U.S. flag An official website of the United States government
  1. Home
  2. Inspections, Compliance, Enforcement, and Criminal Investigations
  3. Compliance Actions and Activities
  4. Warning Letters
  5. Pine Pharmacy and Home Care Products Center, Inc. - 02/13/2015
  1. Compliance Actions and Activities

WARNING LETTER

Pine Pharmacy and Home Care Products Center, Inc. Feb 13, 2015

Pine Pharmacy and Home Care Products Center, Inc. - 02/13/2015


Recipient:
Pine Pharmacy and Home Care Products Center, Inc.


United States

Issuing Office:
New York District Office

United States


  

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

Public Health Service
Food and Drug Administration
 
New York District
158-15 Liberty Ave.
Jamaica, NY 11433
 
Telephone: 718-340-7000
Facsimile: 718-662-5661

 

February 13, 2015
 
WARNING LETTER NYK-2015-24
 
 
FEDERAL EXPRESS
DELIVERY SIGNATURE REQUESTED
 
Alfonse Muto, Sr., Owner
Pine Pharmacy and Home Care Products Center, Inc.
5110 Main Street
Williamsville, NY 14221
 
Dear Mr. Muto:
 
From December 10 to December 16, 2013, U.S. Food and Drug Administration (FDA) investigators inspected your facility, located at 5110 Main Street, Williamsville, NY 11433. This inspection was a follow-up to the inspection conducted on July 16, 17, and 19, 2013. The July 2013 inspection was triggered by a report alleging poor practices and potential contamination in drug products at your firm. During the July inspection, you refused to cooperate with the investigators by refusing to provide certain documentation about your operations necessary for them to conduct a full inspection.  As a result, FDA conducted the December inspection pursuant to an administrative warrant authorizing FDA’s inspection of your facility.   
 
During the December 2013 inspection, the investigators 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 investigators observed serious deficiencies in your practices for producing sterile drug products, which put patients at risk.  For example, investigators observed operators preparing injectable drug products with exposed skin on their faces and wearing non-sterile gowns and gown components.  Furthermore, investigators found that your firm failed to demonstrate through appropriate studies that your hoods are able to provide adequate protection of the ISO 5 area in which sterile products are processed. Therefore, your products may be produced in an environment that poses a significant contamination risk. 
 
FDA also noted that your “Formula Report” dated December 12, 2013, and production logs that you provided to investigators for the months of January through December 2013, identify that you produced domperidone drug products. 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 drug product, and does not appear on a list of bulk drug substances developed by the Secretary under 503A(b)(1)(A)(i)(III) of the Federal Food, Drug, and Cosmetic (FDCA) [21 U.S.C. § 353a]. In addition, FDA obtained sales material listing prices for certain drug products offered by your firm, including Brilliant Blue G. Like domperidone, Brilliant Blue G is not the subject of a USP or NF monograph, a component of an FDA-approved drug product, or on a list of bulk drug substances developed by the Secretary under 503A(b)(1)(A)(i)(III) of the FDCA.
 
FDA issued Forms FDA 483 to your firm on July 19, 2013 and on December 16, 2013. Based on these inspections, it appears your firm is producing drugs that violate the FDCA.  
 
A. Compounded Drugs Under the FDCA
 
At the time FDA first inspected your facility in July 2013, there were conflicting judicial decisions regarding the applicability of section 503A of the FDCA [21 U.S.C. § 353a], which exempts compounded drugs from several key statutory requirements if certain conditions are met.[1]  Nevertheless, receipt of valid prescriptions for individually-identified patients prior to distribution of compounded drugs was relevant for both section 503A of the FDCA and the agency’s Compliance Policy Guide 460.200 on Pharmacy Compounding (CPG) (2002), which was then in effect.[2] During the FDA inspection, investigators observed that your firm does not receive valid prescriptions for individually-identified patients for a portion of the drug products you produce. Based on this factor alone, those drugs were not entitled to the statutory exemptions for compounded drugs described in section 503A of the FDCA and did not qualify for the agency’s exercise of enforcement discretion set forth in the CPG.[3] 
 
In addition, under the CPG, when determining whether enforcement discretion is appropriate, FDA considered whether a firm compounded finished drugs from bulk active ingredients that were not components of FDA-approved drugs without an FDA sanctioned investigational new drug application. Because domperidone is not a component of an FDA-approved drug, your compounded drugs containing domperidone and any drugs that you compound using Brilliant Blue G would not qualify for the exercise of enforcement discretion set forth in the CPG.  Further, the exemptions provided by section 503A do not apply to compounded drug products containing domperidone or Brilliant Blue G because domperidone and Brilliant Blue G are neither the subject of an applicable USP or NF monographs, nor a component of an FDA-approved drug under section 503A(b)(1)(A)(i) of the FDCA, and neither appears on a list developed by the Secretary under 503A(b)(1)(A)(i)(III).
 
On November 27, 2013, the President signed into law the Compounding Quality Act (CQA)[4], which amended FDCA section 503A by eliminating the advertising restrictions that had been the basis for conflicting judicial decisions. The CQA otherwise left section 503A intact, and so clarified that the remainder of section 503A is applicable in every federal judicial circuit, including the requirement for valid prescriptions for individually-identified patients, and the requirement to only compound drug products using bulk drug substances if each bulk drug substance is the subject of an applicable USP or NF monograph, is a component of an FDA-approved human drug, or appears on a list developed by the Secretary under section 503A(b)(1)(A)(i)(III).  Accordingly, the drugs you compound without valid prescriptions for individually-identified patients and the drug products you compound using bulk drug substances, such as domperidone, that are not the subject of an applicable USP or NF monograph, not a component of an FDA-approved human drug, and that do not appear on a list developed by the Secretary under section 503A(b)(1)(A)(i)(III), are not entitled to the exemptions in section 503A.[5]
 
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.[6]
 
B. Violations of the FDCA
 
Because the domperidone drug products that your firm manufactures and delivers for introduction into interstate commerce are not the subject of approved applications, they are unapproved new drugs in violation of section 505(a) of the FDCA [21 U.S.C. §§ 355(a)]. Furthermore, the domperidone drug products that your firm manufacturers and distributes  and the drug products that your firm manufactures and distributes without valid prescriptions for individually-identified patients are misbranded drugs in violation of section 502(f)(1) of the FDCA [21 U.S.C. 352(f)(1)], regardless of whether they are distributed in interstate commerce. 
 
In addition, your sterile drug products are 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. As such, all sterile products you manufacture are 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 drugs without valid prescriptions for individually-identified patientsand also manufacture domperidone drug products (which, as noted above, are not eligible for the exemptions provided by section 503A(a)), the manufacture of those drugs is also subject to FDA’s Current Good Manufacturing Practice (CGMP) regulations for Finished Pharmaceuticals, Title 21, Code of Federal Regulations, Parts 210 and 211 (21 CFR 210 and 211). FDA investigators observed significant CGMP violations at your facility, causing the drug products made without valid prescriptions for individually-identified patients and the domperidone drug products to be adulterated within the meaning of section 501(a)(2)(B) of the FDCA [21 U.S.C. § 351(a)(2)(B)]. 
 
Unapproved New Drug Products
 
You do not have any FDA-approved applications on file for the drug products that you produce from bulk domperidone, which is not permitted to be used in compounding under section 503A .[7]  Under sections 301(d) and 505(a) 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.  Your marketing of these drug products without an approved application violates these provisions of the FDCA.
 
Misbranded Drug Products
 
Because the domperidone products and the drug products for which you have not obtained valid prescriptions for individually-identified patients are intended for conditions that are not amenable to self-diagnosis and treatment by individuals who are not medical practitioners, adequate directions cannot be written for them 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 sections 301(a) of the FDCA [21 U.S.C. § 331(a)].   It is also 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.
 
Adulteration Charges
 
Additionally, FDA investigators 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, our investigators observed operators preparing injectable drug products with the skin on their faces exposed and wearing non-sterile gowns and gown components.  Furthermore, our investigators found that your firm failed to demonstrate through appropriate studies that your hoods are able to provide adequate protection of the ISO 5 area in which sterile products are processed. Therefore, your products may be produced in an environment that poses a significant contamination risk.  
 
FDA investigators also noted CGMP violations at your facility causing the drug products for which you have not obtained valid prescriptions for individually-identified patients and the drug products that you produce from bulk drug substances that are not permitted to be used in compounding under section 503A 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 includes validation of all aseptic and sterilization processes (21 CFR 211.113(b)).
 
2.    Your firm failed to ensure that manufacturing personnel wear clothing appropriate to protect drug product from contamination (21 CFR 211.28(a)).
 
3.    Your firm failed to establish an adequate system for monitoring environmental conditions in aseptic processing areas (21 CFR 211.42(c)(10)(iv)).
 
4.    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)).
 
5.    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 [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 of the components used to make the drug and results in the drug being adulterated.
 
C. Corrective Actions
 
We acknowledge receipt of your firm’s responses to the Form FDA-483s dated August 5, 2013 and January 2, 2014. In your January 2, 2014 response, you referenced your purported compliance with the USP- NF General Chapter <797> Pharmaceutical Compounding-- Sterile Preparations, and you objected to any finding of deficiency in relation to your operations. As noted above, your firm manufactures a portion of drug products without valid prescriptions for individually-identified patients and your firm produces and distributes domperidone drug products, which are not permitted to be compounded from bulk drug substances under section 503A. The manufacture of such drugs is subject to FDA’s drug CGMP regulations (21 CFR 210 and 211).
 
FDA strongly recommends 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. You should fully implement corrections that meet the minimum requirements of 21 CFR 210 and 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.  
 
D. Conclusion
 
The violations cited in this letter are not intended to be an all-inclusive statement of violations existing 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 fifteen working days of receipt of this letter, please notify this office in writing of the specific steps 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 the corrective actions cannot be completed within fifteen working days, state the reason for the delay and the time frame within which the corrections will be implemented.  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 notification should be addressed to:
 
LCDR Frank Verni, Compliance Officer
New York District
158-15 Liberty Ave.
Jamaica, NY 11433
                                                                                                           
If you have questions regarding any issues in this letter, please contact our office at (718) 340-7000.
 
Sincerely,
/S/
Ron Pace
District Director
New York District


[1] Compare Western States Med. Ctr. v. Shalala, 238 F.3d 1090 (9th Cir. 2001) with Medical Ctr. Pharm. v. Mukasey, 536 F.3d 383 (5th Cir. 2008).
[2] The CPG set forth a non-exhaustive list of factors that FDA considered in determining whether to take enforcement action when the scope and nature of a pharmacy's activities raised concerns. This CPG has been withdrawn in light of new legislation. See below.
[3] See 21 U.S.C. § 353a(a) (granting compounded drugs statutory exemptions if, among other things, “the drug product is compounded for an identified individual patient based on the . . . receipt of a valid prescription order or a notation, approved by the prescribing practitioner, on the prescription order that a compounded product is necessary for the identified patient . . . .”); CPG at 2 (“FDA recognizes that pharmacists traditionally have extemporaneously compounded and manipulated reasonable quantities of human drugs upon receipt of a valid prescription for an individually-identified patient from a licensed practitioner.  This traditional activity is not the subject of this guidance.”).
[4] Drug Quality and Security Act, Public Law 113-54, Title I, 127 Stat. 587 (Nov. 27, 2013).
[5]The 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
[6] 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.
[7] 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. 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.