Despite Few Actions On Rx Drug Promos, US FDA Increased Engagement With Stakeholders Last Year
Executive Summary
Office of Prescription Drug Promotion issued six enforcement letters and launched three research projects in 2021. There were more internal changes as the office switched to electronic submissions of promotional materials and went through year-end reorganization.
On the surface, the US Food and Drug Administration’s Office of Prescription Drug Promotion seems to have had a quiet year in 2021 issuing just six enforcement letters and initiating only three research projects. But OPDP was busy behind the scenes as it reviewed more than 130,000 promotional materials, shifted to electronic submissions, and stepped up its communication with stakeholders.
The biggest news was the change in leadership as Catherine Gray became acting and then permanent director in June following the retirement of Tom Abrams in October 2020. Abrams had headed up OPDP and its predecessor, the Division of Drug Marketing, Advertising, and Communications (DDMAC), since 2000. (Also see "Tom Abrams’ Steady Leadership Guided US FDA Through Dramatic Changes In Rx Promotion" - Pink Sheet, 27 Oct, 2020.)
In an email interview, Gray discussed the most significant developments in OPDP over the past two years. The COVID-19 pandemic prompted changes in the office, most notably in the submission process.
“Our concern, first and foremost, was for the health and safety of our stakeholders, and to that end, we knew we had to immediately pivot from paper submissions,” Gray said. “In a matter of weeks, our submission process was updated to accept electronic submissions through the CDER NextGen portal providing paper submitters with an electronic submission option.”
The pandemic also had an impact on OPDP staffing. Many OPDP employees are commissioned officers in the US Public Health Service and have actively assisted in the government’s response to the pandemic. Gray noted that they have deployed more than 30 times in support of the response to COVID-19 and other critical public health missions and are away for at least a month at a time.
The office has also increased its communication with stakeholders through conference presentations, Small Business and Industry Assistance (SBIA) webinars, professional and scholarly publications, and its ListServ.
“My priority is to maintain OPDP’s standard as a transparent and responsive office that’s committed to engaging with our stakeholders,” Gray said. “Sponsors have been very clear in their desire for open dialogue with our office and I firmly believe that early and proactive communication with the office is one of the best practices to ensure regulatory compliance.”
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Digital Platforms In Spotlight
Gray joined FDA in 2004 as a reviewer in DDMAC and became staff supervisor in 2017. Prior to joining the agency she worked in the pharmaceutical research industry and clinical pharmacy. She noted that during her tenure, prescription drug marketing has increased each year, from less than 50,000 unique promotional pieces her first year at the agency to 135,000 in 2021.
There have been major changes in the field as new technologies have transformed the way marketers promote to health care professionals and consumers. Gray pointed to the emergence of digital platforms that provide better real-time communication between sales representatives and HCPs. “As more digital platforms support the use of video, we’re seeing more promotion through video than ever before,” she said.
That is apparent in the enforcement letters the office issued last year. Two of the six letters objected to videos shown on TV. (See table at the end of the story for details on all of OPDP's 2021 letters.)
One of the letters went to CooperSurgical Inc. for a video about its intrauterine contraceptive Paragard that did not include any risk information. The video was presented on an NBC television station in Boston. It was a repeat violation, as OPDP previously objected to CooperSurgical’s promotion of Paragard in a direct-to-consumer TV advertisement. (Also see "US FDA’s ‘Bad Ad’ Program Snares Paragard Contraceptive TV Video Promo" - Pink Sheet, 24 Feb, 2021.)
The office also objected to a video of TV reality show personality Kloé Kardashian promoting Biohaven Pharmaceutical Holding Company Ltd.’s migraine drug Nuretec ODT (rimegepant). The agency said the video, which aired on ABC’s The View, made false or misleading efficacy claims and failed to adequately present risk information. (Also see "Keeping Up With the Kardashians: US FDA Objects To Khloé’s Migraine Drug Promo" - Pink Sheet, 10 Mar, 2021.)
The letters OPDP issues objecting to prescription drug promotions are closely followed by industry as they reflect promotion trends and what the agency finds problematic. The number has steadily declined over the last decade from a high of 51 in 2010. The six issued in 2021 are one more than the record low set in 2017.
The other letters issued last year targeted:
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Eton Pharmaceuticals, Inc.’s sponsored link on Google.com for Alkindi Sprinkles (hydrocortisone oral granules) for failing to include any risk information (Also see "US FDA Once Again Dings Rx Drug Sponsored Link For Excluding Risk Information" - Pink Sheet, 24 Aug, 2021.),
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A false and misleading banner ad for AcelRx Pharmaceuticals, Inc.’s opioid Dsuvia (sufentanil) (Also see "Dsuvia Gets Warning Letter As US FDA’s Opioid Decisions Complicate Commissioner Race" - Pink Sheet, 16 Feb, 2021.), and
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A banner ad for Amgen, Inc.’s Neulasta (pegfilgrastim) that suggested the biologic’s injector is more effective than that used by biosimilars. (Also see "Amgen’s Neulasta Ad Indirectly Targeting Biosimilars Draws US FDA Rebuke" - Pink Sheet, 14 Jul, 2021.)
Final Letter On Complex Ad Package
The most notable letter of the year involved an unusual package of television commercials for Eli Lilly and Company’s migraine drug Emgality (galcanezumab-gnlm). OPDP issued an untitled letter in December saying two direct-to-consumer TV ads featuring Olympic and Paralymic athletes failed to include any risk information and omitted major side effects and contraindications. In its response letter, Lilly then told the agency that these ads aired sequentially along with a full product TV segment that included Emgality indication and risk information. The company had failed to note the coordinated ads in its Form 2253 submission of the two ads the agency objected to. The agency then took the unusual step of posting a close-out letter saying the matter was resolved at the same time it posted the untitled letter.
The case offered a lesson for companies to make sure they provide the agency with all relevant information about an advertising campaign in its submission. OPDP said also said it would be updating its processes to apply a consistent approach to posting close-out letter for all compliance actions. (Also see "Lilly Resolves US FDA Concerns About Emgality TV Ads That Were Not Meant To Run Solo" - Pink Sheet, 17 Jan, 2022.)
The end-of-the year action on broadcast ads that ran during the Tokyo 2021 Summer Olympics boosted the number of enforcement letters to the same tally as the previous year, which was one more than the record low. (See chart.)
The decline in warning and untitled letters may reflect greater regulatory compliance by sponsors. But Gray said they are one component of OPDP’s multi-faceted program for oversight of prescription drug promotion. She said the office encourages voluntary compliance through several avenues, including its work on guidance documents, providing written advice to companies on draft promotional materials, and outreach to stakeholders.
“One cannot get a complete picture of OPDP’s program area by looking at a snapshot in time of compliance letters,” she said.
Enforcement Trends
Gillian Russell, counsel at King & Spalding, noted that one of the trends in OPDP enforcement over the last four or five years has been a focus on drugs with box warnings. Speaking at the firm’s recent webinar on drug and device advertising and promotion, she said that while only one of the six letters OPDP issued in 2021 involved a drug with a box warning (Dsuvia), all six of the letters issued in 2020 went to box warning drugs and three of the six letters issued in 2018 focused on drugs with box warnings.
Russell noted that FDA’s Bad Ad program has also been a driver of enforcement letters. Launched in 2010 to encourage physicians to report improper promotion to the agency, the program also receives complaints from consumers and industry. Russell said that three of the six letters in 2021 stated that they had been triggered by a complaint to the program.
She also cited the agency’s scrutiny of social media promotions. While OPDP did not issue a letter targeting websites or social media last year, it has done so in previous years, and its first letter of letter of 2022 was directed at a social media post. OPDP objected to Eli Lilly and Company’s Instagram ad for its diabetes drug Trulicity (dulaglutide) for not adequately communicating its indication, limits of use and risks. (Also see "Lilly Gets First Of Its Kind FDA Citation For Trulicity Instagram Post" - Pink Sheet, 25 Jan, 2022.)
Fewer Research Projects
The agency also initiated fewer research projects during the year, announcing three projects compared to six the prior year. (Also see "US FDA Actions On Rx Drug Promos Covered New Territory Last Year" - Pink Sheet, 12 Jan, 2021.)
The projects focus on promotions referencing accelerated approval and targeted mechanism of action and assessing the impact of proprietary names.
The “Accelerated Approval Disclosures on Direct-to-Consumer Prescription Drug Websites” study is to determine whether disclosure that a product received accelerated approval impacts consumer perceptions of the drug. The project is particularly noteworthy given the FDA’s approval of Biogen, Inc. and Eisai Co., Ltd.’s Alzheimer’s drug Aduhelm (aducanumab) via this pathway last year. (Also see "DTC For Accelerated Approval Drugs: US FDA Is Taking Another Look At Disclosure On Websites" - Pink Sheet, 10 Jun, 2021.)
The research on “Targeted Mechanism of Action Presentations in Prescription Drug Promotion” consists of a survey of consumers and healthcare providers about their response to promotions about a fictitious cancer drug on a branded website to see how they interpret the term “targeted.”
And the “Text Analysis of Proprietary Drug Name Interpretations” study is assessing how consumers and primary care physicians interpret drug names with and without promotional implications. (Also see "Do Ads Noting A Drug’s ‘Targeted’ Mechanism Of Action Impact Perceptions Of the Product?" - Pink Sheet, 1 Nov, 2021.)
Three years ago, the Pharmaceutical Research and Manufacturers of America criticized OPDP for the number of projects it had initiated. It said the agency had relied on authorities provided under the Food, Drug, and Cosmetic Act at least 22 times in proposing different research projects and failed to articulate how the research related to the goal of protecting public health. (Also see "PhRMA Criticizes 'Exponential Pace' Of FDA Rx Drug Advertising Studies" - Pink Sheet, 13 Aug, 2018.)
To date, OPDP has completed 42 research projects, has eight pending peer review and publication and 15 in progress, including the three proposed last year.
Gray said the projects are developed through collaboration between the social science research team, OPDP reviewers, and OPDP leadership. She noted that project ideas may be informed by emerging issues of interest to FDA and advances in the field.
The office recently co-sponsored a workshop with the Duke-Margolis Center for Health Policy on prescription drug promotion in the digital realm. They asked academicians who have conducted research in the field for advice on coming up with a research agenda. Gray said panel participants identified some gaps that could be addressed by research. (Also see "Evolution of Rx Drug Promotion: Researchers Eye Data Brokers, Digital Tools, Global Influencers" - Pink Sheet, 2 Dec, 2021.)
New Approach To Promotional Materials
OPDP also moved forward with a new procedure for reviewing core prescription drug launch materials, which went into effect in December 2020. The agency added a five-day screening period to the review process to make sure companies submit the appropriate information. (Also see "US FDA To Screen Rx Drug Launch Promos Prior To Initiating Review" - Pink Sheet, 16 Dec, 2020.)
The office divides submissions for advisory review into launch or non-launch materials. Launch materials, disseminated after FDA approves a new drug, are categorized as core or non-core. Gray said the change in the review process has had a positive impact on the quality of submissions and has also improved OPDP’s ability to provide sponsors with timely comments on core launch materials.
Sponsors are required to submit promotional materials through Form 2253 prior to dissemination. In fiscal year 2020 the agency received 68,709 submissions and 131,944 materials submitted along with them. That was up from 60,776 submissions with 112,266 materials the previous fiscal year.
Industry had been watching for further guidance documents from OPDP but none were issued last year. Center for Drug Evaluation and Research deputy center director for regulatory policy Grail Sipes commented at a conference in November 2020 that the agency could not predict whether there would be additional or updated guidance in the coming year, but said it was paying attention to individual influencers and endorsers and information on healthcare sites. (Also see "New Social Media Guidance From US FDA May Be On The Horizon" - Pink Sheet, 3 Nov, 2020.)
The Federal Trade Commission also set its sights on endorsements and testimonials in product promotion. In October, the agency sent notices to more than 700 companies about penalties they will face if these promotions are deceptive. (Also see "Pharma Companies Must Assure Their ‘House Is In Order’ As FTC Takes Aim At Deceptive Endorsements" - Pink Sheet, 20 Oct, 2021.)
OPDP Reorganization
OPDP began 2022 with a new structure in place. The FDA announced in a 3 January Federal Register notice that the office had established a new Division of Promotion Policy, Research and Operations. The agency said the reorganization, which became effective on 24 November, will provide enhanced support, oversight, and direction to OPDP’s social science research program. (Also see "FDA Creates Division To Support First Amendment Policy Development, Oversee Advertising Research" - Pink Sheet, 6 Jan, 2022.)
“The reorganization will provide additional support and increased focus on the regulatory counsel functions necessary to develop sound and legally supportable policy documents and surveillance activities, particularly given First Amendment jurisprudence developments over the last few years,” the FDA stated.
It will also provide enhanced operational support to all OPDP functions, including policy development and clearance, the multi-million-dollar research program, advisory comments to industry, compliance actions, and internal FDA review of approved labeling.
OPDP also debuted a new monthly newsletter, The Brief Summary, to provide updates about office activities. In an introduction, Gray said OPDP’s resolutions for 2022 are to “promote enhanced stakeholder collaboration, meaningful communications, technology enhancements and world-class research.”