Inspections, Compliance, Enforcement, and Criminal Investigations
Huvepharma Inc 6/13/13
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
Kansas City District
June 13, 2013
RETURN RECEIPT REQUESTED
Glen Wilkinson, President
525 Westpark Dr.
Peachtree City, GA 30269
Dear Mr. Wilkinson:
An inspection conducted by the U.S. Food and Drug Administration (FDA) of your firm, Huvepharma, located at 3360 Maury Ave., St. Louis, MO 63116-2029, between February 14 and 28,2013, found significant deviations from FDA regulations for Current Good Manufacturing Practice (cGMP) for Type A medicated articles, Title 21, Code of Federal Regulations, Part 226 (21 CFR Part 226). Such deviations cause Type A medicated articles manufactured, processed, packed, or held at this facility to be adulterated within the meaning of section 501(a)(2)(B) [21 USC 351(a)(2)(B)] of the Federal Food, Drug, and Cosmetic Act (the Act). You may find the Act and FDA's regulations through links in FDA's home page at http://www.fda.gov.
We acknowledge receipt of your letter dated March 11, 2013, explaining the steps you have initiated in response to the Form FDA-483 issued on February 28, 2013. We will verify adequacy of these corrective actions during the next inspection.
The following deviations, observed by our investigator during the inspection, cause Type A medicated articles manufactured, processed, packed, or held at your facility to be adulterated:
• Although you have established potency specifications that apply to incoming active pharmaceutical ingredient (API) that will be used to manufacture Type A medicated articles, as required by 21 CFR 226.58(a), you have not been adhering to these specifications. Specifically, between July 2012 and the date of our inspection, your firm tested (b)(4) lots of API Salinomycin which assayed below your potency specification of (b)(4)%. You used all (b)(4) lots of the subpotent API in manufacturing your Type A medicated article, Sacox 60, adjusting the formulation (b)(4) times. You then distributed the batches in interstate commerce.
In your March 11, 2013 response to the Form FDA-483, you state that the raw material specification submitted to CVM on (b)(4) provides that salinomycin content should be approximately (b)(4)% and that the amount of calcium carbonate is to be adjusted when the salinomycin assay is less than or greater than (b)(4)%. However, the raw material specification to which you refer was superseded by the raw material specification you submitted in your supplemental application of (b)(4), which calls for a potency specification of (b)(4) % for API received from the supplier of the API at issue.
• Containers to be used for drug components are not properly stored in a manner to avoid mix-ups and contamination, as required by 21 CFR 226.40(b). Specifically, (b)(4) bulk bags of rejected Salinomycin Mycelate API (lots (b)(4), and (b)(4)) were being stored outside of the quarantine area.
Also, you failed to correct your SOP QAD-QA-009 "Investigations" as you had promised in your January 5, 2012 letter to FDA regarding a recall of Sacox 60, lot BSB394. That recalled lot was superpotent and should have been stored in quarantine status, but because it was not stored in quarantine, it was released and distributed in interstate commerce. Your January 2012 letter committed to correcting the SOP and training, but the current inspection revealed you have not made these changes.
In your response to the Form FDA-483, you committed to update the SOP and provide training to your personnel, by April 30, 2013. Please include a copy of the updated SOP in your response to this letter.
This is a recurring observation from the June 2011 inspection of your firm.
• Buildings used for the production, packaging, labeling, and holding of Type A medicated articles do not provide adequate temperature and humidity controls as required by 21 CFR 226.20(b). Specifically, raw materials and finished products are stored in an envirorunent which does not provide conditions (i.e. temperature and humidity) favorable for assuring that the identity, strength, quality, and purity of raw materials and finished products are preserved, before, during and after production. Our investigator identified nine of your Type A medicated articles and/or ingredients stored in temperature and/or humidity ranges out of the labeled range for storage of these products. These included Sacox 60 (Salinomycin), Sacox 60 (Salinomycin) with microtracer, Clinacox (Diclazuril), Coyden 25% (Clopidol), (b)(4), API, and (b)(4) API.
As an example, the (b)(4) API is labeled to be stored in a "cool, dry place, protected from direct sunlight", and the Sacox 60 finished product is labeled to be stored in a "cool, dry place". The current USP defines cool as a temperature between go and 15° C ( 46° and 59° F) and defines dry place as a place that does not exceed 40% average relative humidity at 20° C (68° F). Our investigator noted that temperatures in your warehouse in July and August 2012 ranged from 76° to 99° F, and humidity from 26-82%.
We acknowledge your response to the Form FDA-483 where you explain the improvements in the climate control system your firm has made to warehouse 28 since the 2011 inspection. Our concern in the current inspection is with buildings 2C and 2S, and products held there. We also acknowledge that storage conditions for (b)(4) and Clinacox allow "excursions" up to 40°C (104°F), and that there were no excursions above 40°C. However, an excursion is meant to cover a brief exposure; not extended storage in a warehouse. As you are aware, you could address this issue through improving the climate controls in the buildings at issue, and/or by demonstrating product stability at these elevated storage temperatures.
This is a recurring observation from the June 2011 and September 2009 inspections of your firm.
The above identification of violations is not intended to be an all-inclusive list of deficiencies at your facility. As a manufacturer of Type A medicated articles, you are responsible for assuring that your overall operation and the products you manufacture and distribute are in compliance with the law. It is your responsibility to assure adherence with each requirement of the Act and the implementing regulations. You should take immediate steps to attain compliance with the law. This letter notifies you of our findings and provides you an opportunity to correct the above deficiencies.
You should know that these serious violations of the law might result in FDA taking regulatory action without further notice to you. These actions include, but are not limited to, seizure, and/or injunction. Also, other Federal agencies are informed about the Warning Letters issued so they may consider this information when awarding government contracts.
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 which has been taken or will be taken to correct the violations and prevent their recurrence. If corrective action cannot be completed within fifteen (15) 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 corrections have been made.
In your response to this warning letter, please clarify the steps you have taken to determine the root cause of the low potency results for salinomycin sodium. Since salinomycin is known to be hygroscopic, please state if loss on drying (LOD) was tested for each of the lots before manufacture. We request that you determine whether the low potency results were due to excess water or degradation and submit that investigation in your response to this letter. You may also need to revise your specifications for salinomycin sodium and SACOX 60 to include limits for impurities and/or degradation products and submit those revised specifications to your ANADA 200-075 file.
Your response should be sent to Jessica E. Hensley, Compliance Officer, U.S. Food and Drug Administration, Kansas City District, 11630 West 80th Street, Lenexa, Kansas 66214-3340. If you have any questions about this letter, please contact Compliance Officer, Jessica E. Hensley at 913-495-5183.
John W. Thorsky
Kansas City District Office