US Biosimilar Market Formation Isn't Going According To FDA's Plan
This article was originally published in SRA
As user fee negotiations begin, the US Food and Drug Administration has far more biosimilar sponsors in product development phase and far fewer marketing applications than anticipated.
The FDA may have to adjust the structure of its biosimilar user fee program to account for sponsors' appetites for scientific advice.
Among FDA priorities for the biosimilar user fee renewal is to ensure it has the staff and revenue to meet its existing and future workload.
The agency never anticipated that the current number of sponsors would be in development discussions with the agency at the same time, according to Leah Christl, associate director of therapeutic biologics in the Office of New Drugs.
Christl said after a Dec. 18 public hearing to start the BsUFA reauthorization process that not only are many more sponsors opening discussions with FDA, but they also are starting the phase earlier and remaining in it longer than anticipated.
The FDA expects to negotiate the reauthorization with several trade associations representing industry1, likely beginning in early 2016.
The agency anticipated at most 11 biosimilar programs to be in its product development, or pre-marketing application, stage at any one time each year.
Today there are 59 programs in the product development phase.
The FDA also expected each sponsor would require one to two meetings per year during the BPD phase and that there would be about 16 meetings total per year on average.
During the first two years of the program, the agency reported scheduling 45 Type 2 meetings.
Christl said after the hearing that assumptions did not meet reality in part because it appears the FDA did not expect so many sponsors would look for FDA's product development advice even though they would not be able to submit a US biosimilar application for many years.
Many sponsors are conducting global development programs and want to ensure they will be compliant in the US, even though they may file for approval somewhere else first.
There also are fewer marketing applications than the 13 that had been expected by the end of fiscal year 2015.
So far, FDA has approved one biosimilar, Sandoz Inc.'s Zarxio (filgrastim-sndz), which references Amgen Inc.'s Neupogen (filgrastim)2.
Another seven applications have been filed, but the status of many of them is unknown. Several have seen review goal dates pass.
Assumptions Need Revisiting
Janet Woodcock, director at FDA's Center for Drug Evaluation and Research, said during the hearing that a number of biosimilar approvals are expected in the coming years and the program must be prepared to handle it.
"We really need to figure out going forward if… a significant proportion of these 59 products come forward and turn into applications for marketing, how we're going to get this work done and how the biosimilars program in the future would be funded to support getting this work done," Woodcock said.
Theresa Mullin, director of the CDER Office of Strategic Programs, said during the hearing that meeting and workload goals may have to change to ensure the program remains financially sound.
"We may need to revisit how we structure and finance the program to ensure soundness," she said.
The FDA said it needs to be able to recruit new staff as well as retain its in-house experts, which may require more user fee dollars.
The agency collected $6.46m in BsUFA fees in FY 2013 and $14.1m in FY 2014.
In FY 2015 and FY 2016, BsUFA was expected to generate about $21m each year, according to totals included in appropriations legislation.
The biosimilar program has been expected to remain largely under-resourced until more products enter the market.
Industry Willing To Talk About Phased-In Changes
Industry appears willing to talk about fee structure changes to ensure FDA can continue providing timely advice and application reviews, but needs a better look at its operations.
Kay Holcombe, Biotechnology Industry Organization's senior vice-president for science policy, said during the hearing that the group wants to hear from the FDA how the BsUFA program is working, but it will be more important to understand how the agency is allocating resources and how that will change as application volume increases.
Holcombe said BIO expects BsUFA to evolve.
"As interest in the US biosimilars market grows, the structure of this program will undoubtedly need to change," she said. "We welcome the opportunity to discuss with FDA and other stakeholders what changes make sense and how fee changes or fee structure modifications can be phased in effectively and judiciously as the numbers of applications and products increase."
David Gaugh, Generic Pharmaceutical Association's senior vice-president for sciences and regulatory affairs, also said additional funding should help the FDA complete a number of policies essential to biosimilar market growth, which should help review operations.
"At present, FDA is expending a very significant portion of biosimilar resources on regulatory policy issues," Gaugh said. "We're hopeful that these issues will be resolved in the very near future, which will free up significant resources to provide timely and detailed feedback to the sponsors on product reviews."
Gaugh also said there should be clear timelines for follow-up clarifications after BsUFA meetings, application orientation meetings, and that having "additional touch points during the review of a 351(k) is very important."
It is unclear whether the FDA could create mid-cycle communications without asking for more time to complete a 351(k) review. Industry representatives did not indicate that the 10-month review period should be lengthened.
When mid- and late-cycle communications were added to new drug application (NDA) reviews as part of the 2012 prescription drug user fee reauthorization, industry agreed to add two months to the review timeline. Sponsors have found those meetings valuable.
References
1. US FDA's Biosimilar User Fees Could Be Raised Significantly In Renewal Talks, Scrip Regulatory Affairs, Nov. 2, 2015
2. Novartis/Sandoz make US history with 1st biosimilar approval, Scrip Regulatory Affairs, March 9, 2015
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