Overall good, three suggestions for improvement, FDA invites a third party to evaluate the implementation of the BsUFA II Act on biosimilars

The Biosimilar User Fees Act BsUFA II introduced an “increased transparency and communication plan for the original 351(k) BLA review” in the biosimilar drug review process.

The ERG's final report (2022/02/14) provides data and analysis of BsUFA II implementation and results over the four years of fiscal years (FYs) 2018-2021, including sections on introduction, survey methodology, assessment Q&A, survey results and recommendations

BsUFA related information can be found: [FDA announces fee rates for generic drugs and biosimilars in fiscal year 2022] [Simplified licensing of biosimilars is a trend, and global coordination still takes time] [FDA proposes a simplified path for biosimilars to increase indications]

Introduction to the BsUFA II Act and Program

Biosimilars represent an important public health benefit because they can save patients' lives or improve their quality of life at a lower cost

One of the key commitments of BsUFAII, the second authorization of the Act, is to establish a program for enhanced review transparency and communication for 351(k) BLAs, with the goal of improving the efficiency and effectiveness of first-round reviews, enhancing transparency, and communicating with applicants to reduce the review cycle so that patients can obtain safe, effective and high-quality biosimilars in a timely manner

The implementation of the plan is generally good

Data sources for ERGs are primarily 351(k) BLAs that were first filed within those years and received first action (Approval [AP], Full Response [CR], or Post-Submission Withdrawal [WD]) by December 31, 2021

From the report, although it is impossible to assess the significance of the baseline due to the small sample size, it can be considered that the overall implementation of the interview BsUFA II program is good - the review transparency and communication have been successfully improved, and the FDA's first-round review has been improved.

——Improved the ability of the first round of review

Applications with hematology or pure oncology indications were less likely to have first-round approval (33%, 3/9) than applications in other indications (92%, 11/12), which was also true during the baseline period.

- The majority of applicants and FDA reviewers in the survey felt that the communication process was high-quality, constructive, and cooperative, and that the review was very transparent and predictable

-- Planned additions to the 351(k) BLA review process, namely new milestone meetings, Mid-Term Communication (MCC) and Late Meeting (LCM), improve the predictability of the review process

- Good review management principles (GRMP) are well implemented

The GRMP was established by FDA in the context of the BsUFA II program to promote good review management practices based on good fundamental values ​​and principles, and to support an effective and efficient application review process in the first round of reviews

Day 74 Letter means a formal letter sent by the FDA review team to the applicant within 74 calendar days of the initial application submission to communicate potential review issues and FDA's planned review timeline)

ERG's recommendations

The ERG recommends future improvements in only three specific areas, namely, certain biosimilar product development (BPD) meeting practices, post-meeting discussion topics, and timing of requests for information

In addition, the COVID-19 pandemic has caused some inspection delays, which, even with corresponding measures, has resulted in less predictability of inspection times

——Provide suggestions and templates for application content and organization in BPD type 4 meetings to help sponsors prepare applications that meet FDA requirements
.

During the survey, many BsUFA II applicants requested the FDA to hold a BPDtype 4 meeting
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In most BPD type 4 meetings, many of the sponsor's questions are resolved by FDA's feedback on preliminary comments received prior to the meeting, and both the sponsor and the FDA review team believe that this pre-meeting communication is critical for understanding Application expectations are valuable
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In this regard, the ERG recommends that it be established as good practice
.

- Consider soliciting discussion topics from applicants and allocate time in the LCM agenda for discussion topics identified by applicants
.

During interviews, while some FDA reviewers tended to withdraw LCM when there were no major issues to discuss, the applicant felt that LCM would be appropriate if it could discuss other topics of interest with FDA (eg, inspections, PMR/PMCs, labeling).
Very valuable and hope that FDA will provide meeting agendas and discussion topics well in advance of the meeting
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The ERG recommends that consideration be given to soliciting discussion topics from applicants and allocate appropriate discussion time in the LCM agenda
.

- Extending response times for information requests (IRs), or issuing IRs earlier

IR and revisions can be used as a measure of the level of information exchange between FDA review teams and applicants
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FDA publishes more IRs per application in the BsUFA II program than in the baseline, applicants submit more revisions than in the baseline, and IRs are generally related to product quality
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The response time given by the FDA to applicants is only two days, and many applicants have suggested that the FDA extend the time limit for responding to IR and label changes, because sometimes it is very unreasonable for applicants worldwide, and the difference in time zone alone may produce 1~ 2 days delay
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Therefore, ERG recommends that FDA extend the IR response time as much as possible or issue the IR earlier
.

——The new crown makes the inspection time opaque

FDA completed 94% of inspections within 10 months of BsUFA II receipt of applications, but some delays stemmed from COVID-19 travel restrictions, resulting in a probability of 483 well below baseline
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Although to advance the review as much as possible, FDA has developed and implemented a records review process based on a risk assessment to justify this approach as an alternative to on-site inspections
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However, a small number of applicants believed that this measure reduced the predictability of inspection time, and ERG did not make corresponding recommendations
.