Released by FDA: 6/12/00.  Posted by FDA:  6/20/00

Scott Krueger 
Director, Regulatory Affairs 
Alcon Laboratories, Inc. 
6201 South Freeway 
Fort Worth, TX 76134-2099

RE:   NDA 19-992 Ciloxan (ciprofioxacin HCI) 0.3% as base sterile 
        ophthalmic solution 
        MACMIS ID# 8799

Dear Mr. Krueger:

This letter describes Alcon Laboratories, Inc.’s (Alcon) dissemination of violative promotional materials for Ciloxan.  These materials include an unnumbered, two-sided sales aid titled “SOME THINGS AREN’T SO PRETTY IN PINK. CILOXAN wipes out PINK EYE in just 3 days,” a brochure (CNOO5OIVSO) with the same title, a brochure (CN99508VS) titled “FIGHT INFECTIONS FAST WITH CILOXAN,” and “homemade” promotional materials (Attachment 1) for Ciloxan.  The Division of Drug Marketing, Advertising, and Communications (DDMAC) reviewed these promotional materials and concluded that they are false or misleading under the Federal Food, Drug, and Cosmetic Act and its implementing regulations.  Specifically, they promote an unapproved dosing regimen, omit important dosing information, and lack fair balance for Ciloxan.  Our specific objections follow:

Misleading Claims of Effectiveness

Your materials include claims such as ‘Ciloxan wipes out pink eye in just 3 days,” “Three day action,” “QID for 3 days,” and “Ciloxan for Infections QID Dosing/3 Days.”  These claims are misleading because they are inconsistent with the approved product labeling (P1) for Ciloxan and suggest that Ciloxan is only to be used for 3 days for the treatment of bacterial conjunctivitis. however, the P1 states that the dosing regimen for bacterial conjunctivitis with Ciloxan is seven days (one or two drops instilled in the conjunctival sac(s) every two hours while awake for two days, and one or two drops every four hours while awake for the next five days).  Your materials fail to include this material information.  Thus, your suggestion that Ciloxan is to be used for only three days is misleading.

Lack of Fair Balance

Promotional materials are misleading if they fail to present information about the risks associated with the use of the drug with a prominence and readability reasonably comparable to that of the claims for the drug.  The “FIGHT INFECTIONS FAST WITH CILOXAN” brochure is misleading because it lacks fair balance.  Specifically, you prominently present safety and efficacy claims on 10 pages of the brochure.  These claims are presented in large type size, and are bolded and bulleted for emphasis.  In contrast, you present one sentence of risk information, in small type, at the bottom of the last page.  In addition, your brochure fails to present important risk information about the use of Ciloxan identified in the Warnings, Precautions, and Adverse Reactions sections of the P1.

Similarly, the “SOME THINGS AREN’T SO PRETTY IN PINK” 2-sided sales aid presents claims about Ciloxan’s safety and effectiveness, but fails to present information about the risks associated with the use of the drug with a prominence and readability reasonably comparable to that of the claims for the drug.  You present claims about Ciloxan in large type size that is bolded and bulleted for further emphasis. In contrast, you present the risk information in small size, and present the information in running text near the bottom of the rear page.

Your “homemade” pieces for Ciloxan are in violation of the Act because they fail to include ~ risk information about the product (emphasis added).

Misleading Presentation of in Vitro Data

Non-clinical data may not be used in a way that suggests that such data has clinical significance when such clinical significance has not been demonstrated.  In the “FIGHT INFECTIONS FAST WITH CILOXAN” brochure and “SOME THINGS AREN’T SO PRETTY IN PINK” sales aid, you present data on in vitro kill curves.  In the “FIGHT INFECTIONS FAST WITH CILOXAN” brochure, you present the claim that “Ciloxan kills pathogens in minutes.”   However, there is not necessarily a correlation between in vitro activity (MIC₉₀ data) and in vivo results.  Thus, this presentation of non-clinical data is misleading.  In the “FIGHT INFECTIONS FAST WITH CILOXAN” brochure, you present in vitro data on three pages and qualify the in vitro information with the statement, “in vitro activity does not necessarily correlate with in vivo activity.”  However, this qualifying information is presented in small type at the bottom of one of three pages and it fails to correct the suggestion that the data presented is clinically significant.  Thus, this presentation is also misleading.

Requested Actions

In order to address these objections, we request that you immediately cease the dissemination of these violative promotional materials and any other violative promotional materials for Ciloxan that contain the same or similar claims or presentations.

You should respond to me in writing with your intent to comply with our request by June 26, 2000, providing a list of the promotional materials discontinued, and the date Alcon ceased the dissemination of the promotional materials.

If you have any questions, please contact me by facsimile at (301) 594-6771, or write to me at the Division of Drug Marketing, Advertising, and Communications, HFD-42; Room 17B-20; 5600 Fishers Lane; Rockville, MD 20857.  We remind you that only written communications are considered official.

In all future correspondence regarding this matter, please refer to MACMIS # 8799 and NDA 19- 992.

Sincerely,

Warren F. Rumble 
Regulatory Review Officer 
Division of Drug Marketing, 
  Advertising and Communications