FDA Has a Duty to Instill Confidence in Biosimilars, Experts Say

In a session held at the GRx+Biosims 2018 conference in Baltimore, Maryland, Gillian Woollett, MD, DPhil, senior vice president of Avalere Health, and Michelle Lee-Bourner, head of regulatory affairs for biologics and respiratory products at Mylan, discussed experience with and expectations for biosimilar regulation.

Woollett pointed out that whereas much of the world has only 2 options for classifying a biologic product—biologic or biosimilar—the United States has 3 options, adding interchangeable biologic to the list. However, she emphasized, although interchangeability is currently a hot topic of debate in the United States, the science underlying all biologic products, including biosimilars, is the same worldwide, regardless of laws in different jurisdictions that govern regulatory bodies.

Sound scientific and regulatory principles are established for all biologics, said Woollett, and any question about the similarity of reference and biosimilar products was fundamentally solved by 1996 guidance on comparability of biologics pre- and post manufacturing changes. The guidance, she explained, established the “highly similar” standard for biologics, and identical science applies to comparability and biosimilarity, even if regulatory approaches to these matters diverge in the United States.

Click to read more about manufacturing changes.

She added that manufacturing changes, which are common but unknown to US patients or physicians, are subject to review in all markets. Approved manufacturing changes involve complete extrapolation for all indications, interchangeability of the postchange product with the prechange product, and no changes to the product’s label.

Woollett posed the question of why there would then be any question about the safety of switching a patient from a reference to a biosimilar if there is no such question about switching a patient to a product that has undergone a manufacturing change. Pointing to a systematic literature review that demonstrated a low risk of safety concerns or loss of efficacy after a switch, she said that any risk associated is hypothetical only, and added that the FDA’s Leah Christl, PhD, has voiced agreement with European regulators that biosimilars are interchangeable with their references for the purpose of physician prescribing and that US interchangeability designations will serve only for the purpose of nonphysician substitution, not as a confirmation of safety.

Confidence in switching patients matters, said Woollett, because switching determines the initial market for a biosimilar. Clear communication about biosimilars by the FDA must be part of the development of that confidence, as “something must change for a sustainable multisource specialty market to emerge in the United States…if you can’t get market share with a cheaper product, those investments in biosimilar development won’t be made.”

Lee-Bourner, too, hopes for greater FDA communication about biosimilars, saying that the agency has a unique opportunity to increase trust in these products by undertaking educational activities for providers and patients alike and taking a strong stance on misinformation.

From Mylan’s perspective as a developer, communications with the FDA during presubmission meetings have been scientifically robust, well structured, and well organized, and the review process has typically proceeded in a timely fashion. However, she said, feedback from the FDA has not always been consistent, especially on products that are due to transition to regulation as biosimilars in 2020.

While crucial guidance remains underdevelopment, she said, the FDA can likely expect to see an increase in requests for scientific advice. Lee-Bourner said she also hopes to see final interchangeability guidance, clarification on the types of clinical study protocols that might qualify for Special Protocol Assessments, and the opportunity to streamline development by using non-US reference products.