- Lee Pharmacy
June 26, 2014
VIA EMAIL AND FEDERAL EXPRESS
Ms. Rose Ashley
Dallas District Office
Food and Drug Administration
4040 North Central Expressway
Dallas, Texas 75204
Re: Warning Letter Received June 10, 2014, Issued to Sunnymede Pharmacy, Inc., d/b/a Lee and Company and Lee Pharmacy (Ref: 2014-DAL-WL-08)
Dear Ms. Ashley:
This letter is in response to the Warning Letter issued to Sunnymede Pharmacy, Inc., d/b/a Lee and Company and Lee Pharmacy ("Lee Pharmacy"). FDA's Letter, like the related FDA Form 483 that it issued to Lee Pharmacy on February 21, 2013, reveals that the Agency believes that aseptic compounders of parenteral and other sterile drug preparations, that are licensed and regulated by the State of Arkansas as pharmacies, should be held to the standards and regulations applicable to FDA- regulated pharmaceutical manufacturers. Notwithstanding passage of Title I of the Drug Quality and Security Act (the Compounding Quality Act) ("DQSA") on November 27, 2013, Pub. L. No. 113-54, there has been no change in federal law authorizing FDA to regulate lawful compounding pharmacies such as Lee Pharmacy as manufacturers subject to current good manufacturing practices ("cGMPs") and other similar requirements of the Federal Food, Drug, and Cosmetic Act ("FDCA"). The FDA's cGMPs --various violations of which the Agency alleges in its Warning Letter-- do not apply to Lee Pharmacy. Nevertheless, as it has in the past, Lee Pharmacy remains committed to complying with all laws and regulations applicable to compounding pharmacies, and to ensuring high-quality, safe products for its patients.
Lee Pharmacy is a family-owned pharmacy that has been in existence since 1974. Lee Pharmacy's current owner has maintained a pharmacist license in Arkansas since 1996. The Company operates in accordance with the highest quality and safety standards in the compounding profession and has operated, and continues to operate in compliance with all applicable state laws and regulations, as well as the newly enacted DQSA. Lee Pharmacy's sterility controls for its aseptic compounding processes comply with USP <797> --Pharmaceutical Compounding, Sterile Preparations-- standards. For the past ten years, Lee Pharmacy's compounded products have experienced neither contamination nor potency issues, or issues concerning assurance of sterility. In the past 18 months alone, an independent lab conducted thousands of sterility, endotoxin and potency tests on Lee Pharmacy's preparations without a single failure.
At the time of FDA's inspection at Lee Pharmacy back in February 2013, and against the backdrop of unclear federal law concerning compounding (and state law permitting compounding for office use),1 Lee Pharmacy filled orders for drug products that had been discontinued or were otherwise commercially unavailable due to a drug shortage. However, after passage of the DQSA and Congress' clarification of the law, Lee Pharmacy promptly transitioned its compounding pharmacy business model to one that serves only patients with individually identified prescriptions. The Company has not accepted new orders for preparations compounded for office use, transfers all new orders to an outsourcing facility, and only fills prescriptions for individually identified patients pursuant to newly re-enacted Section 503A. Lee Pharmacy spends considerable effort, time and resources on maintaining and enhancing its quality assurance2 and quality control program.
Lee Pharmacy's Response to FDA's June 2014 Warning Letter
FDA's inspection that is the subject the Warning Letter occurred during a three-day period from February; 19 to February 21, 2013. The inspection, and resulting Form 483 Observations, occurred almost nine months prior to President Obama' s signing the DQSA into law on November 27, 2013. FDA's Warning Letter focuses solely on allegations that Lee Pharmacy violated the FDCA in various ways because it did not, in some instances, obtain prescriptions for individually identified patients for the preparations that it compounded. FDA alleges that the failure to compound pursuant to individually identified prescriptions violated the "new drug" provisions (sections 505(a) and 301(d)) and misbranding provisions (section 502(f)(1) and 301(k)) of the FDCA, and violated three cGMP provisions set forth in 21 C.F.R. Part 211. FDA also alleges that Lee Pharmacy's products were adulterated because Lee "failed to demonstrate through appropriate studies that [its] hoods are able to provide adequate protection of the ISO 5 area .... " Warning Letter at 3-4. Lee Pharmacy respectfully submits that FDA's allegations in the Warning Letter are unjustified.
Allegations Related to Office Use Compounding and Violations of 21 C.F.R. Part 211
FDA's Warning Letter asserts that Section 503A applied to Lee Pharmacy when FDA inspected the pharmacy back in February 2013. This assertion is inconsistent with FDA Commissioner Margaret Hamburg, M.D.'s, Congressional testimony concerning FDA's enforcement authority related to compounders on April 16, 2013 - two months after the inspection of Lee Pharmacy. During the Congressional Hearing, Dr. Hamburg testified that FDA's enforcement authority over compounding pharmacies was "hampered by gaps and ambiguities" in the law; the law was "unclear," "ambiguous;" "and the law is not well suited to effectively regulate this evolving industry."3 After the inspection of Lee Pharmacy occurred, Commissioner Hamburg wrote, on March 22, 2013, that there currently are no discernible federal standards to regulate pharmacy compounding. Specifically, she stated, regulatory "authorities are limited and not the right fit for FDA to provide appropriate and efficient oversight of this growing industry."4 Commissioner Hamburg also stated that FDA's ability to take action against compounders "has been hampered by gaps and ambiguities in the law, which has led to legal challenges to FDA's authority to inspect pharmacies and take appropriate enforcement actions."5
Thus, FDA's position in its Warning Letter that Section 503A was enforceable at the time Lee Pharmacy was inspected in February 2013 conflicts with FDA's prior public statements about the degree of its enforcement authority over compounding pharmacies at the time, and the enforceability of FDCA Section 503A prior to its "clarification" upon passage of the DQSA in late November 2013. Furthermore, contrary to statements in the Warning Letter where FDA asserts that its now-withdrawn Compounding Compliance Policy Guide applied at the time of the 2013 inspection (see Warning Letter at 2), that same Compliance Policy Guide confirms that FDA believed at least as far back as 2002 that "presently section 503A in its entirety is invalid."6
In addition, given that the Arkansas State Board of Pharmacy has long regulated compounding pharmacies in Arkansas, Lee Pharmacy had previously engaged in measures to ensure that any office use compounding that it performed complied with applicable state laws. Its actions were consistent with the Arkansas Board of Pharmacy regulations currently in effect, and which were in effect when the pharmacy was inspected by FDA in February of 2013.
It is similarly inexplicable that FDA's Commissioner would specifically and publicly use the terms "unclear" and "ambiguous" to describe FDA's enforcement authority a mere few weeks after its inspection of Lee Pharmacy, and now FDA would assert that Lee Pharmacy has violated the misbranding, adulteration and cGMP provisions of the FDCA because it engaged in office use compounding under that same authority- especially when such activities were specifically permitted by Arkansas state law at the time of the 2013 inspection. Warning Letters should not be based on "unclear and ambiguous" legal provisions.
Specific Allegations in FDA's June 10, 2014 Warning Letter
Lee Pharmacy addressed the allegations raised in FDA's 2013 Form 483 Observations back in 2013. See Lee Pharmacy's Response to FRA' s Form 483 Observations, attached hereto. As stated above, FDA repeats-- without addressing Lee Pharmacy's remedial actions set forth in its 483 Response-- that Lee failed to demonstrate through appropriate studies that its hoods were able to "provide adequate protection of the ISO 5 areas." Warning Letter at 4. As Lee Pharmacy previously stated (Observation 1(a) and (b), Response), although disputing the Observation, Lee Pharmacy drafted a Standard Operating Procedure setting forth enhanced procedures to monitor for viable particles during aseptic filling of sterile drug preparations. (SOP 5.7.1). Lee Pharmacy also now follows a procedure requiring the use of settling plates to monitor for viable air particles during all aseptic filling procedures that involve the filling of more than (b)(4) vials. Employees were trained on the revised procedures, which training was documented. (See Response to Observation No. 1, attached). Results of that monitoring over the past year have shown there have been no colony-forming units or contamination. In addition, Lee Pharmacy validated its settling plates. Lee Pharmacy also performs, as required by USP <797>, smoke studies under static conditions, reflected in documentation from ENV Services, Lee Pharmacy's third party contractor, attached to the Form 483 Response (Response to Observation 1(b)). There also as been no indication at any time that Lee Pharmacy's sterile products were in fact non-sterile; or that there was inadequate assurances of sterility based on any test performed by FDA (or anyone else).
All of the remaining three specifically numbered allegations in the Warning Letter cite to violations of various parts of 21 C.F.R. Part 211. Importantly, this part of the Code of Federal Regulations is applicable to drug manufacturers, which are held to current good manufacturing practices, and not to compounding pharmacies. These cGMP standards do not apply to compounders of drug preparations, especially for the time period when FDA admitted that its own laws were at best ambiguous, that Section 503A was "invalid in its entirety," and FDA's inspectional findings occurred nine months prior to when Congress passed the DQSA.
Current Compounding Practices at Lee Pharmacy
Notwithstanding the foregoing, since passage of the DQSA in November 2013 and Congress' clarification of the law, Lee Pharmacy has transitioned completely from office use compounding. That transition was complete in mid-January 2014. For at least the past six months, Lee Pharmacy has only compounded preparations for individually identified patients pursuant to a prescription in accordance with newly re-enacted Section 503A. Lee Pharmacy will continue to comply with Section 503A, as demonstrated by its elimination of office use compounding and commitment to compounding preparations pursuant to prescriptions for individually identified patients.7 As such, the exemptions set forth in Section 503A, consisting of exemption from Section 501(a)(2)(B) (cGMP), 502(f)(1) (adequate directions for use) and Section 505(new drugs), apply to Lee Pharmacy.
FDA's assertions in its Warning Letter are based not on any analysis or sterility testing of Lee Pharmacy's compounded products, but instead on assertions that Lee Pharmacy's office use preparations back in early 2013 did not comply with inapplicable federal cGMP requirements for drug manufacturers. Lee Pharmacy is not a drug manufacturer; nor is it a newly-created Outsourcing Facility. It does not compound products for office use. Lee Pharmacy cannot be fairly be deemed a drug manufacturer based on office stock compounding last year, since that activity was permitted by Arkansas law and not prohibited by the FDCA for another eight months. Lastly, FDA does not allege any contamination of compounded drug products, allege that products were unsterile, or identify products that should have been recalled because of a lack of assurance of sterility. The Company has engaged in substantial corrective actions to address the allegations raised in FDA's Form 483 Observations, and in fact remediated the one allegation in the Warning letter that is unrelated to compliance with cGMP under 21 C.F.R. Part 211.
Lee Pharmacy respectfully requests that its Responses to FDA's Form 483 Observations from March of 2013 (attached), along with its response to this Warning Letter, be posted on FDA's enforcement activities website.
Please do not hesitate to contact me if you have any questions concerning the foregoing. We look forward to a beneficial collaboration with the Agency going forward.
Very truly yours,
Warren Lee, Pharm. D.
cc: Reynaldo Rodriguez, Dallas District Director, FDA
1 In fact, FDA concedes in its Warning Letter that, prior to the passage of the DQSA in November of 2013, "there were conflicting judicial decisions regarding the applicability of section 503A of the FDCA [21 U.S.C. § 353a] .... " Warning Letter at 1-2.
2 Lee Pharmacy's employees spend approximately (b)(4) percent of their work week on quality assurance or quality control.
3 Subcommittee on Oversight and Investigations, "A Continuing Investigation into the Fungal Meningitis Outbreak and Whether It Could Have Been Prevented," testimony of Margaret A. Hamburg, M.D., at 3, 6 (April 16, 2013).
4 Margaret A. Hamburg, M.D., Commissioner, FDA, FDA Must Have New Authorities to Regulate Pharmacy Compounding (Mar. 22, 2013), available at http://blogs.fda.gov/fdavoice/index.php/2013/03/fda-must-have-new-authorities-to-regulate-pharmacy-compounding.
5 The Fungal Meningitis Outbreak: Could It Have Been Prevented? Hearing Before the Subcomm. on Oversight and Investigations of the H. Comm. On Energy and Commerce 112th Cong. (Nov. 14, 2012) (testimony of Margaret A. Hamburg, M.D., Commissioner, FDA).
6 FDA, Compliance Policy Guide for FDA Staff and Industry, § 460.200 (Pharmacy Compounding) (2002) (emphasis added) (withdrawn December 4, 2013 upon FDA's circulation of draft guidance concerning implementation of Section 503A after passage of the DQSA. (78 Fed. Reg. 72841 (Dec. 4, 2013)).
7 Lee Pharmacy also does not intend to register as an Outsourcing Facility under FDCA Section 503B (where cGMP, including 21 C.F.R. Part 211, likely would be applicable, depending on FDA's promulgation of applicable regulations).