Skip links

Can and Should ANDA Labeling Differ from the RLD?

In the past two months, two appellate courts, the Fifth Circuit and the Eighth Circuit have handed down decisions which essentially state that generic pharmaceutical companies can be sued in state courts for failure-to-warn regarding serious side effects, where the generic companies had conformed their labeling to that of the current Reference Listed Drug.

For a long time, the working model was that the generic companies’ labeling had to be virtually identical to that of the RLD when an ANDA was filed, and to continue to conform to it, i.e., to make any substantive changes in lockstep with the RLD. Originally FDA would send all ANDA holders a letter requesting a CBE (changes becoming effective) supplement following the approval of a substantive label change to the RLD labeling. A number of years ago, FDA shifted the responsibility for monitoring the RLD labeling to the ANDA holders themselves. Everyone at least behaved as if the generic labeling could not deviate from that of the RLD – ever.

Now, the Fifth and Eighth Circuits have said that (and this is a bit of an oversimplification) while they agree that the ANDA labeling must be virtually identical at the time the application is filed, they see nothing in any statute or regulation strictly prohibiting ANDA holders from filing, say, a CBE labeling amendment proposing a labeling change based on their taking note of safety or efficacy issues in their ADE reporting or in, e.g., medical and scientific literature. The courts refused defendant’s argument that 21 CFR 3141.50 will not allow/prevent generic firms from making such changes, or that doing so might prompt FDA to withdraw approval of the ANDA involved.

Needless to say, most generic firms do not devote a great deal of time or resources to monitoring medical and scientific literature or performing detailed analysis of post-marketing Pharmacovigilance data. ADEs are reported and labeling is kept in conformance with the RLD.

What are the implications? Short term, there are probably a LOT of plaintiff’s attorneys looking for folks who have had a serious ADE with a generic drug. The Fifth Circuit decision noted that other federal courts have decided the other way, so those same attorneys are likely doing some serious forum selection. Also, a conflict of decisions in various federal courts usually is a set up for an eventual appeal to the Supreme Court. That is the same Supreme Court which last year in Wyeth v. Levine held that the federal regulatory scheme did not preempt state law failure-to-warn claims against the innovator company. Overall, it might be best for generic companies to at least do some planning as to how to deal with potential suits and a change in legal (but not regulatory) requirements. And perhaps there might be an enterprising company out there who will look over the available safety information for a product and go ahead and file a CBE changing their labeling absent a change to the RLD, and see how OGD responds. And one more question: if FDA accepts the change, and everybody jumps in, what are the implications for substitutability if all the labels are similar but not quite the same?