FDA Commissioner Scott Gottlieb unveiled the agency’s 11-part biosimilar action plan at the Brookings Institution on Wednesday, explaining the “anemic” growth the market has seen so far.
“I’m worried that the market for these products still isn’t established,” Gottlieb said, noting 11 biosimilars have been approved but just three have gained market share. “The ability for these products to penetrate clinical practice, and gain acceptance, is still not firm.”
As part of FDA’s action plan on biosimilars, he said the agency is “actively exploring" whether "in some circumstances" FDA can "facilitate the increased use of non-U.S.-licensed comparator products in certain studies to support" 351k applications, explaining: "When those developing biosimilars use biologics sourced ex-U.S. as their comparator product, it can lower the cost of clinical studies since many of these products can be procured more easily, and cheaply, in European and Asian markets."
He also lamented the “rebating schemes” and “patent thickets that are purely designed to deter the entry of approved biosimilars.
“Long-dated contracts are another toxin,” he said
. “The branded drug makers thwart competition by dangling big rebates to lock up payors in multi-year contracts right on the eve of biosimilar entry.”
Another concern: that volume-based rebates “may encourage dysfunctional clinical treatment pathways. We’ve heard from multiple sources that some payors are requiring step-therapy or prior authorization on the reference biologic before patients can access a biosimilar. We see no clinical rationale for these practices, since a biosimilar must demonstrate, among other things, that it has no clinically meaningful differences from the reference product as a part of demonstrating biosimilarity.”
Among the 11 parts in FDA’s biosimilar action plan
Final Guidance on Labeling
- Implementing new FDA review tools, such as standardized review templates that are tailored to marketing applications for biosimilar and interchangeable products;
- Developing information resources and development tools, such as as in silico models and simulations for sponsors of biosimilar applications;
- Enhancing the Purple Book to include more information about approved biological products, including information relating to reference product exclusivity determinations;
- Establishing a new Office of Therapeutic Biologics and Biosimilars (OTBB) to improve coordination and support of activities under the Biosimilar User Fee Act (BsUFA) program;
- Providing additional clarity for product developers on demonstrating interchangeability, including by publishing final or revised draft guidance;
- Providing additional clarity and flexibility for product developers on analytical approaches to evaluating product structure and function to support a demonstration of biosimilarity, including by publishing revised draft guidance on the use of data analysis methods, including statistical approaches;
- Providing additional support for product developers regarding product quality and manufacturing process, including by identifying physical product quality attributes that are most critical to test and evaluate, and by exploring ways to reduce the number of lots of the reference product required for testing;
- Engaging in a public dialogue through a Part 15 hearing and the opening of a docket to request additional information from the public on what additional policy steps FDA should consider as it seeks to enhance its biosimilar program.
Also on Wednesday, FDA finalized a 15-page guidance, first drafted in April 2016
, on the labeling of biosimilars.
The guidance is intended to assist industry in developing labeling for submissions in proposed biosimilar applications.
FDA requested comment on the draft on whether FDA-approved patient labeling (e.g., Patient Information, Medication Guide, and Instructions for Use) should include a biosimilarity statement.
“Several comments agreed with inclusion of the biosimilarity statement; one comment disagreed. FDA considered the comments received, but decided not to recommend inclusion of a biosimilarity statement in FDA-approved patient labeling at this time,” FDA said.
Another change, according to Hillel Cohen, executive director of scientific affairs at Sandoz, is that the biosimilarity statement was expanded to cover “not just indications but also dosing regimen(s), strength(s), dosage form(s), and route(s) of administration. Not sure how impactful this will be, but it is a change.”
Also, the final guidance does not include details on how interchangeable biologics will be labeled.
FDA said changes made to the guidance (between draft and final versions) took into consideration the comments received, as well as requests regarding the requirements for and/or contents of biosimilar labeling made in citizen petitions submitted by AbbVie, a group of institutional investors including the United Auto Workers (UAW) Retiree Medical Benefits Trust and the Pharmaceutical Research and Manufacturers of America (PhRMA) and the Biotechnology Industry Organization (BIO).
FDA noted that the recommendations for prescription drug labeling in this guidance pertain only to the prescribing information (commonly referred to as the package insert), except for certain recommendations pertaining to FDA-approved patient labeling (e.g., Patient Information, Medication Guide, and Instructions for Use).
Labeling for Biosimilar Products: Guidance for Industry