January 31, 2022

2021 Year in Review: OPDP Enforcement Actions Involving Prescription and Biological Products

The Food and Drug Administration’s Office of Prescription Drug Promotion (OPDP) issued a total of six letters in 2021 — four Untitled Letters and two Warning Letters — to pharmaceutical or biologics companies for promotional materials that allegedly misbranded prescription drug or biologics products. The two Warning Letters issued in 2021 addressed prescription drug promotion. Two of the Untitled Letters also addressed prescription drug promotion, while the other two letters addressed biologic product promotion.

OPDP also sent six letters in 2020; however, the majority that year (four) were Warning Letters, with only two being Untitled Letters. Both Warning and Untitled letters are made public on FDA’s website. Warning Letters are issued for violations of regulatory significance that may lead to enforcement action if not promptly and adequately corrected, whereas Untitled Letters cite violations that do not rise to the threshold of regulatory significance warranting a Warning Letter.1 Untitled Letters serve as the initial notification that FDA has taken notice of a violation and allow the company to come into compliance without further FDA regulatory action. Historically, OPDP has relied more heavily on Untitled Letters. 2020 was an outlier year with four Warning Letters versus two Untitled Letters, but 2021 signified a return to normalcy, as the agency issued twice as many Untitled Letters as Warning Letters.

Overall, the 2020 and 2021 numbers represent a decrease in letters compared to early years. For instance, in 2019 OPDP issued a total of ten letters, including three Warning Letters and seven Untitled Letters. The following summary provides some of the key takeaways and lessons learned from these letters, as well as highlights of a recent OPDP research initiative announced earlier in 2021 related to medical conference exhibit halls.

Key Takeaways

  • Three of the letters involved promotional materials that were submitted to FDA’s Bad Ad Program. The Bad Ad Program is an outreach program run by OPDP that is designed to help healthcare providers recognize when prescription drug promotion is false or misleading. The program allows healthcare providers and others to submit complaints to OPDP regarding potential false or misleading drug promotion.
    • Companies should be aware of the Bad Ad Program and ensure all employees are trained to provide only truthful, balanced and accurately communicated promotions.
    • Promotional materials should also be reviewed and approved through the internal promotional review committee process (some companies call the process MLR or LMR for the medical, legal and regulatory roles involved) to ensure truthfulness, accuracy and fair balance.
  • One letter included violative claims regarding internet-sponsored links that discussed the company’s products.
    • Companies should be aware that, even if a platform includes certain space or character limitations (e.g., a sponsored link), OPDP will still expect compliance with the promotional requirements.
  • Two of the letters included violative claims on banner ads. The letters signify the agency’s continued monitoring and surveillance of activities conducted on the internet.
    • Banner ads typically are associated with space and character limitations. Even though there may be space and character limitations, OPDP will expect the presentation of risks and benefits information to be included in a comparable format.
    • Companies should also ensure that claims presented do not create a false or misleading impression regarding the benefits or risks associated with the product.
  • OPDP continues to focus its enforcement efforts on high-risk drug or biological products, such as opioids or products under a Risk Evaluation and Mitigation Strategy (REMS).
    • 2021 was no different with letters directed towards marketing of at least one opioid product also subject to a REMS, a product used in a vulnerable pediatric patient population that may cause serious adverse reactions, and a product associated with serious and potentially life-threatening risks.
  • Three of the letters cited companies for failing to submit the promotional materials to OPDP under cover of Form FDA-2253 at the time of initial dissemination as required by 21 CFR 314.81(b)(3)(i).2
    • While we do not think this will be the sole reason for a Warning or Untitled Letter, OPDP will certainly include it in a letter that cites other regulatory issues.
  • Two of the letters discussed direct-to-consumer videos, signifying the agency’s monitoring and scrutiny of advertisements directed at consumers, an audience considered more vulnerable compared to healthcare providers.
    • Notably, one of the videos featured an interview of a company spokesperson describing her experience with the product.
      • Although the company included a disclaimer that appeared on the screen that treatment results may vary, OPDP determined that this disclaimer did not mitigate the misleading representation created by a description of the spokesperson’s own personal experience, which was not adequately supported by the clinical trial data in the Prescribing Information for the product.
    • The other video featured a physician being interviewed and included claims and representations about the use and/or benefits of the product. The video, however, failed to communicate any risk information about the product.
      • OPDP noted that viewers are referred to the product website for further information about the product; however, this does not mitigate the complete omission of risk information from the video about the drug’s safety.
  • The total number of letters issued in 2021 is consistent with the trend of fewer enforcement letters issued by OPDP over the course of the past 10-15 years. For instance, in 2010, OPDP issued over 50 letters.
    • The continued decrease in letters in 2021 may signify that FDA is diverting resources to other initiatives and efforts during the ongoing COVID-19 pandemic.
    • It may also be a result of OPDP adapting to promotional activities taking place in a virtual environment instead of at medical conferences and during in-person detailing.
    • The decline in letters may also be a result of First Amendment challenges and the agency’s attempts to strike a balance between First Amendment rights and regulating off-label or misleading product communications.

OPDP Research Initiative Focused on Medical Conference Exhibit Halls

In 2021, FDA also announced that OPDP would initiate a study on pharmaceutical company interactions with health care providers during medical conference exhibit halls at promotional booths and, more specifically, how elements of pharmaceutical booths in medical conference exhibit halls impact attendee perceptions of the drugs that are promoted.3 The impetus behind the study is to provide insight into OPDP’s policymaking in regard to

publication of the advertisement for a prescription drug product. Mailing pieces and labeling that are designed to contain samples of a drug product are required to be complete, except the sample of the drug product may be omitted. Each submission is required to be accompanied by a completed transmittal Form FDA–2253 (Transmittal of Advertisements and Promotional Labeling for Drugs for Human Use) and is required to include a copy of the product's current professional labeling.

promotional content at medical conferences. In addition, as with other prescription drug promotional materials, pharmaceutical companies may voluntarily submit draft versions of their exhibit panels and exhibit materials for FDA review. The study is meant to help inform FDA in its review of these proposed promotional materials. According to the July 2021 Federal Register Notice announcing the study, recent compliance letters issued by OPDP described booth or panel displays that communicated misleading information regarding drug efficacy and safety, provided insufficient information on drug risks, and omitted “material facts” about the promoted drug. A primary reason that physicians and other medical professionals report visiting specific exhibitors at conferences is to obtain product information, and it is important that the information provided by exhibitors to HCPs regarding the risks and efficacy of prescription medications not be false or misleading. Thus, investigating the impact of pharmaceutical booth promotions among medical conference attendees has valuable practical implications for the public health.

The Federal Register Notice also provides that perceived credibility of the representative at the booth and the availability of information on data limitations could influence an attendee’s perceptions of the risks and benefits of the drug product and prescribing decisions. For example, whether the booth representative has a medical/science background or business background may shape perceptions of credibility and seeing the disclosure of data limitations may improve the material’s credibility and appeal by signifying more transparency on the sponsor’s part. Both of these elements will be evaluated during the study.

Conclusion

In 2022, we expect OPDP to continue its focus on high-risk products and promotional activities that extend to a wider audience, such as large-scale medical conferences, social media and internet promotion. While OPDP letters may be on the decline, OPDP is still monitoring and surveilling prescription drug and biologics promotional activities. Therefore, a company’s promotional review process is key to ensuring the success of company marketing activities, especially for products in a high-risk category or advertisements or promotional materials directed to consumers. Companies should also train employees, particularly members of marketing teams and medical affairs personnel attending congresses or other conferences, on expectations and requirements.

Further, Warning and Untitled Letters could lead to scrutiny from other government entities, such as the Department of Justice or Office of Inspector General. Compliance with promotional requirements can also minimize potential risks associated with qui tam whistleblower complaints or other potential litigation issues associated with product promotion. Therefore, companies should be aware of and monitor FDA promotional trends and requirements and ensure promotional activities are compliant.

For questions or additional information, please contact Carolina Wirth or Genevieve Razick.

  1. FDA, Advisory Action Letters (last accessed Jan. 19, 2022), available at Advisory Action Letters | FDA.
  2. In accordance with 21 C.F.R. § 314.81(b)(3)(i), The applicant shall submit specimens of mailing pieces and any other 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 for a prescription drug product. Mailing pieces and labeling that are designed to contain samples of a drug product are required to be complete, except the sample of the drug product may be omitted. Each submission is required to be accompanied by a completed transmittal Form FDA-2253 (Transmittal of Advertisements and Promotional Labeling for Drugs for Human Use) and is required to include a copy of the product's current professional labeling.
  3. 86 Fed. Reg. 132, 37160 (July 14, 2021), available at 2021-14936.pdf (govinfo.gov).
The Faegre Baker Daniels website uses cookies to make your browsing experience as useful as possible. In order to have the full site experience, keep cookies enabled on your web browser. By browsing our site with cookies enabled, you are agreeing to their use. Review Faegre Baker Daniels' cookies information for more details.