Inspections, Compliance, Enforcement, and Criminal Investigations

Tri-Med, Inc. dba Advanced Care Infusion-Shelby 12/18/15

  

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

Public Health Service
Food and Drug Administration
 Detroit District
300 River Place
Suite 5900
Detroit, Ml 48207
Telephone: 313-393-8100
FAX: 313-393-8139 

 

WARNING LETTER
2016-DET-04
 
 
December 18, 2015
 
 
VIA UPS
 
 
Dr. William C. Drake, PharmD
President
Tri-Med, Inc. (dba Advanced Care Infusion – Shelby)
50860 Corporate Drive, Suite 100
Shelby Township, MI 48315-3123
 
Dear Dr. Drake:
 
From February 12, 2015, to February 23, 2015, a U.S. Food and Drug Administration (FDA) investigator conducted an inspection of your facility, Tri-Med, Inc. (dba Advanced Care Infusion – Shelby), located at 50860 Corporate Drive, Suite 100, Shelby Township, MI 48315-3123.
 
During the inspection, the investigator observed serious deficiencies in your practices for producing sterile drug products, which put patients at risk. For example, our investigators observed an operator touching non-sterilized items located outside the ISO 5 area and returning to the ISO 5 area to manipulate sterile products without sanitizing gloves. Your firm did not take remedial action when viable air samples tested positive for bacteria and fungus on various dates in your ISO environment. In addition, your aseptic processing areas were noted to contain hard surfaces that are not easily cleanable such as painted cinderblocks with many small pits and crevices, the ceiling tiles are not all fully sealed, and small gaps in the ceiling were observed by our investigators. Your firm failed to provide evidence that you can ensure pressure differentials are maintained between areas of higher and lower air cleanliness so that air flows from higher air quality areas to lower air quality areas and not the reverse. Furthermore, our 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. 
 
A Form FDA 483 was issued to your firm on February 23, 2015. Based on this inspection, 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 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. Examples of insanitary conditions observed during our inspection include: 
  1. Your operator touched non-sanitized equipment located outside of the ISO 5 laminar flow hood (LFH) area with their gloved hands and the operator’s gloves were not always appropriately sanitized with sterile (b)(4) before the operator’s gloved hands were placed under the ISO 5 LFH to perform aseptic manipulations.
  1. Your firm found fungus in the Buffer Room (ISO7) on July 9, 2014 and did not identify the fungus and did not perform immediate remediation or an investigation into the cause.
  1. Your firm’s walls consisted of painted cinderblock with many small pits and crevices making these surfaces difficult to clean and disinfect. In addition, the ceiling tiles were not all fully sealed and visible gaps in the ceiling tiles of the aseptic processing area were present.
  1. Your firm’s HVAC system for the ISO 7 and ISO 8 rooms do not facilitate an adequate number of air changes per hour and does not provide adequate pressure differentials between areas of higher and lower air cleanliness. Specifically, your firm failed to assure that the clean rooms air supply is being properly filtered through HEPA filters and that positive pressure differential is maintained between the ISO 7 and ISO 8 rooms and between the ISO 8 and unclassified area.
  1. Your firm failed to demonstrate through appropriate studies that the ISO 5 LFH is able to provide adequate protection of the area in which products intended or expected to be sterile are processed.  Specifically, your firm did not perform smoke studies under dynamic conditions to verify that there is no obstruction or alteration of laminar air flow that may contaminate the product.
B. Corrective Actions
 
In your response to the Form FDA 483, dated March 12, 2015, you state that your firm “is a pharmacy that prepares doses pursuant to a valid prescription for an individual patient,” and “meets USP< 797> guidelines.” Please be aware that compounded drug products that qualify for the exemptions in section 503A remain subject to all other applicable provisions of the FDCA, including the requirement that the drug products are not prepared, packed, or held under insanitary conditions (section 501(a)(2)(A) of the FDCA). 
 
While several of your proposed corrective actions that address the identified insanitary conditions appear adequate, others are deficient. The review of your response identified the following deficiencies. You indicated that you will implement a (b)(4). However, your response does not include any information on the type of training that will be done, who will be conducting the training of the staff, and any interim controls until the training is completed if operations are to continue. In addition, your firm’s response does not include any documentation or evidence that the air supply within the clean room area is adequately filtered through the HEPA filters, nor does it include copies of the updated Standard Operating Procedures, or the expected date the clean room will be certified under dynamic conditions. Meanwhile, your firm continues to operate as sterile drug producer with no interim controls to ensure the quality and safety of your sterile drug products until the certification is completed. Finally, your firm committed to (b)(4). However, your firm provided no interim controls on the lack of cleanable floors, walls and ceilings for your clean rooms where sterile drug products continue to be produced.
 
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 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 if you have taken any specific steps 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 corrections will be completed.
 
Your written notification should be addressed to:
 
Cicely Vaughn, Compliance Officer
FDA Detroit District Office
U.S. Food and Drug Administration
300 River Place, Suite 5900  
Detroit, MI 48207
 
If you have questions regarding any issues in this letter, please contact Mrs. Vaughn via email at cicely.vaughn@fda.hhs.gov or by phone at 313-393-8297.
 
Sincerely,
/S/ 
Art Czabaniuk
District Director
Detroit District Office

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