These days, new drugs require a New Drug Application (NDA). Drugs subject to the NDA requirement are sometimes called “pioneer drugs.” But generic drugs get to file an Abbreviated NDA, or ANDA, requiring that the active ingredients have been previously approved. In addition, an ANDA requires bioequivalence and identical labeling, and must not infringe a patent. (Here, Wyeth is currently contesting the validity of Sun’s patent for its generic product.) The FDA has to approve an ANDA for a generic with a single active ingredient unless it finds that the information submitted is insufficient to show that the active ingredient is the same as that of the previously approved drug. The FDA produces the Orange Book, which shows all pioneer drugs and their approved generic equivalents, updated monthly. A generic listed in the Orange Book may be prescribed as a substitute for a costlier pioneer.
Wyeth makes Protonix, a prescription drug that treats various gastro-intestinal disorders by inhibiting the secretion of gastric acid. Its active ingredient is pantoprazole sodium sesquihydrate (“sesquihydrate”). Its NDA was approved in 2000, and it was quite successful, with annual sales approaching $2 billion prior to generic availability. (Wyeth now makes its own generic version.)
Sun makes a generic version of Protonix. Its ANDA was approved in 2007. The Orange Book lists it as an AB-rated generic substitute, meaning that Sun provided adequate studies to establish bioavailability and bioequivalence. But Wyeth alleged that the active ingredient is not sesquihydrate but rather pantoprazole sodium monohydrate (“monohydrate”), a polymorph of sesquihydrate. This means different crystal forms with potentially different properties, including melting point, stability, dissolution, and bioavailability.
Sun argued FDA preclusion; the FDA is currently investigating Wyeth’s allegations. Somewhat puzzlingly, the court stated that “[c]ourts have acknowledged the inherent conflict between the FDA’s exclusive jurisdiction over prescription drug regulation and the Lanham Act’s protection of patents and trademarks involved in prescription drug manufacturing.” The problem is neither patents (not the Lanham Act’s subject matter) nor trademarks (usually, anyway, though I was involved in a trademark case where the defendant leveraged FDA approval of its name into a factor favoring a finding of no likely confusion) but false advertising. The court then wobbled back onto course, noting that the issue is whether a false advertising claim can be proved without using FDA regulations or with reference at most to an unambiguous FDA definition.
The court held that Wyeth was asking it to hold either that the FDA erred/was misled in approving the ANDA, or that Sun received approval to market sesquihydrate, but instead sells a nonapproved monohydrate. The first position is precluded by the FDCA. The second is an extremely serious allegation, potentially subjecting Sun to severe criminal and civil liability. But even if that were proved, there’s no private right of action under the FDCA. (But that’s not the end of it: if there are unambiguous definitions of sesquihydrate and monohydrate, then determining what’s in Sun’s drug doesn’t require interpreting any FDA regulations, only comparing the drug to the definitions. If the claim is that Sun purports to sell sesquihydrate but actually sells monohydrate, that’s a pretty classic false advertising claim, albeit a serious one.)
The court concluded that even if the claims weren’t precluded, the matter should be left to the FDA’s expertise. Wyeth argued that all it was asking was that, just as a seller of orange juice can’t claim “100% orange juice” and add additional ingredients, a pharmaco can’t label a product with a different active ingredient than what it actually contains. But in previous cases, the FDA hadn’t approved or taken other action regarding the products at issue—it never tested the orange juice. So private parties were free to challenge unsubstantiated remarks about the quality or content of competitors’ products. But where a Lanham Act claim requires more than comparing a product to a stated regulation, it encroaches on the FDA’s jurisdiction. The court then cited cases involving interpreting regulations to figure out, for example, whether an ingredient ought to be labeled “active.”
The FDA defines polymorphs and notes that “polymorphic forms of a drug substance ... can have different chemical and physical properties that can have a direct effect on drug product stability, dissolution, and bioavailability, which ultimately can affect the quality, safety, and efficacy of the drug product.” But the same FDA document says that “differences in drug substance polymorphic forms do not render drug substances different active ingredients for the purposes of ANDA approvals within the meaning of the Act and FDA regulations.” So to resolve the claims here, the court would have to interpret FDA regulations on polymorph equivalency. Moreover, ruling in Wyeth’s favor would conflict with the FDA’s approval of Sun’s product. Thus, deference was justified.
Similar problems faced Wyeth’s challenge to Sun’s website statements that its product was a generic equivalent of Protonix. When a defendant has “the backing of the FDA” confirming its equivalency representations, a Lanham Act claim is inappropriate—past cases have gone forward only because the drugs at issue didn’t have ANDAs and Orange Book status, and so there was no FDA-set way to measure equivalency.
The court did conclude that, if the FDA confirms Wyeth’s suspicions, Wyeth might be able to sustain a Lanham Act claim. Thus, the complaint was dismissed without prejudice.