OPDP Finds another Kardashian sister in their 3rd letter this year

 OPDP sent out their first untitled letter (3rd letter overall), in a letter dated Monday, March 8th.   

This letter, sent to Biohaven Pharmaceuticals about their migraine medication Nurtec ODT, involved a testimonial interview with Khloe Kardashian.   Not lost in the irony of this letter is that in 2015 Kim Kardashian was the testimonial-maker in her tweet about how effective Diclegis (Duchesnay Pharmaceuticals) was at treating her morning sickness.  

These two testimonials had a lot in common

• The testimonial-giver presented their own experience which was way above average for what would be expected with the drug they were prescribed. (overstatement of efficacy)
• There were inferred comparative claims
• Both letters were due, in part, to a complaint to FDA's Bad Ad Program.

The most recent letter also had some other elements in it not in the previous letter:

• This testimonial was a video (not a tweet like in the first letter)
• This video was designed to be promotional as it had ISI at the end
• This video was not submitted to OPDP at time of first use.

The main things from a Regulatory standpoint, that were important about this letter were:

• The testimonial contained numerous overstatements of efficacy (e.g., time of onset of action) and comparative claims (e.g., nothing else had worked or only worked for a short while)
• Single words like "gamechanger" represent significant superiority claims
• The ISI was at the end of the interview in small letters which were on the screen for 4 seconds and was preceded by a statement by the moderator ("we'll be right back") that would infer the end of the interview.  So , instead of a callout (signal) that the ISI was coming, the ISI was minimized, similarly to when a press release puts ### above the ISI.
• Failure to submit a clearly promotional piece at time of first use. 

The first two bullets are typical of many OPDP letters in the past and point out the problems with using testimonials.   The spokesperson is not just giving their opinion.   Their words actually become promotional when linked to the manufacturer of drug or even, in some circumstances, with the disease state if that testimonial is tied, in some way, to the product class.  Normally what I have found is that a good testimonial agreement is a good place to start with someone giving the testimonial.   This agreement should note that the product exists in a highly-regulated industry and that company has the right to modify or not use the testimonial if they feel it is overly and unduly promotional.  People who give testimonials rarely understand the guard rails that companies must operate in so inclusion of language in the agreement about what is appropriate and what is not appropriate is always helpful.  

The 3rd bullet talks about minimizing the ISI.  Use of "supers" to point to the ISI at the end and to point out the limitations of use in the product are very helpful in balancing the claims.   Also, if care is taken to avoid statements like "we'll be right back" and other signs that the video content has ended that would help.   

The final bullet, failure to submit under cover of Form 2253, is interesting.   Research I have done shows that when FDA says this they don't always mean that the piece was NEVER submitted.   It also can mean the piece was submitted late compared to when it was first used.   The examples I found had pieces that were submitted to OPDP anywhere from 30 days after they were first used up to 5 years after they were first used.    In this case, as with other cases like this, it is impossible to tell how long it was after first use the piece was submitted to OPDP, if at all.

As a final note, normally videos like this are pulled by companies soon after the OPDP letter goes out. A quick search of YouTube and social media found the following videos that were still up today (March 11th) that contained claims from Kardasian on Nurtec.  Not all of them were company-generated but, normally, this is all cleaned up immediately after OPDP issues a letter like this.   Interestingly, not the case in this situation.

Khloé Kardashian Has Suffered from Migraines Her Whole Life - YouTube

If you google you can also find promotional Twitter and Facebook postings/videos that contain some of the same claims (e.g., 15-30 minute relief) that were mentioned in the OPDP letter.   At least at this point, Biohaven has not removed this information from the internet.   Time will tell to see if it is/can be removed.   

 

Second OPDP Letter of 2021 - Previous Communication Leads to Heightened Surveillance

It didn't take OPDP long to issue its 2nd letter of the year.   This time it was a warning letter to Cooper Surgical for its promotion of PARAGARD” (intrauterine copper contraceptive).  

This letter had familiar aspects to it seen in previous letters from OPDP:

• Resulted from a complaint through FDA's Bad Ad program
• Followed another letter to Cooper Surgical about the same product in 2019
• Concerned a video that mentioned the company and product name and had both inferred and real claims about PARAGUARD but did not have any safety information.
• Video was not submitted under cover of Form 2253 at time of first use
• As a warning letter it required Cooper Surgical to do corrective action

The letter also had some interesting aspects to it:

• The first footnote of the OPDP letter implied that OPDP first saw this video on October 5, 2020 and last accessed it on February 12, 2021, the same date as the letter sent to Cooper Surgical.
• The letter invited Cooper Surgical to contact OPDP if it wanted to discuss OPDP's concerns and to provide evidence that the video was not violative

SUMMARY

On the surface, this letter represents to just represent low-hanging fruit for OPDP. It points out that receiving an OPDP letter places the company, in general, and the product that was the subject of that letter, specifically, under heightened scrutiny for future promotion.   But there is more to this letter than that.

Looking a little deeper it also interesting that both the 2019 and 2021 letters to Cooper for PARAGUARD resulted, at least in part, from complaints through the Bad Ad program which could imply that HCPs are looking at a company's ads more closely after an OPDP letter is issued.   

Also, the description of the violations in the most recent letter to Cooper (no ISI, no submission to OPDP) could imply that Cooper either did not know about this video or that they thought that it was educational and non-promotional.   There have been other examples in the past where a company did not know that a TV commercial had been produced and that the agency that produced it might not have understood FDA regulations on fair balance, etc. required in a drug promotional ad (e.g. Rozerem TV ad).  There are also examples where companies have included reference to a drug in an otherwise educational piece which, of course, rendered the entire educational piece promotional e.g., (Ovide letter).  

It is not clear so I cannot speculate on these possibilities but it is hard to believe that a company could have received an OPDP letter on a TV ad for PARAGUARD and, about a year later, knowingly produced/approved another TV spot that was so obviously violative, as well.   My guess is that there has to be more to the story than what is evident from the letter.

It is also intriguing that this video was viewed by OPDP four months before the Warning Letter was sent out.   Historically it has taken longer for Warning Letters to be issued as they required extra review within FDA before they are sent out.   The interesting part is that the violation was discovered under one political administration, but not acted upon until the next political administration took over.   As I said in my last post this is a trend that will have to be watched in the future as it is my impression that the previous administration believed that FDA was, and should not be, putting up too many roadblocks to the pharmaceutical industry.   Although the number of OPDP letters issued in a given year can vary dramatically from other years and, whenever this happens there has been a lot of speculation regarding trends like this, it is generally not known if there is, in fact, any real reason for this or if it is just yearly variation.  As I said, it will be interesting to watch in the future to see if the trend in an uptick in OPDP letters continues in 2021 and into 2022.  

Finally, although it might not mean anything, it is interesting that OPDP invited Cooper not once but twice in the conclusion to the recent letter to contact OPDP if they wanted to discuss this.  Invitations like this are generally part of the boilerplate language in some OPDP letters but this time that language just struck me as being slightly different in tone than previous times I have seen it.

Hopefully this analysis was helpful to you.

First OPDP Letter of 2021

OPDP did not waste much time in inputting their first letter of 2021, a warning letter to AcelRx Pharmaceuticals for ads regarding their sub-lingual opioid medication, DSUVIA (sufentanil) tablets.

Interestingly, OPDP has included a new document with this first letter.  The document, called the "CDER Statement" outlines OPDP's concerns with the promotional material they are citing.  In addition to summarizing the CDER/OPDP opinion that led to the warning letter, the CDER Statement also, once again, solicited HCPs to report inappropriate promotional activities and everyone to report adverse reactions, medication errors and the like.

The OPD letter concerned two promotional materials but with the same claim "Tongue and Done".   FDA took offense to this claim being in big letters in a tabletop display and on a banner in a pormotional booth, both of which were presented at a conference.

Here is the breakdown:

THE BAD

• They objected to the tag line, itself, as oversimplifying the use of the product which has serious limitations to its use which were outlined in a REMS.  The letter stated that as DSUVIA is an opioid its use and disposal, consisting of 7 steps, is not simple as is implied by the simple tag line.  
• OPDP was also concerned that the PI for the product said not to use more than 12 doses per 24 hours.  The banner included the statement "Minimum dosing interval: 1 hour" but did not include the material fact regarding the maximum number of doses per day, giving the impression that you could take as many as 24 doses in a day.
• Both promotional pieces made claims and representations in large letters that needed fair balance but that fair balance was only present in small font in paragraphed ISI. 

  THE INTEREStiNG

• OPDP did not object to the table top graphic having pointer to information (indication, ISI, limitations of use and boxed warning being available in the convention booth (as opposed to being available from a sales rep in the booth).  Interestingly, this pointer could have meant that the ISI was on a different placard somewhere in the booth.  It is a little confusing as the ISI appeared to actually be on the table top graphic
• OPDP did not comment on why there was no appropriate pointer to the PI.   In fact the ISI on the tabletop graphic did have what I would refer to as a "non-pointer statement" which said "Please see Full Prescribing Information and Directions for Use."  Pointer statements are supposed to point to something but OPDP did not object to this pointer statement not pointing to where the PI was available.  As said above, OPDP likes the PI to be available in the booth without the reader having to go to a sales rep to get the PI.
• OPDP did not object to the second tagline that said "Effective Pain Relief   Efficiently Delivered."  This statement was right above the ISI on the same page.
• These materials were dated 2019, meaning OPDP may have taken 2 years to act on them.   It is not clear whether this was due to the pandemic or whether it might have been due to a change in political/governmental administration.  In any case, it will be interesting to watch whether this the beginning of a trend that sees more letters in 2021 than in previous years due to either or both of these factors.    

SUMMARY OF LETTER AND PROMOTIONAL MATERIAL

FDA (and DOJ) have shown in the past that they are very serious about taking steps to lessen the opioid epidemic.  For OPDP, this means being very precise with language and following the regulations on fair balance and inclusion of material facts, especially in light of these products having REMS that they need to follow which emphasizes, among other things, training on appropriate usage and disposal of opioid-containing pain medications.   

So, for OPDP, this was low-hanging fruit.  But what does it teach those in the rest of pharmaceutical industry about their promotional materials?

This letter points out the risk of leaving out or minimizing fair balance, material facts and other, more general, important safety information.   It is possible that directly including the limitations of use right below the tag line "Tongue and Done" and the claims "Minimum dosing interval: 1 hour", "DSUVIA comes in one strength for acute pain" would have mitigated the risk sufficiently for OPDP.  As said above, OPDP did not comment on the side of the tabletop graphic when the other tag line "Effective Pain Relief  Efficiently Delivered" was used with the ISI right below it, even though the ISI was in small font in paragraph form (i.e., not bulleted).  

I am sure that many of us have seen ISI similar to what is on the tabletop graphic and the banner ad and the ads that use this presentation have not received an OPDP letter.  We have probably also seen tag lines like the ones in this piece, likely where the ISI was separated from the tagline and in small letters, with the ISI maybe even being in paragraph form like this one.   We have likely all seen these tag lines being devoid of mitigating statements with the tag line, with all the mitigation relegated to a block of ISI, minimized by being in small font in paragraphed form.  And none of those pieces ever received an OPDP letter!!!!! 

That is really, for me, the takeaway point of this first OPDP letter of 2021.  Just because you don't get a letter for having tag lines that don't include fair balance or you relegate your ISI to paragraphed form in small font way separated from your claims, doesn't mean it isn't a violation.   My opinion is that it is probably the WORST type of violation for a pharmaceutical company to make in its promotional materials because it could easily be avoided.   So, my request to all of you is to be aware of how tag lines could be misinterpreted.  Where material facts need to be included, give appropriate weight to those facts in conjunction with the claims/tag lines you are using.  Finally, put ISI in bulleted form with white space between the bullets, use some ISI on every page if you can do it and don't minimize the ISI in any way: size, contrast, ordering of ISI or other factors.

To conclude, the first OPDP letter of 2021 could easily be written off to OPDP coming down on an opioid manufacturer with a REMS on their product in the middle of an opioid epidemic, but most of us shouldn't take it that way.  In my opinion, this letter should be seen as a gentle reminder for the rest of us to take more care in balancing the benefit and risk information in our promotional pieces.   That is a message that OPDP has delivered to industry for decades now.   This is just a little reminder to all of us not to forget these important considerations when we are reviewing promotional materials.  

Does Your Ad/Promo Team Need a Refresher Training?

 There are lots of people who are involved in the creation and approval of pharmaceutical and medical device promotion.   Regulatory, Medical, Legal, Marketing, Market Access and Training, to name a few, would benefit from having occasional refresher trainings on ad/promo.  Even executives would benefit from a short refresher/training course on advertising and promotion basics and common pitfalls.

I have found that even if companies offer basic training for their employees, refresher training on advertising and promotion is something that generally falls through the cracks. 

Nosco Consulting offers two courses:

1) Basic/refresher course:  This is a 3 hour training that is done remotely.   It covers the basics of pharmaceutical and medical device promotion and gives plenty of hypotheticals and real life examples that help people navigate through how to create compliant and effective promotional materials.   Even if your team or individuals on the team have had Ad/promo 101 training in the past, this course will likely offer a different, entertaining approach to this subject that will help stimulate thought and create a better process at your company.  

2) Executive course:  This will be a 1 hour remote  course that will focus on current thoughts on promoting pharmaceuticals and medical devices in the current environment.  It is designed to be thought-provoking in regard how the regulatory landscape is changing in medical product promotion and to help align the executives with the promotional review process that is going on in their company.   The course looks at the world through the eyes of pharmaceutical promotion but also should be useful to executives at medical device companies.

If you are interested please feel free to contact me at dnosco@hotmail.com 

New OPDP letter with the type of violations seen in previous letters

 The latest OPDP letter, an untitled letter, came out this week and, as usual, there are interesting aspects to it.   Here are links to the letter and the promotional material:

Link to untitled letter: https://www.fda.gov/media/144115/download 

 Link to promotional material: https://www.fda.gov/media/144114/download

Here are some of the highlights of this letter:

1. The letter, addressed to Azurity Pharmaceuticals which was previously known as CutisPharma and is the parent company of Silvergate Pharmaceuticals which was identified in this untitled letter as the NDA holder at the time of NDA approval.

2. The letter appeared to be prompted somewhat, at least, by advisory comments provided to Silvergate, presumably on launch materials.  Those comments were completely redacted in this untitled letter so it is hard to say what FDA's advisory opinion was, exactly.  However, the mention of the advisory comments appears to signal that what FDA originally told Silvergate was not currently being followed in promotion of the drug in question, XATMEP® (methotrexate) oral solution.  

3. This letter, which dealt with an e-mail sent out by the company to HCPs, has a number of violations, some of which have been mentioned previously by OPDP in letters to other companies. These include:

    a. Put the safety information at the bottom of the e-mail below the signature line.  OPDP said, as it has previously, that putting safety information below a signature line or other signal that the document has ended minimizes that safety information.  In the past they have cited companies for having safety information at the bottom of a long (multipage) e-mail without any pointer to it in the e-mail.  They have also cited companies forplacing safety information at the bottom of press releases that had signals (for example, several hastags in succession) above the safety information indicating that the press release content was finished.

    b.  Had the boxed warning as the only balancing safety information for the claims in this piece.   I have seen this with other companies in recent months, thinking the boxed warning was all the safety information they needed to make significant claims about their product.   It stands to reason that since boxed warning products require the boxed warning just to have a reminder-like ad (product name only, no claims or representations that could be interpreted as real or implied claims), that you would need more safety information that would be contextual to your claims if, in fact, you had claims in your promotional piece. 

    c. Not having the right safety information.  The is an important violation and one not always cited by OPDP.  Azurity made a claim about easy dose titration and OPDP said that this should have triggered inclusion of safety language from the PI saying the drug should be taken weekly and that taking the drug daily could lead to fatal toxicity.  This likely came up in the advisory comments, based on the sentence immediately after the redacted section.

d. expanding the indication by shortening it in a succinct claim.  They e-mail template said: "I wanted to let you know that Xatmep® (methotrexate) oral solution is available for your patients with Acute Lymphoblastic Leukemia." OPDP opined that this implied that Xatmep had no age limitation on its use and had no limitations on its use, including that the statement, as written, implied that Xatmep could be used by itself and, although the OPDP letter didn't say it,  possibly as a first-line treatment.  The actual indication says that Xatmep was approved for pediatric patients and as part of a multicomponent chemotherapy treatment regime.  OPDP said that presenting the exact indication at the bottom of the e-mail didn't offset the expansion of the PI above, once again stating, as it has in many instances previously, that a company cannot mitigate a false or misleading statement by having correct information somewhere else in a promotional piece, especially if the correct information is minimized in some way (e.g., in a footnote or placed far away from the misleading claim).  Most interesting was that the e-mail template, one sentence previously, said "...[I am] a representative for Azurity Pharmaceuticals specializing in pediatric medicine." Apparently OPDP did not consider that the statement that this representative was a pediatric medicine specialist was sufficient to mitigate that the claim did not specifically mention pediatric in its claim language.   OPDP has, over the years for varying reasons, clearly stated that expansion of indication can occur from truncating indication language to save space and has ruled in an advisory comment that I am aware of that even when that truncation did nothing to change the meaning of the indication, OPDP wanted the company to use exactly the indication language as it appeared in the approved indication.  That advisory opinion is consistent with their opinion in this letter.

No one really knows what Azurity could have done to mitigate risk to avoid this letter but here are some simple suggestions that I think might have helped (changes in strikeout and red) without changing the e-mail language substantially:

1. Use a pointer statement to point to the safety information and define the group the drug is indicated for.   An example of how this might have looked would be "I wanted to let you know that talk to you about Xatmep® (methotrexate) oral solution (see Important Safety Information, including Boxed Warning, for Xatmep at the end of this e-mail).  Xatmep is available for your pediatric patients with Acute Lymphoblastic Leukemia.  It is also the first and only FDA‐approved oral  solution that is available..."

2. Include in the Important Safety Information standard safety information and not just the boxed warning.   Normally this would involve inclusion of contraindications and important AND relevant warnings, precautions and use information, in addition to the boxed warning and indication. 

3. Be a little more careful with how claims, including the truncated indication, are made.  For example, the claim pointed out by the FDA could have said:

"Xatmep may benefit your pediatric patients

• 2.5mg/mL provides easy, once weekly dose titration as body surface area‐based dosing is  recommended." 

As is the case with many pieces cited in letters from OPDP, careful choice of wording, appropriate inclusion of safety information, appropriate use of pointers and understanding what OPDP has said in previous letters to other companies and in advisory comments about promotional materials previously for that drug to your company could have changed this outcome for Azurity.  Hopefully you all found this analysis helpful.

Fall brings two warnig letters from OPDP

As the calendar turned to fall OPDP issued two warning letters.   

One letter went to Nalpropion regarding their promotion of Contrave.  Several things stood out about this letter:

1. The letter referenced a previous untitled letter from OPDP to Orexigen, the previous NDA holder, regarding the inappropriate promotion of Contrave (2017).  A search revealed that Nalpropion purchased most of Orexigen's assets in June, 2018 and the current OPDP letter was issued just a little over two years later.   The take home message here is one that has played out previously in a number of OPDP letters when a drug on FDA's radar is sold by a company and the next company may not know of or consider the previous regulatory history of that drug:  If you buy the drug from another company you inherit all the regulatory history, including history with OPDP.  One thing I think ad/promo professionals should do in cases where their company acquires pharmaceuticals and/or medical devices is to explore the regulatory history like original labeling discussions, FDA reviewer communications, submissions of promotional materials for advisory comments and other FDA communications.  In one case I have heard of a company was promoting its drug appropriately and had generated a number of compliant, internally approved promotional materials.  When the drug was purchased the purchasing company created a promotional campaign using a number of the claims that were not allowed by the ad/promo review team at the first company.  The result was an OPDP letter not long after the new marketing campaign went live.   So it might also be a good idea if your company purchases a drug to review the approved promotional materials that were obtained with the drug.   If a claim you think was obvious is not present, there is probably a good reason for that.

2. The letter referenced the use of a sponsored weblink to promote Contrave.   As with previous OPDP letters on the same subject, this letter pointed to 2 issues: 

(a) Sponsored weblinks don't give you much, if any, room for safety information.  The letter reiterates that links to that information are NOT sufficient when the ad actually makes claims, as this one does.  There are mechanisms for including safety information if you can add fields to the meta data in your web search result to include safety information.  Do a Google search for "Enbrel" and if you scroll down the search results you can see an example of how to do this by increasing the number of sub-headings you populate in your search result meta data.   I don't know if Nalpropion was offered that opportunity when they purchased the sponsored weblink space but, if it was an option and they had taken that option, they might have avoided an OPDP letter if they had done this as a means to include safety information.

(b) Sponsored weblinks don't give you much text to work with and so it is very easy to overstate safety and/or efficacy by summarizing in order to meet character limitations.   Using only the space they used in their sponsored ad there is no way to fit in all the necessary information, including limitations to Contrave's indication to help with weight loss.  If Nalpropion had limited their ad to say "See how Contrave can help you with weight loss.  Click here (leading to product website)" instead of "Lose 2-4x more weight on average..." they might have avoided this letter as Contrave is approved for use in conjunction with diet and exercise.

Also, as FDA considered this a serious health risk (Warning letter) Nalpropion will have to do corrective advertising.   As this was a sponsored weblink and it may not be readily known who saw this ad, it could be quite challenging for Nalpropion to execute this corrective messaging.  Also, if you read text OPDP is requiring to be included, it would be difficult to imagine doing it all in a corrective sponsored weblink. 

Finally, it is important to note that OPDP said that this letter, in part, was written to Nalpropion because of the FDA's Bad Ad program, which encourages HCPs to report false or misleading drug promotion. 

The other letter was addressed to Nephron Pharmaceuticals for their e-mails regarding Budesonide.

The letter said that Nephron had issued e-mails talking about the use of Budesonide to treat Covid-19 symptoms.   The issue, of course, is that Budesonide is not indicated for this use.  

There are several points about this letter that I want to highlight:

1. I do not see any reference to these e-mails being submitted to OPDP as promotional labeling.

2. The e-mails were apparently sent by the CEO and at least one of the sales reps, making it appear like promoting Budesonide in this way was a corporate strategy, not just a sales rep doing this on their own.

3. The title of the OPDP letter included the language "(COVID Related)"

4. This was also a Bad Ad letter

5. This was also a Warning Letter requiring corrective action by the company.

This is the first OPDP letter I have run across that referred to COVID and I wonder if there was a reason for them to have added this to the title of their warning letter.  It is not hard to understand that this could be a sensitive area with FDA and that, potentially, they wanted to address this with companies that are thinking about promoting or actually promoting their drugs as treatments for COVID-19.  Similar letters went out during the anthrax mail situation where companies were purporting their medications to treat anthrax and FDA sent out a number of letters saying that these products were not approved for those uses.   I was wondering when the first OPDP letter would come out relative to a company promoting its drug as a cure or symptomatic treatment for COVID-19.   Now we have it.  When you add to the nature of the promotion that no safety information was included, it is interesting to consider  why a company would knowingly sent out communications like this.

One thought that crossed my mind was whether these communications were sent out thinking they were covered under the Caronia court case First Amendment rights.  The letter would seem to indicate that these claims did not result from any scientific publications but rather the support was from anecdotal reports, some of which were from YouTube videos.  It will be interesting to see if any future letters come out about promotion of drugs off-label to treat COVID-19 or if companies will see this letter and not promote their products in this way.

  

First Letter for 2020

OPDP has issued it's first letter for 2020, this one to Outlook Pharmaceuticals.

This letter incorporates two themes OPDP has addressed in the past: (1) having paid search ads with claims but no fair balance and (2) Having an ad for an ADHD drug without risk of suicide in teenagers.

In 2008 OPDP sent out letters to 4 manufacturers of drugs to treat ADHD.   These letters all had one similar theme: No or limited mention of suicidality risks of these medications, especially in teenagers and the elderly.

In 2009 OPDP sent out letters to 14 companies for having claims in their sponsored ads without any fair balance.   This set out a series of events that led to Google actually getting involved and working with industry to come up with standards for these sponsored pharmaceutical ads.   What wasn't addressed was that companies could partially defeat this objection by OPDP by just putting the same information in the html backbone of their website so that Google and other search engines would be more likely to pull that information up as the search result for that particular drug.  In fact, in the screenshots of the sponsored ads for some of those 14 drugs some of the same claims were present in these so-called "organic" (not sponsored) search results.

OPDP later cited another company for placing similarly structured weblinks within a product website for another drug, again without presenting any fair balance for those drugs.

The most recent letter to Outlook Pharmaceuticals has claims without any fair balance which, in turn, means that they failed to mention anything about the suicide risks of their drug.

It should be noted that in my research over the last several years I have encountered a number of companies, especially those with their first drugs, who use sponsored ad search results to give the indication or drug class of their drug.   In most cases these are just statements or summaries of their indication and DO NOT contain any claim language.   Even some of the larger companies who led the way in removing claim language in their sponsored ads are now, years later, putting those claims in their sponsored ads.

As OPDP has done many times in the past, if they want to refresh industry on a subject they find a relatively to very onerous example of something they have sent letters for in the past and send out another letter or two.

The bottom line here is that paying attention to what OPDP has said not to do, even if it is warning or untitled letters from over a decade ago, is something that can keep you out of trouble.   At the same time, following what larger pharmaceutical companies do and accepting that as industry standard and, therefore, a low-risk practice is a good way to get into trouble with OPDP.