William S. McFarland
- Loop Pharmacy & Home Medical
72 6th Avenue
Saint Albans, WV 25177-2769
- Issuing Office:
- New Jersey District Office
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Division of Pharmaceutical Quality Operations I
10 Waterview Blvd, 3rd FL
Parsippany, NJ 07054
Telephone: (973) 331-4900
FAX: (973) 331-4969
WL # 537129
September 20, 2017
William S. McFarland, Owner
Loop Plaza Pharmacy, Co.
dba Loop Pharmacy & Home Medical
72 6th Avenue
Saint Albans, WV 25177-2769
Dear Mr. McFarland,
From December 12, 2016, to December 16, 2016, a U.S. Food and Drug Administration (FDA) investigator inspected your facility, Loop Plaza Pharmacy, Co. dba Loop Pharmacy & Home Medical, located at 72 6th Avenue, Saint Albans, WV 25177-2769. During the inspection, the investigator noted that drug products you produced failed to meet the conditions of section 503A of the Federal Food, Drug, and Cosmetic Act (FDCA) [21 U.S.C. § 353a] for exemption from certain provisions of the FDCA. In addition, the investigator noted serious deficiencies in your practices for producing sterile drug products, which put patients at risk.
FDA issued a Form FDA 483 to your firm on December 16, 2016. FDA acknowledges receipt of your facility’s responses, dated December 22, 2016 and March 3, 2017. FDA also acknowledges the statements in your response letter, dated December 22, 2016, indicating that Loop Pharmacy “will require a patient specific prescription before dispensing any compounds [and] has already discontinued compounding domperidone…” Based on this inspection, it appears that you produced drug products that violate the FDCA.
A. Compounded Drug Products Under the FDCA
Section 503A of the FDCA describes the conditions under which human drug products compounded by a licensed pharmacist in a State licensed pharmacy or a Federal facility, or a licensed physician, qualify for exemptions from three sections of the FDCA: compliance with current good manufacturing practice (CGMP) (section 501(a)(2)(B)); labeling with adequate directions for use (section 502(f)(1)); and FDA approval prior to marketing (section 505) [21 U.S.C. §§ 351(a)(2)(B), 352(f)(1) and 355(a)].1 Receipt of valid prescriptions for individually-identified patients is one of the conditions for the exemptions under section 503A.
In addition, for a compounded drug product to qualify for the exemptions under section 503A, bulk drug substances used to compound it must: (I) comply with the standards of an applicable United States Pharmacopeia (USP) or National Formulary (NF) monograph, if a monograph exists, and the USP chapter on pharmacy compounding; (II) if such a monograph does not exist, be components of drugs approved by the Secretary; or (III) if such a monograph does not exist and the drug substance is not a component of a drug approved by the Secretary, appear on a list developed by the Secretary through regulation (“503A bulks list”) (section 503A(b)(1)(A)(i) of the FDCA).
B. Failure to Meet the Conditions of Section 503A
During the inspection, the FDA investigator noted that drug products produced by your firm failed to meet the conditions of section 503A. For example, the investigator noted:
1. Your firm did not receive valid prescriptions for individually-identified patients for a portion of the drug products you produced.
2. Your firm compounded drug products using domperidone, saw palmetto, melatonin, short chain fatty acid, and zinc picolinate. Drug products compounded using domperidone, saw palmetto, melatonin, short chain fatty acid and zinc picolinate are not eligible for the exemptions provided by section 503A because domperidone, saw palmetto, melatonin, short chain fatty acid and zinc picolinate are not the subjects of applicable USP or NF monographs, are not components of an FDA-approved human drug, and do not appear on the 503A bulks list.2
Therefore, you compounded drug products that do not meet the conditions of section 503A and are not eligible for the exemptions from the FDA approval requirement of section 505 of the FDCA, the requirement under section 502(f)(1) of the FDCA that labeling bear adequate directions for use, and the requirement of compliance with CGMP under section 501(a)(2)(B) of the FDCA. In the remainder of this letter, we refer to your drug products that do not qualify for exemptions under section 503A as the “ineligible drug products”.
Specific violations are described below.
C. Violations of the FDCA
Adulterated Drug Products
The FDA investigator noted that drug products 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. For example, the investigator observed a pharmacist blocking the movement of first pass air from the ISO 5 hood while conducting aseptic manipulations with syringes containing product. The investigator also observed that on multiple days, during aseptic processing, the pressure differentials between your cleanroom and anteroom were inadequate to ensure proper airflow. Additionally, your firm did not use a sporicidal agent to disinfect the ISO 5 hoods.
Furthermore, the manufacture of the ineligible drug products is subject to FDA’s CGMP regulations, Title 21, Code of Federal Regulations (CFR), parts 210 and 211. The FDA investigator observed significant CGMP violations at your facility, causing the ineligible drug products to be adulterated within the meaning of section 501(a)(2)(B) of the FDCA. The violations included, for example:
1. Your firm failed to establish and follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile, and that includes validation of all aseptic and sterilization processes (21 CFR 211.113(b)).
2. Your firm failed to establish an adequate system for monitoring environmental conditions in aseptic processing areas (21 CFR 211.42(c)(10)(iv)).
3. Your firm failed to establish an adequate system for cleaning and disinfecting the clean room and equipment to produce aseptic conditions (21 CFR 211.42(c)(10)(v)).
Misbranded Drug Products
The ineligible drug products you compounded are intended for conditions not amenable to self-diagnosis and treatment by individuals who are not medical practitioners; therefore, adequate directions for use cannot be written so that a layman can use these products safely for their intended uses. Consequently, their labeling fails to bear adequate directions for their intended uses.3 Accordingly, these ineligible drug products are misbranded under section 502(f)(1) of the FDCA. It is a prohibited act under section 301(k) of the FDCA 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 and results in the drug being misbranded.
D. Corrective Actions
We have reviewed your firm’s responses to the Form FDA 483. Regarding the insanitary conditions cited above, some of your corrective actions appear to be adequate. However, we are unable to fully evaluate the following corrective action due to a lack of adequate supporting documentation. Regarding inadequate pressure differentials between your cleanroom and anteroom on December 12, 2016 and December 14, 2016, you stated that a door was installed; however, you did not provide documentation showing that pressure differentials are within range.
Please be aware that section 501(a)(2)(A) of the FDCA concerning insanitary conditions applies regardless of whether drug products you compound meet the conditions of section 503A, including the condition on receipt of a prescription for an identified individual patient prior to compounding and distributing drug products and the condition on compounding drug products using a bulk drug substance that complies with an applicable USP or NF monograph, is a component of an FDA-approved human drug, or appears on the 503A bulks list.
In addition, regarding issues related to the conditions of section 503A of the FDCA, the following corrective actions appear adequate:
1. You state that drug products compounded by Loop Pharmacy will not be dispensed without a patient-specific prescription.
2. You state that you are no longer compounding drug products with domperidone.
As explained above, the compounding of drug products using a bulk drug substance that complies with an applicable USP or NF monograph, is a component of an FDA-approved human drug, or appears on the 503A bulks list is a condition of section 503A, which your firm failed to meet for a portion of the drug products you produced. Should you continue to compound and distribute drug products that do not meet the conditions of section 503A, the compounding and distribution of such drugs would be subject to the new drug approval requirement, the requirement to label drug products with adequate directions for use, and the drug CGMP regulations. Before doing so, you must comply with the requirements of section 505 and 502(f)(1) and fully implement corrections that meet the minimum requirements of the CGMP regulations.4
FDA strongly recommends that your management first undertake a comprehensive assessment of operations, including facility design, procedures, personnel, processes, maintenance, materials, and systems. In particular, this review should assess your aseptic processing operations. A third party consultant with relevant sterile drug manufacturing expertise should assist you in conducting this comprehensive evaluation.
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, including FDA regulations.
Within fifteen (15) working days of receipt of this letter, please notify this office in writing of the specific steps that you have taken to correct the violations. Please include an explanation of each step being taken to prevent the recurrence of the 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 fifteen (15) working days, state the reason for the delay and the time within which you will complete the correction.
Your written notification should refer to the Warning Letter Number above (537129). Please address your reply to:
Ernest F. Bizjak
Compliance Officer, DPQ Div. 1
11919 Rockville Pike
Rockville, MD 20852
If you have questions regarding the contents of this letter, please contact Ernest Bizjak, Compliance Officer, at 301 796-4081, or by email at Ernest.Bizjak@fda.hhs.gov.
Diana Amador Toro
Division Director/OPQ Division 1
New Jersey District Office
1 We remind you that there are conditions other than those discussed in this letter that must be satisfied to qualify for the exemptions in section 503A of the FDCA.
On June 9, 2016, FDA issued a final guidance titled, Interim Policy on Compounding Using Bulk Drug Substances Under Section 503A of the Federal Food, Drug, and Cosmetic Act. This guidance describes FDA’s interim regulatory policy for State-licensed pharmacies, Federal facilities, and licensed physicians that compound human drug products using bulk drug substances that do not otherwise meet the conditions of section 503A(b)(1)(A)(i) while the 503A bulks list is being developed. Specifically, the guidance sets out the conditions under which FDA does not intend to take action against a State- licensed pharmacy, Federal facility, or licensed physician for compounding a drug product using a bulk drug substance that is not the subject of an applicable USP or NF monograph or a component of an FDA-approved drug, until the substance is identified in a final rule as included or not included on the 503A bulks list. These conditions include that the substance may be eligible for inclusion on the 503A bulks list, was nominated with adequate support for FDA to evaluate it, and has not been identified by FDA as a substance that appears to present significant safety risks pending further evaluation. Domperidone was nominated for inclusion on the 503A bulks list. It has been identified as a substance that appears to present significant safety risks. Saw palmetto, melatonin, short chain fatty acid, and zinc picolinate were also nominated for inclusion on the 503A bulks list; however, these substances were not nominated with adequate support for FDA to evaluate the substances. For additional information, see the guidance at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM469120.pdf.
3 Your ineligible drug products are not exempted from the requirements of section 502(f)(1) of the FDCA by regulations issued by the FDA (see, e.g., 21 CFR 201.115).
4 In this letter we do not address whether your proposed corrective actions would resolve the CGMP violations noted above.