Inspections, Compliance, Enforcement, and Criminal Investigations

One Way Drug, LLC 7/22/15

  

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

Public Health Service
Food and Drug Administration
 
San Francisco District
1431 Harbor Bay Parkway
Alameda, CA 94502-7070 

 

WARNING LETTER
           
 
Via UPS                                                                                                         WL: 441276
Delivery Signature Requested
 
July 22, 2015
 
Robert A. Seik, PharmD and Robert M. Sigler, Co-Owners
One Way Drug, LLC dba Partell Specialty Pharmacy
8751 W Charleston Blvd, Suite 120
Las Vegas, NV 89117-5481
 
Dear Dr. Seik and Mr. Sigler:
 
From May 21 to May 30, 2014, U.S. Food and Drug Administration (FDA) investigators conducted an inspection of your facility, Partell Specialty Pharmacy, located at 8751 W. Charleston Blvd, Suite 120, Las Vegas, NV 89117-5481. During the 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. The investigators observed serious deficiencies in your practices for producing sterile drug products, which put patients at risk.  For example, they observed an operator (b)(4) stoppering vials with gloved hands on a table that is only partially separated (by curtains) from a less clean area, and processing sterile drug products with exposed skin on (b)(6) face. Additionally, investigators noted that your firm does not use sporicidal agents to clean the production areas, only infrequently performs viable and non-viable monitoring, and does not monitor pressure differentials throughout the day, including during periods of production. Also, an operator was observed placing bulk drug product containers from the ISO-7 cleanroom into the ISO-5 area without sanitization. Furthermore, investigators noted that your firm failed to demonstrate through appropriate studies that your workbench 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 noted that domperidone products are included in your “Formula Report,” dated May 30, 2014, which you provided to investigators during the inspection.  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 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].
 
A Form FDA 483 was issued to your firm on May 30, 2014. FDA acknowledges receipt of your facility’s response, dated June 20, 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 exemption 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 our inspection, investigators 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.
 
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.[1]
 
B. Violations of the FDCA
 
Because the drug products your firm manufactures and distributes without valid prescriptions for individually-identified patientsare 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 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. 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. 
 
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 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. 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 sections 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, 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 an operator (b)(4) stoppering vials with gloved hands on a table that is only partially separated (by curtains) from a less clean area, and processing sterile drug products with exposed skin on (b)(6) face. Additionally, investigators noted that that your firm does not use sporicidal agents to clean the production areas, only infrequently performs viable and non-viable monitoring, and does not monitor pressure differentials throughout the day, including during periods of production. Also, an operator was observed placing bulk drug product containers from the ISO-7 cleanroom into the ISO-5 area without sanitization.  Furthermore, our investigators found that your firm failed to demonstrate through appropriate studies that your workbench 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.  
 
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 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)).
 
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 system for cleaning and disinfecting the room and equipment to produce aseptic conditions (21 CFR 211.42(c)(10)(v)).
 
4.    Your firm failed to ensure that manufacturing personnel wear clothing appropriate to protect drug product from contamination (21 CFR 211.28(a)).
 
5.    Your firm failed to adequately design the facility with adequate separation or defined areas or such other control systems necessary to prevent contamination or mix-ups (21 CFR 211.42(b)).
 
6.    Your firm failed to clean and, where indicated by the nature of the drug, sterilize and process containers and closures to remove pyrogenic properties to assure they are suitable for their intended use (21 CFR 211.94(c)).
 
7.    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)).
 
8.    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
 
We have reviewed your firm’s planned corrective actions, as documented in your June 20, 2014 response to the Form FDA-483 Inspectional Observations issued at the close of the inspection, and determined that they do not meet the minimum requirements of 21 CFR 210 and 211 and are inadequate to correct the observed insanitary conditions at your facility. For example, although you commit to the performance of an in situ smoke study by a qualified outside vendor, you do not indicate if the smoke studies will be performed under dynamic conditions. You claim compliance with USP <797>; USP <797> states that in situ air pattern analysis via smoke studies shall be conducted under dynamic 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.
 
In your response, you indicated that your firm is a 503A pharmacy registered, licensed, practicing, and inspected under the state jurisdiction of the Nevada Board of Pharmacy (NVBOP). However, as discussed above, your firm has manufactured and distributed drugs without valid prescriptions for individually-identified patients. These drug products do not qualify for the exemptions under section 503A and the manufacture of such drugs is subject to FDA’s finished drug product CGMP regulations, 21 CFR parts 210 and 211.
 
In addition, you should correct the violations of sections 502(f)(1), 501(a)(2)(A), and 505 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 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. 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 response should be addressed 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 any issues in this letter, please contact Russell A. Campbell, Compliance Officer, at 510-337-6861.
 
 
Sincerely,
/S/
Kathleen M. Lewis, J.D.
San Francisco District Director
 
 
cc:       
Larry L. Pinson, Executive Secretary
Nevada Board of Pharmacy
431 W. Plumb Ln.
Reno, NV 89509

[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) [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) of the FDCA [21 U.S.C. 321(p)] because they are not generally recognized as safe and effective for their labeled uses.

Page Last Updated: 11/30/2015
Note: If you need help accessing information in different file formats, see Instructions for Downloading Viewers and Players.
Language Assistance Available: Español | 繁體中文 | Tiếng Việt | 한국어 | Tagalog | Русский | العربية | Kreyòl Ayisyen | Français | Polski | Português | Italiano | Deutsch | 日本語 | فارسی | English