Addressing Concerns Around Interchangeable Biosimilars

Although no biosimilar has earned an interchangeable designation by the FDA to date, the distinction could garner more biosimilar uptake. In a presentation during the American Conference Institute (ACI)’s Summit on Biosimilars, held June 25-27 in New York, New York, various stakeholders discussed how interchangeability is the future of the space.

Ha Kung Wong, JD, partner at Fitzpatrick, Cella, Harper & Scinto, noted that the lack of biosimilar uptake within the United States, offering a seemingly low return on investment, could be due to the fact that none of the biosimilars are substitutable at the pharmacy level. “Analysts have predicted that by the end of 2018, infliximab biosimilars will only get 10% of the total infliximab market. In contrast, in Europe these biosimilars have 53% of the market.”

Concerns around interchangeable biosimilars stem from many patient groups and other industry members fearing that the substitution would be made at a pharmacy level without notification to the patient or physician and would result in a clinically different or harmful result. To pre-emptively address this concern, 44 states thus far and Puerto Rico have passed policies that cover a multitude of concerns, but largely require the notification of a physician that the substitution is being made within a timely manner.

However, Bruce Leicher, senior vice president and general counsel at Momenta Pharmaceuticals, said that there are certain changes seen in reference products throughout a manufacturing life cycle, even though these products are viewed as interchangeable. “Historically, there’s been a view that reference products are interchangeable when we go through manufacturing changes, but you will see significant differences between different lots of reference products.”

Although these changes are within a threshold, as noted by Kristan Lansbery, PhD, JD, director and patent attorney at Regeneron Pharmaceuticals, many of the quality attributes remain the same. The difficulty, she states, “is that a follow-on product can only compare to the originator's final product. The biosimilar developer has no knowledge of the originator's predetermined ranges for quality attributes, and although they can acquire the product and run tests to analyze and identify quality attributes, independently produced follow-on biologics have different qualities.”

The FDA released a draft guidance document in January 2017 around how manufacturers should demonstrate interchangeability of a product and the data that it wanted developers to submit. However, there have been many concerns and questions submitted to the FDA from industry members.

Wong discussed some concerns stakeholders have about the document, including:

• The switching study: The FDA strongly recommends the use of a US-licensed comparator product for the switching study. Developers are confused by this requirement because to prove biosimilarity, the FDA permits use of a non-US licensed comparator.
• Number of switches: Some industry members submitted concerns around the number of switches required by the study, with some stating there are too many required and others stating too few.
• Analytical requirements: The FDA requires the use of pharmacokinetics to prove the interchangeability of a product. Developers want to know if using efficacy as an end point would be sufficient.

According to Wong, many of the questions surrounding a biosimilar achieving interchangeability will be addressed in the finalized guidance by the FDA, “which we can look forward to seeing, hopefully, in 2019.”