Randy Davis, D.Ph.
7304 Jarnigan Road
Chattanooga, Tennessee 3 7 4 21
August 24, 2016
Kari Batey, Compliance Officer
Food and Drug Administration
New Orleans District
404 BNA Drive
Building 200, Suite 500
Nashville, TN 37217
Via E-mail Kari.Batey@fda.hhs.gov
and Overnight Delivery
Re: Response to Warning Letter Issued August 5, 2016, to
The Wellness Center, Inc., d/b/a Designer Drugs ("Designer Drugs")
Reference No. 2016-NOL-11
Dear Ms. Batey:
The Food and Drug Administration ("FDA") conducted an inspection of our pharmacy, Designer Drugs, between May 18, 2015, and May 28, 2015. Following its inspection, we received a FDA Form 483 identifying thirteen observations. We responded to the FDA regarding its observations on June 17, 2015 (the "Response Letter"). In our Response Letter, we detailed the implementation of numerous best practices to provide further assurances to the FDA of the safety of our sterile drug products. We subsequently received an FDA Warning Letter dated August 5, 2016 (the "Warning Letter").
Please accept this letter and the accompanying exhibits as our formal response to the issued Warning Letter. We respectfully request that this letter, excluding the exhibits, be published on the FDA's website next to the Warning Letter and be included every time the FDA provides a copy of such document to a person or entity outside of the agency. Furthermore, as initially requested in June 2015, a copy of the Response Letter should also be published on the FDA's website as well as provided to any person or entity outside of the agency that receives a copy of our FDA Form 483.
In its Warning Letter, the FDA states that the "drugs you compound without valid prescriptions for individually-identified patients and [the] drug products you compound using domperidone are not entitled to the exemptions in Section 503A" and, as a result, "are unapproved new drugs and misbranded drugs" in violation of the Federal Food, Drug and Cosmetic Act ("FDCA"). Please note that we had ceased compounding domperidone capsules prior to the FDA inspection. A prescription log confirming this information is provided as Exhibit A. Specifically, we last filled a prescription for domperidone on May 11, 2015.
In addition, as we stated in our Response Letter, we are a traditional retail pharmacy licensed by the Tennessee Board of Pharmacy. Prior to May 15, 2015, we compounded commercially unavailable medications for office administration upon receipt of orders from licensed practitioners. This practice is permitted by the Tennessee Pharmacy Practice Act of 1996.1 As the practice of compounding for office-use is permitted and regulated by the state Board of Pharmacy, such a practice should also be excluded from FDA oversight in accordance with Congress's repeated instructions to the FDA. Most recently, on June 20, 2016, Congress stated in a letter to the Commissioner of the FDA that "[i]t is unacceptable that the FDA would ignore the Congress and continue to take the position that Section 503A specifically prohibits office-use compounding, despite clear congressional intent to the contrary and despite previous FDA actions that directly contradict that position, including the recent statement by Health and Human Services Secretary Burwell that also directly conflicts with FDA's current position on 'office-use. "'2 As a pharmacy that neither engages in drug manufacturing nor is registered as a 503B outsourcing facility, it is improper to deny us the exemptions afforded to traditional retail pharmacies under section 503A of the FDCA in light of Congress's intent.
Nonetheless, we have phased out compounding without a patient-specific prescription for office administration over the last couple of years and ceased it entirely as of May 15, 2015. Thus, as of May 15, 2015, all of our compounded drug products are dispensed only after the receipt of a patient-specific prescription.
Misbranded Drug Products
One of the exemptions for 503A pharmacies is an exemption from compliance with FDA requirements regarding labeling with adequate directions for use. Because we ceased dispensing any products without a patient-specific prescription prior to the FDA inspection and because we also ceased compounding domperidone prior to the FDA inspection, we are not subject to the labeling requirements set forth under section 502(f)(1) of the FDCA. Thus, the FDA's allegations involving misbranding drug products is improper.
Adulterated Drug Products
The Warning Letter states that drugs compounded at our pharmacy may have been "adulterated" under section 501(a)(2)(A) of the FDCA, which provides that a "drug or device shall be deemed to be adulterated ... if it has been prepared, packed, or held under insanitary conditions whereby it may have been contaminated with filth, or whereby it may have been rendered injurious to health .... " In addition, the FDCA does not further define what constitutes "insanitary conditions." FDA guidance on compounding practices has been typically restricted to current good manufacturing practices ("CGMPs"), which are applicable to drug manufacturers but which are not applicable to our pharmacy operations as a traditional pharmacy. Thus, to the extent that the FDA alleges a violation of Section 501(a)(2)(A) of the FDCA solely by alleging noncompliance with the FDA's CGMPs, we maintain that the indirect application ofrequirements to which it is exempt by statute is improper.
In any event, the outstanding issues identified in the Warning Letter have also been addressed by our current policies and procedures to the extent that such observations constitute a "best practice" that, if adopted, would benefit the safety of our patients. While the FDA states in its Warning Letter that "[s]everal of your proposed corrective actions appear adequate," it also identifies several proposed best practices previously detailed in our Response Letter as "inadequate." We now address each of the FDA's outstanding concerns, along with our corresponding responses and actions, in detail below.
First, the FDA notes that the "use of non-sterile wipes increases the potential for contamination to be introduced into the aseptic processing area and is an insanitary condition." Please note that the "non-sterile wipes" referenced by the FDA and used by our pharmacy were non-shedding, synthetic micro fiber towels that were laundered and packaged in a clean room. In addition, these micro fiber towels were specifically labelled for use in ISO 5-6 areas. However, in the best interest of ensuring a sterile environment, we have purchased sterile wipes (irradiated) for use in the ISO 5 area. Specifications for the sterile wipes are provided as Exhibit B. In addition, we have amended SOP 3.020, Cleaning and Maintenance of the Clean Room Facility, to reflect the use of these wipes. A copy of the amended SOP 3.020 is provided as Exhibit C.
Second, the FDA states that our Response Letter did not provide sufficient documentation to support the effectiveness of the sporicidal agent that we used in the aseptic processing area at the concentration and for the contact time in our policy. United States Pharmacopeia ("USP") <797> Appendix II states that sodium hypochlorite is an effective sporicide and suggests a contact time of 5-10 minutes. A copy of the appendix is provided as Exhibit D. Our cleaning and disinfecting process for at least the last two years has been to use the sodium hypochlorite daily on the ISO 5 area as well as on floors and surfaces in the buffer and ante rooms. SOP 3.020 has been revised to correctly reflect a minimum soak time of ten minutes, as well as to include the use of sodium hypochlorite 0.1 % as a daily agent in addition to a monthly agent. An amended SOP 3.020 was previously provided as Exhibit C. In addition, we purchased a HaloMist™ Hydrogen Peroxide fogging system in April 2016. The system mists a 5% hydrogen peroxide/0.01 % silver spray over the entire room and is proven to kill 99.9% of all bacteria and spores. Additionally, we fog the ISO areas once monthly. SOP 4.150, Use, Verification and Maintenance of the Sanosil Halofogger, reflects this addition to our cleaning process and is provided as Exhibit E.
Third, the FDA notes that the "documentation provided in your response does not establish smoke studies were performed under dynamic conditions during your latest certification." We have provided additional documents relating to our January 2015 testing as Exhibit F. The Comments section of the Report of Cleanroom Compliance documents that all testing was performed under dynamic conditions. In addition, a third-party vendor conducted a certification of our hood and cleanroom on July 26, 2016. A copy of this most recent certification is provided as Exhibit G. The certification report documents "DYNAMIC OPERATION" as the "Condition of Room During Testing." The certification was performed in accordance with USP <797> guidelines, and we have met or exceeded these guidelines as documented in the report.
Fourth, the FDA notes that "our investigator observed environmental sampling taken immediately after cleaning, which could potentially bias the results." As stated in our Response Letter, our SOP 3.030, Environmental Monitoring of Clean Room, requires that environmental sampling be performed after compounding and prior to cleaning, and applicable personnel have been re-trained on this policy. Thus, we believe the FDA's concerns with respect to this matter have been sufficiently addressed. However, in an effort to better assess our environment, we have recently purchased an air impaction machine to collect viable air samples. A description of the air impaction machine is provided as Exhibit H. By purchasing the air impaction machine, we are now able to conduct a more thorough air sampling on a monthly basis. A copy of the amended SOP 3.030 providing for the use of the air impaction machine is provided as Exhibit I.
Fifth, the FDA states that "your firm used non-pharmaceutical grade nitrogen gas in the production of sterile drug products." USP <797> does not specifically impose requirements for the use of nitrogen as a blanket or an overlay gas. Nitrogen, as utilized in our pharmacy operations, is similar to an "added substance" even though it does not become a part of the compound. USP guidelines on non-sterile ingredients and devices recommend that an added substance be a USP or National Formulary ("NF") article. As we stated in our Response Letter, the non-NF nitrogen tank was removed on May 19, 2015, and a nitrogen tank that is an NF article has been used as of June 3, 2015. All future nitrogen purchases will be NF articles. We have attached a copy of the invoice for the NF nitrogen as well as a photograph of the actual product in our lab as Exhibit J. The above information should be sufficient to properly address the FDA's concerns.
Lastly, the FDA states that "your firm used a multiple purpose, household glue as a component within one of your topical drug products." Accordingly, the FDA requested "documentation that this component is appropriate for use within a topical drug product." Please note that this particular ingredient was used one time at the request of a physician who had a specific need for a patient. USP <795> guidelines allow products that are not USP or NF to be used when compounding and allow the compounder to use his or her professional judgment when selecting products. After reviewing the material safety data sheet ("MSDS") for the household glue and determining that the product was completely non-toxic, the pharmacist-in-charge determined that the ingredient would be safe to use in the topical compounded product as requested by the prescribing physician. The MSDS is provided as Exhibit K. The ingredient was used one time in one compound for one patient at the specific request of the doctor, and the pharmacy was within USP guidelines to utilize the product. However, while we have followed USP guidelines in purchasing chemicals for our compounded products, we have changed our SOP 6.010, Product Procurement, Receipt and Inspection, following the FDA inspection so as to purchase only USP or NF chemicals. A copy of the amended SOP 6.010 is provided as Exhibit L.
We believe that we have thoroughly and completely provided corrective actions that exceed USP standards. These actions should satisfy FDA concerns as well. It is important to note that many of the observations cited in the FDA Form 483 and in the Warning Letter had already been corrected prior to the FDA's inspection. Others were corrected immediately upon inspection, even while the inspector was in our facility. In addition, for many observations, we have agreed to comply with the FDA's requirements in order to perform under "best practice" conditions.
It is important to note that we are continually assessing the pharmacy's operations, facility design, procedures, personnel, processes, materials, and systems to provide greater assurances of patient safety. A few examples of these are:
• Purchasing a BioFlow air impaction machine
• Purchasing a Halomist hydrogen peroxide fogger
• Installing ultraviolet lighting in our ductwork
• Installing HEP A filters in our non-sterile lab
• Performing yearly Gap Analysis
• Enrolling aseptic staff and pharmacists in a 40-hour aseptic training through Critical Point
We also continually enlist the services of consultants for advice and direction in improving our methods and environment. These consultants provide guidance in areas that include, but are not limited to:
• USP <800> re-constructions
We believe that this letter, and the actions detailed herein, clearly demonstrate our commitment to patient safety and adequately address the FD A's concerns regarding our pharmacy operations. However, should additional information be necessary, please do not hesitate to
contact me at 423-954-25857.
1 See, for example, Tenn. Code§ 63-10-204(6)(D), which defines "compounding" to include "the preparation, mixing, assembling, packaging or labeling of a drug or device ... for use by a licensed prescribing practitioner's office for administration to the prescribing practitioner's patient or patients when the product is not commercially available upon receipt of an order from the prescriber .... "
2 Letter from Chris Stewart, et al., to Dr. Robert M. Califf, M.D., Commissioner, U.S. Food and Drug Administration (June 20, 2016).