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WARNING LETTER CMS # 647427

March 23, 2023

Dear Mr. Kim:

During an inspection of your firm, Synovo Production, Inc. (Synovo or “the firm”), located in Fullerton, CA, on October 11, 2022, through October 26, 2022, an investigator from the United States Food and Drug Administration (FDA) determined that your firm is a specification developer, manufacturer, and distributor of the “Femoral Resurfacing Cup,” which is distributed both as a stand-alone product and marketed as a component of the “Total Hip System.”¹ Both these products are intended for a range of orthopedic procedures, including, but not limited to, hip arthroplasty and reconstruction. 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 in man, or intended to affect the structure or any function of the body of man.

Our inspection revealed that your firm currently holds a 510(k) clearance for the Femoral Resurfacing Cup. This device was cleared on May 23, 1991 under K904870 with the name “Modified New Jersey Femoral Hip Resurfacing Component” and was assigned product code KXA. This device was cleared, among other things, for painful hip cup arthroplasty. The clearance letter associated with this device further advised that:

1. This device may not be labeled or promoted for non-cemented use.

2. All labeling for this device, including package label and labeling included within the package, must prominently state that the device is intended for cemented use only.

3. Any non-cemented fixation of this device is considered investigational and may only be investigated as a significant risk device in accordance with the investigational device exemption regulation under 21 CFR, Part 812. All users of the device for non-cemented fixation must receive approval from their respective institutional review boards and the Food and Drug Administration to conduct the investigation.

However, since the time it was cleared, the Femoral Resurfacing Cup 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, significant changes to the Femoral Resurfacing Cup’s fixation have been made that include, among other things, a change to the coating specifications and associated differences in intended use. According to the instructions for use collected during the inspection, “the underside of the resurfacing component has a coating for cementless fixation” (emphasis added), which is contradictory to the K904870 clearance letter. The referenced changes, individually and collectively, are likely to expose patients to increased risks of loosening and subsequent revision surgery (e.g., from pain, proximal femur fracture, or component fracture).² 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 further modified Femoral Resurfacing Cup (See 21 CFR 807.81(a)(3)).

You did not submit any new 510(k) for the referenced modifications to the Femoral Resurfacing Cup. The Femoral Resurfacing Cup, when distributed as an individual device separate from the Total Hip System, is therefore misbranded under section 502(o) of 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 this device, as required by section 510(k) of the Act.

Our inspection also revealed that the Femoral Resurfacing Cup is 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 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).

Our inspection revealed that you are also marketing the Femoral Resurfacing Cup as a component of the Total Hip System. Specifically, based on the totality of the labeling collected during inspection, the Total Hip System is intended for use as a semi-constrained total hip joint replacement device composed of an acetabular fixation cup with a polyethylene bearing surface in combination with a femoral resurfacing cup. FDA has classified this type of hip joint replacement device as class III under 21 CFR 888.3410 (product codes KXB for cemented prostheses or OCG for non-cemented prostheses). These class III device types require submission and approval of a PMA in order to obtain marketing authorization.

The Total Hip System is 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 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 Total Hip System is 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).

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 the Total Hip System device and Femoral Resurfacing Cup 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 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 validate according to established procedures where results of a process cannot be fully verified by subsequent inspection and test, as required by 21 CFR 820.75(a). Specifically, you changed the biologic fixation coating for the hip replacement system from a sintered beads porous coating to a Titanium Plasma Spray (TPS) coating in April 2020. You have a Letter to File for the process change, but you could not provide evidence that a validation was performed for the change. You also discontinued the second machining process for the Femoral Resurfacing Component, but you could not provide evidence that a validation was performed for the process change. You did not follow your Process Control SOP2-007, Rev. D which states that re-validation shall be considered, and typically required, for a manufacturing process change.

2. Failure to establish and maintain 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, per a request from a surgeon in July 2022, you manufactured three units of a Femoral Resurfacing Cup Lot 01030049T to shorten the stem by 1cm. You did not follow your Design Control SOP-008, Rev. D in that you did not manage the change by documenting the design change, perform appropriate verification and validation, and keep a record of reviews.

3. Failure to establish procedures for implementing corrective and preventive action as required by 21 CFR 820.100(a). Specifically, your firm opened Process CAR 1008 to address the issue of the TPS coating adhering poorly to the Femoral Resurfacing Component. You determined that a second machining process was causing delamination of the coating and you removed the second machining process. You received sample parts from DOT America and certificates from the supplier SynusBio for the new lot, but you could not provide evidence that the corrective action was found to be effective. You did not follow your Corrective Action and Preventive Action SOP2-014, Rev. D which states that effectivity checks should be performed at an appropriate time after the corrective action file has been closed.

4. Failure to establish and maintain procedures to ensure that all purchased or otherwise received product and services conform to specified requirements, as required by 21 CFR 820.50. Specifically, your firm was unable to provide a supplier assessment form for your re-packager/sterilizer BioPro, Inc. You did not follow your Supplier Qualification SOP2-028, Rev. C which states that a Supplier/Consultant Form (SOP2-028-01) will be completed to document preliminary information about the supplier; that QA/RA will review the information as to whether to proceed with the qualification process; and that qualification occurs before utilizing the supplier/consultant. During the inspection, you also completed an initial supplier assessment for your supplier of raw materials, SynusBio, but had not completed it prior to utilizing the supplier.

5. Failure to document the dates and results of quality system reviews by management with executive responsibility as required by 21 CFR 820.20(c). Specifically, your firm could not provide evidence that it conducted management reviews since its inception in April 2020. You did not follow your Management Review SOP2-011, Rev. D which states that at least once a year top management will meet to review the suitability and effectiveness of the quality system.

6. Failure to conduct quality audits as required by 21 CFR 820.22. Specifically, your firm could not provide evidence that an annual audit had occurred in 2021. You did not follow your Internal Audit SOP2-024, Rev. D which states that each quality system element listed on the audit schedule will be audited at a minimum of once per year.

7. Failure to document personnel training as required by 820.25(b). Specifically, your firm could not provide training records for your Regulatory Affairs (RA) Manager. You did not follow your Training and Personnel Qualification SOP2-018, Rev. D which states that a training record form (SOP-018-91) and electronic documentation of training shall be completed. The RA Manager also stated that your firm does not have training records for your firm’s other employees.

Furthermore, under section 510 of the Act (21 U.S.C. § 360), manufacturers of medical devices are required to annually register with the FDA. In September 2007, section 510 of the Act was amended by the Food and Drug Administration Amendments Act of 2007 (Pub. L. 110-85) to require domestic and foreign device establishments to submit their annual establishment registration and device listing information to FDA by electronic means (section 510(p) of the Act, 21 U.S.C. § 360(p)), during the period beginning October 1st and ending December 31st of each year. Our inspection revealed that your firm was not currently registered with FDA as a device specification developer, manufacturer, or distributor, nor were any of the devices associated with your firm listed with FDA. You indicated to our inspector that you would complete the registration and listing process. As of the date of this letter, our records indicate that your firm has not fulfilled annual registration and listing requirements for fiscal year 2023.

Therefore, all your firm’s devices are misbranded within the meaning of section 502(o) of the Act (21 U.S.C. § 352(0)), in that the devices were manufactured, prepared, propagated, compounded, or processed in an establishment not duly registered under section 510 of the Act (21 U.S.C. § 360) and were not included in a list required by section 510(j) of the Act (21 U.S.C. § 360(j)).

During our inspection of your firm, you indicated that Synovo would respond in writing within fifteen business days after the completion of the inspection. As of the date of this letter, FDA has not received such response.

Your firm should immediately cease manufacture of the Total Hip System and Femoral Resurfacing Cup with the modified underside and labeled for non-cemented use and take prompt action to correct the violations addressed in this letter. Failure to address this matter promptly and adequately 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: Jessica Mu, Director of Compliance Branch at oradevices3firmresponse@fda.hhs.gov. Refer to CMS # 647427 when replying. If you have any questions about the contents of this letter, please contact: Raymond W. Brullo, Compliance Officer at 949-608-2918 or raymond.brullo@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/

CAPT Raquel Peat, PhD, MPH, USPHS
Director
OHT 6: Office of Orthopedic Devices
Office of Product Evaluation and Quality
Center for Devices and Radiological Health

Shari J. Shambaugh
Program Division Director
Office of Medical Device and Radiological Health
Operations Division 3/West

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1 The Total Hip System is also referred to in labeling for the Femoral Resurfacing Cup as the “Synovo Hip Replacement System.” The Total Hip System is also comprised of additional components, including but not limited to the “Acetabular Fixation Cup” and “Acetabular Bearing.”

2 Additionally, you have changed the coating specifications of the “Acetabular Fixation Cup” cleared under K963101 which also exposes patients to increased risks of loosening and subsequent revision surgery.