- Essential Pharmacy Compounding
Kohll's Pharmacy & Homecare
12759 "Q" Street
Omaha, NE 68137
March 24, 2016
FDA Kansas City District Office
U.S. Food and Drug Administration
8050 Marshall Drive, Suite 250
Lenexa, KS 66214
Via Overnight Delivery
Re: Response to FDA Warning Letter Issued March 10,2016,
to Essential Pharmacy Compounding
Dear Mr. Hutchison:
Our office recently received the above-referenced Warning Letter from the Food and Drug Administration ("FDA"). The Warning Letter follows from a review of Essential Pharmacy Compounding's (''Essential Pharmacy") initial and updated responses to the inspectional observations identified in a May 22, 2015, FDA Form 483. The Form 483 was issued as a result of an inspection by the FDA of Essential Pharmacy in May 2015.
This letters serves as Essential Pharmacy's formal response to the Warning Letter, and we ask that the FDA publish this letter, excluding any exhibits, on the FDA's website and disclose this information any time the FDA provides a copy of Essential Pharmacy's Form 483 or the Warning Letter to a person or entity outside of the agency.
As we stated in our initial response letter dated June 11, 2015, the deficiencies cited by the FDA the Form 483 and the Warning Letter are inappropriately based upon the current Good Manufacturing Practices ("cGMPs") for finished pharmaceuticals established in 21 C.F.R. §§ 210 and 211 and further explained in the FDA's Industry Guidance on cGMPs for Sterile Drug Products Produced by Aseptic Processing. Please note that the latter is non-binding guidance only. In addition, as Essential Pharmacy employs a state-licensed pharmacist to compound drug products primarily for identified individual patients pursuant to a valid prescription order, Essential Pharmacy is exempt under 21 U.S.C. § 353a(a) from complying with 21 U.S.C. § 351(a)(2)(8), which requires that a drug product and any facilities used in its manufacturing conform with cGMPs.
In addition, while Essential Pharmacy compounds limited quantities of emergency veterinary medications for office use by Nebraska practitioners, such practice is expressly permitted by the Nebraska Board of Pharmacy and, therefore, should be excluded from FDA oversight in accordance with Congress's June 27, 2014, letter to the FDA regarding the ability of the agency to regulate community-based pharmacies. 1 As a 503A entity that neither engages in drug manufacturing nor is registered as a 503B outsourcing facility, the cGMPs are inapplicable to the operations of Essential Pharmacy. In any event, the outstanding issues identified in the Warning Letter have also been addressed by Essential Pharmacy's current policies and procedures to the extent that such observations constitute a "best practice" that, if adopted, would benefit the safety of Essential Pharmacy's patients. Specifically, the Warning Letter identified three separate areas of concern. These concerns, along with Essential Pharmacy's corresponding responses and actions, are set forth below.
First, the FDA stated that Essential Pharmacy "did not establish an adequate contact time for your sporicidal agent used to disinfect your aseptic processing areas." In particular, the FDA noted that the pharmacy's cleaning and disinfection policy includes a (b)(4)' However, the FDA advised that the manufacturer recommends a (b)(4) contact time for use of the product as a sporicide.
Please note that Essential Pharmacy has utilized (b)(4) as a general disinfectant and not as a sporicidal agent. Per (b)(4) label, use of the product as a (b)(4) requires only that (b)(4)." A copy of the product label is provided on the enclosed flash drive. Thus, Essential Pharmacy's procedures regarding the dwell times for (b)(4) were in compliance with the manufacturer's recommendations for its specific use by the pharmacy. In addition, the use of the product by Essential Pharmacy as a general disinfectant rather than as a sporicidal agent was also in compliance with the then-current United States Pharmacopeia (''USP") <797> guidance which addressed cleaning and disinfecting practices and did not specifically mandate the use of sporicidal agents.
We understand that the FDA's published cGMPs recommend the use of sporicidal disinfectants in ISO 5 areas and classified rooms on a regular basis. In addition, we acknowledge that in September 2015 revisions were proposed affecting the cleaning and disinfecting guidelines of USP <797>. If approved in its current form, such USP revisions would require that entities use sporicidal agents to clean all ISO-classified and segregated compounding areas.
While Essential Pharmacy is not subject to cGMPs standards, we acknowledge that such adoptions may provide additional assurances of a sterile compounding environment. Accordingly, Essential Pharmacy has amended its Policy 3.080, Cleaning and Disinfection of the Aseptic Compounding Area, to include the use of a sporicidal agent with adequate contact dwell time. A copy of the amended policy is provided as Exhibit A. Specifically, Essential Pharmacy has replaced the use of (b)(4) in its cleaning and disinfecting (b)(4) with (b)(4) and (b)(4), and sporicidal activity. Documentation of (b)(4) efficacy data is provided as Exhibit B. In addition, (b)(4) that has a minimum dwell time of (b)(4) for use as a sporicide; such dwell time is reflected in the amended Policy 3.080.
Second, the FDA noted that Essential Pharmacy "did not provide documentation (e.g., description of the conditions at the time of the smoke studies, videos of the smoke studies) to show that these studies. were performed under dynamic conditions." Accordingly, the FDA stated that Essential Pharmacy failed to "demonstrate through appropriate studies that your hoods area able to provide adequate protection of the ISO 5 areas in which sterile products are processed."
During the past year, a (b)(4) testing company conducted several USP-compliant smoke studies at Specifically, on (b)(4), the third party conducted smoke studies in the ante, buffer and chemo rooms as well as for the laminar flow hoods. The USP 797 Pharmacy Clean Room Compliancy Inspection report from the testing company documents "pass" results for these areas accordingly. A copy of the report is provided as Exhibit C. In addition, the summary of the certification of the laminar flow hoods also indicated "dynamic/operational'' conditions. Please note that a video recording of these smoke studies was previously provided to the FDA inspectors. We have also included a video recording of the (b)(4) smoke studies on the enclosed flash drive. As both the video recording and the resulting USP <797> Pharmacy Clean Room Compliancy Inspection Report indicate, the smoke studies were conducted during dynamic conditions.
Smoke studies were also conducted at Essential Pharmacy on (b)(4) as a result of renovations and the installation of new flooring in the compounding area. Unfortunately, Essential Pharmacy has been unable to obtain the video recordings of these smoke studies due, in part, to computer hardware failure on the part of the third-party testing company. Most recently, the third-party testing company conducted a smoke study on (b)(4). A video of that smoke study is also provided on the enclosed flash drive. A copy of the testing company's report can be provided to the FDA upon request once it has been received by the pharmacy. Going forward, Essential Pharmacy will ensure that all future smoke studies conducted as part of its USP <797> (b)(4) are properly recorded and provided to Essential Pharmacy prior to the testing company's exit from the premises.
Lastly, the FDA stated that "the equipment used to measure and verify pressure differentials in your room certification report dated (b)(4) was past due for required calibration." Essential Pharmacy acknowledges the importance of accurate and up-to-date equipment and devices. Accordingly, Essential Pharmacy has amended its Policy 3.040, Environmental Monitoring of the Aseptic Compounding Area: Air Exchange Pressure Differential, to provide for the routine calibration of its differential pressure gages as part of the pharmacy's USP <797> (b)(4). A copy of the amended Policy 3.040 is provided as Exhibit D. In accordance with the amended policy, a(b)(4) independent testing company calibrated the (b)(4) differential pressure gauges currently utilized by Essential Pharmacy on (b)(4). Documentation of the calibration results is provided as Exhibit E.
Through this response, Essential Pharmacy seeks to address all of the FDA's remaining observations and concerns. If the FDA requires additional information or communication from Essential Compounding, it is welcome to contact me at 402-895-6812.
Justin M. Kohll, R.Ph
1 Specifically, Congress stated that "Expecting these small pharmacies that practice in accordance with State law to register as outsourcing facilities solely because products are intended for office use is unreasonable." Letter from H. Morgan Griffith, et al., to Stephen Ostroff, M.D.,Acting Commissioner, U.S. Food and Drug Administration (June 12, 2015).