WARNING LETTER
Globus Medical, Inc.
MARCS-CMS 685606 —
July 15, 2024
Delivery Method:
United Parcel Service
Product:
Medical Devices
Recipient:
Recipient Name
Daniel T. Scavilla
Recipient Title
President & CEO
Globus Medical, Inc.
Valley Forge Business Center
2560 General Armistead Avenue
Audubon
,
PA
19403
United States
Issuing Office:
Office of Medical Device and Radiological Health Division I
United States
Secondary Issuing Offices
Center for Devices and Radiological Health
United States
WARNING LETTER
CMS# 685606
July 15, 2024
Dear Mr. Scavilla:
During an inspection of your firm located at 2560 General Armistead Avenue, Audubon, Pennsylvania 19403 on February 15, 2024, through March 7, 2024, investigators from the United States Food and Drug Administration (FDA) determined that your firm is a manufacturer of the Class II Excelsius GPS (EGPS) surgical robot and associated interbody spine and cranial modules intended for use as an aid for precisely locating anatomical structures and for the spatial positioning and orientation of an instrument holder or guide tube to be used by surgeons for navigating and/or guiding compatible surgical instruments in open or percutaneous procedures provided that the required fiducial markers and rigid patient anatomy can be identified on CT scans or fluoroscopy. 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.
Quality System Regulation
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 responses from Daniel S. Paul, Senior Vice President of Quality Assurance, and Information Technology, dated March 28, 2024, and May 31, 2024, concerning our investigators’ 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 establish and maintain procedures for implementing corrective and preventive actions, including requirements for analyzing processes, work operations, concessions, quality audit reports, quality records, service records, complaints, returned product, and other sources of quality data to identify existing and potential causes of nonconforming product, or other quality problems using appropriate statistical methodology, as required by 21 CFR 820.100(a)(1).
The specifically section of Observation 5 states that you did not follow your Corrective and Preventative Action Procedure (SOP 8.5.2; Rev.K: Eff: 10/18/19) to conduct a CAPA investigation upon receipt of
(b)(4)
. Two examples were provided to highlight that you did not initiate CAPAs despite documentation in complaints COM-20-2011 (10/6/20) and COM-22-0414 (2/1/22) that there were 55 and 76, previous complaints of misplaced screws, respectively. You explained that the subsequent revision of SOP 8.5.2 was changed to require a trend analysis and risk reconciliation before determination of whether a CAPA is warranted.
We reviewed your firm’s responses dated March 28, 2024 and May 31, 2024 and concluded that they are not adequate. In your responses, you provided data showing counts of misplaced screws per 10,000 screws implanted from 2017 to 2024. However, there was no additional level of data analyses, using appropriate statistical methodology, to determine whether there are any trends associated with part numbers, including the spine and cranial modules; lot numbers; patient symptoms; confirmed and alleged defects; causes determined by complaint investigations (e.g., software, components, user error); etc. for complaints specifically related to misplaced screws navigated by the EGPS surgical robot. Therefore, the overarching concern is that the trend analysis you rely on to determine whether CAPAs should be initiated does not employ appropriate statistical methodology to detect recurring quality problems. Furthermore, there was no information provided on how your firm evaluated risk as a factor in determining whether to initiate a CAPA for this issue.
You also provided a revised complaint procedure which includes more details on how to conduct investigations, perform risk reconciliation, and determine when CAPAs should be initiated. Additional corrective actions included restructuring the complaint database to add additional fields for complaint investigations and risk reconciliation and developing a trend analysis procedure. No timelines were provided for corrective actions except to state that the next update will be provided by July 31, 2024. Overall, it is not clear if the identified corrective actions will follow all the requirements of 21 CFR 820.100(a)(2) to (a)(4), including verification that corrective actions are effective.
2. Failure to review, evaluate, and investigate complaints involving the possible failure of a device to meet any of its specifications, as required by 21 CFR 820.198(c).
Specifically, you did not follow your Product Complaint Procedure (SOP 8.3.1; Rev.T, U; Eff: 4/22/20, 1/19/22), which requires comprehensive complaint investigations. Moreover, this procedure did not include details on what constitutes a “comprehensive” investigation. For example, your complaint record lacked details on how you concluded that there was no device malfunction or user error for complaint COM-21-3115 (10/5/21) where the EGPS surgical robot was in use when a patient experienced adverse health effects and passed away. In addition, the complaint record for COM-22-0414 (2/10/22), received for “screw missed pedicle which then went superior into the disc space and the screw was removed,” lacked evidence that you made multiple attempts to verify whether a malfunction occurred.
We reviewed your firm’s responses dated March 28, 2024 and May 31, 2024 and concluded that they are not adequate. In your responses, you acknowledge that autopsy results or a physician statement would have been beneficial in supporting the conclusion that the cause of death was not device-related. You further stated that COM-21-3115 was submitted as an MDR out of abundance of caution after discussion with investigators. You also provided a revised complaint procedure which includes more details on how to conduct investigations, perform risk reconciliation, and determine when CAPAs should be initiated. Additional corrective actions included restructuring the complaint database to add additional fields for complaint investigations and risk reconciliation and developing a trend analysis procedure. No timelines were provided for corrective actions except to state that the next update will be provided by July 31, 2024.
Overall, it is not clear if identified corrective actions will follow the requirements of 21 CFR 820.100(a)(2) to (a)(4), including verification that corrective actions are effective. Also, there was no action identified to retrospectively review complaints for all of your products, for a reasonable period of time, to determine whether there are other examples of inadequate complaint investigations, which require corrections. Lastly, there was no correction identified to obtain information and update COM-21-3115 and COM-22-0414 with additional investigation details.
Medical Device Reporting (MDR)
Our inspection (also) revealed that your firm’s EGPS 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:
1. Failure to submit a report to FDA no later than 30 calendar days after the day that your firm received or otherwise became aware of information, from any source, that reasonably suggests that a device that your firm markets may have caused or contributed to a death or serious injury, as required by 21 CFR 803.50(a)(1).
For example, the information included for Complaint COM-19-2014 (Exhibit 15) describes an event where a patient’s dural lining of the spinal cord was damaged during a procedure with your firm’s EGPS spinal robotic system, necessitating surgical intervention and repair. There is no information reasonably suggesting that the device might not be a contributing factor to the patient’s serious injury. As such, the referenced event meets the criteria for an MDR reportable serious injury, as defined in 21 CFR 803.3. Your firm became aware of this event on September 24, 2019. Although a malfunction MDR corresponding to the referenced event was submitted to FDA, the report was received on March 12, 2024, which is beyond the required 30 calendar day time frame, and it incorrectly identifies the MDR reportable event as a malfunction. A supplement report that correctly identifies referenced MDR reportable event as a Report Type, Serious Injury, must be submitted to the FDA.
We have reviewed your firm’s response dated March 28, 2024, and concluded that it is not adequate. Your firm stated that it submitted MDR 3004142400-2019-00106 for Complaint COM-19-2014. Although we confirmed that the report was received on March 12, 2024, it incorrectly identifies the MDR reportable event as a malfunction. A supplement report that correctly identifies referenced MDR reportable event as a Report Type, Serious Injury, has not yet been received.
The response dated May 31, 2024, did not include new information to address this violation.
2. Failure to submit a report to the FDA no later than 30 calendar days after the day that your firm received or otherwise became aware of information, from any source, that reasonably suggests that a device that it markets has malfunctioned and this device or a similar device that your firm 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).
For example, the information included for Complaints COM-21-0424, COM-21-0467, COM-21-2838, COM-22-0414 and COM-23-2525 reasonably suggests that your firm’s EGPS spinal robotic system malfunctioned (i.e., misplaced screws) while in use. We believe that the referenced malfunction would be likely to cause or contribute to a death or serious injury if it were to recur. There is no information included for the referenced complaints that justifies that the referenced malfunction would not be likely to cause or contribute to a death or serious injury. Therefore, the information included for each referenced complaint represents a reportable malfunction. Your firm became aware of the event referenced in Complaint COM-21-0424 on January 28, 2021, Complaint COM-21-0467 on February 5, 2021, Complaint COM-21-2838 on September 15, 2021, Complaint COM-22-0414 on February 10, 2022, and Complaint COM-23-2525 on May 25, 2023. However, the corresponding MDRs 3004142400-2020-00028, 3004142400-2023-00098, and 3004142400-2023-00123 were received by the FDA on February 9, 2024, which is beyond the required 30 calendar day timeframe. Additionally, the MDRs 3004142400-2020-00023 and 3004142400-2020-00029 have not yet been received by the FDA.
The adequacy of your firm’s response dated March 28, 2024, cannot be determined at this time. The response noted that your firm conducted a retrospective review of complaints received for misplaced screws since the device launched in 2017 and identified 77 complaints that represent MDR reportable events. However, your firm stated it cannot submit all of the MDRs due to duplication issues and is working with the FDA Electronic Submissions Gateway (ESG) helpdesk for resolution.
The adequacy of your firm’s response dated May 31, 2024, cannot be determined at this time. Your firm provided an update to its action plans, including continuing to resolve the eMDR acknowledge process.
3. Failure to maintain copies of all electronic acknowledgments FDA sends you in response to electronic MDR submissions in your MDR event file, as required by 21 CFR 803.18(b)(1)(iii).
For example, during the inspection, your firm was unable to provide the electronic acknowledgments for the following MDRs # 3004142400-2020-00018 (dated January 13, 2020), 3004142400-2020-00030 (dated February 14, 2020, yet not received by FDA), 3004142400-2020-00045 (dated April 29, 2020), 3004142400-2020-00048 (dated May 11, 2020), 3004142400-2020-00049 (dated May 11, 2020), 3004142400-2023-00088 (dated May 11, 2020), and 3004142400-2023-00093 (dated May 23, 2020).
The adequacy of your firm’s response dated March 28, 2024, cannot be determined at this time. The response noted that your firm is conducting systemic corrective actions, including procedure updates to verify MDR submissions. However, your firm did not provide any documentation or evidence to demonstrate the completion of these corrective actions, as they are still ongoing.
The adequacy of your firm’s response dated May 31, 2024, cannot be determined at this time. The response included a red-lined copy of its revised Product Complaint Procedure SOP 8.3.1, Rev. Y, which incorporates the submission verification process, as well as staff training records. However, your firm did not provide any documentation or evidence to demonstrate the completion of all corrective actions, including the planned effectiveness checks.
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 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 # 685606 when replying. If you have any questions about the contents of this letter, please contact: Sargum Morgan at 313.393.8253 or sargum.morgan@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/
Joseph Matrisciano, Jr.
Program Division Director
Office of Medical Device and Radiological Health
Division I
/S/
RDML Raquel Peat, Ph.D., MPH, USPHS
Director
OHT 6: Office of Orthopedic Devices
Office of Product Evaluation and Quality
Center for Devices and Radiological Health
CC: Daniel Paul, Senior VP of Quality Assurance, & IT, dspaul@globusmedical.com
Content current as of:
08/13/2024
Regulated Product(s)
Medical Devices