Inspections, Compliance, Enforcement, and Criminal Investigations
JCB Labs LLC 7/7/14
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
Kansas City District
8050 Marshall Drive, Suite 205
Lenexa, Kansas 66214-1524
Telephone: (913) 495-5100
July 7, 2014
UNITED PARCEL SERVICE
CMS # 410466
Brian D. Williamson
President and CEO
JCB Labs, LLC
7335 West 33rd Street North
Wichita, KS 67205
Dear Mr. Williamson:
Between February 12, 2013, to February 27, 2013, U.S. Food and Drug Administration (FDA) investigators conducted an inspection of your facility, JCB Labs, LLC, located at 7335 West 33rd Street North, in Wichita, Kansas 67205. FDA inspected your firm after receiving reports of adverse events in patients who were administered Propoven (propofol) 1% that your facility repackaged from 100 mL vials into 10 mL syringes.
During FDA’s inspection, investigators observed serious deficiencies in your practices for producing sterile drug products, which could lead to contamination of the products, putting patients at risk. For example, your SOP 3.030, “Cleaning and Maintenance of the Clean Room Facility,” which includes instructions for the cleaning of the ISO-5 areas, specifies the use of disinfectants that are non-sterile and does not specify the use of sterile cleaning pads and towels or sporicidal agents.
In addition, we documented that your firm does not repackage or store propofol injectable infusion properly. Propofol is unstable in oxygen and must be preserved under an inert atmosphere. These observations and others were noted on a Form FDA 483 issued on February 27, 2013.
We note that on January 21, 2014, JCB Labs registered its facility with FDA as a section 503B outsourcing facility.
A. Adulteration Charges
Under section 501(a)(2)(A) of the Federal Food, Drug, and Cosmetic Act (FDCA) [21 U.S.C. § 351(a)(2)(A)], a drug is adulterated if it has been prepared, packed, or held under insanitary conditions whereby it may have been contaminated with filth or rendered injurious to health. Numerous sub-visible microorganisms and other contaminants are ubiquitous in an ordinary environment.
A firm producing sterile drugs must take certain steps in order to ensure removal of contaminants through various controls that focus on safeguarding drug sterility by assuring the quality of the processing environment (e.g., surfaces, personnel, air). Otherwise, drugs that are intended or expected to be sterile may become contaminated during preparation and, when administered to a patient, may result in infections and/or pyrogenic responses that pose a life-threatening health risk to a patient. Failure to take these steps when producing drugs that are intended or expected to be to be sterile causes the drug to be prepared, packed, or held under insanitary conditions.
FDA investigators noted that your drug products that were intended or expected to be sterile were prepared, packed, or held under insanitary conditions, whereby they may have become contaminated with filth or rendered injurious to health, causing your drug products to be adulterated under section 501(a)(2)(A) of the FDCA [21 U.S.C. § 351(a)(2)(A)]. For example, your firm failed to use sterile disinfectants, sterile cleaning pads and towels, or a sporicidal agent to disinfect the clean room and the ISO-5 area. The introduction or delivery for introduction into interstate commerce of any adulterated drug is a prohibited act under section 301(a) of the FDCA [21 U.S.C. § 331(a)]. It is also a prohibited act under section 301(k) of the FDCA [21 U.S.C. § 331(k)] to do any act with respect to a drug if such act is done while the drug is held for sale after shipment in interstate commerce of the components used to make the drug and results in the drug being adulterated.
B. Misbranding Charges
During the inspection, FDA investigators found that your firm does not package propofol in tight containers under an atmosphere of inert gas, which is the standard for packaging and storage of propofol established in the monograph by the United States Pharmacopeia (USP). As noted on the Form FDA 483 issued to your firm, you deviated from your established process during the repackaging of propofol 1% by venting the source vial to the pharmacy atmosphere without adequately determining what effects this has on finished drug product quality attributes. Under section 502(g) of the FDCA [21 U.S.C § 352(g)], a drug is misbranded if it purports to be a drug the name of which is recognized in an official compendium, unless it is packaged and labeled as prescribed therein. The propofol 1% repackaged by your firm is not packaged and stored as prescribed in the USP, causing it to be misbranded under the FDCA. The introduction or delivery for introduction into interstate commerce of any misbranded drug is a prohibited act under section 301(a) of the FDCA [21 U.S.C § 331(a)]. It is also a prohibited act under section 301(k) of the FDCA [21 U.S.C. § 331(k)] to do any act with respect to a drug if such act is done while the drug is held for sale after shipment in interstate commerce of the components used to make the drug and results in the drug being misbranded.
C. Corrective Actions
In your response to the Form FDA 483, you referenced your purported compliance with United States Pharmacopeia (USP)-National Formulary (NF) General Chapter <797> Pharmaceutical Compounding-- Sterile Preparations. As noted above, FDA investigators noted that your sterile drug products were prepared, packed, or held under insanitary conditions, whereby they may have become contaminated with filth or rendered injurious to health. FDA strongly recommends that your management immediately undertake a comprehensive assessment of your operations, including facility design, procedures, personnel, processes, materials, and systems. In particular, this review should assess your aseptic processing operations and design. Although not a requirement, you may wish to consider engaging a third-party consultant with relevant sterile drug manufacturing expertise in conducting this comprehensive evaluation. In addition, you should package and label your propofol, and any other drug recognized in an official compendium, in the manner prescribed therein.
The violations cited in this letter are not intended to be an all-inclusive statement of violations at your facility. 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, without limitation, seizure and injunction.
Within fifteen working days of receipt of this letter, please notify this office in writing of the specific steps that you have taken to correct violations. Please include an explanation of each step being taken to prevent the recurrence of violations, as well as copies of related documentation. If you do not believe that the products discussed above are in violation of the FDCA, include your reasoning and any supporting information for our consideration. If you cannot complete corrective action within 15 working days, state the reason for the delay and the time within which you will complete the correction. Your written notification should be addressed to:
Danial S. Hutchison, Compliance Officer
FDA Kansas City District Office
U.S. Food and Drug Administration
8050 Marshall Drive Suite 205
Lenexa, KS 66214
If you have questions regarding any issues in this letter, please contact our office at 913-495-5100.
Cheryl A. Bigham