Fourth Quarter 2008 Warning Letters CDER

J0386036The pathetic rate of enforcement by CDER continues.  I am so stymied why some smart reporter hasn’t posed the question – what is happening when the amount of PDUFA dollars and money in the federal budget for FDA goes up, and the rates of enforcement continue to go down? 

During the last quarter of 2007, CDER’s DDMAC issued a total of 4 – count ’em 4 letters that were focused on promotion and not a result of inspections.  This results in a total for the year 19 – a record low by my count and anemic when compared to a decade ago. 


2007                                               19

2006                                               22

2005                                               29

2004                                               23

2003                                               25

2002                                               28

2001                                                64

2000                                               75

1999                                              108

1998                                              156

1997                                              139

Looking briefly at the letters:

Two large companies and two not-so-large companies received letters. 

  • In November GlaxoSmithKline received a Warning Letter regarding promotional materials for Tykerb – a treatment for patients with advanced or metastatic breast cancer that has not responded to other treatments and that overexpresses HER2. The material in question involved three Dear Healthcare Practitioner letters issued on connection with the launch campaign for the drug.  DDMAC found that they were misleading and minimized important risk information.   The FDA found that the letters actually omitted important risk information.  The agency also found an overstatement of efficacy because the description of efficacy did not include the range described in the package insert. 
  • Scios Inc., the maker of Natrecor, received an untitled letter in November where the focus was an attempt at "reminder labeling" which is exempt from risk information requirements.  Natrecor treats congestive heart failure.  The agency found that the attempt at reminder labeling failed and therefore the communications vehicles in question (a mouse pad and pen) did violate regulations by not containing indication and risk information.  Here, the interesting basis for the letter is the fact that the mousepad displayed a patient deep in water and even though the indication was not stated, the agency felt that "the image evokes the concept of a sedentary hospital patient drowning…suggests that Natrecor is indicated for seriously ill patients who have difficulty breathing while at rest because of fluid accumulation in the lungs, a suggestion that is consistent with Natrecor’s indication…" Combined with the logo, FDA felt that this was promoting an indication beyond the boundaries of a "reminder" promotion.  The lesson here is to look closely at what is being conveyed by the images used to ensure the reminder at is merely reminder and not suggesting indication. 
  • Morton Grove Pharmaceuticals received a Warning Letter in December for promotional pieces for Lindane Shampoo, indicated as a second line treatment for head lice, on web sites.  The package insert contains a boxed warning.  The Warning Letter stated that the web sites minimized, and in some cases failed to state risk information, which according to the boxed warning, was considerable.  The lesson here is that products with boxed warnings should go to extra lengths to state them in promotional materials. 
  • Lastly, Wyeth received a Warning Letter in December for a professional journal advertisement for Effexor XR.  There were several problems here, involving an overstatement of efficacy for using studies that the agency did not feel substantiated claims made in the ad, and in addition, the ad had language that said over 20 million patients had been treated with Effexor XR, which the agency felt was misleading since the data was based on estimates of daily average consumption and did not reflect "unique patients" which could infer greater efficacy and safety.

All in all, an interesting batch of letters, especially respecting the reminder ad.   

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