PI Episode 1 - SUCRAID Untitled Letter

In this episode, Jason and Virginia break down the recent enforcement letter regarding Sucraid, highlighting its misleading promotional materials. The FDA has flagged two emails targeting healthcare professionals for their claims about the product's indication and presentation of safety.

We dive into the details—what was wrong with the promotional emails?  And what should be done differently to ensure compliance?

This conversation sheds light on the importance of accurate communication in healthcare. Let’s not forget: clarity in presenting risks is crucial for patient safety! 

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Transcript

SPEAKER_00 0:06

Hi everyone, this is uh Virginia and Jason from Compliance Forward. We are um here today with a special edition of the Promotional Intelligence Um podcast, and we're gonna be talking about an enforcement letter that just got posted this week on June 2nd, and um it was for a product called Suit Crade. Uh Jason's gonna break it down. We're gonna talk about the violations, um, the rationale uh we think for why they were cited, and um what makes this one particularly interesting. There are a couple nuggets in there, and um so let's get to it. All right, go ahead, Jason.

SPEAKER_01 0:46

Okay, thanks, Virginia. Let me get my screen share up. Uh so what we're gonna look at today, we have the untitled letter. Uh, we're gonna take a look at the promotional material that the FDA posted, and we're also gonna take a look at the label, which is gonna be really interesting because it's not it's in the non-PLF format, so it's gonna uh look a little bit different than what we're used to seeing. Uh but let's take a look first in the uh cover letter here of the untitled letter. So the letter starts out by talking about the promotional communications that are cited. Uh, there's two materials here, uh, a pediatric email and an adult email. So there's two emails that are subject to this untitled letter. Both of these emails are talking about a trial offer for uh getting a trial of the product and they're directed towards HCPs. And we're going to take a look at the emails here in a minute. Uh the letter also notes that both of these emails were submitted under cover of FDA Form 2253. And finally, the FDA has determined that the emails are false and misleading, which is why they are receiving the untitled letter. The letter then goes on to outline a couple of the claims and presentations. So let's uh flip over to the promotional piece because I think it'll make more sense if we look at this promotional piece to understand how the claims and presentations were assembled in this piece. So, very simple email. There's not a whole lot going on in these emails. Uh there's two emails here. We're just going to take a look at the first page because both the emails in this package look the same. We see at the top we have the logo lockup, and then we have a claim that says uh try-sucrate. Below that, in the middle section, we have another presentation that says, Do you have patients suffering with unresolved IBS-like symptoms, including gas, bloating, diarrhea, and nausea? And then it asks, could it be a CSID, which is uh the condition that sucrate is approved to treat? And then we have some information about how HCPs can get a sucrate four-day trial. We also see a little start here for a footnote. Uh, then it says to learn more about the only FD-approved enzyme replacement therapy for the treatment of CSID. And then the email wraps up with a call to action, and we have the footnote here with the TS uh terms and conditions, excuse me. And then finally, we wrap up with the indication and important safety information. And when we flip back to the letter, we see a few things. So the the letter calls out a few violations. Now the letter breaks the violations into two sections. Uh, the first section talks about efficacy information, and the second section, which we're going to get to in a few minutes, we're going to talk about efficacy first, but the second section of the letter talks about uh the risk presentation. So the first thing here in this first paragraph are the presentations of efficacy information. And what the agency is calling out are a few things. Uh first, they say that the presentation of uh the IBS-like symptoms, uh, it implies that the overland uh overlapping symptoms of congenital sucrase isomotis deficiency, CSID, uh, can be used to treat IBS. They also say that the email implies that sucrate can be used to treat all contributing factors of CSID, which is not the case. Uh, and then it says specifically the email fails to provide material information regarding sucrate's full FDA approved indication. So let's flip over to the label real quick and we'll take a look at what's going on in the label. Uh, as I said, this is a non-PLR uh label, uh, so it looks quite a bit different than what we're usually looking for or what we're used to seeing in labels. Uh but if we scroll down to the indication section here, let's just take a look quickly at the approved indication. Uh, sucrate is an oral solution uh and it's approved for the treatment of sucrase deficiency. So this is really important. It just uh is indicated for the treatment of sucrase deficiency, which is one part of CSID. So CSID, of course, is congenital sucrase, isomatise deficiency. That sucrase deficiency is one part of it. It doesn't address the isomaltise deficiency. And specifically, it's approved for adults and pediatric patients five months of age and older. So, Virginia, what what are your thoughts on this presentation?

SPEAKER_00 5:08

Well, first of all, I think the dinosaur is really cute. Gotta say it. Um, but seriously, you know, I think some of this could have been avoided. So the the letter says that the indication isn't presented in its entirety. So the indication is there. I just have to really, really scroll super far down to find it. So I think in this case, if I was working on this piece, I would have advised my client to bring the full indication up into more of the body of the email. Um, I think that would help a lot. I'm not sure if I'm totally on board with this presentation saying that they're trying to treat IBS. Um, I think it's we can agree to disagree with FDA on that one, but um that seems to be a bit of a stretch. But I do agree that the indication is not presented in its best light. Uh it's really tiny, it's really small, and we're gonna see that in the safety too when we talk about that next.

SPEAKER_01 6:14

Yeah, I agree. Uh when I initially read this too, I I saw that uh the the question uh do you have patients suffering with unresolved IBS-like symptoms? Um I I might not have included IBS-like symptoms. Um that would be my recommendation if I was advising a client. But um again, I you know, like you said, we can agree to disagree with FDA on this. Um I I think it's uh it's just one of those things that uh uh I think it's a little bit of a stretch. But uh moving into the next part of the letter, I I think this is really where uh FDA starts to uh hit on some really uh black and white issues. So when we get into the next part of the efficacy paragraph, uh we see that they acknowledge that the full indication is presented at the bottom of the email with the important safety information, but they say that it's presented in in small plane font after intervening text and eye-catching graphics and colors, and they say it's not sufficient to mitigate the misleading impression. Uh so Virginia, if we scroll down here to the bottom, um what are your thoughts on how they uh how the indication of ISI are presented in this email?

SPEAKER_00 7:21

Oh boy, not sure where to start. I think um I think FDA is spot on, you know, and I actually think that this is a really simple letter, but this is going to be helpful in our day-to-day work because it's it's really hard to, you know, I review hundreds of emails a week, and I think that this is an age-old problem is trying to figure out how to get the indication ISI. Um, and it's not easy to have um safety look as exciting as a cute dinosaur in this case, but you know, we have to do better than this. Um, I think the gray background is not optimal. I think the font size is way too small, and I believe FDA called that out. It's it looks like the same as the TNCs. Um, it's below the TNCs, that would have helped. Um, and and it doesn't have headers, right? Like if we're thinking about the presentation of risk guidance, which isn't cited in the letter, but I think we all still use that in our day-to-day work. Um and again, this isn't coming from PLR format. I haven't seen a non-plr format in years. Um, so that could be part of the problem. You know, it'd be really challenging to write the ISI if you didn't have the headers to kind of guide you in the order of the safety and and just kind of having the headers. Where are the warnings? Where's the contras? You know, you can't find it. It's just kind of a mishmash. So um, not optimal presentation of safety for sure. So I 100% agree with FDA on that part of the letter. What else? Oh, sorry. I was saying keep going. Let's talk about some of the detail of the safety.

SPEAKER_01 8:57

Yeah, so I'm gonna work through the next part because there's a lot going on in the second part of the email, uh, in the second part of the letter here. So uh the next set of violations, and again, I think completely agree with OPDP on this one, um, they really break this down and they really highlight uh and they give us a lot of good insights into you know what should be included in ISI. Uh so I'm gonna break this down. I'm gonna flip back and forth between the promotional piece and the label and highlight you know what's going on here. Uh so the first thing that we see in the section where they're talking about the omission of material facts regarding risk, uh there's a few things going on with that ISI that the FDA is calling out. And uh, if you're new to OPDP letters, it's important to note that whenever they highlight or whenever they underline uh text in their letter, they're signaling that this is the problematic area that should be addressed. So the first thing that we see, and I want to point out with non-PLR uh labels, uh the warnings and precautions are in separate sections. There's a dedicated warning section, there's a dedicated precautions section. Uh so that's why you see these headings uh in the letter formatted this way. So the first thing that we see is this severe hypersensitive re hypersensitivity reactions warning. And what they're highlighting here is first the label classifies this as severe hypersensitivity reactions. So let's flip over to the PI and then look at the ISI, I'm sorry. Uh and when we look at the ISI, the first thing that we see is that in bullet two is that that warning, and it says that sucrate may cause a serious allergic reaction. I think this is the first problem that they're calling out. Uh they I'm inferring uh from what's in the letter that they would rather see this instead of say serious, that they use the term severe, and that reaction should be plural because that's what's presented in the label. Um the next thing that we see is that uh they highlight the fact that the terms rash and paritis are omitted from the uh ISI. So we go back here, we look at the ISI, and we see that they say that patients should stop taking sucrate and get emergency help if any of the following side effects occur. So we see difficulty breathing, we see wheezing, and we see swelling in the face. But again, as they call out here, uh it doesn't include rash and it doesn't include paritis. Um now there is something interesting in this label that I want to call out before we move on because uh in the patient information section, uh you'll see something interesting here. If we scroll down to where the warning is, uh in the in the patient information section, we see that the patient information has difficulty breathing, wheezing, rash, swelling to the face, lips, and tongue, but it doesn't have paritis. So this is really important. Even though there's a uh a patient information section, even though uh it omits paritis, it's still important to remember that this is an HCP-directed promotional communication. Uh, and even if there's any kind of um uh misalignment between what's in the med guide or the PI, uh I'm sorry, the patient information, uh, if that doesn't align to what's in the prescribing information, you should always refer to what's in the prescribing information uh for HCP-directed pieces.

SPEAKER_00 12:14

And I have to say that happens a lot in my experience. We were talking about this earlier. The the PPI or the med guide, certainly the PPI in many cases, is one of the last things to be created uh uh by sponsors. And I've seen a lot of times where things don't sync up, and it's really hard to do our jobs when you don't have to um you know do that compare and contrast. But but you're absolutely right, always default to the the full PI.

SPEAKER_01 12:45

The next thing that they call out here is this uh have been reported, and and this is really important to OPDP. Uh whenever we're talking about these kind of warnings, uh, and there's hypersensitivity reactions, and they have actually been reported either in the trial or uh in reports after the fact, if patients who are taking the product are reporting these conditions, uh this is something that's very important to OPDP and it should be included in the ISI. So they're highlighting the fact that it's not in there, and if we flip back again to the warning, we see that uh there's no mention of the fact that these um that that these conditions have actually been reported. We go to the label, and what are they talking about? Well, the label says under the warning that a pediatric patient in the clinical trials experienced a hypersensitivity reaction uh of severe wheezing that required hospitalization. And there's also been post-marketing cases of uh cutaneous hypersensitivity reactions that have also been reported. So, again, uh anytime that there are actual reports of uh conditions uh that are aligned with a warning, uh it's really important to make sure that it's disclosed in the ISI that those have actually been reported. It's it's not just a theoretical situation where this might happen. If it has happened, it has to be included in the ISI in the eyes of OPDP. Moving on to the next section, we have the precautions. So we have a precaution here for uh blood glucose concentration with patients uh in patients with diabetes. So let's take a look first at what they say in the ISI. Uh so we see that there's a diabetic uh precaution here. It's bullet one, two, three, four, five. So bullet number five is talking about diabetic patients. And what it says is that the physician should consider that sucrate will enable sucrose hydrolysis and the absorption of these hydrolysis products. Uh, and that matches the first sentence that we have here under the precaution. But what it omits is the directive to the HCP to monitor blood glucose concentrations and adjust diet accordingly. So remember it's always important that if there are directives, if there's actionable uh directives to the HCP in the warnings and precautions, those should also be included in the ISI. So that's what they're flagging here. And then finally, we have another precaution for uh a dietary starch restriction. And uh let's flip back to the ISI. So here we see bullet three is where we see the uh uh that that precaution, and it says that uh sucrate provides replacement therapy for uh deficient sucrase. We saw that in the indication, uh, but it does not provide specific replacement therapy for the deficient isomaltese. Again, that wasn't the indication. Uh we know that it the the sucrose deficiency or sucrose deficiency is is what uh sucrate is indicated to treat, and it doesn't treat the isomaltese. But what is omitted and what they're getting at here in this underlying text is what does that mean for a doctor? What does that mean for an HCP? And it says that patients may still experience symptoms of CSID while taking sucrate. And if that happens, it's a directive to the HCP to consider dietary starch restrictions in addition to sucrate, uh, especially in patients whose symptoms are not adequately controlled. So again, we see another example of a directive to the HCP that has not been included in the ISI. And finally, the last point here in this last paragraph, they say that the presentation of risk information and the emails do not appear in a sequence that discloses risk information in order of severity. Uh, and again, this is really important. We go back to the ISI and we see bullet four here is talking about adverse reactions, uh the common AEs, right? And that's uh being presented before that precaution we were just talking about for diabetic patients. And just as a reminder, the the order here should be uh contraindications first, followed by warnings and precautions, and then finally common AEs. That's the order that uh those uh should be presented in in the ISI. So here we see adverse reactions being presented in bullet four, and a precaution is being presented in bullet five uh after that common AEs. So that's a lot to digest. Uh Virginia, what what do you think?

SPEAKER_00 17:04

Um I think that a couple things. Well, one, I just noticed that there's like the house supplied and the storage recommendations. I'm not used to seeing that in an ISI. There might be something really special about this, but a lot of drugs need to be protected from heat and refrigerated. So I don't know, it just seems kind of odd. Um, for me, the net impression of the safety presentation is really key. Um, you know, the the headers aren't there, it's not in the right order. Um, it just feels kind of like a mishmash of information. It's really hard to digest, it's really hard to take away. And you know, if you're thinking about public health, um, it's it's our job to make sure that the doctors know how to use the product, right? As a sponsor. So I don't think that this hit the mark, and and I do think that it definitely has merit. Um I I think that the um the takeaways for me are um you know, make what you just said, you know, if there's something actionable for the HCP, if there's directive language that absolutely needs to be in there. Um, thinking about the order, thinking about the look and feel of the safety, the integration. Um, this is this is definitely a miss. Um, and I I think the indication is interesting because this is something that I struggle with a lot is trying to get that integrated into the main body of an email or a piece. Um so I for me that's a good takeaway. I also like to think about what's missing or what they didn't comment on. Um that's always kind of the fun part. It's like a little hunt. Um, one thing I didn't I noticed because it it I was just talking about this this week with a client, um, is we've got the oral solution in there, but we don't have the um the strength of the product. So as per the regs, we need to have at least one dosage strength in there um nearby the dosage form, and that's typically in the logo lockup. Um, but so that's kind of a miss. Um not a huge miss, but if you're doing a letter, I would have added it in. Um and I just I just think the ISI is really small and it just doesn't pass the red face tests. Like there's no way this is defensible in terms of integration of risk. So um hopefully that's um not too severe, but uh that's my opinion. And I think we they could have done better with that.

SPEAKER_01 19:39

Yeah, I think there's definitely a lot of good insights. Um always good to get insights in how OPDP is looking at things. And uh overall, I think it's a beneficial letter to us in industry. It really kind of helps reiterate some things that we've been trying to uh I know I've been sharing with my regulatory teams, some other people I've talked to share with their regulatory teams. So I think it's it's been a helpful letter overall.

SPEAKER_00 19:58

Yeah, short and sweet. So um, well, thank you. And you know, we're trying to be timely with sharing information. Uh so this letter just got posted two days ago. Uh Jason had the idea to jump on it and do a quick summary. So um I'm hoping that you all find this useful. And um we'd love to hear from you. Let us know uh what else you'd like to hear from us. Thanks for joining the Promotional Intelligence Podcast.