FDA Withdraws Guidance on Biosimilar Analytical Studies

In response to industry concerns, the US Food and Drug Administration (FDA) on Thursday announced it has withdrawn its draft guidance on evaluating studies used to demonstrate analytical similarity between a biosimilar and reference biologic.
 
FDA says it plans to reissue the draft guidance after considering changes to the document that will "promote a more efficient pathway for the development of biosimilar products."
 
"Biosimilars foster competition and can lower the cost of biologic treatments for patients, yet the market for these products is not advancing as quickly as I hoped," FDA Commissioner Scott Gottlieb said in a statement.
To date, FDA has approved 11 biosimilars to eight reference biologics since approving its first biosimilar in 2015. However, only a fraction of those biosimilars are available on the market, with legal challenges often adding years between approval and commercial launch.
 
Unlike generic drugs, which are analyzed for bioequivalence to a reference drug, biosimilars must demonstrate that they are "highly similar" to a reference biologic, with no clinically meaningful differences between the two.
 
Draft Guidance
 
In the now-withdrawn draft guidance, issued for comment in September, FDA laid out recommendations for the information biosimilar sponsors should gather about a reference product and how that information would be used to develop an analytical similarity assessment to show that the products are highly similar. The guidance also included recommendations on statistical methods for evaluating analytical similarity.
 
However, in comments submitted to the public docket for the guidance, industry took issue with many of the agency's recommendations.
 
One of the biggest sticking points has to do with the number of lots of reference product FDA recommended to be sampled.
 
In the guidance, FDA called for a minimum of 10 reference product lots to be sampled in order "to establish meaningful similarity acceptance criteria." The agency also acknowledged that in cases where access to reference product lots is limited, alternative analytical similarity assessments may be considered.
 
Other comments raised concerns about the agency's insistence that those lots come from US-sourced reference, the potential for lot-to-lot variability and the statistical methods for evaluating analytical similarity proposed in the guidance.
 
"The goal is for future draft guidance to address potential challenges faced by biosimilar sponsors in designing studies that are intended to demonstrate that a proposed biosimilar product is highly similar to a reference product, including consideration of appropriate methods to analyze analytical data to account for potential lot-to-lot variability of the reference product," FDA says.
 
FDA