WARNING LETTER
Aurora Pharmaceutical
MARCS-CMS 698797 —
February 07, 2025
Product:
Animal & Veterinary
Drugs
Recipient:
Recipient Name
Michael Strobel
Recipient Title
CEO
Aurora Pharmaceutical
1196 Highway 3 South
Northfield
,
MN
55057
United States
Issuing Office:
Center for Veterinary Medicine
United States
February 7, 2025
Re: ANADAs 200-620 Altren® (altrenogest), 200-621 SwineMate® (altrenogest), 200-718 Barrier™ for dogs (imidacloprid and moxidectin)
CMS #: 698797
WARNING LETTER
Dear Dr. Strobel:
The U.S. Food and Drug Administration (FDA) has reviewed your promotional communications for your FDA-approved products including your company website
1
and linked webpages and noted false or misleading claims and representations about the safety and effectiveness of these products. These promotional communications misbrand your products within the meaning of the Federal Food, Drug, and Cosmetic Act (FD&C Act) section 502(a) [21 U.S.C. 352(a)] and section 502(n) [21 U.S.C. 352(n)]; section 201(n) [21 U.S.C. 321(n)]; and 21 CFR 202.1(e)(5). It is a prohibited act to distribute a misbranded product in interstate commerce. Section 301(a) [21 U.S.C. 331(a)]. This violation is especially concerning from a public health perspective because your products Altren® (altrenogest) and SwineMate® (altrenogest) have serious user safety warnings and your product Barrier™ for dogs (imidacloprid and moxidectin) has a boxed warning regarding oral exposure in dogs and topical exposure in children.
Product Information
2
Altren
®
Altren® is indicated for:
“[S]uppression of estrus in mares. Suppression of estrus allows for a predictable occurrence of estrus following drug withdrawal. This facilitates the attainment of regular cyclicity during the transition from winter anestrus to the physiological breeding season. Suppression of estrus will also facilitate management of prolonged estrus conditions. Suppression of estrus may be used to facilitate scheduled breeding during the physiological breeding season.”
3
Due to human user safety risks, the package insert (PI) for Altren® contains user safety warning language: “Not for use in humans. Keep out of reach of children. Avoid skin contact. Altren® is absorbed through unbroken skin, and exposure may result in serious side effects to both women and men.
Wear vinyl, neoprene, or nitrile gloves when handling or administering Altren®, or when touching contaminated surfaces or equipment. Latex gloves are not protective.”
[Emphasis original].
Additional warning language includes:
“PREGNANT WOMEN OR WOMEN WHO MAY BE PREGNANT SHOULD NOT HANDLE ALTREN®. WOMEN OF CHILDBEARING AGE SHOULD EXERCISE EXTREME CAUTION WHEN HANDLING THIS PRODUCT.
Accidental absorption, such as via direct contact with the skin, could lead to a disruption of the menstrual cycle or prolongation of pregnancy….”
[Emphasis original].
The PI also contains a list of people who should not handle Altren®, instructions on what to do in case of accidental exposure, and reported human effects from exposure.
The PI for Altren® further contains, among other things, additional adverse event, warning, precaution, and contraindication information.
SwineMate®
SwineMate® is indicated for:
“[S]ynchronization of estrus in sexually mature gilts that have had at least one estrous cycle. Treatment with SwineMate® results in estrus (standing heat) 4 to 9 days after completion of the 14-day treatment period.”
4
Due to human user safety risks, the PI for SwineMate® contains user safety warning language stating: “Skin contact must be avoided as SwineMate® is readily absorbed through unbroken skin, and exposure may result in serious side effects to both women and men.
Always wear vinyl, neoprene or nitrile protective gloves when handling SwineMate
or when in contact with equipment or surfaces contaminated by this product.
Latex gloves are not protective.”
[Emphasis original].
Additional warning language includes:
“PREGNANT WOMEN OR WOMEN WHO MAY BE PREGNANT SHOULD NOT HANDLE SwineMate® (altrenogest). WOMEN OF CHILDBEARING AGE SHOULD EXERCISE EXTREME CAUTION WHEN HANDLING THIS PRODUCT.
Accidental absorption, such as absorption through the skin, could lead to a disruption of the menstrual cycle or prolongation of pregnancy....”
[Emphasis original].
The PI also contains a list of people who should not handle the product, instructions on what to do in case of accidental exposure, and information on reported human effects from exposure.
The PI for SwineMate® further contains, among other things, additional adverse event, warning, precaution, and contraindication information.
Barrier™ for dogs
Barrier™ for dogs is indicated for:
“[T]he prevention of heartworm disease caused by
Dirofilaria immitis
and the treatment of
Dirofilaria immitis
circulating microfilariae in heartworm-positive dogs.
Barrier for Dogs
kills adult fleas and is indicated for the treatment of flea infestations
(Ctenocephalides felis)
.
Barrier for Dogs
is indicated for the treatment and control of sarcoptic mange caused by
Sarcoptes scabiei var. canis.
”
5
The PI also contains a chart detailing the intestinal parasites and the associated stages Barrier™ for dogs is indicated to treat or control.
The PI contains a boxed warning stating:
“DO NOT ADMINISTER THIS PRODUCT ORALLY”
“For the first 30 minutes after application ensure that dogs cannot lick the product from application sites on themselves or other treated animals.”
“Children should not come in contact with application sites for two (2) hours after application.
(See Contraindications, Warnings, Human Warnings, and Adverse Reactions, for more information)”
Boxed warnings are the most significant type of warning in a product’s labeling and are used to emphasize serious or life-threatening risks.
6
The Warnings section of the PI states that oral ingestion of this product by dogs may cause “serious adverse reactions including depression, salivation, dilated pupils, incoordination, panting, and generalized muscle tremors.” The Human Warnings section states that human exposure to this product has been reported to cause “headache; dizziness; and redness, burning, tingling or numbness of the skin.”
In addition to the boxed warning, the PI contains, among other things, additional adverse event, warning, precaution, and contraindication information.
False or Misleading Claims
Prescription drug advertisements and labeling (promotional communications) misbrand a drug if they are false or misleading in any particular. See FD&C Act section 502(a),(n) (21 U.S.C 352(a),(n)). The determination of whether a promotional communication is misleading includes, among other things, not only representations made or suggested in the promotional communication, but also the extent to which the promotional communication fails to reveal facts material in the light of its representations or material with respect to consequences that may result from the use of the drug as recommended or suggested in the promotional communication. See FD&C Act section 201(n) (21 U.S.C 321(n)) and 21 CFR 202.1(e)(5).
The website for Aurora Pharmaceutical mentioned above
1
includes a tab at the top of the page titled “Species,” which contains links to product-specific webpages for each product the firm markets. The webpage for Altren®
7
can be found under “Equine;” the webpage for SwineMate®
8
can be found under “Porcine;” and the webpage for Barrier™
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can be found under “Pets.”
Altren®
The product webpage is misleading because it prominently features benefit information about the product in the center of the page, but fails to contain any risk information. See 21 CFR 202.1(e)(5)(ii). The webpage for Altren® omits information from the PI about the significant risks to humans from potential product exposure, as well as important animal safety warning language. This omission of risk information creates a misleading impression about the potential consequences associated with using the drug.
The webpage for Altren® also contains a link to a “Product Sheet”
10
which lacks fair balance because the first page contains information regarding benefits and effectiveness in a larger font and bulleted format, whereas risk information is presented only in a smaller font on the second page.
11
See 21 CFR 202.1(e)(5)(ii). The Product Sheet fails to present information relating to side effects and contraindications with a prominence and readability reasonably comparable with the presentation of information relating to effectiveness of the drug and fails to include on each page the information relating to side effects and contraindications or a prominent reference to its presence and location. 21 CFR 202.1(e)(7)(viii), (e)(7)(xii). Further, at the bottom of the webpage for Altren® there are links to print advertisements
12
which contain benefit information but omit important risk information about human user safety, such as that users should wear vinyl, neoprene, or nitrile gloves when handling or administering Altren®; latex gloves are not protective. Additionally, the risk information that is present on the advertisements, such as “Pregnant women, or women who suspect they are pregnant, should not handle Altren,” is presented in a small, lightweight font which is not reasonably comparable to the presentation of information relating to effectiveness in terms of prominence and readability. See 21 CFR 202.1(e)(7)(viii). It also does not explain that women of childbearing age should exercise extreme caution when handling Altren® because it is readily absorbed through the skin and can disrupt the menstrual cycle or prolong pregnancy.
SwineMate®
The product webpage is misleading because it prominently features benefit information about the product in the center of the page but fails to contain any risk information. See 21 CFR 202.1(e)(5)(ii). The webpage for SwineMate® omits information from the PI about the significant risks to humans from potential product exposure, as well as important animal safety warning language. This omission of risk information creates a misleading impression about the potential consequences associated with using the drug. Further, the webpage for SwineMate® fails to include adequate information for use, such as the effects, routes, methods of administration, and any relevant warnings, hazards, contraindications, side effects, and precautions. See 21 CFR 201.105(d)(1).
The webpage for SwineMate® also contains a link to a “Product Sheet”
13
which lacks fair balance because the first page contains information regarding benefits and effectiveness in a larger font and bulleted format, whereas risk information is presented only in a smaller font on the second page.
14
See 21 CFR 202.1(e)(5)(ii). The Product Sheet fails to present information relating to side effects and contraindications with a prominence and readability
reasonably comparable with the presentation of information relating to effectiveness of the drug and fails to include on each page the information relating to side effects and contraindications or a prominent reference to its presence and location. 21 CFR 202.1(e)(7)(viii), (e)(7)(xii). Further, the print advertisement linked at the bottom of the SwineMate® webpage
15
contains no risk information although there is benefit information presented. See 21 CFR 202.1(e)(1).
Barrier™ for dogs
The product webpage is misleading because it prominently features benefit information about the product in the center of the page, but fails to contain any risk information. See 21 CFR 202.1(e)(5)(ii). The webpage for Barrier™ for dogs omits the boxed warning from the PI, as well as other important animal and human safety information. This omission of risk information creates a misleading impression about the potential consequences associated with using the drug.
The ”Product Sheet”
16
linked on the Barrier™ for dogs webpage lacks fair balance because the first seven pages contain information regarding benefits and effectiveness in a larger font and with numerous charts, images, and visuals, whereas risk information is presented only in a smaller font on a single page at the end of the brochure. See 21 CFR 202.1(e)(5)(ii). The Product Sheet fails to present information relating to side effects and contraindications with a prominence and readability reasonably comparable with the presentation of information relating to effectiveness of the drug and fails to include on each page the information relating to side effects and contraindications or a prominent reference to its presence and location. 21 CFR 202.1(e)(7)(viii), (e)(7)(xii).
Conclusion and Requested Response
For the reasons discussed above, your website misbrands Altren®, SwineMate®, and Barrier™ for dogs within the meaning of the FD&C Act and make their distribution violative.
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FD&C Act section 502(a), (21 U.S.C. 352(a)); section 502(n) [21 U.S.C. 352(n)]; section 201(n) (21 U.S.C. 321(n)); section 301(a) (21 U.S.C. 331(a)), and 21 CFR 202.1(e)(5).
This letter is not intended to be an all-inclusive statement of violations that may exist in connection with your products. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations. It is your responsibility to ensure that your firm complies with all requirements of federal law, including FDA regulations.
This letter notifies you of our concerns and provides you an opportunity to address them. Failure to adequately address this matter may lead to legal action, including without limitation, seizure, and injunction.
Within fifteen (15) working days of receipt of this letter, please submit a written response addressing the concerns described in this letter, listing all promotional communications for Altren®, SwineMate®, and Barrier™ for dogs that contain representations like those described above, and explaining any plan for discontinuing use of such communications, or for ceasing distribution of Altren®, SwineMate®, and Barrier™ for dogs. If you cannot complete the above requested actions within fifteen (15) working days, state the reason for the delay and the time within which you will complete them.
If you believe that your products are not in violation of the FD&C Act, please include in your submission to us your reasoning and any supporting information for our consideration within 15 working days from the date of receipt of this letter.
Please direct your response to the undersigned at the Food and Drug Administration, Center for Veterinary Medicine, Division of Pharmacovigilance and Surveillance, 12225 Wilkins Ave, MPN II Room E436, Rockville, Maryland 20852. Please send a courtesy copy by email to CVMSurveillance@fda.hhs.gov. All correspondence should include a subject line that clearly identifies the submission as a Response to Warning Letter # 698797.
If you have any questions, please contact Dr. Christopher Loss by email at christopher.loss@fda.hhs.gov.
Sincerely,
/S/
Linda Walter-Grimm, DVM
Director, Division of Pharmacovigilance and
Surveillance
Office of Surveillance and Compliance
Center for Veterinary Medicine
________________
1
Veterinary Pharmaceuticals for Livestock, Dogs and Cats https://aurorapharmaceutical.com/ last viewed on 2.6.2025
2
This section does not include all the safety and risk information in the package insert for each product and does not necessarily represent the risk information that should be included in the promotional communication(s) cited in this letter.
3
FDA-approved package insert (PI) for Altren®
4
FDA-approved PI for SwineMate®
5
FDA-approved PI for Barrier™ for Dogs
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See, e.g., “Boxed Warning”, https://www.fda.gov/drugs/prescription-drug-advertising/drug-advertisingglossary-terms
7
EQUINE – Altren® (altrenogest) | Aurora Pharmaceutical
8
Porcine – SwineMate® (altrenogest) | Aurora Pharmaceutical
9
Barrier Pets Demo | Aurora Pharmaceutical. This webpage contains information about both Barrier™ for Dogs and Barrier™ for Cats
10
Identified as “ss000026 04/2020” for Altren®
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We also note that the PI on the second page of the Product Sheet is not the currently approved PI with the updated user safety information.
12
Identified as: Altren Aurora Ad 1 jpeg (ad000040 05/2018), Altren Aurora Ad 2 jpeg (000041 05/2018), Aurora Altren Ad-Florida (Ad000069 10/2019)
13
Identified as “ss000025 04/2020” for SwineMate®
14
We also note that the PI on the second page of the Product Sheet is not the currently approved PI with the updated user safety information.
15
Identified as “ad000048 10/2018”
16
Identified as “ad000174 12/2022” and “br000051 12/2022”
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We note that the website for Aurora Pharmaceuticals contains other product-specific webpages that are misleading because they omit risk information including, but not limited to, EQUISUL-SDT® (sulfadiazine/trimethoprim) found at EQUINE – EQUISUL-SDT® (Sulfadiazine/Trimethoprim) | Aurora Pharmaceutical, EquiCoxib™ (firocoxib) found at EQUINE – EQUICOXIB™ | Aurora Pharmaceutical and Revolt® (selamectin) found at Revolt for Pets | Aurora Pharmaceutical.
Content current as of:
03/11/2025
Regulated Product(s)
Animal & Veterinary
Drugs