Inspections, Compliance, Enforcement, and Criminal Investigations

PCP LV LLC dba Pinnacle Compounding Pharmacy 5/23/16

  

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

Public Health Service
Food and Drug Administration
 San Francisco District Office
1431 Harbor Bay Parkway
Alameda, CA 94502-7070
Telephone:   510-337-6700
FAX: 510-337-6859

 

VIA UPS NEXT DAY AIR
w/ DELIVERY CONFIRMATION
 
WARNING LETTER
WL-492707
May 23, 2016
 
Cecilia R. Ventura
Co-Owner, Executive Director
PCP LV, LLC dba Pinnacle Compounding Pharmacy
 
c/o Maria Nutile, Esq.
Nutile Law
1070 W. Horizon Ridge Parkway, Suite 210
Henderson, NV 89012
 
Dear Ms. Ventura:
 
You registered with the U.S. Food and Drug Administration (FDA) as an outsourcing facility under section 503B of the Federal Food, Drug, and Cosmetic Act (FDCA) [21 U.S.C. § 353b][1] on July 10, 2015, and at the time of FDA’s inspection from July 27, 2015, to July 31, 2015, your facility, PCP LV, LLC dba Pinnacle Compounding Pharmacy, located at 4445 S. Eastern Ave, Las Vegas, NV 89119-7851, was registered as an outsourcing facility.  Although, as of the date of this letter, your facility is no longer registered as an outsourcing facility, this letter discusses violations identified during the time you were registered as an outsourcing facility. Because you are no longer registered as an outsourcing facility, in the corrective action section, this letter discusses the conditions a compounded drug product must meet in order to qualify for the exemptions under section 503A of the FDCA [21 U.S.C. § 353a].
 
During FDA’s inspection of your facility, our investigators observed serious deficiencies in your practices for producing sterile drug products, which put patients at risk. For example, the investigators noted that production occurred in the cleanroom while the positive pressure differential to the anteroom was below your specification.  In addition, your environmental monitoring samples were incubated in a hallway at uncontrolled room temperature, which could potentially bias the results. The investigators also noted that your firm used an expired disinfectant and did not follow the manufacturer’s instructions to ensure an adequate contact time for your sporicidal agent.  Furthermore, 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 products are processed. Therefore, your products may be produced in an environment that poses a significant contamination risk.  
 
In addition, the investigators observed that you failed to meet the conditions under section 503B of the FDCA that applied to your facility at the time of the inspection and that are necessary for drugs produced by an outsourcing facility to qualify for exemptions from certain requirements under the FDCA. FDA issued a Form FDA 483 to your facility on July 31, 2015.  FDA acknowledges receipt of your facility’s undated response, which was received on September 15, 2015.
 
Based on this inspection, it appears your facility is producing drugs that violate the FDCA. 
 
A. Compounded Drugs under the FDCA
 
The Drug Quality and Security Act (DQSA) was enacted on November 27, 2013. Title I of the DQSA, the Compounding Quality Act (CQA), added a new section 503B to the FDCA. Under section 503B(b), a compounder can register as an outsourcing facility with FDA. Drug products compounded by or under the direct supervision of a licensed pharmacist in an outsourcing facility can qualify for exemptions from the drug approval requirements in section 505 of the FDCA [21 U.S.C. § 355(a)], the requirement in section 502(f)(1) of the FDCA [21 U.S.C. § 352(f)(1)] that labeling bear adequate directions for use, and the Drug Supply Chain Security Act requirements in section 582 of the FDCA [21 U.S.C. § 360eee-1] if the conditions in section 503B of the FDCA are met.
 
An outsourcing facility, which is defined in section 503B(d)(4) of the FDCA [21 U.S.C. § 353b(d)(4)], is a facility at one geographic location or address that — (i) is engaged in the compounding of sterile drugs; (ii) has elected to register as an outsourcing facility; and (iii) complies with all of the requirements of this section. Outsourcing facilities must comply with other provisions of the FDCA, including section 501(a)(2)(B) [21 U.S.C. § 351(a)(2)(B)], regarding current good manufacturing practice (CGMP), and section 501(a)(2)(A) [21 U.S.C. § 351(a)(2)(A)], regarding insanitary conditions. Generally, CGMP requirements for the preparation of drug products are established in Title 21 of the Code of Federal Regulations (CFR) parts 210 and 211.
 
B. Violations of the FDCA
 
The investigators noted that drug products that were intended or expected to be sterile were prepared, packed, or held under insanitary conditions whereby they may have been contaminated with filth or rendered injurious to health, causing them to be adulterated within the meaning of section 501(a)(2)(A) of the FDCA. Furthermore, the FDA investigators 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.  
 
In addition, the FDA investigators observed that your facility failed to meet the conditions of section 503B, which applied to your facility at the time of the inspection. For example, during the inspection, the FDA investigators noted that some of your facility’s drug products do not include the following information on the labeling: the date the drug was compounded; information to facilitate adverse event reporting; and the statement, “Not for resale” [Section 503B(a)(10) of the FDCA [21 U.S.C. § 353b(a)(10)]].
 
In addition, your facility failed to submit a report to FDA upon initial registration as an outsourcing facility in July 2015, identifying the drug products that you compounded during the previous 6-month period [Section 503B(b)(2) of the FDCA [21 U.S.C. § 353b(b)(2)]]. 
 
Because your compounded drug products did not meet all of the conditions in section 503B of the FDCA, they were not eligible for the exemptions under section 503B of the FDCA from the FDA approval requirements in section 505 of the FDCA, the requirement under section 502(f)(1) of the FDCA that labeling bear adequate directions for use, and the Drug Supply Chain Security Act requirements described in section 582 of the FDCA.[2] 
 
Specific violations are described below.
 
Adulterated Drug Products
 
The FDA investigators noted that drug products compounded 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 investigators noted that production occurred in the cleanroom while the positive pressure differential to the anteroom was below your specification. The investigators also noted that your firm used an expired disinfectant and did not follow the manufacturer’s instructions to ensure an adequate contact time for your sporicidal agent. Furthermore, 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 products are processed.  Therefore, your products may be produced in an environment that poses a significant contamination risk.   
 
The FDA investigators also noted CGMP violations at your facility, causing your drug products to be adulterated within the meaning of 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)).
 
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 air supply filtered through high-efficiency particulate air filters under positive pressure in the aseptic processing areas (21 CFR 211.42(c)(10)(iii)).
 
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 ensure that manufacturing personnel wear clothing appropriate to protect drug product from contamination (21 CFR 211.28(a)).
 
6.    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)).
 
7.    Your firm failed to ensure that its drug product bore an expiration date that was supported by appropriate stability testing (21 CFR 211.137(a)).
 
Outsourcing facilities must comply with CGMP requirements under section 501(a)(2)(B) of the FDCA. FDA’s regulations regarding CGMP requirements for the preparation of drug products have been established in 21 CFR parts 210 and 211. FDA intends to promulgate more specific CGMP regulations for outsourcing facilities. FDA has issued a draft guidance, Current Good Manufacturing Practice — Interim Guidance for Human Drug Compounding Outsourcing Facilities under Section 503B of the FD&C Act. This draft guidance, when finalized, will describe FDA’s expectations regarding outsourcing facilities and the CGMP requirements in 21 CFR parts 210 and 211 until more specific CGMP regulations for outsourcing facilities are promulgated.  
 
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.
 
Misbranded Drug Products
 
You compounded drug products 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 [21 U.S.C. § 352(f)(1)]. As stated above, because your compounded drug products did not meet all of the conditions in section 503B of the FDCA, they were not exempt from the requirements of section 502(f)(1) of the FDCA (see, e.g., 21 CFR 201.115). 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.
 
Failure to Report Drugs
 
As noted above, your facility failed to submit a report to FDA upon initial registration as an outsourcing facility in July 2015, identifying the drug products that you compounded during the previous 6-month period (Section 503B(b)(2) of the FDCA [21 U.S.C. § 353b(b)(2)]). The failure to report drugs by an entity that is registered with FDA in accordance with section 503B(b) is a prohibited act under section 301(ccc)(3) of the FDCA [21 U.S.C. § 331(ccc)(3)].
 
C. Corrective Actions
 
Your response to the Form FDA 483 issued at the close of FDA’s inspection of your facility, did not describe any corrective actions taken in response to the Form FDA 483 observations; it stated only that you registered as an outsourcing facility in error and that you planned to de-register. We acknowledge your firm’s September 3, 2015, de-registration.  
 
Because your facility is no longer registered as an outsourcing facility, drug products that you produce are no longer eligible to qualify for the exemptions under section 503B of the FDCA.   However, they can qualify for the exemptions under section 503A of the FDCA if they are compounded in accordance with all of the conditions of section 503A. Section 503A describes the conditions under which certain compounded human drug products are entitled to exemption from three sections of the FDCA: compliance with 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)]. Receipt of valid prescriptions for individually-identified patients is one of the conditions for the exemptions under section 503A.   In addition, there are other conditions that must be satisfied to qualify for the exemptions in section 503A of the FDCA. Please be aware that compounded drug products that qualify for the exemptions in section 503A remain subject to all other applicable provisions of the FDCA, including the requirement that the drug products are not prepared, packed, or held under insanitary conditions (section 501(a)(2)(A) of the FDCA).  As described above, our investigators observed insanitary conditions during the July 2015 inspection. You should take prompt action to correct these insanitary conditions.
 
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. You should fully implement necessary corrections in order to ensure that the drug product(s) 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 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. FDA intends to re-inspect your facility to verify corrective actions have been completed.
 
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 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 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 completed.  Your written notification should refer to the Warning Letter Number above (WL-492707). Please address your reply to:
 
Lawton W. Lum, Director of Compliance
FDA San Francisco District Office
U.S. Food and Drug Administration
1431 Harbor Bay Parkway
Alameda, CA 94502-7070
 
 If you have questions regarding the contents of this letter, please contact William Millar, Compliance Officer at 510-337-6896 or by email at william.millar@fda.hhs.gov.
 
 
Sincerely,
/S/
Kathleen M. Lewis, J.D.
San Francisco District Director
U.S. Food and Drug Administration

[1] See Pub. L. No. 113-54, § 102(a), 127 Stat. 587, 587-588 (2013).
[2] See, e.g., section 503B(a)(11) of the FDCA [21 U.S.C. § 353b(a)(11)].

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