FDA Advertising and Promotion Enforcement Activities: Update

FDA Advertising and Promotion Enforcement Activities: Update

August 18, 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 July, the Office of Prescription Drug Promotion (OPDP) posted the following untitled letter on FDA’s website:

• Untitled letter to Amgen, Inc. re: BLA 125031 NEULASTA® (pegfilgrastim) injection, for subcutaneous use MA 1706 (July 7, 2021) (Neulasta Untitled Letter)

The Office of Medical Product Evaluation and Quality (OPEQ) at the Center for Devices and Radiological Health (CDRH) posted the following warning letters in June and July, the former of which was issued in May and the latter of which was cosigned by the Office of Medical Device and Radiological Health Operations (OMDRHO) in the Office of Regulatory Affairs (ORA):

• Warning letter to Nikkiso Medical America, Inc. re: Nikkiso DBB-06® (May 7, 2021) (DBB-06 Warning Letter)
• Warning letter to Innova Medical Group, Inc. re: SARS-CoV-2 Antigen Rapid Qualitative Test (June 10, 2021) (SARS-CoV-2 Antigen Rapid Qualitative Test Warning Letter)

OPEQ also posted 13 warning letters regarding the distribution and promotion of face masks, many of which were initially issued earlier this year.[1] Although this alert does not typically cover letters alleging distribution of devices without marketing approval, clearance, or authorization from FDA, these letters also allege that the labeling creates an impression of official FDA approval, clearance, or authorization.

The Neulasta Untitled Letter is the fourth enforcement letter OPDP has issued this year. OPEQ and OMDRHO previously had not issued any enforcement letters related to advertising and promotion of devices since January 2020. 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.

Office of Prescription Drug Promotion (OPDP)

Neulasta Untitled Letter (July 2021)

OPDP’s untitled letter to Amgen, Inc. (Amgen) states that a professional animated banner misbrands Neulasta by making false or misleading claims and representations about the drug’s benefit. Neulasta is indicated to decrease the incidence of infection, as manifested by febrile neutropenia (FN), in patients with non-myeloid malignancies receiving certain myelosuppressive anti-cancer drugs. It can be delivered via the Onpro® on-body injector (OBI) or via prefilled syringe (PFS). FDA alleges that the banner could cause healthcare providers to conclude that Neulasta delivered through the OBI is more effective than Neulasta delivered via PFS or that it is more effective than biosimilar pegfilgrastim products. The agency states that the FDA Bad Ad Program also received complaints regarding promotional communications with claims and presentations similar to those described in the untitled letter.

False or Misleading Benefit Presentation

OPDP alleges that the banner creates a misleading impression by stating that there is a “statistically significant higher risk” of FN when pegfilgrastim is administered through a PFS compared to the OBI. The banner includes the following claims and presentations on frames one and two (emphasis original):

• In a Real-World Study with nearly 11,000 patients Pegfilgrastim PFS resulted in a significantly higher risk of FN vs. Onpro®”
• Across all cycles of chemotherapy, the incidence of FN associated with prefilled syringe (PFS) was 1.7% (n = 455) vs 1.3% (n = 126) for Neulasta® Onpro®” (frame 1)
• A large presentation of an upward arrow containing the claim, “31%* *p = 0.01”
• With PFS, FN incidence increased by 31% vs Onpro®”

OPDP alleges that “multiple limitations of the cited study preclude the drawing of such conclusions regarding the comparative risk of [FN] in patients taking pegfilgrastim depending on delivery method.” Specifically, OPDP states that the study used an unvalidated algorithm to identify participants and that it was not designed to ensure that the PFS and OBI patient populations were adequately balanced or controlled for potential bias. OPDP acknowledges that frames seven and eight of the banner address two limitations of the study, but it concludes that these frames “[do] not mitigate the misleading claims and presentations in the banner.”

OPDP alleges that “[t]he above misleading claims and presentations are particularly concerning from a public health perspective because they could undermine confidence not just in Neulasta delivered via PFS but also in FDA-licensed biosimilar pegfilgrastim products, which are only delivered via PFS.” OPDP states that the “prominent display” of “Pegfilgrastim PFS” as the comparator arm versus “Neulasta Onpro” and “Onpro” “could result in healthcare providers failing to understand that Amgen’s Neulasta was used in both arms of the study.”[2] Moreover, OPDP states that providers might conclude that a biosimilar delivered via PFS is not as effective as Neulasta Onpro. OPDP alleges that both of these conclusions are unsupported by the data due to the study defects discussed above.

CDRH Office of Product Evaluation and Quality (OPEQ) and ORA Office of Medical Device and Radiological Health Operations (OMDRHO)

DBB-06 Warning Letter (May 2021)

In its letter to Nikkiso Medical America, Inc. (Nikkiso), OPEQ alleges that the DBB-06 is adulterated and misbranded because the company’s marketing materials promote the device beyond the cleared indications for use. OPEQ states that Nikkiso’s marketing materials suggest that the device is intended for dialysis with a physiological closed loop controller (PCLC) system, even though the PCLC function was not cleared under either of the device’s 510(k) clearances. OPEQ provides the following examples as “evidence that the device is intended for dialysis with a PCLC system”:

• A statement in the online version of Nikkiso’s product brochure stating that the DBB-06 Haemo-Master Blood Volume Monitor (BVM) uses “adaptive feedback” to regulate the “blood volume trend”
• A statement on the website that “[t]he unique adaptive feedback feature of the BVM allows for automatic changes of fluid removal to achieve desired outcomes”

OPEQ states “[t]he introduction of a PCLC system is considered a change or modification in the device that could significantly affect the safety or effectiveness of the device, and therefore, requires clearance or approval.”

OPEQ also notes that “[t]his is not the first time that FDA has communicated with your firm that the PCLC function was not cleared under either K091978 or K152938 for the device.” OPEQ states that earlier communications illustrate that “the firm understands FDA’s position on the regulatory status of the DBB-06 device with the PCLC function.”

SARS-CoV-2 Antigen Rapid Qualitative Test (June 2021)

In its letter to Innova Medical Group, Inc. (Innova), OPEQ and OMDRHO allege that the 25T Configuration and 7T Configuration of the SARS-CoV-2 Antigen Rapid Qualitative Test are misbranded because their labeling is false or misleading.[3] FDA states that the relative sensitivity, relative specificity, and accuracy cited in the 25T Configuration labeling “appear[] unsupported by any clinical data,” including data submitted to FDA in Innova’s Emergency Use Authorization (EUA) request and in published reports of clinical studies. FDA also states that the positive percent agreement (PPA) cited in the 7T Configuration “does not appear to align with the PPA observed in the phase 3b prospective clinical study conducted.” Because the performance estimates reported “do not accurately reflect the performance estimates observed during the clinical studies,” FDA concludes that they are “false or misleading.”

The warning letter also notes that the clinical study data submitted in Innova’s EUA request “was identical to data previously provided by other manufacturers in their separate EUA requests.” FDA states that “[t]he data reliability and accuracy issues noted herein raise significant concerns that the performance of the SARS-CoV-2 Antigen Rapid Qualitative Test has not been adequately established, and that the products distributed by Innova without FDA approval, clearance, or authorization could present a serious risk to the public health.”

Warning Letters Related to Face Masks

OPEQ published 13 letters with similar allegations regarding the distribution and labeling of face masks. In addition to alleging that these products are adulterated and misbranded because they are being distributed “without marketing approval, clearance, or authorization from FDA,” OPEQ also alleges that they are further misbranded because their labeling suggests that they are in fact FDA approved, cleared, or authorized. Across these letters, OPEQ cites several ways in which the labeling can create a misleading impression. These include:

• Using the FDA logo without authorization
• Displaying a “Certificate of Registration” next to images of and information about the product
• Stating that the product is “FDA Approved”
• Referencing FDA “certification”

In each letter, OPEQ states that “[s]uch representations are especially concerning from a public health perspective because consumers rely on information provided by sellers to determine whether to purchase a device.”[4]

If you have any questions concerning the material discussed in this client alert, please contact the members of our Food, Drugs, and Devices practice.

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