WARNING LETTER

Spectrum Medical Ltd MARCS-CMS 666543 — September 29, 2023

Delivery Method:: Via Email
Product:: Medical Devices

Recipient:: Recipient Name

Steve Turner; Recipient Title

Chief Executive Officer; Spectrum Medical Ltd; Harrier 4, Meteor Business Park, Cheltenham Road East
Gloucester, Gloucestershire
GL2 9QL
United Kingdom

Issuing Office:: "OHT2: Office of Cardiovascular Devices, Office of Product Evaluation and Quality"; United States

WARNING LETTER

September 29, 2023

Dear Mr. Turner:

During an inspection of your firm located at Harrier 4, Meteor Business Park, Cheltenham Road East, Gloucester, Gloucestershire, GL2 9QL United Kingdom on April 24, 2023 through April 27, 2023, an investigator from the United States Food and Drug Administration (FDA) determined that your firm is a medical device manufacturer of the Quantum Perfusion Systems family of devices, which include, but are not limited to, Quantum Oxygenators, Quantum SuperPAC tubing sets and cannulas, Quantum Perfusion Roller Pumps, Quantum Pump Frames, Quantum Power Supplies, Quantum Ventilation Modules, Quantum Smart Occluders, Quantum PureFlow Centrifugal Drives, and Quantum Heater Cooler. 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.

We received a response from you, dated May 5, 2023, 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 violations.

Unapproved-Device Violations

FDA has reviewed your firm’s U.S. promotional material and user manuals for your Quantum Perfusion devices that were collected during the inspection and determined that, based on the labeling changes in the promotional material and user manuals, your firm markets several devices with indications beyond what FDA has cleared in your premarket notifications for these devices. As explained in Section V.A1 of the guidance document “Deciding When to Submit a 510(k) for a Change to an Existing Device” (“510(k) Modifications Guidance”) (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/deciding-when-submit-510k-change-existing-device), “most labeling changes that affect the substance, meaning, or scope of the indications for use could significantly affect safety or effectiveness and will require submission of a new 510(k).” As discussed below, your firm’s marketing of the above devices for use beyond the cleared 6 hours in cardiopulmonary bypass procedures and for use in the Intensive Care Unit (ICU) as well as patient transport constitute major changes to the scope of the indications for use that impact the intended use and significantly affect the safety or effectiveness of the devices. Therefore, per 21 CFR 807.81(a)(3)(ii), these changes required the submission of a new 510(k).

We discuss below the specific instances where you market indications that go beyond what FDA has cleared in your premarket submissions for these products.

Quantum Pureflow Centrifugal Pumps:

Your Quantum Pureflow Centrifugal Pumps are cleared under marketing submissions K220842, K201320, K202169, and K192850. All cleared indications are similar and are for cardiopulmonary bypass (CPB) surgery, and following is an example of the cleared indications from K201320:

The Quantum Perfusion Centrifugal Blood Pump CP22 with Integrated Sensors indicated for use exclusively with the Quantum Centrifugal Drive of Spectrum Medical is intended to pump the blood through an extracorporeal circuit and to monitor pressure for periods lasting less than 6 hours for the purpose of providing either: (i) Full or partial cardiopulmonary bypass (i.e., circuit includes an oxygenator) during open surgical procedures on the heart or great vessels; or (ii) Temporary circulatory bypass for diversion of flow around a planned disruption of the circulatory pathway necessary for open surgical procedures on the aorta or vena cava.

All cleared indications for your Quantum Centrifugal Pumps specify that the pumps are indicated for open surgical procedures lasting 6 hours or less.

However, on page 22, Section 3.1.1 Intended Use, of your “Quantum Perfusions Systems Hardware Manual, ECLS” which is distributed in the U.S., you state that “Quantum PureFlow Centrifugal Blood Pumps are indicated for use for 29 days. Refer to the Instructions for Use provided with Quantum PureFlow products.” The PureFlow Centrifugal Blood Pumps are not indicated for use for 29 days in the United States. They are indicated for use for up to 6 hours. Further, in your promotional material entitled “Flexible ECLS Solutions for the ICU and Patient Transport” which is material that is distributed in the U.S., you state on page 13 that the CP22 Centrifugal Drive System “can be used to support ECLS circuits” and “can be integrated with either the Charlotte and Toronto Perfusion Systems or directly connected to the new Quantum Workstation Elite during transport.” Your pump is cleared with an indication for open cardiac procedures. These procedures are not performed in the Intensive Care Unit (ICU) nor are they performed during transportation. This change constitutes a major change or modification to its intended use, for which your firm lacks clearance or approval.

Quantum Roller Pumps and Quantum Power Supply Lite

The Quantum Roller Pumps and Quantum Power Supply Lite are cleared under premarket submission K173834 with the following indication:

The Quantum Pump Console is indicated for use for up to 6 hours in cardiopulmonary bypass procedures, when used by a qualified medical professional who is experienced in the operation of this or similar equipment.

However, you have listed both the pumps and the power supply lite as part of the ECLS system on page 21 of your “Quantum Perfusion Systems for ECLS Hardware Manual” which is distributed in the U.S.. Neither of these devices have been cleared with indications for any other form of extracorporeal life support (ECLS), other than CPB. You have a separate manual entitled “Quantum Perfusion Systems for CPB Hardware Manual.” Further, on page 14 of your promotional material entitled “Flexible ECLS Solutions for the ICU and Patient Transport” you list your roller pumps as part of your portfolio for ECLS in the ICU and patient transport. This change constitutes a major change or modification to its intended use, for which your firm lacks clearance or approval.

Quantum SuperPAC with Side Port Technology and Quantum SuperPAC – Dual Lumen Technology

The SuperPAC family of cannulas are cleared under K221353 and K203067. All cleared indications for models in this family contain the following phrase:

“intended for use…during extracorporeal life support procedures for periods of maximum 6 hours”

On pages 22 and 23 of “Flexible ECLS Solutions for the ICU and Patient Transport” you state that the devices are used during extracorporeal life support and VA extracorporeal life support. You do not indicate that the device is indicated to be used only up to 6 hours. This change constitutes a major change or modification to its intended use, for which your firm lacks clearance or approval.

Quantum Ventilation Module

On pages 10 and 11 of “Flexible ECLS Solutions for the ICU and Patient Transport” you list your Quantum Ventilation Module Lite, which, according to the product list provided to the FDA Inspector, was introduced into the U.S. market via a letter to file for your K202733 submission, which is for the Quantum Ventilation Module. In the premarket submission for K202733, the instructions for use provided for FDA review state that “the Quantum Ventilation Module has been designed to be used by experienced and trained clinicians as part of cardiopulmonary bypass therapy.” It further states that the equipment is “suitable for use in a hospital operating environment.” There is no discussion of use for patient transportation or use in the ICU. This change constitutes a major change or modification to its intended use, for which your firm lacks clearance or approval.

Quantum SuperPAC Tubing Set

On page 16 “Flexible ECLS Solutions for the ICU and Patient Transport” you present your Quantum SuperPAC tubing system, which is cleared under K213540 for

“use during cardiopulmonary bypass for a duration of up to 6 hours.”

Cardiopulmonary bypass is not performed in the ICU or during patient transport. This change constitutes a major change or modification to its intended use, for which your firm lacks clearance or approval.

Charlotte Frame Configuration

Our inspection revealed that there are several Quantum Perfusion Frames sold in the U. S. and several have been introduced via letter to file to the submission K173834. One of these is the Charlotte frame configuration. Because it was introduced via a letter to file, FDA has not reviewed this frame configuration. The cleared indications for K173834 are:

However, the Charlotte frame is not listed in your “Quantum Perfusion Systems for CPB Hardware Manual” but it is listed in your “Quantum Perfusion Systems for ECLS Hardware Manual.” In addition, the Charlotte Perfusion System is presented on page 5 of “Flexible ECLS Solutions for the ICU and Patient Transport” and states it is “designed to maximize mobility within the ICU.” The Charlotte frame is being marketed with a different indication (i.e., ECLS other than CPB) than the frames cleared under K173834 (i.e., CPB). Specifically, frames that cannot safely and reliably support the configuration of devices needed for ECLS procedures other than CPB, raise serious public health concerns when used for those procedures, because failure of the frame to safely hold the devices during transportation or treatment of patients could result in serious patient harm or death. These devices are considered life sustaining and require a new premarket submission to assess safety and effectiveness.

Your firm’s response dated May 5, 2023, did not address the violations discussed above and, therefore, is not adequate.

Accordingly, as discussed above, several of the Quantum Perfusion devices 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) for the devices as described and marketed. These devices are also misbranded under section 502(o) the Act, 21 U.S.C. § 352(o), because your firm introduced or delivered for introduction into interstate commerce for commercial distribution these devices with major changes or modifications to the intended use without submitting a new premarket notification to FDA as required by section 510(k) of the Act, 21 U.S.C. § 360(k), and 21 CFR 807.81(a)(3)(ii).

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 https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance/how-study-and-market-your-device. The FDA will evaluate the information that your firm submits and decide whether the product may be legally marketed.

Quality System Regulation (QSR) Violations

This 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 violations include, but are not limited to, the following:

1. Failure to adequately establish and maintain procedures that include requirements for identifying the action(s) needed to correct and prevent recurrence of nonconforming product and other quality problems, as required by 21 CFR 820.100(a)(3).

For example: CAPA number 342, which was opened on January 30, 2023, and closed on March 14, 2023, does not contain an adequate evaluation of actions needed to correct nonconforming product in the field. The CAPA notes that the issue will “be picked up during the general Pre-Install process, through existing checks, the (b)(4) can be swapped out if/when required.” While this addresses the detectability and corrective actions once the failure occurs, there is no evidence of consideration given to the potential risks of the slipping/ failure to lock occurring during use and preventive actions that may be taken to prevent the issue from occurring. This does not identify the action(s) needed to correct the nonconforming product that is in the field, as required by 21 CFR 820.100(a)(3).

We reviewed your firm’s response dated May 5, 2023, and concluded that it is not adequate with respect to CAPA 342, because it notes that a plan will be determined to verify and validate the CAPA actions and that the results will be documented once they are identified and completed. Your response does not address the risk of this nonconformity to fielded devices nor does it identify any plans for corrections or corrective actions for fielded devices.

2. Failure to adequately establish and maintain procedures that include requirements for verifying or validating the corrective and preventive action to ensure that such action is effective and does not adversely affect the finished device, as required by 21 CFR 820.100(a)(4).

For example: CAPA number 315, which was opened on April 12, 2022, and closed on November 11, 2022, does not contain a verification or validation plan and results that demonstrate that the corrective and preventive actions put in place to prevent the heat transfer fluid bag from breaking and leaking during shipping were effective. The packaging for the fluid bag was modified but there was no verification or validation that this change was effective in preventing the bag from being damaged in shipping. There is also no verification or validation that the corrective and preventive actions do not adversely affect the finished device.

We reviewed your firm’s response dated May 5, 2023, and concluded that it is not adequate. In this response, you provided an open CAPA, Number 357, that states effectiveness of the verification/validation plan and results will be documented. Your firm stated that you intended to submit your plans to verify and validate the actions taken in the CAPA by May 31, 2023, and results recorded by August 31, 2023, to FDA. In addition, SOP-018_V16 “Corrective and Preventive Action Procedure” will be reviewed and updated and the “Corrective and Preventative Action Report” will be updated to include an effectiveness of Verification/ Validation plan and results within the form.

This response is not adequate because 1) the plans and results have not been provided to FDA as promised to verify that the actions identified in the CAPA have been verified and validated for effectiveness and that the actions do not adversely impact the final finished device and 2) there is no planned retrospective review to identify other CAPAs whose actions have been implemented without verification and validation.

Your firm should take prompt action to address any violations identified in this letter. 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 implementation regulations into account when considering the award of federal contracts. Additionally, should FDA determine that you have QSR 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.

Please notify this office in writing within fifteen (15) business days from the date you receive this letter of the specific steps your firm has taken to address the noted violations, including 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 action (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. Please provide a translation of documentation not in English to facilitate our review. We will notify you regarding the adequacy of your firm’s response(s) and the need to re-inspect your firm’s facility to verify that the appropriate corrections and/or corrective actions have been made. 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 via email to CDRHWarningLetterResponses@fda.hhs.gov. Refer to CMS case #666543 when replying. If you have any questions about the contents of this letter, please contact: Kathleen Grunder, Biomedical Engineer, at 301-796-2676 or Kathleen.Grunder@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 yours,
/S/

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

CC:
Colleen Powell, US Agent
Spectrum Medical Inc
481 Munn Road, Suite 180
Fort Mills, SC US 29715
Via Email: Colleen.Powell@spectrummedical.com>