Inspections, Compliance, Enforcement, and Criminal Investigations

MasterPharm LLC 1/8/16

  

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

Public Health Service
Food and Drug Administration
 
New York District Office
Northeast Region
158-15 Liberty Avenue
Jamaica, NY 11433    
Telephone: (718) 340-7000
FAX: (718) 662-5434

 

UNITED PARCEL SERVICE
DELIVERY SIGNATURE REQUESTED
 
WARNING LETTER NYK-2016-18
January 8, 2016
 
Steven S. Laddy, CEO
MasterPharm, LLC
115-02 Liberty Avenue
South Richmond Hill, NY 11419-1902
 
Dear Mr. Laddy:
 
From April 22, 2015, to May 6, 2015, a U.S. Food and Drug Administration (FDA) investigator conducted an inspection of your facility, MasterPharm, LLC at 115-02 Liberty Avenue, South Richmond Hill, NY 11419-1902. This inspection was conducted as a result of a complaint received regarding an adverse event reportedly experienced by a patient who received Trimix injection that was prepared by your firm. 
 
During the inspection, the investigator observed serious deficiencies in your practices for producing sterile drug products, which put patients at risk. For example, our investigator observed that your firm produced sterile (b)(4) from non-sterile components and then stored them in stoppered containers, which were subsequently (b)(4) throughout the assigned expiry period of up to 180 days. Puncturing a container compromises the integrity of the container closure system, and each puncture increases the chances of contamination. In addition, some of these (b)(4) were stored at room temperature in an ISO 7 area that was noted to contain wooden tables and a sink. Wooden tables are difficult to clean and disinfect and may harbor microbial contamination. A sink is a potential source of water-borne microbial organisms and is also difficult to clean and disinfect. The conditions observed at your facility during the inspection represent a potential lack of control for bioburden within your (b)(4) and further (b)(4) sterilization performed by your firm would not remove bacterial endotoxin. This was noted to be of particular concern as some of the drug products you compounded from these (b)(4) were intended for intrathecal administration, and you do not test each of your finished drug products to ensure that the amount of endotoxin is within an acceptable limit.   
 
Our investigator also noted that your firm did not use a sporicidal agent to disinfect the ISO 5 areas. Furthermore, our investigator found that your firm failed to demonstrate through appropriate studies that your aseptic work stations are able to provide adequate protection of the ISO 5 areas in which sterile products are processed. Therefore, your products may be produced in an environment that poses a significant contamination risk.
 
Additionally, FDA testing found bacterial contamination in an unopened vial of Trimix injection prepared by your firm.   
 
A Form FDA 483 was issued to your firm on May 6, 2015. FDA acknowledges your May 26, 2015, response to the Form FDA 483. 
 
Based on this inspection and testing, it appears that you are producing drugs that violate the Federal Food, Drug, and Cosmetic Act (FDCA). 
 
A. Violations of the FDCA
 
Adulterated Drug Products
 
The FDA investigator observed that your drug products 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 FDA investigator noted:
  1. Your firm produced sterile (b)(4) from non-sterile components and then stored them in stoppered containers which were subsequently (b)(4) throughout the assigned expiry period of up to 180 days. Puncturing a container compromises the integrity of the container closure system, and each puncture increases the chances of contamination. In addition, some of these (b)(4) were stored at room temperature in an ISO 7 area that was noted to contain wooden tables and a sink. Wooden tables are difficult to clean and disinfect and may harbor microbial contamination. A sink is a potential source of water-borne microbial organisms and is also difficult to clean and disinfect. The conditions observed at your facility during the inspection represent a potential lack of control for bioburden within your (b)(4), and further (b)(4) sterilization performed by your firm would not remove bacterial endotoxin. This was noted to be of particular concern as some of the drug products you compounded from these (b)(4) were intended for intrathecal administration, and you do not test each of your finished drug products to ensure that the amount of endotoxin is within an acceptable limit.
  1. Your firm did not utilize a sporicidal agent to disinfect the ISO 5 work surfaces. Furthermore, previous environmental monitoring performed by your firm identified a spore-forming organism on one of the ISO 5 work surfaces.
  1. Your firm failed to demonstrate through appropriate studies that your aseptic work stations are able to provide adequate protection of the ISO 5 areas in which sterile products are processed. This was noted to be of particular concern in your non-hazardous cleanroom where the ISO 5 areas have no rigid physical barriers in place separating sterile drug production from other clean room operations.
Therefore, your products may be produced in an environment that poses a significant contamination risk. 
 
In addition, as noted, FDA laboratory analysis found bacterial contamination in an unopened vial of Trimix injection prepared by your firm.  Under section 501(c) of the FDCA [21 U.S.C. § 351(c)], a drug is adulterated if its purity or quality falls below that which it purports or is represented to possess. The presence of bacterial contamination in an unopened vial of your product causes it to be adulterated under section 501(c) of the FDCA.
 
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.
 
Misbranded Drug Products
 
Additionally, the Trimix drug product compounded by your firm was misbranded within the meaning of section 502(a) of the FDCA [21 U.S.C. § 352(a)] because its labeling was false or misleading.  Your Trimix products are labeled as “Injectable”.  As discussed above, an unopened Trimix product sample was bacterially contaminated.  Therefore, the contaminated drug product bearing labeling as “Injectable” is misbranded under section 502(a) of the FDCA because the labeled directions for administration misleadingly imply the product is sterile. 
 
B. Corrective Actions
 
We acknowledge your response to the Form FDA 483 inspectional observations, dated May 26, 2015. Although several of your proposed corrective actions appear adequate, others are deficient. For example, in response to our observation of inadequate smoke studies, you indicated that you have scheduled an outside vendor to undertake and record the recommended testing. However, your response did not include any interim controls put in place or a timeframe for completion of testing.
 
In response to our observation that no sporicidal agent was used to disinfect the ISO 5 areas, you indicated that you have added a sporicidal agent to your routine cleaning and disinfecting of work surfaces. However, it is not clear from your response what the concentration of the sporicidal agent will be and how long the contact time will be to achieve sporicidal disinfection.
 
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. 
 
C. 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. 
 
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 the 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 you cannot complete the corrective actions within 15 working days, state the reason for the delay and the time within which the corrections will be completed. Please address your reply to: 
 
CDR Frank Verni, Compliance Officer
FDA New York District Office
U.S. Food and Drug Administration
158-15 Liberty Avenue
Jamaica, NY 11433
 
If you have questions regarding any issues in this letter, please contact CDR Verni via email at Frank.Verni@fda.hhs.gov or by phone at 718-662-5702.
 
 
Sincerely,
/S/
Ronald Pace
District Director
New York District

Page Last Updated: 03/07/2016
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