Warning Letter Summary – 3rd Quarter 2007

Following last week’s chart displaying the quantitative overview of FDA’s DDMAC issuance of Warning Letters and Untitled Letters, I wanted to begin this week with a qualitative perspective on what those letters covered.   Since there are so few letters, it is possible to discuss them individually.

  • Starting with the most recent, in September Eli Lilly received an Untitled Letter for a mailer it sent out regarding Cymbalta.  Cymbalta has three indications, but the mailer only focused on one of the indications having to do with diabetic nerve pain.  The lesson learned here is that the agency found the mailer false and misleading because it said the company had overstated its efficacy when it made claims that relied on pooled data.  The agency stated that this type of post hoc study is not a credible source of data from which such claims can be based.  Secondly, the agency noted that some of the risk information for the product was left out.   
  • Novartis received a Warning Letter in August for the product Exelon which is indicated for the treatment of mild to moderate dementia in Alzheimer’s patients.  The agency said that a professional card file made unsubstantiated superiority claims and by discussing potential uses with other products, there was a recommendation being made for an unapproved use.   Here the lesson learned is that the agency found that the company relied on a single, open-label study without a control group.  Note that when making superiority claims or claims that could reasonably be interpreted to be superiority claims, substantial studies need to underpin the claim and in this a single open-label study without a control was deemed insufficient.    There were many other issues in this letter, including a lack of risk information.
  • In July, there were two letters issued – one to Pfizer for Geodon and one to Doak Dermatologies for Solaraze.  Beginning first with Pfizer, an untitled letter was sent for Geodon, indicated for the treatment of acute agitation in schizophrenics and it is contraindicated in patients with QT prolongation.  However, in reviewing a professional journal ad, the agency found there to be a unsubstantiated superiority claim as well as a minimization of risk information.  While the QT prolongation information was included in the ad, several other risk elements, the agency found, were not.  The real lesson here is, however, a claim that the agent was twice as effective as another, again relying on a single study that was open label, as was the case with Novartis above.  For Doak, the vehicles in question were a detail aid and a journal ad, both the subject of an untitled letter.   The agency said that the uses of the product were being broadened when it discussed use of the Solaraze in conjunction with another product, when it is indicated for monotherapy – and that it failed to contain the full amount of risk information, thus misbranding the product. 

While it is perhaps not always likely that communications folks are going to catch a mistake in a communication that involves a superiority claim, safety information is pretty easy.  It is in the package insert and label.  If it is on the label, put it in the communication vehicle – period. 

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