DDMAC Erupts – A Troika of DDMAC Regulatory Action Letters

(NOTE:  After the initial publication of this posting, information was sent to me regarding FDA's Guidance on Risk Information – the posting was changed to note this important update and re-published.  The change is noted in italics in the third paragraph of this posting.  Thanks.)

Normally, a qualitative look at DDMAC Warning and Notice of Violation NOV) letters is reserved for the end of a quarter.  But this past week proved DDMAC to be nearly as active as an Icelandic volcano, and the issuance of three letters in a row to big name pharmas merits a closer, more timely look because there are some good learning take-aways here, and not just your run-of-the-mill neglect to list risk information.

First there was Astellas which received a NOV letter for a web page for Vesicare, which is indicated for the treatment of overactive bladder with symptoms of urinary incontinence, urgency, and urinary frequency. The letter was generated because DDMAC felt that the Web page made claims of superiority over a competitor product that were unsubstantiated.  The Web page did cite head to head studies when making its claims so what was the issue?  Here the takeaway lesson is that one has to be very careful  about the kinds of studies one uses to substantiate one's claims.  The requirement is that a superiority claim must be substantiated by two adequate and well-controlled head to head clinical trials comparing appropriate doses and dose regimens of the two products.  Here, among other things, one of the studies used was an open-label study and DDMAC does not deem open-label studies to be sufficient.  Also, make sure that the endpoints of the studies used are prospectively defined and entry to the studies requires the condition that is treated  by your product.  

The second letter of the week went to Novartis for an adherence email in connection with Voltaren Gel – a topical NSAID.  The letter was generated for reasons of minimization of risk and overstatement of efficacy.  Yet, looking at the email, one can see that the risk information about the product was clearly included and in fact, takes up much more space in the body of the email than the claims of efficacy.  So what was DDMAC's beef?  Well, the agency felt that presentation of benefit information was in bigger print and in easier language to read than was the risk information.  For me, that is a little out of left field.  I think that latter part – the easier language for risk information – puts manufacturers at some disadvantage.  If one changes the risk information to make it more health literacy-friendly, doesn't one also run the risk of being accused of minimizing the risk if the language somehow fails to convey the same urgency as the more complex language contained in the PI?  I don't know the answer to that, I'm just asking.  To my knowledge, FDA/DDMAC has not issued any standards on how to do this aptly.  (I stand corrected.  According to an esteemed and knowledgeable reader, there is guidance from FDA on this front.)  Also, in fairness to the manufacturer, the heading for the risk information is the same size as the headings for the other information contained in the email, and while the print for the risk information is smaller than the rest of the email, consumers are certain to be used to that fact from the long-standing practice in print ads.  Here, the takeaway lesson is a little muddled in my opinion.  The other factor at work here were claims that use of the product could help you with activities where pain may have stopped you and there the takeaway is more clear:  Be careful about making assumptions about what the use of a product might do for a patient when that specific outcome is not stated in the PI.  

Lastly, there was a NOV issued to GlaxoSmithKline for a journal ad for Azerra (ofatumumab), a treatment for cancer.  One good learning take-away here is that the FDA stated that one of the reasons for the letter was that GSK placed the ad within 120 days of approval.  Azerra had been approved under accelerated approval and any promotion of a medical product within that time frame must be first submitted to FDA for review.  So if you are like me and didn't know that before, you know it now.  Now here is the second good learning take-away.  The journal ad in question did not name the name of the treatment.  Azerra was not mentioned.  What the ad did refer to was "New Treatment Option for Chronic Lymphocytic Leukemia" which is similar to a warning letter situation a few years back where a company referred to a class of drugs rather than their specific drug, but where the drug was the only approved one in the class.  Not mentioning the name of a product does not mean that you won't be cited in a regulatory action that is specific to the product if the communication involved clearly implicates the product.  Then, by virtue of the fact that the ad was deemed to have mentioned the name of the product, the ad fell to all of the risk and indication information which was not there.

All in all, a busy week out of DDMAC and for the most part, some interesting take-aways, though in at least one of the circumstances, DDMAC may have raised more questions than it provided answers through its action.