Recap of FDLI #AdPromo2023

Disclosure: I sit on the Planning Committee for the FDLI Ad-Promo conference. This is an unpaid, volunteer position. The contents of this post were not discussed with or influenced by any member of the FDLI staff.

This post provides some of the highlights from FDLI's ad-promo conference. An on-demand version of the conference presentations is available at: https://www.fdli.org/2023/11/advertising-promotion-for-medical-products-conference-on-demand/

The Food and Drug Law Institute's (FDLI) Advertising & Promotion for Medical Products conference wrapped up last week. I attended the conference and also moderated a panel on data privacy and concerns about the use of health data for the targeting of advertising.

The first day kicked off with a fireside chat with Arun Rao from the Department of Justice (DOJ), Lauren Roth from the Food & Drug Administration (FDA), and Serena Viswanathan from the Federal Trade Commission (FTC), led by Christine Simmon of FDLI.

FDA and FTC both noted their recent guidance updates. For FDA, that means the new Communications From Firms to Health Care Providers Regarding Scientific Information on Unapproved Uses of Approved/Cleared Medical Products Questions and Answers Guidance for Industry (SIUU) and the newly finalized Presenting Quantitative Efficacy and Risk Information in Direct-to-Consumer (DTC) Promotional Labeling and Advertisements. 

FTC has also been busy, providing updated guidance on endorsements, reviews and testimonials, and a distinct Health Products Compliance Guidance.

DOJ, FDA, and FTC also mentioned the extent to which they are still very much digging out from the backlog created by the pandemic. More than three years after COVID-19 first came to our shores, its effects are very much still being felt.

Rao also mentioned a new policy from DOJ to create a safe harbor for self-reported disclosures made in connection with a merger or acquisition. Under this new policy, companies that learn of wrongdoing at a company they have acquired can be protected from later liability if they report the wrongdoing to DOJ within six months of closing the merger or acquisition. This is as Rao described it a "very big juicy carrot" to encourage self-reporting of wrongdoing, and it also ramps up the need for effective due diligence during the M&A to ensure that all wrongdoing is uncovered and can be reported.

One final point mentioned by Roth is the importance to FDA of combatting misinformation about medical products. Commissioner Califf has repeatedly warned about the need to combat misinformation, and it is not a stretch to see FDA's SIUU guidance as one small step in that direction. By providing further guidance about exactly how sponsors can share truthful, not misleading information about unapproved uses, FDA is enabling efforts to get good information from the people who should be seen as the most reliable source of that information, the product's sponsors.

The next session of the day included an update from OPDP, APLB, CDRH, and CVM related to advertising and promotion.

Katie Gray from OPDP gave a detailed presentation on the Recorlev enforcement action from earlier this year and an overview of the SIUU guidance. Lisa Stockbridge from APLB provided a reminder on reminder advertising, indicating that this well-established category of communication continues to cause firms difficulties. Debra Wolf of CDRH emphasized that although there has not been a significant amount of publicly available enforcement actions from CDRH, the Agency continues to have many private communications with firms about their marketing efforts.

The next plenary session covered scientific exchange and pre-approval communications. Elisabethann Wright of Cooley provided particular insight into the EU's approach, which of course varies widely by country, and has been especially active on platforms such as LinkedIn. Of note is the extremely active role played by the industry's own associations in not merely promulgating guidance and establishing codes of conduct but in regularly enforcing violations of those codes against member companies.

After lunch, the first set of breakout sessions occurred including the panel I moderated on data privacy. I found the discussion very lively and enjoyed hearing from Elisa Jillson from the FTC, Lyra Correa from HHS's Office of Civil Rights, and Nancy Perkins from Arnold & Porter. I have previously opined that the 2020s will be most known for its focus on privacy, and while the cookie-less future we keep hearing about gets pushed back once again, there's growing awareness and concern about how much deeply personal information has been given up and on how companies are using (or misusing) that data.

Simultaneous sessions looked at the recently finalized guidance from the FDA on Presenting Quantitative Efficacy and Risk Information in Direct-to-Consumer (DTC) Promotional Labeling and Advertisements while another session looked more into the promotion of veterinary products. Because I was leading another session, I couldn't attend either, but I'm looking forward to using that link provided earlier to view the recordings. 

The afternoon plenary sessions resumed with a look at FTC's role in enforcement of healthcare advertising and closed out with a session on that perennial chestnut of social media usage.

Day two of the conference kicked off with an enlightening discussion of so-called CFL (Consistent with FDA-Labeling) claims. Torrey Cope of Sidley Austin provided an insightful look not just at FDA's enforcement post-guidance for claims that failed to meet the CFL standard, but also for taking the time to examine the nature and wording around the acceptance by FDA of so-called Real-World Evidence (RWE) in the context of product approvals. RWE is not the sole source of CFL claims, but Cope was able to provide some valuable lessons.

The afternoon's breakout sessions included one on artificial intelligence (which I attended), promotional challenges in rare disease treatments, and navigating accelerated approval promotion.

The closing session focused on other avenues for enforcement, including of course, the Better Business Bureau National Advertising Division's (NAD), as well as general counsel to general counsel complaint letters, filing complaints with the FDA, and perhaps even bringing a Lanham Act case.

The NAD's finding against Novartis earlier this year was of course a hot topic. But it is worth noting that in a more recent case, Viiv simply declined to participate in the NAD process. NAD referred the matter to FDA and FTC noting that decision, but as of the writing of this post, no further action by the government has been seen.

Alan Minsk of Arnall Golden Gregory noted the importance of determining your goal when looking at the appropriate path. If your goal is get a competitor in trouble then you really need to rely on the government or the courts, but if your goal is primarily to just get the company to stop the use of misleading promotion, then NAD or a direct complaint letter might be a far more cost-effective solution.

Overall, the conference was a huge success, though my opinion should be viewed as biased because I sit on the conference planning committee. FDA is definitely digging itself out from the pandemic backlog. I fully expect we'll see more from the Agency, as a very active 2023 has already demonstrated.

2020 CDER Guidance Agenda Released

UPDATE: The guidance mentioned below was released. Here's the link.

The FDA has released the CDER Guidance Agenda. For ad-promo professionals, the most most significant item is the inclusion of an item labeled:

• Promotional Labeling and Advertising Considerations for Prescription Biological Reference and Biosimilar Products--Questions and Answers 

Also notable is that no other advertising or promotional guidances are listed. The draft guidance on presenting risk information turned 10 years old last year. It seemed ripe for an update and perhaps even finalization. That seemed even more likely in the context of OPDP's study of the so-called one-click rule. That study was first announced in 2017. There's no update on the FDA website about the study, but I expected it to be completed last year.

FDA's social science research has clearly been influencing recent guidances, so I assumed (and continue to assume) that FDA would want to update the risk presentation guidance in light of its most recent research about presenting risks, including the one-click study. Apparently, we'll have to keep waiting.

BTW, for those interested in the topic of biosimilar promotion, the Drug Information Association's Advertising & Promotion Regulatory Affairs Conference will have a session covering this topic. Full disclosure: I sit on the programming committee for the conference and will be leading the medical device primer the day before the full conference kicks off. 

Preparing for Pricing in DTC TV

UPDATE 2: On August 21, 2019, the government filed a notice of appeal in this case.

UPDATE: On July 8, 2019, the judge in the pending litigation described below issued an order setting aside the CMS rule. The full opinion is available here.

If nothing changes, the new rule about including drug pricing in TV ads from CMS will go into effect one week from today on July 9, 2019.

There are a few wrinkles to keep in mind as we approach this deadline. First, there's a lawsuit pending that could delay the rule's implementation. Second, the operational challenges of abiding by the rule are the biggest hurdle including the expanded 2253 filing requirements. Third, the rule's scope is still unclear. Fourth, the rule doesn't preclude or preempt the PhRMA Principles change from April. Finally, the overlapping but non-identical scope of the rules could lead to some confusion and compliance hiccups. This post addresses each of these points in turn.

Pending Litigation

As I noted in a previous post, several pharmaceutical companies along with the Association of National Advertisers filed a complaint seeking to overturn the CMS rule. The full complaint is available here. The plaintiffs have filed a motion to stay the rule's implementation, and the judge has set a date of July 8 for issuing a decision. So, it is possible that companies will not actually be required to include their drug pricing in TV spots on July 9; however, as a practical matter, companies airing spots on July 9 and soon thereafter have most likely already developed them with the required pricing information included. 

All promotional materials for prescription drugs, biologics, and vaccines must be submitted to the FDA at time of initial dissemination or publication, so the FDA has most likely already begun receiving submissions of TV spots that include the information, and it is unlikely that a company would go to the time and expense of producing two versions of their TV spots (one with the pricing and one without) and submit both the FDA, only to determine on July 8 which spot to air the next day. Consequently, even if the judge issues a stay on the rule, there's a good chance that you'll see at least a few TV spots featuring pricing on July 9.

And that points to one of the issues the rule raises: operational challenges.

Operational Challenges 

Adding a line of copy to a TV ad is not a massive creative endeavor, and because the rule only requires the copy to appear on screen for a long enough time to be read, there are no audio implications, but the CMS rule requires that the pricing information presented is kept up to date. Specifically, the new rule requires that the pricing information provided be:

"as determined on the first day of the quarter during which the advertisement is being aired or otherwise broadcast." 42 CFR 403.1202 (not yet live on the code of federal regulations itself).

That means the pricing information must potentially be updated every quarter. Of course, most companies don't change their drug pricing quarterly, but it is common to have pricing updates twice per year. So, every time a company changes its pricing, it will have to determine what ads are currently airing and whether the pricing updates affect those ads. If the pricing changes affect the ads, then the ads will have to be updated. An updated TV ad both means an expense for the advertiser, but it also means a new 2253 filing with the FDA because updated materials must be resubmitted to the Agency.

And that means that the media buyers placing the ads will have one additional wrinkle to keep in mind as they manage the ad placements. They'll need to make sure that as new pricing comes into affect and ads are updated that the old ads are removed from the rotation, lest they be placed on CMS's naughty list.

That operational challenge is compounded by the fact that the scope of the rule is unclear, so it's not currently possible to say exactly what ads must include drug pricing.

Rule Scope Unclear

As I noted in a previous post, CMS made it clear that the requirement to include pricing does not apply to ALL direct to consumer (DTC) ads, but only to a limited subset of DTC ads. Specifically, the new requirement applies to only ads that appear on broadcast, cable, satellite, and streaming television. Unfortunately, CMS never explained what "streaming television" is. I tried to find a definition somewhere but wasn't able to do so. This matters because there are tons of DTC video ads that MIGHT be considered subject to the rule that are definitely not presented on "broadcast, cable, or satellite television."

Because of this scope unclarity, the operational challenges of managing ad inventory is compounded, and of course, companies must decide how to handle ads that are used on television when they appear in places where the pricing information is not required. It would certainly be easier to develop a version of the ad that doesn't require quarterly updates, but it also is easier to traffic fewer total ad units.

CMS Rule Adds to (Doesn't Replace) PhRMA's Pricing Requirements

The Pharmaceutical Research and Manufacturers of America (PhRMA) updated its Guiding Principles on Direct to Consumer Advertisements about Prescription Medicines in October of 2018. The most significant change was the addition of a requirement for television ads to include a destination where people can find pricing information about the prescription drug being advertised. This requirement became operative in April of 2019. All members of PhRMA are obligated to follow the PhRMA guiding principles, and most companies that are not members of PhRMA also abide by the guiding principles. Consequently, almost all television commercials currently airing include a link to a webpage with pricing information.

Adhering to the CMS rule does NOT meet the PhRMA guiding principles. Consequently, most companies will be providing both a link to a page with additional information and the pricing information required by CMS. We'll see how companies execute this, but my expectation is that a single screen at the end of a television commercial will accommodate both pieces of information.

Of course, not all ads are required to include both pieces (or even either piece!) of information.

Non-identical Overlapping Scopes

The new CMS rule applies to all advertised indications of a pharmaceutical product that are reimbursed via Medicare or Medicaid and whose cost is at least $35 per month (or for a typical course of treatment). 42 CFR 403.1200. Note that some drugs have multiple indications, where only some of the indications are reimbursed by CMS. For those products, only the ads that promote an indication reimbursed by CMS are required to include the pricing information; and only if the drug's list price is at least $35 per month (or for a typical course of treatment).

By contrast, the PhRMA guiding principles apply to all ads for prescription medicines regardless of whether the drug is reimbursed by CMS and regardless of the cost. Of course, the guiding principles are only binding on members of PhRMA and any non-member companies that have chosen to abide by the guiding principles.

TL;DR

Some commercials (but we don't know exactly which ones) might start having pricing information in one week. The addition of this information is allegedly going to address the allegedly high price of prescription drugs. The only guaranteed aspect of the recent changes from PhRMA and CMS is that marketing and regulatory operations groups are going to have challenges ensuring ongoing compliance, and the FDA is about to start getting more 2253 filings, including a likely surge of revised television spots in the next few days.

"New" Means within the Past Six Months

During the Q&A of a presentation at the AdvaMed Advertising and Promotion of Medical Devices conference (slides here), I was asked why I claimed that the word "new" meant within the past six months. I mentioned that FDA had a post noting this and that FTC also had the same position.

On the train home, I decided to hunt down the sources, and this post is the result so I don't have to duplicate the effort again. I didn't realize that FTC's position on the issue went back to 1967.

I still don't think drug ads will include pricing any time soon

So, I was right!
...

Or maybe I was wrong.
...

Or perhaps the jury's still out.

In May, when President Trump released his blueprint for lowering prescription drug pricing, I wrote a blog post saying that I didn't see how FDA had authority under existing regulations to mandate the inclusion of prices in the direct-to-consumer (DTC) ads. I further claimed that getting such a requirement in place would either require a new regulation, or more likely new legal authority.

Well, as some of you might have heard, yesterday, the Trump administration released a new proposed rule that would require pharmaceutical companies to include the Wholesale Acquisition Cost (WAC) in television ads.

I'll have much more to say about this proposed rule as the conversation continues. And I can't decide which verdict to make on my earlier prediction.

I want to make one point here that hasn't been mentioned in any of the coverage I've seen so far.

Too frequently people talk about prescription drug advertising in a vacuum. The assumption seems to be that people know absolutely nothing about anything and on to this tabula rasa the promotions from pharmaceutical companies are forced, brainwashing people into storming their doctors' offices to demand prescription drugs.

That's not true. Not even close.

People care about their health. They care about the health of their children, their parents, their spouses, and others. When they have a health issue, they start looking for information about ways to treat that issue, ideally to cure it, or at least to help mitigate the symptoms and severity of the condition.

Their search for information will (I hope) include an investigation of whether a prescription treatment is the right option, but it will also include the crap that's sold on disreputable websites. Their search will include supplements, with all of the appropriate concerns.

This is relevant to the debate about drug pricing because one reason prescription drugs cost much more than these other options is that they work. We know they work because the FDA has evaluated the science behind them and believes that there's good reason to believe they work.

The other reason they're more expensive is because most people have some form of prescription drug coverage from their insurance, and insurance companies are willing to pay far more to keep their policy holders healthy than most consumers are willing to pay out of pocket.

Throughout the CMS's proposed rule, there are repeated discussions about how information about the WAC will enable consumers to make rational decisions about treatment options. The assumption seems to be that consumers are limited solely to trying to decide between prescription drug A and prescription drug B and that knowing the WAC will somehow enable them to make a better decision between the two. All by itself, this is a deeply suspect proposition.

But the more important point I want to make now is that people aren't trying to decide between prescription drug A and B. They're also considering pseudoscience crap C and possibly dangerous supplement D and over-the-counter treatment E and loads of other options as well.

Currently, people don't know how much prescription drugs cost, and maybe that's a good thing because it keeps people from comparing that $84,000 prescription drug to the $75 pseudoscience product. Acting as if the price is the sole, or even the primary, factor that consumers should use to evaluate treatment options ignores that most of the evaluation doesn't occur purely among different prescription treatments, and it also rarely involves a qualified health care professional.

It's most often a person, maybe a family, alone, or talking with their friends trying to figure out what's wrong and how they can fix it.

The response to including pricing in prescription drug ads could be, as I've said repeatedly, that people are scared away from prescription drugs that would be relatively affordable for the individual.

It also could be that the crap starts getting more expensive. After all, if people grow accustomed to seeing health treatments advertised with a list price of $100,000 or more, then they won't necessarily notice that the item being advertised is a dangerous supplement or pure pseudoscience.

I've noticed over the past few years that more and more ads for supplements have started mimicking prescription drug advertising. They make their logos look like prescription drug logos. They include a risk statement in their ads. To someone who isn't trained in knowing the difference, you could be forgiven for thinking there's no difference between these products and prescription treatments.

Is it really a stretch to think that requiring prescription treatments to include prices will result in those pseudoscience products doing the same, or to worry that the prices they start seeing as their comparator is the now revealed price of the prescription treatment?

FDA Product Name Guidance Finalized

Last week, the FDA published a final version of the Product Name Placement, Size, and Prominence in Promotional Labeling and Advertisements.

FDA has been remarkably active on this topic, as this is now the third update to the guidance in the past five years. People who have been following this guidance will be pleased to hear that there's little new. Though there are many changes, there are no substantial changes from the 2013 version. The most significant development in the new guidance is the provision of examples demonstrating FDA's principles about prominence of the product name.

If you'd like a quick overview of the guidance, I suggest this one from Intouch Solutions.

The Amarin Settlement Created a New Review Process

Frequently, people refer to the process of requesting advisory comments from the Office of Prescription Drug Promotion (OPDP)* on draft promotional materials as getting "preclearance" of those materials. But that's just not accurate.

Technically, FDA never provides "clearance" of materials to use, unlike, for example, the Pharmaceutical Advertising Advisory Board (PAAB) in Canada. Instead, FDA will review and comment on promotional materials, but even assuming that all of the comments are addressed, it is still possible (though unlikely) to receive an enforcement action from the FDA for engaging in violative promotion, and there is no requirement to modify promotional materials to address FDA's comments (though of course failing to do so is generally unwise).

It is true that under certain circumstances, FDA can require that promotional materials be submitted for advisory comments prior to use (e.g., because the product has received accelerated approval), and that this submission is independent of the submission under cover of Form 2253 prior to use, but even in those circumstances, the FDA does not "approve" or "clear" promotional materials. Instead, the FDA simply provides comments on promotional materials and does not typically see how a company addresses (or fails to address) those comments until the materials are submitted under cover of Form 2253 prior to use.

This was the situation until the Amarin settlement on March 8, 2016. For the most part, the final settlement simply codified the terms of the earlier injunction, so, most of my initial post on the topic still seems relevant. There was, though, one significant wrinkle.

In summary, the final settlement included the following provisions:

1. Amarin may promote Vascepa for off-label use of patients with persistently high triglycerides and not have such promotion used as evidence of misbranding.
2. The direction from the injunction regarding the promotional materials and required disclosures stands (based on the information known as of the date of that injunction**).
3. Amarin is responsible for ensuring all of its future statements are truthful and non-misleading.
4. Nothing in the injunction or the final order is to be "construed to limit Amarin's constitutional rights to free speech."
5. There's a new procedure for Amarin to ensure that future communications about off-label uses are also truthful and non-misleading (more on this below). The court retains jurisdiction in the event of a future dispute about whether any given off-label communication is truthful and non-misleading.
6. Additional dispute resolution procedure specified for issues other than new off-label communications.
7. - 11. Assorted provisions about scope, waiving appeals, costs, etc.

It's provisions 5 and 6 that are most interesting for regulatory professionals engaged in reviewing promotional materials.

Traditionally, the advisory comments process is used in the launch phase of promotion to receive feedback from FDA prior to initial promotional materials being released and for television advertising.

And the way that process works is that materials undergo review at the individual company, and then, after being fully vetted, a new submission goes to the FDA with all of the accompanying references. FDA asserts that its goal is have the review completed in 45 days, but often (especially of late), the review takes 60 days or longer.

FDA comments in response and will often point out alleged deficiencies in the draft materials. Because of the lengthy delay involved in submitting materials for review, companies rarely submit revised versions. Instead, they do their best to adjust the materials and then proceed to finalize them, and (assuming they qualify as product promotion) submit the finalized version to the FDA to meet the 2253 filing requirement. 

The settlement establishes a new procedure. The first thing to note is that this procedure only applies to Amarin at the moment. So, whereas any company can submit any materials at any time via the traditional advisory comments, this new procedure is only available to Amarin.

In addition, Amarin can only do this for two communications per year, as opposed to the theoretically limitless number of requests a company may make for advisory comments. And note that although submissions for advisory comment are most often of a single commercial, other requests for advisory comments will typically include multiple communications, not just the two pieces to which Amarin is limited.

This procedure is explicitly identified as a "preclearance procedure," so Amarin won't simply receive comments from FDA akin to the traditional advisory comments that companies are used to receiving. Instead, FDA will provide clearance to use the materials.

FDA will have 60 days to review the communications and present any concerns or objections to Amarin, after which, Amarin will have 45 days to respond, followed by 30 days for FDA to report any remaining objections.

If the two parties cannot reach agreement after this 135-day process, either party can request that the court step in to resolve the dispute, so there is a formal appeal built in and it goes directly to the court.

The chart below summarizes the key differences between the new "preclearance procedure" and standard advisory comments.

One final note is that the settlement explicitly states that this only lasts until December 31, 2020. One hopes that prior to then, this issue will have been resolved without a further series of one-off agreements and lawsuits.

* Note that although I focus on OPDP within CDER in this post, essentially the same points are true of APLB in CBER.
** This is an important but seldom-noticed qualification. Should the scientific underpinnings of the situation change, all bets are off.

Help-Seeking Guidance Withdrawal Update

Last week, FDA withdrew 47 guidance documents, including the disease awareness guidance that has become so central to ad-promo professionals. As I mentioned at the time, this move left those of us who care about these issues in a bit of a quandary.

It certainly seemed from FDA enforcement activities and other statements that many (if not all) of the principles set forth in that guidance still represented FDA's view, but the guidance itself was technically no longer an official statement of FDA's position.

Since I was teaching a two-day ad-promo class for FDAnews this week, I reached out to OPDP about whether I needed to radically alter my treatment of the topic of disease awareness in light of this development.

I received the following statement in response:

FDA continues to believe that disease awareness communications can provide important health information to consumers and health care practitioners, and can encourage consumers to seek, and health care practitioners to provide, appropriate treatment.  While many of the principles in the withdrawn draft guidance are still relevant, we are taking this opportunity to work on an updated draft guidance that considers new technologies and includes information about social science research to better reflect FDA’s current thinking on help-seeking and other disease awareness communications.

I'm sharing this with the community because I think it provides important amplification on the initial withdrawal statement.

FDA is apparently working on a new updated draft guidance (despite that guidance not being listed on the 2015 guidance agenda). Also, FDA continues to endorse the view that disease awareness communications are important and can improve the public health.

I'm particularly excited to see what FDA has to say about new technologies. The 2004 guidance was silent on the use of the Internet, and as readers of this blog might know, I've been curious about this topic for several years.

So stay tuned. Clearly there's more coming.

 

Five Things to Notice About FDA's Electronic 2253 Filing Guidance

Today, FDA produced its long-awaited guidance of submitting promotional materials electronically.

As ad-promo guidances go, this is a hefty one, weighing in at nearly 40 pages. For comparison, last year's two social guidances released on social media guidance day totaled 30 pages combined.

Rather than trying to provide a comprehensive digest of the guidance, I'm going to here provide a framework for understanding the guidance and point out some the items that leapt out at me on a first reading.

1. What is this guidance about?

Up till now, FDA's two primary groups responsible for overseeing the promotion of prescription drugs and biologics, the Office of Prescription Drug Promotion (OPDP) in the Center for Drug Evaluation and Research (CDER) and Advertising and Promotional Labeling Branch (APLB) in the Center for Biologics Evaluation and Research (CBER) have had different policies about accepting electronic filing of promotional materials. APLB accepted them; OPDP didn't.

Moving forward, both agencies will accept promotional material submissions electronically, and they will do so using the common eCTD format used for all other electronic submissions, such as NDAs and BLAs.

2. Which submissions are affected?

This guidance affects only submissions of promotional materials to the FDA, and such submissions are either voluntary or mandatory. All promotional materials for any prescription drug must be filed with FDA at the time of initial dissemination or publication (though see here for an important exception regarding social media). In addition, a small class of products (call subpart H or E) have additional mandatory submissions.

In addition, companies sometimes request voluntarily that FDA provide feedback (so-called advisory comments) on draft promotional materials. Companies do so to minimize the likelihood of receiving an FDA enforcement action, since the worst situation a company can find itself in is having spent money to develop promotional materials only to have FDA take enforcement activity that requires the company pull the existing materials and lose the time and money of creating all new materials. Voluntary submissions of promotional materials primarily include requests for advisory comments from the FDA on a newly approved product in its launch phase, TV spots, new messaging, or perhaps as a result of previous enforcement activity.

Because all submissions of final samples of promotional materials include a completed copy of Form 2253, these submissions are typically referred to as 2253 submissions. Though note that APLB requires that companies include Form 2253 for voluntary submissions of draft materials for advisory comments; and that difference will continue even in the new eCTD submissions as proposed in this guidance.

3. Guidances are usually voluntary; but this one isn't (sort of)

Right now, everything in this guidance is voluntary; and the guidance itself is in draft status. There is no requirement that any company begin adopting the procedures set out in this guidance today.

HOWEVER, after this guidance is finalized by the FDA, then parts of the guidance (the parts addressing mandatory submissions of promotional materials) will become mandatory 24 months later.

So, even after the final guidance is released (and there's no way of knowing when that will be), only parts of this guidance will represent mandatory changes; but the mere fact that some parts of the guidance are mandatory is itself a significant difference from most other guidances.

4. But aren't TV spots required to be submitted for review 45 days prior to use?

No. PhRMA's guiding principles on DTC television advertising recommends that companies submit them to the FDA with sufficient time for FDA to review them, but this is not a regulatory requirement. It is only binding on PhRMA signatories, and even then, the companies are not required to submit the materials for advisory comment, just to give FDA time to comment, should the Agency choose to do so. 

Also, FDASIA granted FDA authority to mandate that TV spots be submitted to FDA 45 days prior to airing for FDA to comment, and FDA issued a draft guidance about how it would implement such a program. However, as this new guidance states repeatedly, that guidance has not yet been implemented, and FDA does not want companies to follow those procedures currently. The process itself is deeply problematic, as I pointed out in an appendix to my primer on the topic.

5. Is there any glaring change from current 2253 submission processes?

This guidance provides far more extensive discussion of the submission of promotional material than previous direction. Most of the discussion will sound familiar to ad-promo professionals. One item that leaps off the page in the section on final samples submission is this passage:

Firms are also encouraged to submit annotated versions of the promotional material(s) cross-referenced to the product labeling and references, if applicable. (page 6)

Standard final samples submissions do not include references, and this "encourage[ment]" appears in a section of the document that otherwise will cover mandatory changes. Adopting this change would be deeply problematic for most promotional materials.

In the standard review and approval process, the references are only included for the initial medical legal regulatory (MLR) review, and then deleted from subsequent check-changes, and final samples submissions to the pharmaceutical company. Adding references back for the final 2253 submission would create significant additional expense, and would create additional possibility for error during the most time-sensitive portion of an elaborate process. 

New Video Lecture Available

The Digital Health Coalition, where I serve as one of the Digital Scholars, has created a new online resource called the Digital Health Coalition Academy. At this online destination, they are providing a series of short videos about topics of interest to people working in the digital health space.

I am pleased that they asked me to create one of the inaugural presentations. I chose to update and slightly expand on the presentation I previously delivered at the FDLI enforcement conference. 

I've previously asked on this blog how much value people get from the slide decks I post on SlideShare when there's no corresponding audio because I sometimes post unaltered decks that were not created as standalone pieces, but were intended to be accompanied by my narrative.

I've also previously declared my intention to start making more video content available, and though this presentation isn't on my YouTube channel, which remains woefully inadequate, I hope the DHC partnership will jump start that process.

Please provide any feedback in the comments or privately about whether you find the presentation useful, especially whether it was significantly more valuable than just the slides alone on SlideShare.

Another Google Search Letter

Just 10 days after issuing its space-limited guidance that included a significant discussion of Google search ads, the Office of Prescription Drug Promotion (OPDP) issued a new letter to Gilead for a a paid search ad.

Here's the violative ad as posted by the FDA:

The infractions don't differ substantially from those cited in the landmark 2009 set of 14 letters for inappropriate paid search campaigns that in many ways began the current emphasis on the unique characteristics of space-limited contexts.

In those 2009 letters, multiple products were cited for three infractions:
1. Failure to use the required established name
2. Omission of risk information
3. Inadequate communication of indication

In addition, one product was cited for overstatement of efficacy.

The new letter includes again the omission of risk information and failure to use the required established name; however, this time the FDA cited a lack of adequate directions for use and a failure to submit under form 2253.

The failure to submit under 2253 is well understood.

The lack of adequate directions for use points to the inclusion of the word "prevention." Viread is currently approved for the treatment but not the prevention of hepatitis B.

As I mentioned previously, I'm working on a new article for the September issue of Regulatory Focus that will revisit Google paid search and pull together everything we have learned from the 2009 enforcement action, subsequent statements from the FDA, and the new draft guidance. This enforcement action definitely adds another piece to that puzzle.

A Different Twitter Proposal

I've been thinking further about the FDA social media guidances delivered this week and especially the "Twitter" guidance, which isn't just about Twitter, but which does have significant implications for brand communications on Twitter.

What if the FDA had proposed a different framework?

Here's the FDA's sample compliant Tweet:

NoFocus (rememberine HCl) for mild to moderate memory loss-May cause seizures in patients with a seizure disorder www.nofocus.com/risk 

This Tweet takes up 134 of the 140 characters available on Twitter. It includes

• Brand name (NoFocus--7 characters)
• Established name (rememberine HCl--17 characters including space and parentheses)
• Link to risk that includes both brand name & indication that risks are presented (www.nofocus.com/risk--20 characters)
• A hyphen to separate benefit from risk info (1 character)

These are the mandatory elements of the Tweet, and they take up 43 characters with the balance available for communicating both the most serious risks and a non-misleading indication statement.*

Of course, the exact length of the brand and established names will change the number of characters that are set aside for accommodating the FDA's proposed mandatory elements. 

One challenge is that almost no brands will be able to provide a non-misleading indication statement and all of the most serious risks** in the space that's available after meeting FDA's mandatory elements. 

Another challenge is that although the FDA might not object to the sample Tweet they provided, users of Twitters certainly would object. Their objection wouldn't be to the regulatory compliance of the Tweet. Their objection would be to its value, as in, it has none. While such a Tweet might occasionally be useful for some products, and perhaps be a promoted Tweet on occasion, not many people would be inclined to follow an account peppered with this type of content.

The sample Tweet provided by the FDA is analogous to someone going on Twitter and saying, "I'm great. Read more about me here." And although some people do in fact use Twitter to do that, people who primarily send out such communications are rarely successful. Instead, communications need to meet the needs of the other users of Twitter, who might be looking for information about a product, news, etc. 

Responding to such information seeking behavior and providing customer service are two of the best uses of Twitter by companies (not just pharmaceutical companies), and it is not unreasonable to believe that most of these needs can be fulfilled without providing any benefit information about the product. So, if, for example, I want to know how to sign up for a co-pay program for your brand, just getting a reminder-style Tweet with a link to the co-pay program link can be very useful. Some companies are already engaging in this type of activity.

That's one reason that it was so disappointing that the guidance didn't address reminder ad formats.

However, on occasion, there might be a need to include benefit information, and when that happens, the format set forth in this guidance is greatly limiting and not likely to be accessible to most brands. So, instead, I was considering a format along the following lines:

The brand name would be presented in the Twitter handle, not the body of the Tweet itself. The Twitter handle has a 15-character limitation, and limited risk information could be presented in the Tweet in a manner that makes clear that additional risk info is available at the destination URL.

Modifying the FDA's Tweet to meet this proposal would yield this sample Tweet:

For mild to moderate memory loss-Risks incl seizures in some ppl bit.ly/isi

Assuming this Tweet was sent from @NoFocus, let's see how that Tweet compares to FDA's format.

Because both the brand name and the generic are omitted from the Tweet itself, that eliminates 25 characters from the Tweet that were taken up by those two elements plus the space between them. I expanded from the hyphen to include the phrase "Risks incl" so that's a growth from one character to 11, but I did that both to provide explanation for users about what the next few characters were going to present as well as to set up the expectation that the link that is provided will have further risk information. It is extremely common on Twitter to abbreviate the word "include" with "incl" so that is likely to be understood by most users of the platform.

Then, I made use of a URL shortener (bit.ly) and a common abbreviation for the page name (isi) where the risk information is provided. This meets the FDA's criterion for the URL that it not be promotional in content or tone, and because I preceded it with the phrase "Risks incl" users expect to find product risks presented at that page, which the FDA accomplished in its example by including the product name and word "risk" in the URL itself.

The phrase "Risks incl" also accomplishes the goal of clearly communicating within the Tweet itself that the brand is NOT providing all of the risks associated with the product within the Tweet itself. So, users are alerted that there are other risks to the product and they can learn more by clicking on the link. 

The revised Tweet is only 75 characters with 21 characters devoted to providing mandatory risk information, not including the risk statement itself which would vary by brand:

• The phrase "-Risks incl" (11 characters)
• A shorter url linking to the risk information (bit.ly/isi--10 characters)

And in that case, I would be able to provide additional links or other information such as directing this Tweet to another user. Imagine the following exchange:***

@phillycooke: My father was prescribed Brandufate by his doctor. What does Brandufate do?

@Brandufate: @phillycooke It's for mild to moderate memory loss-Risks incl seizures in some ppl bit.ly/isi

In the conversation, I have now presumably provided some value to the person who was looking for information about my product, while meeting almost all of the FDA's requirement.

I write "almost all" because I didn't include the generic/established name in this example. My belief is that in this type of space-limited context, it would be better for the FDA to permit that the established name be provided via the landing page with the risk information, not in the Tweet itself. I believe that meets the needs of users better and also provides extremely valuable characters for communication in the Tweets themselves.

The FDA's guidance explicitly points out that it is not addressing the landing pages, home pages for brands on Twitter, etc.. It is worth noting, though, that a brand's participation on Twitter is not limited to the Tweets it sends, but also includes the brand's home page, description, and a Twitter icon. These other locations provide what I believe are more appropriate locations for presenting the full brand and generic names in compliance with all of the FDA requirements for presenting the established name.

And because Twitter has a verification service available, it would be possible for users to understand via the blue checkmark icon that the account providing them information is an official representation of the brand, who is subjected to FDA regulatory oversight and therefore meets a higher standard for accuracy.

I'd love to get some additional feedback on this proposal, so post your comments, send me your emails, and let me know.

* Keep in mind that the FDA is saying that both of these elements are required. It is not OK to omit either the risk or the indication statement.

** And the guidance is unambiguous about the need to include ALL of the most serious risks. Quoting from the guidance: 

At a minimum, a firm should communicate the most serious risks associated with the product together with the benefit information within the individual character-space-limited communication. For a prescription human drug, the most serious risks would generally include all risk concepts from a boxed warning, all risks that are known to be fatal or life-threatening, and all contraindications from the approved product labeling (the PI). (p. 9)

*** For my modified Tweet, I'm changing the brand name because @NoFocus actually exists on Twitter as a user. I created an account for @Brandufate for demonstration purposes. 

Let's have a chat!

Some of you might recall that in the fall, CDRH released a finalized version of its mobile apps guidance (see here and here on that). A few days later, they hosted a live Twitter chat on the topic. They used the hashtag #FDAapps and have actually kept that going for ongoing updates.

I participated, as did I'm sure many of you, and it extremely informative. I commend CDRH for setting the precedent and embracing new platforms for outreach.

In that same spirit, I suggest that now is the perfect time for OPDP, APLB, and CVM's advertising arm to join Twitter (none has an official Twitter presence so far as I'm aware and based on the FDA's official listing of social media accounts) and talk about the new social media guidance on presenting benefit and risk information in space-limited contexts. This seems especially appropriate given that the guidance dwells so heavily on Twitter usage.

I floated the suggestion on Twitter yesterday, and @FDAmedia picked up on it. So, now, I'm hoping you'll help me keep the conversation going by Tweeting, posting, sharing, etc., to see whether we can get FDA to participate.

And even if we can't get FDA's involvement, let's plan on holding a Twitter chat of our own on this topic soon.

FDLI Advertising & Promotion Conference

I have accepted an invitation to speak at this year's Food & Drug Law Institute Advertising and Promotion conference about social media issues.

I'd like to solicit your input on topics for an interesting session. Of course, we'll have to cover OPDP's first social media guidance (see here and here), but what else do you think is particularly interesting or relevant to the participation of prescription-only products in this space.

Are there specific issues that you have not seen previously addressed? Have you seen anyone do something especially interesting in their use of social media that you think the industry as a whole needs to learn more about?

Send me your suggestions, or post a comment below.

Generics Marketing Receives Another Letter

The Office of Prescription Drug Promotion posted a new letter to its website for the marketing of a generic product (disulfarim tablets) by Alvogen.

Alec Gaffney provides a nice overview of the letter in Regulatory Focus.

Traditionally, generics marketing has not received as much attention from OPDP or its predecessor DDMAC. That has probably been true in large part because there was not as much marketing of generics.

But the post-blockbuster era in pharma meant that lots of drugs with extremely high sales volumes lost their patent exclusivity and generics companies have leapt in to more competitive markets attempting to distinguish themselves and promote their offerings.

FDA has not apparently believed there was any need to provide generics-specific guidance on marketing, as none of the generics guidances provided by the Agency have focused on marketing.

With the recent enforcement actions for generics marketing (in addition to disulfarim, see here, here, and here), and the soon-to-be-approved biosimilars with different possible approvals (interchangeability and biosimilarity), it would be good to hear more from FDA about how it views some of the unique aspects of marketing follow-on products.

Searching OPDP Letters Made Easier

John Driscoll, whose book should be on the shelf of every ad/promo professional, has a great tip on his website for searching OPDP's database of enforcement letters.

Instead of entering a phrase such as "FDA Warning Letters" + company name or brand name + issue you want to research, use this link , which is also on John's website. Then just replace the word "misleading" in the first part of the search for whatever issue you want to research (e.g., "patient testimonials" or "comparative claim" or "peanut butter").

That will search most OPDP/DDMAC letters since 1997. There's some finickiness because the OCR isn't always flawless, but it's a much better search technique that starting from scratch.

Facebook at it again--updates layout

That sound you just heard was the collective sigh of the 25 or so marketers who convinced their companies that Facebook is the appropriate venue for their prescription drugs to have a branded presence. They then spent weeks or months in MLR reviews explaining how everything works and discussing the relative merits of different approaches to presenting risk information in this context.

They're sighing because Facebook just announced another update to its page layout. My colleague Samantha Arabolu has the full rundown here: http://ow.ly/uIh6l

The changes themselves are not earth shattering, and in reviewing them with Sam, I didn't see anything that would cause me to think an initiative that was perfectly fine before would suddenly become non-compliant in after the change.

[BTW, if you disagree and think some of these changes seriously jeopardize things, please say so in the comments on this post.]

Nonetheless, the sigh was heard because all of those materials will have to be updated in light of the new layout, and as FDA made clear at the DIA Marketing Pharmaceuticals conference last month, when the third-party platform you're engaging in updates, then you have to re-submit your materials under Form 2253.

Q: #socmed changes platform on you. Must you resubmit the initial piece? #diamktg

— Dale Cooke (@PhillyCooke) February 27, 2014

A: (Abrams) Yes, you do. Could completely change presentation of the piece #diamktg

— Dale Cooke (@PhillyCooke) February 27, 2014

And here's the one and only thing I can guarantee you about Facebook: this is going to happen again. The only guarantee in such arenas is change. And most of those changes will probably be similar to this one. They'll require you to adjust materials, re-review them with MLR, and resubmit to FDA under Form 2253; but they're not likely to revolutionize the platform in a way that significantly alters the core functionality.

So, when you decide to engage in third-party platforms, you simply have to factor in the cost associated with these types of updates because they will happen, and when they do, there will be a cost to update your promotional materials.

RAPS Philadelphia Chapter Presentation

I'll be speaking at the Philadelphia chapter of the Regulatory Affairs Professionals Society on April 1 at the Homewood Suites Hotel in Malvern.

 I'll be covering the first FDA social media guidance, which you can read here.

The presentation will cover my view that is also presented here. In addition, there are updates from the Drug Information Association's Marketing Pharmaceuticals conference last month. BTW, here's one of my presentations from that event.

Here's the registration page on RAPS website for the April 1 event. I hope you'll join me!

OPDP Facebook Regulatory Alert

The Food and Drug Administration's Office of Prescription Drug Promotion released an untitled letter for inappropriate use of Facebook to promote a prescription drug. Digitas Health just released a Regulatory Alert to help other companies marketing prescription products learn from this action and ensure they don't face the same consequences. Here's the alert: http://www.scribd.com/doc/212262834/DH-Regulatory-Alert-OPDP-Issues-First-Letter-for-Facebook-Page-Activity