2020 OPDP Enforcement

Last month we looked at a review of FDA press releases for last year and as one might have expected, there was an enormous spike in communications as a result of the COVID-19 pandemic. Looking now to a review of enforcement by the Office of Prescription Drug Promotion (OPDP) in 2020, we see a different picture. We instead see the same pace as we have the past several years – that is anemic levels of enforcement. And as in recent years, the regulatory action letters were exclusively aimed at smaller, less experienced companies. Whether that is by design, or by virtue of the fact that they are more prone to regulatory error, is not clear. The collection of letters issued by OPDP during 2020 can be found here.

Characteristics of Enforcement for 2020 – One thing that stands out this year was the fact that the bulk of the letters issued to companies regarding violations were Warning Letters rather than Untitled Letters. Warning Letters are the more serious of the two types of letters sent by the agency. So when OPDP did act, they meant business. Let’s look to the other characteristics of the letters for 2020:

  • Five of the six letters were Warning Letters rather than the less serious Untitled Letter
  • Five of the letters involved products with Boxed Warnings
  • Four of the letters involved digital communications, two sponsored links and two emails were the subject of action
  • Two were focused on traditional direct-to-consumer ads – one radio and one television
  • Half of the letters were prompted through the Bad Ad Program (see below)

The Violations – In recent years, there has been an uptick of activity aimed at the promotion of an unapproved drugs. While this year did not see such a violation, there was a violation related to promotion of an unapproved use. In addition, the omission or limitation of risk information – the most common subject matter of a regulatory action letter by FDA, was represented in each of the letters issued during 2020. In all there were 6 letters containing 13 violations – 6 for risk; 1 for an unsubstantiated claim; 2 for broadening indication; 1 for unapproved use and 3 in the “other” category which included a failure to use the established name in the promotion.

  • All of the letters involved risk minimization or omission
    • A reminder that risk information cannot be incorporated by link to “full prescribing information” or any other source
    • Risk information cannot be cherry-picked, particularly from a Boxed Warning
    • One of the letters involved a promotion that did include the boxed warning in the communication, but lacked other risk information and placed the risk information out of proximity to the statements of benefit – Presence of risk information alone is not adequate, but rather the presentation must be balanced
  • One letter included a violation for promotion of an unapproved use where there was a suggestion that the compound relieved respiratory symptoms associated with COVID-19

Heightened Role for “Bad Ad Program” – A recent interview with the new Acting Director of OPDP revealed that a primary focus for the office this past year was in relation to the biosimilars market. It was also noted that the “Bad Ad” program turned 10 years old this year. The Bad Ad program, for those new to this, was instituted to deputize healthcare professionals in the role of helping to referee when promotional communications are perceived to go outside regulatory parameters. Notably, it appears that at least half of the six regulatory action letters issued this year were prompted through Bad Ad program reporting. The article states that the program had received over 2000 reports over its lifetime. Since there have been no where near that number of enforcement actions by OPDP during that time, it appears that there is a lot to sift through.

Social and Digital Work Left Undone – With regard to social and digital media, the Acting Director echoed the sentiments of the past when saying that FDA is focused more on the message than the medium. This is despite the fact that the guidance work that was put into motion in April 2009 framework set up during the public meetings about social media remains partially undone. There are still distinct questions relatable to digital and social media which have never been addressed which are platform specific – such as optimization of a branded web site for mobile, the responsible use of links, and adverse event reporting. CDER Guidance Agendas in the past had included some of these topics, but are no longer included in the recent agendas and appear to have been dropped.

One resource to examine when considering the potential directions for OPDP enforcement and guidance development is the identified “Research in Progress” which the office is undertaking that often informs future direction. If interested to see what they are looking at in terms of digital and social, you will be disappointed. The agenda still has a focus on DTC print and television ads. Nothing about risk presentation on mobile sites.

Conclusion – Finally, in the OPDP interview referenced above, it was indicated that a priority for the coming year will be to make the work of the office more visible and relatable, as well as to continue vigilance for claims being made around COVID-19 treatments. Overall, it would seem that despite the change in leadership, priorities remain the same – reviewing launch materials for new drugs and focusing on enforcement with respect to specific categories where there is high risk (pain medications) and situations where there is a greater risk as represented by the presence of a boxed warning. In other words, they are concentrating their resources on the greatest risk areas rather than spreading it out across the spectrum as was done when the number of regulatory action letters in a year far exceeded the current output.

For 2021? So far, no letters. Last year, the first regulatory action by OPDP did not occur until March. Stay tuned.

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What They Said – Overview of FDA Press Releases for 2020

Well. They said a lot. A lot more than ever, as one might expect. This past year, FDA issued a whopping 420 press releases, more so by far than any year previously.

COVID certainly made a big impact – a whopping 65 percent of FDA press releases had to do with the subject of the pandemic. In late March FDA began issuing Coronavirus Updates labeled as a “Daily Roundup” except they weren’t actually always a daily release – some days got skipped. In all there were 165 of them. Then in addition, FDA began issuing releases containing updates independently of the daily updates that relayed news of a special development. And then on top of that, sometimes the agency issued a regular press release having to do with a COVID-related matter. In any case, they talked a lot about COVID-19 this year, as one might expect. In all there were 274 releases about COVID.

What were they talking about? There were 104 releases involving approvals (compared to 92 the previous year) – 58 of which were about the approval of drugs; 42 of which involved the approval of devices; 1 gene therapy; 1 involving an animal product and 2 of which were vaccines. Approval announcements includes those related to Emergency Use Authorization (EUA) which is not technically an approval. There were 28 releases announcing an approval related to an EUA, which overwhelmingly involved the approval of one of the many tests authorized by the agency this past year, as well as those involving the use of remdesivir and blood plasma.

Outside of COVID, there were some notable approvals, including the first treatment for peanut allergies in children, the first therapy for children with a rare and disfiguring rare disease, a new therapy for heart failure, the first treatment for Ebola and the first imaging for Tau Pathology in patients being evaluated for Alzheimers.

FDA’s policy for translating press releases into Spanish is mystical. Some releases are translated, some are not. The subject matter sometimes seems to be a guiding factor, but it is really unclear. It is a handy thing, of course, for the nation’s Spanish-language newspapers and for patient organizations making information available. But this year, they only got about 20 percent of the time, 12 percent of the COVID-related releases. The Daily COVID-19 updates were not translated.

One additional note on FDA’s communications this past year. As late as December, FDA continued the ill-advised though infrequent practice of politicizing press releases with the use of the term “Trump Administration” in the headline. While that temptation will necessarily evaporate in a few days time, it speaks to an issue that FDA has before it for 2021 which is specifically to restore any damage to the agency’s credibility from the events of this year. The agency took some pains to demonstrate transparency during the vaccine authorization process – holding an advisory committee meeting on each vaccine and issuing a press release prior and subsequent to the meetings. That is a beginning. During 2021, the agency will have to do more.

Photo by AbsolutVision on Unsplash

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Approvals in the Crazy Year of 2020

Each year in January, it is relevant to look back on the activities of FDA during the course of the previous year and look at how it was the same or different from prior years, and to look at trends in new direction. This past year, needless to say was a doozy on all fronts. Let’s begin by looking at approvals.

One might have surmised that the advent of the COVID-era might have thrown off new approvals and that NMEs approved would go diminish. That, however, was not really the case. During 2020, FDA was able to approve 53 – not surpassing the 2018 all time record of 59, but certainly an admirable second place.

One has to also take into account that the approval mechanism at FDA was particularly busy this year. The agency had a number of Emergency Use Authorization (EUA) applications to consider, many of which were for devices (tests) but some for therapeutics and two for vaccines that included the staging of two advisory committee meetings within a week of one another, resulting in the authorization of two mRNA vaccines – a platform never before commercially available. While not full licensure, the mechanisms for approval did utilize agency resources.

Notably, the 2020 NME approvals included 22 related to oncology, with 2 new GIST treatments, 3 in breast cancer and 2 approvals in prostate cancer. There were 2 new treatments for Ebola as well as an approval for a diagnostic in Alzheimer’s. And there were at least 14 approvals for conditions considered rare.

The number of FDA Advisory Committee meetings held for 2020 to consider new drug or biologic applications numbered 19, down from the previous year when there were 23 which was down from 2018 when there were 28. That may be less a reflection on the impact of COVID than it is the fact that so many investigational compounds come through the system with an enhanced status that may diminish the need for advisory committee input.

It was certainly reasonable on the part of many to expect that FDA’s capacity for keeping the pipeline moving through the regulatory process might have been negatively affected by the COVID-19 pandemic. Certainly the shift to virtual advisory committees must have been a challenge (and trying at times to listen to) as was the shift to remote work for employees, but in the end, the agency and the pipeline delivered the second highest number of NMEs to date, while some PDUFA dates have been missed or postponed.

Looking ahead, the interesting question for the year to come will be whether or not the pandemic will have affected the completion of clinical trials for new investigative compounds that were underway or recruiting during 2020 and what impact, if any, that will have on future numbers of approvals and NMEs.

Happy New Year, by the way.

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Vaccine Development and Approval in a Time of Pandemic

Sometimes in the midst of events, perspective is elusive. Today the Food and Drug Administration will hold a meeting of the Vaccines and Related Biologics Advisory Committee (VRBAC) to consider the application for an Emergency Use Authorization (EUA) submitted by Pfizer/BioNTech for their investigative vaccine for COVID-19. Usually prior to an FDA Advisory Committee meeting where a product is being considered for approval, the posting of the FDA Reviewer comments is greatly anticipated for what it will say about the potential shortcomings of the investigative compound under consideration. The review that was posted regarding the vaccine candidate was extremely positive. Three other countries (United Kingdom, Bahrain and Canada) have already approved the vaccine for emergency use.

We are at a point in time in the United States where this could not come soon enough. We are running out of intensive care beds in hospitals across the nation. Yesterday the U.S. set a world record with over 3000 deaths, nearly as many people dying daily as died in the 9/11 attack. And there were approximately 220,000 new cases reported yesterday and the day before alone. Worse, there is complacency among some about these numbers and their impact on individual human lives. It is as if the lives, and the process for the development of a solution, have been taken for granted. Experience has taught us well that should not be the case.

It is not even a year ago that this virus emerged to threaten pandemic, lives and livelihoods. Within that short amount of time, research identified the virus, routes of transmission and began exploring therapeutics to treat and pathways to prevention. Phase 1 trials of vaccine candidates were designed and executed while plans were underway to engage in Phase 3 trials involving tens of thousands of people around the world. Study subjects had to be administered vaccine or placebo in huge numbers, wait and receive a second dose, and then to wait and see if it worked to prevent illness. All of this has brought us to this day to a VRBAC meeting to consider an EUA for a candidate vaccine for the first of at least two applications, with more to follow.

By contrast, looking back to the AIDS epidemic, the first really effective therapeutic took a decade and a half, an extremely painful and bleak time for people who were infected and their care partners. There has been criticism of the governmental response in COVID-19, but the AIDS epidemic began in 1981 and it was not until 1985 that President Reagan referred publicly to the epidemic. By the end of 1985, there had been a cumulative total of over 44,000 cases diagnosed in the United States with over 24,000 dead. After nearly 40 years, a vaccine still eludes us.

It is not simply the speed of the COVID-19 research response that has been breathtaking, but there has been a dogged determination in overcoming substantial obstacles that were in the way to get us to this point – practical, political, bureaucratic and even financial barriers – that frankly merit our admiration at the accomplishment.

While the speed and process for approval have been a point of concern and criticism for many, there is also the prospect of what weighs against those concerns. As of yesterday over 286,000 people have died from COVID-19. Many others suffer lingering illness. Economies are strained. The global pandemic out of control, but particularly in the U.S. These things are a heavy counterweight. We should not lose sight of it. FDA will likely make its decision in very short order after the conclusion of the meeting.

In the coming days and weeks, as people are considering their personal decisions about whether to vaccinate, other people will be getting this jab and will experience adverse events and reactions. Many of these will be reported on in the media and exploited by some with political agendas as well as vaccine deniers, all of which will be discouraging to those who are fence sitting about whether to take a vaccine. There will be problems in distribution, in uptake and in administration. In some respects, all of these are good problems to have because they come to us solely as a result of the fact that we have viable choices. And there is much for an individual to weigh – from their own health status to that of those with whom they live, among other things.

Speaking for myself, roll up a van to my front door right now. My sleeve is pulled up and my arm is out there and I’m waiting. And as I do so, I’m thanking my lucky stars that this time, it was not a fifteen-year wait.

Photo by Elena Mozhvilo on Unsplash

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COVID-19 Vaccinations – Where a Commitment to Diversity is Essential

In my last posting on preparedness for a post-vaccination world I touched on some of the questions facing employers in general – policy questions that should be considered now for the eventualities of later. But digging a little deeper, there are also questions to consider with respect to support for ensuring access to vaccines by communities of color. All employers have a stake in the issue of enhancing access for minorities to vaccination, but large multi-state employers, those that may be smaller/regional employers with a disproportionate share of minority employees, and of course minority owned businesses all are enhanced stakeholders. Particularly for those businesses that have supported initiatives for diversity and inclusion as a response to the issues of social justice, this is where the rubber meets the road.

Here is the issue. First of all disparities in healthcare have had an overwhelming impact on minority outcomes and causing a disproportionate impact of burden across many disease states. COVID-19 has cast a particularly harsh light on this fact where minorities in the U.S. are dying at younger agents and in greater numbers than non-minorities. Conversely, while vaccine hesitancy has been identified as a factor in the uptake of vaccines, there is a higher reserve of mistrust regarding vaccines on the part of African-Americans. With higher and harsher incidence, and higher mistrust, access to, and education about, COVID-19 vaccines is an imperative – both ethically and from a public health perspective.

However, once a COVID-19 vaccine, or multiple vaccines, are licensed and approved, distribution of the vaccines will be guided by states. The Centers for Disease Control (CDC) directed U.S. health jurisdictions to develop plans for distribution which were submitted and reviewed by the agency. A recent review of these state plans by the Kaiser Family Foundation (KFF) found the following:

  • 53 percent of the states had “at least one mention incorporating racial and/or ethnic minorities or health equity considerations in their targeting of priority populations”, meaning that nearly half do not;
  • In identifying providers for vaccinations, only one-fourth of the state plans discuss making use of providers needed to reach racial minorities;
  • Only half of the plans address communications approaches/needs for outreach to minorities or vulnerable populations;
  • Only one-third of the plans mentions the consideration for addressing vaccine misinformation, but even those that did lacked specific strategies for countering misinformation
  • In addition, states indicated that there were limitations in collecting ethnicity data on vaccinated individuals.

That there are deficits in these plans comes as no surprise given the gravity of the situation and the compressed timeframe for response. So what should businesses be considering? Given the high level of need and the considerable gaps there are some public affairs opportunities that may serve to help the situation.

  • Large employers may wish to review state plans in which they are doing business to assess the deficits that may exist with respect to their employees with particular regard to minority issues related to vaccination. A list of the state plans compiled by KFF can be found here.
  • Identify the gaps in planning and communications that might be addressed through employer-based programs:
    • Development of mechanisms to address vaccine misinformation and enhance education – or alternatively programs that curate third-party information and make it available;
    • Assess potential of public/private partnerships that might address state or regional planning and communications deficits;
  • Perform company-specific research of employee knowledge, attitudes and beliefs around vaccination to inform messaging and program development;
  • Leverage public affairs clout to pressure state health officials to address gaps in planning and communications vis a vis minorities;
  • Consider public statements of support (op-eds, paid advertising) for addressing healthcare disparities in COVID care and vaccination programs and seek and enter into coalitions with other employers.

How well we come out of this will depend on how well we manage the vaccination of enough people to actually make a difference in the course of the pandemic. Anything that falls short for any of us, falls short for all of us.

Photo by Clay Banks on Unsplash

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