WARNING LETTER
Medivance Instruments Ltd.
MARCS-CMS 647562 —
February 13, 2023
Product:
Medical Devices
Recipient:
Recipient Name
Mr. Sidney Grant
Recipient Title
Managing Director, CEO
Medivance Instruments Ltd.
Barretts Green Road
Harlesden
London
NW10 7AE
United Kingdom
Issuing Office:
Center for Devices and Radiological Health
United States
WARNING LETTER
February 13, 2023
Dear Mr. Grant:
During an inspection of your firm located in Harlesden, London, United Kingdom on August 8, 2022, through August 11, 2022, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures the Velopex Aquacut Fluid Abrasion Unit (“Velopex Device”) and various accessories as part of the Velopex AquaCare Dental Abrasion line of products. These products are intended for use in a range of dental procedures, including sealant preparation, composite removal and restoration, and cavity preparation. 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 function of the body.
We received a response from you dated September 1, 2022, concerning our investigator’s observations noted on the Form FDA 483 (“FDA 483”), List of Inspectional Observations, which was issued to your firm. We address this response below, in relation to each of the noted violations. These violations include, but are not limited to, the following:
Your firm currently holds a 510(k) clearance (K024105) for the Velopex Device, which was issued on October 9, 2003. However, since the time it was cleared, the Velopex 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 incorporation of a new air regulator and changes to the materials used in the powder tubing/valves. Firm documents inspected by FDA noted that the incorporation of a new air regulator is intended to address the risk or reliability and pipe stress failure of the device by changing the parameters of the air flow and operating pressure range that are factory set. The changes to the air regulator may impact the ratio of the air/water/powder mixture that contacts the surface of the dentition and the efficiency of how that mixture moves through the system. Further, the changed powder tubing/valve materials included a container molded insert and slide insider, which may impact the performance of the drip of the powder.
The changes outlined in this warning letter 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 Velopex devices (“Modified Velopex Devices”). (See 21 CFR 807.81(a)(3).)
You did not submit any new 510(k) in association with the Modified Velopex Devices. The Modified Velopex 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 Velopex Devices, as required by section 510(k) of the Act.
Our inspection revealed that the Modified Velopex 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 procedures for the identification, documentation, validation or where appropriate verification, review and approval of design changes before their implementation as required by 21 CFR 820.30(i). For example, your firm has not verified or validated design changes during and after your firm’s design and development process prior to implementation. Your firm also stated to FDA that certain design changes for your AquaCare devices, including the Aquacut and AquaCare Single and Twin devices, were validated but not adequately documented.
The response dated 09/01/2022 is not adequate. Your firm identified its plan to revise its Design and Development procedure to meet the requirements of 21 CFR 820.30(i). Also, your firm states it plans to conduct effectiveness checks of these revised procedures. Your firm additionally provided red-lined portions of the current Design and Development procedure to describe the specific changes that were made to the procedure. However, your firm’s response failed to provide a plan on how it would retrospectively validate and, where appropriate, verify that the changes to its 510(k) cleared device were safe and effective for the device’s current intended use. Your response also failed to explain how your firm was going to establish and maintain procedures for the identification, documentation, validation (or, where appropriate, verification), review, and approval of design changes before their implementation on devices currently distributed in the US marketplace.
2. Failure to establish and maintain procedures for implementing corrective and preventive action, as required by 21 CFR 820.100(a). Your firm failed to conduct CAPA investigations and failed to verify the effectiveness of Corrective Actions taken as part of a CAPA, or indicate that verification was not required, as required by your firm’s corrective and preventive action (CAPA) procedure. For example, your firm’s corrective and preventive action (CAPA) procedure does not have a requirement to verify or validate corrective and/or preventive action for every CAPA activity. Upon review of thirty CAPA records from 2019to 2021 (including CAPAs 2019-1 to 2019-5, 2019-7 to 2019-16, 2020-1, 2020-2, and 2021-1 to 2021-13), it was observed that none of these records were evaluated for effectiveness. Further, some CAPA activity lacked corrective and/or preventive actions. Accordingly, your firm failed to verify or validate the effectiveness of CAPA actions to ensure the finished device was not adversely affected.
The response dated 09/01/2022 is not adequate. Your firm identified its plan to revise its CAPA procedure, CAPA Request form and CAPA Log (and provided copies of these revised documents as part of your response) to meet the requirements of 21 CFR 820.100(a). Your firm also noted that staff would be trained on how to implement the updated CAPA procedure, form, and log. However, the firm’s plan did not describe how it planned to address currently outstanding CAPAs, nor provide a timeline on when it anticipated these outstanding CAPAs to be resolved.
3. Failure to review and evaluate all complaints to determine whether an investigation is necessary. When no investigation is made, the manufacturer shall maintain a record that includes the reason no investigation was made and the name of the individual responsible for the decision not to investigate, as required by 21 CFR 820.198(b). For example, your Customer Complaints procedure states all customer complaints must be investigated and if rejected, a justification must be documented. During inspection, your firm stated to FDA that complaint investigations are carried out but might not have been documented. However, forty-eight customer complaints from 2019-2022 were reviewed where no investigation was performed, and a justification was not documented as to why no investigation was performed.
The response dated 09/01/2022 is not adequate. Your firm identified its plan to revise its Customer Complaints procedure to meet the requirements of 21 CFR 820.198(b). Also, your firm has plans to revise the Customer Complaints Form; generate a new Faults Investigation form and retrain all required personnel. Your firm provided copies of the revised procedure, revised Customer Complaints form and a new Faults Investigation form as part of your investigation. Your firm has yet to complete personnel training. Although your firm’s plan indicates a commitment to resolve new complaints that you receive, it does not address a commitment and timeline to investigate and resolve current, pending complaints such as the ones identified as part of FDA’s investigation. Investigation and resolution of complaints is required per your firm’s revised SOP; which states in part that complaints shall be evaluated to determine whether a CAPA will be required, shall be conducted; and if required the QA/RA department will be notified to coordinate initiation and resolution of the CAPA.
4. Failure to maintain device history records (DHR's). Each manufacturer shall establish and maintain procedures to ensure that DHR's for each batch, lot, or unit are maintained to demonstrate that the device is manufactured in accordance with the device master record(DMR) and the requirements of this part, as required by 21 CFR 820.184. For example, your firm does not have procedures to ensure the DHR for each unit of your device is manufactured in accordance with the DMR and requirements of the regulation. Your firm does not have a DHR procedure. In addition, your firm’s device DHRs for your AquaCare device lacks identification labeling as well as a Unique Device Identifier (UDI) or Universal Product Code (UPC) for each device unit.
The adequacy of the response dated 09/01/2022 cannot be determined at this time. Your firm identified its plan to revise its AquaCare Final test Certificate and generate a new Device History Records procedure to meet the requirements of 21 CFR 820.184. The plan may be appropriate based on the documentation provided in the response, but your firm has not completed implementation of the plan, nor documented the plan’s effectiveness. Without this documentation in hand, FDA cannot make an assessment with respect to adequacy.
Our inspection also revealed that your firm’s Velopex AquaCare Dental Abrasion System 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 submit an MDR report no later than 30 calendar days after the day you receive or otherwise become aware of information that reasonably suggests a marketed device either may have caused or contributed to a death or serious injury, or has malfunctioned and 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). For example, the information included for your firm’s incident report
(b)(4)
reasonably suggests that a patient sustained an injury (i.e., surgical emphysema and an observed area of traumatic ulceration) from your firm’s AquaCare device and subsequently underwent antibiotic treatment. There is no information included in the complaint that rules out that the device may not have caused or contributed to the referenced injury. Further, the information described in the complaint meets the definition of a serious injury under 21 CFR 803.3(w) because medical intervention was necessary to preclude permanent impairment of a body function or permanent damage to a body structure. Your firm became aware of the referenced event on April 12, 2019. However, your firm didn’t submit an MDR for the referenced event.
Your firm’s response dated September 1, 2022, is not adequate. Your response noted that your firm developed an MDR procedure and is in process of establishing an eMDR account for the submission of the referenced report. Based on FDA’s records, your firm had a certificate with Electronic Submissions Gateway (ESG) on August 22, 2022. However, your firm did not complete its load test and guidance compliance submission for eMDR. Your firm should follow the instructions located at How to Enroll in eMDR Program | FDA under step 2 of “Low Volume Enrollment Process” to complete the testing in order to obtain its Web Trader production account. Further, our review concluded that the newly developed MDR procedure is deficient as indicated above and your firm does not plan to take the systemic corrective actions including a retrospective review of complaints for reportability.
Your firm also failed to develop, maintain, and implement written MDR procedures as required by 21 CFR 803.17. For example, during the inspection, your firm identified the documents titled “Vigilance System”, Document
(b)(4)
, dated 03/10/2021 and “Vigilance System – Incident Reporting Procedures”, Document
(b)(4)
, dated 07/11/2021 as its MDR procedure. However, the procedure does not contain information that would indicate that it is an MDR procedure created in accordance with the requirements of 21 CFR 803.17. Your firm’s response dated September 1, 2022, is not adequate. Your response provided a copy of a newly created MDR procedure titled “Vigilance System – Incident Reporting Procedure in the USA”, Document
(b)(4)
, dated 8/1/2022. After reviewing the procedure outlined in your response, the following deficiencies were noted:
a. 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 omits definitions of the terms “malfunction”, “caused or contributed” and “serious injury”. The exclusion of the definitions for these terms from the procedure may lead your firm to make an incorrect reportability decision when evaluating a complaint that may meet the criteria for reporting under 21 CFR 803.50(a).
b. The procedure does not describe how your firm will address documentation and recordkeeping requirements, as required by 21 CFR 803.17(b), including information that was evaluated to determine if an event was reportable. Additionally, the procedure, as written, designates the initial importer Velopex International as the authorized reporter to fulfil the manufacturer’s reporting obligation. Under the MDR regulation, both manufacturers and importers are required to make reports as described in 21 CFR Part803.The section 19(b) of your firm’s procedure states that Velopex International will be required to act as the Manufacturer and will need to report to the FDA directly as required by 21 CFR 803.50 and 803.52. However, this statement does not exempt any mandatory reporting entity from fulfilling its individual reporting requirements.
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.
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.
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, 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 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. Please provide a translation of documentation not in English to facilitate our review. 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 by email to CDRHWarningLetterResponses@fda.hhs.gov or by mail to Food and Drug Administration, Center for Devices and Radiological Health, Office of Regulatory Programs, Division of Regulatory Programs 2: Establishment Support, Regulatory Inspections and Audits Team, White Oak Building 66, 10903 New Hampshire Ave., Silver Spring, MD 20993. Refer to CMS case #647562 when replying. If you have any questions about the contents of this letter, please contact: Michael Adjodha at (301) 796-6276.
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/
Malvina B. Eydelman, M.D.
Director
OHT1: Office of Ophthalmic, Anesthesia, Respiratory,
ENT and Dental Devices
Office of Product Evaluation and Quality
Center for Devices and Radiological Health
CC:
Registered Agent Solutions Inc.
1701 Directors Boulevard, Suite 300
Austin, TX 78744
Content current as of:
04/25/2023
Regulated Product(s)
Medical Devices