As set forth in a July 1, 2016 letter from Merck, and as reported in the RAPS newsletter, the claim was that there was no agreed definition at FDA of what the term "interchangeability" might mean, in a biosimilar context. That seemed increasingly unlikely, as I thought back on the efforts of Sandoz in early 2015, to have a filigrastim biosimilar approved, by reference to the Amgen reference product, under the brand Neupogen®. [The Sandoz version is Zarxio®.]
So, this evening, I did a little digging -- but only a very little, truthfully. For right there, in the slides from FDA staffers at that meeting, on slide 8, was an FDA accepted definition of "interchangeability." True enough, it does not come with a citation to the CFR, so I suppose Merck may mean that the FDA hasn't formally adopted the below definition by a full-on rule-making process. But as Merck itself points out, most of the below appears in the ACA of 2010, or the law which ushered in Obamacare. So the below is presumably good law.
It now seems clear, that FDA staffers at least will adhere to the below definition, since they vetted and approved these slides in connection with the early 2015 advisory committee materials (and thus the later FDA approval, on which it was based): the Sandoz biologics license application no. 125553, for EP2006, a proposed biosimilar to Amgen's Neupogen (filgrastim). So -- here it is, for a complete record:
. . . .Definition: Interchangeability
Interchangeable or Interchangeability means:
▪ the biological product is biosimilar to the reference product;
▪ it can be expected to produce the same clinical result as the reference product in any given patient; and
▪ for a product that is administered more than once to an individual, the risk in terms of safety or diminished efficacy of alternating or switching between use of the product and its reference product is not greater than the risk of using the reference product without such alternation or switch.
Note: The interchangeable product may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product. . . .
Maybe then, Merck's main point in its July 1, 2016 comment letter to FDA is really to "disagree" with the above definition, now in use at least at FDA Advisory Committee meetings, and largely lifted from the Obamacare enabling law, at Patient Protection and Affordable Care Act §7002.
And of course, what this all ultimately drives toward is a largely laudable effort -- to reduce the overall cost of care, by substituting biosims -- for higher priced reference product brands -- (or thereby cause a decrease in the reference product pricing) and thereby achieve lower per patient cost of care, either way, under the ACA. But it is not accurate to say there is no definition.
Now you know. Smiling widely, and beaming brightly. . . tonight.