- Delivery Method:
- Via Email
Recipient NameMr. Pujan A. Patel
- Foothills Professional Pharmacy, LTD
4545 E. Chandler Blvd., Suite 100
Phoenix, AZ 85048
- Issuing Office:
- Division of Pharmaceutical Quality Operations IV
September 9, 2020
Dear Mr. Patel:
From July 9, 2018, to October 24, 2018, U.S. Food and Drug Administration (FDA) investigators inspected your facility, Foothills Professional Pharmacy, Ltd., located at 4545 E. Chandler Boulevard, Suite 100, Phoenix, Arizona 85048. During the inspection, the investigators 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 investigators noted serious deficiencies in your practices for producing drug products, which put patients at risk.
FDA issued a Form FDA 483 to your firm on October 24, 2018 and issued an amended Form FDA 483 to your firm on December 20, 2018. FDA acknowledges receipt of your firm’s response, dated November 14, 2018. 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.
B. Failure to Meet the Conditions of Section 503A
During the inspection, the FDA investigators noted that drug products produced by your firm failed to meet the conditions of section 503A. For example, the investigators noted that your firm did not receive valid prescriptions for individually-identified patients for a portion of the drug products you produced and distributed, including Lidocaine/Tetracaine/Phenylepherine in Poly-Poloxamer 23%/7%/0.8% Gel and Benzocaine/Lidocaine/Tetracaine/Phenylephrine 20/6/4/0.5% (b)(4). Therefore, you compounded drug products that do not meet the conditions of section 503A and are not eligible for the exemptions in that section, including 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 investigators noted that drug products 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 [21 U.S.C. §§ 351(a)(2)(A)]. For example, the investigators observed:
1. Apparent loose powder and dried product splatter inside hoods within each production room while drug products were being produced.
2. Household brand blenders were used to (b)(4) for use in the production of capsules. Mixing cups for the household brand blenders were damaged and discolored. In addition, loose powder and a dry white substance were observed on equipment used to (b)(4) produce capsules including retail gift cards used to scrape powder into capsules. Silicone mixing blades used for cream production contained multiple discolored cracks. Apparent loose powder and a semi-dry smeared substances were observed on multiple pieces of equipment designated as “clean” and used for cream production.
3. Your firm did not use adequate deactivation agents in the production areas to prevent potential cross-contamination.
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 investigators 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 perform operations within specifically defined areas of adequate size and to have separate or defined areas or such other control systems necessary to prevent contamination or mix ups (21 CFR 211.42(c)).
2. Your firm failed to have, for each batch of drug product, appropriate laboratory determination of satisfactory conformance to final specifications for the drug product, including the identity and strength of each active ingredient, prior to release (21 CFR 211.165(a)).
3. Your firm failed to establish adequate control procedures to monitor the output and to validate the performance of those manufacturing processes that may be responsible for causing variability in the characteristics of in-process material and the drug product (21 CFR 211.110(a)).
4. Your firm failed to use equipment in the manufacture, processing, packing, or holding of drug products that is of appropriate design, adequate size, and suitably located to facilitate operations for its intended use and for its cleaning and maintenance (21 CFR 211.63).
5. Your firm failed to establish a written testing program designed to assess the stability characteristics of drug products and to use results of stability testing to determine appropriate storage conditions and expiration dates (21 CFR 211.166(a)).
6. Your firm failed to establish laboratory controls that include scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that components, drug product containers, closures, in-process materials, labeling, and drug products conform to appropriate standards of identity, strength, quality, and purity (21 CFR 211.160(b)).
7. Your firm’s quality control unit failed to review and approve all drug product production and control records to determine compliance with all established, approved written procedures before a batch is released or distributed (21 CFR 211.192).
Under section 301(a) of the FDCA [21 U.S.C. § 331(a)], the introduction or delivery for introduction into interstate commerce of any drug that is adulterated is a prohibited act. Further, it is a prohibited act under section 301(k) of the FDCA [21 U.S.C. § 331(k)] 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 adulterated.
Unapproved New Drug Products
You do not have any FDA-approved applications on file for the ineligible drug products that you compounded.2 Under sections 505(a) and 301(d) of the FDCA [21 U.S.C. § 331(d)], a new drug may not be introduced into or delivered for introduction into interstate commerce unless an application approved by FDA under section 505 of the FDCA is in effect for the drug. Marketing of these products, or other applicable products, without an approved application violates these provisions of the FDCA.
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. The introduction or delivery for introduction into interstate commerce of these products therefore violates section 301(a) of the FDCA. It is also 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. Production of Domperidone
We also note that in June 2018, your records indicate that you compounded a domperidone product. Drug products compounded using domperidone are not eligible for the exemptions provided by section 503A of the FDCA because domperidone is not the subject of an applicable United States Pharmacopeia (USP) or National Formulary (NF) monograph, is not a component of an FDA-approved human drug, and does not appear on the 503A bulks list.4
Please be advised that domperidone has been identified by the Agency as a substance that appears to present significant safety risks.5
E. Corrective Actions
We have reviewed your firm’s response to the Form FDA 483, dated November 14, 2018.
Regarding the insanitary condition observations in the Form FDA 483, some of your corrective actions appear to be adequate. However, we cannot fully evaluate the adequacy of the following corrective action described in your response because you did not include sufficient information or supporting documentation. It is not clear from the revised SOP 1.25 Cleaning Agents provided in your response if your firm continues to use (b)(4) as your primary cleaning and deactivation agent. Your procedural instructions allow for a wide personnel interpretation including such provisions as use of “(b)(4)… or other (b)(4)” and “(b)(4) or other (b)(4).”
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.
In addition, regarding issues related to the conditions of section 503A of the FDCA, your corrective action appears adequate, in that you stated in your response to the Form FDA 483 that “Foothills Professional Pharmacy ceased all office-use compounding, effective July 9, 2018.”
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, 502(f)(1), and fully implement corrections that meet the minimum requirements of the CGMP regulations.6
In addition to the issues discussed above, you should note that CGMP requires the implementation of quality oversight and controls over the manufacture of drugs, including the safety of raw materials, materials used in drug manufacturing, and finished drug products. See section 501 of the FDCA. If you choose to contract with a laboratory to perform some functions required by CGMP, it is essential that you select a qualified contractor and that you maintain sufficient oversight of the contractor’s operations to ensure that it is fully CGMP compliant. Regardless of whether you rely on a contract facility, you are responsible for assuring that drugs you produce are neither adulterated nor misbranded. [See 21 CFR 210.1(b), 21 CFR 200.10(b)].
FDA strongly recommends that your management undertake a comprehensive assessment of operations, including facility design, procedures, personnel, processes, maintenance, materials, and systems. A third-party consultant with relevant 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.
You should take prompt action to correct the violations cited in this letter. Failure to promptly correct these violations may result in legal action without further notice, including, without limitation, seizure and injunction.
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 violations. Please include an explanation of each step being taken to prevent the recurrence of 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.
Send your written responses to:
CDR Steven E. Porter, Jr.
Director, Division of Pharmaceutical Quality Operations IV
19701 Fairchild Road
Irvine, CA 92612
Please identify your response with unique identifier 598883. Electronic responses may also be submitted to ORAPHARM4_Responses@fda.hhs.gov.
If you have questions regarding any issues in this letter, please contact CAPT Matthew R. Dionne, Compliance Officer, at (303)-349-0301, or Matthew.Dionne@fda.hhs.gov.
CAPT Katherine E. Jacobitz
Acting Director, Division of Pharmaceutical Quality Operations IV
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.
2 The specific products made by your firm are drugs within the meaning of section 201(g) of the Act, [21 U.S.C. § 321(g)] because they are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of diseases and/or because they are intended to affect the structure or any function of the body. Further, they are “new drugs” within the meaning of section 201(p) [21 U.S.C. § 321(p)] of the FDCA because they are not generally recognized as safe and effective for their labeled uses.
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 On January 2017, 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. For additional information, see the guidance at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM469120.pdf.
5 See id.
6 In this letter we do not address whether your proposed corrective actions would resolve the CGMP violations noted above.