In April, the US Food and Drug Administration (FDA) published draft guidance on the labelling of biosimilar products, recommending the inclusion of a statement describing the product’s relationship to its reference biologic.
In comments sent to the Agency, Sandoz laid out its concerns about the inclusion of a statement marking whether a biosimilar's approved indications had been based on the extrapolation of clinical data, a request made by reference drugmaker AbbVie in a citizen’s petition last year.
“It is self-evident that the very act of highlighting the indications that are extrapolated is being proposed by some groups in order to raise doubts as to the safety and efficacy of the biosimilar for those indications, and perhaps to also imply inferiority of biosimilars across the board,” the Novartis subsidiary said.
“We believe that these are the true purposes of requests that the PI [Package Insert] highlight the extrapolated indications for biosimilars, and in the future for interchangeable biologics. The FDA should not accept imputations that the Agency has approved biologics, in the form of biosimilars, that are any less safe and effective than the originator products to which they refer.”
Label purpose
Speaking at a media day in June, Sandoz’s global head of biopharmaceutical development Mark McCamish described a biopharmaceutical’s label as an instruction for the use of the product, and not a “history book” about the product’s development and approval history.
“The label itself informs the doctor how to use the product, so if there is any change in that product use, or a different indication then you revise the label,” he said.
“What it doesn’t do is it doesn’t provide the regulatory history or development history of the product: which pathway did it go down, what decisions were made by the analytical data, and that’s a key thing. What good would it be to have a size exclusion chromatography (SEC) [methodology] in there when the doctor has never seen an SEC?”
Such differences are not clinically important, he said, but to a doctor having them on a label would suggest a biosimilar could be different or inferior to its reference.
Furthermore, he added there is no call to present information that due to their very nature, all biologics vary from batch to batch, and nearly all major reference biologics have undergone manufacturing changes through their lifetimes without the need to inform physicians or patients.
Janssen’s Remicade (infliximab), for example, has seen over 30 changes in its manufacturing process since it was first approved, he said.
Interchangeability
In other comments on the guidance, reference drugmakers AbbVie and Janssen both called on the Agency to include information regarding the interchangeability of a biosimilar product on the label itself.
In the US an interchangeable product is defined as one that can be substituted for the originator product without the intervention of the prescribing healthcare provider.
However, the FDA is yet to have released draft guidelines on the issue, and as such the two approved biosimilars in the US – Sandoz’s Zarxio and Pfizer’s Inflectra – have not been deemed interchangeable by the Agency.