substantial evidence or “substantial clinical experience” to support them.This dovetails with the caution we issued last year:that substantial evidence was the “watchword” for companies trying to avoid running afoul of DDMAC.Interestingly, these five letters target a particular therapeutic class – ADHD products – and for claims made in a range of material, from sales aids to a video featuring Ty Pennington posted on youtube.com.Specifically, DDMAC sent Warning Letters to the following companies for promotional claims on the following drugs:(1) Johnson & Johnson, Concerta® extended-related tablets; (2) Novartis Pharmaceuticals Corporation, Focalin XR® extended-related capsules; (3) Shire Development Inc., Adderall XR® capsules; (4) Eli Lilly & Corporation, Strattera®; and (5) Mallinckrodt Inc., Methylin® chewable tablets and oral solution (generic Ritalin).The alleged FDA violations are broken down as follows:DrugAlleged Violations Adderall XR® capsules (Shire)Drug was misbranded under 21 U.S.C. §§ 352(a), 352(n), and 321(n) by promotional claims included on a webpage anda video posted on YouTube.com that:(1) Overstated its efficacy;(2) Broadened its indication; (3) Omitted risk information; and(4) Was not submitting properly pursuant to 21 C.F.R. § 314.81(b)(3)(k).Concerta® extended-related tablets (Johnson & Johnson)Drug was misbranded under 21 U.S.C. §§ 352(a), 352(n), and 321(n) by promotional claims included on convention panels and a webpage that:(1) Overstated its efficacy; and (2) Omitted facts.

as aimed at marketing Stratus to deliver Kenalog rather than saline.” With respect to design, the evidence reflected that the size of Stratus’s pores had been calibrated to accommodate Kenalog’s specific viscosity – meaning that Stratus did not even work to deliver saline, which is much less viscous and would rapidly seep out. With respect to sales, the government introduced evidence that Stratus “was promoted with a sales strategy devised to get physicians to associate Stratus with Kenalog and consider using it for drug delivery.” For example, sales trainees were not taught or given marketing materials for Stratus describing benefits of use with saline, and instead focused on the off-label uses related to Kenalog.After a jury trial, Acclarent’s former CEO and former vice president of sales were convicted of 10 misdemeanor counts for distributing an adulterated and misbranded device by failing to submit a required premarket notification under 21 U.S.C. §§ 331(a), 333(a)(1), 351(f) and 352(o). The defendants challenged their convictions on appeal, arguing (among other things) that the convictions violated the First and Fifth Amendments.First Amendment does not preclude use of speech as evidence of intended useThe defendants challenged the government’s use of their promotional speech as evidence to support a misbranding violation, arguing that such use effectively criminalizes the speech itself in violation of the First Amendment.In 1993, the Supreme Court ruled in Wisconsin v. Mitchell that the First Amendment does not generally apply to the “evidentiary use of speech to establish the elements of a crime or to prove motive or intent.” However, the Facteau defendants relied on a 2012 Second Circuit ruling (US v. Caronia), where the court held that a misbranding conviction violated the First Amendment. In that case, “the prosecution repeatedly argued that [the defendant] engaged in criminal conduct by promoting and marketing the off-label use of an FDA-approved drug.” In oth

ritical hardware of the device is manufactured by contracted suppliers.FDA determined RightEye had not demonstrated any plans to implement specific corrective actions.Additional ConsiderationsThe Warning Letter indicated that a failure to address the noted violations could have serious and varying consequences. Failure to adequately address the notice could result in regulatory action, including seizure, injunction and civil monetary penalties. Non-compliance with the FDCA could impact the award of federal contracts and grant of Certificates to Foreign Governments. FDA’s determination of Quality System violations related to Class III device premarket approval applications could delay the approval of such devices.FOOTNOTES Untitled letter available here: https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/righteye-llc-643192-12202022. K181771 Indications for Use available here: https://www.accessdata.fda.gov/cdrh_docs/pdf18/K181771.pdf.See 21 U.S.C. § 352(o), 21 U.S.C. § 360(k), 21 CFR 807.81(a)(3)(ii).See 21 U.S.C. § 352(t)(2), 21 U.S.C. § 360i, 21 CFR 830.See 21 U.S.C. § 351(f)(1)(B).See 21 CFR 820.

approval or clearance of the product or its new use; however, for device companies this has come in the form of non-binding guidance that lacks a formal anchor in the statutory language. The inclusion of the legislation previously known as the PIE Act in the omnibus spending bill formally establishes a statutory pathway built on FDA’s 2018 final guidance for both drug and medical device companies to engage in pre-market communications about health care economic information with payors, formulary committees, and similar entities.Under the title “Facilitating Exchange of Product Information Prior to Approval,” Section 3630 of the omnibus spending bill first expands the FDCA’s existing language on health care economic information to make it applicable to both drugs and devices. Previously, this section of the statute only covered drugs and, on enactment, will be updated as so noted in bold below with the following references to the US Code:Section 502(a) of the Food, Drug & Cosmetic Act (21 U.S.C. §352) – Misbranded drugs and devicesA drug or device shall be deemed to be misbranded–(a) False or misleading label(1) If its labeling is false or misleading in any particular. Health care economic information provided to a payor, formulary committee, or other similar entity with knowledge and expertise in the area of health care economic analysis, carrying out its responsibilities for the selection of drugs or devices for coverage or reimbursement, shall not be considered to be false or misleading under this paragraph if the health care economic information relates to an indication approved under section 355 of this title or under section 262(a) of title 42section 505, 510(k), 513(f)(2), or 515 of this Act or section 351 of the Public Health Service Act for such drug or device, is based on competent and reliable scientific evidence, and includes, where applicable, a conspicuous and prominent statement describing any material differences between the health care economic information and the

at 38322 (“FDA would refuse to approve an application for a nonprescription drug product with an ACNU if FDA has determined that the applicant failed to demonstrate that labeling is insufficient to ensure consumers’ appropriate self-selection and/or appropriate actual use, of the nonprescription drug product without the supervision of a healthcare practitioner ….”); see also id. at 38324.28See 21 U.S.C. § 352(f).2987 Fed. Reg. at 38324.

False or misleading advertising of a drug is by definition a form of misbranding under the Federal Food, Drug, and Cosmetic Act. 21 U.S.C. § 352(q)(1). Truthful, non-misleading off-label promotion can also be proof of misbranding, the FDA has argued, if it demonstrates that a drug is being sold for an unapproved intended use – another form of statutory misbranding.

The factual basis for that liability is set forth in an Information that charges two separate misdemeanor FDCA violations.Promotion of Juxtapid for Unapproved Uses. The Information charges that Aegerion misbranded Juxtapid by promoting it for uses for which the drug’s label lacked adequate directions for use, in violation of 21 U.S.C. § 352(f). The Information asserted that Aegerion: sought and received Orphan approval for Juxtapid because it was intended to treat HoFH, a malady expected to occur in approximately one in 1 million patients; nevertheless trained sales representatives to more broadly promote Juxtapid by intentionally failing to define HoFH, discouraging the use of genetic testing and established diagnostic criteria to identify HoFH patients, misleading prescribers regarding the clinical profiles of patients in the Juxtapid pivotal trial, and identifying patients whose clinical profiles did not meet established diagnostic criteria for HoFH; trained sales representatives to tell prescribers and patients that using Juxtapid would prevent “impending” heart attacks or strokes, although Aegerion did not have data showing Juxtapid had a meaningful effect on cardiovascular mortality or morbidity;3 and promoted Juxtapid for use as monotherapy, despite the drug’s indication as adjunctive therapy.Noncompliance Wi

21 U.S.C. § 331(k) – Prohibiting any act with respect to a regulated product after shipment in interstate commerce that results in the product being adulterated or misbranded.21 U.S.C. § 352(f)(1) – Deeming a drug or device misbranded if the labeling does not bear adequate directions for its intended use.And to a lesser extent, 21 U.S.C. § 352(a) – Deeming a drug or device misbranded if the labeling is false or misleading.These statutory sections have been in force since the FDCA was first enacted in 1938 and are common references throughout the history of FDA’s regulation of off-label communication.

The increased reserve of approximately $28 million was recorded in the first quarter of 2016.Under the terms of the preliminary agreement in principle with the DOJ, the Company would plead guilty to two misdemeanor misbranding violations of the Food, Drug and Cosmetic Act. One count would be based on the Company’s alleged marketing of JUXTAPID with inadequate directions for use (21 U.S.C. §§ 352(f)), and the second count would involve an alleged failure to comply with a requirement of the JUXTAPID Risk Evaluation and Mitigation Strategies (“REMS”) program (21 U.S.C. §§ 352(y)). The Company would separately enter into a five-year deferred prosecution agreement with regard to charges that the Company violated the Health Insurance Portability and Accountability Act and engaged in obstruction of justice relating to the REMS program.

The evidence was insufficient to support a conviction on these counts of the indictment and the conviction was reversed.United States v. Milstein, 401 F.3d 53 (2d Cir. 2005)The defendant was charged with violating 21 U.S.C. § 352 (misbranding drugs). The indictment alleged that the offense was committed by repackaging the drugs.