FDA's Leah Christl Provides an Update on the Biosimilar Action Plan

During the fifth DIA Biosimilars Conference, held October 22 to 23, 2018, in London, United Kingdom, Leah Christl, PhD, associate director for therapeutic biologics, director of the therapeutic biologics and biosimilars staff in the office of new drugs in the FDA’s Center for Drug Evaluation and Research, presented on the FDA’s Biosimilar Action Plan.

While it is indeed the case that the current administration has made drug pricing and biosimilars a priority, and while the plan was hailed as a major step forward for biosimilars in the United States, “It’s not the only plan that’s going to exist,” said Christl.

She explained that the action plan, as put forth in the document announced by FDA Commissioner Scott Gottlieb, MD, in July of this year has served as the FDA’s way to bring together initiatives that the agency was already undertaking, and that the document is “not the end of what we’re going to do.” New elements may be added to the strategy, and new commitments may also be included in the future, she said.

Christl also reviewed the status of some of the planned deliverables for the 4 major elements of the plan:

Improving the efficiency of the biosimilar and interchangeable product development and approval process. As part of addressing this objective, the FDA will soon pilot its standardized review templates for biosimilars and will release an index of critical quality attributes.

Christl explained that the agency is working to develop and validate pharmacodynamic (PD) biomarkers in-house. She explained that current PD endpoints for products like filgrastim and pegfilgrastim relate well to clinical outcomes, but for rheumatology products, PD endpoints—such as B-cell depletion with rituximab—are less refined.

While the FDA has “had conversations about this” with developers, “we want to put resources behind this internally” to try to establish PD endpoints that will eliminate the need for developers to conduct large studies as one way to improve the efficiency of development.

Maximizing scientific and regulatory clarity for the biosimilar product development community. The FDA is well aware that the patent landscape or other factors may make it desirable for a biosimilar developer to seek approval for only some indications of a reference product, so the agency is working on guidance on carve-ins and carve-outs for indications that should give sponsors more clarity on this topic.

Another key deliverable for the FDA is an enhanced Purple Book. “Right now, it’s just 2 Excel spreadsheets,” Christl acknowledged. Given the variety of stakeholder needs for Purple Book development, “We’re likely going to push out a couple different versions” and seek feedback before arriving at a final version of the document.

Furthermore, the FDA is seeking to facilitate the use of non—US-licensed comparator products. “From day 1, we took an approach recognizing that [biosimilars] are global development projects,” said Christl, and the agency is assessing ways to address data-sharing agreements and legal issues that may affect the use of such products.

Developing effective communications to improve understanding of biosimilars among patients, providers, and payers. The agency is developing additional educational materials, including a 1-page document directed to patients, as well as video communications appropriate for use on social media.

Notably, the agency is also seeking to “move the education and outreach into school” for providers; the FDA wants providers to know, well before they enter practice, about the safety and efficacy of biosimilars. She likened current efforts to educate providers about these drugs to “Reading a drivers’ manual about how to dive your car, and then somebody putting you on the Autobahn.” She hopes that earlier education will eliminate some of the lack of provider knowledge about biosimilars observed currently.

Supporting market competition by reducing gaming of FDA requirements or other attempts to unfairly delay market competition to follow-on products. Finally, the agency is working to evaluate whether statutory or regulatory requirements are being used to inappropriately delay biosimilar of interchangeable competitors, and this process involves greater coordination with the Federal Trade Commission. It is also seeking to work together with legislators to address loopholes in current law. The FDA is able to provide technical support for legislation, Christl explained, that seeks to curb such practices as the refusal to sell samples of products for biosimilar testing.