Avanthi OPDP Letter

Just as you might have thought that the OPDP calendar year was going to go out like a lamb, the Office sent out their 4th letter (3rd warning letter) of the year, this one to Avanthi for their promotion of Lomaira (TM) at two meetings in early 2017.   Lomaira is manufactured by KVK Tech which has the same address as Avanthi Inc.   The relationship appears complicated as each of Avanthi and KVK Tech have separate ANDAs for this drug and it is unclear if KVK Tech was involved in the creation or use of these graphics, as well.

Warning Letter

Promotional material

The letter cites Avanthi for not providing ANY risk information on this graphic used at these two meetings.   It is not clear if these graphics are from booth panels for Lomaira for an Avanthi/KVK Tech booth at these meetings but it is reasonable to assume that this is the case. The company is also cited for not being clear about what Lomaira was indicated for, as the indication limited Lomaira to short term use in patients with certain body mass indices and/or co-morbid conditions.  As a warning letter it asked Avanthi to provide corrective information to all those who may have seen the booth panels which, for two national meetings of this size, would be quite extensive and expensive remediation. 

Given what is presented in the letter, it appears OPDP is standing on strong ground in citing Avanthi.  Clearly, limitations of the product are not captured on the graphic cited by OPDP and no ISI is presented on the graphic nor is the language on the graphic moderated in any way to take into account the approved product labeling. 

Interestingly, however, is that there is a product website for HCPs, https://www.lomaira.com/hcp/, which contains the same graphic but has the Important Safety Information (ISI) and other balancing information on the same webpage.  OPDP did not cite any of the information on this product website nor on a separate website, https://lomairaonline.com/ which may or may not be associated with Avanthi or KVK Tech but contains the same graphic and has claims about Lomaira but no safety information.  The boilerplate language in the OPDP letter covers OPDP from having to mention other uses of the supposed violative material but, generally, companies receiving OPDP letters immediately remove violative material from all sources following receipt of such a letter.  In this case, KVK Tech chose NOT to remove the graphic from its product website, possibly because the website contains the balancing information that the graphic at these conventions didn't have.   That is, they may have felt that the graphic was OK if the appropriate balancing information was presented in prominence similar to the graphic.

An interesting point that is worth consideration is whether Avanthi/KVK Tech had a booth at these meetings.  If not and this graphic was just presented in some rotating/flashing billboard in the main hall then OPDP's points are well-taken.  However, if this graphic was a booth panel at a product promotional booth at these meetings then the question remains why was there not ISI or balancing language associated with this graphic?  I have seen companies in the past use, for whatever reason, free standing ISI placards next to promotional graphics in a booth.  While I have seen these used they can be problematic as someone may forget to bring them or place them appropriately, they may be moved away from the graphic for some reason or they even may be obscured by desks, plants, etc., the latter having been cited before in OPDP letters.  Also, I have seen (very rarely) booths where the ISI is not on every booth graphic, which made me think that the company felt that the booth was one big promotional material and that they only needed to have ISI visible in the same prominence in some places in the booth to cover the claims they made throughout the booth. This would assume, of course, that the booth was always used in tact at all meetings.   It would be interesting if, indeed, these were booth graphics, to see what the overall layout of the booth was like and what the thinking of Avanthi/KVK Tech was in how they set up the booth and whether they had ISI. 

It would also be interesting to see who owns www.lomairaonline.com as, from the OPDP letter, one might have expected that website to be changed due to the OPDP letter and the lack of ISI/fair balance on that website.

Amherst Pharma/Magna Pharma OPDP Warning Letter

Author's Note: This is the official launch of this blog that will deal with issues impacting the marketing of pharma drugs, devices and combination products.   The opinions here are just those of the author based on my understanding of the area of drug and device advertising and promotion.

In Nov. 2017 OPDP issued a warning letter regarding the promotion of Zolpimist(R).  The letter was issued to the license holder for the drug, Magna Pharma, and its partner, Amherst Pharma.  The first thing that strikes me about this letter is that it is sent to the manufacturer and their partner, both of whom generated supposed violative materials.   We don't know if the promotional claims used by the partner were given to them by the manufacturer.   However, what we do know is that OPDP considers if a person or a company has a relationship with the manufacturer (e.g., KOL, distributor, partner, etc.) that this person or company is acting FOR the manufacturer.   Thus, the reason OPDP sent letters to both companies as both had violative claims.  This shows once again that market authorization holders need to monitor the companies or persons they are involved with to make sure those companies or persons are not doing inappropriate promotion of the drug involved.

This letter, the 3rd of the year by OPDP, contained nothing unusual besides the above.   The companies were cited for pretty standard violations:

• Failure to submit their promotional materials at time of first use
• Failure to include any risk information
• Overstating efficacy by language that would imply that Zolpimist, as a 505(b)(2) drug, was superior to the brand and generics containing the active ingredient zolpidem.
• Not providing material information.  For example, not providing the indication which would limit the time that this drug had been shown to be effective and indicating that there were no food effects with this mist when those effects were clearly listed in the label

So, what do we make of this most recent warning letter from OPDP?

Three things make it difficult to project the true meaning of any particular OPDP letter or series of letters:

• Context - was there any driving force (e.g., competitor complaints, previous communication by FDA with the sponsor, etc.) we don't know about that caused OPDP to single out this manufacturer for this promotion?
• Agenda - did any agenda at OPDP cause them to pick this drug class or this type of violation to cite?
• Background - did recent events and/or decisions on resource usage cause OPDP to pick out this type of violation?

For these reasons it is difficult to say if there is a pattern in ANY year of OPDP enforcement letters and particularly this year with only 3 letters being issued.  There could be any number of reasons for the issuance of this particular letter.  For example, there are so many competitors to Zolpimist that it is likely that one or more competitors, sensing the potential perceived advantage of the only zolpidem mist (vs tablets and sublingual) in this space, might have been keenly aware of Zolpimist promotion and complained to OPDP.   Considering that violations cited were in pretty public, easily accessible places (a website and a large convention) it is likely that these violations were seen by all these competitors.  So, potentially the weight of complaints might have been enough to get OPDP's attention and convince them to write this letter.

My opinion is, as Tom Abrams, the director of OPDP, has repeatedly said, is that Pharma is getting better at policing themselves in the area of ad/promo.  That being said, knowing the vast number of drug companies out there today, the competition within markets not only with generics but also with new brands coming to market and the number of new marketing areas being explored by drug companies, it seems obvious to me that there have been many potential violations reported to OPDP by physicians or advocacy groups (Bad Ad) or competitors in addition to those that were discovered independently by OPDP reviewers.   Yet, we only have 3 letters so far this year.

Another thought is that, given that there have been so few letters that have come out this year, it is possible that they all have something in common that OPDP is trying to remind us about. 

If there is a connection between these 3 letters, it is that they all mention not enough risk information.  The most recent 2 failed to include ANY risk information in their ads and the first one of the year, to Orexigen Therapeutics, cited specific risk information that had been omitted.  Omitting risk information is not, to my knowledge, something that has successfully been challenged in court as being a first amendment right so it still represents safe, low-hanging fruit for OPDP to write letters about that would be immune to court challenge.  Still, even if you believed this was true, you have to believe that more companies than Amherst/Magna and Cipher created and implemented materials this year that failed to provide ANY risk information this year and MANY more companies than the three cited this year that had insufficient risk information in their promotional materials.  This doesn't even mention those who failed to submit their materials at time of first use, although my hope is that this latter number was a couple of orders of magnitude smaller than these other potential violations.  So why were these three chosen?

I can't see any other obvious connection between these drugs or the type of promotion, or type of compliance letter sent that would link these letters together as some overall message by OPDP.    Even if that connection could be postulated, the small number of letters overall this year doesn't lend itself to any pattern being identifiable.

Finally, if you REALLY wanted to grasp at straws, one could postulate that the low number of letters this year could signal that the role of OPDP has, internally at FDA, been significantly redefined almost exclusively to one of education and prevention with only a really minor portion of its role being surveillance and enforcement.  Given that the environment in President Trump's administration seems to be more of helping pharma get new products approved faster rather than slowing anything about drug development or sales, this could be plausible, I guess.  However, any speculation that the current administration is stifling the issuance of compliance letters by OPDP for ANY reason would be very premature. 

The rest of 2017 and, indeed, all of 2018 will be interesting to watch to determine if 2017 is just an anomaly or if it signals a historic change in the role of OPDP.  "Experts" in this area have been chasing their tails for years trying to find patterns in OPDP letters and, for the most part, we have all come up dry.   While it makes for interesting and stimulating conversation if you are a regulatory ad/promo geek like I am, without sufficient information for the three bulleted things above, I don't know that we will ever know...and I am thinking that OPDP won't be opening their internal thinking process to any of us in the near future.  Their position has always been that the rules are out there, the rules are clear and all Pharma has to do is follow them to stay within the guard rails of appropriate promotion.  It's up to all of us to make sure that we effectively, yet appropriately promote our products.