Posted 24 July 2014
By Alexander Gaffney, RAC
Biopharmaceutical company Sandoz, a Novartis subsidiary, has announced that it has filed the first-ever biosimilar application in the US with the Food and Drug Administration (FDA) using its 351(k) pathway.
The company's announcement, made 24 July 2014, says FDA has already accepted its filing for a biosimilar Neupogen (filgrastim), an FDA-approved treatment used to decrease rates of infection in patients with nonmyeloid malignancies who are already receiving chemotherapy.
While FDA has reportedly received several investigational new drug applications (INDs) supporting potential future biosimilar applications, Sandoz's application marks the first yet submitted for full marketing approval under the 351(k) pathway instead of the traditional 351(a) pathway.
In a statement, Sandoz called the filing a "significant step toward making high-quality biologics more accessible in the US."
If approved, the drug could also be an early indicator of how biosimilar-producing companies will price their products relative to their reference products. At the time of the passage of the Biologics Price Competition and Innovation Act in 2010, congressional budget forecasters said they believed biosimilar drugs could save consumers and the federal government billions each year by incentivizing market competition. However, given the difficulties of bringing biosimilar drugs to market so far, some analysts have expressed concerns that the true savings to US consumers could be much lower than anticipated.
Zarzio, First 351(k) Filed, First to Face Regulatory Questions
If approved, Sandoz's biosimilar, which will be marketed under the brand name Zarzio, will also likely answer many outstanding questions about FDA's as-yet-unexplored 351(k) pathway.
Chief among those questions seems to be how FDA will define "similarity" for the purposes of a biologic. As a result of their manufacturing processes, it is nearly impossible to exactly replicate an existing biologic without having access to the identical cell line and manufacturing process. As a result, regulators are primarily concerned with characterizing the differences between the reference biologic and the biosimilar medicine, and understanding whether those differences are clinically meaningful for patients.
In May 2014, FDA issued a guidance document that, among other things, explained that it would have a four-part standard for biosimilarity:
- not similar
- highly similar
- highly similar with a fingerprint-like similarity
But aside from explaining that the standard would be used by regulators, FDA offered little in the way of details about how drugs might find themselves in each of the four categories.
Other issues that are almost certain to come up are substitutability and interchangeability—legal and practical concepts that refer to a drug's ability to be used instead of another drug. Some states have already passed legislation stating that unless FDA explicitly finds a drug to be interchangeable, then pharmacists cannot substitute a biosimilar drug for a reference biologic without permission from the prescribing doctor.
Finally, the drug—if approved—will be subject to another ferocious debate: What should it be called? Many branded biologic entities have called for distinct generic names for the drugs, saying that using the same names for different medicines could make pharmacovigilance more difficult. Biosimilar companies, meanwhile, have maintained that the naming issue could confuse patients into believing that a drug isn't as safe or effective as the original.
Whatever the challenges to be faced, Sandoz's Zarzio seems well prepared to answer them. The company notes the drug is already approved in 40 countries, and has nearly six million patient-exposure days' worth of data to back it up. That amount of data could prove extremely valuable to regulators, who now seem to have as many questions about the process as the companies hoping to bring their biosimilar products to market.