Virtual Reality – FDA and AdComms

Vaccination has been robust. Cities are opening up. Plans are underway for back-to-school. Travel is robust. Offices are cautiously re-opening. There are multiple hallmarks that, whatever the consequences, we are going back to normal. The age of COVID-19 will likely continue, but with the emergence of a significant proportion of the population with vaccines pumped into them, we headed back on almost every level. Not FDA.

Today the FDA announced an upcoming meeting of the Cardiovascular and Renal Drugs Advisory Committee set for July 15 and once again, it is slated to be virtual. As the rest of the country prepares for Return to Travel, Return to Work, Return to School, this raises the question of “when” FDA is going to get off the virtual dime and migrate back to in-person meetings? One has to think that is is highly likely that nearly all people who attend an FDA Advisory Committee meeting as members are going to be vaccinated individuals. And that while travel might be required, CDC has stated that vaccinated persons “who are fully vaccinated with an FDA-authorized vaccine of a vaccine authorized for emergency use by the World Health Organization can travel safely within the United States.”

At a time when almost everyone is returning – at least partially – to pre-COVID patterns – what signal does it send when the agency responsible for approving the vaccines many of us just took is not? One branch of Health and Human Services (HHS) – the CDC has said – albeit in uncertain fashion and with an indelicate process – that masking is no longer necessary for the vaccinated while another HHS agency stays virtual.

As anyone who has had to sit through the misery of a virtual FDA Advisory Committee meeting can attest, and as recently noted on this blog, there is a significant amount of wasted time and inefficiency with an e-meeting over the old fashioned in-person variety, not to mention pain for those of us having to endure it. Moreover, while virtual platforms (when they work) have been a lifesaving substitute – from telemedicine to online cocktail parties – they lack the important nuances of human interaction as well as that je ne sais quoi that adds quality to the experience.

Also noteworthy, application has been made for full approval by one manufacturer for the COVID-19 vaccine and another will soon follow suit. Presumably there will be an advisory committee meeting associated with those applications – one that might be soon given that the application is a Priority Review. One has to consider that an advisory committee meeting for that deliberation would certainly raise some eyebrows if not held in person. It would be ironic to say the least.

FDA appears to be swimming outside the current. Perhaps there are policy and logistical questions to consider. Thinning out the seating pattern might be one – requiring people to produce evidence of vaccinated status might be another. But the world is moving on. Hey there FDA, think about the optics if nothing else. Let’s get together again.

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Passport Please – An App to Verify Your Status in a World Re-Shaped by COVID-19

This week New York became the first state to make available a means for mobile digital confirmation that an individual has been vaccinated for COVID-19. Popularly known as “immunity passports” they are in fact more than that. The New York app, dubbed “Excelsior Pass” can also carry information regarding an person’s latest COVID-19 test result. The idea has been floated for some time, and while New York is the first state in the U.S. others are poised to follow. And outside the U.S., Israel – much further along in its vaccination process – has implemented their version called “Green Pass” and France is set to launch one soon. We have upon us a new aspect of the pandemic. There are questions that immediately arise.

First, how does it work? It is an opt-in program whereby people can utilize an app to supply evidence of their status if it is needed, just the way you download your boarding pass to get on an airplane – except instead of a seat number, this explains your vaccine status or you negative PCR or antigen test for COVID. When you download the app, you will be directed to provide information to confirm your identity. Once you do, a QR code is posted in your app that can be scanned when you need to provide proof of status. (For those who do not have a smart phone, there is an ability to print out the code which presumes ability to access a computer and printer). Those who are screening will have an app that will read your passport and provide verification. Which leads to the second important question.

Why have this? What is to be gained? Plenty, for both businesses seeking a pathway to recovery as well as individuals who wish to have more normalized access. Emerging from the pandemic, particularly as recovery may be undermined by emergent strains and complicated further by vaccine hesitancy, individuals may want to be reassurance regarding any environment they want to access. This can include a health care provider to a theatre to perhaps even in their own workplace. And therefore it follows suit that in the future businesses may see it as a competitive edge to offer an environment where both patrons and employees all have provided evidence of vaccination. Would you rather stay in a hotel that offers a stay where all staff and guests have been vaccinated or one that could not make that claim?

Who would use it? From theoretical to real – specific uses for the app are already emerging. In the New York announcement it was noted that several venues in New York State were already planning on its use, including Madison Square Garden with statements of support from the New York State Hospitality and Tourism Association, the New York State Tourism Industry Association, the New York State Restaurant Association, the Empire State Restaurant and Tavern Association and the MTA all citing the app as a means to resume in-person events and to return to more normal times. From your gym to your doctor to your employer, the possibilities are vast.

What is the impact? The app is not just about the mechanics of having a “pass” but ultimately in what having it means in one’s life. Some may not choose to participate – it does require one to opt-in. Choice has played a big role in this pandemic, with some seeing it as a choice whether to restrict their movements, socially distance or to wear a mask. And whether or not one gets vaccinated is clearly at this point a matter of choice, but the existence of the app may heavily influence that choice. Someone who is reticent about getting vaccinated may feel passionate about attending a football game. For many, the existence of the app and the requisite for vaccination for entry to multiple venues and services may be more of an incentive than protecting one’s health.

And as foreign countries consider opening up their borders once again, vaccination may be a foundational requisite for entry. In the old days, all sorts of shots were often required as a means for entry into foreign countries. Now your phone will serve just as an important means of entry as your actual passport. The app facilitates decision making regarding access not only to countries, but to many venues and services and perhaps even employment, particularly once the vaccine migrates from emergency use authorization to full licensure in the future. Having an app such as this, or one instituted by airlines, will likely be essential to at least foreign travel. And we all remember the stress of passengers on cruises early in the pandemic.

It almost certainly appears we are about to enter a new vista in the complex terrain of this pandemic and one that will most certainly raise ethical and legal questions as it plays out. But it will also raise practical questions. Will the various states be able to coordinate the technology so that a reading from the Excelsior Pass will be read when going to a sports game in New Jersey or to a government building in Washington, D.C.? Will it be translatable to whatever platform the airlines use. Will hotels be able to read the apps from all 50 states? These questions are all as inevitable as the emergence of the app itself. Stay tuned.

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“Can You Hear Me?” – The (Hopefully) Coming Transition from Virtual Meetings

Today, FDA published notice in the Federal Register of an upcoming meeting of the Arthritis Drugs Advisory Committee that will be held May 6. The meeting will be held virtually.

Last year when the pandemic reality started setting in, like everyone else FDA had to change operations – in some cases shutting down or curtailing activities altogether and moving others to a virtual stage. The last in-person meeting of an advisory committee – by coincidence a meeting of the Vaccines and Related Biological Products Advisory Committee – occurred on March 4, 2020. A meeting of the Non-prescription Drugs Advisory Committee scheduled for one week later was “postponed” with subsequent meetings scheduled for April either postponed or cancelled entirely. A meeting scheduled for May 8 of the Cellular, Tissue and Gene Therapies Advisory Committee was slated to be a hybrid event – with members of the committee participating virtually and FDA staff appearing onsite at the agency campus, but was altered to become an all-virtual event via Adobe Connect.

You get the idea. Afterward there were more cancelled meetings, but by mid-June the agency was moving all meetings to a virtual platform as the realization that the pandemic was going to be long-term sank in. FDA expanded the types of platforms utilized in making the meetings available to view, including use of YouTube. I recently attended all three Vaccines and Related Biological Products Advisory Committee meetings on the COVID-19 vaccine candidates.

Those meetings included multiple exchanges like this:

“Hi. Good Afternoon. Can you hear me now?”

“We can hear you just fine. We are having trouble seeing your slides.”

“I see them. I don’t know why other people don’t see them.”

While the virtual meeting has become a regular fixture now, the exchanges such as the one above are nevertheless common and extremely repetitive and time consuming. In fact, if you added up the time spent addressing technical issues associated with the virtual meeting, you would probably find that several minutes had been eaten up, depriving the conversation of valuable time and thereby eroding the quality of the deliberation. Operating virtually is obviously better than not operating at all, whether we are talking about advisory committee meetings, our offices or even our personal relationships. But it becomes painfully obvious that it is not a substitute for the real thing.

In May the American College of Cardiology will be holding their annual meeting – ACC.21. Originally and perhaps optimistically it was envisioned as a hybrid meeting model – half in- person and half virtual, but has now transitioned to an all virtual meeting, leaving open the question as to who will have the first in-person meeting. As noted in the ACC statement on the switch to an all virtual venue, the decision was made not only based on the continued spread of the virus – and now in the form of a new strain which may be more readily transmissible, but by policies in place by institutions that are restricting travel during this time. You can’t hold an in-person meeting if no one is allowed to come.

So which will come first, the chicken or the egg? As we move from a non-vaccinated world to a partially vaccinated world to a mostly vaccinated world, where will the tipping point? Yesterday the New York Times noted that 26 percent of Americans have had at least one dose of vaccine and that if we continue at the same trajectory, by May 11 (just a few days after ACC.21) we will reach the half way mark of first vaccine dosing, with 9 in 10 being reached by the end of July. In the meantime, what policies will be in place to usher in a new era as we approach mass vaccination? Will there eventually be vaccine requirements imposed for entry to some venues, services or to take public forms of transportation?

We are fortunate in the respect that the pandemic has occurred at a time when we were able to pivot to virtual platforms. Can you imagine had it been otherwise – how much more damage would have been done. But it is time to start thinking about how we engineer the return journey.

There will be a tipping point and it will likely be sometime in the coming months, perhaps the autumn when enough people are vaccinated that it seems safe to go out in the world again.. And when it comes, hopefully we will be spared the pain – and the loss of benefit from in-person deliberation – and we will finally be able to throw the phrase “you are muted…” into our verbal trash bin. And hopefully someday later this year, we will have the first FDA Advisory Committee meeting that is held in person, or at least is a hybrid.

Can you hear me?

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OPDP Warning and Untitled Letters – A Separation; a New Letter from OPDP

This is sort of a two-for posting. First we will look at a change in how FDA is reporting regulatory actions by OPDP on the FDA website, and second we will cover the most recent such action.

OPDP Warning Letter Change. Not as compelling perhaps as Harry and Meghan splitting from Buckingham Palace, but there has been a split at FDA’s OPDP between Warning and Untitled letters. For anyone tracking enforcement, take note. It just got a little more difficult.

As an agency, FDA issues Warning Letters from multiple sources covering a span of topics and concentrated on various segments of the subject matter jurisdiction of the agency – from food to devices to cosmetics and of course, to the communication by the manufacturers of medicine about their products.

When it comes to the Office of Prescription Drug Promotion (OPDP), the regulatory actions that came from that source were up until now all stored on a single page within the OPDP portion of the FDA website listing the letters in chronological order and making distinct which ones were Warning Letters and which ones were Untitled Letters. No more.

For reasons indiscernible to this author, the agency recently split Warning Letters from Untitled Letters and now displays them in separate parts of the FDA site. Untitled Letters are still located on the OPDP site, but the Warning Letters have been moved to a portion of the FDA website where all agency-wide warning letters are being housed – no matter from where they originated. To find those specific to OPDP you must now (inconveniently) conduct a search.

That sounds easy enough, though it deprives you of the former chronological view of what OPDP is doing by way of enforcement. You will have to put the two groups into your own chronology. Not a big deal, but it adds a step. However, the way the new page/search function has been set up may also lead to some confusion. There is a drop down menu that includes all of the various points of origin for a Warning Letter within FDA. When looking for letters from OPDP the drop down menu includes the option to search for Warning Letters from either “Office of Prescription Drug Promotion” or “The Office of Prescription Drug Promotion”. But if you happen to search under both, you will get different results. When you select the tab for “The Office of Prescription Drug Promotion“, you will see the two letters issued and posted this year. When you select the tab for “Office of Prescription Drug Promotion” you get a different result that lists two additional Warning Letters posted in 2021, but which were sent in 2017.

This is hopefully a bug to be worked out over time, but the separation of Warning and Untitled nevertheless will likely stand. Hopefully FDA will sort out the different results for different tabs for the same office. Ultimately not a huge deal, just inconvenient.

However, perhaps most importantly, the search tool for Warning Letters does not go past 2017 and there is no link from the search page to the archives. So it is unclear whether or not one can access letters prior to that year when using this new page. In fact, if you visit yet another page, you can find a link to the archives, even though there is no direction in relation to that on the Warning Letters search page. This is on a page entitled “Warning Letters and Notice of Violation Letters to Pharmaceutical Companies” even though this page only actually contains links/tabs to Untitled Letters. When you go to the Archives, the tabs are all labeled “Warning Letters” but in fact, if you click on them, you go to archives that contain both Warning Letters and Untitled Letters. All in all this is a rather confusing reconfiguration.

OPDP Issues First Untitled Letter of the Year. With two Warning Letters having already been issued this year, OPDP has issued its first Untitled Letter of the year, with two of the three regulatory actions so far this year being attributed to the “Bad Ad” program. Remarkably, this is the second letter to be issued by OPDP involving a Kardashian. Go figure – though also remarkably – it involves a second Kardashian. The subject matter was a DTC video. While there are many takeaways from this letter, here are a few of the highlights:

  • A point I have always made when conducting a training related to promotional communications is that the use of a spokesperson is one of the riskier tactics one can undertake. That is because personal experience with a medication is highly subjective – the “what it did for me” factor, which is not always in lock step with what was found in the clinical trials. That is what happened here – a statement made that “[i]t literally works within, for me, 15 minutes…” was different from the clinical studies of the drug which was closer to two hours for expected relief. A statement included in the video that “results may vary” was considered insufficient by OPDP to mitigate what they considered to be a misleading statement;
  • Further use of language referring to the medicine as a “game changer” and comparing it to other medicines sets up a superiority claim;
  • Finally the presentation of risk information in the context of relating a personal experience with a medication can be challenging and here the information appeared briefly in text format at the end of the video where the agency felt it was unlikely to draw viewer attention.

That is the third regulatory action by OPDP three months into the year. If that keeps up, 2021 should be a much more active year than those in recent memory. Even if we have to hunt and pick to find them all.

Photo by Goh Rhy Yan on Unsplash

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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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