FDA Warning Letter Confirms DDMAC Focus on Accurate Presentation of Safety Information and Comparative Claims

April 25, 2007

On April 20, 2007, FDA’s Division of Drug Marketing, Advertising, and Communications (“DDMAC”) issued a Warning Letter to Alcon Laboratories, Inc. concerning the company’s promotion of CIPRODEX (ciprofloxacin, 0.3%; dexamethasone, 0.1%) Sterile Otic Suspension in a retail sell sheet and a sales aid.  FDA approved CIPRODEX in 2003 for the treatment of acute otitis media and acute otitis externa in certain pediatric patients. 

According to DDMAC’s Warning Letter:

Both the retail sell sheet and sales aid omit material facts about Ciprodex, including important risk information and limits to Ciprodex’s indication; the sales aid also makes numerous unsubstantiated superiority claims. Therefore, the materials misbrand the drug in violation of the [FDC Act], 21 U.S.C. §§352(a) and 321(n). These violations are concerning from a public health perspective because they suggest that Ciprodex is safer or more effective than has been demonstrated, and they encourage use in circumstances other than those for which the drug has been shown to be safe and effective.

DDMAC found that the main page of the retail sell sheet contains efficacy claims for CIPRODEX, but no risk information.  Further, “the retail sell sheet claims Ciprodex is ‘approved for the treatment of acute otitis media with tympanostomy tubes and acute otitis externa.’ This claim misleadingly broadens the drug’s indication by failing to reveal, for example, that it is only approved for use in the treatment of certain susceptible isolates of the designated microorganisms causing acute otitis media and acute otitis externa infections.”

DDMAC’s Warning Letter also cites Alcon’s sales aid for making several unsubstantiated CIPRODEX superiority claims over CORTISPORIN (neomycin, 0.35%; polymyxin B, 10,000 IU/mL; hydrocortisone, 1%) Otic, including that:

  • CIPRODEX superiority claims about cure rates are not valid, as the referenced study found no significant difference in cure rates between the two drugs (although there were numerical differences);
  • Comparisons of the two drugs in the area of pain relief are considered inappropriate because the references cited do not prespecify this comparison as a study endpoint;
  • Claims about superior efficacy as an anti-inflammatory are not substantiated, as the study did not demonstrate a significant difference between the drug at three of the four time points studied;
  • Claims that CIPRODEX has a lower rate of treatment failures are not supported by references, because this was not a prespecified analysis in the references and the results are not consistent across studies; and
  • Claims about superior safety are not substantiated, because the claims exaggerate the risk of CORTISPORIN and are based on results found in experimental conditions that did not mimic clinical usage.

The Warning Letter also cites as an “omission of material fact” the failure of the sales aid to present a warning of skin rash and hypersensitivity associated with CIPRODEX.

DDMAC’s Warning Letter to Alcon is yet another indication that the Division, due to limited resources, will continue to focus its enforcement efforts on marketing materials that have the potential to most adversely affect the public health.  That is, those materials that omit or minimize risk information, and those materials that use misleading (comparative) safety and efficacy claims.  In 2006, of the 22 Warning Letters issued by DDMAC, only one did not cite the omission or minimization of risk as a violation. 

Earlier this year, FDA proposed the creation of a user fee system to fund the review of direct-to-consumer advertisements.  If implemented as part of the reauthorization of the Prescription Drug User Fee Act (“PDUFA IV”), it is possible that DDMAC will have the resources to broaden the Division’s enforcement focus.


By Dara Katcher Levy

Categories: Enforcement