GRx+Biosims: Panelists Discuss Regulatory Shifts in Biosimilar Interchangeability

At the GRx+Biosims 2024 conference, panelists discussed the evolving regulatory landscape for biosimilar interchangeability, highlighting some of the remaining challenges regarding the label in the US and the path forward.¹ The conference is taking place October 21 to 23 in Rockville, Maryland.

Mustafa Unlu, PhD, JD, policy staff director, Office of Therapeutic Biologics and Biosimilars, Office of New Drugs, Center for Drug Evaluation and Research, the FDA, opened the discussion by explaining interchangeability, a US-specific designation rooted in early concerns over the unknown risks of biosimilars.

“Interchangeability, which is basically a designation that only exists in US law, is based on a fear of the unknown…. And the fear comes from the familiar, where generics are supposed to be identical in every atomic detail to their reference drugs. And you cannot have that with [biosimilars],” he explained.

He detailed the statutory requirements for interchangeability, noting that fears about immunogenicity have not been realized, citing data from switching studies and real-world evidence. Unlu also discussed the FDA’s new draft guidance removing switching study requirements for interchangeability and labeling efforts aimed at streamlining the interchangeability process.

Arlene Wolny, PhD, global head of regulatory affairs, Biocon Biologics, provided an industry perspective, addressing the historical concerns about immunogenicity. She outlined how requirements for obtaining interchangeability impacted stakeholders, often creating confusion and high entry barriers.

“Is an interchangeable biosimilar safer? Does it have better shape? Better quality? Is there a higher standard for approval? The answer is no, and even in 2024, [the Biosimilars Council] said that misinformation undermines perception of safety and efficacy. But I will always say that the FDA has always stated that on both biosimilars and interchangeable biosimilars. They have to meet the same high-quality standards.”

Wolny emphasized reducing uncertainty through analytics and functional assays and highlighted the evolution of FDA guidance toward a more streamlined approach to interchangeability. She underscored the importance of educational programs and timely feedback from the FDA to avoid development delays. Wolny also addressed the challenges of amendments and supplements for interchangeability designation, calling for more transparency from the FDA. She further discussed the FDA's updated guidance, such as the removal of the interchangeability statement from labeling and the focus on essential information.²

Jessica Greenbaum, JD, director, Regulatory Affairs Policy US, Sandoz, echoed this, celebrating the FDA’s changing mindset around switching studies for interchangeable biosimilars. “I think the shift that the FDA has made in only a couple of years, in terms of the understanding of going from switching studies to where we are now with the updated guidance, for a huge agency like the FDA, I think this has been extremely impressive, and really shows how science-driven focus really can change the regulatory framework."

Greenbaum also discussed legislative proposals to eliminate the distinction between biosimilars and interchangeable biosimilars, advocating for a unified standard. She pointed out the difficulties in maintaining separate pathways and stressed the need for early feedback to prevent development delays. Greenbaum emphasized that a single standard would bring clarity and reduce the need for additional clinical data.

The discussion then turned to the problem of misinformation, with Unlu emphasizing the need for educational programs to boost biosimilar uptake. He noted the role of the FDA in creating educational materials and participating in professional conferences to reach health care professionals and patients. Unlu encouraged the industry to amplify the FDA’s educational efforts and engage with patients and clinicians to address biosimilar concerns effectively.

Unlu explored hypothetical future scenarios, focusing on the need for more flexible regulatory standards to accommodate the diversity of biologics and streamline the interchangeability process. He emphasized that a single standard would provide clarity and reduce the need for extra clinical trials. Additionally, he discussed the issue of first interchangeable exclusivity and called for more transparent FDA feedback to avoid delays.

Greenbaum concluded that more work is still needed to ensure complications surrounding interchangeability are addressed. “I think making sure that we can do what we can to have that system be reformed in a meaningful way is really important. Because while the work that the FDA does is extremely critical to get the products approved, that’s definitely not the end of the conversation.”

References

1. Greenbaum J, Randazzo G, Unlu M, Wolny A. Interchangeability. Presented at: GRx+Biosims; October 21-23, 2024; Rockville, Maryland.

2. Jeremias S. FDA draft guidance removes switching study requirements for biosimilar interchangeability. The Center for Biosimilars^®. June 20, 2024. Accessed October 21, 2024. https://www.centerforbiosimilars.com/view/fda-draft-guidance-removes-switching-study-requirements-for-biosimilar-interchangeability