After Mutual Pharmaceutical Co. v. Bartlett, 133 S. Ct. 2466 (2013), and PLIVA v. Mensing, 131 S. Ct. 2567 (2011), one thing is perfectly clear – “impossibility” preemption in the prescription drug context depends on whether (as in Wyeth v. Levine, 555 U.S. 555 (2009)) or not (as in Bartlett and Mensing) the defendant drug manufacturer can change its label without prior FDA approval. This bright preemption line is summarized by the statement in Mensing: “[W]hen a party cannot satisfy its state duties without the Federal Government’s special permission and assistance, which is dependent on the exercise of judgment by a federal agency, that party cannot independently satisfy those state duties for pre-emption purposes.” 131 S. Ct. at 2581.
As discussed in Levine, the FDA’s so called “Changes Being Effected” (“CBE”) process allows a number of label changes for prescription drugs to be independently initiated by manufacturers without a requirement of prior FDA approval.
But not all label changes.
Some prescription drug label changes are considered sufficiently “major” that they require FDA prior approval – so says the FDA. If the FDA states that certain kinds of changes to drug label changes need pre-approval, even for innovator drugs, then under Levine, Mensing, and Bartlett, product liability claims demanding those sorts of label changes should be preempted. Moreover, such pronouncements – the FDA interpreting its own CBE regulation – should be entitled to judicial deference even under Levine.
The current FDA guidance document on this subject appears to be FDA, CDER, “Guidance for Industry: Changes to an Approved NDA or ANDA,” 2004 WL3199016 (FDA, April 1, 2004), available here, so you can follow along at home. This guidance categorizes six different types of changes, with the category we’re discussing – labeling – at *18-20. The following quotation delineates what the FDA considers “major” changes to labeling that: (1) require
pre-approval, and (2) can’t be done via CBE.
B. Major Changes (Prior Approval Supplement)
Any proposed change in the labeling, except changes designated as moderate or minor by regulation or guidance, must be submitted as a prior approval supplement (§314.70(b)(2)(v)(A)). . . . The following list contains some examples of changes currently considered by CDER to fall into this reporting category.
1. Changes based on postmarketing study results, including, but not limited to, labeling changes associated with new indications and usage.
2. Change in, or addition of, pharmacoeconomic claims based on clinical studies.
3. Changes to the clinical pharmacology or the clinical study section reflecting new or modified data.
4. Changes based on data from preclinical studies.
5. Revision (expansion or contraction) of population based on data.
6. Claims of superiority to another drug product.
7. Change in the labeled storage conditions, unless exempted by regulation or guidance.
FDA Guidance, 2004 WL 3199016, at *19 (discussion of changes to medication guides omitted). First, note the word “must” in the first paragraph.
Next, review the FDA’s list. If a claimed “warning defect” is based on any of these things – and we’ve seen plenty based on new “postmarketing” and “clinical” studies – then what the plaintiff is advancing should be preempted for falling on the far side of the CBE line. Moreover, the reference to “superiority claims” strongly suggests to us that the converse: a claimed duty to warn that a product has inferior safety/effectiveness compared to a competing product, would also be a “major” change requiring FDA pre-approval, and would thus be preempted.
By comparison, here are the types of label changes that the FDA thinks may be effectuated through CBE:
C. Moderate Changes (Supplement – Changes Being Effected)
Under §314.70(c)(6)(iii), a changes-being-effected supplement must be submitted for any labeling change that (1) adds or strengthens a contraindication, warning, precaution, or adverse reaction, (2) adds or strengthens a statement about drug abuse, dependence, psychological effect, or overdosage, (3) adds or strengthens an instruction about dosage and administration that is intended to increase the safe use of the drug product, (4) deletes false, misleading, or unsupported indications for use or claims for effectiveness, or (5) normally requires a supplement submission and approval prior to distribution of the drug product that FDA specifically requests be submitted under this provision. . . . The following list includes some examples of changes currently considered by CDER to fall into this reporting category.
1. Addition of an adverse event due to information reported to the applicant or Agency.
2. Addition of a precaution arising out of a postmarketing study.
3. Clarification of the administration statement to ensure proper administration of the drug product.
Id. at *25 (CBE filing requirements discussion omitted).
Okay, some things seem to overlap – how does one approach, say, the strengthening of a warning, where the reason for the change is the result of a postmarketing study? The FDA more-or-less addresses that, too, in its guidance:
For multiple related changes where the recommended reporting categories for the individual changes differ, CDER recommends that the submission be in accordance with the most restrictive of the categories recommended for the individual changes.
Id. at *21 (emphasis added). That’s not exactly the same thing, but it’s pretty close, since the warning section is only one of a number of places in the labeling where the results of a significant postmarketing study (or clinical trial, or something else in category “B”) would require labeling changes under FDA regulations. A manufacturer can’t “just” strengthen a warning in this situation without making multiple related updates. The FDA thus states, that the “most restrictive” (that is to say, agency pre-approval of “major” changes) procedure should be followed.
In light of the FDA’s opinions, as expressed in this guidance – admittedly consisting of “non-binding recommendations” – defense counsel in innovator drug cases otherwise subject to Levine might want to consider (and discuss with regulatory counsel/experts) whether impossibility preemption applies to particular types (but ordinarily not all) of warning-related claims in any given case. The FDA’s guidance demonstrates that CBE is not the be-all and end-all of label changes under the FDCA.
Finally, we emphasize that this analysis is not being offered just for the first defense counsel with enough guts to try it. Remember what happened in Levine. Post-Levine, innovator drug preemption is an area where brains counts for more than any other part of the anatomy. Defense counsel must evaluate any possible application of preemption rationally and dispassionately. Arguments along these lines should emerge from the strongest possible fact scenario, and their venue selected with equal care. It would be very easy to provoke bad law in this area, so don’t be the first to try it unless your facts are top notch,
and your judge will give the argument a fair shake.