What Does FDA's Biosimilar Workload Reveal About Emerging U.S. Market?

By Anna Rose Welch, Editorial & Community Director, Advancing RNA

Over the last few months, the FDA has faced questions and criticism over its slow progress with biosimilar-related policies. A lack of resources — both money and employees — has been blamed for the agency’s leisurely pace. Janet Woodcock, the FDA’s director of the Center for Drug Evaluation and Research (CDER), was faced with another round of these questions at a recent hearing convened by the Committee on Energy and Commerce’s Subcommittee on Health. What came to light was the lack of funding the FDA received from Congress at the launch of the Biologics Price Competition and Innovation Act (BPCIA) in 2010. Not provided in this meeting, however, were any estimates or figures from Woodcock about the size of the biosimilars review team to date or the extent of the FDA’s biosimilar program workload. Well, now we have some answers in the form of “Eastern Research Group’s (ERG’s) Review of Biosimilar Biologic Product Applications: Study Of Workload Volume And Full Costs.”

Key Biosimilar Workload Figures

To date, the FDA has 57 biosimilar programs in development. Seven biosimilars have been submitted for regulatory approval. (There are currently six outstanding applications, as one of these seven — Sandoz’s Zarxio — was approved last fall.) According to the report, the FDA spent $81.7 million on biosimilar-related work from 2013 to September 2015. ERG estimates the FDA spent $26 million in FY 2013. Though 2014 spending came in a bit lower at $23.5 million, in 2015, the agency shelled out $32.3 million. It took 295 full-time equivalents (FTEs) to accomplish the work carried out in the last two years. The ERG report totaled the amount of work spent on the following areas:

• Biosimilar development program activities (i.e., Investigational New Drug reviews [INDs] and Biosimilar Product Development [BPD] meetings, etc.)
• 351 (k) Biologics License Application (BLA) reviews
• CDER meetings
• Policy work
• Science and research
• Training
• Educational outreach

Overall, biosimilar development program activities required the most work from employees (85.4 FTEs). Policy work (30.3 FTEs) followed by 351 (k) BLA reviews (25.9 FTEs) came in second and third place, respectively.

What Do FDA’s BPD Meetings Records Tell Us?

As a whole, the ERG report is chock-full of tables and figures for those with an obsession for numbers. However, the figures that spoke most about the progression of the industry were the BPD meeting trends. As Regulatory Affairs Professional Society (RAPS) pointed out in its article on the ERG report, there have been some interesting fluctuations and decreases in the meeting trends. There have only been four BPD type 1 meetings — perhaps reassuring news for those still questioning the safety of biosimilars. (BPD-1 programs often have to do with safety issues or clinical holds.)

ERG also revealed a rather abrupt drop in the number of candidates seeking out BPD type 3 meetings in 2015. Though there were six scheduled meetings in 2013 and nine in 2014, there was only one in 2015. Type 3 meetings involve an in-depth review of data gleaned from an ongoing BPD program, including analytical similarity data and full-study clinical reports. Developers moving forward can then propose additional studies or extrapolation goals.

It could be there were fewer biosimilar makers in 2015 that were far enough along in the process to justify type 3 meetings. It could also be indicative of the drug candidates that companies have chosen to develop. There’s been a mad dash among first-wave players to tackle Remicade, Neupogen, Enbrel, and Humira biosimilars. But there are also a number of players that have set sights on candidates outside of the first wave of expiring biologics. Take for instance EPIRUS Biopharmaceuticals, which, just recently, forecasted global regulatory submissions for its Soliris, Actemra, Stelara, and Simponi biosimilars as far ahead as 2019 and 2022.

But BPD type 2 meetings, in which companies meet to discuss summary data or study designs/endpoints, saw a notable jump between 2014 and 2015. In FY 2013 and FY 2014, there were 20 and 25 scheduled BPD type 2 meetings, respectively. By 2015 however, this number leapt to 41. This indicates there were (and are) a number of development programs making headway within the clinical trial sphere with intentions to enter the market in upcoming years.

Perhaps we can be heartened by the rise in BPD type 2 meetings. The rise in scheduled meetings could suggest that a number of companies are progressing with their studies and that there is a willingness between both the FDA and the companies to get the products to market properly. And there is a nice number of BPDs (57) at play to date.

However, it’s also important to keep in mind that these figures are surface level only. While the number of meetings being scheduled is on the rise, there is no indication that these meetings have been held as scheduled. In fact, recent conversations I’ve had with industry members have suggested that this is, unfortunately, not always the case. Similarly, it’s hard to determine from these figures whether these meetings are all for different candidates, or if this number comprises the same parties scheduling multiple meetings. It’s no secret the U.S. regulatory landscape is undefined in certain key aspects, such as interchangeability and labeling. Drugmakers are also seeking to demonstrate biosimilarity, and, as such, need more clearly defined statistical parameters. An increased number of meetings could suggest candidates are making progress in development. However, given the amount of uncertainty about the current regulatory pathway, it’s more likely that the increase in meetings signifies biosimilar makers’ heightened need for guidance and answers.