FDA has proposed extending biosimilar review times and moving the products into a model similar to one used for NDAs in order to increase first-cycle approvals.

Biosimilars now receive a 10-month clock, but there is no formal structure in place to promote communication between the sponsor and FDA during the review.

Agency officials proposed creating a "Program" for biosimilar applications as part of the biosimilar user fee reauthorization. Minutes of a March 31 meeting indicate that FDA intends it to resemble the system for NDAs and BLAs that was put in place for PDUFA V.

FDA would not start the review clock until after a 60-day filing period, effectively creating a 12-month goal. But sponsors would receive a mid-cycle communication and late-cycle meeting, where application issues could be discussed and potentially corrected.

The agency said a BsUFA "Program" could "promote efficiency and effectiveness of the first-cycle review process for biosimilars and minimize the number of review cycles necessary for approval," according to the minutes.

Industry officials in attendance at the meeting, which included representatives of the Pharmaceutical Research and Manufacturers of America and Biotechnology Innovation Organization – groups that helped negotiate the Program for PDUFA V – told FDA they would share the proposal with their members and provide further input at a future negotiating session.

After hearing from their members, the trade groups also may need to reach consensus themselves on the issue. BsUFA negotiations began in mid-March with FDA asking the four industry groups at the table to try and agree on one package of reforms to put forward Also see "Biosimilar User Fee Talks Begin With Industry Negotiating Amongst Itself" - Pink Sheet, 11 April, 2016..

If FDA's proposed changes to reviews are implemented, the impact could be substantial, but may be worthwhile given the complexity of biosimilar products and the agency's experience with the applications.

Only two 351(k) applications have been approved to date. Sandoz Inc.'s Zarxio (filgrastim-sndz), a biosimilar of Amgen Inc.'s Neupogen (filgrastim), became the first in 2015 ([A#14150306001]). It was followed April 5 by Celltrion Inc.'s Inflectra (infliximab-dyyb), a biosimilar of Janssen Biotech Inc.'s Remicade (infliximab) ([A#14160405006]).

Six other biosimilar applications remain pending, however, some well beyond their initial user fee dates ([A#00150727009]).

At least two have received "complete response" letters, including Inflectra, which had its advisory committee meeting delayed 11 months because of pending information requests ([A#14160115001]).

FDA said in the minutes that first-cycle approval rates for biosimilars are low, but "if additional review time had been available, issues encountered in some of these applications may have been addressed in the first review cycle," which would have avoided a complete response letter and potentially months of delays.

The agency made similar arguments to the brand industry when it pushed for the review process extension for the prescription drug user fee program.

By allowing more time for an application review, FDA and the sponsor could increase the likelihood of losing more time later by avoiding multiple review cycles Also see "Buying Time: Industry Sacrifices Early To Gain Later With PDUFA V Review Model" - Pink Sheet, 1 October, 2012..

The change also would further align BsUFA and PDUFA. BsUFA application fees already are tied to those set for the prescription drug user fee ([A#00150803021]).

System Could Become More Complicated, Labor Intensive

If implemented, FDA's biosimilar development and review system would become more elaborate, potentially increasing workload problems.

The agency already allows sponsors formal meetings with its staff before an application is filed to review data and ask questions. The process is intended to help sponsors keep their development programs on track Also see "How To Get A Meeting With FDA: Guidance Describes Formal Meetings For Biosimilars" - Pink Sheet, 29 March, 2013..

Allowing formal meetings during application reviews would create another level of complexity for agency staff as it moves more 351(k) applications to the market.

An interim assessment of the PDUFA "Program" found that many of the formal meetings increased the burden on FDA staff, although sponsors gave it glowing reviews ([A#00150406021]).

FDA has indicated that its biosimilar program is overloaded. Center for Drug Evaluation and Research Director Janet Woodcock said it could "explode" ([A#14160204002]).

Biosimilar application reviews also have proven tougher than anticipated. Following the Zarxio approval, FDA assigned more staff members to subsequent 351(k) submissions ([A#00150928008]).

FDA Still Has Policy Obligations

FDA also would have to balance the increased review workload with its other obligations to the biosimilar program, namely policy development.

Several issues remain unresolved, including interchangeability standards, which may be hindering market growth in the US.

Indeed, stakeholders, as well as Congress, have continually demanded the agency issue biosimilar guidances.

FDA recently issued draft guidance on labeling and has included interchangeability guidance on its 2016 guidance agenda. Draft guidance and a proposed rule on product naming were issued last year, but have yet to be finalized ([A#14160331004]).

FDA spent more hours on policy development in the first few years of BsUFA than application reviews ([A#00150914003]).

The agency also appears to want to change the financing structure for the biosimilar program, in part to help it deal with the much higher volume of biosimilar development programs than were expected when BsUFA launched in 2012 ([A#14151218004]).

Biosimilars Reviews Could Be Extended Two Months In BsUFA II

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