Inspections, Compliance, Enforcement, and Criminal Investigations
Innovacyn Inc. 7/23/12
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
|Los Angeles District|
Irvine, CA 92612-2506
VIA UNITED PARCEL SERVICE
July 23, 2012
Mr. Robert C. Burlingame, CEO
3546 N. Riverside Ave.
Rialto, CA 92377
Dear Mr. Burlingame:
This letter concerns your firm's marketing of numerous veterinary products under the Vetericyn brand name (collectively, Vetericyn® products). Vetericyn® products include various wound care, spray, eye wash, rinse, and gel products being marketed by your firm for use in horses, dogs, cats, birds, and cattle to treat a variety of animal diseases. The Food and Drug Administration (FDA) recently reviewed labels and other promotional materials for these products, including statements on your firm's websites at www.innovacyn.com and www.vetericyn.com. As discussed below, we have determined that the Vetericyn products marketed by your firm are unapproved new animal drugs in violation of sections 512(a), 501 (a)(5) and 301(a) of the Federal Food, Drug, and Cosmetic Act (the Act) [21 U.S.C. §§ 360b(a), 351(a)(5), and 331(a)].
In addition, an inspection of your firm conducted by FDA on November 21 through December 2, 2011, revealed significant violations of Current Good Manufacturing Practice (CGMP) requirements which cause your veterinary products to be adulterated under section 501(a)(2)(B) of the Act [21 U.S.C. § 351(a)(2)(B)].
Unapproved New Animal Drugs
Your firm currently manufactures and markets various veterinary products under the Vetericyn® brand name, including: Vetericyn® Teat Spray; Veterieyn® Canine Hot Spot Spray; Vetericyn® All Animal Eye Wash; Vetericyn® All Animal Ear Rinse; Vetericyn® Feline Wound and Infection Treatment Liquid; Vetericyn® All Animal Wound and Infection Treatment Liquid; Vetericyn® Equine Wound and Infection Treatment Liquid; Vetericyn® All Animal Pink Eye Spray; Vetericyn® VF Opthalmic Wash; Vetericyn® VF Otic Rinse; Vetericyn® VF Wound and Infection Liquid; Vetericyn® VF Hydrogel Spray; Vetericyn® All Animal Wound and Infection Hydrogel; Vetericin® All Animal Ophthalmic Gel; and Vetericyn® Umbilical, Navel and Udder Gel; Vetericyn® Wound and Infection Care.
The promotional materials for these Vetericyn® products represent these products as topical antimicrobials, ophthalmic washes and gels, otic rinses, and teat sprays and udder gels for use in treating, controlling or preventing various diseases in animals after exposure to serious pathogenic organisms. For example, the Vetericyn® Teat Spray label reads in part, "Treat Spray for use as an aid in controlling the spread of bacteria that cause bovine mastitis. Promotes healing of cracked teats*** may assist in prevention and control of herd outbreak of bacteria that may cause bovine mastitis.***" In addition, statements appearing on your firm's website at www.vetericyn.com under the "Vetericyn Benefits" tab describe Vetericyn® as a "One-step wound and infection treatment that works naturally with your animal" Also under "Vetericyn Benefits," the web site further describes Vetericyn® wound products as "[a] scientifically engineered topical solution that mimics the body's immune system response to viruses, bacteria, fungi and spores.*** Vetericyn is used to care for a host of infections and wounds including, hot spots, scratches, outer ear infections, ring worm, skin fungus, rain rot, cinch fungus, dryland distemper/Pigeon Fever/Strangles, eye infections including conjunctivitis. ***Vetericyn significantly increases the oxygen content at the wound site within 30 seconds and maintains that oxyen level for up to 36 hours. This increase in oxygen along with the reduction of infection is responsible for these accelerated healing times."
Furthermore, many of the Vetericyn® product labels contain statements describing an antimicrobial effect. For example, the Vetericyn® VF Otic Rinse, VF Wound & Skin Care, Eye Wash, Hot Spot Spray, and Wound and Infection product labels reviewed by FDA state in part:
"This product, in solution, kills 99.999% of bacteria, viruses, fungi and spores including E. coli, Staph (MRSA), Strep, Moraxella bovis, Pasteurella, Actinomyces and Pseudomonas aeruginosa."
Statements throughout your firm's websites also promote the Vetericyn® products as having antimicrobial effects. For example, the "Product Features" section of your website includes the following claims which appear to apply to all Vetericyn products:
• "Vetericyn animal wellness products are innovative topical solutions for the care of wounds, infections and irritations caused by bacteria, viruses, fungi or spores. ***These products, in solution, kill 99.999% of bacteria, viruses, fungi and spores including E.coli, Staph (MRSA), Strep, Moraxella bovis, Pasteurella, Actinomyces and Pseudomonas aeruginosa."
• "In solution, kills 99.999% of most bacteria, fungi, viruses and spores (including MRSA, Coli, Strep, Staph, Pasteurella) in just 30 seconds"
Similar claims appear in the "Vetericyn Benefits" section of your website, which states in part, "Vetericyn technology kills 99.999% of all single cell organisms in just 30 seconds! ***In solution this product kills 99.999% of bacteria, single-cell organisms and fungi making it ideal for infections caused by bacteria such as E.coli, Staph (MRSA), Strep, Moraxella bovis, Pasteurella, Actinomyces and Pseudomonas aeruginosa"
Additionally, under the heading "Why Vetericyn is Superior" the website further describes Vetericyn as "a scientifically engineered topical solution that kills virtually any infection. *** Vetericyn is completely bio-compatible because it mimics the body's natural immune system's response to an infection. In addition, bacteria, virus, fungi and spores have not demonstrated the ability to develop resistance to Vetericyn. In fact, Vetericyn kills all these single-cell pathogens within 30 seconds of contact. Vetericyn is so potent it kills staph, E.coli and even MRSA. *** There are also two other significant benefits to Vetericyn. Wounds treated with Vetericyn have demonstrated a reduction in healing time by up to 60%. *** Second, Vetericyn treats and reduces chronic inflammation by inhibiting the release of histamines by the mast cells. Chronic inflammation is a barrier to healing. To summarize, Vetericyn is a completely non-toxic anti-bacterial, anti-fungal and anti-viral that is environmentally friendly and safe as water."
The "Vetericyn Frequently Asked Questions" portion of the www.vetericyn.com website indicates that Vetericyn products were developed based on technology from wound cleansing products that have already received 510(k) clearance from FDA. A letter from your company, dated December 20, 2011, (Innovacyn Response) which was provided to FDA following the inspection identified the relevant 510(k) clearances as K060113 and K093585. A review of our records indicates that the 510(k) clearances you rely on describe these devices as "a wound cleansing solution that is intended for the moistening and debriding of dermal wounds. The mechanical action of fluid moving across the wound provides for the mechanism of action and aids in the removal of foreign objects such as dirt and debris." Furthermore, the clearances you rely on do not include claims of bacteria reduction as an indication for use. As discussed above, the labels and labeling for the Vetericyn® products, including statements on your firm's websites, make various claims regarding bacteria reduction.
The Vetericyn® products, as presently labeled and promoted, are not animal devices¹, because they achieve their primary intended purpose (treatment of infections/wound healing) through chemical action (osmotic pressure imbalance, cell lysis) within the animal's body. As such, the Vetericyn® products are drugs within the meaning of section 201(g)(1) of the Act [21 U.S.C. § 321 (g)(1)]. The products are also new animal drugs under section 201(v) of the Act [21 U.S.C. § 321(v)] because they are not generally recognized among expelis qualified by scientific training and experience to evaluate the safety and effectiveness of animal drugs, as safe and effective for use under the conditions prescribed, recommended, or suggested in the labeling. Furthermore, the Vetericyn® products are not the subject of an approved new animal drug application (NADA), abbreviated new animal drug application (ANADA), conditionally approved new animal drug application (CNADA), or an index listing under sections 512, 571, or 572 of the Act [21 U.S.C. §§ 360b, 360ccc, and 360ccc-1]. Therefore, the Vetericyn® products are unsafe within the meaning of section 512(a) of the Act [21 U.S.C. §360b(a)] and adulterated under section 501(a)(5) of the Act [21 U.S.C. §351(a)(5)]. Introduction of an adulterated drug into interstate commerce is prohibited under section 301(a) of the Act [21 U.S.C. §331(a)].
Additionally, during an inspection conducted at your firm between November 21 and December 2, 2011, our investigator identified significant violations of the CGMP regulations at 21 C.F.R. Parts 210 and 211. These violations cause your drug products to be adulterated within the meaning of section 501(a)(2)(B) of the Act [21 U.S.C. 351(a)(2)(B)]. We reviewed your December 20, 2011, response to the FDA-483 observations and note that some of the deficiencies listed lack sufficient corrective actions. Specific violations not adequately addressed by the response include the following:
1) Your firm's Quality Control Unit (QCU) failed to ensure a thorough investigation in accordance with 21 C.F.R. § 211.192 with conclusions and follow up accomplished as required by 21 C.F.R. § 211.198.
For example, the QCU failed to investigate, or did not fully investigate complaints, in numerous documented instances. Specifically, numerous complaints were received by your firm from June to November 2011, for Vetericyn® Ophthalmic Gel, Vetericyn® Wound and Infection Equine, Vetericyn® All Animal Wound & Infection, and Vetericyn® Pink Eye Spray. For example, consumers reported adverse events relating to use in their animals, such as an eyelid being stuck to the cornea, skin initation and reactions, inflamed wound after product use, leaking and damaged bottles, eye irritation after product use, and that the product was ineffective for the intended use.
We have concluded your company did not conduct timely, comprehensive investigations. Your firm's management, including the QCU, failed to respond to consumer complaints. Moreover, in your company's response, (b)(6) that prior to the FDA inspection, Innovacyn "identified the nonconformance of not completely executing complaint handling in accordance with the referenced procedure." (Innovacyn Response at pg. 5). Quality problems must be thoroughly investigated; root cause determined; and appropriate corrective and preventive actions implemented.
Furthermore, the Innovacyn Response states that complaints will be handled under a revised complaint handling system, which appears to be designed to meet the requirements of 21 C.P.R. Part 820 for human devices. However, manufacturers of new animal drug products are required to comply with 21 C.P.R. Parts 210 and 211. We also note the Innovacyn Response neither addressed whether additional investigation of the complaints referenced in the Form FDA-483 was conducted, nor stated the outcome of any such investigations.
2) Your firm has not established laboratory controls that include scientifically sound and appropriate specifications to assure that components and drug products conform to appropriate standards of identity, strength, quality and purity, as required by 21 CFR § 211.160(b). For example, your firm has not established microbial specifications or conducted microbial testing on the purified water used in the formulation of your veterinary drug products. Your firm conducts bioburden testing, but this test method fails to demonstrate microorganism recovery. Also, your firm does not conduct growth promotion testing on the media. In the Innovacyn Response, a bioburden testing chart from 2011 was included; however, this response is inadequate because it fails to include testing data. We acknowledge your commitment to conduct microbial testing, but your response failed to include the microbial testing method proposed by your firm.
This letter is not intended to be an all-inclusive review of the products that your firm markets. It is your responsibility to ensure that all products marketed by your firm comply with the Act and its implementing regulations.
We request that you take prompt action to correct the noted violations. Failure to promptly connect these violations may result in enforcement action being initiated by the Food and Drug Administration without further notice. These actions include, but are not limited to, seizure and/or injunction. In addition, other federal agencies are advised of the issuance of Warning Letters pertaining to drugs so that they can consider this information when awarding contracts.
You should be aware that unapproved products that lack a required application or index listing are subject to FDA enforcement action to remove them from the market at any time. We also remind you that all drugs, whether marketed with approval or not, must, among other things, be listed with the FDA by a registered firm; manufactured according to CGMP; and have labels and labeling that meet the requirements of the Act and its implementing regulations. You may obtain information on the drug application approval process on our web page www.fda.gov/cvm
Please notify this office in writing within fifteen (15) working days of receipt of this letter of the specific steps that you have taken to correct the noted violations, including an explanation of steps taken to prevent the recurrence of similar violations. If corrective action cannot be completed within fifteen working days, state the reason for the delay and the time within which the corrections will be completed.
Your response should be sent to:
Mr. Blake Bevill
Director, Compliance Branch
Food and Drug Administration
Irvine, CA 92612-2506
If you have any questions about the content of this letter please contact Dr. William Vitale, Compliance Officer at 949-608-2919.
Alonza E. Cruse, Director
Los Angeles District
cc: Ms. Ingeborg Small, Chief
California Department of Public Health
Food and Drug Branch
1500 Capitol Avenue, MS 760
Sacramento, California 95899-7377
¹ Section 201(h) of the Act (21 U.S.C. 321(h)) provides that the term "device" means:
... an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including any component, part, or accessory, which is-
(1) recognized in the official National Formulary, or the United States Pharmacopeia, or any supplement to them,
(2) intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals, or
(3) intended to affect the structure or any function of the body of man or other animals, and which does not achieve its primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of its primary intended purposes.