WARNING LETTER
Argon Medical Productions & Vertrieb Gesellschaft MBH & CO MARCS-CMS 694763 —
- Delivery Method:
- Via Email
- Product:
- Medical Devices
- Recipient:
-
Recipient NameMr. Richard Donaca
-
Recipient TitleCEO
- Argon Medical Productions & Vertrieb Gesellschaft MBH & CO
Franz Kirsten Str. 1
Bingen Am-Rhein
55411 Rhineland-Palatinate
Germany-
- r.donaca@argon-group.de
- Issuing Office:
- Center for Devices and Radiological Health
United States
WARNING LETTER
October 22, 2024
Dear Mr. Donaca:
During an inspection of your firm located in Bingen am-Rhein, Germany on 7/29/2024 through 7/31/2024, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures K3Pro and K3Pro Rapid Implant (Konus Dental Implant System), K3Pro Konus Additional Abutments and Implants, and K3Pro Konus New Abutments and Implants. 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.
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 a response from Mr. Marcel Kumpa-Management Representative dated 08/21/2024, 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:
1. Failure to review, evaluate, and investigate any complaint involving the possible failure of a device, labeling, or package to meet any of its specification unless such investigation has already been performed for a similar complaint and another investigation is not necessary, as required by 21 CFR 820.198(c). For example:
Complaints involving potential device failures, such as the failure of dental implants to osseointegrate, were not investigated as required. During the inspection, the investigator identified Complaint number 23.058, titled "Osseointegration guarantee," as lacking both an investigation and a reference to a prior investigation.
According to your firm’s AA_005_complaint processing procedure, all complaints must be investigated through a technical assessment, as outlined on page 4. However, your firm justified its approach by stating that it does not investigate osseointegration complaints due to the complexity of patient-specific factors, such as smoking or diabetes, which can influence the outcome.
By failing to conduct or document the required technical assessment, your firm is in violation of your own complaint processing procedure, which does not provide any additional instruction on complaints that do not require an investigation. Also, your firm’s records do not make reference to any investigation to similar complaints to justify why a duplicative investigation for the aforementioned complaint is not necessary.
We reviewed your firm’s response dated 08/21/2024 and conclude that it is not adequate. Your firm determined that complaints involving nonconformities are considered low risk and are not investigated. Your firm explained that the root causes of these complaints are managed as part of your osseointegration guarantee, with the complaints being processed as returns rather than being investigated. As part of your proposed corrective action, your firm plans to revise your process instructions, work instructions, and forms for handling complaints. In your response, your firm committed to treating osseointegration cases as separate complaints, ensuring that any cases involving serious patient injury will be investigated and reported in accordance with FDA's Medical Device Reporting (MDR) requirements under 21 CFR 803. Your firm also proposed to review 2023 and 2024 complaint statistics to evaluate whether there is an obligation to report certain cases. Your firm's response does address the need for a retrospective review of previous complaints and product returns to assess whether any past cases should have been treated as quality complaints or reported under MDR requirements.
Additionally, your firm's response did not include any documentation or evidence of the proposed corrective actions, as these measures are still in progress. Without evidence or timelines for completion, it is difficult to assess the adequacy and effectiveness of the planned corrections.
Our inspection also revealed that your firm’s K3Pro dental implants 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 adequately develop, maintain, and implement written MDR procedures as required by 21 CFR 803.17(a). For example, during the inspection, your firm acknowledged the procedure Post Market Surveillance procedure A002 as its written MDR procedure, and agreed with the investigator that the procedure have the following deficiencies:
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, there are no definitions of what your firm will consider to be a reportable event under 21 CFR Part 803.
b) The procedure does not establish internal systems that provide for timely transmission of complete medical device reports, as required by 21 CFR 803.17(a)(3).
Additionally, as of September 13, 2023, your firm had not completed its load test and guidance compliance submission for electronic Medical Device Reporting (eMDR). We recommend your firm follow the instructions provided at https://www.fda.gov/medical-devices/emdr-electronic-medical-device-reporting/how-enroll-emdr-program under “Low Volume Enrollment Process” to obtain its WebTrader production account. A tutorial video is also available at https://youtu.be/EdKy5wl8F18 to guide low-volume submissions for eMDR. Furthermore, the MDR procedure is written in a foreign language. Without an English translation, we are unable to fully assess your firm’s MDR procedure.
The adequacy of your firm’s response dated August 21, 2024, cannot be determined at this time. In the response, your firm referenced the 21 CFR 803 requirements and states that it plans to revise it adverse event reporting work instructions AA_002 to incorporate these requirements and conduct staff training. However, your firm has not provided English-translated documents for the revised MDR procedure, as the revision is still in progress.
2. 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, during the inspection, your firm acknowledged that Complaints 23.058, 23.060, and 23.062 describe events where patients experienced osseointegration failure after using your firm’s K3Pro dental implants. We believe osseointegration failure necessitates medical or surgical intervention to preclude permanent impairment of a body function or permanent damage to a body structure. Your firm also acknowledge that there is no information indicating that the device might not be a contributing factor leading to the osseointegration failure. Therefore, the referenced events meet the criteria for MDR reportable serious injury, as defined in 21 CFR 803.3. Your firm became aware of the events for Complaint 23.058 on April 3, 2023, 23.060 on April 17, 2023, and 23.062 on April 19, 2023. However, your firm has not submitted a serious injury MDR for each of these adverse events.
Your firm’s response dated August 21, 2024, cannot be determined at this time. In the response, your firm states that it continuously monitors complaint statistics related to osseointegration failure and highlighted that osseointegration is highly patient-dependent, influenced by various factors such as pre-existing conditions, oral hygiene, smoking, and diet. Your firm also promised to conduct a retrospective review of complaints from the past two years to assess reportability. However, your firm has not provided any documents or evidence indicating the completion of this retrospective review.
The inspection revealed that your devices are misbranded within the meaning of section 502(c) of the Act, 21 U.S.C. § 352(c), because a word, statement, or other information required by or under authority of section 519 of the Act, 21 U.S.C. § 360i, to appear on the label or labeling of the devices was not prominently placed thereon with such conspicuousness (as compared with other words, statements, designs, or devices, in the labeling) and in such terms as to render it likely to be read and understood by the ordinary individual under customary conditions of purchase and use. In particular, 21 CFR 801.20(a) – which was promulgated under authority of section 519 of the Act, among other provisions – requires, with exceptions not relevant here, that the label and device package of every medical device bear a unique device identifier (UDI) that meets the requirements of 21 CFR Part 801, subpart B, and 21 CFR Part 830. The labels of the K3Pro Kronus Dental implant devices do not bear such a UDI.
Specifically, the labels for the K3Pro Kronus Dental implant devices do not include a device identifier within the meaning of 21 CFR 801.3 or 830.3, and there is no UDI presented in easily readable plain-text on the label of the K3Pro Rapid (Ref 40009K3PRO.R), K3Pro XP-Line (Ref BSP.XP 35020/3), and K3Pro S-line (Ref 45011K3PRO.S) (see 21 CFR 801.40(a)(1)), and there is no UDI presented in machine-readable form that uses automatic identification and data capture (AIDC) technology on the label of K3Pro XP-Line (Ref BSP.XP 35020/3) (see 21 CFR 801.40(a)(2)).
In addition, the K3Pro XP-Line (Ref BSP.XP 35020/3) devices are misbranded within the meaning of section 502(t)(2) of the Act, 21 U.S.C. § 352(t)(2), in that there was a failure or refusal to furnish any material or information required by or under section 519 of the Act, 21 U.S.C. § 360i, respecting these devices. In particular, 21 CFR 830.300(a) and 830.320(b) – both of which were promulgated under section 519 of the Act, among other provisions – require that the labeler of a device submit electronically to FDA’s Global Unique Device Identification Database (GUDID) the information required by 21 CFR Part 830, subpart E, for each version or model required to bear a UDI. FDA has determined that your firm causes a label to be applied to a device with the intent that the device will be commercially distributed without any subsequent replacement or modification of the label. Argon Medical Productions & Vertrieb Gesellschaft MBH & CO is therefore a “labeler” within the meaning of 21 CFR 830.3 and has not submitted to GUDID information required by 21 CFR Part 830, subpart E, respecting these devices.
The failure or refusal to furnish any notification or other material or information required by or under section 519 of the Act, 21 U.S.C. § 360i, also constitutes a prohibited act under section 301(q)(1)(B) of the Act, 21 U.S.C. § 331(q)(1)(B).
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 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 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 or by mail to Food and Drug Administration, Center for Devices and Radiological Health, Office of Regulatory Programs, Division of Regulatory Programs 2, FDA Regulatory Inspections and Audits Team, White Oak Building 66, 10903 New Hampshire Ave., Silver Spring, MD 20993. Refer to CMS case #694763 when replying. If you have any questions about the contents of this letter, please contact: Andrew I. Steen at 301-796-6284.
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:
Celline Lakus
Argon Dental USA LLC
1000 Corporate Dr
Marshfield, WI US 54449
Phone: 715 8981434 ext
Fax: 715 3874100
Email: cellinel@argondentalusa.com