- Animal & Veterinary
- Vetix Inc.
- Issuing Office:
- Cincinnati District Office
Department of Health and Human Services
|Public Health Service
Food and Drug Administration
6751 Steger Drive
Cincinnati, OH 45237-7070
October 12, 2016
Via United Parcel Service
Dr. Stuart L. Pierce
President and Co-Owner
961 Beasley St., Suite 270
Lexington, KY 40509
Dear Dr. Pierce:
An inspection of your facility located at 961 Beasley St., Suite 270, Lexington, KY 40509 was conducted by investigators from the U.S. Food and Drug Administration (FDA) on May 2, 2016 through June 3, 2016. This inspection found that your company distributes multiple drug products for animal use. An FDA Form 483 was issued to you on June 3, 2016 outlining some of FDA’s concerns.
As discussed further below, our investigators identified significant violations of Current Good Manufacturing Practice (CGMP) regulations for Finished Pharmaceuticals, Title 21, Code of Federal Regulations, Parts 210 and 211. These violations cause your animal drug products to be adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug and Cosmetic Act (FD&C Act) [21 U.S.C. § 351(a)(2)(B)] in that the methods used in, or the facilities or controls used for, their manufacture, processing, packing, or holding do not conform to, or are not operated or administered in conformity with CGMP. In addition, FDA laboratory analysis of samples of your products collected during the inspection confirmed the presence of microbial growth in your OptiMend, OptiVet, and Hy-Optic products, which are purported to be sterile. These products are thus adulterated under section 501(a)(1) of the FD&C Act in that they consist in whole or in part of any filthy, putrid, or decomposed substance. Finally, our review of your product labeling and website at the internet address www.kinetictech.net indicates that your OptiMend, OptiVet, and Hy-Optic drugs are unapproved new animal drugs. Therefore, these products are deemed unsafe within the meaning of section 512(a) of the FD&C Act, [21 U.S.C. § 360b(a)], and are adulterated under section 501(a)(5) of the FD&C Act [21 U.S.C. § 351(a)(5)].
Unapproved New Animal Drugs
As previously discussed in the Untitled Letter that was issued to your firm on April 2, 2015, your OptiMend, OptiVet, and Hy-Optic products are drugs under section 201(g)(1) of the FD&C Act [21 U.S.C. § 321(g)(1)], as they are intended for use in the mitigation, treatment, or prevention of diseases in animals and/or to affect the structure or function of the body of animals. Statements on your product labeling, including your website, that establish these intended uses of your products include, but are not limited to, the following:
- “Corneal Repair Drops for Horses, Dogs & Cats”
- “OPTIMEND Corneal Repair Drops enhance the natural healing process for corneal ulcers presented in horses, dogs & cats. The 0.2% Hyaluronic Acid gel binds to the eye surfaces to facilitate healing.”
- “Eye Irrigating Solution with Sodium Hyaluronate”
- “Opti Vet Eye Drops are formulated to enhance healing of corneal ulcers & reduce the ocular surface irritation & damage associated with KCS.”
- “Eye Irrigating Solution” … “Sodium Hyaluronate”
- “Refreshes eyes” … “Cleanses Eyes” … “Relieves Itching and Burning”
- “Hy-Optic is a veterinarian-researched and developed Sodium Hyaluronate (HA) eye solution that has been shown to be effective for several eye conditions in companion animals.”
- “This eye irrigating solution containing Sodium Hyaluronate also contains Vitamin B6 and Taurine to support eye tissue and the overall health of the visual system.”
Moreover, these products are new animal drugs, as defined by section 201(v) of the FD&C Act, [21 U.S.C. § 321(v)], because they are not generally recognized among experts 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. The products are not the subject of an approved new animal drug application, conditionally approved new animal drug application, or index listing under sections 512, 571, and 572 of the FD&CAct [21 U.S.C. § 360b, 360ccc, and 360ccc-1]. Therefore, the products are unsafe within the meaning of section 512(a) [21 U.S.C . § 360b(a)] of the FD&C Act, and adulterated under section 501(a)(5) of the FD&C Act [21 U.S.C. § 351(a)(5)]. Introduction of an adulterated drug into interstate commerce is prohibited under section 301(a) of the FD&C Act [21 U.S.C. § 331(a)].
In your letter to FDA dated September 19, 2016, you indicated that you have discontinued manufacture and distribution of your OptiMend, OptiVet, and Hy-Optic products. However, you also indicated that you would notify FDA prior to manufacturing and distributing the products in the future. You should be aware that if in the future you resume marketing these new animal drugs in the United States without obtaining an approved new animal drug application for them, you and the products may be subject to enforcement action without further notice.
Your OptiMend, OptiVet, and Hy-Optic animal drug products are also adulterated under section 501(a)(1) of the FD&C Act [21 U.S.C. § 351(a)(1)] in that they consist in whole or in part of any filthy, putrid, or decomposed substance. Finished product samples of the drugs were collected by an FDA investigator during the inspection. The products, which are purported to be sterile, were analyzed by an FDA laboratory and found to contain microbial growth, including burkholderia cepacia (Hy-Optic), burkholderia multivorans (Hy-Optic and OptiVet), serratia marcescens (OptiMend), and acinetobacter johnsonii (OptiMend).
We acknowledge your corrective action of initiating a recall of the products in August of 2016, and your assertion in your letter of September 19, 2016, that you would discontinue manufacturing and distributing the products. However, we remain concerned that the problems with these products are indicative of your company’s broader CGMP issues that are discussed further below.
FDA investigators also identified significant CGMP violations at your facility, causing your drug products to be adulterated under section 501(a)(2)(B) of the FD&C Act. Several CGMP violations were also identified by investigators at your previous inspection and in the subsequent Untitled Letter issued to your firm on April 2, 2015. We received and reviewed your written response dated June 14, 2016, concerning our investigator’s observations noted on the FDA Form 483, List of Inspectional Observations that was issued to you following your most recent inspection. We address this response below, in relation to each of the noted violations. FDA acknowledges that you are working to develop and implement procedures to attempt to bring your facility into compliance with the CGMP regulations. However, FDA still has concerns regarding your firm’s compliance with CGMP regulations. Specific violations observed during the inspection include, but are not limited to, the following:
1. Your firm failed to establish in writing and fully follow certain responsibilities and procedures applicable to the quality control unit [21 CFR § 211.22(d)]. Specifically:
The roles and responsibilities between your firm and your contract manufacturing facilities are not in writing. Your firm works with approximately 18 different contract manufacturing facilities to manufacture your drug products.
Your firm has failed to follow your following standard operating procedures:
(a) GEN-014 - External Auditing of Manufacturer: Your procedure indicates: “The External audit system has to assure, that all relevant GMP areas will be audited at periodic intervals.” However, your firm has not performed audits at periodic intervals at any of the approximately 18 contract manufacturing facilities used to manufacture your drug products.
(b) GEN-016 - Manufacturer Qualification Program: Your procedure states: “Manufacturers will be assessed and classified regularly based on their quality status. … This SOP defines the process to qualify manufacturers and to continuously monitor their quality status. … Manufacturer audits will be done according to SOP QA-14 External Auditing of Manufacturer. The audit report has to state whether the manufacturer is deemed to be qualified or not. The audit will be deemed acceptable for qualification of the manufacturer only if no critical observations have showed up. … All associated vendor documentation will be stored in the central archive within the Documentation System (DS) department.” However, your firm has not qualified any of the approximately 18 contact manufacturers used to manufacture your drug products.
FDA acknowledges your proposed corrective action that you will qualify your contract manufacturers and establish quality agreements with each of them. However, none of these operations have been completed since you promised to make similar corrections in your response letter dated May 14, 2015, following your previous FDA inspection and subsequent Untitled Letter issued to you on April 2, 2015.
2. Your firm failed to ensure testing of drug product which includes appropriate laboratory determination of satisfactory conformance to the final specifications and identity and strength of each active ingredient prior to release. [21 CFR § 211.165(a)]. Specifically:
Your firm accepts certificates of analysis for the release of your drug products without verifying the reliability of the certificates of analysis received. For example, your firm received OptiVet, lot 12032015, from the distributor along with a certificate of analysis issued by the distributor. You accepted this certificate of analysis and placed this product in inventory for distribution. You failed to verify that the testing is being performed according to established methods and using qualified equipment.
FDA acknowledges that you indicate in your written response that your contract manufacturers will go through a Qualification Program and that the reliability of their testing methods and equipment used will be verified and documented. However, you have not included any immediate corrective actions that will adequately verify the reliability of the certificate of analyses received prior to the completion of the contract manufacturer qualification.
3. Your firm failed to ensure drug products bear an expiration date determined by appropriate stability data to assure they meet applicable standards of identity, strength, quality and purity at the time of use. [21 CFR § 211.137(a)]. Specifically:
At the inspection, you indicated your firm has not performed stability studies to support the expiration dates assigned to your drug products. You indicated that your contract manufacturer assigned the two year expiration date to your Hy-Optic, Optivet and Optimend products. However, you indicated you were unaware whether your contract manufacturer had performed any stability studies. You have no data to support that your products meet applicable standards of identity, strength, quality and purity two years from the date of manufacture.
We acknowledge that in your response to the FDA Form 483 you indicate you plan to perform a review of each contract manufacturer as part of your qualification program to determine which contract manufacturers have appropriate supporting data. As the owner of the animal drug product, it is your responsibility to review and assure that the expiration dates appearing on your products are supported by scientific data.
4. Your firm failed to ensure there are written procedures for production and process controls designed to assure that the drug products have the identity, strength, quality, and purity they purport or are represented to possess. [21 CFR § 211.100(a)]. Specifically:
As noted above, your firm uses approximately 18 different contact manufacturing facilities to manufacturer the animal drug products owned and distributed by your firm. However, you were not able to provide documentation that the processes for manufacturing your drug products have been validated. You have no quality agreements in place with your contract manufacturers and have not qualified them or determined that they are manufacturing your products on qualified equipment according to a validated process.
FDA acknowledges your response in which you indicated that you will establish quality agreements with your contract manufacturers and implement a manufacturer qualification program, which you indicated will address this issue. However, none of these operations have been completed since you promised to make similar corrections in your letter of May 14, 2015 responding to the Untitled Letter issued to your firm on April 2, 2015. Additionally, based on the documents you reference in your response, which include QA-001 Quality Agreement and GEN-016 Standard Operating Procedure Manufacturer Qualification Program, it is unclear how you intend to verify that your contract manufacturers have adequate procedures for production and process controls. As the owner of animal drug products, it is your responsibility to ensure procedures for production and process controls are adequate and valid.
5. Your firm failed to ensure that the establishment of specifications including any changes thereto, are drafted, reviewed and approved by the appropriate organizational unit. [21 CFR § 211.160(a)]. Specifically:
You have not established the specifications your drug products should meet during finished product testing. For example, you developed the formula for Hy-Optic, OptiMend and OptiVet. However, you did not inform the contract manufacturer of the testing to be performed on the finished products or the specifications the finished product should meet in order for release. You indicated you left it up to the contract manufacturer to establish specifications, but did not review or verify those specifications. As the owner of the animal drug product, it is your responsibility to ensure that specifications are established, drafted, approved and followed for finished products and finished product testing.
FDA acknowledges your corrective action to implement specifications for your animal drug products and to distribute those specifications to your contract manufacturers within 90 days. However, according to the response letter you submitted to FDA on May 14, 2015, similar corrections for production and process controls and product specifications were planned after the previous inspection, but these were not completed as promised.
6. Your firm failed to ensure that the reserve sample of drug product consists of at least twice the quantity necessary to perform all the required tests of drug product. [21 CFR § 211.170(b)]. Specifically:
Your firm does not retain a reserve sample of at least twice the quantity needed to perform full testing. In addition, you have not verified that these reserve samples are being maintained by any of the approximately 18 contract manufacturers used to manufacture your drug products.
FDA acknowledges that the written agreements you indicate you plan to implement with your contract manufacturers include direction regarding which party is responsible for retention samples. However, no signed agreements were submitted with your response to indicate that this is currently being done. There is currently no evidence provided that shows if and how retention samples for your animal drug products are currently being maintained.
FDA will further evaluate the adequacy of your implementation of the proposed corrective actions in your written response, and your overall compliance with cGMP regulations, during the next inspection of your facility.
The issues and violations cited in this letter are not intended to be an all-inclusive statement of violations that exist in connection with your products. You are responsible for investigating and determining the causes of the violations identified above 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 and FDA regulations.
You should take prompt action to correct the violations cited in this letter. Failure to promptly correct these violations may result in legal action, without further notice, including and without limitation, seizure and injunction. Other federal agencies may take this Warning Letter into account when considering the award of contracts.
Within fifteen (15) working days of receipt of this letter, please notify this office in writing of the specific steps that you have taken to correct violations. Include an explanation of each step being taken to prevent the recurrence of violations, as well as copies of related documentation. If you cannot complete corrective action within fifteen working days, state the reason for the delay and the time within which you will complete the correction. Address your reply to the Food and Drug Administration, 6751 Steger Drive, Cincinnati, Ohio 45237, Attention: Andrew J. Lang, Compliance Officer.
Steven B. Barber