Inspections, Compliance, Enforcement, and Criminal Investigations

Civic Center Pharmacy 8/20/15

  

Department of Health and Human Services logoDepartment of Health and Human Services

Public Health Service
Food and Drug Administration
 Los Angeles District
Pacifit Region
19701 Fairchild
lrvlne, CA 92612-2506 

 

WARNING LETTER
 
VIA UNITED PARCEL SERVICE
SIGNATURE REQUIRED
 
August 20, 2015
                WL# 32-15
Tenille D. Davis, Pharm.D., R.Ph., Pharmacy Manager
Civic Center Pharmacy
7331 E. Osborn Dr., Ste. 208
Scottsdale, Arizona 85251
 
Dear Dr. Davis:
 
From September 10, 2014, to October 9, 2014, a U.S. Food and Drug Administration (FDA) investigator conducted an inspection of your facility, Civic Center Pharmacy, located at 7331 E. Osborn Dr., Ste. 208, Scottsdale, Arizona.  During the inspection, the investigator noted that you were not receiving valid prescriptions for individually-identified patients for a portion of the drug products you were producing.  The investigator also noted that your firm produces domperidone products.  Domperidone is not the subject of an applicable United States Pharmacopeia (USP) or National Formulary (NF) monograph, nor is it a component of an FDA-approved human drug product, and it does not appear on a list developed by the Secretary under 503A(b)(1)(A)(i)(III) of the Federal Food, Drug, and Cosmetic Act (FDCA) [21 U.S.C. § 353a(b)(1)(A)(i)(III)]. In addition, the investigator observed serious deficiencies in your practices for producing sterile drug products, which put patients at risk.  For example, the investigator observed an operator’s arm moving directly over open vials as they were being filled with sterile drug product. In addition, your firm did not use sterile disinfectants to adequately disinfect the ISO 5 area. Furthermore, the investigator noted that your firm failed to demonstrate through appropriate studies that your hood is able to provide adequate protection of the ISO 5 area in which sterile drug products are produced. Therefore, your products may be produced in an environment that poses a significant contamination risk.  FDA issued a Form FDA 483 to your firm on October 9, 2014. FDA acknowledges your facility’s response dated October 10, 2014.  
 
Based on this inspection, it appears that you are producing drugs that violate the FDCA. 
 
A. Compounded Drugs under the FDCA
 
Section 503A of the FDCA describes the conditions under which certain compounded human drug products are entitled to exemptions from three sections of the FDCA: compliance with current good manufacturing practices (CGMP), section 501(a)(2)(B) of the FDCA [21 U.S.C. § 351(a)(2)(B)]; labeling with adequate directions for use, section 502(f)(1) of the FDCA [21 U.S.C. § 352(f)(1)]; and FDA approval prior to marketing, section 505 of the FDCA [21 U.S.C. § 355].  Receipt of valid prescriptions for individually-identified patients is one of the conditions for the exemptions under section 503A of the FDCA. 
 
During the FDA inspection, the investigator observed that your firm does not receive valid prescriptions for individually-identified patients for a portion of the drug products you produce. Accordingly, the drugs you compound without valid prescriptions for individually-identified patients are not entitled to the exemptions in section 503A of the FDCA. [1]  
 
In addition, compounded drug products containing domperidone are not eligible for the exemptions provided by subsection (a) of 503A because domperidone is not the subject of an applicable USP or NF monograph, is not a component of an FDA-approved human drug, and it does not appear on a list of bulk drug substances that may be used for compounding developed by the secretary under 503A(b)(1)(A)(i)(III) of the FDCA.
 
On December 16, 2008, FDA issued a Warning Letter (Reference WL #07-09) to you stating, in part, that our investigation at that time revealed that your firm was compounding drugs using a bulk drug substance, which was not an active ingredient contained in any FDA-approved drug and was not demonstrated under FDA standards to be safe and effective for any use.  
 
In addition, we remind you that there are a number of other conditions that must be satisfied to qualify for the exemptions in section 503A of the FDCA.[2]
 
B. Violations of the FDCA
 
Because the drug products you manufacture and distribute without valid prescriptions for individually-identified patients are not the subject of approved applications, they are unapproved new drugs and misbranded drugs in violation of sections 505(a) and 502(f)(1) of the FDCA, respectively.  Furthermore, the domperidone products you produce are also unapproved new drugs and misbranded drugs in violation of sections 505(a) and 502(f)(1) of the FDCA, respectively.
 
In addition, drug products that are intended or expected to be sterile were prepared, packed, or held under insanitary conditions whereby they may have been contaminated with filth, or whereby they may have been rendered injurious to health causing them to be adulterated within the meaning of section 501(a)(2)(A) of the FDCA [21 U.S.C. § 351(a)(2)(A)]. Furthermore, because you manufacture and distribute a portion of your drugs without valid prescriptions for individually-identified patients, the manufacture of those drugs is subject to FDA’s Current Good Manufacturing Practice (CGMP) regulations for Finished Pharmaceuticals, Title 21, Code of Federal Regulations (CFR), Parts 210 and 211.  The FDA investigator observed significant CGMP violations at your facility, causing your drug products to be adulterated within the meaning of section 501(a)(2)(B) of the FDCA. 
 
Unapproved New Drug Products
 
You do not have any FDA approved applications on file for the drug products for which you have not obtained valid prescriptions for individually-identified patients, or for the domperidone products you produce.[3] Under sections 505(a) and 301(d) of the FDCA [21 USC §  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.  Your marketing of these products, or other applicable products, without an approved application violates these provisions of the FDCA.
 
Misbranded Drug Products
 
You compound domperidone drug products and drug products for which you have not obtained valid prescriptions for individually-identified patients that are intended for conditions that are 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, causing them to be misbranded under section 502(f)(1) of the FDCA, and they are not exempt from the requirements of section 502(f)(1) of the FDCA [see, e.g., 21 CFR § 201.115]. The introduction or delivery for introduction into interstate commerce of these products therefore violates section 301(a) of the FDCA [21 U.S.C, § 331(a)].
 
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 of the components used to make the drug and results in the drug being misbranded.
 
Adulterated Drug Products
 
Additionally, the FDA investigator noted that your sterile 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. For example, the investigator observed an operator’s arm moving directly over open vials as they were being filled with sterile drug product. In addition, your firm did not use sterile disinfectants to adequately disinfect the ISO 5 area. Furthermore, the investigator noted that your firm failed to demonstrate through appropriate studies that your hood is able to provide adequate protection of the ISO 5 area in which sterile drug products are produced.  Therefore, your products may be produced in an environment that poses a significant contamination risk.
 
The FDA investigator also noted CGMP violations at your facility, causing the drug products for which you have not obtained valid prescriptions for individually-identified patients to be adulterated under section 501(a)(2)(B) of the FDCA. The violations include, 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 include validation of all aseptic and sterilization processes (21 CFR 211.113(b)).
  1. Your firm failed to establish an adequate system for monitoring environmental conditions in aseptic processing areas (21 CFR 211.42(c)(10)(iv)).
  1. Your firm failed to establish an adequate system for cleaning and disinfecting the room and equipment to produce aseptic conditions (21 CFR 211.42(c)(10)(v)).  
  1. Your firm failed to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed (21 CFR 211.192).
  1. Your firm does not have, for each batch of drug product purporting to be sterile and/or pyrogen-free, appropriate laboratory determination of satisfactory conformance to final specifications for the drug product (21 CFR 211.167(a)).   
Under section 301(a) of the FDCA, 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 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.
 
C. Corrective Actions
 
FDA acknowledges receipt of your letter dated September 15, 2014, in which you state that your firm “no longer provide[s] compounded medications to doctors’ offices for office use” and “every medication [you] dispense requires a prescription.” In addition, we acknowledge receipt of your response to the Form FDA 483 dated October 10, 2014, in which you reference your purported compliance with the United States Pharmacopeia (USP)-National Formulary (NF) General Chapter <797> Pharmaceutical Compounding – Sterile Preparations.  Although in your responses you indicate you are taking steps to correct the insanitary conditions observed at your facility, your response cannot be evaluated due to lack of supporting documentation.
 
Please be aware that section 501(a)(2)(A) of the FDCA concerning insanitary conditions applies regardless of whether the drugs are compounded and distributed after receipt of a prescription for an individually-identified patient.  
 
In addition, should you continue to manufacture and distribute drug products without valid prescriptions for individually-identified patients, the manufacture of such drugs would be subject to FDA’s drug CGMP regulations (21 CFR Parts 210 and 211), among other requirements described above, and, before doing so, you should fully implement corrections that meet the minimum requirements of 21 CFR Part 211, in order to provide assurance that the drug products produced by your firm conform to the basic quality standards that ensure safety, identity, strength, quality, and purity. 
 
FDA strongly recommends that your management immediately undertake a comprehensive assessment of your operations, including facility design, procedures, personnel, processes, materials, and systems.  In particular, this review should assess aseptic processing operations.  A third party consultant with relevant sterile drug manufacturing expertise could be useful in conducting this comprehensive evaluation.
 
In addition, you should also correct the violations of sections 501(a)(2)(A), 502(f)(1), and 505(a) of the FDCA, noted above.
 
D. Conclusion
 
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 and 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 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 actions within 15 working days, state the reason for the delay and the time frame within which you will complete the corrections.  Your written response should be addressed to:
 
CAPT Daniel W. Cline, Acting Director, Compliance Branch
Los Angeles District Office
U.S. Food and Drug Administration
19701 Fairchild
Irvine, CA 92612-2506
 
If you have questions about the content of this letter, please contact Ms. Mariza Jafary, Compliance Officer, at (949) 608-2977.
 
Sincerely,
/S/
Alonza E. Cruse, Director
Los Angeles District


[1]The Compounding Quality Act (CQA) contains a number of other provisions, including new exemptions and requirements for compounders seeking to operate as outsourcing facilities. A discussion of the CQA and the agency’s plans to implement the new law may be found at http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/default.htm.
[2] For example, section 503A also addresses anticipatory compounding, which includes compounding (not distribution) before receipt of a valid prescription order for an individual patient. We are not addressing anticipatory compounding here.
[3] The specific products made by your firm are drugs within the meaning of section 201(g) [21 U.S.C. § 321(g)] of the FDCA 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.

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