The FDA recently released draft guidance concerning the labeling of biosimilar products (analogous in the biologic context to generic drugs). It’s called, not surprisingly “Labeling for Biosimilar Products Guidance for Industry.” Here’s a link to it on the FDA’s website.
When we think of bioequivalence, we think of generic drugs, and more specifically generic drug preemption under PLIVA v. Mensing, 131 S. Ct. 2567 (2011), and its progeny. Generic preemption, as we’ve discussed many times, depends on the impossibility of making an immediate change to a product (including its labeling) as required by state law, where the same change necessitates prior approval by the FDA under federal law. So we took a look at the guidance to see whether biosimilar products were likely to enjoy the same protection from state-law product liability.
It doesn’t look that way.
The key part of the guidance is “Updating Safety Information” on pages 10-11. The guidance states:
When new information becomes available that causes information in labeling to be inaccurate, the application holder must take steps to change the content of its product labeling, in accordance with 21 CFR 601.12. All holders of marketing applications for biological products have an ongoing obligation to ensure their labeling is accurate and up to date.
Biosimilar Labeling Draft Guidance at 10-11 (footnote omitted).
So we took a look at §601.12, although we had a pretty good idea what we would find – a “changes being effected” provision (§601.12(f)(2)(i)) quite similar to the one that defeated preemption in Wyeth v. Levine, 555 U.S. 555 (2009).
So, is there a statutory sameness requirement for biosimilars that the FDA is conveniently forgetting about?
So we looked at the FDCA. Oddly, we found ourselves referred to a completely different title of the U.S. Code: 42 U.S.C. §262, entitled “regulation of biological products.” We searched for “same” and “identical” and did get some relevant hits on the former. In applying for a biosimilar license the applicant must “include information demonstrating that . . . the biological product and reference product utilize the same mechanism or mechanisms of action for the condition . . . in the proposed labeling but only to the extent the mechanism or mechanisms of action are known for the reference product.” §262(k)(2)(A)(II) (emphasis added). Likewise, the “route of administration,” “dosage form,” “strength” must be “the same as those of the reference product.” §262(k)(2)(A)(IV). The biosimilar must also “be expected to produce the same clinical result as the reference product in any given patient.” §262(k)(4)(A)(ii).
Elsewhere, biosimilars are defined only as “highly similar to the reference product.” §262(i)(2)(A).
So no, there doesn’t appear to be anything in the biosimilar statute like 21 U.S.C. §355(j)(2)(A)(v), which required generic drugs to have labeling “the same as the labeling approved for the listed drug.”
Presumably the FDA could require prior approval of labeling changes that would introduce discrepancies with the listed product that involve safety and effectiveness, but this draft guidance doesn’t, and frankly we didn’t expect the same agency that has been trying for years to torpedo generic preemption to create more of the same unless the statute forced it to (and maybe not even then). Thus, to the extent of the information encompassed by 21 C.F.R. §601.12(f)(2)(i), it appears that biosimilar manufacturers will be stuck with the same kind of product liability litigation as are their listed counterparts.
If anybody has any bright ideas to the contrary, by all means tell us.