WARNING LETTER
InfuTronix LLC
MARCS-CMS 631050 —
June 16, 2022
Delivery Method:
VIA EMAIL AND UNITED PARCEL SERVICE
Product:
Medical Devices
Recipient:
Recipient Name
Chaoyoung Lee
Recipient Title
CEO & Founder
InfuTronix LLC
177 Pine Street
Natick
,
MA
01760
United States
Issuing Office:
Office of Medical Devices and Radiological Health Operations Div. 1 East
United States
WARNING LETTER
CMS# 631050
June 16, 2022
Dear Dr. Lee:
During an inspection of your firm located at 177 Pine Street, Natick, MA 01760 on January 29, 2022 through February 15, 2022, an investigator from the United States Food and Drug Administration (FDA) determined that your firm is a manufacturer of infusion pumps and associated administration sets, including, but not limited to, the Nimbus II Pain PRO Ambulatory Infusion Pump, Model Number IT1072, the Halo II Ambulatory Infusion System, the Nimbus II Ambulatory Infusion System, and the EVAA Ambulatory Infusion Pump. Under section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. § 321(h), these products are devices because they are intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body.
This inspection revealed that these devices are adulterated within the meaning of section 501(h) of the Act, 21 U.S.C. § 351(h), in that the methods used in, or the facilities or controls used for, their manufacture, packing, storage, or installation are not in conformity with the current good manufacturing practice requirements of the Quality System regulation found at Title 21,
Code of Federal Regulations
(CFR), Part 820. We received an initial response from Lorraine Hanley, VP Global Quality and Regulatory Affairs dated March 8, 2022, along with three updated responses dated April 11, 2022, May 11, 2022, and June 13, 2022, concerning our investigator’s observations noted on the Form FDA 483 (FDA 483), List of Inspectional Observations, that was issued to your firm. We address these responses below, in relation to each of the noted violations. These violations include, but are not limited to, the following:
1. Failure to analyze processes, work operations, concessions, quality audits reports, quality records, service records, complaints, returned product, and other sources of quality data to identify existing and potential causes of non-conforming product, or other quality data problems; and failure to employ appropriate statistical methodology where necessary to detect recurring quality problems, as required by 21 CFR Part 820.100(a)(1). Specifically,
Your firm’s procedure, Quality System SOP: Corrective and Preventive Action (CAPA) Procedure (IT-006-SOP; Rev. J; dated 2/23/2021), includes section 7.1.2 (added to IT-006-SOP under Rev 6; dated 5/16/2019) which states: “appropriate statistical methodology shall be employed when necessary to detect recurring quality problems.” Additionally, section 7.12.1 states: “Any product-related complaint which has been reported ten times over the past rolling 12 months will automatically trigger a CAPA Request”. The Director of Regulatory Affairs and Design Assurance stated during FDA’s inspection that there was no statistical rationale for the threshold of 10 complaints but explained that this threshold was selected after a review of your baseline complaint numbers. Your firm did not follow this process of CAPA initiation for the following:
Approximately 31 complaints reporting battery related issues from September 2020 through August 2021
Approximately 80 complaints reporting power related issues from September 2020 through August 2021
Approximately 20 complaints reporting flow-rate (over/under infusion) issues from June 2020 through May 2021
Approximately 67 complaints reporting administration set leaking issues from August 2020 through December 2020.
Although CAPA IT2021-17 was opened on 09/24/2021 after 104 complaints reporting administration set leaking were received, no corrective actions have been taken as all identified corrective actions remain in-progress.
The adequacy of your firm’s response cannot be determined at this time. We acknowledge your commitments to perform several action items in your March 8, 2022 response related to remediation of this violation including revisions to CAPA related procedures & forms, issuance of new CAPAs for battery-related, power-related, and flow rate issues, performing a retrospective review of CAPAs, and complaint trending to determine the need for additional CAPAs. However, none of your promised actions have been completed and anticipated timeframes for the conduction and completion of your promised actions were still in progress of being finalized as indicated in your most recent June 13, 2022 response. In your response, provide a timeframe for the activities promised as well as the results of activities as they become available. Additionally, please explain how your CAPA procedural requirement that any product-related complaint which has reported ten times over the past rolling 12 months will automatically trigger a CAPA Request is an appropriate statistical methodology as noted in your current SOPs.
2. Failure to adequately establish and maintain procedures for receiving, reviewing, and evaluating complaints by a formally designated unit, as required by 21 CFR § 820.198(a). Specifically,
Your firm’s complaint handling procedure, Quality System SOP: Complaint Handling (IT-004-SOP; Rev. J; dated 2/26/2021), includes the following requirement in section 6.2.5: “Where there is insufficient information to populate the complaint and/or fully understand the event, a CHU Member will contact the complaint reporter in an effort to obtain the missing information.
(b)(4)
. Each attempted communication is documented in the complaint record, including name and date the InfuTronix associate making the attempt.” Your firm did not follow this process of attempting to obtain adequate information to perform review and evaluation of complaints received. The following are examples where the complaint record does not include sufficient information to populate the complaint and/or fully understand the event and no attempted communications are recorded to obtain this information:
Complaint number IT2021N-178, dated 4/21/2021 alleging the pump was off when the patient came in for a disconnect and the patient said they did not turn it off. Your firm does not indicate in the complaint record any attempts to obtain and document any information on whether alerts or alarms sounded prior to the malfunction or any other situation information regarding the complaint.
Complaint number IT2021N-421, dated 9/20/2021 alleging the pump didn’t alarm downstream occlusion. Your firm does not indicate in the complaint record any attempts to obtain and document additional information such as the medication infusing, patient name, or situational details which were expected to lead to the alarm sounding.
Complaint number IT2021v-006, dated 2/22/2021 alleging a crack in the filter of an administration set. Your firm does not indicate in the complaint record any attempts to obtain and document additional information such as the name of medication, patient information, and other situational details such as flow rate programmed at the time of the leak.
The adequacy of your firm’s response cannot be determined at this time. We acknowledge your commitments to perform several actions in your March 8, 2022 response related to remediation of this violation including revisions to your complaint system to include procedures, work instructions, tools and templates, remediation of complaint files having incomplete or no investigations, and a retrospective review of complaints. However, none of your promised actions have been completed and anticipated timeframes for the conduction and completion of your promised actions were still in progress of being finalized as indicated in your most recent June 13, 2022 response. In your response, provide a timeframe for the activities promised as well as the results of activities as they become available.
3. Failure to adequately review, evaluate, and investigate any complaint involving the possible failure of a device to meet any of its specifications, unless such investigation has already been performed and another investigation is not necessary, as required by 21 CFR § 820.198(c). Specifically,
Your firm’s complaint handling procedure, Quality System SOP: Complaint Handling (IT-004-SOP; Rev. J; dated 2/26/2021), includes the following requirement in section 6.3.3: “Any complaint involving the possible failure of a medical device product, labeling, or packaging to meet any of its specifications shall be reviewed, evaluated, and investigated. If an investigation has already been performed for a similar complaint, another investigation may not be required, pending the complaint details. It is the best practice to reference the previous investigation results in the complaint record, as well as noting any important differences between cases.” The following are examples of complaint records reviewed that involved the possible failure of the device to meet specifications and no failure investigation was performed:
Complaint number IT2020N-181, dated 9/24/2020 alleging that seven pumps did not have their library protocols preloaded. However in the investigation/conclusion section of the complaint record it states: “The affected device was not returned. Therefore, no investigation could be performed and no cause could be established” No additional investigation was conducted and no other information is provided in the record that references another investigation performed for a similar complaint.
Complaint number IT2020v-091, dated 12/10/2020 alleging that the catheter became disconnected from the pump. However in the investigation/conclusion section of the complaint record it states: “The affected device was not returned Therefore, no investigation could be performed and no cause could be established.” No additional investigation was conducted and no other information is provided in the record that references another investigation performed for a similar complaint.
Compliant number IT2021v-008, dated 3/5/2021 alleging a loose connection and leaking between the pump connector going to the catheter connector. However in the investigation/conclusion section of the complaint record it states: “The affected device was not returned Therefore, no investigation could be performed and no cause could be established.” No additional investigation was conducted and no other information is provided in the record that references another investigation performed for a similar complaint.
The adequacy of your firm’s response cannot be determined at this time. We acknowledge your commitments to perform several action items in your March 8, 2022 response related to remediation of this violation including revisions to your complaint system to include procedures, work instructions, tools and templates, remediation of complaint files having incomplete or no investigations, and a retrospective review of complaints. However, none of your promised actions have been completed and anticipated timeframes for the conduction and completion of your promised actions were still in progress of being finalized as indicated in your most recent June 13, 2022 response. In your response, provide a timeframe for the activities promised as well as the results of activities as they become available.
Our inspection also revealed that your firm’s Nimbus II PainPRO Ambulatory Infusion Pump, Model Number IT1072, devices are misbranded under section 502(t)(2) of the Act, 21 U.S.C. § 352(t)(2), in that your firm failed or refused to furnish material or information respecting the device that is required by or under section 519 of the Act, 21 U.S.C. § 360i, and 21 CFR Part 806 – Medical Devices; Reports of Corrections and Removals. Significant violations include, but are not limited to, the following:
Failure to submit any report required within 10‐working days of initiating such correction or removal, as required by 21 CFR § 806.10. Specifically,
Your firm failed to submit a written report to FDA regarding the correction that your firm made to 74 Nimbus II PainPro H Ambulatory Infusion Pumps that contained an unreleased library configuration. Your firm issued a customer letter on October 19, 2021 after you were made aware that the unreleased Version 4 Protocol Library was installed on a customer’s Nimbus PainPro (H) infusion pumps. Your firm did not report this removal to FDA based on a calculated hazard/risk index of none/negligible but stated in the customer letter this error may impact patient safety. Therefore, your firm should have submitted a Report of Correction or Removal to FDA.
The adequacy of your firm’s response cannot be determined at this time. FDA received the Report of Correction or Removal for the noted action on March 9, 2022. Your response does not list the actions taken or planned by your firm to ensure that all corrections or removals which are required to be reported to FDA are reported for past or future events. In your response, please explain how your firm has or plans to determine if other corrections and removals were not reported to FDA as required by 21 CFR Part 806.
Our inspection (also) revealed that your firm’s Nimbus II PainPRO Ambulatory Infusion Pump, Model Number IT1072, devices are misbranded under section 502(t)(2) of the Act, 21 U.S.C. § 352(t)(2), in that your firm failed or refused to furnish material or information respecting the device that is required by or under section 519 of the Act, 21 U.S.C. § 360i, and 21 CFR Part 803 - Medical Device Reporting. Significant violations include, but are not limited to, the following:
Failure to adequately develop, maintain and implement written MDR procedures, as required by 21 CFR 803.17. Specifically, during the review of your MDR procedure, the following deficiencies were noted:
1. The procedure does not establish internal systems that provide for timely and effective identification, communication and evaluation of events that may be subject to MDR requirements, as required by 21 CFR 803.17(a)(1). For example, the procedure does not include instructions for how the firm will evaluate information about an event to make MDR reportability determination in a timely manner.
2. The procedure does not establish internal systems that provide for timely transmission of complete medical device reports, as required by 21 CFR 803.17(a)(3). For example, the procedure does not include how your firm will ensure that all information reasonably known to it is submitted for each event. Specifically, which sections of the Form 3500A will need to be completed to include all information found in the firm’s possession and any information that becomes available as a result of a reasonable follow up within the firm.
3. The procedure does not describe how your firm will address documentation and record-keeping requirements, as required by 21 CFR 803.17(b), including:
documentation of adverse event related information maintained as MDR event files;
documentation of the deliberations and decision-making processes used to determine if a device-related death, serious injury or malfunction was or was not reportable, as required by 21 CFR 803.18(b)(1)(i); and
systems that ensure access to information that facilitates timely follow-up and inspection by FDA.
The adequacy of your response dated March 8, 2022, cannot be determined at this time. The response noted that your firm will revise its MDR procedure to better define the reportability process and will conduct a retrospective review of complaints in accordance with newly revised procedures. However, your firm did not provide documentation or evidence of the systemic corrective actions as they are still presently ongoing.
The responses dated April 11, May 11, and June 13, 2022, did not address the deficiencies noted above.
Our inspection also revealed that the InfuTronix Administration Sets (various configurations) are adulterated under section 501(f)(1)(B) of the Act, 21 U.S.C. § 351(f)(1)(B), because your firm does not have an approved application for premarket approval (PMA) in effect pursuant to section 515(a) of the Act, 21 U.S.C. § 360e(a), or an approved application for an investigational device exemption under section 520(g) of the Act, 21 U.S.C. § 360j(g). The devices are also misbranded under section 502(o) the Act, 21 U.S.C. § 352(o), because your firm did not notify the agency of its intent to introduce the device into commercial distribution, as required by section 510(k) of the Act, 21 U.S.C. § 360(k).
Specifically, your firm made significant labeling and design changes to the administration set after FDA’s clearance of that device on August 30, 2016 (
(b)(4)
). For example, the proposed labeling in the premarket notification (510(k)) for the “Halo II Ambulatory Infusion System (also with trade names Nimbus II Ambulatory Infusion System; EVAA Ambulatory Infusion System)” contained the following description of the single approved administration set to be used as part of the infusion pump system:
PART #
Administration set description
(b)(4)
(b)(4)
In addition, your firm made significant changes to the Administration sets, by introducing in the market additional set configurations with the following modifications from the set cleared in
(b)(4)
:
•
(b)(4)
;
•
(b)(4)
•
(b)(4)
.
(b)(4)
could significantly affect the fluid flow rate that could result in over or underdosing of infused drugs. Further, the replacement of a traditional
(b)(4)
could affect the compatibility and connections of the administrations sets with the pump and other devices. Thus, these changes could significantly affect the safety or effectiveness of the device and require the submission of a new 510(k).
For a device requiring premarket approval, the notification required by section 510(k) is deemed satisfied when a PMA is pending before the agency. [21 CFR 807.81(b)] The kind of information that your firm needs to submit in order to obtain approval or clearance for the device is described on the Internet at
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/default.htm
. The FDA will evaluate the information that your firm submits and decide whether the product may be legally marketed.
This letter notifies you of our findings and provides you an opportunity to address the circumstances above. Failure to adequately address this matter may result in regulatory action being initiated by the FDA without further notice. These actions include, but are not limited to, seizure, injunction, and civil money penalties.
Other federal agencies may take your compliance with the FD&C Act and its implementing regulations into account when considering the award of federal contracts. Additionally, should FDA determine that you have Quality System regulation violations that are reasonably related to premarket approval applications for Class III devices, such devices will not be approved until the violations have been addressed. Should FDA determine that your devices or facilities do not meet the requirements of the Act, requests for Certificates to Foreign Governments (CFG) may not be granted.
Please notify this office in writing within fifteen business days from the date you receive this letter of the specific steps your firm has taken to address the noted violations, as well as an explanation of how your firm plans to prevent these violations, or similar violations, from occurring again. Include documentation of the corrections and/or corrective actions (which must address systemic problems) that your firm has taken. If your firm’s planned corrections and/or corrective actions will occur over time, please include a timetable for implementation of those activities. If corrections and/or corrective actions cannot be completed within fifteen business days, state the reason for the delay and the time within which these activities will be completed. Your firm’s response should be comprehensive and address any violations included in this Warning Letter. If you believe that your products are not in violation of the FD&C Act, include your reasoning and any supporting information for our consideration as part of your response.
Your firm’s response should be sent to: Gina Brackett, Director of Compliance Branch, at oradevices1firmresponse@fda.hhs.gov. Refer to CMS # 631050 when replying. If you have any questions about the contents of this letter, please contact: Sean Moynihan at 410-779-5134 or sean.moynihan@fda.hhs.gov.
Finally, you should know that this letter is not intended to be an all-inclusive list of the violations at your firm’s facility. It is your firm’s responsibility to ensure compliance with applicable laws and regulations administered by FDA. The specific violations noted in this letter and in the Inspectional Observations, FDA 483, issued at the close of the inspection may be symptomatic of serious problems in your firm’s manufacturing and quality management systems. Your firm should investigate and determine the causes of any violations and take prompt actions to address any violations and bring the products into compliance.
Sincerely,
/S/
Courtney H. Lias, Ph. D.
Director, OHT 3: Office of
Office of GastroRenal, ObGyn,
General Hospital and Urology Devices
Office of Product Evaluation and Quality
Center for Devices and Radiological Health
/S/
Joseph Matrisciano, Jr.
Program Division Director
Office of Medical Device and Radiological Health
Division 1 - East
Content current as of:
08/09/2022
Regulated Product(s)
Medical Devices