Warning and NOV Letter Summary – 3rd Quarter 2011

Last week it was noted that enforcement at DDMAC, newly renamed the Office of Prescription Drug Promotion (OPDP)  has slowed down.  Last quarter, the division, now an office, issued only four letters.  Not only is it worthwhile to look at the quantitative patterns of these regulatory actions, it is our custom to look at these letters qualitatively as well to see what communications vehicles were involved, what violations were deemed to occur and what lessons are to be taken from the actions.

The four letters from last quarter involved 2 Notice of Violation (NOV) letters and 2 Warning Letters and involved four companies.  One letter was issued in July, 3 in August and none in September.

The communications vehicles being cited were evenly divided between digital platforms (Web pages) and traditional media (a flyer and a booklet).

The violations numbered 6 in total:  2 were for the minimization or omission of risk information (the most common of any violation); 1 involved unsubstantiated claim, 1 involved a broadening of the indication, 1 was for omission of material facts, and 1 was for the relatively rare circumstance of promoting a product prior to approval.  Let’s take a look at them in order:

• Risk Information – In one of the cases, a printed flyer about an approved treatment contained no risk information whatsoever.  In the other violation, the material was digital and incorporated the bulk of the risk information by supplying a link, which is well known not to suffice to anyone watching FDA’s position on this matter.  Lesson:  Risk information needs to be included wherever indication appears, must be balanced in presentation and risk information cannot be incorporated by reference.
• Unsubstantiated Claim – Here a claim was made implying a method of administration and a superiority over another treatment citing data that was comprised of a retrospective review of several studies among different patient populations and under varying protocols and doses.  The agency did not consider such a broad net to comprise substantial evidence or substantial clinical experience upon which to base a claim.  Lesson:  The exact characterization and make up of the kind of data that suffices as substantial should be devised by companies as a standard for the company when making such claims.
• Broadening of Indication – Here a booklet was the subject matter cited.  The treatment in question had a specific indication with some limitations inherent in its use.  The booklet contained reprint of a series of slides that provided an array of circumstances for which the treatment could be utilized, the totality of which the agency felt would lead one to the conclusion that it was approved for use in all circumstances associated with the indication when it was only approved for some circumstances to treat the underlying condition.  Lesson:  Even if a single portrayal of the use of the treatment does not broaden the indication, it is the totality of the presentation of the information that is examined.
• Omission of Material Facts – This was deemed to have occurred when a new treatment was presented replacing a prior treatment.  As it was presented as a replacement, it implied that the dosing information was also the same.  Not only did it differ, but the difference was important when it came to safe administration said the FDA.  The difference was was not noted – therefore deemed an omission of a material fact.  Lesson:  Dosing omission is one of the most common.  Pay particular attention that dosing is not implied by circumstances in the presentation to be other than it is.
• Promotion of an Investigational Drug – Prior to approval, a web page containing statements of safety and efficacy of the compound in addition to referring to the drug as “the first” to accomplish treatment goals.  Lesson:  Avoid language that characterizes investigational compounds.  Avoid adjectives, conclusions and stick to data.

Note that these observations are not legal advice and do not substitute for consultation with regulatory counsel – they are meant to be the presentation of red flags for those engaged in preparing communications.