Inspections, Compliance, Enforcement, and Criminal Investigations

Edge Pharmacy Services, LLC 11/12/15

  

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

Public Health Service
Food and Drug Administration
 
New England District Office
One Montvale Avenue, 4th floor
Stoneham, MA 02180
Phone 781.587.7500
Fax 781.587.7556 
           
WARNING LETTER
CMS # 447006
 
VIA UPS Next Day Air
 
November 12, 2015
 
William Chatoff, R.Ph., BCNP
President/CEO
Edge Pharmacy Services, L.L.C
856 Hercules Drive, Suite 30
Colchester, VT 05446
 
Dear Mr. Chatoff:
 
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 January 21, 2014, and again on January 15, 2015. From July 22 to August 20, 2014, an FDA investigator inspected your facility, located at 856 Hercules Drive, Suite 30, Colchester, VT 05446. During the inspection, the investigator observed serious deficiencies in your practices for producing sterile drug products, which put patients at risk. For example, the investigator noted 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 produced. Therefore, your products may be produced in an environment that poses a significant contamination risk.  In addition, the investigator observed that you failed to meet the conditions under section 503B of the FDCA 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 August 20, 2014. FDA acknowledges receipt of your facility’s response, dated September 9, 2014.
 
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 investigator 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 investigator 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 investigator observed that your facility failed to meet the conditions of section 503B. For example, during the inspection, the FDA investigator noted that some of your facility’s drug products do not include the following information on the label: a list of active and inactive ingredients, storage and handling instructions, and the statements, “This is a compounded drug” and “Not for Resale” and/or does not include information to facilitate adverse event reporting and a list of active and inactive ingredients (if there is no space on the label for such information) on the container. [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 in June 2014, and again in December 2014, 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, they are not eligible for the exemptions under section 503B from the FDA approval requirements in section 505, the requirement under section 502(f)(1) 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 investigator 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 been 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 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 produced. Therefore, your products may be produced in an environment that poses a significant contamination risk.
 
The FDA investigator 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 test each component for conformity with all appropriate written specifications for purity, strength and quality (21 CFR 211.84(d)(2)).
 
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, 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.   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 misbranded.
 
Failure to Report Drugs
 
As noted above, your facility failed to submit a report to FDA in June 2014, and again in December 2014, 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
 
In your September 9, 2014, response you described certain corrective actions you took in response to the Form FDA 483 observations. Although several of your proposed corrective actions appear adequate, others are deficient.   You did not indicate implementation dates nor have you provided sufficient detail or description regarding revised procedures for the Agency to evaluate the adequacy of your corrective actions.
 
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.
  
Additionally, in your September 9, 2014, response, you stated that your firm is currently operating as a 503A pharmacy and a 503B outsourcing facility. You stated that on or before January 31, 2015, you would undertake a thorough review of all labels being produced, and that “[a]ll labels will have compliant language for all 503B products being dispensed as orders and 503A prescriptions being dispensed directly to patients, each respectively being compliant with the appropriate regulatory agencies.” FDA reminds you that drug products produced in a 503B-registered outsourcing facility must be labeled in accordance with section 503B as one of the conditions necessary to qualify for the exemptions under section 503B of the FDCA (Section 503B(a)(11), [21 U.S.C. § 353b(b)(2)]).[4] 
 
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 response should be sent to the Food and Drug Administration, Attention: Scott M. Loughan, One Montvale Avenue, Stoneham, Massachusetts 02180. If you have questions regarding any issues in this letter, please contact Mr. Loughan at 781-587-7619.
 
Sincerely,
/S/ 
Joseph Matrisciano
Acting District Director
New England District
 
 
Cc:
Colin Benjamin, Director (redacted copy)
Vermont Office of Professional Regulation
89 Main Street, 3rd Floor
Montpelier, Vermont 05620-3402
 
 
______________________________________
[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. 
[4] One of the conditions that must be met in order for a drug product to qualify for the exemptions provided in section 503B is that “[T]he drug is compounded in an outsourcing facility in which the compounding of drugs occurs only in accordance with [section 503B].” [Section 503B(a)(11) of the FDCA [21 U.S.C. §353b(a)(11)]].

 

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