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.
- 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.
