As noted last week, there has been a great deal of concern expressed over the Bush Administration’s lax approach to the FDA’s mission. In my mind, one marker of that has been the lack of leadership at the FDA, either due to transience (Mark McClellan) or politics. As noted in a recent editorial in North Carolina, one piece of evidence is the diminishing number of Warning Letters issued by the FDA. That said, it does bear noting that the number of MedWatch alerts, on the other hand, has more than doubled, something not taken into account by Public Citizen, the Center for Science in the Public Interest or Congressman Waxman in their charges last week.
Last quarter, I began a quarterly review of Warning Letters issued by CDER as a tool for marketers and communications professionals to learn what trips the Warning Letter wire. Note that the "Resources by Me" section to the left has been amended to include these letters in the overview and summary.
General Profile of Warning Letters of First Quarter – In the first quarter there were six letters issued by DDMAC to companies. In the second there were five, two of which made it on the books the last day of the quarter. Both large seasoned and small companies were represented among those receiving Warning or Untitled letters. Surprisingly, the most common violation was the failure to include risk information. The vehicles included promotional brochures, print (reminder) ads, Web information and sales aids.
Important Specific Learnings from Warning Letters of Second Quarter –
- You would think that by now, everyone would understand that you have to include risk information on everything. Nearly all of the companies getting a letter this quarter neglected to either include some risk information and more than one failed to include any risk information.One of the companies receiving a letter produced a product brochure that was on its Web site that neglected to include risk information from the label that was both serious and substantial. On top of that, the brochure stated that safety was "guaranteed" because the product was FDA approved – which not only goes a long way to minimize risk, it is impossible. The FDA also felt that the company broadened the indication of the drug by not listing those people who should not be candidates for its use. One important note, the company used the term "preferred" treatment which suggests that a comparison study has been performed. When one has not, to suggest something is the right treatment, or safer treatment or preferred treatment risks a warning for an unsubstantiated claim.
- One company got a warning because a promotional piece that centered alerted patients that one formulation of its product would be going off the market and promoted a new formulation, but failed to mention the drug was commercially available in another form.
- Another company ran a reminder ad for a drug with a boxed warning without including a brief summary of side effects. Reminder ads are not permitted for drugs with boxed warnings.
- Lastly, one product with a PI that stated explicitly that the product had not shown clinical benefit in nonimmunocompromised patients nevertheless had information on their Web site that so broadly addressed benefit, it was counter to the PI, which broadens the indication and is an overstatement of efficacy.