedures Fiscal Years 2018 Through 2022. Commonly referred to as the “goals letter” or “commitment letter,” the publication represents discussions among FDA, the regulated industry, and public stakeholders regarding reauthorization of the Biosimilar User Fee Act (“BsUFA”).
BsUFA authorizes FDA to collect user fees for the review of biosimilar biological product applications. The current legislative authority for biosimilar user fees expires in September 2017, and FDA cannot continue to collect user fees without reauthorization. Relatedly, on Monday, FDA announced that it will hold an upcoming public meeting to discuss proposals for reauthorization. The proposals include enhancements to the existing biosimilars user fee program in four key areas: (i) review performance; (ii) meeting management; (iii) guidance development, and (iv) fee/program administration.
I. Review Performance
FDA has proposed implementing a “Program for Enhanced Review Transparency and Communication for Original 351(k) BLAs” (“the Program”). Based on a similar model established in the fifth authorization of the Prescription Drug User Fee Act, the Program aims to minimize the need for multiple review cycles by providing additional communication between FDA and biosimilar applicants during the first cycle review process. The Program contemplates, among other things, additional communication in the form of: (i) pre-submission meetings—to discuss the planned content of an application; (ii) mid-cycle communications—to allow FDA to update applicants about the review of their application, including about significant issues, information requests, and/or major issues with certain data; and (iii) late-cycle meetings—to discuss the status of the review and any remaining issues potentially affecting approval. To accommodate these additional interactions, FDA proposed adding 60 days to the respective review timeframes.
Another significant proposal that relates to review performance involves clarifying when an applicant may utilize the special protocol question assessment and agreement. Under this agreement, a biosimilar applicant may specifically request that the Agency evaluate certain protocols and related issues to assess whether a proposed design is adequate to meet scientific and regulatory requirements identified by the sponsor. Protocols that qualify include any necessary clinical study or studies to prove biosimilarity and/or interchangeability. To avoid any confusion, FDA proposed adding pharmacokinetic and pharmacodynamic similarity studies to the list of examples that that qualify for this program. The examples include protocols for pharmacokinetics and pharmacodynamics studies, comparative clinical studies to show no clinically meaningful differences between the biosimilar and the reference product, and clinical studies to demonstrate interchangeability.
II. Meeting Management
FDA has recommended altering the timing for certain biosimilar-application meetings and providing applicants with additional options for feedback from FDA. There are five types of meetings that applicants may have with FDA: (i) Biosimilar Initial Advisory Meeting—to provide initial assessments regarding the feasibility of particular biosimilar project; (ii) BPD Type 1 Meeting—to discuss an otherwise stalled drug development program, a special protocol assessment, or an important safety issue; (iii) BPD Type 2 Meeting—to obtain FDA advice regarding specific issues or questions; (iv) BPD Type 3 Meeting—to provide an in-depth data review and advice from FDA; and (v) BPD Type 4 Meeting—to discuss the format and content of an application before its submission.
Under the proposal, FDA recommended that the timeframe for scheduling BPD Type 2 Meetings, given their typical complexity, be extended from 75 to 90 calendar days. Conversely, FDA proposed shortening the timeframe for scheduling BIA Meetings, which typically involve only limited, high-level discussions about a biosimilar product development program, from 90 to 75 calendar days. FDA also recommended that the sponsors be able to request written responses from the Agency for BIA and BPD Type 2 meetings rather than be required to attend face-to-face, videoconference, or teleconference meetings.
III. Guidance Development
Through talks with industry, FDA has acknowledged the need for additional clarity regarding the regulatory process and scientific criteria related to biosimilar development and approval. To that end, FDA has proposed updating existing draft and final guidance document concerning biosimilars, as well as issuing new guidance documents. More specifically, FDA has committed to the updating at least the following guidance documents: (i) Good Review Management Principles and Practices—to ensure that it encompasses all review activities for biosimilar and interchangeable products; (ii) Formal Meetings Between the FDA and Biosimilar Biological Product Sponsors or Applicants; (iii) Best Practices for Communication Between IND Sponsors and FDA During Drug Development—to cover biosimilar product development; (iv) Clinical Pharmacology Data to Support a Demonstration of Biosimilarity to a Reference Product; (v) Nonproprietary Naming of Biological Products; and (vi) Labeling for Biosimilar Biological Products. FDA also proposed publishing new guidance documents on at least the following: (i) considerations for interchangeability; (ii) statistical considerations for the analysis of analytic similarity data intended to support a demonstration of “highly similar”; and (iii) processes and further considerations related to post-approval manufacturing changes.
IV. Fee/Program Administrative
FDA identified certain areas in which the administration of the BsUFA user fees and programs could be improved. For example, FDA proposed various improvements to the hiring, retaining, and training of biosimilar review staff. They include: (i) modernizing the hiring system; (ii) establishing a dedicated unit to continuously recruit, staff, and retain scientific, technical, and professional staff for BsUFA review; (iii) setting and monitoring goals for the hiring, training, and retaining of BsUFA review staff; and (iv) engaging a qualified contractor to support these efforts. In addition to assisting with BsUFA review, these improvements should aid FDA in meeting its recognized need for a more focused and better resourced capacity to coordinate key legal, scientific, review, and outreach functions in FDA’s development phase advice and premarket review, including strengthening FDA’s capacity: (i) to develop new biosimilar regulations and guidance documents; (ii) to facilitate the update and application of new policies and guidance; (iii) to develop and deliver timely and comprehensive staff training; and (iv) to deliver timely information to the public.
FDA and industry also agreed that the BsUFA II fee structure and the fee setting process could be amended to improve FDA’s ability to engage in long-term financial planning. Currently, the BsUFA fee structure references PDUFA fees, but FDA and industry agreed that under BsUFA II user fee revenue amounts and fee amounts should be independent of PDUFA and based on BsUFA program costs. Both also agreed that an independent user fee structure and fee amount would help ensure stable and predictable user fee funding, improve the predictability of FDA funding and sponsor invoices, improve efficiency by simplifying the administration of user fees, and enhance flexibility of financial mechanisms to improve management of BsUFA program funding.
FDA’s proposed recommendations, as well as the upcoming public meeting, which is to be held on October 20, 2016 at FDA’s White Oak Campus, are part of the requirements for the reauthorization of the biosimilar user fees. As further part of these requirements, FDA is accepting public comments regarding the proposed recommendations though October 19, 2016.