On 01 April 2013, the FDA released its fourth guidance regarding the development of biosimilar products: Formal Meetings Between the FDA and Biosimilar Biological Product Sponsors or Applicants. Biosimilars are biological products that are demonstrated to be “highly similar” or “interchangeable” to an approved biological product. The process for the approval of biosimilar products was initiated with the Biologics Price Competition and Innovation Act of 2009 (BPCI), which was part of the Affordable Care Act. The first three guidances released regarding biosimilars detail scientific considerations for demonstrating biosimilarity to a reference product; quality considerations in demonstrating biosimilarity to a reference protein product; and a Q&A guidance about the implementation of BPCI. This newest guidance creates a process for formal meetings with the FDA regarding biosimilar product development.
The guidance introduces five types of formal meetings:
1) Biosimilar Initial Advisory Meeting:
A preliminary meeting for the sponsor to obtain feedback and advice regarding if licensure of the proposed product as a biosimilar is feasible. The sponsor should provide “preliminary comparative analytical similarity data” as well as an overview of the proposed development plan.
*Scheduled to occur within 90 calendar days of FDA receipt of written meeting request and meeting package.
2) Biological Product Development (BPD) Type 1 Meeting:
A meeting to discuss otherwise stalled development programs. Examples of topics to be discussed at a BPD Type 1 meeting include clinical holds, special protocol assessments, safety issues, and dispute resolution.
*Scheduled to occur within 30 calendar days of FDA receipt of written meeting request and meeting package. Before requesting a BPD Type 1 meeting, sponsors should first consult with the relevant division in CBER or CDER regarding the suitability of the request.
3) BPD Type 2 Meeting:
To discuss specific issues (such as a proposed study design) or questions regarding targeted advice for an ongoing BPD program. Sponsors should be prepared for a “substantive review of summary data”, but not of full study reports.
*Scheduled to occur within 75 calendar days of FDA receipt of written meeting request and meeting package.
4) BPD Type 3 Meeting:
In-depth data review and advice meeting regarding an ongoing BPD program. Topics for discussion include substantive reviews of full study reports, FDA advice regarding similarity of the biosimilar and reference product; and FDA input on need and design of additional studies.
*Scheduled to occur within 120 calendar days of FDA receipt of written meeting request and meeting package.
5) BPD Type 4 Meeting:
Discussion of format and content of biosimilar product application or supplement.
*Scheduled to occur within 60 calendar days of FDA receipt of written meeting request and meeting package.
To participate in the BPD program, both an initial BPD and an annual BPD fee are required.
The initial BPD fee is due within 5 calendar days after the FDA grants a Type 1, 2, 3, or 4 meeting or on the date an IND is filed for the biological product, whichever occurs first. The initial BPD fee is equal to 10% of the PDUFA rate for a marketing application requiring clinical data (for 2013, that fee is $1,958,800. Thus, the initial BPD fee for 2013 is $195,880). There is no fee required for a Biosimilar Initial Advisory meeting.
The annual BPD fee will be assessed beginning the following year until a marketing application for the biosimilar product is submitted or the development of the biosimilar is discontinued. The fee amount is the same as the initial fee ($195,880 for 2013) and is due the first business day on or after October 1 of each year.
Additionally, if a biosimilar program is discontinued and the sponsor wants to restart the program at a later date, a BPD reactivation fee is required. This fee is 20% of that year’s PDUFA fee ($391,760 for 2013). The BPD reactivation fee is due within 5 calendar days after the FDA grants a Type 1, 2, 3, or 4 meeting or on the date an IND is filed for the biological product, whichever occurs first.
Upon filing a marketing application or supplement, “the fee for the application is reduced by the cumulative amount of these previously paid fees.”