FDA Faulted for Biosimilar Release Without Safety Guidance

March 10, 2015

The American Autoimmune Related Diseases Association has criticized the FDA for approving the first US biosimilar without establishing policies to guard public safety.

The American Autoimmune Related Diseases Association (AARDA) has responded to FDA approval of the first US biosimilar by charging it with inadequate attention to the implications for public safety.

AARDA is concerned that FDA took the action "without first having published any final standards" on "issues that will impact patient safety, including interchangeability, naming and indication extrapolation," the nonprofit organization said in a statement released March 6.

Because a biosimilar for the rheumatologic drug infliximab is to be considered at a March 17 FDA hearing, these safety-related policy issues may soon become relevant to rheumatologists.

For people with compromised immune systems, the AARDA statement declares, "differences in manufacturing, however small, have the potential to cause a ... negative immune response...For this very reason, clarity and transparency about biologics and biosimilars are critical."

At a press briefing on the day the biosimilar for the anticancer drug filgrastim was approved, FDA officials minimized the risk to patients from taking the new drug. The Agency's regulatory focus for biosimilars is on showing there is "no clinically significant difference" from the reference product and that the two are "highly similar from an analytical standpoint" including chemical, in vitro, and pharmacokinetic studies, said John Denkins MD, director of the Office of New Drugs in FDA's Center for Drug Evaluation and Research.

There is "variability within any biological system," he added, and different batches of the reference drug may have subtly different results in the body. In this case, he said, the biosimilar Zarxio "should behave the same in patients from the safety point of view" as the original reference drug, Neupogen.

A white paper about biosimilars released by AARDA points to the following policy issues, among others:

•   Names:  A biosimilar should have a "distinguishable name" suitably different from that of the reference drug so that the two are never confused. (FDA refers to the filgrastim biosimilar as "filgrastim-sndz," referring to its manufacturer, Sandoz.)

•   Interchangeability:  The Affordable Care Act mandates that, if the biosimilar and the reference product can be used interchangeably, FDA must establish that there are "no clinically meaningful differences between the biological product and the reference product in terms of the safety, purity, and potency of the product.” FDA has deemed that Zarxio is not interchangeable with Neupogen, but has yet to define standards for interchangeability. Some states have enacted laws awaiting this definition, which will govern when pharmacists and health plans may allow switching between biosimilars and reference drugs.

•   Indication extrapolation:  It is not yet clear to what extent manufacturers of biosimilars approved for one condition will be allowed to apply for faster approval for additional indications for which the reference drug is also approved. (For example, if an infliximab biosimilar is approved for psoriatic arthritis, would different safety issues pertain in using it for ankylosing spondylitis, for which the reference medication, Remicade, is also approved?)