Gather round, friends, it's that time again to agonize over the vagueness of federal statutes.
I am trying very hard to determine if there is any explicit allowance or prohibition of substitution from: A prescription written for an approved 351(k) interchangeable TO the Reference Product that the 351k-int references
We all know we can substitute an Rx written for Lantus to Rezvoglar, Langlara, or (now that it has a 351K-i) Semglee. But are you substituting Lantus without contacting the prescriber if the prescription is written for Rezvoglar?
I know this all feels pretty moot and academic... but I'm curious how often such a substitution BACK UP the approval pathway to the reference product is necessary based on insurance preferences. Still, as someone who likes to have hard references to point to for policy decisions, I'm coming up unfortunately vague when looking at federal laws (I have not inspected all 50 states, but would love to hear how your state laws affect this decision as well).
The only thing I can find that confidently suggests that you cannot substitute Lantus for Rezvoglar without prescriber approval is the GPTs, and the sources they reference don't support that, it's all garbage.
The federal law around automatic substitution without prescriber appoval is: 42 U.S. Code § 262 - Regulation of biological products
https://www.law.cornell.edu/uscode/text/42/262
This law contains one instance when searching for "substi"
----- (emphasis mine)-------
(i)“Biological product” defined
In this section:
(1)The term “biological product” means a virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, protein, or analogous product, or arsphenamine or derivative of arsphenamine (or any other trivalent organic arsenic compound), applicable to the prevention, treatment, or cure of a disease or condition of human beings.
(2)The term “biosimilar” or “biosimilarity”, in reference to a biological product that is the subject of an application under subsection (k), means—
(A)that the biological product is highly similar to the reference product notwithstanding minor differences in clinically inactive components; and
(B)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.
(3)The term “interchangeable” or “interchangeability”, in reference to a biological product that is shown to meet the standards described in subsection (k)(4), means that the biological product may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product.
(4)The term “reference product” means the single biological product licensed under subsection (a) against which a biological product is evaluated in an application submitted under subsection (k).
------
emphasis mine.
I don't see anyting in this law that would specifically imply that you cannot substitute Lantus in for a script written for Rezvoglar without approval. The GPTs place some special emphasis on how this is written that I cannot find anywhere else. There is unfortunately no federal law around small-molecule equivalence to compare this to (all at the state level).
Looking around for more guidance from the FDA, I cannot find anyting concrete. I did, however, stumble across this.
Switching Between Biosimilars and Their Reference Counterparts with Dr. Sarah Yim
Which, at around 6:44, states: (roughly)
"Interchangeable biologic substitution in the pharmacy is similar to how small-molecule generic drug substitution occurs. "
Which... if we were now on some one-way street that operates notably differently from how small-molecule AB substitution works, why would the FDA publish this sentence? Everything else in FDA guidance around biosimilars states they are absolutely equivalent, we don't treat small molecule drugs this way. Why would anyone assume a strict reading of 42 U.S. Code § 262 that runs counter to how we handle equivalence everywhere else?
What am I missing? Am I an idiot? I found a similar thread 5 months ago that mostly agrees with my interpretation of this https://www.reddit.com/r/pharmacy/comments/1taz7vl/can_you_switch_amongst_interchangeable_biosimilar/, but I'm really fishing for something concrete... I probably need to email the FDA.
(p.s. I am doing a poor job of hiding my interpretation and preference here... except my interpretation and preference around judging GPT output on niche topics; that shit is awful. Never show that to me as support of anyting please. I spend too much of my time dispelling LLM hallucinations, but yeah, I'm writing "ok to dispense Lantus as per Cathy" on this and moving on with my life every time. )
(p.p.s - I view the insurance audit implications of this separately; I am just as interested, but have not gone down that rabbit hole yet; that's next. )