Inspections, Compliance, Enforcement, and Criminal Investigations

Qualgen 6/3/16

  

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

Public Health Service
Food and Drug Administration
 Dallas District Office
4040 North Central Expressway
Suite 300
Dallas, Texas 75204-3128
 

 

June 3, 2016
 
2016-DAL-WL-25
 
VIA UPS Express
WARNING LETTER
 
Carol Ann Tutera and Adam Stempel, Managing Members
Wild West Group, LLC
RE: Qualgen, LLC
8412 E. Shea Blvd., Suite 101
Scottsdale, Arizona 85260
 
Dear Ms. Tutera and Mr. Stempel:
 
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 May 23, 2014, May 8, 2015, and January 14, 2016. From August 24, 2015, to September 17, 2015, FDA investigators inspected your facility, Qualgen, LLC, 14844 Bristol Park Boulevard, Edmond, Oklahoma 70313.   During the inspection, the investigators observed serious deficiencies in your practices for producing sterile drug products, which put patients at risk. For example, the investigators observed that the ceiling tiles of your ISO 7 cleanrooms were not fully sealed, allowing ingress of unfiltered air from the surrounding non-classified area.   Furthermore, the process used to render the implantable hormone pellets sterile is not adequate as evidenced by the multiple sterility failures. Moreover, the investigators also noted that your firm failed to perform adequate investigations into these sterility failures. In addition, the investigators observed that you failed to meet the conditions under section 503B of the FDCA [21 U.S.C. § 353b] that are necessary for drugs produced by an outsourcing facility to qualify for exemptions from certain requirements under the FDCA. FDA issued a FDA 483 to your facility on September 17, 2015. FDA acknowledges receipt of your facility’s response, dated October 7, 2015, to the FDA 483; your October 9, 2015 letter notifying FDA of your voluntary recall of certain products and your October 22, 26, 28, and 30, 2015, responses to FDA’s October 20, 2015, record request. 
 
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) of the FDCA [21 U.S.C. § 353b(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 [21 U.S.C. § 353b] 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
 
FDA 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 [21 U.S.C. § 351(a)(2)(A)]. 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 [21 U.S.C. § 351(a)(2)(B)].
 
In addition, the FDA investigators observed that your facility failed to meet the conditions of section 503B of the FDCA [21 U.S.C. § 353b(b)]. For example, during the inspection, FDA investigators noted the following: Some of your facility’s drug products do not include the following statements on the product labels: “This is a compounded drug,” and “Not for resale.” The storage and handling instructions are also not included. Additionally, the containers for some of your drug products do not contain the following information: the route of administration. [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 May 2014, and again in December 2014 and June 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 have not met all of the conditions in section 503B of the FDCA [21 U.S.C. § 353B], they are not eligible for the exemptions under section 503B from the FDA approval requirements in section 505 of the FDCA [21 U.S.C. § 355(a)], the requirement under 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 described in section 582 of the FDCA [21 U.S.C. § 360eee-1].[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 [21 U.S.C. § 351(a)(2)(A)]. For example, the investigators observed that the ceiling tiles of your ISO 7 cleanrooms were not fully sealed, allowing ingress of unfiltered air from the surrounding non-classified area. 
 
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 [21 U.S.C. § 351(a)(2)(B)].  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 have facilities used in the manufacturing, process, packaging and holding of a drug product of appropriate construction to facilitate cleaning, maintenance and proper operations. (21 CFR 211.42a)).
 
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 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).
 
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)). 
 
6.     Your firm’s quality control unit failed to approve or reject all procedures or specifications impacting on the identity, strength, quality, and purity of the drug product (21 CFR 211.22(c)). 
 
7.     Your firm failed to establish written procedures for production and process control designed to assure that the drug products have the identity, strength, quality, and purity they purport or are represented to possess (21 CFR 211.100(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.  
 
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 and results in the drug being adulterated.
 
Unapproved New Drug Products
 
You do not have any FDA-approved applications on file for your drug products.[3] Under sections 301(d) and 505(a) of the FDCA [21 U.S.C. §§ 331(d) and 355(a)], a new drug may not be introduced 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. 
 
Misbranded Drug Products
 
You compound 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)], 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)]. 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 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 May 2014, and again in December 2014 and June 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) of the FDCA [21 U.S.C. §353b(b)(2)] is a prohibited act under section 301(ccc)(3) of the FDCA [21 U.S.C. § 331(ccc)(3)].
 
C. Corrective Actions
 
In your October 7, 2015 response, you describe corrective actions you have taken to address the FDA 483 observations. On October 20, 2015, FDA requested additional information regarding the status of your corrections. FDA acknowledges receipt of your responses and supplementary information on October 22, 26, 28, and 30, 2015.   Although some of your proposed corrective actions appear adequate, others are deficient. For example, your October 7, 2015 response stated that the root cause for the sterility failures was the use of an unvalidated sterilization cycle. However, based on the investigation report dated October 27, 2015, it appears that your firm did not consider the sterilization cycle as a potential cause of the sterility failures.   Moreover, it is unclear if the (b)(4) and implantable pellets to ensure their sterility. Your responses also did not provide sufficient detail on the blending processes, sterilization parameters, and other quality factors used in the process validation studies conducted by your firm. In addition, your responses did not provide information regarding the stability data to support the four (4) month expiration date applied to the implantable hormone pellets. Finally, your (b)(4) monitoring procedure did not include actions to be taken when established action and alert levels are exceeded.
 
In addition, due to the deficiencies in the practices at your outsourcing facility, your firm initiated a recall in October 2015. On October 8, 2015, FDA recommended that your firm initiate a voluntary recall of all lots of non-expired drug products intended to be sterile due to lack of sterility and quality assurance and cease sterile operations until appropriate corrective actions had been implemented. 
 
On October 9, 2015, your firm agreed to only recall lots A001-A067, and did not agree to cease sterile operations, stating your firm had already implemented corrective actions, which were detailed in your October 7, 2015, response to the FDA 483. You indicated that the lots produced after September 1, 2015 (beginning with lot (b)(4)), were produced using a validated sterilization process and that there had not been any sterility failures in lots (b)(4).  
 
The implemented corrective actions in reference to the observed 503B labeling deficiencies appear to be adequate.
 
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 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 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 firm’s response to this letter should be sent to: Dallas District Office, ATTN: John W. Diehl, 4040 North Central Expressway, Suite 300, Dallas, Texas 75204. If you have any questions about the contents of this letter, please contact: John W. Diehl, Compliance Officer, at 214-253-5288.
 
Sincerely,
/S/                                                           
Reynaldo R. Rodriguez, Jr.
Dallas District Director
  
 
CC:
 
John A. Foust, Pharm.D.
Executive Director
Oklahoma State Board of Pharmacy
2920 N Lincoln Blvd, Suite A
Oklahoma City, Oklahoma 73105
 
Chelsea Church, Pharm.D.
Pharmacist Compliance Officer
Oklahoma State Board of Pharmacy
2920 N Lincoln Blvd, Suite A
Oklahoma City, Oklahoma 73105
 
Shaun P. Riney, General Manager
Qualgen, LLC
14844 Bristol Park Blvd.
Edmond, Oklahoma 70313
 
Ken Kotowich, Co-Owner
8412 E. Shea Blvd., Suite 101
Scottsdale, Arizona 85260
 
Charles Riney, Co-Owners
14844 Bristol Park Blvd.
Edmond, Oklahoma 70313
 
Ryan Orton, Co-Owner
3300 NW 56th Street, Suite 101
Oklahoma City, Oklahoma 73112
_______________________________________

[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)].
[3] 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 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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