Recipient NameDaniel E. Greenleaf
Recipient TitlePresident and CEO
- Infusion Partners, LLC
1600 Broadway, Suite 700
Denver, CO 80202
- Issuing Office:
- Division of Pharmaceutical Quality Operations III
300 River Place, Suite 5900
Detroit, MI 48207
- (313) 393-8100
March 20, 2019
Case # 575451
UPS NEXT DAY
Daniel E. Greenleaf, President and CEO
1600 Broadway, Suite 700
Denver, Colorado 80202
Dear Mr. Greenleaf;
From January 22, 2018, to January 26, 2018, U.S. Food and Drug Administration (FDA) investigators inspected your facility, Infusion Partners, LLC located at 4137 Boardman Canfield Road, Suite L104, Canfield, OH 4406-8087. The investigators noted serious deficiencies in your practices for producing sterile drug products, which put patients at risk.
FDA issued a Form FDA 483 to your firm on January 26, 2018. FDA acknowledges receipt of your facility’s responses, dated February 15, 2018, and August 8, 2018. Based on this inspection, it appears that you produced drug products that violate the Federal Food, Drug, and Cosmetic Act (FDCA).
A. Violations of the FDCA
Adulterated Drug Products
The FDA investigators noted that 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,
1. The design of the ISO 5 area does not appear adequate. The front work areas in your ISO 5 hoods are not directly under the HEPA filters and your smoke study did not demonstrate that these areas are protected by laminar air flow. Your operators were observed to perform aseptic processing in these areas.
2. The HEPA filter guards in the ISO 5 hoods had visible white and rust-colored residue. The HEPA filter guards in the ISO 7 cleanroom had flaking paint and rust-color discoloration.
3. Our investigators observed poor aseptic practices, including an operator frequently moving their entire upper body into the ISO 5 hood during aseptic processing, an operator moving rapidly in the vicinity of the ISO 5 areas, an operator failing to change or disinfect gloves after exiting and re-entering the ISO 5 area, and operators failing to disinfect items when moving them from the unclassified area to the ISO 7 cleanroom via the (b)(4).
4. The (b)(4) between the ISO 7 cleanroom and an unclassified room allowed the influx of unclassified air into your cleanroom. In addition, the (b)(4) had un-sealable doors, exposed particle board, rust-like discoloration, and visible dust.
5. Your firm produced beta-lactam drugs without providing adequate containment and segregation to prevent cross-contamination. Multiple penicillin and cephalosporin drug products were produced in the same positive pressure ISO 5 laminar airflow hoods that are used to produce other injectable drugs, and you did not have adequate procedures to clean potential spills.
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. Furthermore, 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.
B. Corrective Actions
We have reviewed your facility’s responses, dated February 15, 2018, and August 8, 2018. Although some of your proposed corrective actions appear adequate, other corrective actions appear deficient:
1. The smoke study video provided in your response failed to show that the front area of the ISO 5 hood is protected by laminar flow air. In addition, because of the hood design, it is highly likely that aseptic operators may move their upper bodies into the ISO 5 area during aseptic processing, in order to perform aseptic operations under the HEPA filters. Furthermore, your operators may introduce exposed facial skin into the ISO 5 areas when leaning into the hoods.
2. Regarding the (b)(4), you committed to repair or replace the unit. You also stated that “The (b)(4) of the room prevents the influx of poor quality air into the cleanroom.” However, the (b)(4) is not equipped with a HEPA filter, is not monitored continuously for (b)(4), and does not appear to be included in your environmental sampling plan. Therefore, we remain concerned with the use of the (b)(4), even with the (b)(4), as it may allow the influx of poor quality air and potential contamination into the ISO 7 cleanroom used for sterile drug production.
3. Regarding decontamination of hazardous/cytotoxic agents, you provided a revised SOP that includes the use of an oxidizing cleaner. However, it is unclear whether your revised SOP is applicable to spills of penicillin and cephalosporin drugs.
For more information on compounding, please see FDA’s website, at https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/default.htm.
FDA strongly recommends that your management undertake a comprehensive assessment of operations, including facility design, procedures, personnel, processes, maintenance, materials, and systems. In particular, this review should assess your aseptic processing operations. A third-party consultant with relevant sterile drug production expertise should assist you in conducting this comprehensive evaluation.
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 (15) working days of receipt of this letter, please notify this office in writing of the specific steps that 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 you cannot complete corrective action within 15 working days, state the reason for the delay and the time within which you will complete the correction.
Please send your electronic reply to: ORAPHARM3_RESPONSES@fda.hhs.gov.
Attn: Eric Mueller
U. S. Food and Drug Administration
Division of Pharmaceutical Quality Operations III
Refer to the Unique Identification Number (Case# 575451) when replying. If you have questions regarding the contents of this letter, please contact Eric Mueller, Compliance Officer, at (402) 331-8536 ext. 101.
Art O. Czabaniuk
Program Division Director
Division of Pharmaceutical Quality Operations III
Tonya Sutton, General Manager,
Infusion Partners, LLC
4137 Boardman Canfield Rd., Suite Ll04
Canfield, OH 44406-8087