FDA Advertising and Promotion Enforcement Activities: Update

March 9, 2021, Covington Alert

This e-alert is part of a series of e-alerts summarizing publicly available FDA enforcement letters (i.e., warning letters and untitled letters) relating to the advertising and promotion of prescription drugs, medical devices, and biologics.

In February, the Office of Prescription Drug Promotion (OPDP) posted the following warning letters on FDA’s website[1]:

• Warning letter to AcelRx Pharmaceuticals, Inc., re: NDA 209128 DSUVIA® (sufentanil) sublingual tablet, CII MA 18, 23 (Feb. 11, 2021) (Dsuvia Warning Letter)
• Warning letter to CooperSurgical, Inc. re: NDA 018680 PARAGARD® (intrauterine copper contraceptive), MA 628 (Feb. 12, 2021) (Paragard Warning Letter)

The Dsuvia Warning Letter and Paragard Warning Letter are the first and second enforcement letters OPDP has issued this year. The Office of Product Evaluation and Quality (OPEQ) at the Center for Devices and Radiological Health (CDRH) and the Office of Medical Device and Radiological Health Operations (OMDRHO) in the Office of Regulatory Affairs (ORA) have not yet posted any enforcement letters related to advertising and promotion in 2021. FDA’s Advertising and Promotional Labeling Branch (APLB) in the Office of Compliance and Biologics Quality (OCBQ) has not posted any enforcement letters since 2018.

This alert merely summarizes the allegations contained in FDA’s letters.  It does not contain any analyses, opinions, characterizations, or conclusions by or of Covington & Burling LLP.  As a result, the information presented herein does not necessarily reflect the views of Covington & Burling LLP or any of its clients.

Dsuvia Warning Letter (February 2021)

OPDP’s warning letter to AcelRx Pharmaceuticals, Inc., states that an “SDS Banner Ad”[2] (banner) and tabletop display (display) misbrand Dsuvia, an oral opioid. OPDP alleges that the promotional materials, which were submitted under cover of Form FDA 2253, make false or misleading claims and representations about the drug’s risks and efficacy. 

OPDP alleges that “[t]hese violations are especially concerning from a public health perspective given the importance of the administration instructions intended to protect from the serious and potentially life-threatening risks that may result from the accidental exposure to misplaced tablets of Dsuvia or overdosage with Dsuvia.” Because accidental ingestion of oral opioids like Dsuvia may lead to fatal respiratory depression, Dsuvia is subject to a Risk Evaluation and Mitigation Strategy (REMS) that restricts its use to certain healthcare settings. Additionally, Dsuvia’s labeling includes limitations on its use and detailed administration instructions. 

False or Misleading Risk and Benefit Presentations

OPDP alleges that the promotional materials misbrand Dsuvia by failing to adequately present the drug’s risks and benefits. Both the banner and the display include the claim “Tongue and Done” (emphasis original). OPDP states that such presentations “imply that the administration of Dsuvia consists of a simple, one-step process, when this is not the case.” According to OPDP, Dsuvia’s Prescribing Information (PI) includes “numerous administration steps,” which “reflect the complexity of use of Dsuvia.” OPDP states further that these presentations “oversimplif[y] the administration process” and “are particularly concerning considering a REMS program was required for Dsuvia to ensure that the benefits of the drug outweigh the risk of respiratory depression that can result from accidental exposure.”

Additionally, OPDP alleges that the banner does not communicate important risk information. For example, OPDP states that the banner includes claims about minimum and average redosing intervals while omitting material information from the PI about the maximum daily dosage. OPDP further alleges that the banner makes representations about the use of Dsuvia “for acute pain” but “fails to adequately convey material information regarding Dsuvia’s limitations of use.” 

OPDP acknowledges that the banner states that Dsuvia “is for use only in a certified medically supervised healthcare setting” and provides the drug’s full indication, including the limitations of use.  However, OPDP states that “unlike the benefit claims in the banner, which utilized a color background and large font, the full indication with the limitations of use are intermingled with risk information in a paragraph format in a much smaller font size and a plain white background, and are accessible only if viewers ‘scroll’ down the banner.” Similarly, OPDP alleges that both the banner and the display “fail to present information relating to the Boxed Warning, Contraindications, Warnings and Precautions, and Adverse Reactions for Dsuvia with a prominence and readability reasonably comparable with the presentation of information relating to the benefits of Dsuvia.”

Paragard Warning Letter (February 2021)

OPDP’s warning letter to CooperSurgical, Inc. (CSI), alleges that a direct-to-consumer (DTC) video misbrands the intrauterine contraceptive by presenting efficacy claims without communicating any risk information. The video, titled “Paragard: Family Planning During The Pandemic,” was presented on WBTS’s The Hub Today[3] and resulted in a complaint to FDA’s Bad Ad Program. OPDP also alleges that CSI did not submit the video to FDA at the time of initial dissemination or publication. 

The warning letter notes that OPDP issued an untitled letter to CSI on July 25, 2019, regarding a DTC television advertisement that “omitted important risk information.” OPDP states further that “CSI appears to be promoting Paragard without presenting the serious risks of the drug in a truthful and non-misleading manner, despite concerns previously expressed by OPDP.”

False or Misleading Risk Presentation

OPDP alleges that the video, which features a physician being interviewed, “includes claims and representations about the use and/or benefits of Paragard” but “fails to communicate any risk information about the product.”  The video opens with the voiceover statement, “This segment is sponsored by Paragard,” while simultaneously presenting the logo and proprietary and established names for Paragard along with the Paragard URL. The following superimposed text is included throughout the video: “FAMILY PLANNING DURING THE PANDEMIC PARAGARD’S NON-HORMONAL OPTION” (bolded emphasis in original).  OPDP acknowledges that viewers are directed to the Paragard website for further information but states that “this does not mitigate the complete omission of risk information from the video.”

OPDP states further that the “misleading presentation is particularly concerning from a public health perspective due to the serious and potentially life-threatening risks associated with the drug.”  Paragard’s PI includes warnings and precautions regarding ectopic pregnancy, risks with intrauterine pregnancy, and sepsis, among others.

Failure to Submit Under Form FDA-2253

OPDP also alleges that CSI did not submit the promotional material to OPDP as required under federal regulations. 21 C.F.R. § 314.81(b)(3)(i) requires the submission of “labeling or advertising devised for promotion of the drug product at the time of initial dissemination of the labeling and at the time of initial publication of the advertisement.” Each submission must be accompanied by a completed transmittal Form FDA-2253 (Transmittal of Advertisements and Promotional Labeling for Drugs for Human Use) and a copy of the product’s current professional labeling.

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