Regulatory Focus™ > News Articles > 3 > Review Finds Switching From Reference Product to Biosimilar 'Not Inherently Dangerous'

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Posted 05 March 2018 | By Zachary Brennan 

Review Finds Switching From Reference Product to Biosimilar 'Not Inherently Dangerous'

2986 In what may be part of a growing body of evidence that helps green light the development of new interchangeable biosimilars, a review published Saturday in Drugs found that data collected to date suggest that switching from a reference medicine to a biosimilar “is not inherently dangerous, and that patients, healthcare professionals, and the public should not assume that it is problematic.”

The review of rheumatoid arthritis, psoriasis, inflammatory bowel disease and dozens of other trials and real-world evidence for other diseases - conducted by researchers from Novartis’ Sandoz, Oregon Medical Research Center, Rocky Mountain Cancer Centers, Milan-based Humanitas Clinical and Research Hospital and elsewhere - sought to evaluate whether such switching could lead to altered clinical outcomes, such as enhanced immunogenicity, compromised safety or diminished efficacy.

The review also may be relevant for companies deciding whether to invest in developing interchangeable biosimilars as switching studies are part of what’s necessary to win approval for such a designation in the US, according to draft guidance from the US Food and Drug Administration (FDA).


As of 30 June 2017, data from 90 studies enrolling 14,225 unique individuals were found, and the researchers sought to evaluate the concern that there might be an increase in immunogenicity related to switching between the reference biologic and biosimilar.

“Three large multiple switch studies with different biosimilars did not show differences in efficacy or safety after multiple switches between reference medicine and biosimilar. Two publications reported a loss of efficacy or increased dropout rates,” the authors wrote.

One of the two raising safety concerns was a review of a Turkish claims database where 148 patients were switched from reference infliximab (Remicade) to biosimilar infliximab and there was an 82% drop-out rate in patients who switched, compared to a 24% drop-out rate in patients who remained on reference infliximab.

“It is possible that these were chance results because no such large differences in drop-out rates were seen in switched versus control patients in the 46 other studies that evaluated switching between these same biologics,” the review noted.

Most studies only evaluated a single switch from reference biologic to biosimilar, though the authors said that patients “have already been exposed to de facto multiple switches for many originator biologics when product quality attributes changed after one or more manufacturing process modifications were introduced.”

And while use of each biologic must be assessed individually, the authors said: “These results provide reassurance to healthcare professionals and the public that the risk of immunogenicity-related safety concerns or diminished efficacy is unchanged after switching from a reference biologic to a biosimilar medicine.”

They also explained how continued pharmacovigilance is necessary to monitor for rare safety events and other unexpected changes in efficacy or safety that may occur after a manufacturing change.

“Furthermore, continued and thorough pharmacovigilance for all biologics should increase confidence of patients, healthcare professionals, and the public in biosimilars, leading to increased acceptance of these safe and effective medicines,” the authors wrote.

Switching Reference Medicines to Biosimilars: A Systematic Literature Review of Clinical Outcomes


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