Regulatory Guidance on Biosimilar Development, Plus a Look at the Biosimilar Pipeline

Eighteen biosimilars have been licensed by the Food and Drug Administration (FDA) since 2015, seven of which have launched. When submitting a biosimilar to the FDA, manufacturers must show the following:

  • Biosimilarity to reference product
  • Same mechanism(s) of action (if known)
  • Condition(s) for use (i.e., indications) were previously approved for reference product
  • Same route, dosage form, and strength
  • Manufacturing facility meets standards to ensure safety, purity, and potency

Former FDA Commissioner Scott Gottlieb, MD, said the agency is focused on advancing policies that make the process of developing biosimilar more efficient. The key areas of focus include:

  • Improving the efficiency of the biosimilar and interchangeable product development and approval process
  • Maximizing scientific and regulatory clarity for the biosimilar product development community
  • Supporting market competition by reducing gaming of FDA requirements or other attempts to unfairly delay competition
  • Developing effective communications to improve understanding of biosimilars among patients, clinicians, and payers

Since last year, the FDA has released several guidance documents for biosimilars, including information on labeling, licensing, and nonproprietary naming. And since 2013, 45 states and Puerto Rico have passed substitution laws for switching to a biosimilar. They include:

  • Must first be FDA-approved as “interchangeable”
  • Prescriber may prevent with “no substitutions” on prescription
  • Almost all require RPh communication to prescriber
  • Many require RPh to retain records
  • Many require patients be informed

Per the Bipartisan Budget Act of 2018, biosimilars can be included in coverage gap manufacturer discount program within Medicare Part D. A policy change from the Centers for Medicare & Medicaid Services resulted in lower cost-sharing for low-income Medicare Part D beneficiaries and promotes medication adherence and biosimilar utilization.

Dr. Day then discussed U.S. biosimilar uptake patterns. Filgrastim-sndz launched in September 2015, and currently holds 44.3% of the filgrastim market share, according to January 2019 IMS Health data. However, in another drug class, despite having two infliximab biosimilar products available, the reference product, Remicade®, continues to hold 93% of the market share.

Barriers persist surrounding the uptake of biosimilars. Some of the key areas that need improvement are education for clinicians and patients, improved informational materials, interchangeability requirements, healthcare and public acceptance of these agents, and the “nocebo” effect. Other barriers include new competition from reformulated therapies, long-term contracts and rebates for reference products, skinny labels and off-label use of drugs, and patent litigation and settlements for reference products.

She said that in the next 10 years, the market could see biosimilars become available for aflibercept, alemtuzumab, certolizumab pegol, denosumab, eculizumab, golimumab, natalizumab, omalizumab, onabotulinumtoxinA, panitumumab, ranibizumab, tocilizumab, and ustekinumab.

Dr. Day concluded by noting a statistic from the RAND Corporation: “We estimate that biosimilars will lead to a reduction of $54 billion in direct spending on biologic drugs from 2017 to 2026 (range $24 to $150 billion).”