Inspections, Compliance, Enforcement, and Criminal Investigations
Centaur, Inc. 1/8/10
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
|Kansas City District|
11630 West 80 Street
Lenexa, Kansas 66214-3340
Telephone: (913) 752-2100
January 8, 2010
RETURN RECEIPT REQUESTED
Ref. KAN 2010-03
President & Chief Executive Officer
1351 Old 56 Hwy, Building C
Olathe, KS 66061
Dear Mr. Metrokotsas:
During an inspection of your firm located at 1351 Old 56 Highway, Building C, Olathe, KS 66061 on June 17 through 26, 2009, investigators from the United States Food and Drug Administration (FDA) documented numerous violations of current Good Manufacturing Practice regulations, Title 21 Code of Federal Regulations, Parts 210 and 211 (21 C.F.R. Parts 210 and 211). The documented violations cause drug products manufactured at your facility to be adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug and Cosmetic Act (the "Act"), [21 U.S.C. § 351(a)(2)(B)], which provides that a drug is adulterated "if the methods used in, or the facilities or controls used for its manufacture, processing, packing, or holding do not conform to .... current good manufacturing practice to assure that such drug meets the requirements of this Act as to the safety and has the identity and strength, and meets the quality and purity characteristics, which it purports or is represented to possess."
The Agency has set out regulations containing current good manufacturing practices for finished pharmaceuticals in 21 C.F.R. Parts 210 and 211. Specifically, your violations of good manufacturing practice regulations include, but are not limited to, the following:
1. Failure to make written records of investigations into unexplained discrepancies as required by 21 C.F.R. 211.192. For example, a specific gravity analysis for isopropyl alcohol did not meet specifications. There was, however, no documented record regarding this failure to meet specifications. There was also no written record of any related investigation, including documentation of conclusions and follow-up, as required by 21 C.F.R 211.192.
2. Failure to provide and/or document education, training, and experience, or any combination thereof, to enable employees to perform their assigned functions as required by 21 C.F.R. 211.25(a). For example your firm failed to provide documentation establishing that your lab analyst, who performs QC laboratory analyses, including microbial tests, was trained and qualified to perform laboratory tests. Your standard operating procedure, SOP #(b)(4) Employee Training, states that a (b)(4)." No such log was available to establish that your lab analyst was adequately trained in accordance with this procedure.
3. Failure to include the initials or signature of a second person showing that the original records have been reviewed for accuracy, completeness, and compliance with established standards as required by 21 C.F.R 211.194(a)(8). Copies of testing records from your laboratory notebook were collected of 3 different product lots to show examples of original records without required initials or signature of a second person.
4. Failure to follow written procedures applicable to the quality control unit, as required by 21 C.F.R. 211.22(d). For example, there are documented instances of failure to follow SOP #(b)(4) Oven Temperature Mapping; SOP #(b)(4), USP Purified Water System; SOP #(b)(4), Sampling and Testing; SOP #(b)(4), Employee Training; and SOP #(b)(4) version #(b)(4), Investigation.
5. Failure to identify and control rejected in-process materials under a quarantine system designed to prevent their use in manufacturing or processing operations for which they are unsuitable as required by 21 C.F.R. 211.110(d). For example, three expired laboratory reagents were in use during the inspection.
6. Failure to provide adequate equipment for the control of humidity and temperature when appropriate for the manufacture, processing, packing or holding of a drug product as required by 21 C.F.R. 211.46(b). For example, your warehouse used for storage of raw materials, containers, and finished goods has no equipment to control temperature and humidity. This is especially critical considering that several of your drug products are labeled to be stored in controlled temperature ranges. These include (b)(4)%, (b)(4), (b)(4)%, (b)(4)%, and (b)(4)- all of which are labeled with instructions to store between (b)(4) and (b)(4) degrees Fahrenheit. (b)(4)%, (b)(4)%, and (b)(4)% are all labeled with instructions to store between (b)(4) and (b)(4) degrees Fahrenheit.
This letter is not intended to be an all-inclusive list of violations at your facility. It is your responsibility to ensure compliance with applicable laws and regulations administered by FDA. The specific violations noted in this letter and in the Form FDA 483 issued at the end of this inspection may be symptomatic of serious problems in your firm's quality assurance and laboratory systems. Some of these observations are repeats of violations noted in 2007, 2005, and 2003. You should investigate and determine the causes of the violations, and take prompt actions to correct the violations and to bring your products into compliance. Failure to promptly correct these violations may result in regulatory action being initiated by the Food and Drug Administration without further notice. These actions include, but are not limited to, seizure and/or injunction. Also, federal agencies are advised of the issuance of all Warning Letters so that they may take this information into account when considering the award of contracts.
We acknowledge your August 17, 2009 response to the June 26, 2009 form FDA 483. We have no objections to your planned corrections, but request more specific documentation to support your reply.
Please notify this office within fifteen (15) working days of receiving this letter of the current status of steps you have taken to bring your firm into compliance with the law. Your response should include a description of the status of corrective actions taken to address the violations as well as detailed plans on how you will prevent the violations from recurring. It should include a description of changes made to your quality system to ensure violations do not recur. If your planned corrections will occur over time, please include a timetable for implementation of those corrections. If corrective action cannot be completed within fifteen (15) working days, state the reason for the delay and the time frame within which the corrections will be completed.
Your reply to this Warning Letter should be sent to Matthew A. Walburger, Compliance Officer, Food & Drug Administration, Kansas City District, Southwest Region, 11630 West 80t Street, Lenexa, Kansas 66214-3340. If you have any questions about the content of this letter, please contact Mr. Walburger at 913-752-2719.
John W. Thorsky
Kansas City District