Citizen petitions are often used by private individuals and interest groups to attempt to persuade the FDA to order changes to drug and medical device labeling, particularly with respect to warnings. The FDA’s response to a petition in this context can have wide-ranging consequences for a pharmaceutical company and could require development and dissemination of an entirely new label for a drug or medical device. But what are the consequences of the FDA’s outright denial of such a petition? The purpose of this article is to answer this question with a practical example from a recent pharmaceutical case and offer some additional considerations for determining the potential legal value of the FDA’s denial of a citizen petition.

What Exactly is a Citizen Petition?

The citizen petition is one piece of the FDA’s broader regulatory effort to “encourage public participation in all agency activities.”[1] As one federal court recently described it, citizen petitions “provide[] a forum for individuals or business to express and support genuine concerns about the safety, scientific, or legal issues regarding a product at any time before, or after, market entry.”[2] Stated another way, the citizen petition is a method by which private citizens and organizations can participate directly in FDA policymaking by asking the FDA to take (or refrain from taking) certain regulatory actions.

Any “interested person” may submit a citizen petition to the FDA,[3] including individuals, partnerships, corporations, associations or other legal entities.[4] In granting a petition, the FDA Commissioner may “issue, amend, or revoke a regulation or order, or [] take or refrain from taking any other form of administrative action.”[5] The regulations governing citizen petitions make clear that the FDA has primary jurisdiction to make an initial determination on “issues within its statutory mandate.” Courts are instructed to dismiss, hold in abeyance or transfer to the FDA any issue that has not previously been determined by the FDA or which the FDA concludes should be reconsidered.[6] Thus, the citizen petition process can be utilized as an alternative to litigating unique technical or factual issues in court without the benefit of input from the FDA.[7]

The Commissioner of the FDA must respond to a citizen petition within 180 days after receiving it.[8] The Commissioner can either approve the petition, deny the petition, dismiss the petition if a change of circumstances has rendered the petition moot or provide a tentative response indicating why the FDA was unable to reach a decision.[9] The FDA’s grant or denial of a citizen petition constitutes final agency action that is subject to judicial review under the Administrative Procedures Act.[10]

The Denial of a Citizen Petition as Evidence of Preemption

The FDA’s denial of a citizen petition can be a useful tool for the defense in pharmaceutical litigation, but the specific legal impact of an FDA denial depends heavily on many factors, including (1) the type of product at issue, (2) the claims involved in the litigation, (3) the scope of the relief requested in the petition, (4) the FDA’s stated reason for its denial and (5) the timing of the denial. Each of these factors must be considered in determining whether the FDA’s rejection of a citizen petition is of any value to your defense. 

The FDA’s denial of a citizen petition is commonly utilized by litigants in the context of federal preemption. Under the doctrine of “impossibility preemption,” a requirement imposed by state law, including a tort claim, is deemed to be preempted by federal law if it would be impossible for the defendant to comply with both the state requirement and a federal requirement governing the same subject matter.[11] In other words, if a plaintiff brings a claim under state law alleging that the defendant failed to do something that federal law would not allow him to do, the plaintiff’s state-law claim is preempted. In the drug and medical device arena, this doctrine is implicated when a plaintiff files a lawsuit alleging that a manufacturer failed to warn users of a specific risk or side effect associated with a drug or medical device. If the manufacturer can present “clear evidence” that the FDA would not have approved the warning that the plaintiff claims was necessary under state law, the plaintiff’s claim cannot proceed.[12] One method of satisfying this “clear evidence” standard is by showing that the FDA had previously considered and rejected a citizen petition that would have required the manufacturer to include the same warning that the plaintiff claims was necessary to fulfill a state law duty. At the very least, the FDA’s response to a citizen petition concerning a drug or medical device’s label is indicative of whether the FDA would reject a proposed labeling change.

Preemption in Practice: Cerveny v. Aventis, Inc.

The Tenth Circuit’s recent decisions in Cerveny v. Aventis, Inc. show how the doctrine of impossibility preemption can be invoked under the right circumstances. Cerveny involved the fertility drug Clomid, which was first approved by the FDA in 1967.[13] Clomid’s label has always warned that the drug should not be used by pregnant women because it could harm the fetus.[14] However, the FDA never required the manufacturer to include a warning that Clomid could cause birth defects if used prior to pregnancy.[15] In 2007, an individual[16] submitted a citizen petition asking the FDA to “order changes to the labeling and package insert for Clomid and its generics to include warnings of Clomid’s ability to cause birth defects if ingested prior to conception[.]”[17] After reviewing the research submitted by the petitioner and conducting its own survey of the relevant medical literature, the FDA denied the petition, finding that the scientific evidence did not support an association between the use of Clomid prior to pregnancy and the fetal defects identified in the petition.[18]

In 2014, a Utah family filed suit against the manufacturer of Clomid, alleging that the mother’s use of the drug prior to pregnancy had caused her son to be born with birth defects in 1992.[19] In their complaint, the plaintiffs cited numerous scientific studies linking Clomid and birth defects, all of which had been presented to the FDA in the 2007 citizen petition.[20] The manufacturer moved for summary judgment, arguing that the plaintiffs’ claim was preempted because the FDA would not have approved the warnings suggested by the plaintiffs, as evidenced by the FDA’s denial of the 2007 citizen petition.[21] In granting summary judgment, the trial court concluded that the FDA had heard and rejected the plaintiffs’ failure-to-warn theories in 2007—15 years after the plaintiffs’ injury occurred.[22] Accordingly, “[t]he FDA’s denials of Mix’s citizen petitions, standing alone, is clear evidence that the FDA would not have permitted Aventis to strengthen Clomid’s label to include warnings of the risks of birth defects if taken prior to pregnancy.”[23]

Plaintiffs argued on appeal that the denial of a citizen petition, standing alone, can never constitute clear evidence supporting preemption.[24] The plaintiffs also claimed that the FDA afforded greater weight to petitions submitted by manufacturers than by private citizens.[25] The Tenth Circuit rejected both arguments. The Tenth Circuit found “no persuasive authority” supporting a bright-line rule that the denial of a citizen petition can never amount to clear evidence under Levine.[26] In so holding, the Tenth Circuit went to great lengths to discuss and distinguish the majority of then-existing federal and state case law on citizen petitions.[27] The court also concluded that the FDA’s own regulations setting the standard for revising warning labels did not discriminate between proposed revisions submitted by manufacturers and those submitted by citizens.[28] In fact, in denying the Clomid citizen petition, the FDA stated repeatedly that it was applying the same “reasonable evidence” standard that would have applied if the proposed label change had been submitted by the manufacturer.[29] Accordingly, the FDA’s consideration and rejection of claims and data virtually identical to those submitted by the plaintiffs constituted clear evidence that the FDA would not have approved the label change that formed the basis of the plaintiff’s failure to warn claim.[30]

In a subsequent appeal following remand to address the plaintiff’s remaining claims, the plaintiffs contended that the United States Supreme Court’s recent decision in Merck Sharp & Dohme Corp. v. Albrecht contradicted the Tenth Circuit’s prior ruling and confirmed that only labeling changes sought by a manufacturer can lead to preemption under Levine.[31] The Tenth Circuit disagreed, finding that neither Albrecht nor Levine excluded a manufacturer from relying on the FDA’s denial of a citizen petition submitted by a non-manufacturer as support for a preemption defense.[32] Instead, the Tenth Circuit interpreted Albrecht as clarifying the preemption analysis “[i]n a case like Wyeth v. Levine,” where the proposed labeling change was submitted by the manufacturer itself rather than a third party.[33]

Considerations Affecting the Value of a Citizen Petition Denial

While the FDA’s denial of a citizen petition can be a powerful tool under the right circumstances, it is important to note that this is not always the case. There are many factors that affect the weight of this evidence. One obvious factor is product identity. In Cerveny, the court gave dispositive weight to the fact that the FDA had denied a citizen petition concerning the label of the same drug that was at issue in the plaintiffs’ case. However, acourt may give little to no weight to the denial of a citizen petition involving a different product, even if that product is substantially similar to the one at issue in the plaintiff’s case.[34]

Courts also consider the temporal relationship between the FDA’s decision and the plaintiff’s injury. The plaintiffs in Cerveny suffered their injuries in 1992 when their son was born with birth defects, 15 years before the FDA denied the Clomid citizen petition. Thus, the plaintiffs could not argue that the state of the scientific data had evolved since the FDA’s consideration of the petition. But other courts have held that the denial of a citizen petition is insufficient to support a preemption defense if the denial was too remote in time from the plaintiff’s injury.[35] Scientific data necessarily evolves as time progresses, especially in the pharmaceutical field, and the publication of newer studies that support the plaintiff’s legal theory could lessen or even negate the value of the prior denial.

Additionally, it is important to consider the scope of the relief sought in a citizen petition and the FDA’s reason for denying it. In affirming the trial court’s finding of preemption in Cerveny I, the Tenth Circuit emphasized that the FDA had considered and rejected the exact data cited in the plaintiffs’ complaint and had concluded that the exact warning proposed by the plaintiffs was not supported by reliable medical evidence. On the other hand, the denial of a citizen petition is not entitled to preemptive effect if the petition did not address the precise legal theories asserted in the plaintiff’s lawsuit.[36] In other words, a manufacturer cannot prove that the FDA would have rejected a warning for a specific risk if that risk was not addressed in the FDA’s response to a prior citizen petition. It is therefore critical to ensure that the plaintiff’s specific arguments regarding a drug or device’s warnings can be linked to the contentions presented in a citizen petition. Unless the FDA expressly rejected the theories asserted by the plaintiff—as the Tenth Circuit found in Cerveny I—it is unlikely that a court will ascribe any weight to the FDA’s denial.

Conclusion

Because impossibility preemption is such a highly fact-specific inquiry, it may not be an appropriate defense in every case in which the FDA has denied a citizen petition concerning the product at issue. However, the Tenth Circuit’s analyses in Cerveny I and Cerveny II demonstrate that, under the right circumstances, the FDA’s denial of a citizen petition can, standing alone, amount to “clear evidence” supporting a preemption defense under Wyeth v. Levine. And even if the factors discussed above do not align perfectly, a citizen petition denial may still be used in conjunction with other evidence to persuade the court that the “clear evidence” standard is satisfied.

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[1] 21 C.F.R. § 10.10.

[2] In re Suboxone (Buprenorphine Hydrochloride and Naloxone) Antitrust Litig., No. 13-md-2445 (MDL No. 2445), 2019 WL 4735520, at *3 (E.D. Pa. Sept. 27, 2019).

[3] Id.

[4] 21 C.F.R. § 10.3. The term “interested person” also is not limited to United States citizens. 21 C.F.R. § 10.30(a).

[5] 21 C.F.R. § 10.25(a).

[6] 21 C.F.R. § 10.25(b); see also 21 C.F.R. § 10.60 (authorizing courts to refer matters to the FDA for administrative determination).

[7] See, e.g., Stevens v. Boston Scientific Corp., 152 F. Supp. 3d 527 (S.D. W. Va. 2016) (referring medical device case to the FDA for administrative proceedings and reasoning that “[t]he FDA is in the best position to determine whether Boston Scientific’s mesh device is in compliance with the FDA’s own statutes, regulations, and directives”).

[8] 21 C.F.R. § 10.30(e)(2).

[9] Id. at (e)(2)(i)-(iv).

[10] 21 C.F.R. § 10.45(d).

[11] Mt. Olivet Cemetery Ass’n v. Salt Lake City, 164 F.3d 480, 486 (10th Cir. 1998).

[12] Wyeth v. Levine, 555 U.S. 555, 571 (2009).

[13] Cerveny v. Aventis, Inc., 155 F. Supp. 3d 1203, 1206 (D. Utah 2016).

[14] Id. at 1207.

[15] Id.

[16] Notably, the petitioner was an attorney who had been involved in litigation concerning birth defects allegedly caused by Clomid.

[17] Id. at 1208.

[18] Id. at 1208-09.

[19] Id. at 1209.

[20] Id. at 1210.

[21] Id. at 1212.

[22] Id. at 1217.

[23] Id. at 1218. The court also found dispositive the fact that the FDA had consistently approved labels for Clomid that contained affirmative rejections of the plaintiffs’ theories. Id.

[24] Cerveny v. Aventis, Inc., 855 F.3d 1091, 1101 (10th Cir. 2017) (“Cerveny I”).

[25] Id.

[26] Id. at 1105.

[27] Id. at 1103-05. This portion of the Tenth Circuit’s opinion is particularly helpful for identifying the circumstances under which a court may find that the denial of a citizen’s petition does not support preemption.

[28] Id. at 1102.

[29] Id.

[30] Id. at 1105.

[31] Cerveny v. Aventis, Inc., 783 F. App’x 804, 808 n.9 (10th Cir. 2019) (“Cerveny II”).

[32] Id.

[33] Id.

[34] See Mason v. SmithKline Beecham Corp., 596 F.3d 387, 396 (7th Cir. 2010) (finding that the FDA’s denial of a citizen petition involving Prozac was of little weight in determining whether the FDA would have rejected a proposed labeling change for Paxil).

[35] See Mason, 596 F.3d at 395 (noting that the “temporal gap is especially important in the analysis of prescription drugs because it constantly evolves as new data emerges”); Dorsett v. Sandoz, 699 F. Supp. 2d 1142, 1157 (C.D. Cal. 2010); Koho v. Forest Labs., Inc., 17 F. Supp. 3d 1109, 1117 (W.D. Wash. 2014).

[36] See Hunt v. McNeil Consumer Healthcare, 6 F. Supp. 3d 694, 701 (E.D. La. 2014) (noting that the FDA’s prior denial of a citizen petition was unpersuasive because the FDA did not reject any of the specific warnings proposed by the plaintiff).

Finis