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U.S. Department of Health and Human Services

Animal & Veterinary

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2009 Action Letter - NADA 141-068 Baytril® 100 (enrofloxacin) Injectable Solution

July 17, 2009

NADA 141-068

Janet Cunningham
Regulatory Affairs Consultant
Bayer HealthCare LLC
Animal Health Division
P.O. Box 390
Shawnee Mission, Kansas 66201

Re: NADA 141-068 Baytril® 100 (enrofloxacin) Injectable Solution;
Breathe Easy Kit Press Release (BL09560n);
McGuirk Brochure (BL08866);
Baytril® 100 Website Revision (BL08543n) section entitled “Baytril Kills Four Key Pathogens

Dear Ms. Cunningham,

The U.S. Food and Drug Administration, Center for Veterinary Medicine (CVM), Division of Surveillance has reviewed three promotional labeling pieces (BL09560n, BL08866, and  BL08543n) for the product Baytril®100 (enrofloxacin) Injectable Solution NADA 141-068.  We have determined that these promotional pieces contain misleading animal safety and effectiveness information, causing Baytril® 100 to be misbranded within the meaning of sections 502(a) and (n) of the Federal Food, Drug, and Cosmetic Act (the Act) [21 U.S.C. §352(a) and (n)] and FDA implementing regulations.  21 CFR 202.1(e)(6)(ii) and (vii). 

Background

Baytril® 100 (enrofloxacin) Injectable Solution is for subcutaneous use in beef cattle, non-lactating dairy cattle and swine only.  It is not for use in female dairy cattle 20 months of age or older or in calves to be processed for veal.

Indications:


Cattle:

Baytril® 100 is indicated for the treatment of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida and Histophilus somni (previously Haemophilus somnus) in beef and non-lactating dairy cattle.

Swine:

Baytril® 100 is indicated for the treatment and control of swine respiratory disease (SRD) associated with Actinobacillus pleuropneumoniae, Pasteurella multocida, Haemophilus parasuis and Streptococcus suis.

Lack of Substantial Evidence to Support Claims of Clinical Speed of Action

We reviewed the advertising piece identified as Baytril® 100 Website Revisions (BL08543n).  Specifically, the section entitled “Baytril 100 Kills Four Key Pathogens” contains the statement “Baytril 100 works fast and starts killing bacteria within a matter of minutes.”  In another section of the website, it states that “concentration dependent Baytril 100 Works Fast” and “…it achieves high drug levels at the site of infection to quickly kill bacteria.”  The website further states “Unlike slower antibiotics that require days to achieve therapeutic results, Baytril 100 goes directly to the site of infection and starts killing respiratory disease causing bacteria in minutes, not days…”.  This information was viewed on the website www.baytril100.com as recently as July 9, 2009.  The reference cited for these statements in the advertisement is an in vitro study testing the killing of clinical isolates of Mannheimia Hemolytica by enrofloxacin using minimum inhibitory and mutant prevention concentrations.  However, in vitro studies do not necessarily reflect the behavior of a drug in vivo, and are inadequate to demonstrate that the drug works quickly in a clinical setting.  An adequately designed clinical study would be necessary to substantiate the claim that enrofloxacin starts killing bacteria in cattle and swine “fast”or “within a matter of minutes,” or that it “quickly kills bacteria.”  These statements cause the promotional labeling to be misleading and to violate section 502(n) of the act.  See 21 CFR 202.1(e)(6)(vii).  Furthermore, the statement that “Unlike slower antibiotics that require days to achieve therapeutic results, Baytril 100 goes directly to the site of infection and starts killing respiratory disease causing bacteria in minutes, not days…” constitutes a drug comparison suggesting that enrofloxacin is superior to other antibiotics because it has a faster speed of clinical action, a claim that is not supported by substantial evidence  or substantial clinical experience and causes the promotional labeling to be misleading and to violate section 502(n) of the act.  See 21 CFR 202.1(e)(6)(ii).

We also reviewed the promotional labeling piece identified as Breathe Easy Kit Press Release (BL09560n). This piece was submitted to FDA as promotional material. It has been described by your regulatory affairs consultant as "a press release, intended to be picked up by any number of industry news outlets, publications, and newswires for further publication as industry news.  The final audience would be dairy cattle industry (producers, veterinarians, etc.)."  Because the final audience for this piece is the prospective customers for your product, we conclude that this piece is promotional labeling for that product.  This piece uses similar language and communicates a similar theme as BL08543n regarding the clinical speed of action of the drug.  Specifically, this piece states that “Baytril 100 reaches therapeutic lung levels in just 60 minutes and peak killing concentration levels in only 4.5 hours.”  The reference cited is a plasma pharmacokinetic study. This study may show that enrofloxacin quickly attains its Cmax in the blood stream of animals, but it does not demonstrate that those pharmacokinetic results correlate with faster clinical outcomes.  Therefore, this statement causes the promotional labeling to be misleading and to violate section 502(n) of the act.  The piece also states “Time matters when treating BRD, making the fast-acting…Baytril 100…the premier treatment option.” This constitutes a drug comparison suggesting that enrofloxacin is superior to other antibiotics, at least in part, because of its faster speed of clinical action, a claim that is not supported by substantial evidence or substantial clinical experience and causes the promotional labeling to be misleading and to violate section 502(n) of the act.  See 21 CFR 202.1(e)(6)(ii).

Finally, we reviewed the promotional labeling piece identified as McGuirk Brochure (BL08866), which again includes similar language and communicates a similar theme as BL08543n and BL09560n regarding the speed of action of the drug.  Specifically, FDA objects to several statements contained on the page of information entitled “Baytril®100 (enrofloxacin) is built to stop BRD fast.”  In addition to objecting to the statement “built to stop BRD fast,” we object to the following language:  “designed to stop BRD fast, “…it achieves high drug levels at the site of infection to quickly kill bacteria,” “…It goes directly to the site of infection and starts killing BRD-causing bacteria in minutes, not days.”  These statements are supported by the same plasma pharmacokinetic study referenced for BL09560n and an in vitro study; both studies are insufficient to support these statements.  Pharmacokinetic studies do not correlate with what occurs in a clinical setting and in vitro studies do not necessarily reflect the behavior of a drug in vivo.  Therefore, these statements cause the promotional labeling to be misleading and to violate section 502(n) of the act.  Furthermore, FDA objects to the statement “Some BRD treatments are time-dependent:  they need to be at therapeutic levels at the site of the infection for a long period of time to be effective.”  Although the statement itself is accurate, in the context of other statements made on this page it implies that Baytril 100 is superior to other BRD treatments because of its faster speed of clinical action, a claim that is not supported by substantial evidence or substantial clinical experience and causes the promotional labeling to be misleading and to violate section 502(n) of the act.  See 21 CFR 202.1(e)(6)(ii).

Conclusion and Requested Action

These unsubstantiated claims misbrand Baytril® 100 within the meaning of sections 502(a) and (n) of the Act, [21 U.S.C. 352(a) and (n)].

The violations discussed in this letter do not necessarily constitute an exhaustive list.  It is your responsibility to see that your promotional materials for Baytril® 100, as well as other Bayer HealthCare products, comply with the requirements of the Act and its implementing regulations.

The Division of Surveillance requests that Bayer HealthCare immediately cease the use of the promotional labeling materials identified in this letter and all similar promotional items.  Future promotional materials should contain truthful and non-misleading information that is consistent with the approved labeling.  Please submit a written response within thirty (30) calendar days of receipt of this letter describing your intent to comply with this request.  Please direct your response to me at the Food and Drug Administration, Center for Veterinary Medicine, Division of Surveillance, HFV-210, 7519 Standish Place, Rockville, MD 20855.  We remind you that only written communications are official.

                                                                       Sincerely yours,


                                                                        Lynn O. Post, DVM, PhD, DABVT
                                                                        Director, Division of Surveillance
                                                                        HFV-210
                                                                        Center for Veterinary Medicine