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WARNING LETTER
CMS: 621738

February 11, 2022

Dear Mr. Platt,

During an inspection of your firm located in College Station, TX from August 19, 2021 through September 17, 2021, an Investigator from the United States Food and Drug Administration (FDA) observed that your firm manufactures a cardiac heater-cooler product in various configurations. Under section 201(h)(1) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. § 321(h)(1), each of these products is a device because it is an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, which is 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.

We received a written response from you dated October 4, 2021, 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 this response below, in relation to each of the noted concerns. These concerns include, but are not necessarily limited to, the following:

Your firm currently holds a 510(k) clearance (K102147) for the CardioQuip Modular Cooler-Heater Model MCH-1000 device (“MCH-1000 Device”), which was issued on November 19, 2010. However, since the time it was cleared, the MCH-1000 Device has been, in multiple ways, significantly changed or modified in design, components, method of manufacture, or intended use within the meaning of 21 CFR 807.81(a)(3). Specifically, your firm has made significant changes that include, among other things, the addition of an optional airflow hood, a dripless external hose kit, and thermoelectric cooling technology in certain MCH models. The addition of an optional airflow hood is intended to reduce the risk of infection via aerosolization of contaminated water. The airflow hood impacts how potentially contaminated water droplets are dispersed in the operating room.

The addition of a dripless antimicrobial external hose kit modifies the same risk by attempting to mitigate biofilm and water-borne pathogen buildup in the hose kit. The final significant change outlined in this warning letter, the addition of thermoelectric cooling technology, is a major operating principle change as the original 510(k) (K102147) was cleared with the use of optional compressor cooling and not thermoelectric cooling. These and other changes could significantly affect the safety or effectiveness of the device within the meaning of 21 CFR 807.81(a)(3). Accordingly, your firm was required to submit a new premarket notification submission under section 510(k) of the Act, 21 U.S.C. § 360(k), to FDA at least 90 days before you proposed to begin the introduction or delivery for introduction into interstate commerce for commercial distribution of the modified Modular Cooler-Heater devices (“Modified MCH Devices”). (See 21 CFR 807.81(a)(3).)

You did not submit any new 510(k) in association with the Modified MCH Devices despite your statement made October 4, 2021, in your written response, that your firm is (b)(4) The Modified MCH Devices are therefore misbranded under section 502(o) the Act, 21 U.S.C. § 352(o), because your firm did not timely notify FDA of its intent to begin the introduction or delivery for introduction into interstate commerce for commercial distribution of the Modified MCH Devices, as required by section 510(k) of the Act.

Our inspection revealed that the Modular Cooler-Heater (MCH) devices are also 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).

For a device requiring premarket approval, the notification required by section 510(k) of the Act, 21 U.S.C. § 360(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.

Our inspection also 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. These deficiencies include, but are not limited to, the following:

1. Failure to establish and maintain adequate procedures to control the design of the device in order to ensure that specified design requirements are met, as required by 21 CFR 820.30(a). Specifically, your firm has not adequately controlled and documented the design of your MCH devices. Specifically,

a. Your firm has not adequately conducted design validation for your MCH devices as required by 21 CFR 820.30(g) or validated changes as required by 21 CFR 820.30(i). For example,

i. Your firm changed your specification for microbial load measured by heterotrophic plate count (HPC) from (b)(4) CFU/ml to (b)(4) CFU/ml and removed requirements for (b)(4) testing. Your firm did not validate this change to ensure that it meets the intended uses for the device.

ii. On March 3, 2020, your firm added an optional airflow hood to your MCH devices intended to redirect the flow of exhaust air downward. Your firm did not validate this change to ensure that it meets the intended use of the device. Your firm’s validation of this change only addressed impact to temperature of the unit. The change validation did not address impact to potential microbiological infection to patients.

iii. Your firm modified the external tubing of your device between November 23, 2015 and November 11, 2016 to change to a PVC antimicrobial tubing. However, your firm did not adequately document or validate this change. Your firm conducted microbial testing between November 24, 2015 and February 3, 2016 as a water quality comparison when using the old hose and the antimicrobial hose. However, your firm’s testing was not conducted to an approved protocol that identified full test methods, sample methods, acceptance criteria, or support for sample sizes.

iv. On July 29, 2016, you effected a change to the MCH-1000 Mini allowing for optional refrigeration technology using (b)(4) technology. This change was not validated.

b. Your firm has not adequately conducted risk analysis for your MCH devices, as required by 21 CFR 820.30(g). Specifically, your firm added a new hazard of “Bacteria such as m. chimaera or other biological agents being aerosolized into patient environments” to your MCH-10ARH Risk Assessment document on August 6, 2021; however, your firm has been aware of this hazard since at least 2018. Additionally, this hazard has not been considered as part of your design activities, see item “a” above.

c. Your firm failed to establish and maintain adequate procedures to ensure that the design requirements relating to a device are appropriate and address the intended use of the device, including the needs of the user and patient, as required by 21 CFR 820.30(c). For example, some of your design inputs are ambiguous and do not align with known risks and user needs.

i. Design input #001-DI-02, titled “Cleanability,” states “(b)(4)” and documents the Target Specification as “(b)(4)”. This design input does not establish a specific target criteria for cleanliness.

ii. Design input #001-DI-10, titled “Device Stability,” states “(b)(4)” and documents the Target Specification as “(b)(4)”. This design input does not define “easily”.

iii. Design input #001-DI-32, titled “Air Exhaust Vent on Cooling Unit,” states “(b)(4),” and documents the Target Specification as “(b)(4).” This design input does not address potential impact on exhaust air disruption of the cleanroom environment which is one of your firm’s identified risks.

2. Failure to ensure that when the results of a process cannot be fully verified by subsequent inspection and test, the process shall be validated with a high degree of assurance and approved according to established procedure, as required by 21 CFR 820.75(a). Specifically,

Your firm has not validated your cleaning processes recommended in your product manuals and utilized during servicing of your devices. Your firm conducted HPC testing on water samples collected pre- and post-cleaning in February 2016 and March 2017; however, these tests do not have the necessary information to support that the process consistently meets specification. For example, the records do not identify sample collection methods, sample sizes, disinfectant residue, or acceptance criteria.

We acknowledge your firm has initiated CAPA 63 to address deficiencies with process validations to include your cleaning processes. However, your firm has not provided evidence you have completed an adequate validation of your cleaning processes. Additionally, your response does not include a systemic review of your processes to verify that all processes requiring validation have been validated.

3. Failure to establish and maintain procedures for implementing corrective and preventive action, as required by 21 CFR 820.100(a). For example,

a. Your firm initiated CAPA 77 in response to an increase of complaints for device contamination with NTM on December 14, 2020. Your firm closed this CAPA on June 2, 2021. However, the CAPA does not show your firm accurately investigated the cause of this quality problem. Your CAPA records state your firm has not linked your device to patient infection; however, your firm has reported events in which you confirmed your device was linked to infection. Additionally, your firm identified revisions to your cleaning procedures as a corrective action for this CAPA. However, your firm has not validated these cleaning procedures despite the closure of this CAPA.

b. Your firm initiated CAPA 63, on August 6, 2020, to address lack of validation of your MCH cleaning processes. Your firm has not yet validated your cleaning process despite this CAPA being open for over 15 months.

c. Your firm initiated CAPA 2018-027 on January 29, 2018 to address complaints associated with leaking MCH devices. Your firm determined the cause of this issue involved tolerance stacking with certain device specifications when manufactured at the edges of your specification limits. Your firm determined to add a bushing to the device to address this issue. However, the CAPA record does not include documentation to show this change was affected or verification activities to show this corrected the quality problem. Additionally, the CAPA states this corrective action was not feasible on the MCH 1000(m) and it does not identify what corrective actions if any were taken for those devices. Lastly, your CAPA record states the effectiveness checks for this CAPA would include monitoring of complaints over time; however, there is no record of this having been conducted in relation to this CAPA. This CAPA was closed on, or about, August 15, 2018.

4. Failure to maintain complaint files and establish and maintain adequate 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 Procedure”, CQ-SOP-12 Ver 11, dated January 7, 2021 is inadequate. Specifically, your procedure does not provide adequate details to ensure complaints are processed in a uniform and timely manner. Your complaint procedures do not define what methods of investigation may be used when conducting investigations under 21 CFR 820.198(e). Additionally, section 7.9 of your procedure requires a complaint committee to review complaints against your risk analysis procedures. However, the procedure does not provide clear instruction on the frequency and scheduling of these reviews. For example,

a. Your firm received 11 complaints on July 28, 2021 in which a hospital reported finding bacterial contamination on several of your MCH devices. Your firm’s complaint records assert these isolates did not match the environmental and patient isolates and therefore further investigation was not conducted. However, your firm did not investigate the level of contamination or the cause of the contamination. All of these complaints were subsequently reported under 21 CFR 803.

b. Your firm received complaint DI-13886 on January 29, 2021 which alleged biofilm buildup in the tubing of a MCH device. The risk assessment section of this complaint record states, “No change in risk as the device did not malfunction and no new risk identified.” However, your firm’s current risk matrix “MCH-1000” dated June 11, 2021 does not identify biofilm growth. Additionally, risks associated with bacterial contamination were not added until April 1, 2021. Your complaint record is unclear as to what risk evaluations were conducted as part of this complaint’s risk assessment.

c. Your firm received complaint DI-13930 on March 15, 2021 involving an alleged patient infection. This complaint does not include an Investigation Questionnaire which your firm provides to some complainants to obtain information associated with the alleged event. Your firm’s Director of Quality and Regulatory acknowledged this was an oversight. “Complaint Procedure”, CQ-SOP-12 Ver 11, dated January 7, 2021 does not address the use of your “Investigation Questionnaire” form.

Our inspection also revealed that your firm’s MCH 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 concerns include the following:

1. Failure to submit a report to FDA no later than 30 calendar days after the day that the firm received or otherwise became aware of information, from any source, that reasonably suggests that a device that the firm markets has malfunctioned and this device or a similar device that it markets would be likely to cause or contribute to a death or serious injury, if the malfunction were to recur, as required by 21 CFR 803.50(a)(2).

a. For example, the information included for #DI-14346 reasonably suggests that your firm’s MCH malfunctioned in that the water level sensor did not function as designed. Such malfunction resulted in a fire inside the unit that burned out device components. The service form states that the PVC assemblies were burnt out and inoperable due to the fire inside the unit. The fire department was called. A device malfunction that results in fire, and burning of the device components, represents a malfunction that would be likely to cause or contribute to a death or serious injury, if it were to recur. As such, the referenced complaint meets the definition of a reportable malfunction, as defined in 21 CFR 803.3. The date your firm became aware of the event was October 28, 2020. However, no MDR for the referenced complaint has been received by FDA.

We have reviewed your firm’s response dated October 4, 2021. While acknowledging the “need” for your firm to make “improvements,” your response contains insufficient detail or supporting records to show these corrective actions will be adequate to address any violations or planned timeframes for their completion.

We request that your firm immediately cease any activities that result in the misbranding or adulteration of the MCH devices, such as their commercial distribution as discussed above.

We further request in response to this letter you provide a more comprehensive corrective action plan. Please include supporting records to show completion of your corrective actions and timeframes for ongoing corrections. Additionally, we request you continue to provide ongoing updates to these actions monthly through completion of all corrective actions.

This letter notifies you of our concerns and provides you with an opportunity to address them. Your firm should take prompt action to correct any violations. If you believe that your products are not in violation of the FD&C Act, please provide your reasoning and any supporting information for our consideration within 15 days.

Failure to adequately address the matters discussed in this letter may result in legal action being initiated by the FDA without further notice. These actions may include, but are not necessarily limited to, seizure, injunction, and civil money penalties. Other federal agencies may take your compliance history into account when considering the award of contracts. 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 corrected. Should FDA determine that your devices or facilities do not meet the requirements of the FD&C Act, requests for Certificates to Foreign Governments (CFG) may not be granted. More information on processes for persons denied a CFG can be found at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/process-request-review-fdas-decision-not-issue-certain-export-certificates-devices.

We ask that you 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 concerns noted in this letter. Include documentation of any corrections and/or corrective action (which must address systemic problems) that your firm has taken. If any corrections and/or corrective actions your firm plans to take will require more time, please include a timetable for implementation of those activities. If any corrections and/or corrective actions your firm plans to take cannot be completed within fifteen business days, state the reason for requiring additional time and the time within which these activities will be completed. Please provide a translation of documentation not in English to facilitate our review. We will communicate with you regarding your firm’s response(s) and any need to re-inspect your firm’s facility to verify that any appropriate corrections and/or corrective actions have been made.

Your firm’s response should be sent to: US Food and Drug Administration, Division 3/West, Office of Medical Device and Radiological Health Operations at ORADevices3 [email protected]. Please identify your response with FEI 3007899424.

If you have any questions about the contents of this letter, please contact Compliance Officer Jeff R. Wooley at 214-253-5251, or via e-mail at [email protected].

Finally, you should know that this letter is not intended to provide an all-inclusive list of any deficiencies at your firm’s facility or associated with your firm’s devices. It is your firm’s responsibility to ensure compliance with applicable laws and regulations administered by FDA. The specific concerns noted in this letter and in the Inspectional Observations, FDA 483, issued at the close of the inspection may be indicative of, or in addition to, other issues with your firm’s devices, manufacturing, and quality management systems. Your firm should investigate and determine the causes of any deficiencies and take prompt actions to correct any violations and bring the products into compliance.

Sincerely,
/S/

Bram Zuckerman, M.D.
Director
OHT 2: Office of Cardiovascular Devices
Office of Product Evaluation and Quality
Center for Devices and Radiological Health

/S/

Shari J. Shambaugh
Program Division Director
Office of Medical Device and Radiological
Health, Division 3