Inspections, Compliance, Enforcement, and Criminal Investigations

Auro Pharmacies, Inc. 12/13/16

 

  

Black HHS-Blue FDA Logo

 

 

 
Los Angeles District
19701 Fairchild Road
Los Angeles, CA  92612 

 

WARNING LETTER
 
VIA UNITED PARCEL SERVICE
SIGNATURE REQUIRED
 
 
December 13, 2016                                                                                    
WL 8-17
Nayan Patel, PharmD, President
Auro Pharmacies, Inc., dba Central Drugs Compounding Pharmacy
520 West La Habra Blvd.
La Habra, California 90631-5308
 
Dear Dr. Patel:
 
Between September 22, 2015 and November 5, 2015, a U.S. Food and Drug Administration (FDA) investigator conducted an inspection of your facility, Auro Pharmacies, Inc., dba Central Drugs Compounding Pharmacy, located at 520 W. La Habra Blvd, La Habra, CA 90631-5308.   
 
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. In addition, the investigator observed serious deficiencies in your practices for producing sterile drug products, which put patients at risk. For example, our investigator noted (b)(4) vials that were exposed to lower than ISO 5 quality air while being transferred from an ISO 5 hood to a (b)(4). Our investigator also observed poor aseptic practices, including an operator placing gloved hands and elbows on the surface of the ISO 5 hood. In addition, the investigator noted that your firm did not use a sporicidal agent to disinfect your aseptic processing area. Our investigator also observed sterilized items stored in your cleanroom in (b)(4) containers without an established hold time to ensure that these items remain sterile. Furthermore, our investigator observed that an operator performed fingertip monitoring after glove sanitization, which could potentially bias the results.
 
FDA issued a Form FDA 483 to your firm on November 5, 2015. FDA acknowledges receipt of your facility’s response to the Form FDA 483, dated November 20, 2015.
 
Based on this inspection, it appears that you are producing drugs that violate the Federal Food, Drug, and Cosmetic Act (FDCA). 
 
A. Compounded Drugs Under the FDCA
 
Section 503A of the FDCA [21 U.S.C. § 353a] describes the conditions under which certain compounded human drug products qualify for exemptions from three sections of the FDCA: compliance with current good manufacturing practice (CGMP) requirements (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)].  Receipt of valid prescriptions for individually-identified patients is one of the conditions for the exemptions under section 503A. 
 
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.
 
In addition, we remind you that there are other conditions that must be satisfied to qualify for the exemptions in section 503A of the FDCA.[1]
 
B. Violations of the FDCA
 
Because the drug products that 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.
 
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 such 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 such 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. [2] Under sections 301(d) [21 U.S.C. § 331(d)] and 505(a) of the FDCA, 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 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 and results in the drug being misbranded.
 
Adulterated Drug Products
 
Additionally, the FDA investigator noted that drug products in your facility that were 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 noted (b)(4) vials that were exposed to lower than ISO 5 quality air while being transferred from an ISO 5 hood to a (b)(4). The investigator also observed poor aseptic practices, including an operator placing gloved hands and elbows on the surface of the ISO 5 hood. In addition, the investigator noted that your firm did not use a sporicidal agent to disinfect your aseptic processing area. The investigator also observed sterilized items stored in your cleanroom in (b)(4) containers without an established hold time to ensure that these items remain sterile. Furthermore, the investigator observed that an operator performed fingertip monitoring after glove sanitization, which could potentially bias the results.
 
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 cleaning and disinfecting the room and equipment to produce aseptic conditions (21 CFR 211.42(c)(10)(v)).
  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 clean, maintain, and, as appropriate for the nature of the drug, sanitize and/or sterilize equipment and utensils at appropriate intervals to prevent malfunctions or contamination that would alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements (21 CFR 211.67(a)). 
  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)).  
  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 failed to establish and follow an adequate written testing program designed to assess the stability characteristics of drug products and to use results of such stability testing to determine appropriate storage conditions and expiration dates (21 CFR 211.166(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 response to Form FDA 483, dated November 20, 2015. Although several of your corrective actions appear adequate, others are deficient or cannot be evaluated due to a lack of documentation. For example, in response to our observation regarding the transfer of (b)(4) vials as part of the (b)(4) process, you provided SOP-SC-01.1270.01, entitled (b)(4). However, your SOP did not include the ISO conditions for transferring (b)(4) vials from the ISO 5 hood to the (b)(4). Transferring (b)(4) vials should occur under ISO 5 conditions.
 
In response to our observation regarding lack of sporicidal agent used to disinfect the ISO 5 hood, you revised your SOP-SC-01.1255.01, entitled Central Drugs Sterile Compounding Cleaning Procedure. This SOP instructs to disinfect the ISO 5 hood with (b)(4) and (b)(4), neither of which is a sporicidal agent. In addition, your SOP did not specify the contact time required to ensure adequate disinfection. 
 
In response to the observation regarding hold time of sterilized items, you stated that you would complete a hold time study. However, your response did not include supporting documentation for us to evaluate the adequacy of your proposed corrective actions.  
 
In response to our observation of inadequate environmental and personnel monitoring, you provided SOP-SC-01.1320.01, entitled Central Drugs Sterile Compounding Environmental Monitoring Procedure. However, your response did not state that glove disinfection prior to fingertip monitoring is no longer allowed.  
 
In addition, your response referenced your purported compliance with the United States Pharmacopeia (USP)-National Formulary (NF) General Chapter <797> Pharmaceutical Compounding--Sterile Preparations. As noted above, your firm has manufactured and distributed drugs without valid prescriptions for individually-identified patients, and the manufacture of such drugs is subject to FDA’s finished drug product CGMP regulations, 21 CFR parts 210 and 211.
 
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 your aseptic processing operations. A third party consultant with relevant sterile drug manufacturing expertise could be useful in conducting this comprehensive evaluation. 
 
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 identified individual 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, among other requirements described above, and, before doing so, you should fully implement corrections that meet the minimum requirements of 21 CFR Part 211 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. 
 
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, as amended by the Food and Drug Administration Safety and Innovation Act (Pub.L. 112-144, Title VII, section 711). 
 
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, 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 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.                               
 
Your written notification should be addressed to:
 
Kelly D. Sheppard, Director
Compliance Branch
U.S. Food and Drug Administration
Los Angeles District
19701 Fairchild
Irvine, California 92612-2445
                                                                       
If you have questions regarding any issues in this letter, please contact Ms. Mariza Jafary, Compliance Officer via email at mariza.jafary@fda.hhs.gov or by phone at (949) 608-2977.
 
Sincerely,
/S/
CDR Steven E. Porter, Jr.
Los Angeles District Director
  
           
Cc:      
Virginia Harold, Executive Officer
California State Board of Pharmacy
1625 N Market Blvd, N219
Sacramento, CA 95834
(Via email)


[1] 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.
[2] The specific products made by your firm are drugs within the meaning of section 201(g) of the FDCA [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) of the FDCA [21 U.S.C. § 321(p)] because they are not generally recognized as safe and effective for their labeled uses.

 

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