I.T.S. GmbH

During an inspection of your firm located in Lassnithohe, Steiermark, 8301 on January 16, 2023, through January 19, 2023, investigators from the United States Food and Drug Administration (FDA) determined that your firm manufactures bone fixation devices and other class II devices. 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 Ing. Florian Grill dated February 7, 2023, and March 20, 2023, 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 adequately establish and maintain procedures for implementing corrective and preventive action, per 21 CFR 820.100(a).

For example:

a) Your firm's procedure titled CAPA System (Corrective and Preventive Actions), ITS PB-7.6-2 Edition 9 Effective June 17, 2021, does not include adequate requirements to ensure investigations of the cause of nonconformities, or adequate requirements to ensure the implementing and recording changes in methods and procedures needed to correct and prevent identified quality problems and corrective and preventive actions. Specifically, section 2.3 of the procedure titled Investigation and Analysis states: "The event will be investigated together with the members of the department, in which the non-conformity was detected. The results of the investigation will be analyzed and stated in the CAPA form. The cause will be defined, and the corrective action created." This section does not define methods of investigation which would provide employees a means to investigate recurring nonconformities across all possible processes/areas where the nonconformities may affect product. In addition, your procedure does not include adequate requirements to ensure the information related to quality problems or nonconforming products is adequately disseminated to persons responsible for assuring the quality of the product and prevention of such problems.

b) CAPA form, Form F-8.5.1_CAPA_Formblatt_REV06_015_2022, was initiated on September 7, 2022, as a result of three similar errors found during Incoming QC (IQC) inspections of deliveries from the supplier (b)(4) due to dimensional deviation of the (b)(4) A Supplier Corrective Action Request, SCAR 11_679/2022, was sent to (b)(4) requesting an investigation and corrective actions to fix the deviations in dimensions. However, your firm did not include documentation to demonstrate adequate investigation of this quality issue, implementation of corrective actions and distribution of this quality issue to persons required to ensure the quality of the products.

We reviewed your firm's response dated February 7, 2023, and March 20, 2023, and conclude that your firm's response to this observation is inadequate.

You provided a revised version of your CAPA procedure, CAPA System (Corrective and Preventative Actions) PB-7.6-2, Revision 10, effective date 01/27/2023. Sections 2.2 was revised to include causes of nonconformities that may trigger an investigation to include external complaint, internal complaint, self-identified potential for improvement, audits/inspection, recall and supplier failure. Your procedure outlined steps for when to open a CAPA or NCR (Nonconformance Report). Procedural step for creation and processing of a CAPA report is outlined in section 2.2 and 2.2.1 of this revised procedure. Sections 2.3 and 2.3.1 were revised to outline conducting of a root cause analysis (by means of Ishikawa, 5-why or the like) and potential root causes defined, such as events caused by employees, equipment, document failure, or other causes. Your revised procedure explicitly states that a CAPA can only be closed after completion of effectiveness check and that this is to be documented. Requirement for training of necessary personnel is stated in section 2.4 of your revised procedure. Your also updated CAPA Form, F_8.5.1_CAPA_Formblatt_Rev07 to address the deficiencies noted in observation, including providing clear method for documentation of investigation and implementation of actions. Your revised SOP references form F-8.5.1_CAPA_Formblatt in several sections (as needed to initiate the CAPA process, and document investigation, event classification, corrective and preventive action, and effectiveness checks).

Your revised procedure is accompanied by documentation (i.e., signatures on Form F-6.2.2.2) of training to four "management staff'. However, you have not provided evidence of training of additional personnel directly responsible for assuring the quality of product or the prevention of product quality problems. Your firm should provide documentation of training of all relevant personnel responsible for assuring the quality of products. Also, confirm that you have conducted review of prior CAPA(s) per the revised procedure and taken necessary actions to ensure that the revised procedure is adequately implemented, including CAPA investigations are adequately documented. Your firm's future response should provide detailed activities conducted and status of those activities to ensure compliance with the revised CAPA procedure.

2. Failure to maintain adequate device history records (DHR's), as required by 21 CFR 820.184. For example: Your firm did not maintain the primary identification label and labeling used for each production unit in your DHR as required by 21 CFR 820.184 (e). During walkthrough of your facility, the FDA investigator observed that your firm "do check the accuracy of the label prior to initiating labeling operations". However, the FDA investigator also noted that "this is not documented in the DHR" . This deficiency was discussed with your firm management at the end of the inspection.

Your firm's response dated February 7, 2023, and March 21, 2023, did not address this deficiency as it was discussed with your firm's management at the close of the Inspection and not cited as an observation on the FDA-483. Your firm's future response should address what systemic measures were taken to address this deficiency and provide evidence of implementation of your corrective actions.

Our inspection also revealed that your firm's implantable orthopedic 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:

3. Failure to adequately develop, maintain, and implement written MDR procedures as required by 21 CFR 803.17. For example, during the inspection, your firm presented the following documents as your written MDR procedure.

Document titled "Feedback Handling", VA-8.2.1, Revision 14, dated September 19,2022

Document titled "MDR (Medical Device Reporting)", PD-8.5, Revision 5, dated May 17, 2022

After reviewing the procedure, the following deficiencies were noted:

1) 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:

a. The procedure omits the definitions from 21 CFR Part 803.3 for the terms "become aware" and "caused or contributed", and the definition for the term "reasonable suggests", found in 803.20(c)(1). 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 include instructions for how your firm will evaluate information about an event to make MDR reportability determinations in a timely manner.

2) The procedure does not describe how your firm will address documentation and recordkeeping requirements, as required by 21 CFR 803.17(b), including:

a. Documentation of adverse event related information maintained as MDR event files.

b. Documentation of the deliberations and decision-making processes used to determine if a device-related death, serious injury, or malfunction was or was not reportable, as required under 21 CFR 803.18(b)(1)(i).

We reviewed your firm's response dated February 7,2023 and conclude that it is not adequate. The response includes your revised procedure titled "MDR (Medical Device Reporting)", PD-8.5, Revision 6, dated 2/2/2023, and staff training records. However, after reviewing the referenced document, the following deficiencies were noted:

3) 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). However, the procedure omits the definition from 21 CFR Part 803.3 for the term "caused or contributed", and the definition for the term "reasonably suggests", found in 803.20(c)(1). 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).

4) The procedure does not describe how your firm will address documentation and recordkeeping requirements, as required by 21 CFR 803.17(b), including documentation of the deliberations and decision-making processes used to determine if a device-related death, serious injury, or malfunction was or was not reportable, as required under 21 CFR 803.18(b)(1)(i).

We reviewed your firm's response dated March 20, 2023, and conclude that it is not adequate. The response includes a revised Complaint Form (Form No. F-8.2.1-1) titled "DATA Acquisition I.T.S Products", Revision 04, dated February 1,2023, and staff training records. However, upon collectively reviewing your firm's MDR procedure, Revision 6, dated February 2,2023, we conclude that the written MDR procedure lacks definitions of the terms used for the reportability determination outlined above. Please provide your revised procedure incorporating the missing procedural requirements outlined above. Also, confirm that you have retrospectively reviewed relevant MDRs to ensure appropriate actions are taken per the revised procedure. In your future response, please provide detailed activities conducted and status of those activities to ensure compliance with the revised MDR procedure.

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.

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 #657885 when replying. If you have any questions about the contents of this letter, please contact: Shumaya Ali, Assistant Director, Stereotaxic, Bone Growth Stimulator, and Fracture Fixation Devices Team at 301-796-2356.

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.