How To Make The Most Of Your FDA Biosimilar Meetings
By Anna Rose Welch, Editorial & Community Director, Advancing RNA
One thing was made clear from the keynote address at the DIA Biosimilars 2016 conference: there is a lot of excitement (and urgency) around biosimilar development. The FDA currently has 66 biosimilars programs enrolled for 20 different reference products. In his keynote address, John Jenkins, the director of the FDA’s Office of New Drugs, described what the FDA has learned since the Biologics Price Competition and Innovation Act (BPCIA) was initiated in 2010. In addition to the creation of the Therapeutic Biologics and Biosimilars Staff (TBBS), which manages biosimilar policies and the Senior Biosimilar Review Committee, he also outlined the “cultural and cognitive transformation” that needed to occur when reviewing biosimilars. But an even more valuable layer to his discussion was what the agency has learned in terms of working with biosimilar developers. Wrapped throughout his presentation were a series of best practices, many of which suggest biosimilar companies, no matter what stage of development, are eager to (and often do) hit the ground running. But Jenkins shared several reasons why biosimilar makers shouldn’t let their eagerness to get to market drive their development program.
A Glance At The FDA Biosimilar Development Meetings
As the number of biosimilars in development proves, the FDA biosimilar program has seen impressive growth over the past few years. The agency began holding meetings with interested biosimilar companies just a few months after the approval of the BPCIA. But the majority of meeting requests began funneling in after the launch of the user fee program in 2013.
Jenkins provided a quick refresher in terms of the goals for each Biosimilar Biological Product Development (BPD) meeting. (A more thorough description of these meetings exists in an FDA guidance.) Essentially, there are five types of meetings: The initial advisory meeting, and the type-1, type-2, type-3, and type-4 meeting. According to Jenkins, the real “meat” of biosimilar development is discussed in the type-2 and type-3 meetings. For instance, in a type-3 meeting, companies can seek scientific advice on an extensive data package (not summaries).
Over the last fiscal year, a majority of biosimilar program meetings have been type 2 meetings. This isn’t necessarily a surprise. An article I wrote earlier this year described how many companies in the early and middle phases of development have found themselves scheduling additional type-2 meetings because of the case-by-case nature of the FDA’s biosimilar reviews.
“Choose Your Meetings Wisely”
This might seem like a no-brainer, but Jenkin's continued emphasis on this best practice suggests there are some basic misunderstandings in terms of what can be accomplished in each meeting type. The company is responsible for ensuring it has selected the right type of meeting to garner the necessary answers in a timely fashion. For instance, the initial biosimilar advisory meeting, which tells companies interested in biosimilar development how to proceed, will not be the place to get answers on study design, endpoints, or a data package.
Similarly, as Jenkins described, “The timelines for those meetings are different, so you need to anticipate when you’re going to need a meeting so you can schedule it into your timeline in a way that doesn’t cause you undue delays. This attention will also ensure you don’t put pressure on the agency to rush scheduling a meeting or rush its advice.”
Paying attention to meeting timelines is especially important for companies preparing to file a Biologics License Application (BLA). One of the biggest hang-ups for companies is not submitting a completed application. It should go without saying that an incomplete application stalls a development program and the FDA’s review. Jenkins urged companies to schedule a type-4 meeting before submitting the BLA, and to schedule it early enough so there’s time to review the agency’s advice. “We’ve seen situations where companies have had type-4 meetings and then submitted their application before they even got the notes from the meeting,” said Jenkins. This oversight could ultimately lead the FDA to refuse to file your application.
It was interesting to hear the FDA’s perspective on the timing of meetings, as one of the biosimilar industry’s biggest complaints has been the FDA’s inability to keep up with meetings. Obviously, the FDA plays just as much a role in keeping its meeting schedule on track as a manufacturer. Over the past year, the agency has openly acknowledged its staffing challenges. However, it has including hiring goals in the latest rendition of the Biosimilar User Fee Act (BsUFA II), so there will, hopefully, be more muscle behind the biosimilar review program in the years ahead.
The Importance Of The “Step-Wise Approach”
An increasingly familiar phrase in the U.S. biosimilar market is “a step-wise approach to proving biosimilarity.” This phrase was used regularly throughout the conference by members of the FDA to, essentially, encourage drugmakers not to bite off more than they can chew. Jenkins instructed attendees to “Tell the biosimilar story.” This involves moving step-wise from analytical comparisons to animal studies, clinical pharmacokinetic and pharmacodynamic (PK/PD) studies, immunogenicity assessments, and any other clinical studies that might be necessary. After accomplishing each step, a company should evaluate what needs to come next to eliminate any residual uncertainty about the molecule. However, “We often see sponsors taking the ‘shotgun approach,’” said Jenkins. “They try to take all the steps at the same time and hope for the best. It often doesn’t work out very well.”
Overall, urging biosimilar makers to take their time preparing proper questions and determining their needs from the FDA was a major undercurrent throughout Jenkin’s keynote address. There are likely a variety of reasons companies might choose the shotgun approach to biosimilar development. But one of the more reassuring aspects to Jenkins’ talk, as well as some of the other FDA officials’ presentations, was the agency’s emphasis on the pathway remaining abbreviated. In overlooking the stepwise approach, a company could find it misses a valuable opportunity to embrace a novel program, which could ultimately shorten the overall development timeline.