Warning Letter - IPQ
Warning Letter - IPQ
Warning Letter - IPQ
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Franck's Lab Inc., d.b.a. Franck's Compounding Lab 7/9/12<br />
Department of Health and Human Services<br />
Public Health Service<br />
Food and Drug Administration<br />
Florida District<br />
555 Winderley Place, Suite 200<br />
Maitland, Florida 32751<br />
Telephone: 407-475-4700<br />
FAX: 407-475-4770<br />
CERTIFIED MAIL<br />
RETURN RECEIPT REQUESTED<br />
WARNING LETTER<br />
FLA-12-38<br />
July 9, 2012<br />
Paul W. Franck<br />
President and Chief Executive Officer<br />
Franck's Lab, Inc. dba Franck's Compounding Lab<br />
1210 SW 33rd Avenue<br />
Ocala, Florida 34474<br />
Dear Mr. Franck:<br />
During our March 9 May 11, 2012 inspection of your pharmacy, Franck's. Compounding Lab, located at<br />
1210 SW 33rd Avenue, Ocala, FL, investigators from the Food and Drug Administration (FDA)<br />
determined that your firm compounds drugs for intraocular injection, including Brilliant Blue G (BBG)<br />
Injection, Preservative-Free, in various concentrations, and Triamcinolone Injection, Preservative-Free. In<br />
addition, your firm compounds other sterile drug products.<br />
The inspection revealed that your BBG Injection drug product is adulterated within the meaning of<br />
section 501(a)(1) of the Act [21 U.S.C. § 351(a)(1)] in that it consists in whole or in part of any filthy,<br />
putrid, or decomposed substance. This inspection further revealed that this drug is adulterated within the<br />
meaning of Section 501(c) of the Act [21 U.S.C. 351(c)], in that its strength differs from, or its purity or<br />
quality falls below, that which it purports or is represented to possess. Furthermore, this drug and all<br />
sterile drugs compounded by your firm are also adulterated under section 501(a)(2)(A) of the Act [21<br />
U.S.C. § 351(a)(2)(A)], in that they have been prepared, packed, or held under insanitary conditions<br />
whereby they may have been contaminated with filth, or whereby they may have been rendered injurious<br />
to health.<br />
In addition, BBG Injection drug products compounded by your firm were misbranded within the meaning<br />
of Section 502(a) of the Act [21 USC 352(a)] because their labeling was false or misleading.
ADULTERATION CHARGES<br />
FDA laboratory analysis identified the presence of Fusarium incarnatum-equiseti species complex, as<br />
well as other microorganisms, in samples of your compounded drug product BBG Injection collected<br />
during the inspection. This Fusarium incarnatum-equiseti species complex genetically matched Fusarium<br />
clinical isolates from patients who developed fungal endophthalmitis after the administration of your<br />
compounded BBG Injection. These findings demonstrate that lots of Brilliant Blue G are adulterated<br />
within the meaning of section 501 (a)(1) of the Act [21 U.S.C. § 351 (a)(1)], in that it consists in whole or<br />
in part of any filthy, putrid, or decomposed substance. Furthermore, these BBG Injection drug products<br />
were labeled as being sterile, and are therefore adulterated within the meaning of Section 501 (c) of the<br />
Act [21 U.S.C. 351(c)], in that its strength differs from, or its purity or quality falls below, that which it<br />
purports or is represented to possess.<br />
Also, multiple bacterial and fungal species were found in several locations within one of your firm's ISO<br />
Class 5 laminar flow hoods and the ISO Class 7 clean room where you compound sterile drugs. These<br />
products are adulterated within the meaning of Section 501(a)(2)(A) of the Act [21 USC§ 351(a)(2)(A)]<br />
in that they were prepared, packed, or held under insanitary conditions whereby they may have been<br />
contaminated with filth, or whereby they may have been rendered injurious to health. The inspection<br />
revealed additional insanitary conditions under which your firm compounds sterile drugs, including but<br />
not limited to, the following:<br />
1. A compounding technician twice left and re-entered the cleanroom without changing the lab coat,<br />
foot covers, or any other personal protective equipment (PPE). This practice of re-entering the<br />
cleanroom without changing into new PPE creates an unacceptable hazard as the technician<br />
increased the potential for conveying uncontrolled microbial load from the unclassified pharmacy<br />
room into the cleanroom environment and the laminar flow hoods where sterile products are<br />
manipulated.<br />
2. While putting on sterile gloves, a compounding technician touched the outside of one of the gloves<br />
with a bare hand before putting on the second glove. This breach of asepsis created a significant<br />
microbial contamination hazard from bare skin when the technician then proceeded to perform sterile<br />
drug compounding in the laminar flow hood.<br />
3. A compounding technician was observed to touch the hood's outer surfaces with both gloved<br />
hands and then began sterile compounding. This technician's unnecessary actions presented a<br />
significant risk that microorganisms from the hood's outer surfaces would be transferred into the<br />
laminar flow hood and contaminate compounded sterile products. Notably, environmental sampling<br />
of the outer surfaces of the hood collected two days earlier found multiple sites contaminated with<br />
microorganisms.<br />
MISBRANDING CHARGES<br />
Your contaminated BBG drug products are indicated for ophthalmic use through intraocular injection.<br />
Drugs with this route of administration are required to be sterile. Although your BBG drug products were<br />
labeled as being sterile, clinical and drug product samples indicate that BBG drug products were<br />
contaminated with Fusarium. Therefore, the contaminated drug products bearing this labeling were<br />
misbranded under Section 502(a) of the Act because the labeled sterility claim and directions for<br />
intraocular administration misleadingly implied the products were sterile.
Neither this letter nor the observations noted on the FDA-483 is intended to be an all-inclusive list of<br />
the deficiencies that may exist at your facility. In addition, the Agency may send further<br />
correspondence based upon continued review of the inspectional findings. You are responsible for<br />
investigating and determining the causes of the deviations identified above and for preventing their<br />
recurrence and the occurrence of other deviations. We note that the following observations, if<br />
adequately addressed, could help prevent the violations of the Act described above:<br />
1. Your firm failed to adequately assess compounding personnel aseptic practices. For example, there<br />
was no indication that fingertip sampling, demonstrating competency in proper hand hygiene and<br />
garbing procedures, were performed as part of either an initial competency evaluation or a routine<br />
monitoring program. As direct human touch contamination is the most likely source of introducing<br />
microorganisms into sterile products, your firm's programs and practices were inadequate to assure<br />
that personnel were capable of maintaining asepsis to prevent serious microbial contamination<br />
hazards to the ISO Class 5 laminar flow hood environment, and ultimately, to product sterility.<br />
2. In your firm's performance of environmental monitoring tests, you failed to use a fungal growth<br />
media and your firm was not able to reliably detect the presence of fungi in the environment. It<br />
should be noted that when environmental samples of your cleanroom were cultivated in suitable<br />
growth media to recover fungi, multiple fungal species were identified at various sampling sites.<br />
3. Your firm does not perform environmental viable airborne particle testing under routine<br />
operational conditions to evaluate the competency of compounding personnel work practices.<br />
Furthermore, your SOP 3.060, "Environmental Monitoring of the Aseptic Compounding Area:<br />
Microbial Organism," is deficient in that it does not contain an environmental monitoring sampling<br />
plan that is based upon a risk assessment of the compounding activities performed. For example, the<br />
sampling plan does not specify method of collection, type of microbial growth media to be used,<br />
volume of air sampled, when samples are to be taken, or action or alert levels. You lack assurance<br />
that the current state of your ISO Class 7 cleanroom; ISO Class 5 laminar flow hoods; and personnel<br />
cleansing, garbing, and compounding practices sufficiently minimize airborne viable particles to<br />
prevent microbial contamination of your products during routine operations.<br />
4. Your firm does not perform nonviable (particulates) monitoring in the ISO Class 5 area of your<br />
cleanroom. Furthermore, your firm does not conduct smoke studies for your laminar flow hoods to<br />
demonstrate unidirectional air flow and sweeping action over and away from compounded drug<br />
products under dynamic conditions. You have no assurances that the laminar flow hoods are<br />
Working properly to keep particles shed by personnel from contaminating compounded sterile drugs.<br />
5. The ceiling of your firm's clean room consists of inlaid panels which have neither been<br />
impregnated with a polymer to render them impervious and hydrophobic, nor caulked around each<br />
perimeter to seal them to the support frame. As such, these areas are prone to the accumulation of<br />
dust and other particles and are potential sites for microbial contamination of your ISO Class 7<br />
cleanroom.<br />
It is your responsibility to assure that your sterile compounding operations comply with all requirements<br />
of federal law and FDA regulations.<br />
You should take prompt action to correct the deviations detailed in this letter. Failure to promptly correct<br />
these deviations may result in legal action without further notice including, without limitation, an<br />
injunction. Other federal agencies may take this <strong>Warning</strong> <strong>Letter</strong> into account when considering the award<br />
of contracts. FDA may re-inspect to verify corrective actions have been completed.
We acknowledge your firm's response of June 15, 2012 and your continued commitment to recall all<br />
human and veterinary drug products compounded since November 21, 2012 and to suspend sterile<br />
compounding operations at least until observations documented on the Form FDA 483 issued to your firm<br />
on May 11, 2012, have been adequately resolved. If at a later date your firm decides to resume sterile<br />
compounding operations, FDA strongly recommends that you retain an independent expert, who is<br />
knowledgeable and experienced in sterile compounding, to assist you in implementing appropriate sterile<br />
compounding procedures and conditions, as required by law. In addition, we acknowledge your<br />
commitment to notify FDA well in advance of any resumption of sterile compounding operations and<br />
request that you submit all relevant SOPs to the Agency at that time for our review.<br />
Within fifteen working days of receipt of this letter, please notify this office in writing of the specific<br />
steps that you have taken to correct violations. Include an explanation of each step being taken to prevent<br />
the recurrence of violations and copies of supporting documentation. If you cannot complete corrective<br />
action within fifteen working days, state the reason for the delay and the date by which you will have<br />
completed the correction. Your reply should be sent to the attention of: Winston Alejo, Compliance<br />
Officer, Food and Drug Administration 555 Winderley Place, Suite 200, Maitland, Florida 32751. If you<br />
have questions regarding any issues in this letter, please contact Mr. Alejo at (407) 475-4731.<br />
Sincerely,<br />
/S/<br />
Emma R. Singleton<br />
Director, Florida District