Inspections, Compliance, Enforcement, and Criminal Investigations

Alexander Infusion LLC D/B/A Avanti Health Care 3/27/15

  

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

 

March 27, 2015
 
WARNING LETTER NYK-2015-27 
 
VIA UNITED PARCEL SERVICE
DELIVERY SIGNATURE REQUESTED
 
Pietro Piacquadio, Chief Executive Officer
Alexander Infusion, LLC (dba Avanti Health Care Services)
75 Nassau Terminal Road                                    
New Hyde Park, NY 11040-4927
 
Dear Mr. Piacquadio:
 
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 April 21, 2014, and again on January 7, 2015. From June 23 to July 9, 2014, an FDA investigator inspected your facility, Alexander Infusion, LLC (dba Avanti Health Care Services), located at 75 Nassau Terminal Road, New Hyde Park, NY 11040-4927. 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 observed operators processing sterile drug products in ISO 5 areas with exposed facial skin and hair, as well as using sterile gloves placed over non-sterile, non-disinfected gloves without using proper aseptic technique. In addition, the investigator 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. 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 July 9, 2014. FDA acknowledges receipt of your facility’s response, dated September 3, 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, FDA investigators noted:
 
  1. Some of your facility’s drug products do not include the following information on the labeling: the lot number, information to facilitate adverse event reporting, and the statements, “This is a compounded drug,” and “Not for Resale” (Section 503B(a)(10) of the FDCA [21 U.S.C. § 353b(a)(10)]).
 
  1. Your facility failed to submit a report to FDA upon initial registration as an outsourcing facility in April 2014, and again in June 2014 and 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, 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 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 investigator observed operators processing sterile drug products in ISO 5 areas with exposed facial skin and hair, as well as using sterile gloves placed over non-sterile, non-disinfected gloves without using proper aseptic technique. In addition, the investigator 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.
 
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 ensure that manufacturing personnel wear clothing appropriate to protect drug products from contamination (21 CFR 211.28(a)).
 
3.      Your firm failed to establish a system for maintaining any equipment used to control the aseptic conditions (21 CFR 211.42(c)(10)(vi)).
 
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 an adequate system for monitoring environmental conditions in aseptic processing areas (21 CFR 211.42(c)(10)(iv)).
 
6.      Your firm does not have, for each batch of drug product purporting to be sterile and/or pyrogen-free, an appropriate laboratory determination of satisfactory conformance to final specifications for the drug product (21 CFR 211.167(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 compound drug products that are intended for conditions that are not amenable to self-diagnosis and treatment by individuals who are not medical practitioners, and 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).  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 upon initial registration as an outsourcing facility in April 2014, and again in June 2014 and 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 3, 2014 response you described certain corrective actions you are planning to take in response to the Form FDA 483 observations 7 and 8 regarding separate areas for processing and packing of penicillin and non-penicillin beta-lactams. However, your letter did not provide corrective actions for any of the other issues included in the Form FDA 483 or the date of implementation for your proposed corrective action.   
 
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 (NYK-2015-27). Please address your reply to Lillian C. Aveta, Compliance Officer, at the address above.
 
If you have questions regarding the contents of this letter, please contact Lillian C. Aveta at 718-662-5576.
 
Sincerely,
/S/ 
Ronald M. Pace
District Director
New York District
  
cc: New York State Education Department
     Office of the Professions
     State Board of Pharmacy
     Attn: Lawrence H. Mokhiber, Executive Secretary
     89 Washington Avenue
     Albany, New York 12234-1000
 
cc: New York State Department of Health
     Attn: Dr. Howard A. Zucker, Acting Commissioner
     Corning Tower
     Empire State Plaza,
     Albany, NY 12237


[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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