Digital drug promotion: Marvel or minefield of regulatory risk?

Today, healthcare professionals (HCPs) and patients expect to receive information about pharmaceutical products consistent with how they receive other consumer messaging: digitally, quickly, thoroughly and easily. And U.S. pharmaceutical companies have taken note. They have made the most of social media—using it for end-to-end marketing and advertising strategies that capture consumers’ attention while delivering key messages about treatments for serious medical conditions. In the U.S., pharma companies can also reach consumers and HCPs through TV advertisements, online ads, emails, print ads and more.

But with every new advertising channel comes new risks to weigh. While these mediums have helped pharma products reach more consumers, they have also attracted more scrutiny from the U.S. Food and Drug Administration (FDA) for inappropriately promoting drugs and medical devices. In recent years, the FDA has intensified its focus on potential promotional violations occurring on social media. When the COVID-19 pandemic limited in-person oversight, the FDA strengthened its digital capabilities for this work, and it appears these oversight activities are here to stay for now.

To help pharma companies avoid unnecessary scrutiny, this article proposes three strategies for avoiding enforcement actions by the FDA. Our recommendations are the result of a ZS analysis of over 10,000 warning letters sent out by the FDA, in which we sought to gain a better understanding of the specific advertising channels, practices and product claims the agency has been targeting.

According to our analysis, between 2019 and 2022, the FDA greatly increased the number of warning letters it sent to pharma companies for inappropriate advertising, marketing or misbranding of drugs or medical devices. In fact, warning letters issued by the FDA for content published on social media platforms such as Facebook, Twitter, YouTube and LinkedIn more than doubled between 2019 and 2021. In parallel, the number of letters issued for Current Good Manufacturing Practice (CGMP) violations have decreased, indicating a shift in focus from facility inspections to online platform monitoring.

The majority of warning letters issued for social media content between 2020 and 2021 were related to unapproved or misbranded treatments for COVID-19, as well as unsubstantiated claims based on personal experiences of a user or consumer. 

Pharmaceutical companies have significantly increased the volume of content posted on social media platforms in recent years. One of the primary reasons for this is the ease of access coupled with low cost. Importantly, there’s limited concrete regulation specific to the use of social media by pharmaceutical companies. Typical content varies but can include short video snippets no longer than a few seconds, to five-minute-long videos touting benefits of a drug. While these ads may have striking visuals, FDA warning letters often cite failure to include adequate risk and benefit information. Social media content is often not in compliance with the requirements of the Federal Food, Drug, and Cosmetic Act in the following ways:

• Misleading posts. Posts give a misleading impression about the scope of the FDA-approved indications or omit important risk information, especially for drugs with a boxed warning.
• Posts use individual patient experiences to make general statements. For instance, before-and-after images of patients going from 10 lesions to no lesions after using a particular drug is not adequate evidence to establish that all patients treated with the drug will achieve similar results.
• Paid spokespersons are not balancing claims or representation of benefits with risk data. For example, a physician spokesperson may claim in a video that adverse reactions only last for one or two treatments, while data indicates the adverse reaction may last for weeks beyond the second treatment.
• Distracting elements in ads. Ads present a large amount of information using fast-paced visuals, distracting elements and frequent scene changes. This includes listing the common side effects alongside before-and-after images of patients and physician spokesperson’s statements.

TV advertisements were the earliest video-based direct-to-consumer communication. They have been an integral part of the drug marketing and advertising mix since 1983 when Boots aired the first broadcast television commercial in the U.S. for a prescription drug. However, the ads caught the attention of the FDA when reports of misrepresentation and miscommunications emerged. Over the years the FDA has attempted to ensure pharma and device companies balanced risk and benefit information in advertisements to avoid misleading statements.

In 2010, the FDA launched the Bad Ad Program to help HCPs, pharmacists, pharmacy technicians and trainees recognize potentially false or misleading prescription drug promotions. The program’s goal is to raise awareness about potentially false or misleading claims, while providing an easy way to report noncompliant content to the FDA. In pursuit of this goal, the FDA issues untitled letters, which are used for violations that may not meet the threshold of regulatory significance for a warning letter, to pharmaceutical companies for the following issues:

• Failure to make risk information prominent. Examples of violations include ads where risk information is displayed in text-only format in a small font at the bottom of the TV screen while benefits are touted more prominently in large text or in voiceovers.
• Physician spokespersons make unsupported claims. For instance, a spokesperson may claim superior efficacy of a drug compared to alternative treatments using phrases such as “drug of choice” or “superior efficacy” when this claim has not been demonstrated clinically.
• Misleading age information. Ads may present misleading information about the age group a drug is approved for, which could create a false impression about its FDA-approved indication.
• Failure to submit Form FDA 2253. The FDA requires companies to submit Form FDA 2253 to begin the regulatory review process for promotional content.
• Ads overstate ease of use of drug or device. Some ads are claiming a device or drug is “easy to use,” when preparation and administration actually involves multiple steps that could make it difficult for patients to use. 

Email is now a primary method of correspondence in healthcare. When promotional content is shared via email from pharma companies to HCPs, it should contain an introduction to the drug or medical device, followed by the corresponding medical analysis, including benefits and risks. Some violations, as noted by the FDA, include:

• Inappropriate placement of risk information. The prominence and readability of benefits are not well balanced with the presentation of risk information. Often, risk information is relegated to the bottom of the email after the signature block.
• Inadequate focus on boxed warning. Boxed warnings are not prominently noted in the email, which may suggest the drug is safer than has been clinically demonstrated.
• Misleading indication information. For example, an email may state the drug can be used to treat all the HCP’s patients with a particular condition in cases where it has only been FDA approved for a specific age group.

Without question, drug and device manufacturers can reach wide audiences with their own websites. But this promotional venue is starting to open manufacturers up to regulatory scrutiny. The FDA has flagged the following issues recently:

• Misplaced risk information. The omission of risk information such as boxed warnings, or overly prominent placement of benefit information, may lead regulators to issue untitled letters.
  
• Misleading safety and efficacy information about an investigational drug. An investigational drug cannot be promoted as safe before it is approved for commercial distribution.
• Claims unsubstantiated by clinical evidence. Websites often overstate the efficacy of drugs without adequate clinical support. For example, a website may state that a drug has been proven effective for faster weight loss, without stating it’s only indicated as an adjunct to a reduced-calorie diet and increased physical activity.
• Promotional content overstating a drug’s benefits. Promotional content about opioids sometimes describes benefits and abuse-deterrent properties without accurately warning about the risks of overuse and addiction—particularly for drugs with boxed warnings. For example, promotional content may not specify that abuse-deterrent properties are established only for certain routes of administration. Additionally, some content may omit the fact that if the drug is administered via unapproved routes, overuse and abuse may still occur. Even when abuse-deterrent properties exist, opioid abuse may only be rendered more difficult, not impossible.

Based on our analysis of FDA warning letters and untitled letters, pharma companies should take note of some of the following best practices when planning new promotional content:

• Companies cannot continue to gloss over the risks of their products and showcase only the benefits. They must put equal emphasis on the risks and benefits of their products.
• Claims about benefits should be grounded in scientific data and evidence to avoid overstating the efficacy or safety of the product. This enables well-informed discussions and decision-making for patients and HCPs alike.
• Companies should invest in training personnel involved in promotional activities. Employees should avoid inadvertently promoting investigational uses of drugs and false claims by spokespersons, while balancing the sharing of safety and risk information.

The FDA’s expectations and actions are rooted in protecting the patient’s interests and enabling improved patient outcomes. It’s critical pharmaceutical companies strike the right balance between meeting the FDA’s expectations and leveraging technology to increase their outreach to patients. However, promotional content review and approval is becoming more challenging and complex due to a variety of factors, including:

• Speed. Time is of the essence as marketers seek to engage customers more often across channels.
• Personalization. Differentiated messages to different kinds of customers requires highly personalized content.
• Adaptation. Channel affinity by healthcare professionals and patients requires content adaptations across multiple channels.
• Standardization. Limited standardization results in inconsistent development experience and times.

Pharmaceutical companies should consider a three-pronged process for making the promotional content review and approval process efficient, scalable and compliant. This process should include:

1. Process transformation

• Perform an assessment and design an agile review process involving modular contents and balanced content templates.
• Create submission package guidelines using a pre-submission checklist.
• Create an accelerated approval pathway with business rules and risk tiering.

2. Artificial AI-assisted review

• Leverage artificial intelligence (AI) to assist medical, legal and regulatory review to enable technology-driven content assembly and accelerated approval.
• Generate meaningful content tags for modular and composite content to enrich qualitative information.
• Generate a content similarity score or risk score by comparing new contents to previously approved contents.
• Automate style sheet checks to support compliance related to disclaimers and important safety information.

3. Functional governance

• Reinforce dual accountability for marketing and regulatory operations.
• Redesign functional roles and strengthen capabilities to support new processes and ways of working.
• Establish governance with cross-functional teams and actively manage change.
• Perform compliance advanced analytics monitoring to detect deviations prior to risk and exposure.

Embedded risk management and intelligent compliance monitoring can streamline the development and distribution of social media content that’s competitive and in line with regulations. However, for many companies, the process of monitoring the promotional content being shared on social media channels is often resource intensive. 

Pharma companies can reap the significant benefits of engaging with patients digitally while also staying in compliance with FDA regulations around drug and medical device promotions. Success in the digital arena will require better strategies, strengthened processes and practical controls. These improvements will support the communication of important information about products and diseases, which will facilitate the ultimate goal of improving patient outcomes.