Did the FDA act arbitrarily and capriciously when it denied respondents' applications to market flavored e-cigarette products? Specifically, did the agency unlawfully change its position on requirements for scientific evidence, comparative efficacy, and device type relative to its predecisional guidance? Additionally, was the FDA's failure to consider marketing plans a harmless error under the Administrative Procedure Act (APA)?

• The denial orders were sufficiently consistent with predecisional guidance regarding scientific evidence, comparative efficacy, and device type.
• The agency maintained broad discretion under the Family Smoking Prevention and Tobacco Control Act (TCA) to determine what constitutes "valid scientific evidence."
• Any error in failing to evaluate marketing plans was harmless because other manufacturers with materially indistinguishable plans were also denied authorization.
• The shift in enforcement focus toward non-cartridge products was based on reasonable inferences from data showing youth demand had shifted to disposable products.

• The FDA acted arbitrarily by secretly requiring randomized controlled trials or longitudinal cohort studies, contradicting guidance that no "specific studies" were required.
• The agency imposed a new requirement for specific comparisons between flavored and tobacco-flavored products that was not articulated in predecisional guidance.
• The FDA abandoned its 2020 guidance prioritizing cartridge-based products by effectively banning all flavored products regardless of device type.
• The agency's failure to review marketing plans, which it had previously described as "critical," constituted a prejudicial error requiring remand.

• The Court applied the change-in-position doctrine from *Encino Motorcars, LLC v. Navarro* and *FCC v. Fox Television Stations, Inc.*, analyzing whether the agency changed policy and provided a reasoned explanation for doing so.
• Regarding scientific evidence, the Court found no change in position because 21 U.S.C. § 387j(c)(5)(A)–(B) grants the FDA broad discretion to define "well-controlled investigations" or "valid scientific evidence."
• The Court held that requiring comparisons between flavored and tobacco-flavored products was a "natural consequence" of the TCA's comparative requirements in 21 U.S.C. § 387j(b)(1)(A) and § 387j(c)(4).
• On device type, the Court ruled that the FDA's 2020 guidance created no "safe harbor" for non-cartridge products; even if a change occurred, the FDA provided "good reasons" based on youth demand shifts.
• The Court determined the Fifth Circuit read *Calcutt v. FDIC* too broadly by suggesting APA errors are only harmless if the agency was required to take the same action regardless of the error.
• Citing *Massachusetts Trustees of Eastern Gas & Fuel Associates v. United States*, the Court noted that remand is not necessary when an agency's decision is supported by a plethora of factual findings and one unsound finding has no bearing on the result.
• The Court declined to reach arguments regarding whether notice-and-comment rulemaking was required under the APA or TCA, noting the issue lacked adequate briefing.