WARNING LETTER
Puget Sound Drug Corporation dba Key Pharmacy and Compounding Center MARCS-CMS 552431 —
- Recipient:
- Puget Sound Drug Corporation dba Key Pharmacy and Compounding Center
United States
- Issuing Office:
- Los Angeles District Office
United States
| |
Division of Pharmaceutical Quality Operations IV 19701 Fairchild Road Los Angeles, CA 92612 |
WARNING LETTER
VIA UNITED PARCEL SERVICE
SIGNATURE REQUESTED
CMS# 552431
April 4, 2018
HeeJoo Park
Owner and Chief Executive Officer
Puget Sound Drug Corporation
dba Key Compounding Pharmacy
530 S. 336th Street
Federal Way, WA 98003
Dear Ms. Park:
From January 26, 2017, to March 8, 2017, U.S. Food and Drug Administration (FDA) investigators inspected your facility, Puget Sound Drug Corporation, dba Key Compounding Pharmacy, located at 530 S. 336th Street Federal Way, WA 98003. During the inspection, the investigators noted serious deficiencies in your practices for producing sterile and non-sterile drug products, which put patients at risk.
FDA issued a Form FDA 483 to your firm on March 8, 2017. FDA acknowledges receipt of your facility’s responses, dated March 24, 2017, and June 2, 2017. FDA also acknowledges your action on March 31, 2017, to voluntarily recall all sterile drug products produced between November 16, 2016, and January 26, 2017, and your action on April 13, 2017, to extend the recall through February 23, 2017.
Based on this inspection, it appears that you produced drug products that violate the FDCA.
A. Violations of the FDCA
Adulterated Drug Products
The FDA investigators noted that both non-sterile drug products and 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 investigators noted that:
1. Your firm continued to produce and distribute drug products intended to be sterile even after identifying instances of microbial contamination in your ISO-5 and ISO-7 areas.
2. Your firm’s cleaning and disinfecting procedures and practices are inadequate for aseptic processing. Specifically, our investigators observed operators using non-sterile wipes to clean the surface of the ISO-5 work area during sterile drug production; preparing a sterile drug product in an ISO-5 hood containing a soiled mop head; preparing a sterile drug product in an ISO-5 hood without first cleaning the hood’s interior ceiling or return grate; and using an expired cleaning agent to clean the floors, walls, and surfaces of the ISO-5, ISO-7, and ISO-8 areas.
3. Your firm engaged in poor aseptic practices during the production of drug products intended to be sterile. Specifically, the investigators observed that operators failed to disinfect or change gloves frequently enough to prevent contamination. One of the operators was observed to don sterile gloves, sanitize the ISO-5 hood, and then clean the outer packaging of containers and closures. However, the same operator began sterile drug preparation without re-sanitizing or changing his/her gloves.
4. Your firm handled hazardous drugs without providing adequate cleaning of equipment and personnel to prevent cross contamination with other products being compounded in your pharmacy. Specifically, an operator was observed blowing air directly onto equipment in a powder hood, dispersing the powdered residue throughout the hood area; failing to clean visible particulate residues from the ceiling of the powder hood; allowing the sleeves of his/her lab coat to come in contact with apparent hazardous drug residue on the surface of the powder hood without changing lab coats between preparations of different products for up to one week; and cleaning the powder hood with tap water and 70% isopropyl alcohol with no data to support the procedure’s effectiveness in neutralizing hazardous drug residue.
5. Your firm’s aseptic practices are deficient regarding the system for maintaining an environment suitable for production of a sterile drug. Specifically, the investigators observed cardboard boxes in the ISO 7 compounding room, as well as operators passing a paper note pad through the ‘(b)(4)’ between the ISO 7 compounding room and the ISO 8 preparation room; both of which are a potential source of contamination.
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.
B. Corrective Actions
We have reviewed your firm’s responses to the Form FDA 483. We acknowledge your recall on March 31, 2017, and its extension on April 13, 2017, of all aseptically produced drug products within expiry.
Regarding the insanitary conditions observed during the inspection, some of your corrective actions appear to be adequate. However, we are unable to fully evaluate the following corrective actions due to a lack of adequate supporting documentation:
1. In response to our observation regarding inadequate procedures for cleaning aseptic processing areas and equipment, you stated that your firm began using sterile wipes in January 2017, but were observed using non-sterile wipes on February 22, 2017, because you ran out of the sterile wipes. Our review of SOP # 3.02 Cleaning and Maintenance of the Cleanroom Facility (submitted as attachment 3 to your written FDA-483 response, dated March 24, 2017)found it references the use of both sterile and non-sterile wipes and does not specify where and when the use of sterile wipes is required. Additionally, your response does not explain what, if any, steps have been taken to prevent a reoccurrence. In addition, in your response to our observation regarding the use of an expired cleaning agent, you stated that you discarded the expired cleaning agent and replaced it with new product. However, your response does not explain what, if any, steps have been taken to prevent a reoccurrence.
2. In response to our observation regarding your firm’s failure to disinfect or change gloves frequently enough to prevent contamination, you revised SOP # 1.04 titled General Aseptic Technique and implemented an updated assessment form titled Assessing Aseptic Technique and Related Practices for Compounding Personnel. However, you did not provide a copy of the written procedure and you did not provide any additional information specifically describing hand hygiene and sanitization procedures.
3. In response to our observation regarding your firm’s failure to maintain an environment suitable for the production of sterile drugs, you stated that paper and cardboard had been removed from the ISO-7 area. You noted that SOP # 3.01 titled Sterile Compounding Area Requirements was revised on May 1, 2017; however, you did not include a copy of the revised written procedure for evaluation. Additionally, your response suggests that the movement of paper notes between the ISO-7 compounding room and ISO-8 preparation room was an isolated instance, due in part to the fact that the batteries in your walkie-talkies had died. However, you have not provided adequate information to ensure this deficiency has been adequately corrected.
The following corrective actions appear inadequate to address the insanitary conditions noted:
1. In response to our observation regarding microbial contamination, you indicated that you increased the frequency of environmental monitoring and would use the data to establish appropriate environmental monitoring alert and action levels. However, you did not submit a copy of an updated version of your environmental monitoring procedure, so we cannot verify if appropriate alert and/or action levels have been established. You also noted the implementation of an updated cleaning procedure on January 11, 2017. However, you have not provided environmental monitoring data to support the effectiveness of those procedures. In fact, environmental samples collected by FDA microbiologists from inside the ISO-5 hood on February 22, 2017 were positive for microbial growth. We remain concerned with the effectiveness of your cleaning procedures and aseptic practices.
2. In response to our observation that you failed to handle highly potent drugs so as to prevent cross-contamination, you stated that there was a HEPA filtered air system running when air was blown into the hood containing powdered residue. In addition, your response notes that you had revised SOP # 3.05 titled Cleaning and Maintenance of the Non-Sterile Compounding Area, and that you are planning a renovation of your facility to comply with USP 800> requirements. However, your response does not describe methods to prevent cross-contamination until that project is complete. And while you reference the implementation of revised cleaning procedures, you did not provide any data to support the effectiveness of those procedures in neutralizing hazardous and/or potent drugs. Also, you did not include a copy of SOP 3.05 Cleaning and Maintenance of the Non-Sterile Compounding Area for evaluation. Lastly, although you stated that SOP 9.13 Required Garb for Non-Sterile Compounding Area has been revised, in part, to require gowns used in non-sterile compounding be changed daily, there is no requirement for them to be changed between preparations of different drug products. Also, you did not include a copy of the revised SOP 9.13 for evaluation.
Please be aware that section 501(a)(2)(A) of the FDCA concerning insanitary conditions applies regardless of whether drug products you compound meet the conditions of section 503A.
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 processing expertise should assist you 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 (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 address your reply to:
CDR Steven E. Porter, Jr.
Director, Division of Pharmaceutical Quality Operations IV
United States Food and Drug Administration
19701 Fairchild
Irvine, California 92612
If you have any questions about the content of this letter, please contact Jessica Mu, Compliance Officer, at 949-608-4477 and reference unique identifier CMS 552431 on all correspondence.
Sincerely,
/S/
CDR Steven E. Porter, Jr.
Director, Division of Pharmaceutical Quality Operations IV