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Enforcement Actions

Schering-Plough Animal Health Corporation 11-Jul-07

Department of Health and Human Services' logoDepartment of Health and Human Services

Public Health Service
Food and Drug Administration

 

Rockville MD 20857


JUL 11 2007

WARNING LETTER

Certified Mail
Return Receint Requested

NADA 141-264 (L3)

Nancy Thompson-Brown
Senior Regulatory Compliance Specialist
Schering-Plough Animal Health Corporation
1095 Morris Avenue
Union, New Jersey 07083-1982

RE: NADA 141-264, Nuflor® (florfenicol) Type A Medicated Article for Swine
Promotional labeling piece Product Bulletin (SPAH-NFP-10)

Dear Ms. Thompson-Brown:

The Center for Veterinary Medicine (CVM) has reviewed a promotional piece (product bulletin) for Nuflor® (florfenicol) Type A Medicated Article for Swine submitted by your firm in a special Drug Experience Report (DER) on March 8, 2007. This piece makes unsubstantiated claims of effectiveness and thus misbrands the drug within the meaning of sections 502(a) [21 U.S.C. 352(a)] and 201(n) [21 U.S.C. 321(n)] of the Federal Food, Drug, and Cosmetic Act (the Act). Additionally, the piece promotes Nuflor® for a new intended use that is not the subject of an approved New Animal Drug Application (NADA). When promoted for this new, unapproved intended use, Nuflor® is unsafe within the meaning of section 512(a)(1) of the Act [21 U.S.C. 360b(a)(1)] and adulterated under section 501 (a)(5) of the Act [21 U.S.C. 351(a)(5)].

Background

Nuflor® (florfenicol) Type A Medicated Article for Swine is indicated for the control of swine respiratory disease (SRD) associated with Actinobacillus pleuropneumoniae, Pasteurella multocida, Streptococcus suis, and Bordetella bronchiseptica in groups of swine in buildings experiencing an outbreak of SRD. It was approved as a Veterinary Feed Directive (VFD) drug in December 2006.

Unsubstantiated Claims of Effectiveness

The promotional piece presents six bulleted points under the heading "Advantages." Three of the bullet points are false or misleading because they present claims that go beyond those approved and have not otherwise been substantiated. These three bullet points are:

• "Fast acting - Reaches therapeutic concentrations in serum and lungs within 4-5 hours."
• "Highly palatable - Ensures intake of full dose."
• "VFD status ensures long-term effectiveness."

The first bullet is false and misleading within the meaning of section 502(a) [21 U.S.C.352(a)] of the Act. The statement that the drug reaches therapeutic concentrations in the serum within 4-5 hours is misleading because it suggests this is a valid measure of the effectiveness at the target site of infection. However, there is no substantiation that serum concentration is relevant to treating lung infections. Tissues often contain bound drug which is not available for activity, so serum concentrations are not a sound measure of the drug's effectiveness at the target site. The statement that the drug reaches therapeutic concentrations in the lung within 4-5 hours of administration is also not substantiated by clinical evidence.

The second bullet is false and misleading within the meaning of section 502(a) [21 U.S.C. 352(a)] of the Act because the fact that a medicated article is fed in a palatable base does not ensure intake of a full dose by each treated animal. In the Freedom of Information (FOI) Summary for Nuflor® Type A Medicated Article for Swine, the results of a pharmacokinetic study (Study No. NO1-061-01: "Pharmacokinetics of Florfenicol in Swine Following Administration of Nuflor Swine Premix in Feed for 5 days") were presented. It was noted that one pig exhibited very poor food intake and consequently had substantially lower AUC and Cmax values compared to other study subjects. It was additionally noted that "blood levels observed when administered in feed exhibited large inter- and intra-subject variation, which is attributable to variability in animal feeding behavior and thus drug intake."

The third bullet is false and misleading within the meaning of section 502(a) [21 U.S.C. 352(a)] of the Act because restricting a drug to use in the form of a Veterinary Feed Directive does not relate to long-term effectiveness and will not necessarily eliminate the risk of antimicrobial resistance developing over some time period.

Promotion for a New Intended Use

An additional bullet in the promotional piece claims the drug "Significantly. . . increased average daily gain compared to untreated controls." Nuflor® is not approved to increase average daily gain. A supplemental NADA must be approved for this indication. Promotion of Nuflor® for this new intended use without an approved NADA renders the drug unsafe under section 512(a)(1) of the Act [21 U.S.C. 360b(a)(1)] and adulterated under section 501(a)(5) of the Act [21 U.S.C. 351(a)(5)].

Conclusion and Requested Action

The promotional piece is false or misleading because it presents unsubstantiated effectiveness claims for Nuflor® (florfenicol) Type A Medicated Article for Swine. Accordingly, the drug is misbranded within the meaning of section 502(a) [21 U.S.C. 352(a)] of the Act. Additionally, the promotional piece promotes Nuflor® for a new intended use that is not the subject of an approved NADA. Accordingly, the drug is unsafe within the meaning of section 512(a)(1) of the Act [21 U.S.C. 360b(a)(1)] and adulterated under section 501(a)(5) of the Act [21 U.S.C. 351(a)(5)).

The Division of Surveillance requests that Schering-Plough immediately cease the dissemination of the piece described above. In addition, future promotional and advertising materials should refrain from presenting the unsubstantiated claims as noted above, specifically references to "therapeutic lung concentrations", "palatability ensures intake of full dose", and VFD status used as a measure of "long-term effectiveness." Additionally promotional and advertising materials should not promote Nuflor® for new, unapproved intended uses.

The violations discussed in this letter do not necessarily constitute an exhaustive list. It is your responsibility to ensure that your promotional materials for Nuflor® Type A Medicated Article for Swine, as well as for your other products, comply with the requirements of the Act and its implementing regulations. Failure to correct the violations discussed above may result in FDA regulatory action without further notice such as seizure and/or injunction.

You should notify this office in writing of the steps you have taken to bring your firm into compliance with the law within fifteen (15) working days of receiving this letter. Your response should include each step that has been taken or will be taken to correct the violations and prevent their recurrence. If corrective action cannot be completed within fifteen (15) working days, state the reason for the delay and the time frame within which the corrections will be completed. Please include copies of any available documentation demonstrating that corrections have been made.

Please direct your response to me at the Food and Drug Administration, Center for Veterinary Medicine, Division of Surveillance, 7519 Standish Place, Rockville, MD 20855. We remind you that only written communications are official.

Sincerely yours,

/S/

Daniel G. McChesney, Ph.D.
Director,
Office of Surveillance and Compliance
Center for Veterinary Medicine