Biosimilars Raise Analytical and Policy Challenges

FDA approved seven biosimilars through October 2017, based on the agency’s now well-established “step-wise” approach for assessing analytical similarity through biological and physiochemical product characterization. Still the debate continues over biosimilar naming, interchangeability, and patent protection, as well as lingering concerns in the medical community about the safety of switching patients to new therapies.

One result is that biosimilars have experienced limited uptake, prompting FDA to launch an educational and outreach campaign to encourage prescribing and health plan coverage of these therapies, as recently described by FDA Commissioner Scott Gottlieb.

Key guidance documents from FDA aim to help manufacturers utilize recommended methods for developing and testing biosimilars, including a recent draft guidance that outlines statistical approaches for evaluating analytical similarity. This much-anticipated advisory recommends a risk-based approach to documenting that the product is “highly similar” and has no “clinically meaningful differences” to the reference product. It outlines how to develop an analytical similarity assessment plan for determining the quality attributes most critical in characterizing the structural and functional properties of the reference product and for evaluating these attributes based on potential impact on clinical performance.

Some manufacturers, however, question FDA’s recommendation for assessing key quality attributes through statistical comparison to a pre-set mean for the reference product, as opposed to an appropriate range of quality attributes. Martin Schiestl, chief science officer at Novartis’ Sandoz, raised these concerns at the Biosimilars Conference sponsored by the Drug Information Association (DIA) in October 2017, noting that FDA’s approach creates “a substantial pitfall” for biosimilar developers that could lead regulators to reject true biosimilars at random. But Patrick Lynch, product quality reviewer in CDER’s Office of Biotechnology Products, commented that failure to meet pre-defined acceptance criteria on a statistical test does not necessarily preclude a determination of “highly similar.” FDA will review comments on the guidance, which are due in November 2017, and work with industry to reach consensus on a viable approach.

Common ground on coding

Biosimilar reimbursement also remains a contentious issue, with innovators maintaining the need for distinct names to facilitate postmarket identification and tracking of safety issues for brand vs. follow-on therapies. However, all sides applauded a new final rule from the Centers for Medicare and Medicaid Services (CMS) that assigns separate healthcare product codes for biosimilars covered under Medicare Part B. This reverses the current policy that groups biosimilars to the same reference product under the same Healthcare Common Procedure Coding System (HCPCS) code, an approach that puts common biosimilars together in calculating reimbursement rates.

The Biosimilars Council, which represents biosimilar makers, praised the CMS decision, citing an analysis that separate codes would save the federal government $11.4 billion over the next 10 years. And the Biosimilars Forum backed by innovator firms stated that unique codes for biosimilars will support development of “a thriving biosimilars market in the United States.” Although it may take years to see how the policy change actually affects prices and payments in the market, analysts anticipate that although a unique code for each approved biosimilar may initially limit competition among multiple therapies, over time this approach will encourage more manufacturers to develop follow-on products, generating more market competition that lowers prices overall.